review lung deposition predictions of airborne …deposition means the event of a particle to adhere...
TRANSCRIPT
Introduction
Utilization of fossil fuels to power heavy indus-
try and motorized transport results in increased
airborne pollutants. Biota (plants and animals)
come into direct contact with suspended atmos-
pheric aerosol particles by gas exchange or
via the dermis/cuticula. In humans, aerosol par-
ticles in the range of 1 nm to 10 µm such as
cigarette smoke and occupational as well as
environmental aerosols are inhalable and can
deposit in the respiratory system. Inhaled and
deposited particles may cause many diseases
in the human respiratory tract and the occur-
rence of such diseases depends not only on the
amount of mass deposited but also on the ad-
sorbed substances they carry into specific re-
gions of the lungs. Hence, the determination of
aerosol deposition in the lung, their uptake
(absorption into the blood), redistribution, stor-
age, and removal (clearance and excretion)
from the body are the most important proc-
esses involved to assess the extent of conse-
quent harmful effects.
It is worth to mention that knowledge of re-
gional deposition in the airways may have
important practical applications in the case of
therapeutic aerosols as well. Understanding
aerosol deposition in the lung is a complex
phenomenon, since it depends on the aerosol
properties, lung morphemetry, and respiratory
physiology.1 Aerosol deposition in the human
respiratory tract has been determined experi-
mentally, for certain aerosol systems either in
vivo or via in vitro studies. While in vivo studies
are ethically problematic, in vitro models also
have severe limitations in simulating realistic
physiological conditions. Therefore, several
mathematical models of the human respiratory
system have been developed to calculate the
deposition of inhaled aerosols. 2-6 Different
modeling and computation techniques such as,
a) semi-empirical models, 1, 7 b) deterministic,
symmetric generation or single-pathway mod-
els, 4, 8 c) one-dimensional cross section or
“trumpet” models, 9, 10, 11 d) deterministic
asymmetric multiple path modes, 12, 13 e) sto-
chastic, asymmetric generation models 6, 14 and
computational fluid dynamics (CFD) based
models 15-17 have been employed to estimate
the deposition efficiency within the lung. How-
ever, the calculated deposition fractions vary
primarily with respect to lung morphometry
and mathematical modeling technique. There-
fore, it is always on the user to select any of
the available techniques for deposition calcula-
tions depending on the purpose of its use and
Lung deposition predictions of airborne particles and the emergence of contemporary diseases Part-I
Inhaled particles can cause a variety of pulmonary illnesses such as asthma, bronchitis, chronic
obstructive pulmonary diseases (COPD) and even secondary organismic diseases. Thus,
predictions of inhaled aerosol deposition in the respiratory tract are essential not only to assess
their possible consequences but also to optimize drug delivery using pharmaceutical aerosols.
Deposition of inhaled aerosols is a complex phenomenon that depends on the physico-chemical
properties of the particles, lung anatomy, and respiratory patterns of the subject. Hence, the
prediction of particle deposition for an individual person poses real challenges. Different
conceptual particle deposition models are employed for the estimation of deposition fraction in
different region of the lung. However, these deposition fractions vary with the above mentioned
parameters in addition to the modeling and computational technique. Part-I of this review article
briefly describes the deposition behaviour of inhaled particulate matter and the currently
available approaches for the prediction of aerosol deposition in the respiratory tract. Part-II
continues this thread and provides a broad view of the health-related issues of particle exposure.
Hussain M1,2, Madl P1, Khan A1,2 1Division of Physics and Biophysics, Department of Materials Research and Physics, University of Salzburg, Austria, 2Higher Education Commission, Islamabad, Pakistan
theHealth 2011; 2(2):51-59
Correspondence
Majid Hussain
Division of Physics and
Biophysics, Department of
Materials Research and Physics,
University of Salzburg,
Hellbrunnerstrasse 34, A-5020,
Salzburg, Austria
E-mail:
Keywords:
Lung Deposition, Deposition
Mechanisms, Modeling,
Clearance
Funding
This work was funded in part
by European Union, Contract
No. 516483 (Alpha Risk) and
by the Higher Education
Commission of Pakistan under
the scholarship program
(Overseas Scholarship for
Pakistani Nationals)
Competing Interest
None declared.
Received: March 29, 2011
Accepted: May 4, 2011
Abstract
ISSN (print): 2218-3299
ISSN (online): 2219-8083
Review
51 | theHealth | Volume 2 | Issue 2
on the available input information.
In this review, we shall briefly discuss the, 1) human lung
structure, 2) particle deposition mechanisms, 3) particle clear-
ance mechanisms in the lung, 4) introduction to basic compo-
nents of a computational model and of different modeling
techniques, 5) deposition patterns in human airway bifurca-
tions along with identification of high density deposition ar-
eas (hotspots), and 6) effects of particle size, flow rate, age,
and gender that affect deposition. Furthermore, possible con-
sequences as a result of the deposited aerosol fraction in
terms of possible health effects shall also be highlighted in
Part-II of this paper.
Human lung structure
Airflow, aerosol transport and aerosol deposition in airways
are strongly influenced by the dimensions and orientation of
flow passages in the respiratory tract. The lung volume ex-
pands during inhalation and contracts during exhalation, re-
sulting in a variable airways geometry. Lung airway structure
starts with oro-nasal passages, i.e. extrathoracic (ET) region
followed by the larynx, trachea, main broncholi, all the way
down to the gas-exchange tissue, the alveoli. Moving down to
the lower airways, the number of airways in humans multiply
mostly via diachotomous branching patterns. 18 With each
bifurcation also the airway dimensions become reduced
(Figure 1). At the same time and as one proceeds further
towards the alveolar regime, multiple bifurcation patterns
cause the overall lung volume to increase in non-linear fash-
ion. 4 The human respiratory tract can be divided into four
anatomical regions and 23 lung generations, which are
adopted for the calculation of deposition fractions of inhaled
aerosol particles. 1
Extrathoracic region (ET)
Under normal circumstances, air is inspired through the nose
and the pharynx into the larynx. In case of nasal obstruction
or when respiratory demand exceeds the nasal airflow ca-
pacity, air is inspired through the mouth. Nasal or oral path-
ways are known as ET regions (Figure 1). This region of the
human respiratory tract serves as an important first stage
filter for inhaled particles entering the lung. This region also
contains associated lymph vessels and lymph nodes called
bronchus-associated lymphoid tissue (BALT). Therefore, from
the point of view of toxicology and human health, under-
standing the nature of airflow, and particle transport in the
human nasal-oral passages is important.
Bronchial (BB) region
This region is a part of the air conducting system within the
thoracic region. BB consists of the trachea (assigned genera-
tion 0, Figure 1), the main bronchi, and the intrapulmonary
bronchi (usually grouped around generation 8). The region
also includes associated lymph vessels and lymph nodes. The
epithelium of the trachea primarily consists of ciliated cells
ending with mucus secreting goblet cells and specialized mu-
cus secreting glands. 1 The cilia reveal synchronized beating
patterns in order to propel mucus and deposited matter up to
the larynx where they are either expelled or ingested.
Bronchiolar (bb) region
This region is the second part of the air conducting system
within the thorax. It consists of the bronchioles comprising
generations 9 to 16 (Figure 1). The branches of the last gen-
eration are called terminal bronchioles; all airways beyond
the terminal bronchioles carry alveoli. The bronchioles are
airways without cartilage and glands. Basal cells are rarely
found in bronchioles. The surfaces of the bronchioles have
ciliated cells that clear secretory fluid towards the base of BB
region. 1
Alveolar-interstitial region (AI)
The AI compartment comprises the respiratory tract system up
to the terminal bronchioles that groups together generations
16 to 26 known as the respiratory bronchioles and the alveo-
lar ducts (Figure 1). It includes interstitial lymphatic tissues
and lymph vessels as well as bronchial lymph nodes. The gas-
exchange region is represented by the alveolar sacs, which
are closed at the peripheral end by a group of alveoli. The
target cells in the alveolar-interstitial region are the secretory
(Clara) cells of the respiratory bronchiole, type I and type II
epithelial cells covering the alveolar surface.
Particle deposition mechanisms in the lung
Deposition means the event of a particle to adhere or stick to
a surface. The most important mechanisms by which airborne
particles can deposit in the lung are diffusion, sedimentation
and impaction (Figure 2). Whereas some minor mechanism su-
Figure 1: ICRP1 anatomical regions and airway generation model;
Tracheobronchial region (generations 0-16) and pulmonary region
(generations 17-23). (modified 19)
theHealth | Volume 2 | Issue 2 | 52
Lung deposition predictions of airborne particles
ch as particle electrostatic charge and particle interception
(particles contact with the surface even if its trajectory does
not deviate from the streamline) also cause deposition. These
mechanisms are briefly described in this section.
Diffusion
Deposition by diffusion is caused by Brownian motion or a
larger diffusion coefficient. Diffusion is the deposition mecha-
nism for small particles (< 0.5 µm) due to collision with air
molecules (Figure 2). Diffusion may cause the particle to
move across the streamline and deposit upon contact with the
airway wall. Deposition by diffusion increases with decreas-
ing particle size and flow rate. Increased diffusion deposition
occurs in the alveoli region because of longer residence time
and smaller airways. The deposition probability by diffusion
in cylindrical airways is calculated as:
P(s) = ∆/R [1]
where R is the airway diameter, and is the parti-
cle mean displacement in the airway. ∆ is proportional to
the square root of the diffusion coefficient D defined by the
well known Stokes-Einstein equation:
D = kTCc/3πda [2]
where Cc is the correction factor for slip flow conditions, k the
Boltzmann constant, T the absolute temperature, the gas
viscosity, and da the particle diameter.
Sedimentation
Sedimentation is due to the dominating gravitational force
acting on the inhaled particles over the air resistance. Thus,
as a result of balancing between the gravitational force and
drag force of air, particle may deposit on lower surfaces of
the airway (Figure 2). This mechanism is important for particle
sizes greater than about 0.5 µm and becomes dominant in
the bb and Al where air flow decelerates. Sedimentation
deposition increases with an increase in particle size and a
decrease in flow rate. The deposition probability by sedi-
mentation in cylindrical airways is calculated as:
P(s) = Ut t/R [3]
where t is the particle residence time in the airway and Ut =
gd2a/18 is the terminal settling velocity of the particle
which depends on the particle density ρ and gravitational
constant g.
Impaction
Large-sized particles with higher momentum simply do not
follow the curvature of the air stream due to inertia and de-
posit on the airway wall. Because momentum is the product of
mass and velocity (mV), inertial impaction is important for
large particles, usually greater than 1 µm in size. Deposition
by impaction increases both with growing particle sizes an
flow rates (Figure 2). Impaction events take place predomi-
nantly in the naso-pharyngeal and TB region. The deposition
efficiencies of the nose or oral breathing patterns are plotted
as a function of the inertial impaction parameter, d2aQ,
where da is the aerodynamic particle diameter, and Q is the
volumetric flow rate. The deposition probability by impaction
in cylindrical airways is calculated as:
P(I) = hs/R [4]
Where hs is the particle stopping distance and it becomes
Stokes number ρda2QCC / (36μR) (µ is the air viscosity, ρ is
the particle density and Cc is the Cunningham slip correction
factor for the particle) if divided by airway radius R.
Particle clearance mechanism in the lung
Getting rid of deposited particles from the respiratory tract
by particle transport or by absorption into blood is called
clearance. Different clearance mechanisms operate in differ-
ent regions of the lungs to eliminate the trapped foreign ma-
terial.
Figure 2: Major mechanisms of particle deposition in the respiratory
tract. 20
Figure 3: Schematic drawing of airway showing different clearance
mechanism of the inhaled particles. 21
53 | theHealth | Volume 2 | Issue 2
Dt2
Lung deposition predictions of airborne particles
Mechanical clearance
Mechanical clearance is primarily associated with the ET re-
gion, while clearance takes place by sneezing, coughing or
swallowing of the deposited material. This phenomenon takes
place immediately after the deposition event of a particle
load still within the nasal or oral pathway. Coughing is a ma-
jor clearance mechanism and therefore critically important
for airway hygiene and for increased mucus production.
Typically, particles over 5.0 µm diameter are stopped and
deposited by nostril hair filters.
Mucociliary clearance
Mucociliary clearance is the primary clearance mechanism to
remove insoluble deposited particles in the TB region. The
mucociliary escalator operates in the TB region to transport
the aerosol loaded mucus towards the larynx where the mu-
cus is eventually swallowed or removed as sputum (Figure 3).
It has been estimated that in the absence of any disease the
majority of the deposited particles are cleared within 24 h
from the trachea and bronchi. 1 However, mucociliary clear-
ance progressively decreases from the larger airways (BB) to
the smaller airways (bb).
Macrophage-mediated clearance
Macrophages are white blood cells produced by the differ-
entiation of monocytes in tissues. Macrophages operate in the
alveolar region and help to engulf and relocate the depos-
ited foreign material towards bronchiolar airways. If upward
translocation is no longer possible, the material is routed to
the circulatory or lymphatic system. Since only a restricted
number of macrophages can deal with the deposited parti-
cles, the macrophage-mediated clearance is considered a
slow clearance mechanism and it may take years to clear the
lung from the deposited material.
Translocation
The transfer of material absorbed from the respiratory tract
to other tissues in the body is called translocation. Ultrafine
(UF) particles (< 0.1 µm) and relatively insoluble particles
can be translocated from the TB or alveolar region to other
lung compartments and body tissues as explained in figure 4.
In the TB region, translocation usually occurs via the peribron-
chial region. Whereas in the Al region, this process takes
place via the Al epithelium straight into the interstitum (Figure
4).
A small fraction of the UF particles can be translocated to the
circulatory system and hence can reach extrapulmonary or-
gans via the blood stream. 22 Inhalation of nano sized parti-
cles refers to the translocation from the nasal epithelium to
the brain. Elder et al, 23 showed that UF manganese oxide
particles translocate to the olfactory bulb and other regions
of the central nervous system. However, according to current
knowledge, particle translocation and accumulation in extra-
pulmonary organs is a minor clearance mechanism as com-
pared to macrophage mediated clearance and still requires
further study to investigate its effect on human health. 22
Absorption into circulation system (blood absorption)
Movement of the soluble substances and material dissociated
into blood stream regardless of the mechanism is called ab-
sorption. Absorption into blood is a two stage process, a) the
dissociation of the particles into material that can be ab-
sorbed into the blood (dissolution) and b) the uptake of ma-
terial dissolved from particles or of material deposited in a
soluble form. Each stage can be time-dependent. Absorption
mechanism is a material specific phenomenon. 24 Soluble in-
haled particles can slowly absorb into the blood depending
on their absorption properties and their history that is, spe-
cific activity (radioactive particles), temperature treatment,
and surface area. The particle dissolution rate is a major
determinant controlling the rate of absorption for the mate-
rial retained in the respiratory tract. Absorption clearance
takes place in entire of the respiratory tract with different
absorption rates in different regions. Materials have been
categorized in fast, medium, and slow materials depending
upon their specific dissolution rate. 24 Accordingly, toxicity is
also tightly related to their velocity of dissolution.
Aerosol deposition models
Semi-empirical models
The International Commission on Radiological Protection
(ICRP) has proposed a semi-empirical model for regional
deposition and clearance from the human respiratory tract. 1
The purpose of this model was to calculate radiation doses
to the respiratory tract of workers resulting from the intake
airborne radionuclides. The models consider human respira-
tory tract as a series of anatomical compartments through
which aerosol pass during inhalation and exhalation. Each
compartment is treated as a filter in which deposition is calcu-
Figure 4: Schematic drawing of the alveolar tissue showing different
clearance mechanism of deposited particles. Pulmonary alveolar
macrophage (PAM) mediated removal from the lungs away towards
other excretory organs. Inlet: PAM loaded with 80 nm particles.
Approximately 40 nm-sized caveolar openings disappear and
reappear, forming vesicles that constitute pathways through the cells
for encapsulated macromolecules. 25
theHealth | Volume 2 | Issue 2 | 54
Lung deposition predictions of airborne particles
lated by semi-empirical equations 26 derived from fitting
experimental data as a function of particle size and flow
rate. The advantages of such semi-empirical models are that
they are easy to use with less computational work. Yet, they
can neither be used for deposition calculations at the airway
generation level, nor for flow rates and particles sizes be-
yond the limits of the experimental data sets on which the
semi-empirical model is based upon.
Deterministic or single-path models
Deterministic models 4, 8 are simple and can be applied to an
average path without having detailed knowledge about the
branching structure of the lung. In a deterministic or single
path model, airway generations have identical linear dimen-
sions in which each parent airway branches into two identical
daughter airways. 2 Thus all pathways of an inhaled particle
from the trachea to the alveolar sacs are identical and thus
can be represented by a single path. Because of symmetric
branching and equal diameters of daughter airways, the
inhaled air flow and hence deposition fraction is equally dis-
tributed among all airways in a given generation. Deposition
fractions in each airway are computed by applying analyti-
cal deposition equations for a defined flow rate. The deposi-
tion fraction for a given generation is obtained by summing
up deposition fractions of each airway of that particular
generation.
Trumpet models (one dimensional)
The trumpet lung model was proposed by Yu 9, which uses
Weibel’s 2 morphometry of the human lung and treats air-
ways as a one-dimensional airway system in which the flow
cross-sectional area varies along the airway depth. In this
approach, the cross-sectional area of each generation is
plotted as one parameter, thereby yielding a single enve-
lope-function that is shaped like a trumpet (Figure 5). The
breathing process is viewed as the movement of air into and
out of this trumpet since airways and alveoli expand and
contract uniformly. The model was developed for stable and
monodisperse particles. The transport of inhaled particles
occurs via convective and diffusive processes while their ulti-
mate deposition along the axis of the trumpet takes place by
mixing between tidal air and reserve air volume as de-
scribed mathematically by mass balance equations using
various deposition mechanisms. The aerosol concentration
during breathing is found to be a function of airways depth
and time. Once the concentration is known, the deposition in
each region can be calculated.
Deterministic, asymmetric multiple-path models (MPPD)
Multiple-path lung deposition models were developed by the
Center for Health Research (CIIT, currently the Hamner Insti-
tutes for Health Sciences, Research Traingle Park, NC, USA).
The models are more realistic than single-path models be-
cause they are based on actual airway measurements rather
than on average values and thus consider the asymmetric
branching pattern of the lung. The theoretical approaches for
the MPPD model were described by Anjilvel and Asgharian. 28 Later, the multiple-path bronchial airway models have
been derived on the basis of the stochastic lung model. 12, 13
For each airway of the lung, particle concentrations are de-
termined as a function of time for the proximal and distal
ends. Knowing the concentration of particles at the proximal
end of an airway, the concentration at its distal end is calcu-
lated by considering the deposition efficiencies for the vari-
ous deposition mechanisms.
Stochastic, asymmetric generation models
The stochastic nature of the lung structure that is, the variabil-
ity in morphometric, physiologic, and histologic parameters
used for lung dosimetry may cause significant variations in
dose calculations at the cellular level. Such parameter vari-
ability is dealt mathematically by stochastic models, in which
these parameters are selected randomly from their probabil-
ity distributions using Monte Carlo methods. Inhaled particles
are transported through this stochastic airway structure by
randomly selecting a sequence of airways for each particle
until deposition occurs. A fully stochastic deposition model
(IDEAL), simulating the trajectories of single particles was
presented by Koblinger and Hofmann 6 and Hofmann and
Koblinger, 14 and further developed by Hofmann et al. 13, 29,
30, 31 By simulating the random paths of many particles, typi-
cally of the order of tens of thousand trajectories, statistical
means can be calculated for total, regional and generation-
by generation deposition.
Computation fluid dynamics (CFD)-based model
Contrary to the whole lung model, CFD models utilize de-
tailed three-dimensional fluid flow and particle transport
equations. The airways are divided into small volumetric ele-
ments allowing the calculation of local deposition for each
airway surface element. Detailed airway geometry including
axial and lateral airway surface morphological variations
can be incorporated in a CFD model. A CFD model utilizes
transport equations and solves them simultaneously assuming
major deposition mechanisms and symmetric flow conditions.
55 | theHealth | Volume 2 | Issue 2
Lung deposition predictions of airborne particles
Figure 5: Schematic illustration of a trumpet shaped lung model 27
Most CFD based aerosol deposition models address the oro-
nasal and upper respiratory tracts (to generations 5-6) only,
and some focus on the alveolar regions only. These models
still needed validation based on fundamental principles.
Deposition patterns in human airways
The shape of deposition patterns strongly depends on the
inhaled particle sizes, breathing pattern and the lung airway
geometry. Generally speaking, lung deposition is a superpo-
sition of two separate deposition patterns - sedimentation as
well as impaction for submicron particles and diffusion for
nanometer-sized particles. As deposition decreases with
smaller submicron particle diameter, it reaches a minimal
deposition efficiency at the intersection between the two pat-
terns. With further decrease in particle size into the nanome-
ter scale, deposition picks up again as one proceeds towards
the alveolar domain (Figure 6). Due to consideration of real-
istic airway geometry that is, with a rounded carinal ridge
and smooth transitions between the parent and daughter
branches, deposition preferentially takes place at the bifur-
cation sites. Characteristic inspiratory deposition patterns as
a result of sitting breathing conditions are shown in Figure 7
for 0.2 and 5 µm diameter unit density particles near the
vicinity of the carinal ridge. The submicron, 0.2 µm particle
size is characteristic of cigarette smoke and radon progeny
attached to indoor aerosols, whereas the large, 5 µm size is
commonly observed in urban environments or produced by
therapeutic inhalation devices. The deposition patterns for
both particle sizes result in the formation of hot spots at the
top and bottom parts of the central bifurcation zone where
the cross sectional area is decreasing downstream into the
daughter branches.
Identification of high density area (hot spots)
Deposition fractions are analyzed in a way that enhancement
factors are used to account for such high density areas. The
enhancement factor is defined as the ratio of the maximum
number of deposited particles per unit area to the number of
deposited particles in the whole bifurcation surface area.
Thus, enhancement in the carinal ridge of central airways
attain values that range from 50 to 400. 33 These values
indicate that there are areas within the bifurcation where the
local dose caused by aerosolized air pollutants can be more
than two orders of magnitude higher than the average dose.
The probability of occurrence of such high density areas in-
creases with growing particle size where inertial impaction
becomes the more dominant deposition mechanism. 33
Factors affecting deposition
Effect of particle size
The preferential deposition sites in terms of deposition frac-
tion in different regions of the lung as a function of particle
diameter are shown in Figure 6. Total Deposition Fraction
(TDF) increases for large particle (> 0.4 µm) and for small
particle sizes (< 0.2 µm) for a given breathing pattern. The
most common one found in publications related to deposition
is that particles in the range of 1-5 µm are deposited in the
deep lungs (BB and bb airways); while UF and coarse (>5
µm) particles generally deposited in the ET region. 34-37
theHealth | Volume 2 | Issue 2 | 56
Figure 6: Average predicted total and regional lung deposition
based on ICRP 1 deposition model for nose breathing for light
exercise breathing condition. Highest deposition (ET region for 0.001
and 10 µm particles, bronchi region for 0.005 to 0.007 µm particles
and alveolar region for 0.01 to 0.05 µm particles).
Figure 7:
a) Illustrations of carinal
ridges in vivo taken during
broncho-fiberscope
examinations 32 b) Projected
inspiratory spatial deposition
patterns and related
deposition efficiencies for
particle diameter 0.2 and 5
µm in a physiologically
realistic model bifurcation on
the basis of 100, 000
randomly selected particles.
Where A and B are two
daughter airways. 33
Lung deposition predictions of airborne particles
Studies by Newman and Chan suggest that a particle size of
3 µm as an upper limit for related deposition in the deep
lungs. 38 Whereas, the deposition of the smaller particles
take place in the smaller airways (peripheral lung region).
Effect of flow rate
Flow rate is an index for representing the breathing intensity
of human lung ventilation that is, the volume of air inspired or
exhaled per unit of time. Deposition fractions of inhaled par-
ticulates are significantly influenced by this flow rate, which
varies with activity level and age of a person. The ICRP has
defined four different breathing conditions and relevant flow
rates according to the human activity condition, i.e. sleeping,
sitting, light exercise and heavy exercise breathing conditions
with flow rates of 15, 18, 50, and 100 L/min respectively.
The flow rate itself exerts different effects on the deposition
of fine (< 0.2 µm) and coarse (> 0.4 µm) particle sizes. The
deposition fraction decreases with an increase of flow rate
for fine particle and increases for coarse particles for both
nasal and oral breathing conditions (Figure 8).
Effect of age and gender
As a person ages, anatomical changes of the respiratory
tract also affect deposition fraction. 39 When ventilatory
conditions are held constant, age dependent changes in mor-
phology of the lung results in a decrease of the deposition
fraction with age (Figure 9 and 10). For any person, de-
creasing lung volume not only increases the deposition frac-
tion but also causes the major site of particle deposition
within the airways to shift from the lung periphery to more
central airways. 40 At low lung volumes, airways have
smaller cross-sectional areas, higher linear velocities, and thus
enhanced deposition by impaction in central airways for a
given flow rate. Children under 8 years old who are breath-
ing at rest have higher total, ET, and TB deposition fractions
and lower alveolar deposition fraction than adults. 41-44 The
studies conducted by Kim et al. 45 for young and elderly
suggest that healthy elderly subjects are not subjected to
greater lung deposition of ultrafine particulate matter than
younger ones.
Gender differences in laryngeal and airway geometries may
cause women to have greater upper airway deposition as
compared with men. 47 However, comparable to or smaller
deposition in woman than those of men in the deep lung is
found in studies by Kim et al. 48 Total lung deposition was
comparable between men and women for fine (0.1 to 2.5
µm) but was consistently greater in women than men for
coarse particles (>2.5 µm) regardless of the flow rates used:
it ranges from 9 to 31 % and are probably related to the
smaller dimensions of their upper airways and subsequent
enhancement of inertial impaction (Figure 10).
Ultrafine aerosols characteristics
Ultrafine (UF) aerosol constitutes the major concentration of
ambient aerosols. The major contributors of these aerosols
are the combustion aerosols emitting from motor vehicles. The
combustion aerosols contain heavy metals, including lead and
mercury. UF can produce toxicity even at low concentrations
due to their small size and surface characteristics. 49 The non-
soluble UF particles deposited in the pulmonary region (with
slow clearance mechanism) have sufficient time to penetrate
into interstitial region and ultimately accumulate there for
years. 50 The UF particles translocated to other organs can
interact with organs at the cellular level. The scientific commu-
nity is working hard to determine the mechanisms of these
interactions and their impact at the sub-cellular and molecu-
lar levels.
Conclusion
Presently, available deposition models predict almost similar
total, regional and to some extent, also local deposition. In g-
Figure 8: Nasal, oral and thoracic deposition fractions as function of
particle diameter during sleeping, sitting, light exercise and heavy
exercise breathing conditions calculated using stochastic lung
depositing code IDEAL.
Figure 9: Deposition fraction as a function of lung airway generation
for children of ages 5, 10, and 15 years and for adults for 3 µm
particle size under sitting breathing conditions. (modified 46)
57 | theHealth | Volume 2 | Issue 2
Lung deposition predictions of airborne particles
eneral, empirical and semi-empirical models are more reli-
able predictive tools than the theoretical models. However,
the stochastic lung deposition model takes care of the sto-
chastic nature of the lung structure and particle transport
within the lung thereby providing information about the sta-
tistical distribution of deposition pattern, reflecting intra and
inter subject variability in particle deposition. The results ob-
tained with different modeling approaches reveal that the
structure of the deposition patterns strongly depends on the
flow rates and the inhaled particle sizes. The deposition pat-
terns reveal enhanced deposition at the top and bottom parts
of a central bifurcation unit for all particle sizes, even for
nanometer-sized ultrafine particles and flow rates. TDF in-
creases for both large particle sizes (> 0.4 µm) and for small
particle sizes (< 0.2 µm) for a given breathing pattern. Chil-
dren exhibit higher deposition efficiency than adults for all
inhalable particle size ranges and states of activity. Similarly,
females are consistently found to have greater deposition
than men for coarse particles regardless of flow rates.
Acknowledgements
The authors wish to thank Prof. Werner Hofman and Dr.
Renate Winkler-Heil for their support in modifying and using
the IDEAL code.
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