Modeling Deposition of Inhaled Particles - Aerosols: Measurement, Dosimetry, and Health Effects - page 101

5.4.6.1.2 Effect of Disease on Mucociliary Clearance
Mucociliary clearance is inhibited by numerous respiratory diseases. Acute respiratory infections
such as pneumonia and inluenza have been shown to impair clearance. 180,185,186 Chronic respiratory
infections such as chronic bronchitis and bronchiectasis often result in an accumulation of mucus
in the ciliary transport system, hindering mucociliary clearance. 187 While chronic obstructive pul-
monary disease (COPD) patients generally have varied and erratic clearance rates, 169,170 asthma can
result in reduced mucus transport rates and mucus plugging of the bronchi. 168,173,188,189 Patients with
cystic ibrosis (CF) have been shown to have whole lung clearance impairment, as well as regional
clearance impairment. 190 Small airway dysfunction or disease from chronic cigarette smoke also
results in slowed mucociliary clearance. 182
5.4.6.1.3 Effect of Age and Activity on Mucociliary Clearance
Mucociliary clearance has been shown to decrease with age, starting at the age of 20, with large
differences between adults >54 years old and adults 21-37 years. 191-194 Ho et al. 195 showed that
adults over the age of 40 have decreased ciliary beat frequency, thus leading to slowed mucociliary
clearance.
Increased physical activity, particularly aerobic exercise, has been shown to increase mucocili-
ary clearance in humans. 165,189,196,197 Normal activities that do not require signiicant exertion have no
effect on mucociliary clearance, while sleep signiicantly slows mucociliary clearance. 165,189
5.4.6.2 Macrophage Clearance or Phagocytosis
Macrophage (or slow phase) clearance occurs in the alveolar region of the lung. As alveoli do not
have cilia, deposited particles are engulfed by large bodies called macrophages (phagocytosis).
These alveolar macrophages then migrate to the cilia surface and are cleared by mucociliary clear-
ance, or move into the lymphatic system or bloodstream for removal. This type of clearance may
take months or years. 165
5.4.6.2.1 Effect of Particle Size/Fiber Length and Shape on Macrophage Clearance
Particle size affects macrophage clearance rates, with clearance eficiency decreasing for particles
smaller than 1 μm, 198 and optimal clearance occurring for particles between 1.5 and 3 μm. 165 Studies
have shown that particle/iber length affects alveolar clearance, with shorter ibers cleared more
readily than longer ibers. 199-201 Particles such as asbestos and other nonsoluble ibers are often
unable to be removed by phagocytosis because the macrophage is unable to engulf the entire iber.
This may result in incomplete phagocytosis, damage to the macrophage, and the release of the mac-
rophage's digestive enzymes. These digestive enzymes can cause extensive tissue damage. Thus, the
persistence of these ibers in the lung can result in inlammation and disease. 202,203
In addition, toxic non-iber particles such as silica, that persist in the alveoli, provoke reactions
that can lead to lung disease (i.e., silicosis). When a macrophage engulfs silica particles, the mac-
rophage may release enzymes that cause ibroblast proliferation. This release of enzymes results
from the crystalline structure of silica, the crystalline structure having been linked to the particle's
ibrogenic potential. 204
5.4.6.2.2 Effect of Drugs and Inhaled Contaminants on Macrophage Clearance
Inhaled contaminants such as ozone, nitrogen dioxide, and cigarette smoke affect alveolar macrophage
activity. Ozone and nitrogen dioxide reduce phagocytosis as well as the bactericidal activity of
macrophages, making it more dificult to ight bacterial lung infections. 205 Acute cigarette smoke
exposures, as well as high-level cigarette smoke exposures, have been shown to inhibit macrophage
action while low levels of cigarette smoke exposure have been shown to increase macrophage
action. 206,207 Exposure to nongaseous aerosolized contaminants such as nickel, cadmium, lead,
manganese, chromium, and vanadium has been shown to damage alveolar macrophages. 204,205 Such