Modeling Deposition of Inhaled Particles - Aerosols: Measurement, Dosimetry, and Health Effects - page 98

by Heyder et al., 133 Stahlhofen et al., 134 and Svartengren et al. 135 utilized regulated breathing in
the determination of particle deposition in the human respiratory tract.
5.4.5 r esPiratory s ysteM e nvironMent
Temperature and relative humidity (RH) in the human respiratory system varies with mode of res-
piration and anatomical location. Table 5.1 provides temperature and humidity data 136-145 for differ-
ent anatomical locations for both oral and nasal respiration. In general, a temperature of 37°C and
an RH of 99.5% may be assumed for nasal respiration. 146 For oral respiration, 37°C and 90% RH
may be assumed for air entering the trachea, with RH increasing by 1% per airway generation until
reaching 99.5% at the tenth generation. 146
RH and temperature affect the growth of hygroscopic particles in the human lung. Hygroscopic
growth occurs when the absorption of water from a humid environment causes changes in particle
diameter and density. Since RH and temperature vary throughout the human lung, a particle's size
and density may change while traveling through the respiratory system. Thus, a measured size
distribution for hygroscopic particles is not likely to relect actual particle sizes in vivo . A more
extensive discussion of hygroscopicity and its effect on particle deposition in the human lungs may
be found in Chapter 6.
Hygroscopic growth has been widely observed in many environmental and pharmaceutical aero-
sols 147-158 (Table 5.2). Therefore, it is often desirable to account for hygroscopic growth in particle
deposition modeling. Deposition modeling studies 7,32 have accounted for hygroscopicity by incorpo-
rating the growth rate of aerosol particles as a function of residence time in the lung. Such experi-
mental growth rate measurements for different aerosols have been presented. 159,160 The growth of
aerosol particles has also been computationally predicted. 161-164
5.4.6 c learance
Inhaled foreign material is continually cleared from the respiratory tract. From a simpliied per-
spective, inhaled insoluble particles are cleared from the human lung in two phases, mucociliary
(or fast phase) clearance and phagocytosis (or slow phase) clearance. In addition, free particles may
translocate out of the alveolar region of the lung into the lymphatic system or the lung interstitium.
Depending on their lipophilicity, hydrophilicity, and/or size, soluble particles may be dissolved prior
to physical clearance. Other particles, such as asbestos ibers and other biopersistent ibrous minerals,
are often unable to be cleared from the lung; their retention may result in inlammation, tissue damage,
and eventual disease. Oberdörster 165 provides a review of the clearance of both soluble and insoluble
particles. Because the toxicity of a substance may be related to its time of residence in the respiratory
system, clearance is an importance consideration in the risk assessment of inhaled particles. Thus, we
will present a brief overview of its mediation by drugs, inhaled contaminants, age, and activity.
5.4.6.1 Mucociliary Clearance
Mucociliary (or fast phase) clearance occurs in the TB airways of the lung. Mucus is secreted by
mucous glands in the bronchial walls and by goblet cells in the bronchial epithelium. This mucus is
propelled by millions of cilia (collectively referred to as the mucociliary escalator) toward the phar-
ynx, in the process transporting particles out of the conducting airways. At the pharynx, the mucus
and particles are swallowed. The velocity of the mucus varies from a rate of 1 mm/min in the smaller
airways to 2 cm/min in the trachea. 166 Mucociliary clearance of deposited particles generally occurs
within 24 h after deposition in healthy individuals. 166-169 A comprehensive review of mucociliary
clearance is presented by Yeates et al. 170
5.4.6.1.1 Effect of Drugs and Inhaled Contaminants on Mucociliary Clearance
Numerous studies have shown that drugs can have a signiicant effect on mucociliary clearance.
Beta-andrenergics, histamines, and amiloride have all been shown to increase mucociliary clearance