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Guilherme J.M. Garcia, Ph.D., Earl W. Tewksbury, B.A., Brian A. Wong, Ph.D., and Julia S. Kimbell, Ph.D.
Abstract
Key words: nasal replica cast, nasal mold, aerosol experiments, particle deposition efficiency, nasal drug de-
livery, risk assessment, interhuman variability.
The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina.
139
140 GARCIA ET AL.
FIG. 1. Nasal replicas produced by stereolithography. (Left) Four healthy adults. (Right) Atrophic rhinitis patient. Note:
plaster filling was used in the atrophic nasal mold to fill the space between the external Plexiglas box and the face of the
plastic replica. This approach prevented air circulation in the Plexiglas box, making the entrance to the nostrils consistent
with the other models.
the nose filters most particles with aerodynamic diameter ethnicities,(18) and within population subsets.(6,14,15,22) This
(da) larger than 10 m. Nasal filtration efficiency falls sharply is expected, given that nasal deposition is a function of
as particle size decreases from 10 to 1 m, so that nasal fil- nasal geometry and ventilation, both of which vary across
tration is almost zero for 1-m particles. Nasal deposition the population.(42–45) The long-term goal of the current
increases sharply again for particles smaller than 10 nm, study is the mathematical description of interindividual
achieving approximately 80% deposition for 1-nm particles differences in nasal filtration and the identification of pop-
(flow rate 15 L/min(27)). The spatial distribution of de- ulation subsets that may be more susceptible to adverse ef-
posited particles has also been investigated.(17,19,21,30) In the fects when exposed to air pollutants.
inertial regime (da 1 m), most particles deposit in the an- In theory, the dependence of nasal filtration on anatomy,
terior nose, and the percentage of particles deposited in the ventilation, and particle size can be put into a functional form
anterior nose increases as particle size increases. This means that explains interindividual differences in nasal filtration in
that medical aerosols must have droplet sizes small enough terms of differences in anatomy and ventilation. As dis-
to traverse the vestibule and nasal valve region; otherwise, cussed in the next section, a number of attempts to define
the medicine will not penetrate beyond the anterior third of such relationship have been made,(8,11,12,14–16,18,20,22,26–28) but
the nasal cavity, and therefore will not reach target tissues, a universal relationship is still lacking. In vitro measurement
such as the turbinates or the paranasal sinuses.(30,40) Another of nasal deposition in plastic nasal replicas is a powerful
major site of deposition is the anterior portion of the middle technique that allows for systematic investigation of the de-
turbinate, where particles have been observed to accumulate pendence of nasal filtration on ventilation, anatomy, and par-
in woodworkers in the furniture industry.(19,41) ticle size. Such systematic investigation is difficult in in vivo
Although the general features of nasal filtration have studies due to limitations on the number of particle sizes and
been described, it is still unknown how nasal filtration de- flow rates that can be studied. Here we report deposition
pends on age, ethnicity, and the presence or absence of measurements of micron-sized particles in nasal replica casts
nasal deformities. Also, it is unknown to what extent nasal of four healthy individuals and one atrophic rhinitis patient.
filtration varies among individuals in a given population We use our data to investigate how filtration efficiency re-
subset (e.g., healthy Caucasian adults). In vivo investiga- lates to nasal geometry. We propose a new, simple method
tions report significant interindividual variability in nasal to compute a characteristic diameter of the nasal geometry
filtration among different age groups,(8–10) among different that collapses the data of different individuals onto a single
INTERHUMAN VARIABILITY IN NASAL FILTRATION 141
TABLE 1. ANTHROPOLOGIC AND GEOMETRIC DATA FOR THE FIVE ADULT HUMANS INCLUDED IN THIS STUDY
curve when deposition efficiency is plotted against the extended at the nasopharynx by a few centimeters (as de-
Stokes number. scribed in Ref.(47) prior to printing the nasal replicas by stere-
olithography. Addition of the artificial extension of the naso-
Materials and Methods pharynx in these three individuals was expected to have a
minor effect on deposition measurements because the cross-
Nasal replicas
sectional area of the nasopharynx is much larger than the
Plastic replicas of the nasal airways of four healthy indi- cross-sectional area of the nasal chamber. The paranasal si-
viduals and one atrophic rhinitis patient were created as fol- nuses were not included in the nasal replicas, so that this pa-
lows. The diagnosis of healthy versus pathologic nose was per focuses on nasal deposition alone. The replicas of the
determined by ear–nose–throat physicians. The nasal geome- normal individuals did not include the exterior nose, while
tries of the healthy volunteers were captured by magnetic the replica of the AR nose had an exterior nose. To make the
resonance imaging (MRI) scans of 3-mm spacing. The air- inhalation conditions of the AR replica consistent with that
way outlines on the scans were digitized and used to create of the other models, a Plexiglas box was mounted in front
three-dimensional hexahedral meshes of the nasal passages of the face of the replica and filled with plaster (Fig. 1), so
as described in detail elsewhere.(46,47) Healthy Nose 1 is the that air was provided directly to the nostrils.
same individual used in our previous investigation of nasal The surface area and volumes of the nasal replicas are
filtration.(23,24) Healthy Noses 2, 3, and 4 were carefully se- given in Table 1. These geometric attributes were measured
lected from a sample of scans of 15 healthy volunteers to rep- in ICEM-CFD® (Ansys, Canonsburg, PA) using the three-di-
resent complete nasal passages and a range of surface area mensional computer reconstructions. Age, sex, and ethnicity
to volume ratios in order to maximize anatomical variabil- for the five individuals, when available, are also provided in
ity.(43,47) Table 1.
The atrophic rhinitis nose was included in this study to
represent an individual with abnormally wide nasal pas-
Deposition measurements
sages and potentially higher susceptibility to airborne par-
ticulate matter due to greater lung deposition (low nasal The experimental setup was described in detail in an ear-
filtration). Atrophic rhinitis (AR) is a chronic disease char- lier report,(24) and will be outlined here briefly. A Vibrating
acterized by atrophy of the nasal turbinates, which leads to Orifice Aerosol Generator (Model 3450, TSI Incorporated,
an enlarged nasal space; it is sometimes referred to as “empty Shoreview, MN) was used to produce monodisperse drop-
nose syndrome” when the disease develops after excessive lets of Di-2-ethylhexyl Sebacate (DEHS; density 914 kg/
surgical removal of the turbinates.(48,49) The geometry of the m3) with aerodynamic diameters ranging from 1 to 12 m.
AR nose was captured by computed tomography (CT) scans A source of dry, filtered air and a vacuum source provided
of 0.6-mm spacing.(48) Medical imaging software (Mimics®, a constant airflow rate that was adjusted to 10, 20, and 30
Materialise, Ann Arbor, MI) was used to delimit the nasal L/min. Data for 40 L/min were collected for the atrophic
geometry and reconstruct the anatomy in three dimensions. nose and were also available from our earlier study on
The computer reconstructions of the nasal airways of the Healthy Nose 1.(24) These airflow rates are characteristic of
AR patient and the healthy volunteers were used to produce nasal breathing at rest.(5) It should be highlighted that oral
hard-plastic nasal replicas using stereolithography (Fig. 1). breathing and oronasal breathing, which are typical of phys-
All nasal replicas were made using 0.051-mm build layers, a ical exercise, lead to different deposition patterns.(27)
laser spot diameter of 0.075 mm, and Somos WaterShed Instead of using realistic cyclic breathing in our experi-
11120 material. All nasal replicas included both the left and ments, constant airflow was adopted to reduce the number
right sides of the nose and extended from the nostrils to the of variables in the system and to focus on the role of nasal
nasopharynx. Because the MRI scans of Healthy Noses 2, 3, anatomy. The role of nasal anatomy on deposition efficiency
and 4 did not include the whole nasopharynx, the three-di- is still poorly understood, even for steady airflow. Therefore,
mensional computer reconstructions were computationally this study is a first step toward describing interhuman vari-
142 GARCIA ET AL.
pdp2 0d2a Thus, aerosol theory predicts that experimental data for dif-
, (2) ferent individuals and different airflow rates should collapse
18 18
onto a single curve in a plot versus da2Q/d3c. This predic-
where p 914 kg/m3 is the particle density, dp is the par- tion assumes that the nasal airways of different individuals
ticle geometric diameter, 0 1000 kg/m3 is the density of have the same overall shape. Individuals with anatomical
water, da dp/0 p is the particle aerodynamic diameter, abnormalities, such as septal perforations or atrophic rhini-
and 1.8 105 kg/m sec is the air dynamic viscosity. tis, may not fall on the same curve as healthy subjects.
Substituting this expression for in Equation (1), the Stokes In most previous studies of nasal deposition, a single nasal
number becomes geometry was investigated, so that dc was a constant. In such
cases, the Stokes number can be further simplified and is
0 d2aU
Stk1
. (3) then usually called the Impaction Parameter (IP):
18 dc
This definition of the Stokes number is accurate for Re0 IP d2aQ. (6)
1.0, where Re0 gdpU/ is the Reynolds number based on
particle diameter.(50) Here, g 1.20 kg/m3 is the air den- In vitro studies using nasal replicas of a single individual
sity. A more general expression is available for Re0 1500, have shown that the curves for different airflow rates col-
namely(50) lapse onto a single curve when nasal deposition efficiency is
plotted as a function of the Impaction Parameter.(24,25,27)
pdp Re01/3
Stk2
arctan
Re01/3 6 . (4) These observations validate the view that nasal deposition
gdc 6 of 1–12 m particles is governed by inertial impaction.
INTERHUMAN VARIABILITY IN NASAL FILTRATION 143
TABLE 2. SUMMARY OF ALL PARAMETERS SUGGESTED IN THE LITERATURE AND TESTED IN THIS STUDY AS CANDIDATES TO
REDUCE INTERINDIVIDUAL VARIABILITY IN NASAL FILTRATION EFFICIENCY
da particle aerodynamic diameter; Q airflow rate; p transnasal pressure drop; Amin minimum cross-sectional area obtained by
acoustic rhinometry; E ellipticity of the nostrils (ratio of the long to the short axis of the nostril); R nasal resistance obtained by rhino-
manometry; ki exponents determined by fitting equations to the experimental data; dc characteristic diameter of the nasal geometry; Re
Reynolds number; Stk Stokes number; V volume of the geometry; L centerline path length; Lnose linear distance from the nostrils
to the end of the septum; Rnose nasal resistance defined by Equation (8a); dhydraulic hydraulic diameter of the nostrils; Acoronal
min minimum
coronal cross-sectional area of the nasal cavity; SAVR surface-area-to-volume ratio of the nasal cavity.
TABLE 3. THE PRESSURE DROP (p, Pa) VERSUS AIR FLOW RATE (Q, m3/s) DATA WERE
FITTED WITH THE CURVE p aQb, Q [30, 75] L/MIN, YIELDING THE CONSTANTS A AND B
AND THE CORRELATION COEFFICIENT r2 BELOW
Subject a b r2
alternative definitions of dc. We measured the transnasal elled by air in the nasal cavity. Because the nasopharynx con-
pressure drop p in our five nasal replicas for inspiratory tributes little to the transnasal pressure drop, we defined
airflow rates ranging from 0 to 75 L/min (Fig. 3). The pres- Lnose as the linear distance from the nostrils to the end of the
sure drop was measured with a VelociCalc® Plus Air Ve- septum (Table 4). The value of the constant k is unknown.
locity Meter Model 8386 (TSI Incorporated, Shoreview, MN), However, k does not affect the ratio (dc)i/(dc)j of the charac-
while the air flow rate was measured with a Mass Flowme- teristic diameters of subjects i and j and, therefore, k also does
ter Model 4040 (TSI Incorporated, Shoreview, MN). not affect the ratio (Stk)i/(Stk)j. Given this freedom to select
We defined the characteristic diameter dc by fitting the p a value for k, we chose to use k 0.2413/41/4 0.0181
versus Q data as follows. Experimental studies of the nasal kg/[(m10/4) (sec1/4)]. Thus, the characteristic diameter dc
airflow patterns(54,55) have observed turbulence when the air- was given by
flow per nostril exceeds 200 mL/sec (24 L/min for both nos-
dc (0.0181Lnose/Rnose)4/19. (9)
trils). For turbulent flow, the pressure drop in a circular pipe
of diameter d and length L is given by:(56) The characteristic diameters obtained via Equation (9) are
given in Table 4. It was observed that almost identical esti-
p 0.241L3/41/4d19/4 Q1.75, (7)
mates were obtained when all flow rates were used to fit
where all variables are in SI units. By fitting the p versus Equation (8a), instead of limiting Q to the interval [30, 75]
Q data for each nasal replica with the curve p aQb, where L/min. In addition, it was observed that Rnose varied more
a and b are constants and Q [30, 75] L/min to ensure tur- than Lnose, so that the characteristic diameter dc was primar-
bulence, we obtained b in the range 1.76 to 1.85 for the four ily a function of the nasal resistance Rnose.
healthy noses, while an exponent of 1.87 was found for the The characteristic diameter defined by Equation (9) re-
atrophic nose (Table 3). All curve fits were made in quires measurements of p and Q for turbulent flow [Equa-
SigmaPlot™ 9.0 (Systat Software, Inc., San Jose, CA). The tion (8a)]. The characteristic diameter, however, is a geo-
similarity between these experimental estimates of the ex- metric attribute that does not depend on whether the flow
ponent b and the theoretical value of 1.75 gave us confidence is laminar or turbulent. For instance, the characteristic di-
that Equation (7) was valid for the nasal geometry, even ameter of a cylinder is its diameter (or radius) irrespective
though the constant 0.241 was expected to be specific to the of the flow regime. Therefore, the definition given by Equa-
cylindrical geometry. tion (9) should be interpreted as simply a method to mea-
The characteristic diameter dc was therefore determined sure the characteristic diameter of the nasal geometry. Al-
by fitting the p versus Q data with the equation though data from the turbulent regime is used to calculate
dc, in theory this characteristic diameter describes the nasal
p Rnose Q1.75, (8a)
geometry for both laminar and turbulent flows.
where the nasal resistance (Rnose) is Finally, we must note that our definition of nasal resis-
tance in Equation (8a) is different from the convention in rhi-
Rnose k Lnose dc19/4. (8b)
nomanometry studies. We defined nasal resistance by fitting
Here, k is a constant and Lnose is the average distance trav- a range of pressure drops and airflow rates with Equation
TABLE 4. CHARACTERISTIC DIAMETER (dc) OF THE NASAL CAVITY CALCULATED VIA EQUATION
(9) AND LENGTH FROM THE NOSTRILS TO THE END OF THE SEPTUM (Lnose).
The nasal resistance (Rnose) was calculated fitting the pressure drop versus flow rate data with
Equation (8a). r2 is the correlation coefficient of the fitting.
INTERHUMAN VARIABILITY IN NASAL FILTRATION 145
Amin Acoronal
min dhydraulic SAVR
Subject (cm2) (cm2) (mm) (mm1)
(8a), while in rhinomanometry studies nasal resistance is de- nasal cavities combined (Table 5). Table 2 summarizes all pa-
fined as the ratio p/Q for a transnasal pressure drop of 150 rameters tested in this study as candidates to describe how
Pa.(57,58) depends on nasal anatomy.
A B
FIG. 4. Deposition efficiency of micron-sized particles in the nasal cavity of a healthy individual (Healthy Nose 3) as a
function of (A) the particle aerodynamic diameter and (B) the Impaction Parameter.
146 GARCIA ET AL.
FIG. 5. Deposition efficiency in the four healthy subjects and the atrophic rhinitis patient as a function of (A) the Impaction
Parameter da2Q, (B) the modified-Impaction Parameter da2Q/Amin proposed by Rasmussen and collaborators,(22) (C) the mod-
ified-Impaction Parameter da2p proposed by Hounam and coworkers,(16) and (D) the modified-Impaction Parameter da2p2/3
proposed by Heyder and Rudolf.(12)
in detail in the Discussion and in Appendix A. In order to cavity (Table 5 and Ref.(48)). For IP 1000 m2L/min, only
simplify visualization and focus on interindividual variabil- 15% of the inhaled particles were filtered by the atrophic
ity, which is the main goal of this study, only the data for nose in contrast to the 90% filtration efficiency of Healthy
20, 30, and 40 L/min are plotted in the figures in the fol- Nose 2.
lowing discussion. We tested whether the various modified-Impaction Pa-
Significant interhuman variability was observed among rameters proposed in the literature (see Table 2) reduced in-
the four healthy individuals when nasal deposition efficiency terindividual variability. For most modified-Impaction Pa-
was plotted versus Impaction Parameter (Fig. 5A). For IP rameters, interindividual variability was reduced only
1000 m2L/min, nasal filtration ranged from approximately slightly. Figures 5B and 5C illustrate the persistent in-
40% to 90% among the four healthy subjects. The AR patient terindividual variability when is plotted versus da2Q/Amin
demonstrated poor nasal filtration compared to the healthy and da2p, respectively. In contrast, interindividual variabil-
subjects, which is consistent with his abnormally wide nasal ity was significantly reduced when deposition efficiency was
INTERHUMAN VARIABILITY IN NASAL FILTRATION 147
FIG. 5. Continued.
plotted as a function of da2p2/3 (Fig. 5D). The data for the Cheng,(27) interindividual variability was reduced but not
healthy individuals virtually collapsed onto a single curve, eliminated (Fig. 6A). Definitions of dc based on other geo-
while the data for the atrophic nose was described by a curve metrical measurements (minimum coronal cross-sectional
slightly shifted towards lower deposition. This difference be- area, surface-area-to-volume ratio, hydraulic diameter of the
tween the AR patient and the healthy subjects may be due nostrils; Table 2) were also attempted, but provided results
to the smaller surface roughness of the AR nasal replica com- similar to those displayed on Figure 6A, namely, reduced in-
pared to the replicas of the healthy noses (see Discussion). terhuman variability, but not a perfect collapse. Using the
Despite the good data collapse provided by the modified- modified-Stokes number Re0.37 Stk proposed by Grgic and
Impaction Parameter da2p2/3, this is only a phenomenologi- colleagues(52,53) also did not collapse the data for different
cal parameter, which is not based on theoretical grounds. subjects (Fig. 6B). The best collapse of the data for the four
Aerosol theory predicts that nasal deposition of micron-sized healthy individuals was obtained when the characteristic di-
particles is a function of the Stokes number (see Methods). ameter of the nasal geometry was based on pressure-flow
We experimented with various strategies (summarized in measurements [Equation (9)]. This definition of the Stokes
Table 2) to define the characteristic diameter dc of the nasal number led to an excellent data collapse, as shown in Fig-
cavity. When dc was defined as dc (Amin/)1/2, following ure 6C.
148 GARCIA ET AL.
FIG. 6. Deposition efficiency as a function of (A) the Stokes number Stk da2Q/(Amin)3/2 defined by Cheng,(27) (B) the
modified-Stokes number Re0.37 Stk proposed by Grgic and colleagues,(52,53) and (C) the Stokes number Stk da2Q/dc3, where
dc is calculated from the pressure-flow curve using Equation (9).
INTERHUMAN VARIABILITY IN NASAL FILTRATION 149
dc 19/6
Stk
FIG. 7. Curve fittings for nasal deposition efficiency () as a function (A) the modified-Impaction Parameter da2p2/3 and
(B) the Stokes number Stk da2Q/d 3c, where dc was calculated from the pressure-flow data using Equation (9). r is the cor-
relation coefficient of the fit.
In theory, nasal deposition for cyclic flow can be estimated ing at rest, f 0.25 Hz (15 breaths/min), L 7 cm and U
by dividing the inspiratory phase in a large number of in- 1.5 m/sec, so that Sr 0.01. Therefore, time-dependent ef-
finitesimal time intervals and then using Equation (11) to cal- fects are expected to be secondary and, in theory, measure-
culate the deposition efficiency for each interval. This ap- ments of nasal deposition at steady flows can be used to es-
proach is supported because the Strouhal number for nasal timate nasal deposition at cyclic breathing. This approach,
airflow at rest is small. The Strouhal number (Sr fL/U, however, still needs experimental validation. To the best of
where f is the frequency of oscillation, L is the axial length our knowledge, Haußermann and collaborators(64) made the
of the geometry, and U is the characteristic velocity) is a mea- only attempt to validate this approach. In their study, nasal
surement of the importance of time-dependent flow fea- deposition measurements for cyclic flow were lower than the
tures.(63) When Sr 1, the flow is quasi-steady, and at any corresponding estimates based on steady-state measure-
moment of time, the flow patterns are the same as those of ments. In contrast to other studies,(24,25,27) however, their
flow at steady state for the same flow rate. For nasal breath- data points for different airflow rates did not collapse onto
INTERHUMAN VARIABILITY IN NASAL FILTRATION 151
a single curve in a versus IP plot. Therefore, more studies whether the abnormal behavior of the 10 L/min data in our
are necessary to clarify the relationship between nasal de- study was due to sedimentation effects or due to the sim-
position for steady and unsteady flows. plification of the definition of Stk [Equation (4)], but these
Another possible source of deviation between nasal filtra- attempts were not successful (see Appendix A). The fact that
tion in vivo and our in vitro measurements is the finite the behavior of the 10 L/min data was not consistent among
anatomical resolution of the plastic nasal replicas. Kelly and all subjects, falling below the curve for the other flow rates
collaborators(24) established that surface roughness in nasal in one subject and above it for the other subjects (see Re-
replicas enhances particle deposition. By comparing two sults), suggests that the spurious behavior of the 10 L/min
nasal models built from MRI scans of the same individual, data was caused by a problem in the experimental setup.
but with different stereolithography techniques, these au- However, at this time, it is unclear what this problem might
thors showed that deposition is larger when surface rough- have been. It is also possible that the spurious behavior of
ness is larger. Because the nasal mucosa is smooth in a real the 10 L/min data is a Reynolds number effect that was not
person, in vitro measurements tend to overpredict deposi- considered in our analysis.
tion. We attempted to minimize such effects by using high- Finally, another limitation of this study is the small size
resolution stereolithography. In addition, it should be ac- of our cohort. The new definition of the characteristic diam-
knowledged that the geometry of the nasal replicas was not eter of the nasal passage [Equation (9)] and the curve fits
compared to the MRI scans of the healthy volunteers nor to [Equation (11)] reported here must be tested in larger cohorts
the CT scans of the AR patient. Despite the high precision of to determine whether these remain valid when different eth-
the imaging software and stereolithography technique em- nicities and different age groups are included.
ployed to construct the models, it is possible that the nasal
replicas did not reproduce the nasal anatomy perfectly.
Conclusions
Given the narrowness of the nasal geometry, even small im-
perfections in the reconstructed geometry can affect the de- It is unknown to what extent nasal filtration varies among
position measurements. These considerations mean that humans. Factors such as ethnicity, age, body size, and health
Equation (11) should be used with caution as a surrogate for status modify nasal anatomy and breathing rate, thereby
nasal filtration in vivo. Future studies should investigate the leading to interindividual variability in filtration efficiency.
importance of surface roughness and finite anatomical reso- The description of interindividual differences in nasal filtra-
lution by comparing in vitro measurements in nasal replicas tion is important to devise nasal spray devices and risk as-
to in vivo measurements performed in the same subject. sessment guidelines that are effective for the population at
Other limitations of this research need to be acknowl- large. In this study we quantified the filtration of 1–12-m
edged. First, the nasal replica of the atrophic nose was built particles in nasal replicas of five adults (four healthy volun-
from CT scans of 0.6 mm spacing, while the nasal replicas teers and one atrophic rhinitis patient). The wide nasal pas-
of the healthy noses were built from MRI scans of 3-mm spac- sages of the atrophic rhinitis patient led to a reduction in
ing. The higher resolution of the images of the AR nose pro- nasal filtration efficiency compared to the four healthy indi-
vided a nasal replica with smoother internal surface, which viduals. This finding is consistent with the expectation that
partially explains the decreased air filtration in the AR nasal filtration decreases as the characteristic diameter of the
replica compared to the nasal replicas of the normal indi- nasal passages increases. If confirmed for larger cohorts, this
viduals. It is possible that the differences between the AR finding would mean that people with wide nasal passages
nose and the healthy individuals in the versus da2p2/3 plot may receive greater lung doses of inhaled aerosols, and
and versus Stk plot (Figs. 5D and 6C) are fully explained therefore be at greater risk when exposed to airborne pollu-
by these differences in surface roughness. However, the re- tants. This reasoning is in agreement with the findings of
markable anatomic differences between the AR nose and the Lehman,(6) who observed increased incidence of silicosis in
normal nasal anatomy (Table 5 and Ref.(48)) imply that dy- workers with poor nasal filtration in a cohort of miners and
namic similarity is not perfect; therefore, aerosol theory does industry workers exposed to silica-containing rock dust.
not require that data points of the AR nose and healthy noses We proposed in the present study a new method to cal-
collapse onto the same curve. Future studies should build all culate a characteristic diameter of the nasal cavity based on
nasal replicas using the same methodology to avoid differ- pressure-flow measurements. This characteristic diameter
ences in surface roughness, and thus clarify whether patho- led to a definition of the Stokes number that nearly elimi-
logic noses follow the same curve as normal noses. nated interindividual variability in nasal deposition effi-
A second limitation of the present manuscript is the ab- ciency among the healthy noses studied. We also observed
normal behavior of the 10 L/min data. According to the a significant reduction in interhuman variability when the
Buckingham Pi theorem,(56) particle deposition for steady modified-Impaction Parameter da2p2/3 was used. However,
flows is a function of two nondimensional variables: the Stk should be favored over da2p2/3 because the latter is a phe-
Stokes number Stk and the Reynolds number Re. We ob- nomenological parameter, while aerosol theory predicts that
tained a good collapse of data for 20, 30, and 40 L/min by particle deposition is a function of the Stokes number.(50)
plotting versus Stk (or versus IP; Fig. 4B). In addition, Currently, only a limited number of individual nasal
Swift(25) also measured particle deposition in nasal replicas anatomies can be investigated through in vitro experiments
and observed a collapse of the data for 7, 15, 30, and 50 L/min due to the high-cost and labor-intensive nature of such ex-
in a versus IP plot. This suggests that particle deposition periments. In vivo measurements of nasal filtration are like-
in the nose is governed primarily by Stk, with Re playing wise problematic due to ethical concerns. In contrast, in vivo
only a secondary role because a good data collapse was ob- measurements of transnasal pressure drop are much easier
tained for different airflow rates (different Re). We tested and cheaper to perform. Therefore, the method introduced
152 GARCIA ET AL.
FIG. A-1. (A) Deposition efficiency by sedimentation ((SED)) in a straight horizontal tube that has the same length and
characteristic diameter as the nasal cavity of Healthy Nose 3. (B) Experimental deposition efficiency ((EXP)) in the nasal
replica of Healthy Nose 3 subtracted by the contribution of sedimentation ((SED)) as a function of the Impaction Parameter.
here is an appealing possibility. If this methodology remains test whether the more general definition of the Stokes num-
accurate for larger cohorts, it may be used as a noninvasive ber [Equation (4)] collapsed all data onto a single curve, we
and cost-effective technique to investigate interindividual plotted versus Stk2. However, the 10 L/min data still did
differences in nasal filtration among different age groups and not collapse with the other flow rates.
ethnicities. Another potential explanation for the abnormal behavior
of the 10 L/min data is the effect of sedimentation. To test
this hypothesis, we estimated the contribution of sedimen-
Appendix A
tation for nasal deposition of micron-sized particles by treat-
A potential explanation for the higher-than-expected de- ing the nasal airway as an effective cylinder (see below). Our
position of the 10 L/min data in three out of four subjects calculation suggested that less than 2% of 1–12-m particles
for which these measurements were available (no measure- deposit in the nose by sedimentation for air flow rates of 20
ments were made for Healthy Nose 1) is that our experi- and 30 L/min (Fig. A-1). Sedimentation was predicted to be
ments lie in the range of Reynolds numbers for which the more relevant for 10 L/min with up to 4% of the particles
definition Stk1 da2Q/d3c ceases to be valid (see Methods). To depositing due to gravity, but this effect was too small to ac-
INTERHUMAN VARIABILITY IN NASAL FILTRATION 153
count for the differences between the 10 L/min data and the 2. Black A, Evans JC, Hadfield EH, Macbeth RG, Morgan A,
other flow rates in the versus IP plot (Fig. A-1). and Walsh M: Impairment of nasal mucociliary clearance in
woodworkers in the furniture industry. Br J Ind Med. 1974;
Estimating the contribution of sedimentation 31:10–17.
to nasal deposition 3. Virtue JA: The relationship between the refining of nickel
and cancer of the nasal cavity. Can J Otolaryngol. 1972;1:
The fraction of particles depositing by sedimentation for 37–42.
laminar flow in a horizontal, circular tube of diameter d and 4. Mickiewicz L, Mikulski T, Kuzna-Grygiel W, and Swiech Z:
length L is given by:(65) Assessment of the nasal mucosa in workers exposed to the
prolonged effect of phosphorite and apatite dusts. Pol J Oc-
2
(SED)
[(2 1/3)1
2/3
arcsin 1/3] cup Med Environ Health. 1993;6:277–285.
5. Annals of the ICRP 24. ICRP (International Commission on Ra-
where diological Protection) Publication 66. Human Respiratory Tract
3L
VS
4dU
Model for Radiological Protection. Pergamon Press, Oxford;
1994.
6. Lehmann G: The dust filtering efficiency of the human nose
is a nondimensional parameter. Here, U is the mean veloc- and its significance in the causation of silicosis. J Indust Hy-
ity of the flow and VS is the settling velocity of the particle. giene. 1935;17:37–40.
For a particle with aerodynamic diameter da, the settling ve- 7. Asgharian B, Menache MG, and Miller FJ: Modeling age-re-
locity is given by:(50) lated particle deposition in humans. J Aerosol Med Deposit
pda2g Clearance Effects Lung. 2004;17:213–224.
VS
, 8. Becquemin MH, Swift DL, Bouchikhi A, Roy M, and Teillac
18 A: Particle deposition and resistance in the noses of adults
where p 1000 kg/m3 is the particle density, g 9.81 m2/s and children. Eur Respir J. 1991;4:694–702.
is the acceleration of gravity, and 1.8 105 kg/m sec 9. Schiller-Scotland CF, Hlawa R, and Gebhart J: Experimental
is the air dynamic viscosity. data for total deposition in the respiratory tract of children.
To estimate the role of sedimentation on particle deposi- Toxicol Lett. 1994;72:137–144.
tion in the nasal cavity, we approximated the nasal airway 10. Bennett WD, and Zeman KL: Effect of body size on breath-
as an effective cylinder. We estimated the mean velocity in ing pattern and fine-particle deposition in children. J Appl
the nasal airway as U Q/Amin. The tube diameter d and Physiol. 2004;97:821–826.
11. Kesavan J, Bascom R, Laube B, and Swift DL: The relation-
length L were approximated as dc and Lnose taken from Table
ship between particle deposition in the anterior nasal pas-
4. The deposition efficiency by sedimentation (SED) calcu-
sage and nasal passage characteristics. J Aerosol Med. 2000;
lated by this procedure is shown in Figure A-1 for air flow
13:17–23.
rates of 10, 20, and 30 L/min.
12. Heyder J, and Rudolf G. Deposition of aerosol particles in
We should note here that treating the nasal airways as an the human nose. In: Walton WH (ed). Inhaled Particles IV.
effective cylinder is a dramatic approximation. Although the Pergamon Press, Oxford; 107–125, 1977.
diameters dc calculated from Equation (9) range from 5.5 to 13. Giacomelli-Maltoni G, Melandri C, Prodi V, and Tarroni G:
7.3 mm (Table 4), the nasal airways resemble more a slit with Deposition efficiency of monodisperse particles in human
a thickness of approximately 1–2 mm than a cylinder. De- respiratory tract. Am Ind Hyg Assoc J. 1972;33:603–610.
creasing the diameter of the effective cylinder in the equa- 14. Cheng KH, Cheng YS, Yeh HC, Guilmette RA, Simpson SQ,
tions above would increase sedimentation. Therefore, it is Yang YH, and Swift DL: In vivo measurements of nasal air-
possible that our estimate underpredicts the contribution of way dimensions and ultrafine aerosol deposition in the hu-
sedimentation to nasal deposition of micron-sized particles. man nasal and oral airways. J Aerosol Sci. 1996;27:785–801.
15. Kesavanathan J, Bascom R, and Swift DL: The effect of nasal
Acknowledgments passage characteristics on particle deposition. J Aerosol Med
Deposit Clearance Effects Lung. 1998;11:27–39.
The authors gratefully acknowledge contributions to this
16. Hounam RF, Black A, and Walsh M: The deposition of aero-
research by Jeffry Schroeter (The Hamner), Bahman As- sol particles in the nasopharyngeal region of the human res-
gharian (The Hamner), Andy Howard (The Hamner), Darin piratory tract. Aerosol Sci. 1971;2:47–61.
Kalisak (The Hamner), William Bennett (UNC-Chapel Hill, 17. Fry FA, and Black A: Regional deposition and clearance of
USA), and Dário Martins (Santa Casa, Belo Horizonte, particles in the human nose. J Aerosol Sci. 1973;4:113–124.
Brazil). Funding for this work was provided by the Ameri- 18. Bennett WD, and Zeman KL: Effect of race on fine particle
can Chemistry Council (USA) and CNPq (Brazil). deposition for oral and nasal breathing. Inhal Toxicol. 2005;
17:641–648.
Author Disclosure Statement 19. Itoh H, Smaldone GC, Swift DL, and Wagner HN: Mecha-
nisms of aerosol deposition in a nasal model. J Aerosol Sci.
The authors have no conflict of interest in the research pre-
1985;16:529–534.
sented in this manuscript.
20. Phalen RF, Oldham MJ, and Mautz WJ: Aerosol deposition
in the nose as a function of body size. Health Phys. 1989;57
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