Routes of Exposure, Dose, and Metabolism of Metals - Toxicology of Metals - page 45

3.1.3 Clearance of Particles from the
Respiratory System

Mucociliary clearance of inhaled particles depends
on genetic factors (Bohning et al. , 1975; Camner et al. ,
1972). Clearance can also be affected by many different
agents (e.g., tobacco smoke and other air pollutants,
drugs, and infectious agents). The effect of tobacco
smoke on mucociliary transport has been the sub-
ject of numerous investigations. In many in vitro and
in vivo studies in animals, an immediate impairment
of the transport rate was seen after exposure to ciga-
rette smoke (see e.g., Asmundsson and Kilburn, 1973).
In man, however, the average short-term effect of
smoking cigarettes is an increased mucociliary trans-
port (Albert et al. , 1976; Camner et al. , 1971). The aver-
age effect of long-term cigarette smoking is impaired
mucociliary transport (Camner and Philipson, 1972;
Lourenco et al. , 1971). However, some individuals who
have smoked for 20-30 years do not have impaired
clearance develop. The impaired clearance after long-
term smoking is at least partially reversible (Camner
et al. , 1973d).
Inhalation of agents other than tobacco smoke, car-
bon dust, sulfur dioxide, or sulfuric acid can immedi-
ately give rise to an increased mucociliary transport
(Camner et al. , 1973a; Newhouse et al. , 1978; Wolff
et al. , 1975). It is well known that inhalation of all three
of these pollutants can give increased airway resist-
ance mediated by the vagus. Because the administra-
tion of cholinergic compounds increases mucociliary
transport, it seems probable that the vagus has a role
in mediation of the effect of pollutants (Camner and
Philipson, 1974; Camner et al. , 1974). High concen-
trations of sulfuric acid mist (980

Mechanisms for clearance or translocation of par-
ticles depend on the regions of deposition. Sneezing,
nose wiping or blowing, mucociliary transport, disso-
lution and absorption into the blood or lymph, or endo-
cytosis by macrophages or epithelial cells may remove
particles deposited in the extrathoracic or tracheo-
bronchial regions. Particles deposited in the alveolar
region may be removed by dissolution and absorption
into the blood or lymph, endocytosis by macrophages
or epithelial cells, or translocation into the systemic
circulation (Schlesinger, 1995).

3.1.3.1 Tracheobronchial Clearance
3.1.3.1.1 Mucociliary Clearance The upper air-
ways, the nasal passages, the paranasal sinuses, the
auditory tube, and the upper part of the pharynx are
provided with ciliated epithelium as are the lower air-
ways from the lower parts of the larynx down to and in-
cluding the terminal bronchioli. The upper airways cilia
drive mucus backward and downward to the pharynx,
and the lower airways cilia drive mucus upward to the
pharynx whereafter it is swallowed. Lucas and Doug-
las (1934) proposed a two-layer model for mucociliary
transport. The lower layer, in which the cilia beat, was
proposed to consist of a low viscous secretion (the sol
layer) and the upper layer of a highly viscous secre-
tion (mucus or gel layer). Most particles deposited on
the ciliated epithelium of the large airways are rapidly
cleared (within hours to days) by this mechanism.
The importance attached to mucociliary transport
in the airways has been motivated by theoretical con-
siderations. If mucociliary transport is impaired, the
concentration of particles per unit surface area should
increase, and the particles should remain for a longer
time on the area. People with congenitally immotile
cilia have been identifi ed and studied by Eliasson et al.
(1977), Levison et al. (1983), Mossberg et al. (1983) and
Pedersen and Stafanger (1983). Studies on these per-
sons provide a unique opportunity to evaluate the
importance of mucociliary transport. Such patients
often have chronic infections in the upper and lower
airways since childhood and commonly have bron-
chiectasis and obstructed airways.
In healthy humans, the tracheal mucus transport
rate has been estimated to be in the range of about
4-20 mm/min (Santa Cruz et al. , 1974; Yeates et al. ,
1975). The velocity is lower in the more peripheral
airways. The particles deposited in the most periph-
eral ciliated airways are eliminated from the lung usu-
ally within 24 hours (Albert et al. , 1967; Camner and
Philipson, 1978).

g/m 3 ) produce a
transient slowing of clearance (Leikauf et al. , 1981).
Because more than 99% of SO 2 at common ambi-
ent concentrations is absorbed in the nose, its effect on
mucociliary transport should also be most pronounced
in this organ. Andersen et al. (1974) found a reduced
transport after exposure to approximately 15 mg SO 2 /m 3
for 3 hours. A tendency toward reduced mucociliary
transport in the nose was seen even after exposure
to 3 mg/m 3 over a period of 6 hours. In experiments
on animals for longer exposure times, SO 2 reduced
mucociliary transport in rats after exposure to about
3 mg/m 3 for 770 hours (Ferin and Leach, 1973), and
in dogs after exposure to approximately 3 mg/m 3
for 12 months (Hirsch et al. , 1975). NO 2 has also been
reported to impair mucociliary transport in animals
after long-term exposure. In rats, exposure to approxi-
mately 12 mg N0 2 /m 3 for 6 weeks caused decreased
transport (Giordano and Morrow, 1972).
Not only administration of cholinergic compounds
but also of adrenergic compounds has been shown
to increase the mucociliary transport rate in man to
a high degree (Camner et al. , 1976; Foster et al. , 1976;

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