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Computer Simulations of Particle Deposition in the
Developing Human Lung
a
b
Cynthia J. Musante & Ted B. Martonen
a
Curriculum in Toxicology , University of North Carolina , Chapel Hill , North
Carolina , USA
b
Experimental Toxicology Division , National Health and Environmental Effects
Research Laboratory, U.S. Environmental Protection Agency , Research Triangle Park ,
North Carolina , USA
Published online: 27 Dec 2011.
To cite this article: Cynthia J. Musante & Ted B. Martonen (2000) Computer Simulations of Particle Deposition
in the Developing Human Lung, Journal of the Air & Waste Management Association, 50:8, 1426-1432, DOI:
10.1080/10473289.2000.10464176
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MT Eu Cs aH nNt eI Ca An Ld PM Aa Pr tEo Rn en
ISSN 1047-3289 J. Air & Waste Manage. Assoc. 50:1426-1432
Copyright 2000 Air & Waste Management Association
Computer Simulations of Particle Deposition in
the Developing Human Lung
Cynthia J. Musante
Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina
Ted B. Martonen
Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S.
Environmental Protection Agency, Research Triangle Park, North Carolina
ABSTRACT
INTRODUCTION
An age-dependent theoretical model has been developed
to predict PM dosimetry in children’s lungs. Computer
codes have been written that describe the dimensions of
individual airways and the geometry of branching airway
networks within developing lungs. Breathing parameters
have also been formulated as functions of subject age.
Our computer simulations suggest that particle size, age,
and activity level markedly affect deposition patterns of
inhaled air pollutants. For example, the predicted lung
deposition fraction is 38% in an adult but is nearly twice
as high (73%) in a 7-month-old for 2-µm particles inhaled
during heavy breathing. Tracheobronchial (TB) and pul-
monary (or alveolated airways, P) deposition patterns may
also be calculated using the model. Due to different clear-
ance processes in the TB and P airways (i.e., mucociliary
transport and macrophage action, respectively), the de-
termination of compartmental dose is important for PM
risk assessment analyses. Furthermore, the results of such
simulations may aid in the setting of regulatory standards
for air pollutants, as the data provide a scientific basis for
estimating dose delivered to a designated sensitive sub-
population (children).
Children have been identified as a sensitive subpopula-
tion to be addressed in the determination of regulatory
1
standards for air pollutants. For a variety of reasons, how-
ever, experimental data describing the deposition patterns
2
of inhaled PM in children are rare. In the pharmaceuti-
cal industry, where the administration of aerosolized drugs
to children is increasing, age-dependent dosimetry infor-
3
mation is also lacking. The limited data available suggest
that children have greater deposition efficiencies than
4
,5
adults under resting conditions, a factor that may con-
tribute to increased health risk from airborne substances.
To aid in the risk assessment process, we have devel-
oped an age-dependent mathematical model that de-
scribes the behavior and fate of inhaled particles in human
lungs. Knowledge of particle deposition and clearance is
a first step in understanding the biological mechanisms
that lead to adverse health effects. Therefore, the model,
which has been validated by comparison with experimen-
tal data from adult subjects, may provide additional in-
sight into health risks associated with inhalation exposure
to PM.
METHODS
A physiologically realistic mathematical model describ-
ing particle deposition in the developing human lung has
IMPLICATIONS
Children have been identified as a sensitive subpopula-
tion to be addressed in the determination of regulatory
standards for air pollutants. To aid in this process, we
have developed an age-dependent mathematical model
that describes the behavior and fate of inhaled particles
in human lungs. Our results suggest that when differences
in deposition fraction, ventilation rate, and cumulative air-
way surface area are taken into account, children may
receive a localized dose that is 3 times higher than adults
receive. Therefore, children may experience increased
injury to the cells that line the respiratory tract as com-
pared with adults in the same exposure environment.
6
previously been reported. Age-dependent lung morpholo-
7
gies are based on the descriptions of Hofmann for the
8
tracheobronchial (TB) airways and of Dunnill for the
alveolated, or pulmonary (P), region. The number of TB
airways is considered fixed at birth, but the number of P
airways changes as the lung develops. We refer the reader
to other age-dependent lung morphologies and particle
9
–11
deposition codes that have been proposed
and com-
6
parisons that have been summarized elsewhere.
Data in Table 1 were used to simulate sedentary and
heavy human activity levels and corresponding variations
1426 Journal of the Air & Waste Management Association
Volume 50 August 2000

Musante and Martonen
Table 1. Definition of age-dependent breathing patterns for sedentary and heavy human activity levels.
Sedentary Heavy
given in Figures 4–6. Depo-
sition fractions are mass-
based (assuming unit
densities and spherical par-
ticles), and are normalized to
the amount entering the tra-
chea. This normalization
was performed because the
experimental data used as
comparison with the origi-
nal dosimetry model for
Age (months)
Flow Rate (mL/sec)
Tidal Vol. (mL)
Flow Rate (mL/sec)
Tidal Vol. (mL)
7
49
78
42
84
600
810
222
308
2
4
9
3
2
8
112
159
234
152
266
500
1070
1368
2007
460
8
903
60
2449
in respiratory parameters as a function of age. The values
adults were presented in that format.
7
,11
are based on equations formulated by Hofmann.
For sedentary breathing and each monodisperse aero-
sol considered, the predicted lung deposition fraction was
highest for the 22- and 48-month-olds, and lowest for
the adult. This was in contrast to heavy respiratory activ-
ity, wherein lung deposition generally decreased with age
for each particle size category.
A variety of monodisperse aerosols were studied, rang-
ing from 0.25 to 5.0 µm unit density spheres. These par-
ticle diameters were chosen to reflect typical constituents
of ambient PM. Deposition of a polydisperse aerosol with
a log-normal particle size distribution was also consid-
ered. The residual oil fly ash (ROFA) aerosol, an emission
source particulate pollutant, was assumed to have a mass
median aerodynamic diameter of 1.95 µm, a geometric
standard deviation of 2.19, and a count median diameter
TB deposition also decreased with age, for both venti-
latory states. P deposition was generally highest for the 48-
and 98-month-olds under resting conditions, but was an
increasing function of age during enhanced respiration.
The effect of physical activity level on PM deposition
was largely dependent upon particle size. For example,
when going from a resting to an active state within a par-
ticular age group, TB deposition decreased by approxi-
mately one-half for 0.25-µm particles, but increased nearly
2-fold for an aerosol composed of 5-µm particles. The former
effect (i.e., halving) is due to the reduction in residence
times of particles within the conducting airways, resulting
3
of 0.53 (assuming a particle density of 0.34 g/cm ).
RESULTS AND DISCUSSION
Monodisperse Aerosol Deposition
Lung (L = TB + P), TB, and P deposition fractions are shown
in Figures 1–3, respectively, as a function of particle di-
ameter and subject age for sedentary breathing conditions.
Corresponding charts for increased (heavy) activity are
1.00
1.00
0
0
0
0
.75
7
2
mos.
2 mos.
.50
.25
.00
48 mos.
8 mos.
adult
9
0.25 0.50 0.75 1.00
2.00 3.00 4.00 5.00
Particle Diameter (µm)
Figure 1. Lung (TB and P) deposition in the developing human lung under sedentary conditions (see Table 1).
Volume 50 August 2000
Journal of the Air & Waste Management Association 1427

Musante and Martonen
1
.00
1
0
0
0
0
.00
.75
.50
.25
.00
7
2
mos.
2 mos.
48 mos.
8 mos.
adult
9
0.25 0.50 0.75 1.00 2.00 3.00 4.00 5.00
Particle Diameter (µm)
Figure 2. TB deposition in the developing human lung under sedentary conditions (see Table 1).
1
0
0
0
0
.00
.75
.50
.25
.00
7
2
mos.
2 mos.
48 mos.
8 mos.
9
adult
0
.25 0.50 0.75 1.00 2.00 3.00 4.00 5.00
Particle Diameter (µm)
Figure 3. P (alveolated airways) deposition in the developing human lung under sedentary conditions (see Table 1).
1428 Journal of the Air & Waste Management Association
Volume 50 August 2000

Musante and Martonen
1
0
0
0
0
.00
.75
.50
.25
.00
7
2
mos.
2 mos.
48 mos.
8 mos.
adult
9
0
.25 0.50 0.75 1.00 2.00 3.00 4.00 5.00
Particle Diameter (µm)
Figure 4. Lung deposition in the developing human lung under increased (heavy) activity (see Table 1).
1
0
0
0
0
.00
.75
.50
.25
.00
7
2
mos.
2 mos.
48 mos.
8 mos.
adult
9
0
.25 0.50 0.75 1.00 2.00 3.00 4.00 5.00
Particle Diameter (µm)
Figure 5. TB deposition in the developing human lung under increased (heavy) activity (see Table 1).
Volume 50 August 2000
Journal of the Air & Waste Management Association 1429

Musante and Martonen
1
0
0
0
0
.00
.75
.50
.25
.00
7
2
mos.
2 mos.
48 mos.
8 mos.
adult
9
0
.25 0.50 0.75 1.00 2.00 3.00 4.00 5.00
Particle Diameter (µm)
Figure 6. P (alveolated airways) deposition in the developing human lung under increased (heavy) activity (see Table 1).
in decreased probabilities of deposition by diffusion (the
primary deposition mechanism for submicron particles).
The latter characteristic (i.e., doubling) is due to the in-
creased effectiveness of the inertial impaction mechanism
at high flow rates. This, of course, affects the deposition
patterns of PM downstream, in distal pulmonary airways.
The filtering of the 5-µm particles in the TB region at the
higher flow rate resulted in a decrease in P deposition as
compared with the sedentary state. For the submicron
This suggests that deposition is skewed toward the
alveolated airways under resting conditions but is con-
centrated in the conducting airways during enhanced
ventilation. TB ROFA deposition increased by a factor of
2 during periods of exercise or heavy breathing, while pul-
monary deposition decreased. This phenomenon may
contribute to the exacerbation of upper respiratory ill-
1
2
nesses such as asthma in children exposed to ambient
PM. Environmental factors, including physical location,
breathing zones, and oxygen consumption, may also lead
(0.25 µm) case, because a greater percentage of particles
1
3
reach the pulmonary region during heavy activity, P depo-
sition fractions for the resting and active states are actu-
ally quite similar.
to greater susceptibility in children.
Care must be taken when making comparisons of
deposition between age groups. Our analyses so far have
been made in terms of “deposition fraction,” defined as
the number (or mass) of particles deposited divided by
the total number (or mass) of particles entering the tra-
chea. While this term is useful in the study of qualitative
differences in aerosol deposition behavior, it is just one
component of a complex interplay of parameters affect-
ing quantitative estimates of deposition. Differences in
minute ventilation and cumulative airway surface area
must also be considered when making predictions of ROFA
deposition for PM risk assessments.
Polydisperse Aerosol Deposition
In Figure 7, deposition of ROFA within the lungs of a 4-
year-old subject is shown as a function of respiratory in-
tensity and airway generation. This figure is included to
illustrate shifts in regional deposition that may occur with
changes in ventilation. For example, based on this data,
the predicted mass-based deposition fraction (TB + P) was
similar for sedentary (30%) and heavy (35%) conditions,
but the regional doses differed considerably. The TB/P ra-
tio, an indicator of uniformity of PM deposition, was 0.676
for the sedentary case and 3.193 for enhanced respiration.
In Figure 8, a comparison of inhalation rate (i.e., aero-
sol volume inspired per hour), cumulative airway surface
1430 Journal of the Air & Waste Management Association
Volume 50 August 2000

Musante and Martonen
PM risk assessment analyses, as it suggests that although
the total body burden of ROFA may be higher in adults,
the localized dose (i.e., the mass distribution to the cells
that line the respiratory tract) may be lower. This can be
seen in Figure 9, where the deposition rate and the nor-
malized deposition rate (i.e., the deposition rate divided
by the cumulative airway surface area) are compared for
each age group.
Specifically, assuming sedentary activity levels, the
ROFA deposition rate is 8 µg/hr for the 4-year-old, com-
pared to 12 µg/hr in the adult, whereas the deposition
rate per unit surface area is 3 times higher in the child.
This difference in localized ROFA concentration suggests
that children may experience increased injury to the cells
that line the respiratory tract as compared with an adult
in the same exposure environment.
0
.05
0
.04
.03
.02
0
0
Heavy
0
.01
0
Sedentary
0
2
4
6
8
1
0
1
2
1
Airway Generation
4
1
6
1
8
2
0
22
Figure 7. Mass-based deposition fractions for a ROFA aerosol in the
lungs of a 4-year-old subject as a function of airway generation and
respiratory intensity (see Table 1). The TB region includes generations
0
–16, whereas generations 17–23 are considered to be P (alveolated)
airways.
SUMMARY
area (SA), and lung deposition fraction is given for the
ROFA aerosol described above, assuming sedentary
breathing conditions. In general, deposition fraction
decreases with age, whereas SA and ventilation rate in-
crease with age. To fully understand the complex inter-
action of these parameters, the data in Figure 8 were used
to calculate the mass-based ROFA deposition rate (i.e.,
the total mass of ROFA deposited per hour) for each age
The physiologically realistic dosimetry model presented
herein agrees with experimental data from inhalation
exposure experiments in adults. The model has a wide
variety of input and output options. Input parameters
include aerosol characteristics (e.g., particle size and den-
sity), lung morphology (e.g., human or laboratory ani-
mal, adult or child), and breathing pattern (e.g., tidal
volume and frequency). Data output, in terms of aerosol
deposition fractions, may be calculated at desired levels
of spatial resolution; that is, lung, compartmental (TB and
P), and localized (airway-by-airway).
3
group, assuming an ambient concentration of 65 µg/m .
The deposition rate monotonically increased with age,
ranging from ~3 µg/hr in the youngest child to 12 µg/hr
in the adult. One should consider, however, that the to-
tal airway surface area is an order of magnitude higher
in the adult model. This has immediate implications for
Although deposition in the thoracic airways is affected
by many factors, some specific observations can be made
regarding the effects of subject age.
•
•
•
Lung (TB + P) deposition fraction was generally
higher in children than adults. The differences
may be significant, depending on particle size,
respiratory intensity, and subject age.
9
8
7
6
5
4
3
2
1
00000
00000
00000
00000
00000
00000
00000
00000
00000
0
0.35
The TB deposition fraction was a monotonically
decreasing function of age for both sedentary and
heavy respiratory activity levels and all particle
sizes considered.
The P deposition fraction was highest in the 48-
and 98-month-old subjects under resting con-
ditions for all particle sizes examined, but was
an increasing function of age during enhanced
activity.
0
0
0
0
.3
.25
.2
.15
Airway surface area
Inhalation rate
0.1
Lung dep. fraction
0
.05
•
•
For a 4-year-old child, ROFA deposition was
skewed toward the alveolated (P) airways under
sedentary conditions, but was concentrated in the
conducting (TB) airways during heavy activity.
When ventilation rate and cumulative airway sur-
face area are considered, children may receive a
localized dose that is 3 times higher than adults
receive.
0
7
22
48
98
ad
ult
Age (months)
Figure 8. Comparison of ventilation rate, cumulative airway surface
area, and mass-based lung deposition fraction for a ROFA aerosol for
each age group under resting conditions (see Table 1).
Volume 50 August 2000
Journal of the Air & Waste Management Association 1431

Musante and Martonen
0
.0003
14
1
1
8
6
4
2
0
2
0
0
0
0
.00025
0
.0002
Normalized
deposition rate
Deposition rate
.00015
.0001
0
.00005
0
7
22
48
98
ad
ult
Age (months)
Figure 9. Total ROFA mass deposited in the lung per hour (line plot) normalized to total airway surface area (columns) for each human subject age
3
under resting conditions (see Table 1). The ambient ROFA concentration was assumed to be 65 µg/m .
on Deposition and Clearance of Aerosols in the Human Respiratory Tract;
Hofmann, W., Ed.; Salzburg, Austria, 1986; pp 18-22.
These validated theoretical models may provide additional
insight into PM distribution in the developing human lung,
and may thereby aid in the integration of children into
risk assessment protocols for particulate air pollutants.
5. Schiller-Scotland, C.F.; Hlawa, R.; Gebhart, J. Experimental Data for
Total Deposition in the Respiratory Tract of Children; Toxicol. Lett.
1
994, 72, 137-144.
6.
Martonen, T.B.; Graham, R.C.; Hofmann, W. Human Subject Age and
Activity Level: Factors Addressed in a Biomathematical Deposition
Program for Extrapolation Modeling; Health Phys. 1989, 57, 49-59.
Hofmann, W. Mathematical Model for the Postnatal Growth of the
Human Lung; Respiration Physiol. 1982, 49, 115-129.
7
.
ACKNOWLEDGMENTS
C.J. Musante was funded by the U.S. Environmental Pro-
tection Agency/University of North Carolina Toxicology
Research Program, Training Agreement CT902908, with
the Curriculum in Toxicology, University of North Caro-
lina at Chapel Hill.
8. Dunnill, M.S. Postnatal Growth of the Lung; Thorax 1962, 17, 329-
333.
9
.
Phalen, R.F.; Oldham, M.J.; Beaucage, C.B.; Crocker, T.T.; Mortensen,
J.D. Postnatal Enlargement of Human Tracheobronchial Airways and
Implications for Particle Deposition; The Anatomical Record 1985, 212,
368-380.
1
1
0. Xu, G.B.; Yu, C.P. Effects of Age on Deposition of Inhaled Aerosols in
the Human Lung; Aerosol Sci. Technol. 1986, 5, 349-357.
1. Hofmann, W.; Martonen, T.B.; Graham, R.C. Predicted Deposition of
Nonhygroscopic Aerosols in the Human Lung as a Function of Age; J.
Aerosol Med. 1989, 2, 49-68.
2. Koren, H.S. Associations between Citeria Air Pollutants and Asthma;
Environ. Health Perspect. 1995, 103, 235-242.
DISCLAIMER
1
This manuscript has been reviewed in accordance with
the policy of the National Health and Environmental Ef-
fects Research Laboratory and the U.S. Environmental
Protection Agency, and has been approved for publica-
tion. Approval does not signify that the contents neces-
sarily reflect the views and policies of the agency, nor does
mention of trade names or commercial products consti-
tute endorsement or recommendation for use.
13. Bearer, C.F. How Are Children Different from Adults? Environ. Health
Perspect. 1995, 103, 7-12.
About the Authors
C.J. Musante, Ph.D., is a postdoctoral trainee with the Cur-
riculum in Toxicology at the University of North Carolina at
Chapel Hill, c/o U.S. Environmental Protection Agency, Mail
Drop 74 ETD NHEERL, Research Triangle Park, NC 27711;
e-mail: musante.cynthia@epa.gov. T.B. Martonen, Ph.D., is
a senior research scientist in the Experimental Toxicology
Division with the National Health and Environmental Effects
Research Laboratory at the U.S. Environmental Protection
Agency, Mail Drop 74, Research Triangle Park, NC 27711;
e-mail: martonen.ted@epa.gov.
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Volume 50 August 2000