Effect of microgravity and hypergravity on deposition of 0.5- to 3

Effect of microgravity and hypergravity on deposition
of 0.5- to 3-µm-diameter aerosol in the human lung
CHANTAL DARQUENNE,1 MANUEL PAIVA,2 JOHN B. WEST,1 AND G. KIM PRISK1
of Medicine, University of California, San Diego, La Jolla, California 92093-0931;
and 2Biomedical Physics Laboratory, Université Libre de Bruxelles, Brussels, Belgium
1Department
aerosol deposition; gravity; human lung
in the human lung is
primarily due to the mechanisms of inertial impaction,
sedimentation, and Brownian diffusion. Inertial impaction causes most of the particles .5 µm to deposit in the
upper airways. Brownian diffusion affects smaller particles (,0.5 µm), which deposit mainly in the alveolar
region. Sedimentation is the gravitational settling of
particles and mainly affects particles in the size range
1–5 µm. Of these three mechanisms, sedimentation is a
gravitation-dependent process and is therefore expected to be changed in altered gravity (G) environments. Besides affecting sedimentation, G is also responsible for regional differences in ventilation. Because the
lung distorts under its own weight, the alveoli at the
base of the lung are relatively compressed compared
with the apical alveoli, and, because poorly expanded
alveoli are more compliant, ventilation is greatest near
the bottom of the lung and becomes progressively
reduced near the top. Changes in the G level (i.e., in
lung weight) will affect the distribution of ventilation
and are therefore expected to affect the distribution and
deposition of aerosols.
In a theoretical analysis in 1967, Muir (15) examined
the influence of G on aerosol deposition in the lungs of
subjects on the surface of the moon (1⁄6 G) for particle
sizes up to 8 µm. On the basis of knowledge of such
deposition on Earth, he predicted a reduction in the
THE DEPOSITION OF AEROSOLS
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overall deposition but an increase in deposition in the
alveolar region. He suggested, therefore, that astronauts might be more susceptible to infection by bacteria penetrating more deeply into the lung. Beeckmans
(2) developed a computer program based on experimental data available at 1 G to predict deposition within the
respiratory tract. He computed deposition for particle
size ranging from 0.2 to 15 µm at decreased G levels,
and his computations suggested a lower alveolar deposition than that suggested by Muir (15) at 1⁄6 G.
Hoffman and Billingham (13) conducted the only experimental study to date to obtain deposition data at
various G levels on a National Aeronautics and Space
Administration (NASA) LearJet. They measured the
deposition of only 2-µm-diameter particles in three
different subjects. They found an almost linear increase
in deposition, with increasing G in the range 0–2 G.
However, at 0 G, deposition was lower than that
predicted by Beeckmans (2). Thus the amount of deposition of aerosol particles of different sizes in the absence
of G is largely unknown.
In a spacecraft environment, the potential for significant airborne particle concentrations is high because
the environment is closed and no sedimentation occurs.
Measurements in the US Space Shuttle air environment have shown a substantial increase in microbial
counts during missions (9, 14), and a large variety of
airborne particles, including hair, food, paint chips, and
synthetic fibers, has been found. It is therefore of
considerable interest to determine the fate of inhaled
aerosols in an environment that has altered gravitational levels, and hence altered deposition, and a
potentially large airborne particulate load. Furthermore, many drugs are now administered by aerosolized
drug-delivery systems, and a further understanding of
how gravity affects aerosol deposition is clearly desirable in the terrestrial environment.
In the present study, we measured total deposition in
normal subjects of aerosols having a diameter spanning
the range from 0.5 to 3 µm. Data were collected on the
ground (in 1 G) and aboard the NASA Microgravity
Research Aircraft during parabolic flights in both the
weightless phase (microgravity; µG) and the ,1.6-G
pullout phase. The data are compared with the previous studies (2, 13, 15) and with predicted numerical
values from Darquenne and Paiva’s model (3). The
comparison of data obtained in µG and ,1.6 G with
deposition at 1 G helps to elucidate the impact of
gravitational sedimentation on deposition processes.
For convenience, the ,1.6 G condition will be referred
to as 1.6 G in the text.
0161-7567/97 $5.00 Copyright r 1997 the American Physiological Society
2029
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Darquenne, Chantal, Manuel Paiva, John B. West,
and G. Kim Prisk. Effect of microgravity and hypergravity
on deposition of 0.5- to 3-µm-diameter aerosol in the human
lung. J. Appl. Physiol. 83(6): 2029–2036, 1997.—We measured intrapulmonary deposition of 0.5-, 1-, 2-, and 3-µmdiameter particles in four subjects on the ground (1 G) and
during parabolic flights both in microgravity (µG) and at ,1.6
G. Subjects breathed aerosols at a constant flow rate (0.4 l/s)
and tidal volume (0.75 liter). At 1 G and ,1.6 G, deposition
increased with increasing particle size. In µG, differences in
deposition as a function of particle size were almost abolished. Deposition was a nearly linear function of the G level
for 2- and 3-µm-diameter particles, whereas for 0.5- and
1.0-µm-diameter particles, deposition increased less between
µG and 1 G than between 1 G and ,1.6 G. Comparison with
numerical predictions showed good agreement for 1-, 2-, and
3-µm-diameter particles at 1 and ,1.6 G, whereas the model
consistently underestimated deposition in µG. The higher
deposition observed in µG compared with model predictions
might be explained by a larger deposition by diffusion because
of a higher alveolar concentration of aerosol in µG and to the
nonreversibility of the flow, causing additional mixing of the
aerosols.
2030
GRAVITY AND AEROSOL DEPOSITION
METHODS
Subject
No.
Gender
Age,
yr
Height,
cm
Weight,
kg
FVC,
%pred
FEV1/FVC,
%pred
1
2
3
4
F
F
M
M
29
26
45
39
164
163
191
185
62
67
95
108
108
114
121
104
97
86
98
108
F, female; M, male; FVC, forced vital capacity; FEV1, forced
expiratory volume in 1 s; pred, predicted.
Instrument, DAQ700) was used for data acquisition. Signals
from the photometer, a G sensor, a barometric pressure
transducer, and the pneumotachograph were sampled at 100
Hz. Custom software was developed for the data acquisition
by using National Instruments Lab Windows CVI.
Data were collected on the ground and aboard the NASA
Microgravity Research Aircraft. A typical flight consisted of a
climb to an altitude of ,10,000 m with the cabin pressurized
to ,600 Torr. A ‘‘roller-coaster’’ flight profile was then performed. The aircraft was pitched up at 1.6 Gz to a 45°
nose-high attitude. Then, the nose was lowered to abolish
wing lift, and thrust was reduced to balance drag (thus
maintaining µG). A ballistic flight profile resulted and was
maintained until the aircraft’s nose was 45° below the
horizon. In this manner, µG was maintained for ,27 s. An
averaging 1.6-Gz pullout maintained for ,40 s caused the
nose to pitch up to a 45° nose-high attitude and allowed the
cycle to be repeated.
Subjects and protocol. Four healthy subjects participated
in the study. Their relevant anthropometric data are listed in
Table 1. They were asked to breathe through the mouthpiece
at a constant flow rate (,0.4 l/s) and tidal volume (,0.75
liter) over a period covering the duration of four parabolas
including the hyper-G phase between maneuvers. A flowmeter provided visual feedback to the subject, and an audible
metronome was used to maintain a constant breathing frequency. This protocol was repeated twice with each particle
size. Before the flight, a set of data was also collected on the
ground (1 G) with the same protocol. The protocol was
approved by both the Committee on Investigations Involving
Human Subjects at the University of California, San Diego,
and by the Human Research Policy and Procedures Committee at the Johnson Space Center, Houston, TX.
Data analysis. For each breath, total deposition (DE) was
calculated by using the following equation
DE 5 1 2
Fig. 1. Schematic representation of experimental setup. Subject
breathes aerosol from a reservoir. A 2-way nonrebreathing valve
allows subject to inhale from reservoir and to exhale into room
through a filter. An additional 3-way valve is connected to inhalation
port of nonrebreathing valve, allowing subject to breathe pure air
through a filter before start of experiment. Measurement of aerosol
concentration and flow rate is provided by a photometer and a
pneumotachograph (Fleisch no. 1), respectively. A diffusion dryer is
located between photometer and mouthpiece to remove water vapors
from exhaled air.
Nex
Nin
p
Vin
Vex
(1)
where Nin and Nex are the number of inspired and expired
particles, and Vin and Vex are the inspired and expired
volumes, respectively. Only the breaths where Vin and Vex
differed by ,3% were considered in the analysis. For the data
acquired during the flights, we excluded from the analysis the
breaths occurring during the transition from µG to 1.6 G and
from 1.6 G to µG as well as the first breath after each
transition because these breaths were considered likely to
contain data from different and unknown gravitational loadings.
Statistical analysis was performed by using Systat V5.0
(Systat, Evanston, IL). Data were grouped in three categorial
variables: G level (µG, 1 G, and 1.6 G), particle size (0.5-, 1-,
2-, and 3 µm), and subject (subjects 1–4). A two-way analysis
of variance was then performed to test for differences between
the chosen categorial variables. Post hoc testing by using
Bonferroni adjustment was performed for tests showing
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Equipment. Deposition data were collected by using the
equipment shown in Fig. 1. The subject breathed aerosol from
a reservoir at constant inspiratory and expiratory flow rates
(,0.4 l/s) and tidal volume (,0.75 liter). A two-way nonrebreathing valve (NRV) allowed the subject to inhale from the
reservoir and to exhale into the room through a filter. An
additional three-way valve was connected to the inhalation
port of the NRV, allowing the subject to breathe pure air
through a filter before the start of the experiment. The
measurement of the aerosol concentration and the flow rate
was provided by a photometer (model 993000, Pari) (24) and a
Validyne M-45 differential pressure transducer connected via
short tubes to the two ports of a pneumotachograph (Fleisch
no. 1, OEM Medical, Richmond, VA), respectively. The photometer, the pneumotachograph, and the NRV were heated to
body temperature to prevent water condensation. A diffusion
dryer was located between the photometer and the mouthpiece. It removed the water vapor from the exhaled air to
avoid condensation on the lenses of the photometer.
Aerosol generation. The reservoir was filled with aerosol
containing monodisperse polystyrene latex particles (Duke
Scientific). The particles were supplied in suspension (water),
and the concentrate was diluted and dispensed via two Acorn
II nebulizers (Marquest Medical Products). Before entering
the reservoir, the aerosol flowed through a heated hose and a
diffusion dryer to remove water droplets. The following
particle sizes, as provided by the manufacturer, were used in
the study: 0.497 6 0.0094, 1.07 6 0.014, 2.04 6 0.044, and
2.92 6 0.081 (SD) µm. For convenience, these are hereafter
referred to as 0.5-, 1-, 2-, and 3-µm-diameter particles,
respectively. The aerosol concentrations were ,104 particles/ml of air for 0.5- and 1-µm particles, ,5 3 103 particles/ml of air for 2-µm particles, and ,103 particles/ml of air
for 3-µm particles.
Data recording and analysis. A PC (IBM ThinkPad 360
CSE) equipped with a 12-bit analog-to-digital card (National
Table 1. Anthropometric data
GRAVITY AND AEROSOL DEPOSITION
significant F-ratios. Significant differences were accepted at
the P , 0.05 level.
RESULTS
The effect of G level and particle size on deposition is
displayed in Fig. 2. In Fig. 2A, total deposition averaged
over the four subjects (mean 6 SD) is plotted as a
function of the particle size for each G level. In Fig. 2B,
deposition values are plotted as a function of the
particle size for each G level. The open symbols refer to
our data, and the closed circles refer to data obtained by
Hoffman and Billingham (13) by using 2-µm particles.
At 1 and 1.6 G, deposition is strongly size dependent,
with the greatest deposition occurring for the largest
particle sizes. Deposition ranged from 16.5 to 44.0% at
1 G and from 20.0 to 60.7% at 1.6 G. In µG, differences
in deposition between particle sizes are almost abolished, with deposition ranging from 12.9 to 14.9%.
For a given particle size, significant (P , 0.01)
variations from one G level to the other was found, with
lower deposition being present at lower G levels. Significant (P , 0.03) differences in deposition were also
present between different particle sizes at each G level,
except for the deposition of 2- and 3-µm particles in µG,
which was not different. Although differences are
smaller in µG, deposition of 0.5-µm particles was found
to be significantly larger than deposition of 1-µm
particles. Intrasubject variability is illustrated in Fig.
3, where total deposition in each subject is plotted as a
function of particle size for each G level. Intrasubject
variability was sufficiently low so that clear differences
in deposition were visible among G levels.
Our data were compared with numerical results
obtained by using a one-dimensional (1D) model developed by Darquenne and Paiva (3). In that model, a 1D
equation describing the transport and deposition of
aerosols is solved in a lung structure based on data of
Haefeli-Bleuer and Weibel (8). The main equations
used in the simulations are summarized in the APPENDIX. The comparison between the numerical and experimental results is shown on Fig. 4 for each G level. For
the experimental data, the mean values averaged over
the four subjects are displayed as well as the standard
deviation (SD; left bar of each pair), whereas the
numerical results (right bar of each pair) are shown
with the contribution of each mechanism of deposition
considered in the numerical simulations: impaction is
represented by the open segment, sedimentation by the
hatched segment, and diffusion by the solid segment. In
1 and 1.6 G, the experiments agree with the numerical
data within 1.5 SD, except in the case of 0.5-µm
particles in 1.6 G, for which the simulations predict a
lower deposition than we measured. In µG, the numerical data significantly underestimate measured deposition for each particle size except 3 µm. Although the
model underestimates deposition in µG, it should be
noted that the model predicts a minimum deposition for
1.0-µm-diameter particles, and this is consistent with
the experimental observations.
Figure 5 shows the total deposition values obtained
on the ground. In Fig. 5A, deposition data are shown for
each subject separately. They are represented by their
mean and SD, the SD being an indication of the
intrasubject variability. In Fig. 5B, our data averaged
over the four subjects (r) are compared with experimental data of Heyder et al. (11, 12): data obtained for a
tidal volume of 0.5 liter and a flow rate of 0.25 l/s (n)
and data obtained for a 1-liter tidal volume and a flow
rate of 0.5 l/s (o). Note that these protocols do not
exactly match ours in either flow rate or tidal volume.
The last set of data (k) in Fig. 5B refers to data
obtained in 20 subjects for a flow rate of 0.4 l/s and a
tidal volume of 0.8 liter (12), a protocol very similar to
ours, although these data are only available for 1- and
3-µm particles. For the purpose of clarity, this last set of
data has been slightly shifted to the right. Note that in
Fig. 5B, the SD in our data reflects both the intersubject and intrasubject variability.
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Fig. 2. Total deposition of aerosol particles (DE; mean 6 SD)
averaged over 4 subjects. A: total deposition as a function of particle
size. G, gravity. r, microgravity (µG); j, 1 G; l, ,1.6 G. B: total
deposition as a function of G level. s, 0.5 µm particle diameter (dp );
k, dp 5 1 µm; n, dp 5 2 µm; o, dp 5 3 µm; r, data from Hoffman and
Billingham obtained with 2-µm-diameter particles (13).
2031
2032
GRAVITY AND AEROSOL DEPOSITION
Fig. 3. Total deposition of aerosol particles
(mean 6 SD) for each subject as a function of
particle size for each G level. A-D: subjects
1–4, respectively; r, µG; j, 1 G; l, ,1.6 G.
Effect of gravity. Figure 2A shows the strong size
dependence of total deposition at 1 G and 1.6 G and the
virtual absence of such effect in µG. The analysis of
variance shows, however, that there is a small but
significant difference in deposition in µG for different
particle sizes, except for particles between 2 and 3 µm
in diameter. Although the deposition differences are
small, the much smaller data variability in µG makes
this difference significant. For 0.5- and 1-µm particles,
deposition increases less between µG and 1 G than
between 1 and 1.6 G, whereas deposition is an approximately linear function of G level for 2- and 3-µm
particles (Fig. 2B). This is in agreement with the work
of Hoffman and Billingham (13), who also found an
essentially linear increase in total deposition with
increasing G levels between 0 and 2 G for 2-µm
particles. They measured a deposition of 19.74, 33.47,
and 46.25% in µG, 1 G, and 2 G, respectively, compared
with 15.5 6 1.5, 37.1 6 8.5, and 52.4 6 7.2% in µG, 1 G,
and 1.6 G, respectively, in our experiments. For purposes of comparison, their data are plotted (r) in Fig.
2B. Although both sets of data show an almost linear
increase of deposition with increasing G level, the
increasing rate is higher in our study than in Hoffman
and Billingham’s study.
If the different mechanisms of deposition were independent, the change in G level would only affect
deposition by sedimentation, which is a gravitational
process. According to Stokes’ law, particles sediment
with a velocity (vs )
vs 5
rpd 2p
18µ
G
(2)
where rp is particle density, dp is particle diameter, and
µ is gas viscosity. With the assumption of an unlimited
source of aerosols, deposition by sedimentation should
increase linearly with G and in a quadratic way with dp.
For the biggest particles (2 and 3 µm), diffusion may be
neglected and deposition is mainly due to sedimentation in the distal airways and impaction in the upper
airways. Impaction is gravity independent and increases also in a quadratic way with dp (see Eq. A4). For
a given particle size, deposition by sedimentation should
increase linearly and deposition by impaction should be
constant. Therefore, total deposition should increase
linearly with G.
On the other hand, for a given G level, both deposition by sedimentation and impaction should vary in a
quadratic way with the particle size. Deposition by
impaction occurs in the upper airways and affects the
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DISCUSSION
GRAVITY AND AEROSOL DEPOSITION
2033
these small particles, a plausible explanation for the
results in µG might be a larger deposition by diffusion
because sedimentation is absent in µG. The absence of
deposition by sedimentation increases the aerosol concentration in the small airways, leaving a larger number of particles available for deposition by diffusion
and/or for being transported more deeply in the lung,
where deposition by diffusion may also occur. This is
reflected in the results of the simulation, which show a
much increased deposition component because of diffusion in µG compared with 1 and 1.6 G (Fig. 4). Deposition by diffusion decreases from 8.4% in µG to 7.3% at
1.6 G for 0.5-µm particles, from 5.6 to 3.6% for 1-µm
particles, from 3.8 to 1.4% for 2-µm particles, and from
3.0 to 0.6% for 3-µm particles. Despite this, deposition
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Fig. 4. Comparison between experimental data and numerical data
obtained within a 1-dimensional model (3). A-C: µG, 1 G, and 1.6 G,
respectively. For each particle size, left bar of each pair represents
experimental value, and right bar of each pair represents numerical
value with contribution of each mechanism of deposition; solid
segments, deposition by diffusion; hatched segments, deposition by
sedimentation; open segments, deposition by impaction.
number of particles available for deposition by sedimentation in the smaller airways. Thus the number of
particles available to deposit by sedimentation decreases with increasing particle size, and the use of Eq.
2 to describe total deposition is no longer as straightforward as it was for a given particle size at different G
levels.
As we would expect, deposition of 2- and 3-µm
particles varies almost linearly with altered G level
(Fig. 2). For 0.5- and 1-µm particles, however, if we
assume that the relationship between 1 and 1.6 G
defines the gravitational influence, then the extrapolation to µG predicts a deposition less than that measured, especially for 1.0-µm-diameter particles, where
deposition in µG would be expected to approach zero.
Because the deposition by impaction is negligible for
Fig. 5. Total deposition of aerosol particles measured at 1 G. A:
deposition (mean 6 SD) for each subject. Tidal volume (VT ) is 0.75
liter, and flow rate (Q̇) is 0.4 l/s. s, Subject 1; k, subject 2; n, subject 3;
o, subject 4. B: comparison with data of Heyder et al. (11, 12). r, Data
from this study averaged over 4 subjects; n, data from Heyder et al.
(11) with VT 5 0.5 liter and Q̇ 5 0.25 l/s; o, data from Heyder et al.
(11) with VT 5 1 liter and Q̇ 5 0.5 l/s; k, data from Heyder et al. (12)
with VT 5 0.8 liter and Q̇ 5 0.4 l/s (for clarity, data have been slightly
shifted to right).
2034
GRAVITY AND AEROSOL DEPOSITION
Figure 3 shows that in subjects 2, 3, and 4, the largest
difference between 1 G and µG occurs for the largest
(3-µm) particles, whereas in subject 1 the difference
seems to plateau between 2- and 3-µm-diameter particles. This difference is consistent with the results of
the simulation (Fig. 4), which show that deposition due
to sedimentation is greatest for the largest particles at
the highest G level. It is predictable, also on the basis of
Fig. 4, that in µG, for particles larger than 3 µm,
deposition would increase due to impaction. Comparisons between simulations and experiments in 1 G (Fig.
4B) show an almost linear increase of deposition with
particle diameter for the simulated results, whereas
the experimental observations show higher deposition
for the smallest particles than predicted, and lower
deposition for the largest particles. The higher deposition for the smallest particles might be explained by the
additional diffusional losses because of the nonreversibility of the flows, as already discussed above.
Figure 4 shows the contribution of each mechanism
of deposition as computed by the numerical model. In
µG, there is, by definition, no deposition by sedimentation. Small particles (0.5 and 1.0 µm) deposit almost
only by diffusion, whereas deposition by impaction
becomes more and more predominant with increasing
particle size. For each particle size, the fraction of
particles that deposit by impaction (open segment of
right bar of each pair) is independent of the G level,
whereas deposition by diffusion decreases with increasing G level, i.e., when deposition by sedimentation
increases. The interdependence of deposition by diffusion and deposition by sedimentation might be explained by the fact that they both take place in the
same region of the lung (the distal airways), whereas
deposition by impaction occurs in the first generations
of the respiratory tract.
Comparison with previous studies. Particle deposition at 1 G was compared with data previously obtained
by Heyder et al. (11, 12) for slightly different breathing
patterns (Fig. 5). The first of the three protocols has
higher tidal volume and flow rate than ours, the second
one has lower tidal volume and flow rate, and the last
one is similar to ours. In all their protocols, however,
the residence time, defined as the duration of one
breath, is the same and is equal to 4 s. In our protocol,
the residence time of 3.75 s is similar. We found particle
deposition similar to the data of Heyder et al., with the
exception of 0.5-µm particles, whereby our results show
a slightly higher deposition: 16.2 6 3.0% compared
with 12%. However, given the intersubject and intrasubject variability, there are no significant differences
between our results and those of Heyder et al. The large
dispersion of aerosol deposition in different subjects is
one of the reasons for the difficulties in the interpretation of aerosol data. Comparing the first two breathing
protocols, Heyder et al. found the same average deposition for 0.5- and 1-µm particles. For 2- and 3-µmdiameter particles, deposition is higher for the larger
tidal volume, higher flow rate protocol because these
particles deposit mainly by inertial impaction and
gravitational sedimentation. Deposition by inertial im-
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is still underestimated by the model. A possible effect is
the nonreversibility of flows in the airways of the
human lung (19). During reciprocal tidal breathing,
unequal time constants in different parts of the lung
and other perturbations, such as the mechanical pulsations of the heart, all serve to make flow reversals
within the lung asymmetric. Thus an additional mixing
effect is introduced that will serve to move the particles
in the direction of the alveoli. This would have the effect
of increasing the apparent contribution of diffusional
loss of particles in the lung. In the absence of gravity,
with the reduction in losses due to sedimentation, this
effect will become more prominent than in 1 G.
Another factor that may explain that deposition in
µG is larger than we expected is the reduction in the
functional residual capacity (FRC) that occurs in the
weightless environment (6, 7, 16, 17). Elliot et al. (7)
found that during sustained periods of µG, FRC decreased significantly by 15% (500 ml) compared with 1
G standing FRC. Paiva et al. (16) and Edyvean et al. (6)
also demonstrated a 200- to 500-ml decrease in FRC
during short periods of µG. Davies et al. (5) and Heyder
et al. (10) showed that deposition increased as the
resting expiratory reserve volume was decreased. For
0.5-µm-diameter particles, Davies et al. (5) found an
,2.5% increase in deposition when the tests were
performed from (FRC 2 500 ml) instead of FRC.
Therefore, the reduction in FRC observed in µG likely
contributes to the higher deposition than would be
expected if the tests were performed from the same
FRC as in 1 G. However, this increase remains lower
than what we observed in our measurements. Thus,
even if we correct for the reduction in FRC in µG by
using a controlled protocol, deposition will still be
higher than that predicted by the model.
An interesting observation shown in Fig. 3 is the very
small intrasubject variability of the µG data. This
result seems surprising, in view of the more difficult
experimental conditions during a parabolic trajectory
than on the ground. A potential explanation may be the
sensitivity of deposition by gravitational sedimentation
to the conditions of the test, such as flow or tidal
volume. This observation is very promising in the sense
that experiments in µG will help in studying the
different mechanisms (except gravitational sedimentation) that affect aerosol behavior in the lung without
the disturbing influence of gravity. In particular, the
use of aerosol boli in µG will allow the determination of
deposition at different depths within the lung. Performing the bolus tests with small or large particles will
allow better estimates of deposition by diffusion or
impaction, respectively. These experimental data could
also be used to improve present 1D models, and, more
particularly, the deposition functions used in the 1D
equation describing aerosol transport and deposition in
the bronchial tree. These improvements, in conjunction
with further developments of the 1D models suggested
by multidimensional studies on aerosol transport in the
alveolar zone of the lung (4, 21, 22), will allow more
accurate predictions of deposition in the respiratory
tract.
2035
GRAVITY AND AEROSOL DEPOSITION
Table 2. Comparison between deposition obtained
on the ground and aboard aircraft at 1 G
Subject No.
dp, µm
DEground, %
DEaircraft, %
4
3
2
2
0.5
1
2
3
17.1 6 1.4
12.2 6 1.4
49.4 6 4.2
57.7 6 3.6
17.0 6 1.8
14.4 6 2.2
51.0 6 2.1
56.9 6 3.1
Values are means 6 SD. dp, Particle diameter; DEground, total
deposition obtained within subject on the ground; DEaircraft, total
deposition obtained in subject during parabolic flight aboard
National Aeronautics and Space Administration aircraft during a
1-G phase.
the flow, producing an apparent mixing effect, and by a
smaller FRC. Comparison with model predictions
showed good agreement for 1-, 2-, and 3-µm-diameter
particles at 1 and 1.6 G, whereas the numerical model
consistently underestimates deposition in µG. This
difference arises probably from the fact that the model
does not incorporate the effect of the apparent diffusion
because of the nonreversibility of the flow.
APPENDIX
The Numerical Model
A 1D equation of aerosol transport and deposition is solved
in a human lung model (3). The lung model is a trumpet
model based on morphometric data of Weibel (23) and HaefeliBleuer and Weibel (8). This structure is referred as model C in
Darquenne and Paiva’s paper (3). The equation incorporates
aerosol bulk flow, convective mixing, and deposition and is
written as
­C
­t
5
s
S
D
­2C
­x
2
1
1 ­(sD) ­C
S ­x
­x
2
Q̇ ­C
S ­x
2
L
S
(A1)
where C is aerosol concentration, t is time, D is the diffusion
coefficient, s is the total airway cross section, S is alveoli plus
the airway cross section, x is the axial coordinate, Q̇ is the flow
rate, and L is a deposition term.
Diffusion coefficient. D incorporates both Brownian diffusion (DB ) and convective mixing (Da ) and is expressed by
D 5 DB 1 Da
(A2)
with
Da 5 2,400 cm2/s
Vcum # 49.3 ml
Da 5 0.167 ul
Vcum . 49.3 ml
(A3)
where u is mean axial velocity in the airway, l is airway
length, and Vcum is the cumulated volume from the entrance
of the mouth. The first 49.3 ml correspond to the volume from
the mouth to the entrance of the trachea, and Eq. A3 accounts
for dispersion within the oropharyngeal cavity.
Deposition term. L incorporates deposition due to inertial
impaction (Li ), gravitational sedimentation (Ls ), and Brownian diffusion (Ld ). These functions are described in the study
by Darquenne and Paiva (3). The function describing deposition by inertial impaction is based on experimental data
measured in a cast of the upper airways (18) and is expressed
by
Li 5 13
Li 5 0
CQ̇
l
(St 2 0.0001)
St $ 0.0001
St , 0.0001
(A4)
where St is Stokes’ number ( 5 rp d2pu/18µd; u is the mean gas
velocity in the airway, and d is the airway diameter). The
higher the value of the Stokes’ number, the more readily
particles will diverge from the airflow streamlines and the
more likely they are, therefore, to deposit by impaction on the
airway walls.
The functions describing deposition by gravitational sedimentation and Brownian diffusion are derived from a theoretical approach (1, 20). The deposition functions are expressed
Downloaded from http://jap.physiology.org/ by 10.220.33.6 on June 17, 2017
paction increases with the flow. Sedimentation is a
time-dependent process that mainly occurs in the distal
generations of the lung, where the airway dimensions
are smaller. Because the residence time in both protocols is the same, the increase in deposition in the larger
tidal volume, higher flow rate protocol could be attributed in the higher tidal volume, allowing particles to
reach more distal airways than in the smaller tidal
volume, lower flow rate protocol. In the third protocol,
which closely approximates our protocol of a 0.4 l/s flow
rate and 0.75-liter tidal volume, Heyder et al. (12)
measured a total deposition of 15 6 4% for 1.0-µmdiameter particles and 45 6 6% for 3.0-µm-diameter
particles. Our data show a deposition of 17.0 6 5.8 and
44.4 6 11% for 1.0- and 3.0-µm-diameter particles,
respectively, suggesting that our results may safely be
compared with those of previous terrestrial studies of
total intrapulmonary deposition.
Effect of altitude. Four flights (1/particle size) were
performed to collect all the data. During each flight,
before the start of the first parabola, we were able to
collect data at 1 G with one subject and compare the
deposition with that obtained on the ground with the
same subject. These values are shown in Table 2. The
data obtained in the aircraft refer to 6–10 breaths,
whereas the data on the ground refer to over 50
breaths. Because the order in which the subjects performed the tests differed on each flight, the data do not
necessarily correspond to a single subject. Data for the
subject in whom these measurements were made are
shown in Table 2. The comparison shows that analogous results are obtained in both environments, with
no statistical differences between aircraft and ground
data. This means that there were no systematic differences in our data introduced by the lower barometric
pressure in the aircraft cabin and that we may therefore valuably compare aircraft and ground data.
In summary, aerosol deposition was measured in four
subjects on the ground and aboard the KC-135 aircraft
during both the weightlessness and the hyper-G phases,
with particles having diameters ranging from 0.5 to 3
µm. Deposition was an almost linear function of the G
level for 2- and 3-µm-diameter particles. For 0.5- and
1.0-µm particles, however, deposition increased less
between µG and 1 G than between 1 and 1.6 G. The
higher deposition observed in µG might be explained by
a larger deposition by diffusion because of both the
absence of sedimentation and the nonreversibility of
2036
GRAVITY AND AEROSOL DEPOSITION
by
Ls 5
CQ̇
l
5
3 Î
(1 2 a) 1 2 exp 2 2
N(z) vsls
ps
Q̇
46
1 fs
Na(z)
l
(A5)
for gravitational sedimentation and by
36DBlN(z)
Na(z)
1 fdsa
(1 2 a) 1 2 exp 2
(A6)
l
l
Q̇
for diffusion, where a is fraction of alveolated surface of
airway, N(z) is the number of airways in generation z, vs is
gravitational settling velocity, fs is deposition rate by sedimentation, Na(z) is number of alveoli in generation z, fd is
deposition rate by diffusion, and sa is inner surface area of
alveolus.
Ld 2
CQ̇
5
3
46
Received 24 March 1997; accepted in final form 20 August 1997.
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