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Department of Chemical Engineering, Pennsylvania State University, University Park, Pennslyvania 16802
ABSTRACT
INTRODUCTION
THEORETICAL CONSIDERATIONS
EXPERIMENTAL METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
Bush, Michele L., Patrick T. Asplund, Kristen A. Miles,
Abdellaziz Ben-Jebria, and James S. Ultman. Longitudinal
distribution of O3 absorption in
the lung: gender differences and intersubject variability.
J. Appl. Physiol. 81(4):
1651-1657, 1996.
Because the National Ambient Air Quality
Standard for ozone (O3) is
intended to protect the most sensitive individuals in the general
population, it is necessary to identify sources of intersubject
variation in the exposure-dose-response cascade. We hypothesize that
differences in lung anatomy can modulate exposure-dose relationships
between individuals, and this results in differences between their
responsiveness to O3 at a fixed
exposure condition. During quiet breathing, the conducting airways
remove the majority of inhaled O3,
so the volume of this region should have an important impact on
O3 dose distribution. Employing
the bolus inhalation method, we measured the distribution of
O3 absorption with respect to
penetration volume (VP), and using the Fowler single-breath N2
washout method, we determined the dead space volume
(VD) in the lungs of 10 men
and 10 women at a fixed respiratory flow of 250 ml/s. On average, the
women absorbed O3 at smaller
VP than the men, and the women had
smaller VD than the men. When
expressed in terms of
VP/ VD,
the absorption distribution of the men and women was indistinguishable.
Moreover, an interpretation of the
O3 distribution in terms of an
intrinsic mass transfer parameter
(Ka) indicated that differences
between the O3 dosimetry in all
subjects, whether men or women, could be explained by a unique
correlation with anatomic dead space: Ka (in
s
1) = 610 VD1.05
(in ml). Application of this result to measurements of
O3 exposure response indicated
that previously reported gender differences may be due to a failure in
properly accounting for tissue surface within the conducting airways.
conducting airways; inhalation toxicology; lung dosimetry; regional
uptake
INTRODUCTION OZONE IS AN AMBIENT AIR pollutant that is highly
reactive with biological substrates in the respiratory system.
Controlled laboratory exposures of humans have shown that
O3 causes a decrement in lung
function parameters, particularly forced expired flow and specific
airway resistance, that depends on the inhaled concentration and the
level of physical activity (19). Although the responses of individuals
to O3 appear to be reproducible
(15), there is a marked variability between individuals (16). For
example, when 29 healthy young men were exposured to 0.4 parts/million (ppm) O3 under intermittent
moderate exercise conditions, the mean decrease in forced expired
volume in 1 s (FEV1) was 17%, but 3 men exhibited a decrement of It is not clear that the presence of chronic lung disease predisposes
people to O3-induced decrements in
lung function (10, 13). On the other hand, young people are more
responsive to O3 exposure than the
elderly (18), and women may be more responsive than men (12, 17). We
believe that these intersubject variations in response are largely an
artifact of substituting a dose surrogate, such as exposure
concentration or inhaled dose, for the uptake of
O3 into the affected tissue. In
particular, we hypothesize that natural variations in lung anatomy
induce differences in O3 uptake
that lead to intersubject variations in response.
During quiet breathing and light-to-moderate exercise, the conducting
airways remove the majority of O3
from inhaled air before it reaches the respiratory region (9). Thus the
luminal volume and mucosal surface area of the conducting airways can
strongly influence O3 uptake. The
larger the surface-to-volume ratio, the greater the
O3 uptake rate will be. Because
the upper airways and the tracheobronchial tree are essentially a
collection of cylindrical tube segments, their surface-to-volume ratio
is inversely proportional to the cube root of their volume.
Consequently, individuals with relatively small conducting airways
would be expected to remove a relatively large fraction of inhaled
O3 in the proximal regions of
their respiratory system.
The objective of the present study was to evaluate the influence of
lung anatomy on intersubject variation of
O3 dose. We used the previously
developed bolus inhalation method (8) to measure the longitudinal
distribution of O3 under quiet
breathing conditions in a population of 10 men and 10 women. The
O3 distribution was regressed with
a diffusion model to provide a value of an intrinsic mass transfer
parameter (Ka) for each subject.
Lung anatomy was characterized by forced vital capacity (FVC), total lung capacity (TLC), and single-breath
N2 dead space
(VD).
THEORETICAL CONSIDERATIONS To obtain a single parameter to express the intrinsic rate of
O3 uptake into the conducting
airways, a one-dimensional steady-state diffusion model (3) was applied
to the bolus inhalation data of each subject. To account for tidal
flow, it was assumed that 1) the
respiratory system can be represented as a single tube with a volume
that is twice the penetration volume of the bolus (VP) less the volume of the
nonabsorbing breathing assembly
(VP0) and
2) absorption during inhalation and
absorption during exhalation are independent steady-state processes
that are governed by the same overall mass transfer coefficient
(K). In that case, the fraction of
O3 that is absorbed within a
single breath (
40%. An understanding of the source of such hyperresponsiveness is necessary to formulate a National
Ambient Air Quality Standard that will protect the most sensitive
segment of the population.
) is given by Hu et al. (9)
where
a is the surface-to-volume ratio of
the airway and
![&Lgr; = 1 − exp[− (2<IT>Ka</IT>/<A><AC>V</AC><AC>˙</AC></A>)(V<SUB>P</SUB> − V<SUB>PO</SUB>)]](/content/vol81/issue4/fulltext/1651/img001.gif)
(1)
is the respiratory flow.
Equation 1 implies that a linear
regression of ln(1 
) vs.
VP can be used to estimate the
values of Ka and VP0.
The theoretical basis of K can be understood from a resistance-in-series model of an airway segment. As O3 absorbs into an airway, it encounters a diffusional resistance created by a respiratory gas boundary layer and a second resistance imposed by the surrounding tissue. The overall resistance (1/K) can be equated to the sum of the diffusion resistances through these two layers (21)
|
(2) |
g-ti is the equilibrium
partition coefficient of O3
between gas and tissue. Of particular importance is the fact that
kg depends on the
geometry and gas flow in the airway lumen. The dimensional analysis of
lateral O3 diffusion through air
flowing in a tube can be expressed by the customary relationship (20)
|
(3) |
,
n, and
p are constants under given flow
conditions. The Sherwood (Sh), Reynolds (Re), and Schmidt (Sc) numbers are dimensionless groups defined by
|
|
(4) |
|
is the
kinematic viscosity of air.
For the absorption of O3 into an
airway, the only variables are and
d, so Eqs.
3 and 4 can be written
in a simpler form as
|
(5) |
as well as the gas
physical properties and the proportionality constant between
A and
d2. The intrinsic
mass transfer parameter can then be formulated by combining
Eqs. 2 and 5
|
(6) |
can be
used to estimate the value of n.
EXPERIMENTAL METHODS
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was
computed as 1 minus the ratio of the integrals of the expired and
inspired O3 concentration curves
(Fig.
1A).
VP was computed as the centroid of
the inspired O3 concentration
curve relative to the end of inhalation. The
-VP distribution was obtained
by cross plotting the data collected for all test breaths (Fig.
1B).
-VP distribution from 1 subject
(B). Absorbed fraction ()
represents amount of O3 that does
not reappear during exhalation relative to amount inhaled, and
penetration VP represents mean
airway volume traversed by
O3 molecules during inhalation, if
they were not absorbed. MB and MR,
amounts of O3 inhaled and exhaled, respectively.
Anatomy. The anatomy of the respiratory system was characterized by three volumes: FVC, VD, and TLC. FVC was determined by using a commercial instrument (model 110 Automated Spirometer, CDX) in which the highest two of three forced expired measurements were averaged. VD and residual volume were measured by single-breath and multibreath N2 washouts, respectively, with apparatus of our own design. TLC was computed as the sum of FVC and residual volume. The N2 washout apparatus consisted of a two-way Hans Rudolph breathing valve with its inlet port connected to a 2-liter anesthesia bag, its outlet port vented to the room, and its common port connected to a Fleisch no. 1 pneumotachograph fitted with a rubber mouthpiece. The sampling needle of a nitrogen analyzer (505 Nitralyzer, Medscience) was inserted through a small hole in the body of the Hans Rudolph valve. Before each experimental session, the Nitralyzer was calibrated in accordance with the manufacturer's instructions by use of pure O2 and room air at respective set points of 0.0 and 79.6% N2. The analyzer continuously sampled 3 ml/min of the respired airstream, and the instrumental dead space from the rubber mouthpiece to the sampling needle was 20 ml. The data-acquisition system used in the bolus inhalation apparatus also served to record N2 analyzer and pneumotachograph signals in the washout measurements. Immediately before each measurement, the Hans Rudolph valve and anesthesia bag were purged with O2 until a 0.0% reading was displayed on the Nitralyzer. To measure VD, a seated subject took one breath through the mouthpiece beginning at functional residual capacity while tracking his or her breathing pattern on the same monitor that was used in the bolus inhalation experiments. The subject was instructed to expire as long as possible to ensure that the alveolar plateau was recorded. When residual volume was measured, a Tissot spirometer was connected to the outlet port of the Hans Rudolph valve. The spirometer was initially purged with O2 and then emptied. Beginning at TLC, the subject breathed quietly through the mouthpiece while the anesthesia bag was continuously supplied with O2. This multibreath test was terminated when the end-expired N2 level dropped to
1%.
To determine VD, a set of
expired N2 concentration data was
first aligned with the corresponding expired flow data by correcting for the Nitralyzer time delay of 125 ms. Then the linear portion of the
alveolar plateau was manually identified,
VD was calculated by numerical
integration according to Fowler's method (4), and 20 ml were
subtracted to correct for the instrumental dead space. Of the five or
more single-breath N2 washout
maneuvers taken by each subject, the highest and lowest
VD values were discarded, and
the remaining VD values were
averaged together. Residual volume was determined from the amount of
N2 in the Tissot spirometer at the
end of the multibreath washout by assuming that there was no transfer
of N2 from respiratory tissue.
Only one of these TLC measurements was made on each subject.
RESULTS
The participants were university students who were selected without regard to body size. By statistical analysis, the women were less tall, weighed less, and had smaller TLC and FVC than the men (Table 1). Within these two subpopulations there was little correlation of VD with TLC (men, r2 = 0.47; women, r2 < 0.01) or FVC (men, r2 = 0.17; women, r2 = 0.19), but the difference in VD between the women and men was almost significant (P = 0.065). These observations are consistent with previous studies of dysanapsis, a theory of unequal lung growth that explains intersubject discrepancies between the sizes of airways and air spaces (6, 14). Although VD was poorly correlated with height within the gender groups (men, r2 = 0.24; women, r2 < 0.01), average height was a reasonable predictor of the VD difference between the groups: on the basis of average height, the VD of the women was predicted to be 37 ml smaller than the VD of the men (7), which is close to the 32-ml observed difference.
In a two-stage analysis of the absorbed fraction data, values from
individual test breaths were first sorted and averaged within 10-ml
increments of VP for each woman.
These averaged data were then pooled for all the women to determine the
overall mean and intersubject standard error of within each
VP increment. This process was
repeated for the male population, and the results (Fig.
2A)
suggest that women absorb O3 at
more proximal penetrations than men. To determine the extent to which
VD could explain this difference, the abscissa of the women's and men's
-VP distributions were each
recomputed as (VP VP0)/VD,
where VP0 was equated to the
measured 20-ml volume of the breathing assembly and
VD was equated to the average
dead space for each gender group (Table 1). By normalizing the
VP variable in this manner, the
women's and men's absorption data were virtually superimposed (Fig.
2B).
-VP distribution separately
pooled for women and men (A) and
their normalization by mean dead space volume
(VD;
B). Data points, average values
within a 10-ml increment of VP;
vertical bars, intersubject standard errors.
VP0 value of 20 ml and
VD values of 148 and 180 ml for
women and men, respectively, were used in normalizing abscissa.
A statistical test was applied to the normalized absorption distributions to determine whether there was any influence of gender beyond its indirect effect through VD. In particular, the pooled data of the men and the women were simultaneously regressed to a quadratic model
|
(7) |
(VP VP0)/VD
and Ig is an indicator variable
that is equal to 1 for men and 0 for women. The three
gender-independent coefficients,
b0
(P < 0.01),
b2
(P < 0.01), and
b4
(P < 0.01), were significant at a
95% level. The three gender-dependent coefficients, b1
(P = 0.24),
b3
(P = 0.18), and
b5
(P = 0.13), were not significant.
Individual Ka and
VP0 values were determined for
each subject by performing a linear least squares regression of ln(1 ) vs. VP for all his or
her test breaths within the conducting airways (i.e.,
VP < VD). The resulting fits for a
woman with a small VD and a man
with a large VD are shown in
Fig. 3. The correlation coefficient for the
20 individual regressions was 0.97 > r2 > 0.86. A
summary of the Ka and
VP0 values determined for the women and for the men is given in Table 1. At a 95% significance level, the mass transfer parameter Ka
was significantly greater for women than for men. The regressed value
of VP0 was not significantly affected by gender, nor was it significantly different from the actual
instrumental dead space of 20 ml for the women
(P = 0.56) or for the men
(P = 0.09).
-VP
data of individual subjects. Results are for a woman with a dead space
of 130 ml (A) and a man with a dead
space of 227 ml (B).
A forward stepwise regression procedure (MINITAB) was used to determine which variables, i.e., height, weight, age, gender, VD, FVC, or TLC, directly influenced Ka. At the 95% significance level, VD (P < 0.01) was clearly significant, whereas height (P = 0.45), weight (P = 0.31), FVC (P = 0.41), TLC (P = 0.14), and age (P = 0.45) were not significant. Gender (P = 0.11) was second in importance to VD but was not significant at the 95% confidence level. A more detailed analysis indicated that gender influenced Ka indirectly because of its interaction with VD. Because a logarithmic plot linearized the data (empirical observation: Fig. 4), the dependence of Ka on VD was assumed to follow a "power law" model, Ka = r(VD)s. To determine whether a separate set of (r,s) coefficients was necessary for men and women, the data were linearly regressed according to the transformed model
|
(8) |
ln(r) and
(a2 + a3Ig)
s. As expected from the results of
the stepwise regression procedure, the gender-dependent coefficients,
a1
(P = 0.22) and
a3
(P = 0.24), were not significant at
the 95% level, and Ka could be
expressed for the men and women as
|
(9) |
1) = 610 VD1.05 ± 0.2
(ml).
DISCUSSION
To understand the influence of gender and lung anatomy on O3 dosimetry, the longitudinal distribution of O3 absorption as well as the VD, TLC, and FVC of 10 men and 10 women were measured during quiet oral breathing. From a qualitative point of view, the pooled data (Fig. 2A) indicate that the women absorbed O3 more proximally in their respiratory system than the men. This result is consistent with the hypothesis that O3 uptake is inversely related to VD, because small airways have a relatively large surface-to-volume ratio. In the men and the women, absorption was essentially complete within their anatomic dead space. This explains why the Ka rate parameter was correlated with VD but not with TLC or FVC.
The fact that the women absorbed O3 from inhaled air at a lower VP than the men does not necessarily mean that the women removed O3 in more proximal airway generations than did the men. As a consequence of having smaller airways, the women probably had a smaller airway volume per airway generation. In fact, if there was exact geometric similarity between different individual's respiratory systems, then the volume per airway generation would be directly proportional to VD and VP/VD would have the same values for all subjects at each airway bifurcation.
The success of the normalized penetration,
(VP VP0)/VD,
in collapsing the uptake distribution data (Fig.
2B) parallels the finding that
Ka is inversely proportional to
VD (Eq. 9). To appreciate the significance of this result,
consider d to be a characteristic diameter of the conducting airways and assume that
1) airways are cylindrical so that
a 
1/d,
2) there is exact geometric
similarity between different individual's lungs so that
VD d3, and
3) the tissue resistance is small
compared with the gas-phase resistance so that
Ka a n/dn + 1
(Eq. 6). The combination of these
three proportionalities predicts that
Ka n/VD(n + 2)/3,
and comparison to Eq. 9
implies that n = 1. This result
further suggests that K , a hypothesis that can be tested by analyzing
O3 uptake distributions obtained
at alternative respiratory flows.
We previously collected -VP
data on nine men at respiratory flows between 150 and 1,000 ml/s and
determined the distribution of Ka
values in six serial subcompartments of the conducting airways (9). To
be consistent with the present research, we reanalyzed these data by
using a single compartment to represent the conducting airways and
obtained one Ka value for each subject
at each of the five respiratory flows that were tested. By using a
nonlinear least square regression (SAS Institute), these 45 values of
Ka were regressed to
Eq. 6 with the result
that
|
(10) |
From this result it is clear that, at quiet breathing conditions,
the tissue resistance (0.074 s1) is only 15% of the
overall diffusion resistance (0.508 s1), the value of
n is close to unity, and the intrinsic
mass transfer does scale as Ka /VD.
The general applicability of this result may be limited for a number of
reasons. First, the diffusion theory represented by Eq. 1 assumes that
Ka is constant. Because of the
branching structure of the tracheobronchial tree, the surface-to-volume
parameter a is a sharply increasing
function of VP, and it is unlikely
that the Ka product is constant. Even
so, Eq. 1 provided good regressions of
-Vp data, and the associated
Ka may be viewed as a spatially averaged parameter. Second, the gas phase resistance employed in
Eq. 6 incorporates a characteristic
diameter, d, that is assumed to be
constant. The size of those airways exposed to
O3 is, however, influenced by
respiratory flow. When respiratory flow is made larger,
O3 penetrates to more distal
airways, so that d is a decreasing function of . Third, the present analysis assumes
that mucus resistance can be neglected. At respiratory flows above
those incorporated in the current experiments, Eq. 6 implies that the gas phase diffusion resistance may
be reduced to the point that the mucus resistance is an important
consideration. We conclude that Ka /VD
when respiratory flow is 1,000 ml/s, but further work is needed to
confirm this scaling rule at higher flows characteristic of
moderate-to-heavy exercise conditions. Experiments in which VD values and
-Vp distributions are measured
on a single group of subjects over a broad range of
would be particularly useful.
A unique dose-response curve for
O3 or any other toxic compound is
only ensured at the level of the target tissue. When inhalation studies
are conducted on humans, measurements of dose are usually restricted to
the airway opening, and it is necessary to select a surrogate for the
tissue dose. Ideally, a surrogate dose should eliminate apparent
variations in an individual's response due to different patterns of
exposure concentration, time, and physical activity. A frequently used
surrogate is the "effective dose," the simple product of
concentration × time × ventilation rate (2). Because of the
inclusion of ventilation rate, effective dose should partially account
for a variation in the response of different individuals. Intersubject
variations might also be due to differences in anatomy, tissue
transport properties, or the sensitivity of target tissue. An obvious
feature of lung anatomy that affects dose to a specific tissue is the
surface over which the inhaled pollutant is spread. To correct for
intersubject differences in lung anatomy, many investigators have
selected some lung volume parameter that may be viewed as a crude
measure of tissue surface. Whereas TLC, FVC, or maximal oxygen
consumption (O2 max)
has frequently been used in this manner, bolus inhalation studies indicate that most O3 is absorbed
in the conducting airways, suggesting that
VD is a more appropriate
parameter. In our mass transfer analysis, the rate of
O3 absorption per concentration
per tissue surface was defined as the overall mass transfer coeficient,
K. An "internal effective dose"
that accounts for differences in subjects' airway surface can
therefore be defined as the product of
K and the exposure concentration. The
fact that Ka /VD and
a (VD)2/3
implies that K /(VD)1/3,
and the internal effective dose is equivalent to the effective dose
divided by
VD1/3.
The extent to which gender differences in pulmonary response to
O3 can be explained by anatomic
differences is an open question. Lauritzen and Adams (12) performed
forced expiratory spirometry on a group of six young women who were
exposed orally to 0.2, 0.3, or 0.4 ppm
O3 for 1 h while continuously
exercising. The level of physical activity was selected to evoke
alternative minute ventilations of 23, 35, and 46 l/min. Data from
these women were compared with those from a group of young men who were
previously studied by using a similar protocol (2). When separated by gender, FEV1 and forced expiratory
flow at 25-75% FVC
(FEF25-75) decrements were
each well correlated with effective doses from 300 to 1,100 ppm · l, but gender differences between the responses at equal effective doses were substantial. The use of TLC or
O2 max to normalize
effective dose greatly reduced, but far from eliminated, gender
differences. Although anatomic dead space was not measured, predictions
based on the subjects' mean body surface (7) indicate that the
normalization of effective dose by
VD1/3 would
not account for more of the gender difference than did TLC or
O2 max. In another
study, Adams and associates (1) found that decrements in
FEV1 and
FEF25-75 were similar in a
group of 20 young women and a group of 20 young men who were orally
exposed to 0.3 ppm O3 during
continuous heavy exercise. Because of the higher ventilation rate of
the men, their effective dose of 1,300 ppm · l was
1.4 times that of the women. Yet, the relative doses of the two groups
were similar when normalized by FVC or
O2 max.
Messineo and Adams (17) compared decrements in pulmonary function in 14 young women with small lungs (FVC = 3.76 liters) with that in 14 young
women with large lungs (FVC = 5.11 liters) during continuous oral
exposure to 0.18 or 0.3 ppm O3 at
a single ventilation rate of 47 l/min. Although not statistically
significant, the mean decrement of
FEV1 in the large-lung group was
~1.1 times that in the small-lung group (Fig. 1 in Ref. 17). Whereas
their relative TLC and FVC were on the order of 1.4, the relative
VD1/3
predicted for the two groups was ~1.1. It was also reported that the
mean FEV1 decrement for all 28 women at an effective dose of 900 ppm · l was equal
to the mean decrement in a previously studied group of young men at an
effective dose of 1,200 ppm · l. This implies that
the ratio of internal doses between the men and the women was 1.3, which is somewhat greater than would be expected from the typical
VD1/3
ratios between men and women. Seal et al. (18) found no difference in
FEV1 decrements between 372 men
and women who inhaled O3 in an
exposure chamber for 2.3 h while intermittently exercising such that
their minute ventilation per body surface was constant at 25 l · min1 · m2.
Because VD can be directly
correlated with body surface (7), these results demonstrate that the
use of internal dose can eliminate apparent gender difference over a
wide range of exposure concentrations from 0.12 to 0.40. Similarly,
Weinmann and colleagues (22) found no gender differences in
isovolumetric FEF25-75 when
subjects inhaled from 0.12 to 0.40 ppm
O3 for 3 h in an exposure chamber while intermittently exercising such that their ventilation rate was a
constant factor of 10 times their FVC.
To summarize, the -VP
distribution of O3 in a group of
10 women was steeper than that in a group of 10 men. When expressed in
terms of
VP/VD,
however, the absorption distributions of the men and women were
indistinguishable. Alternatively, by interpreting the
-VP data in terms of an
intrinsic mass transfer parameter, Ka,
differences between the O3
dosimetry in all subjects, whether men or women, could be explained by
a unique correlation with anatomic dead space:
Ka
(s1) = 610 VD1.05
(ml). Applying these results to measurements of lung response to
O3 exposure implies that
previously reported gender differences may be due to a failure in
accounting for tissue surface within the conducting airways.
ACKNOWLEDGEMENTS
L. Bellini and M. Ocampo provided technical assistance in performing the regression analyses.
FOOTNOTES
Address for reprint requests: J. S. Ultman, Dept. of Chemical Engineering, Penn State University, 106 Fenske Lab, University Park, PA 16802 (E-mail: JSU{at}PSUVM.PSU.EDU).
Received 9 November 1995; accepted in final form 29 May 1996.
REFERENCES
| 1. | Adams, W. C., K. A. Brookes, and E. S. Schelegle. Effects of NO2 alone and in combination with O3 on young men and women. J. Appl. Physiol. 62: 1698-1704, 1987. |
| 2. | Adams, W. C., W. M. Savin, and A. E. Christo. Detection of ozone toxicity during continuous exercise via the effective dose concept. J. Appl. Physiol. 51: 415-422, 1981. |
| 3. | Ben-Jebria, A., S.-C. Hu, E. Kitzmiller, and J. S. Ultman. Ozone absorption into excised porcine and sheep tracheae by a bolus-response method. Environ. Res. 56: 144-157, 1991. |
| 4. | Fowler, W. S. Lung function studies. II. The respiratory dead space. Am. J. Physiol. 154: 405-416, 1948. |
| 5. | Fox, S. D., W. C. Adams, K. A. Brookes, and B. L. Lasley. Enhanced response to ozone exposure during the follicular phase of the menstrual cycle. Environ. Health Perspect. 101: 242-244, 1993. |
| 6. | Green, M., J. Mead, and J. M. Turner. Variability of maximum expiratory flow-volume curves. J. Appl. Physiol. 37: 67-74, 1974. |
| 7. | Hart, M. C., M. M. Orzaleski, and C. D. Cook. Relation between anatomic respiratory dead space and body size and lung volume. J. Appl. Physiol. 18: 519-522, 1963. |
| 8. | Hu, S.-C., A. Ben-Jebria, and J. S. Ultman. Longitudinal distribution of ozone in the lung: quiet respiration in healthy subjects. J. Appl. Physiol. 73: 1665-1661, 1992. |
| 9. | Hu, S.-C., A. Ben-Jebria, and J. S. Ultman. Longitudinal distribution of ozone absorption in the lung: effects of respiratory flow. J. Appl. Physiol. 77: 574-583, 1994. |
| 10. | Kehrl, H. R., M. J. Hazucha, J. J. Solic, and P. A. Bromberg. Responses of subjects with chronic obstructive disease after exposures to 0.3 ppm ozone. Am. Rev. Respir. Dis. 131: 719-724, 1985. |
| 11. | Knudsen, R. J., R. C. Slatin, M. D. Lebowitz, and B. Burrows. The maximal expiratory flow-volume curve. Am. Rev. Respir. Dis. 113: 587-600, 1976. |
| 12. | Lauritzen, S. K., and W. C. Adams. Ozone inhalation effects consequent to continuous exercise in females: comparison to males. J. Appl. Physiol. 59: 1601-1606, 1985. |
| 13. | Linn, W. S., D. A. Fischer, D. A. Medway, U. T. Anzar, C. E. Spier, L. M. Valencia, T. G. Venet, and J. D. Hackney. Short-term respiratory effects of 0.12 ppm ozone exposure in volunteers with chronic obstructive pulmonary disease. Am. Rev. Respir. Dis. 125: 658-663, 1982. |
| 14. | Martin, T. R., R. G. Castile, J. J. Fredberg, M. E. Wohl, and J. Mead. Airway size is related to sex but not lung size in normal adults. J. Appl. Physiol. 63: 2042-2047, 1978. |
| 15. | McDonnell, W. F., D. H. Hortsman, S. Abdul-Salaam, and D. E. House. Reproducibility of individual responses to ozone exposure. Am. Rev. Respir. Dis. 131: 36-40, 1985. |
| 16. | McDonnell, W. F., D. H. Hortsman, M. J. Hazucha, E. Seal, E. D. Haak, S. A. Salaam, and D. E. House. Pulmonary effects of ozone exposure during exercise: dose-response characteristics. J. Appl. Physiol. 54: 1345-1352, 1983. |
| 17. | Messineo, T. D., and W. C. Adams. Ozone inhalation effects in females varying widely in lung size: comparison with males. J. Appl. Physiol. 69: 96-103, 1990. |
| 18. | Seal, E., W. F. McDonnell, D. E. House, S. A. Salaam, P. J. Dewitt, S. O. Butler, J. Green, and L. Raggio. The pulmonary response of white and black adults to six concentrations of ozone. Am. Rev. Respir. Dis. 147: 804-810, 1993. |
| 19. | Tilton, B. B. Health effects of tropospheric ozone. Environ. Sci. Technol. 23: 257-263, 1989. |
| 20. | Treybal, R. E. Mass-Transfer Operations (3rd ed.). New York: McGraw-Hill, 1980. chapt. 3. |
| 21. | Ultman, J. S. Transport, and uptake of inhaled gases. In: Air Pollution, the Automobile and Public Health, edited by A. Y. Watson, R. R. Bates, and D. Kennedy. Washington, DC: Natl. Acad. Press, 1988, p. 323-366. |
| 22. | Weinmann, G. G., M. Weidenbach-Gerbase, W. M. Foster, H. Zacur, and R. Frank. Evidence for ozone-induced small-airway dysfunction: lack of menstrual-cycle and gender effects. Am. J. Respir. Crit. Care Med. 152: 988-996, 1995. |
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