Vol. 87, Issue 6, 2073-2080, December 1999
Longitudinal distribution of chlorine absorption in human
airways: a comparison to ozone absorption
Vladislav
Nodelman and
James S.
Ultman
Biomolecular Transport Dynamics Laboratory, Department of Chemical
Engineering, Pennsylvania State University, University Park,
Pennsylvania 16802
 |
ABSTRACT |
The bolus
inhalation method was used to measure the fraction of inhaled chlorine
(Cl2) and ozone
(O3) absorbed during a single breath as a function of longitudinal position in the respiratory system
of 10 healthy nonsmokers during oral and nasal breathing at respired
flows of 150, 250, and 1,000 ml/s. At all experimental conditions,
<5% of inspired Cl2 penetrated
beyond the upper airways and none reached the respiratory air spaces.
On the other hand, larger penetrations of
O3 beyond the upper airways
occurred as flow increased and during nasal than during oral breathing.
In the extreme case of oral breathing at 1,000 ml/s, 35% of inhaled O3 penetrated beyond the upper
airways and ~10% reached the respiratory air spaces. Mass transfer
theory indicated that the diffusion resistance of the tissue phase was
negligible for Cl2 but important for O3. The gas phase resistances
were the same for Cl2 and
O3 and were directly correlated
with the volume of the nose and mouth during nasal and oral breathing, respectively.
air pollution; inhalation toxicology; lung dosimetry; mass transfer
coefficient; regional uptake
| |
INTRODUCTION |
CHLORINE (Cl2)
and ozone (O3) are gaseous
pollutants that can irritate the human respiratory tract. The
time-weighted exposure limit of
Cl2 and
O3 exposure for an 8-h work shift
are 0.5 and 0.1 parts per million (ppm) by volume, respectively (1).
Short-term exposure of volunteers to
Cl2 concentrations as low as 1.0 ppm and O3 concentrations as low
as 0.12 ppm can cause decrements in forced vital capacity and forced
expiratory volume in 1 s (11, 14). Although the health effects of
long-term Cl2 and
O3 exposure in humans have not
been determined, nonneoplastic lesions have been observed in animals
chronically exposed to O3 or
Cl2. In rats and monkeys, airway
lesions resulting from Cl2
exposure were focused primarily in the nasal cavities (10, 16), whereas lesions resulting from O3 exposure
were observed in alveolated air spaces (2, 4). It is possible that
these differences in lesion distribution were due to corresponding
differences between the uptake patterns of
Cl2 and
O3.
The uptake of O3 has been
determined by direct sampling of respired gas within the human
respiratory tract (5, 6). These experiments made use of indwelling
tubes that limited measurements to only a few large airway sites and
undoubtedly disturbed local flow and concentration profiles. To
circumvent these problems, the distribution of
O3 uptake in the human respiratory
tract can be noninvasively measured by bolus inhalation, an indirect
method that utilizes gas sampling at the airway opening alone (7). Bolus inhalation measurements indicated that the portion of inhaled O3 absorbed in the upper airways
of healthy adult nonsmokers is 80% during quiet nasal breathing
compared with 50% during quiet oral breathing. In neither case did
O3 reach the respiratory air spaces (9). When oral flow was increased to a light exercise condition
of 1,000 ml/s, however, 25% of inhaled
O3 reached the respiratory air
spaces (8). Recently, the bolus inhalation method was adapted to
Cl2. During nasal and oral quiet
breathing, >90% of inhaled Cl2
was absorbed in the upper airways of healthy nonsmokers (12).
In the present work the longitudinal distributions of
Cl2 and
O3 were directly compared in the
same group of healthy nonsmokers during nasal and oral breathing at
respiratory flows of 150, 250, and 1,000 ml/s. Because
O3 is a poorly soluble gas whereas
Cl2 rapidly and reversibly
hydrolyzes in aqueous solution, it is hypothesized that increasing the
respiratory flow will increase the amount of
O3 but not
Cl2 that reaches the respiratory
air spaces during either mode of breathing. The availability of uptake
data from these two gases of widely different solubilities also
provides an opportunity to study the relative role of their gas phase
and mucus phase diffusion resistances. Although a bolus inhalation study of O3 uptake during oral
breathing at 150-1,000 ml/s has been carried out (8), it was
important to repeat these experiments on the same group of subjects and
with the identical breathing apparatus used to obtain the
Cl2 bolus inhalation data.
| |
MATHEMATICAL MODELING |
As previously described by Nodelman and Ultman (12), the human airways
were modeled as a series of nasal/oral (N/O), pharyngeal (PH), lower
airway (LA), and respiratory air space (RA) compartments. On the basis
of a simplified solution of the one-dimensional unsteady diffusion
equation, Hu and associates (8) derived the relationship between the
absorbed fraction (
) and the penetration volume
(VP) of a reactive gas bolus
inhaled into such a compartmental model. For ease in applying a linear
regression analysis, this relationship can be expressed as
follows
}](/content/vol87/issue6/fulltext/2073/img003.gif)
|
(1)
|
where 
is the respiratory flow rate and
(Ka)i
is the product of an overall mass transfer coefficient
(K) and the surface-to-volume ratio
(a) in compartment
i (i.e., N/O, PH, or LA).
VP0,
VP1, and
VP2 are the penetration volumes
that correspond to the entrance of the N/O, PH, and LA compartments,
respectively. I1 and
I2 are indicator variables defined
as follows: I1 = 1 if VP > VP1, and
I1 = 0 otherwise;
I2 = 1 if
VP > VP2, and
I2 = 0 otherwise. The RA
compartment has been omitted from Eq. 1, because the reactive gas reaching this compartment
was never sufficient to allow a reliable estimation of
(Ka)RA.
The local absorption of Cl2 and
O3 can be better understood by
considering the individual factors that contribute to
Ka. As Cl2 or
O3 absorbs into an airway (or air
space), it encounters a diffusion resistance created by a respiratory
gas boundary layer and a second resistance imposed by the surrounding
mucus (or surfactant) film. The overall resistance to mass transfer
within a compartment is equal to the sum of these diffusion resistances
(15)
|
(2)
|
where
kg and
kti are the
individual mass transfer coefficients in the gas boundary layer and the
mucus layer, respectively, and 
is the equilibrium partition
coefficient of Cl2 or
O3 concentration between gas and
mucus. Of particular importance is the fact that kg depends on the
geometry and gas flow in the airway lumen.
The value of kg
in a specific geometry is often predicted from equations of the
following form (15)
|
(3)
|
where
m', n, and
p are constants. As applied to radial
absorption of Cl2 or
O3 in an airway, the Sherwood
(Sh), Reynolds (Re), and Schmidt (Sc) numbers are dimensionless groups
defined by
|
(4)
|
where
d is the airway diameter,
A is the cross section available for
flow, Dg is the
binary diffusivity of Cl2 or
O3 in air, and 
is the
kinematic gas viscosity. Combining Eqs.
3 and 4 results in
|
(5)
|
where
|
(6)
|
The
value of can be approximated by the viscosity of pure air,
(Dg)Cl2/(Dg)O3
is estimated to be 0.8 (15), and
p = 0.8-1.3 in human
airways (13). It follows from Eq. 6
that m has similar values for
Cl2 and
O3 and from Eq. 5 that
kg is essentially
the same for the two gases. In addition, the average value of
n for inspiration and expiration is close to unity (13), so
Eq. 5 may be approximated as
|
(7)
|
where
m can be considered to be a constant,
whereas a and
A depend on compartment geometry.
Because
kga/
is essentially the same for both test gases, Eq. 2 can be simultaneously applied to
Cl2 and
O3
|
(8)
|
where
I = 1 when Ka corresponds to
Cl2 absorption and I = 0 when
Ka refers to
O3 absorption. Within a particular
airway compartment of a particular subject, Eq. 7 implies that
kga/
is constant, and Eq. 8 further implies
that plots of 1/Ka vs.
1/ for Cl2 and
for O3 should be parallel lines
with a common slope of
/kga but different intercepts of
(/ktia)Cl2
and
(/ktia)O3, respectively.
| |
METHODS |
Subject population.
Five healthy men and five healthy nonpregnant women, all nonsmokers
with no history of cardiovascular, pulmonary, and upper airway disease
or allergy, were accepted in the investigation. For each subject, nasal
volume (VNS) and cross-sectional
area (ANS),
oral volume (VOR) and
cross-sectional area
(AOR), and
pharyngeal volume (VPH) and
cross-sectional area
(APH) were
measured by acoustic reflection. Conducting airway volume
(VD) was determined by
single-breath nitrogen washout during oral breathing. Lower conducting
airway volume (VLA) was defined
as VD 
(VOR + VPH). The subjects in this study
were the same as those in a study of
Cl2 uptake during quiet breathing,
for which more detailed descriptions of the screening procedures and
the respiratory system volume measurements were previously reported
(12). All procedures employed in the present experiments, including the
informed consent of each subject, were approved by the Institutional
Review Board of the Pennsylvania State University.
Bolus measurements.
The bolus inhalation apparatus consisted of a custom-designed Teflon
breathing assembly that monitored respiratory flow and Cl2 and
O3 concentration and injected
boluses containing a peak pollutant concentration of 3.0 ppm
Cl2 or 1.0 ppm
O3. A mouthpiece or a nasal
cannula fixture could be attached to the proximal end of the breathing
assembly for oral or nasal breathing maneuvers, respectively. The
volume of both fixtures was 20 ml. The detailed design and performance
of the bolus inhalation system were described previously (12). The only
modification of the apparatus made in this study was the use of a
larger heated pneumotachometer (model 4719, Hans Rudolph) to monitor
respired flow in the 1,000 ml/s experiments than was used in the
previous quiet breathing experiments.
During a research session, the subject was seated comfortably on a
stool, wore noseclips during oral breathing, and maintained a closed
mouth during nasal breathing. To carry out a bolus test breath, the
subject donned the mouthpiece or nasal cannula, activated the
inhalation apparatus by depressing a hand-held switch, and inhaled
beginning at functional residual capacity while viewing a computer
monitor on which the integrated pneumotachometer signal (i.e., the
respired volume) was displayed in real time. Throughout the breath, the
subject corrected his or her respiratory flow rate so that respired
volume coincided, as closely as possible, with a predrawn isosceles
triangle corresponding to equal inspiratory and expiratory flows of
150, 250, or 1,000 ml/s and an inhaled tidal volume of 500 ml. At a
predetermined time during inhalation, a
Cl2-air or
O3-air bolus was automatically
injected into the inspiratory flow. Because the subject always began a
test breath at functional residual capacity, the penetration of the
bolus into the respiratory system could be systematically varied from breath to breath by changing the injection time. A complete experiment consisted of 50-70 bolus test breaths recorded at penetrations of
0-200 ml.
All 10 subjects participated in six sessions lasting 2-4 h, in
which Cl2 or
O3 bolus measurements were made
during nasal and oral breathing at a fixed respired flow of 150, 250, or 1,000 ml/s. For each subject, a
Cl2 session at 250 ml/s was
carried out first. This was followed by
Cl2 sessions at 150 and 1,000 ml/s
that were performed in an order that was randomized among subjects. The
same sessions were then repeated using
O3 as a test gas. Within each
session, the order of nasal and oral experiments was randomized, and
bolus test breaths were carried out at increasing penetrations in some
experiments but at decreasing penetrations in other experiments. To
minimize carryover of exposure effects, each session was separated by
1 wk.
Data analysis.
As previously described in detail (12), the
Cl2 and
O3 concentration curves of each
bolus test breath were numerically integrated with respect to respired
volume to determine (the amount of pollutant absorbed during a
single respiratory cycle relative to the inhaled amount) and
VP (the mean airway volume that
would be reached by inhaled Cl2 or
O3 molecules relative to the gas sampling point if no absorption occurred). To estimate compartmental values of the overall mass transfer parameter
(Ka), a splined linear least-squares
regression of Eq. 1 to each subject's
-VP test breath data was
separately performed at each respiratory flow, for nasal and oral
breathing, and for Cl2 or
O3 absorption.
Values of
/kga,
(/ktia)Cl2,
and
(/ktia)O3
were estimated within the N/O and PH compartments of each subject
by regression of Eq. 8 to the
Ka values for
Cl2 and
O3 at the 150, 250, and 1,000 ml/s
respired flows. Regression was performed with a nonlinear weighted
least-squares Marquart algorithm (Sigma-Plot, SPSS) in which
/kga,
(/ktia)Cl2,
and
(/ktia)O3
were treated as adjustable parameters, and the weights were inversely
proportional to the standard errors of the subject's
Ka estimates (Fig.
1). The LA compartment was excluded from
this analysis because of extensive absorption of
Cl2 in the more proximal
compartments.
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Fig. 1.
Representative
(1/Ka)-(1/)
regression, where K is mass transfer
coefficient, a is surface-to-volume
ratio, and is respiratory flow rate. Data points and
vertical bars represent means ± SE of
1/Ka in oral (OR) compartment of an
individual subject. According to Eq. 8, intercept of O3
line is
(/ktia)O3,
intercept of Cl2 line is
(/ktia)Cl2,
and common slope of 2 lines
is (/kga),
where is equilibrium partition coefficient and
kg and
kti are mass
transfer coefficients in gas boundary and mucus layers, respectively.
|
|
To calculate the fraction of inhaled
Cl2 or
O3 that was absorbed within each
of the five compartments (
), the values of Cl2 or
O3 at the proximal boundaries of
the PH, LA, and RA compartments were first calculated from
Eq. 1. within a compartment was then calculated as the difference between the values of
Cl2 or
O3 at the distal and proximal
boundaries of the compartment.
A two-tailed Student's t-test was
used to compare parameter values between different experimental
conditions. Comparisons were made only if at least eight values were
available at each condition. Paired comparisons were made when values
for all 10 subjects were available in both compared conditions.
Otherwise, an unpaired comparison was made. The risk of making a type I
error in the comparisons was controlled at 
= 0.05.
| |
RESULTS |
Characteristics of subjects.
The anthropometric characteristics of the 10 healthy, young, adult
nonsmokers who participated in the study are given elsewhere (12), and
their compartmental volumes and average cross-sectional areas are given
in Table 1. Whereas
VNS was somewhat smaller than
VOR
(P = 0.18) for the subject population
as a whole, there was no correlation between
VNS and
VOR [coefficient of
determination adjusted for number of subjects
(r2) = 0.00]. The values of VOR and
AOR for different
subjects were highly correlated
(r2 = 0.85), the
values of VPH and
APH were
reasonably correlated (r2 = 0.50), but
the values of VNS and
ANS were not
correlated (r2 = 0.00).
Absorbed fraction.
In Fig. 2 the
-VP distributions are pooled
for all participants at each experimental condition. On average,
Cl2 was absorbed more efficiently
than O3 during nasal and oral
breathing. Furthermore, the difference between the absorption
efficiency of Cl2 and
O3 increased with increasing
respiratory flow rate during nasal and oral breathing. For example,
during nasal breathing at a respiratory flow rate of 150 ml/s, values
of at the proximal end of the pharynx in an average subject (i.e.,
VP = 64 ml) were ~0.95 for Cl2 and 0.90 for
O3. When the respiratory flow was
increased to 1,000 ml/s, decreased to 0.90 for
Cl2 and 0.45 for
O3. Similarly, during oral
breathing at 150 ml/s, the values of at the proximal end of the
pharynx in an average subject (i.e.,
VP = 74 ml) were 0.95 for
Cl2 and 0.80 for
O3, but decreased to 0.85 for
Cl2 and 0.25 for
O3 when the respiratory flow
increased to 1,000 ml/s.
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Fig. 2.
-VP distributions pooled for 10 subjects. Data points and vertical bars represent means ± SE of
absorbed fraction () within 10-ml increments of penetration volume
(VP). SE includes between- and
within-subject variations. Peak inspired
Cl2 concentration was 3.0 parts
per million (ppm), and peak inspired
O3 concentration was 1.0 ppm.
|
|
Figure 2 also indicates that Cl2
absorption was similar during nasal and oral breathing but
O3 absorption was more efficient during nasal breathing, particularly at the higher respiratory flows.
For example, for Cl2 at the
proximal boundary of the pharynx was 0.95 during nasal and oral
breathing at 150 ml/s and 0.90 during nasal breathing and 0.85 during
oral breathing at 1,000 ml/s. In contrast, the corresponding values of
for O3 were 0.90 during nasal
breathing and 0.80 during oral breathing at 150 ml/s and 0.45 during
nasal breathing and 0.25 during oral breathing at 1,000 ml/s. As a
result, a higher dose of inspired O3 was absorbed in the PH, LA, and
RA compartments during oral breathing than during nasal breathing.
of Cl2 and
O3 in each of the four airway
compartments is shown in Fig. 3. Relative
to O3, the dose distribution of
Cl2 exhibits a much weaker
dependence on respiratory flow rate. For example, at a resting
respiratory flow rate of 150 ml/s, ~95% of the inspired
Cl2 and 80-90% of the
inspired O3 was absorbed in the
N/O compartment and <1% of the inspired
Cl2 or
O3 was absorbed in the RA. At a
higher respiratory flow rate of 1,000 ml/s, the Cl2 dose distribution changed only
slightly: 90 and 85% of the inspired
Cl2 was absorbed in the NS and OR
compartments, respectively, and <1% of the inspired
Cl2 was absorbed in the RA. The
dose distribution of O3, however,
changed substantially: only 45 and 25% of the inspired
O3 was absorbed in the NS and OR
compartments, respectively, and 5-10% of the inspired
O3 was absorbed in the RA.
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Fig. 3.
Compartmental absorption pooled for 10 subjects. Histogram units
represent mean for nasal (NS), oral (OR), pharyngeal (PH), lower
airway (LA), and respiratory air space (RA) compartments. Vertical bars
represent SD of among subjects. * Significant difference
between
Cl2 and
O3
(P < 0.05).
|
|
Mass transfer coefficients.
Table 2 summarizes the
Ka values that were calculated from
the individual regression of each subject's
-VP distribution. At all three
respiratory flow rates, the values of
Ka were significantly higher for
Cl2 than for
O3 in the NS and OR compartments
(P < 0.04), but not in the PH and LA
compartments (P > 0.1). Furthermore, the values of Ka for
O3 were always significantly
higher in the NS compartment than in the OR compartment
(P < 0.02) but were similar in the
PH compartment during both modes of breathing
(P > 0.2). In contrast, the
Ka values for
Cl2 were larger in the NS
compartment than in the OR compartment at the higher respiratory flow
rates (P < 0.04), but not at the
lowest respiratory flow (P = 0.5).
Because of extensive absorption of
Cl2 and
O3 in the proximal compartments,
there was a paucity of -VP data
in the PH and LA compartments, resulting in large uncertainties in the Ka values. In some subjects, there
were insufficient data to even compute
Ka in the PH and LA compartments.
Table 3 summarizes the values
of the gas phase absorption parameter
(kga/)
and the mucus phase absorption parameter
(ktia/) that were estimated by regression of each subject's
Ka values in the NS, OR, and PH
compartments according to Eq. 8.
Because of extensive absorption in the NS and OR compartments, however, the Ka data were only sufficient to
compute absorption parameters for the PH compartment in one subject
during nasal breathing and two subjects during oral breathing.
Theoretically,
kga/
is essentially the same for Cl2
and O3, but
ktia/
can have separate values for the two gases. In fact, the value of
(/ktia)Cl2
was so small that the tissue phase did not limit the rate of
Cl2 absorption. On the other hand,
(ktia/)O3
did have a significant effect on O3 absorption. As suggested by the
standard deviations in Table 3, there was no significant difference
between
kga/
values in the NS and OR compartments
(P = 0.9), but the value of
(ktia/)O3 was larger in the NS compartment than in the OR compartment
(P = 0.09).
| |
DISCUSSION |
The primary objective of this research was to determine how the
physical-chemical properties of
Cl2 and
O3 affect their uptake distributions in the intact respiratory tract. To be absorbed into the
epithelial lining fluid (ELF), both gases must overcome the in-series
diffusion resistances of the respired gas and adjacent liquid film
(Eq. 2). Because both gases have
similar diffusion coefficients in respired air, their gas phase
diffusion resistances should be similar, an expectation that is
illustrated by the parallelism of the lines in the
(1/Ka)-(1/)
correlation (Fig. 1). It follows that differences between the
absorption rates of these two gases are due to their interactions with
the ELF.
The physical solubilities of Cl2
and O3 in ELF are low, but
Cl2 reacts with water to form
hypochlorous and hydrochloride acids, whereas
O3 irreversibly oxidizes
biochemical substrates such as albumin, fatty acids, urate, and
ascorbate. Because of the abundance of water in ELF, the
Cl2 hydrolysis reaction occurs
rapidly and with such a large equilibrium constant that the
concentration of Cl2 in the form
of the acid ions is ~120,000 times the concentration of molecular
Cl2 (12). In other words,
hydrolysis suppresses the backpressure of
Cl2 everywhere in ELF and thereby
minimizes the diffusion resistance of
Cl2 in ELF. The concentrations of oxidizable substrates in ELF are low, however, so the reaction rate of
O3 is not sufficiently fast to
eliminate the backpressure of O3
as an impediment to absorption. One would therefore expect that the
diffusion resistance of Cl2 in ELF
would be smaller than that of O3.
This is exemplified by the intercepts of the
(1/Ka)-(1/) correlation (Fig. 1).
Because the liquid phase diffusion resistance of
Cl2 is so small, the absorption
rate of Cl2 is generally limited
by gas phase diffusion, which is proportional to respiratory flow rate.
This is exactly counterbalanced by the inverse dependence of bolus residence time on respiratory flow rate, explaining why the
-VP distribution for
Cl2 is relatively insensitive to
respiratory flow (Fig. 2). On the other hand, the
O3 absorption rate is sensitive to
diffusion through ELF, which is independent of respiratory flow rate.
Therefore, a progressive reduction of absorption occurs in the proximal
airways as increases in respiratory flow shorten the residence time of
a bolus. This is the basis of the progressive distal shift of the
O3 distribution that occurs as
respiratory flow rate increases.
At the lowest nasal respiratory flow of 150 ml/min, the gas phase
diffusion resistances of Cl2 and
O3 dominate their liquid phase
resistances, so that the -VP
distributions for the two gases are similar (Fig. 2). During an oral
flow of 150 ml/min, however, a significant resistance of
O3 diffusion through ELF causes a
distal shift of the O3
distribution relative to the corresponding Cl2 distribution. Because the
saliva in the mouth probably lacks much of the antioxidant capacity of
nasal mucus, it is not surprising that the diffusion resistance of
O3 is more important in the mouth than in the nose. The hydrolysis of
Cl2, on the other hand, should suppress the diffusion resistance of the liquid film in the nose and
the mouth.
The specific values of the liquid phase resistance
(/ktia)
for O3 were 0.042 s in the nasal
compartment and 0.18 s in the oral compartment, whereas
/ktia
values estimated for Cl2 were not
significantly different from zero. Because of this, the gas phase
resistance of Cl2 accounted for
100% of the overall diffusion resistance in the nasal and oral
compartments at all respiratory flow rates. On the other hand, the gas
phase resistance of O3 at
respiratory flow rates of 150, 250, and 1,000 ml/s made contributions to the overall nasal diffusion resistance of 86, 79, and 49%, respectively, and contributions to the overall oral diffusion resistance of 64, 51, and 21%, respectively.
Although Ka values in the nose and
mouth were generally larger for
Cl2 than for
O3, most paired comparisons of
Ka values in the PH and LA
compartments showed a lack of significant differences between
Cl2 and
O3. A post hoc power analysis
indicated, however, that the probability of a type II error (i.e.,
falsely concluding that the values of
Ka for
Cl2 and
O3 were similar) was ~0.75. Reduction of this probability to an acceptable level of 0.2 would require testing approximately twice as many subjects or improving the
precision of the test breath concentration data, possibly by increasing
the peak inhaled bolus concentration.
A substantial dose of O3 was
absorbed in the LA compartment under all experimental conditions and in
the RA compartment during oral breathing at the highest respiratory
flow rate of 1,000 ml/s (Fig. 3). This suggests that an increase in
respiratory flow coupled with a switch from nasal to oral breathing, as
normally occurs during exercise, is likely to cause a distal shift in
the O3 dose distribution, which
increases the likelihood of damage to alveolar and bronchiolar tissues.
In contrast, inspired Cl2 was
primarily absorbed in the NS and OR compartments. Even during oral
breathing at a respiratory flow of 1,000 ml/s, >85% of the inspired
Cl2 was still absorbed in the OR
compartment compared with only 25% of the inspired
O3 (Fig. 3). Because this result
was consistent for all 10 subjects, it is likely that
Cl2-induced tissue damage is
localized in the upper airways of the human respiratory tract, irrespective of the mode of breathing or respiratory flow rate.
The measurements of O3 bolus
inhalation in this study are consistent with the results of previous
studies that used healthy nonsmokers. Hu et al. (8) showed that was
~0.50 at a VP of 50 ml and 0.90 at a VP of 170 ml during oral
breathing at 150 ml/s. When the oral flow was increased to 1,000 ml/s,
decreased to ~0.10 at a VP
of 50 ml and to 0.75 at a VP of
170 ml. In the present study the corresponding values of were
~0.60 and 0.95 during oral breathing at 150 ml/s and 0.10 and 0.90 during oral breathing at 1,000 ml/s (Fig. 2). Therefore, the values
obtained during oral breathing of
O3 in this study were slightly
higher than those reported previously. This previous study did not
include female subjects, who are known to exhibit higher values
than men during oral breathing (3). During nasal breathing at a respired flow rate of 250 ml/s, Kabel et al. (9) reported of
~0.70 at a VP of 50 ml and 0.90 at a VP of 170 ml. In this study,
corresponding values of were ~0.65 and 0.95. Thus the values
obtained during nasal quiet breathing were quite similar in the present
and the previous study.
Previous studies have shown that
Cl2 and
O3 uptake rates during quiet
breathing are related to airway geometry because of its effect on the
gas phase diffusion resistance (3, 12). To further explore this
phenomenon in the present study, Eq. 7 was applied to the N/O compartment. By writing
a in an explicit manner,
Eq. 7 becomes
|
(9)
|
where
V, S, and
A are the airway volume, surface area,
and average cross-sectional area, respectively. If the geometric shape of an airway was the same in everyone, then the
S/A ratio would be a constant from
subject to subject and
kga/
would be inversely proportional to the airway volume. To test this
possibility, a weighted log-log regression of the individual subject's
values of
kga/
to the corresponding values of V was performed in the NS as well as in
the OR compartment. Weights were computed as the squared reciprocal of
the standard error of each value of kga/.
The results of the two regressions were as follows (Fig.
4)
|
(10)
|
and
|
(11)
|
where
the standard error is shown for the regressed value of the exponent.
For the OR compartment described by Eq. 10, variations in
(kga/)OR
were almost completely predicted by variations in VOR
(r2 = 0.89), and
the exponent on airway volume was not much different from the expected
value of 1.0 (P = 0.043). This
indicates that everyone's mouth had a similar shape, as was also
suggested by the strong correlation between
VOR and
AOR
(r2 = 0.85). For
the NS compartment described by Eq. 11, variations in
(kga/)NS
were not as well predicted by variations in
VNS (r2 = 0.61), and
the exponent on VNS deviated from
1.0 (P = 0.033) by a greater
amount. These results suggest that the shape of the nasal compartment
was not constant among the 10 subjects. This conclusion is also
consistent with the fact that VNS
was not correlated with
ANS
(r2 = 0.00).
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Fig. 4.
Influence of volume in nasal or oral cavity
(VN/O) on gas phase mass
transfer parameter
(kga/).
Each data point represents value of
kga/
in mouth (OR) or nose (NS) of an individual subject. Solid lines,
weighted least-squares regression of
ln(kga/)
against ln(VOR) for oral data
and against ln(VNS) for nasal
data.
|
|
At the highest respiratory flow employed in this study, the spatial
resolution of the bolus inhalation method was limited. During each test
breath, a pulse of Cl2-air (or
O3-air) was injected into the
inhaled airstream by using a miniature solenoid valve that was opened
for 0.1 s. At the lowest airflow of 150 ml/s, the
Cl2 pulse formed an inhaled bolus
by mixing with the 15 ml of air that passed the injection point during
0.1 s. At the highest airflow of 1,000 ml/s, the
Cl2 pulse mixed with 100 ml of air to form the inhaled bolus. In other words, the volume of the inhaled Cl2-air (or
O3-air) bolus ranged from 15 ml at
150 ml/s, which was smaller than the smallest compartmental volume, to
100 ml at 1,000 ml/s, which was somewhat larger than the largest
compartmental volume (Table 1). In addition to dispersive mixing of the
inhaled bolus, dispersion occurred as the bolus was convected within
the respiratory system (12). This further compromised the spatial resolution of the absorption data.
Summary.
The longitudinal distribution of
Cl2 and
O3 absorption was measured by the
bolus inhalation method in 10 subjects during nasal and oral breathing
at flow rates of 150, 250, and 1,000 ml/s. Irrespective of the mode of
breathing and respiratory flow rate, >95% of the inspired
Cl2 was absorbed in the upper
airways, whereas the dose delivered to the lower airways was <5%. In
contrast, the dose distribution of
O3 was relatively sensitive to the
mode of breathing as well as to respiratory flow rate. As respiratory flow increased, the O3 dose
delivered to the upper airways ranged from 95 to 50%, whereas the dose
delivered to the LA ranged from 0 to 35%. These differences between
Cl2 and
O3 dosimetry were attributed to
the greater tissue phase resistance of
O3 than of Cl2. During quiet oral breathing,
tissue phase diffusion resistance accounted for ~50% of the overall
absorption resistance of O3 but
for virtually none of the overall absorption resistance of Cl2. The lack of a tissue phase
resistance for Cl2 probably
resulted from its rapid hydrolysis in the airway mucosa. The gas phase resistances of Cl2 and
O3 were similar and were related
in an inverse manner to the volumes of the oral and nasal cavities.
| |
ACKNOWLEDGEMENTS |
The authors are grateful to S. Arnold, R. Bascom, and A. Ben-Jebria
for insightful suggestions.
| |
FOOTNOTES |
This work was supported in part by the Chlorine Institute through a
subcontract with the Chemical Industry Institute of Toxicology and by
National Institute of Environmental Health Sciences Research Grant
ES-06075. Clinical support was provided by the General Clinical Research Center through funding by National Institutes of Health Grant
M01 RR-10732.
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: J. S. Ultman,
Dept. of Chemical Engineering, Penn State University, 106 Fenske Lab,
University Park, PA 16802 (E-mail: JSU{at}PSU.EDU).
Received 23 November 1998; accepted in final form 26 July 1999.
| |
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