Modeling Deposition of Inhaled Particles - Aerosols: Measurement, Dosimetry, and Health Effects - page 102

exposures may result in disease (i.e., cadmium inhalation causing emphysema), potentially leaving
the alveolar region unable to defend itself against or remove other inhaled contaminants, as well as
causing the macrophages to release enzymes that damage the neighboring lung tissue. As discussed
previously, toxic particulate contaminants such as silica and asbestos can cause macrophage
impairment and damage, resulting in particle persistence and disease. The next section discusses
inhaled particle overload in the alveolar region of the lung and resulting particle translocation.
5.4.6.3 Free Particle Uptake and Translocation to the Interstitium
Particles, particularly ultraines, that are not rapidly cleared by macrophage action may persist in
the alveoli or be taken up by epithelial cells and translocated from the alveolar region of the lung to
the interstitial tissues and regional lymph nodes. 165,208-210 These particles may remain in the intersti-
tium or regional lymph nodes for years, building up over time, 211 or may be removed by interstitial
macrophages and/or penetrate into the post-nodal lymph circulation. 210-212 It has been suggested
that impaired clearance or a signiicant burden of particles in the lung (particle overload) increases
translocation of particles to the interstitium. 208,213 Studies in animals have found that increasing
particle number and dose rate, and decreasing particle size enhances translocation of particles to the
interstitium. 214-216 Enhanced interstitium translocation, particularly when toxic dusts (i.e., silica) are
involved, has been linked with tissue damage, tumors, and ibrosis. 168,208,217
5.4.6.4 Importance of Clearance in Particle Deposition Modeling
Several computational models of clearance mechanisms have been developed. 218-220 As clearance
will affect both the residence time and local distribution of inhaled particles, the implementation of
such models into particle deposition simulations would be desirable.
Hofmann et al. 221 developed a model of particle clearance in which different clearance rates
(derived from experimental studies) were associated with different generations of TB airways.
Furthermore, Martonen and Hofmann 222 described a model of clearance as a function of spatial
location within airway branching sites. Speciically, they incorporated distinct clearance rates for
tubular airway segments, bifurcation zones, and carinal ridges.
As discussed in the previous sections, age, activity level, drugs, inhaled contaminants, and dis-
ease can affect the eficiency of particle clearance, in turn inluencing the number and local con-
centrations of inhaled particles. Particle deposition models that consider these overlapping factors
could be of great use in both inhalation toxicology and aerosol therapy. Although we have discussed
its inluence as it relates to clearance, we will now provide a more complete discussion of the effects
of disease on particle deposition and distribution.
5.4.7 d isease
Airway disease has a dual effect on particle deposition, both inluencing breathing pattern and phys-
ically changing airway morphology. In this section, we will discuss common respiratory diseases
and how they affect airlow and airway morphology, thus affecting the deposition and distribution
of inhaled aerosols.
5.4.7.1 Chronic Obstructive Pulmonary Disease
COPD is a term that is generally applied to patients with emphysema and/or chronic bronchitis.
Both of these diseases modify the structure of the human lung, 168 resulting in either obstructed air-
ways and/or degeneration of the alveolar structure.
Emphysema may affect the respiratory or terminal bronchioles or the peripheral alveoli. Cigarette
smoke and air pollution are the likely causes of emphysema, resulting in the destruction of elastin in
the alveolar wall. This elastin destruction leads to enlarged airspaces and loss of alveolar structure,
often resulting in intrapulmonary bronchi collapse during expiration. 117,168 In addition, the loss of the
alveolar structure results in the loss of capillary bed that transfers oxygen from the lungs to the blood. 168