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JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY

Volume 22, Number 2, 2009


© Mary Ann Liebert, Inc.
Pp. 139–155
DOI: 10.1089/jamp.2008.0713

Interindividual Variability in Nasal Filtration as a Function


of Nasal Cavity Geometry

Guilherme J.M. Garcia, Ph.D., Earl W. Tewksbury, B.A., Brian A. Wong, Ph.D., and Julia S. Kimbell, Ph.D.

Abstract

Background: Interindividual variability in nasal filtration is significant due to interindividual differences in


nasal anatomy and breathing rate. Two important consequences arise from this variation among humans. First,
devices for nasal drug delivery may furnish quite different doses in the nasal passages of different individu-
als, leading to different responses to therapeutic treatment. Second, people with poor nasal filtration may be
more susceptible to adverse health effects when exposed to airborne particulate matter (PM) due to greater
lung deposition. Although interindividual variability of nasal filtration has been reported by several authors,
a relationship for predicting filtration efficiency from nasal anatomy and ventilation is still lacking. Such a re-
lationship is needed to (1) devise nasal drug delivery systems and (2) define limits of exposure to PM that are
effective for the human population at large.
Methods: Anatomically correct nasal replicas of five adults (four healthy individuals and one atrophic rhinitis
patient) were used in aerosol experiments to measure nasal deposition of 1–12-m particles. The dependence
of nasal filtration on nasal anatomy and breathing rate was investigated using various definitions of the Stokes
number as well as phenomenological Impaction Parameters proposed in the literature.
Results: Interindividual variability among the healthy adults was nearly eliminated when nasal filtration was
plotted against a specific definition of the Stokes number or against a pressure-based Impaction Parameter.
Nasal filtration in the atrophic rhinitis patient was lower than in the healthy subjects.
Conclusions: The new definition of the Stokes number introduced in this study, which is based on a new def-
inition of the characteristic diameter of the nasal passages, nearly eliminated interindividual differences in nasal
filtration. Our results suggest that it is possible to estimate nasal filtering efficiency using measurements of
transnasal pressure drop.

Key words: nasal replica cast, nasal mold, aerosol experiments, particle deposition efficiency, nasal drug de-
livery, risk assessment, interhuman variability.

Introduction widespread use of sprays and nebulizers to deliver thera-


peutic compounds. To be effective, these devices must have
10,000 liters/day of air that
A N ADULT HUMAN BREATHES
may contain dust, microorganisms, photochemical
smog, and other irritants. As the portal of entry to the res-
plume properties (droplet size and velocity) such that the
desired dose of the medical compound is delivered to its tar-
get site (e.g., the nasal turbinates, the olfactory epithelium,
piratory tract, the nose is responsible for protecting the lungs or the paranasal sinuses). A quantitative description of nasal
by scrubbing inhaled air of potentially toxic material. Expo- filtration is therefore imperative to assess both the health
sure to airborne irritants can also harm the nasal epithelium risks and the therapeutic effectiveness of inhaled particles.
itself, leading to nasal cancer, impaired mucociliary clear- There have been a myriad of investigations of nasal fil-
ance, and other nasal diseases.(1–4) Therefore, characterizing tration in the last 50 years, including in vivo measure-
nasal filtration is essential to quantify the doses of airborne ments,(8–18) in vitro studies using nasal replicas,(19–25) semi-
material to various regions of the respiratory tract.(5–7) An- empirical theoretical analyses,(26–29) and more recently,
other motivation for understanding nasal filtration is the computer simulations.(30–40) These studies established that

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

Healthy Healthy Healthy Healthy Atrophic


Subject nose 1 nose 2 nose 3 nose 4 nose

Gender Male Female Male Female Male


Age 53 years — — — 26 years
Ethnicity Caucasian — — — Caucasian
Body mass (kg) 73 55.7 74 61.2 —
SA of nasal cavitya (mm2) 20,085 16,683 23,219 20,688 13,350
Volume of nasal cavitya (ml) 18.0 15.4 26.5 23.8 34.5
SAVR of nasal cavitya (mm1) 1.12 1.09 0.88 0.87 0.39
SA of nasal cavity  nasopharynx (mm2) 24,327 21,968 27,994 24,243 16,496
Volume of nasal cavity  nasopharynx (ml) 33.3 26.8 46.5 35.9 45.1
Length from nostrils to end of septum (mm) 60.7 55.0 70.1 66.6 58.5

SA  surface area; SAVR  surface-area-to-volume ratio.


aThe nasal cavity is defined as the region between the nostrils and the posterior end of the septum.

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.

ability in nasal filtration, with the goal of identifying how


nasal geometry affects deposition efficiency at steady flow.
The next steps, which should be pursued by future studies,
will be (1) to test whether the role of anatomy described here
for steady airflow remains valid for unsteady airflow, and
(2) to incorporate interindividual variability in breathing pat-
terns in the description of interindividual variability in nasal
filtration.(44,45) Thus, the reader should keep in mind that the
constant airflow rates used here correspond to average in-
spiratory airflow, so that our deposition measurements are
an approximation of the average deposition during the in-
spiratory phase of the breathing cycle.
The aerosol concentration in air was measured before and
after the nasal replica using an Aerodynamic Particle Sizer
FIG. 2. Comparison of the simplified version of the Stokes
(Model 3321, TSI Incorporated, Shoreview, MN). Nasal fil-
number Stk1  0da2U/18dc, valid for Re0  1.0, with the
tration efficiency () was calculated as   [(inlet concen-
more general expression Stk2  (pdp/gdc)[Re01/3  6 arc-
tration)  (outlet concentration)] / (inlet concentration). At
tan(Re01/3/6)], valid for Re0  1500. Although the differ-
least three measurements were performed for each flow rate ence between the two formulas increases with flow rate and
and particle size and were subsequently averaged. particle size, the two expressions are within 25% for all flow
rates and particle sizes used in this study.
Calculation of the Stokes Number
Mathematical description of nasal deposition
For our experimental conditions, we estimate that Re0 0.8,
Aerosol theory predicts that particle motion is dominated 1.6, 2.4, and 3.2 for the air flow rates Q  10, 20, 30, and 40
by diffusion for small particle sizes and by inertial impaction L/min, respectively. These estimates are based on da 
for large particle sizes. In the regime dominated by inertia [1, 12]m and on literature results showing that U 1.5
(particle diameter 1 m), deposition efficiency is charac- m/sec for Q  15 L/min.(46,51) Equation (3) is therefore mar-
terized by a dimensionless number called the Stokes num- ginally valid for the particle sizes and air flow rates used in
ber (Stk):(50) this study. However, the Stokes numbers provided by Equa-
tions (3) and (4) differ by less than 25% for all particle sizes
U
Stk 
, (1) and airflow rates used in this study (Fig. 2). Thus, we opted
dc
to use Equation (3), because it is much simpler than Equa-
where  is the relaxation time of the particle, U is the char- tion (4). This approach has been broadly used in the litera-
acteristic velocity of the flow, and dc is the characteristic di- ture, and it is justified by the good description of the exper-
ameter of the geometry. The Stokes number can be inter- imental data it provides.(24,25,27)
preted as the ratio of the time  a particle takes to adjust to Substituting the characteristic velocity by the airflow rate
changes in the flow field to the time dc /U available for ad- (U  Q/kdc2, where k is a constant) in Equation (3) and drop-
justment. Therefore, if Stk  1, particles continue to move ping out the constants, we can redefine the Stokes num-
in a straight line when the fluid changes direction. On the ber as
other hand, particles follow the streamlines almost perfectly
d2a Q
when Stk  1. Stk 
. (5)
The particle relaxation time () is d3c

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

Parameter Comments Reference

d2a Q Impaction Parameter Aerosol theory (Hinds, 1999)


d2a p Modified-Impaction Parameter Hounam et al. (1971)
d2a p2/3 Modified-Impaction Parameter Heyder and Rudolf (1977)
(da)k1(Amin)k2(E)k3 Modified-Impaction Parameter Kesavanathan et al. (1998)
(da)k4(R)k5 Modified-Impaction Parameter Kesavanathan et al. (1998)
d2a Q/Amin Modified-Impaction Parameter Rasmussen et al. (2000)
d2a Q/(dc)3 Stokes number Cheng (2003)
dc  (Amin/)1/2
Re0.37 d2a Q/(dc)3 Modified-Stokes number Grgic et al. (2004a,b)
dc  2V/L

d2a Q/(dc)3 Stokes number This study
dc  (0.181Lnose/Rnose)4/19
dc  dhydraulic
dc  (4Acoronal
min /)1/2
dc  SAVR1

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.

Interindividual variability in nasal A new definition for the characteristic diameter dc


deposition—literature review
We introduce here a novel strategy to define the Stokes
Many researchers have observed significant interindivid- number by using measurements of transnasal pressure drop
ual variability in nasal filtration, probably due to differences to compute the characteristic diameter of the nasal geome-
in nasal anatomy and breathing patterns.(8–11,15,18) These re- try (dc). As shown in the Results section, this definition of
searchers found that the data from different individuals fol- the Stokes number reduced the interindividual variability in
low different curves on a  versus IP plot, as expected, be- our data to a greater extent than Stokes numbers based on
cause IP does not include anatomical information. After an
extensive literature review, we summarize in Table 2 all the
parameters that have been proposed by previous investiga-
tors as candidates to reduce interindividual variability. Var-
ious authors introduced phenomenological modified-Im-
paction Parameters, such as da2 p2/3, where p is the
transnasal pressure drop, as a means to reduce intersubject
variability.(12,15,16,22) Other authors chose to use Stk or a mod-
ified Stk to reduce variability.(27,52,53) Generally speaking, in-
terindividual variability was reduced, but not eliminated, in
all these studies. The only exception is the study by
Cheng,(27) where the deposition efficiency of a 53-year-old
male and a 6-week-old infant, measured through nasal repli-
cas, collapsed onto a single curve in a plot of  versus Stk.
Cheng(27) defined the characteristic diameter of the nasal pas-
sages as dc  (Amin/)1/2, where Amin is the minimum cross-
sectional area obtained via acoustic rhinometry. In the Re- FIG. 3. Pressure drop ( p) as a function of air flow rate (Q)
sults section, we use our dataset to test whether any of the in the four healthy noses and the atrophic nose. The data
parameters given in Table 2 eliminates interindividual vari- points are the actual experimental measurements, while the
ability in nasal filtration in our dataset. lines are curve fittings [see Equation (8a) and Table 3].
144 GARCIA ET AL.

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

Healthy nose 1 (4.59 0.57)  107 1.79 0.02 0.9994


Healthy nose 2 (6.58 0.58)  107 1.78 0.01 0.9997
Healthy nose 3 (1.87 0.20)  107 1.76 0.02 0.9996
Healthy nose 4 (6.27 0.48)  107 1.85 0.01 0.9998
Atrophic nose (3.55 0.47)  107 1.87 0.02 0.9994

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).

Subject dc (mm) Lnose (cm) Rnose [107 Pa/(m3/sec)1.75] r2

Healthy nose 1 6.17 6.07 3.45 0.01 0.9991


Healthy nose 2 5.47 5.50 5.55 0.02 0.9996
Healthy nose 3 7.32 7.01 1.76 0.01 0.9996
Healthy nose 4 6.39 6.66 3.19 0.02 0.9979
Atrophic nose 7.18 5.85 1.61 0.01 0.9968

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

TABLE 5. GEOMETRIC MEASUREMENTS OF THE NASAL ANATOMY USED TO DEFINE VARIOUS


ALTERNATIVES OF THE CHARACTERISTIC DIAMETER (dc)

Amin Acoronal
min dhydraulic SAVR
Subject (cm2) (cm2) (mm) (mm1)

Healthy nose 1 1.71 1.50 6.08 1.12


Healthy nose 2 1.59 1.69 8.31 1.09
Healthy nose 3 2.09 1.97 7.94 0.88
Healthy nose 4 1.56 2.21 5.80 0.87
Atrophic nose 1.81 3.06 10.90 0.39

Amin  minimum cross-sectional area; Acoronal


min  minimum coronal cross-sectional area; dhyraulic 
hydraulic diameter of the nostrils; SAVR  surface-area-to-volume ratio of the nose from the nostrils to
the end of the septum. All variables refer to the left and right cavities combined. Acoustic rhinometry
was employed to obtain Amin, while the remaining parameters were measured from the three-dimen-
sional computational reconstructions used to produce the nasal replicas.

(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.

Other definitions for the characteristic diameter dc Results


We also investigated how other definitions of the charac- A typical plot of nasal deposition versus particle size is
teristic diameter dc affected the data collapse in the  versus shown in Figure 4A. Individual measurements are shown
Stk plot. To test whether Cheng’s definition dc  (Amin/)1/2, before averaging for each particle size and air flow rate to
which leads to Stk  da2Q/(Amin)3/2, collapsed the data for provide a sense of the experimental variability. A rapid in-
our four healthy noses, we measured the minimum cross- crease in nasal deposition was observed as particle size in-
sectional area Amin of our plastic nasal replicas using acoustic creased from 1 to 12 m. For instance, for Q  30 L/min,
rhinometry (Table 5). In addition, we also studied the fol- nasal deposition increased from 0% to 100% in this particle
lowing alternative definitions of the characteristic diameter: size range. In agreement with previous investigations, nasal
dc  dhydraulic, where dhydraulic is the hydraulic diameter of filtering efficiency was significantly affected by ventilation
the nostrils; dc  (4Amin
coronal/)1/2, where Acoronal is the mini-
min rate.
mum coronal cross-sectional area of the nose; and dc  The effect of ventilation was reduced substantially when
(SAVR)1, where SAVR is the surface-area-to-volume ratio deposition efficiency was plotted versus Impaction Parame-
of the nasal cavity from the nostrils to the end of the sep- ter (Fig. 4B). The data for 20 L/min, 30 L/min, and 40 L/min
tum. The hydraulic diameter of the nostrils was calculated (when available) collapsed onto a single curve. In contrast,
as dhydraulic  4Anostrils/Pnostrils, where Anostrils is the cross- the 10 L/min data displayed an abnormal behavior. The 10
sectional area of the nostrils and Pnostrils is the perimeter of L/min data fell above the curve defined by the other flow
the nostrils. The measurements of Anostrils, Pnostrils, Amin coronal, rates (see Fig. 4B) for all nasal replicas, except for the Healthy
and SAVR were made in ICEM-CFD® using the computa- Nose 2 replica, in which the 10 L/min data fell under the
tional reconstructions of the nasal airways. All variables curve defined by the other flow rates. This spurious behav-
coronal, and SAVR) refer to the left and right
(Amin, dhydraulic, Amin ior of the 10 L/min data was unexpected, and it is examined

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 da2 p proposed by Hounam and coworkers,(16) and (D) the modified-Impaction Parameter da2 p2/3
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 da2 p, 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 da2 p2/3 (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 da2 p2/3, 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

Discussion larity in the descriptions provided by the modified-Im-


paction Parameter da2 p2/3 and the Stokes number da2Q/dc3.
Aerosol theory predicts that nasal deposition is a function
The description of interindividual variability in nasal fil-
of the Stokes number; therefore, it is not surprising that most
tration obtained in the present study may be useful for op-
modified-Impaction Parameters did not eliminate interindi-
timizing nebulizers for nasal drug delivery. Assessment of
vidual variability. However, it was unexpected that Cheng’s
interindividual variability is important to devise drug de-
Stokes number Stk  da2Q/(Amin)3/2 did not eliminate inter-
livery devices that are effective for the population at large.
human variability. Inhaled particles in the 1–12-m range
Because interhuman variability in nasal filtration due to age,
deposit mostly in the anterior nose;(19,21,30) thus, Cheng’s def-
gender, and ethnicity is mostly unknown, the nasal dose de-
inition dc  (Amin/)1/2 is logical because the narrowest
livered by nebulizers is currently calculated for a small num-
cross-section of the nasal passages (Amin) is representative of
ber of individuals who are assumed representative of the hu-
the anterior nose geometry. The poor performance of this
man population.(40,59) A similar scenario is observed in risk
definition in eliminating interindividual variation in the cur-
assessment of inhaled particles, where safety guidelines rely
rent study might be due to experimental error in our acoustic
on a theoretical factor of 10 to account for interhuman vari-
rhinometry measurements. The nasal replicas are made of
ation.(60) Our results suggest the possibility of estimating in-
hard plastic; thus, a perfect fit between the tip of the acoustic
terhuman variability in nasal filtration by measuring inter-
rhinometer and the nostrils was not possible. Measurements
human variability in transnasal pressure drop. Our data are
were repeated several times to give an average value and
described by (see Fig. 7)
minimize experimental uncertainty. However, any experi-
mental error was amplified by the power 3/2 in Cheng’s def-   1  exp((1 da2 p2/3)1) (11a)
inition of Stokes number, so that even a small experimental
or
error may have caused large differences among subjects in
the  versus Stk plot.   1  exp((2 Stk)2) (11b)
Stokes numbers based on some other definitions of dc (dc 
coronal/)1/2, d  (SAVR)1; Table 2) also where 1  (2.14 0.01)  103, 1  2.21 0.04, 2 
dhydraulic, dc  (4Amin c
(2.41 0.02)  104, 2  2.20 0.06 are constants deter-
did not collapse the data for different individuals. Compar-
coronal, and SAVR (Table mined using SigmaPlot™ 9.0; the correlation coefficients are
ing the values of Amin, dhydraulic, Amin
r1  0.997 and r2  0.994, respectively. Here p is the pres-
5), one observes that there is no clear correlation between
sure drop for a constant ventilation rate and Stk is the Stokes
these measurements. This observation highlights the chal-
number based on dc calculated from Equation (9). If these re-
lenge of defining a meaningful characteristic dimension of a
lationships hold true for larger datasets that include various
geometry as complex as the nasal airways. Using the rescal-
ethnicities and children of different ages, nasal filtration may
ing factor Re0.37 suggested by Grgic and colleagues(52,53) did
be estimated from in vivo measurements of transnasal pres-
not collapse the data either. Grgic and colleagues suggested
sure drop using rhinomanometry.(58) Such measurements are
this rescaling factor after their data for 30 and 90 L/min
easy to perform, even in children. Therefore, the equations
failed to fall onto the same curve in the  versus Stk plot. Be-
above may become a noninvasive and cost-effective strategy
cause a single mouth and throat geometry was investigated
to characterize interindividual variability in nasal filtration
in their first study,(53) it is not surprising that a rescaling fac-
by measuring variability in transnasal pressure drop.
tor could be found that collapsed the curves for these two
A few comments should be made about applying Equa-
flow rates; this rescaling factor was written as a function of
tion (11) to estimate nasal filtration in vivo. In our experi-
the Reynolds number as Re0.37. In their later study of seven
ments, the nasal replicas of the healthy individuals had no
mouth and throat geometries,(52) these authors applied the
exterior nose and the particles were delivered directly to the
same rescaling factor. Interindividual variability was re-
nostril surfaces by plastic tubing. In contrast, the amount of
duced, but not eliminated, which is consistent with our find-
particles inhaled in vivo differs from the atmospheric con-
ings (Fig. 6B).
centration because large particles may impact on the exte-
Among all parameters tested in this study, only two were
rior nose or settle before being inhaled. Thus, the particle
effective in eliminating interindividual variability in nasal
mass filtered by a human nose in vivo is proportional to the
filtration: the modified-Impaction Parameter da2 p2/3 and the
product of inhalability and nasal filtering efficiency. Equa-
Stokes number da2Q/dc3, where dc is calculated from the pres-
tions for inhalability as a function of particle size have been
sure-flow data according to Equation (9). The similarity be-
reported by other investigators,(61,62) and must be taken into
tween the descriptions provided by these two parameters
account when using Equation (11) to estimate nasal filtration
can be explained as follows. Using Equations (8a) and (8b),
in vivo. These inhalability effects may partially explain why
we have that
previous investigators found a correlation between nostril
Q7/6 k4L4noseQ shape and nasal filtration.(15,18) For instance, Bennett and Ze-
da2 p2/3  d2a(kLnose)2/3

dc 19/6 
 Stk

dc  1/6 (10) man(18) found lower nasal filtration in African Americans


than in Caucasians, which was shown to be statistically cor-
Thus, da2 p2/3 differs from our definition of the Stokes num- related to the broader nostrils of African Americans.
ber only by the quantity (k4L4noseQ/dc)1/6, which can be bro- A second possible source of discrepancy between Equa-
ken up into a flow rate contribution (k4Q)1/6 and a geome- tion (11) and in vivo measurements is that airflow was steady
4
try contribution (Lnose /dc)1/6. Using data from Table 4, we in this study, while in reality airflow is cyclic. Therefore,
4
find that (Lnose/dc)1/6 varies only from 0.34 meter0.5 to 0.39 Equation (11) provides an average for the deposition effi-
meter0.5 among our five humans, thus explaining the simi- ciency during the inspiratory phase of the breathing cycle.
150 GARCIA ET AL.

FIG. 7. Curve fittings for nasal deposition efficiency () as a function (A) the modified-Impaction Parameter da2 p2/3 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 da2 p2/3 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 da2 p2/3 was used. However,
flows is a function of two nondimensional variables: the Stk should be favored over da2 p2/3 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
References
(Suppl 1):299–305.
1. Acheson ED, Winter PD, Hadfield E, and Macbeth RG: Is 21. Zwartz GJ, and Guilmette RA: Effect of flow rate on parti-
nasal adenocarcinoma in the Buckinghamshire furniture in- cle deposition in a replica of a human nasal airway. Inhal
dustry declining? Nature. 1982;299:263–265. Toxicol. 2001;13:109–127.
154 GARCIA ET AL.

22. Rasmussen TR, Andersen A, and Pedersen OF: Particle de- putational fluid dynamics model of the human nasal pas-
position in the nose related to nasal cavity geometry. Rhi- sages. J Aerosol Med. 2007;20:59–74.
nology. 2000;38:102–107. 41. Hadfield EH, and Macbeth RG: Adenocarcinoma of eth-
23. Kelly JT, Asgharian B, Kimbell JS, and Wong BA: Particle moids in furniture workers. Ann Otol Rhinol Laryngol.
deposition in human nasal airway replicas manufactured by 1971;80:699–703.
different methods. Part II: ultrafine particles. Aerosol Sci 42. Yokley TR. The Functional and Adaptive Significance of Anatom-
Technol. 2004;38:1072–1079. ical Variation in Recent and Fossil Human Nasal Passages. Duke
24. Kelly JT, Asgharian B, Kimbell JS, and Wong BA: Particle University, Durham, NC; 2006.
deposition in human nasal airway replicas manufactured by 43. Guilmette RA, Cheng YS, and Griffith WC: Characterising
different methods. Part I: inertial regime particles. Aerosol the variability in adult human nasal airway dimensions. Ann
Sci Technol. 2004;38:1063–1071. Occup Hyg. 1997;41:491–496.
25. Swift DL: Inspiratory inertial deposition of aerosols in hu- 44. Arcus-Arth A, and Blaisdell RJ: Statistical distributions of
man nasal airway replicate casts: implication for the pro- daily breathing rates for narrow age groups of infants and
posed NCRP lung model. Radiat Protect Dosimetr. 1991;38: children. Risk Anal. 2007;27:97–110.
29–34. 45. Brochu P, DucrÇ-Robitaille J-F, and Brodeur J: Physiologi-
26. Swift DL: Age-related scaling for aerosol and vapor deposi- cal daily inhalation rates for free-living individuals aged 1
tion in the upper airways of humans. Health Phys. 1989;57 month to 96 years, using data from doubly labeled water
(Suppl 1):293–297. measurements: a proposal for air quality criteria, standard
27. Cheng YS: Aerosol deposition in the extrathoracic region. calculations and health risk assessment. Hum Ecol Risk As-
Aerosol Sci Technol. 2003;37:659–671. sess. 2006;12:675–701.
28. Mercer TT: The deposition model of the Task Group on Lung 46. Subramaniam RP, Richardson RB, Morgan KT, Kimbell JS,
Dynamics: a comparison with recent experimental data. and Guilmette RA: Computational fluid dynamics simula-
Health Phys. 1975;29:673–680. tions of inspiratory airflow in the human nose and na-
29. Xu GB, and Yu CP: Effects of age on deposition of inhaled sopharynx. Inhal Toxicol. 1998;10:91–120.
aerosols in the human-lung. Aerosol Sci Technol. 1986;5:349– 47. Segal RA, Kepler GM, and Kimbell JS: Effect of differences
357. in nasal anatomy on airflow distribution: a comparison of
30. Schroeter JD, Kimbell JS, and Asgharian B: Analysis of par- four individuals at rest. Ann Biomed Eng. 2008;36:1870–1882.
ticle deposition in the turbinate and olfactory regions using 48. Garcia GJM, Bailie N, Martins DA, and Kimbell JS: Atrophic
a human nasal computational fluid dynamics model. J Aero- rhinitis: A CFD study of air conditioning in the nasal cav-
sol Med. 2006;19:301–313. ity. J Appl Physiol. 2007;103:1082–1092.
31. Zamankhan P, Ahmadi G, Wang ZC, Hopke PK, Cheng YS, 49. Moore EJ, and Kern EB: Atrophic rhinitis: a review of 242
Su WC, and Leonard D: Airflow and deposition of nano- cases. Am J Rhinol. 2001;15:355–361.
particles in a human nasal cavity. Aerosol Sci Technol. 50. Hinds WC. Aerosol Technology: Properties, Behavior, and Mea-
2006;40:463–476. surement of Airborne Particles. Wiley-Interscience, New York;
32. Inthavong K, Tian ZF, Li HF, Tu JY, Yang W, Xue CL, and 1999.
Li CG: A numerical study of spray particle deposition in a 51. Keyhani K, Scherer PW, and Mozell MM: Numerical simu-
human nasal cavity. Aerosol Sci Technol. 2006;40:U1034– lation of airflow in the human nasal cavity. J Biomech Eng.
U1033. 1995;117:429–441.
33. Kleven M, MeLaaen MC, Reimers M, Rotnes JS, Aurdal L, 52. Grgic B, Finlay WH, Burnell PKP, and Heenan AF: In vitro
and Djupesland PG: Using computational fluid dynamics intersubject and intrasubject deposition measurements in
(CFD) to improve the bi-directional nasal drug delivery con- realistic mouth-throat geometries. J Aerosol Sci. 2004;35:
cept. Food Bioprod Process. 2005;83:107–117. 1025–1040.
34. Liu Y, Matida EA, Gu J, and Johnson MR: Numerical simu- 53. Grgic B, Finlay WH, and Heenan AF: Regional aerosol de-
lation of aerosol deposition in a 3-D human nasal cavity us- position and flow measurements in an idealized mouth and
ing RANS, RANS/EIM, and LES. J Aerosol Sci. 2007;38:683– throat. J Aerosol Sci. 2004;35:21–32.
700. 54. Hahn I, Scherer PW, and Mozell MM: Velocity profiles mea-
35. Martonen TB, Zhang ZQ, Yue G, and Musante CJ: Fine par- sured for air-flow through a large-scale model of the human
ticle deposition within human nasal airways. Inhal Toxicol. nasal cavity. J Appl Physiol. 1993;75:2273–2287.
2003;15:283–303. 55. Schreck S, Sullivan KJ, Ho CM, and Chang HK: Correlations
36. Moskal A, Makowski L, Sosnowski TR, and Gradon L: De- between flow resistance and geometry in a model of the hu-
position of fractal-like aerosol aggregates in a model of hu- man nose. J Appl Physiol. 1993;75:1767–1775.
man nasal cavity. Inhal Toxicol. 2006;18:725–731. 56. White FM. Fluid Mechanics. McGraw-Hill Companies, Inc.,
37. Sarangapani R, and Wexler AS: Modeling particle deposi- New York; 2008.
tion in extrathoracic airways. Aerosol Sci Technol. 2000;32: 57. Calhoun KH, House W, Hokanson JA, and Quinn FB: Nor-
72–89. mal nasal airway-resistance in noses of different sizes and
38. Shi HA, Kleinstreuer C, and Zhang Z: Modeling of inertial shapes. Otolaryngol Head Neck Surg. 1990;103:605–609.
particle transport and deposition in human nasal cavities 58. Cole P: Nasal airflow resistance: a survey of 2500 assess-
with wall roughness. J Aerosol Sci. 2007;38:398–419. ments. Am J Rhinol. 1997;11:415–420.
39. Tian ZF, Inthavong K, and Tu JY: Deposition of inhaled 59. Laube BL: Devices for aerosol delivery to treat sinusitis. J
wood dust in the nasal cavity. Inhala Toxicol. 2007;19:1155– Aerosol Med. 2007;20:S5–S18.
1165. 60. U.S. E.P.A. Methods for Derivation of Inhaled Reference Con-
40. Kimbell JS, Segal RA, Asgharian B, Wong BA, Schroeter JD, centrations and Application of Inhalation Dosimetry. Environ-
Southall JP, Dickens CJ, Brace G, and Miller FJ: Characteri- mental Criteria and Assessment Office, Office of Health and
zation of deposition from nasal spray devices using a com- Environmental Assessment, Cincinnati, OH. EPA/600/8-
INTERHUMAN VARIABILITY IN NASAL FILTRATION 155

90/066F: Available from the National Technical Information Received on July 11, 2008
Service, Springfield, VA, PB2000-500023, and online at in final form, November 29, 2008
http://www.epa.gov/ncea, 1994.
61. Hsu DJ, and Swift DL: The measurements of human inhal- Reviewed by:
ability of ultralarge aerosols in calm air using mannikins. J Warren Finlay
Aerosol Sci. 1999;30:1331–1343. Beth Laube
62. Liden G, and Harper M: The need for an international sam-
pling convention for inhalable dust in calm air. J Occupat
Environ Hygiene. 2006;3:D94–D101.
63. Çengel YA, and Cimbala JM. Fluid Mechanics: Fundamentals
and Applications. McGraw-Hill Companies, Inc., New York; Address reprint requests to:
2006. Dr. Julia S. Kimbell
64. Haubermann S, Bailey AG, Bailey MR, Etherington G, and The Hamner Institutes for Health Sciences
Youngman M: The influence of breathing patterns on parti- 6 Davis Drive
cle deposition in a nasal replicate cast. Aerosol Sci. 2002;33: P.O. Box 12137
923–933. Research Triangle Park, NC 27709
65. Pich J: Theory of gravitational deposition of particles from
laminar flows in channels. Aerosol Sci. 1972;3:351–361. E-mail: kimbell@thehamner.org

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