Articol 1 - Diffusion Microchannels - Balan Et Al.

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C. Kleinstreuer1,2 and Z. Zhang1

1
Department of Mechanical and Aerospace Engineering and 2 Department of Biomedical
Engineering, North Carolina State University, Raleigh, North Carolina 27695;
email: ck@eos.ncsu.edu, zhezhang@eos.ncsu.edu
Annu. Rev. Fluid Mech. 2010. 42:301–34 Key Words

First published online as a Review in Advance on human respiratory airway models, experimental observations and computer
September 2, 2009
simulations, laminar/turbulent airflow structures, dilute suspensions of
The Annual Review of Fluid Mechanics is online at nanomaterial, solid particles or droplets, inhaled/exhaled aerosol transport
fluid.annualreviews.org
and deposition
This article’s doi:
10.1146/annurev-fluid-121108-145453 Abstract
Copyright c 2010 by Annual Reviews. Airflows in the nasal cavities and oral airways are rather complex, possibly fea-
All rights reserved
turing a transition to turbulent jet-like flow, recirculating flow, Dean’s flow,
0066-4189/10/0115-0301$20.00 vortical flows, large pressure drops, prevailing secondary flows, and merg-
ing streams in the case of exhalation. Such complex flows propagate subse-
quently into the tracheobronchial airways. The underlying assumptions for
particle transport and deposition are that the aerosols are spherical, nonin-
teracting, and monodisperse and deposit upon contact with the airway sur-
face. Such dilute particle suspensions are typically modeled with the Euler-
Lagrange approach for micron particles and in the Euler-Euler framework
for nanoparticles. Micron particles deposit nonuniformly with very high con-
centrations at some local sites (e.g., carinal ridges of large bronchial airways).
In contrast, nanomaterial almost coats the airway surfaces, which has impli-
cations of detrimental health effects in the case of inhaled toxic nanoparticles.
Geometric airway features, as well as histories of airflow fields and particle
distributions, may significantly affect particle deposition.
301
1. INTRODUCTION
Accurate experimental/computational simulations and predictions of airflow structures and related
particle depositions in realistic models of the human respiratory system are of fundamental impor-
tance. The basic goals of these models are an in-depth understanding of the O2 -CO2 gas exchange,
inhaled toxic material deposition, and possible mucus clearance, as well as optimal drug-aerosol
targeting to combat lung and systemic diseases. These are challenging tasks because of the complex
airway geometries, three-phase flow phenomena, fluid-structure interactions, cell mechanics, and
heat and species mass transfer. For example, human nasal cavities, with an effective length of only
10 cm, feature a wide array of basic flow phenomena because of their complex geometries and
inhalation/exhalation waveforms. Thus, in addition to being transient three dimensional (3D),
they may include laminar/turbulent flows, stagnation point and boundary-layer flows, and flow
separation with recirculation zones and may be impacted by distensible walls and heat and mass
transfer.
Clearly, the fluid dynamics and biomechanics phenomena occurring in a complete set of realistic
pulmonary airways cannot yet be simulated, let alone patient-specific ones. In fact, presently, stan-
dard experimental/computational simplifications for air-particle flow analyses include steady lam-
inar, isothermal airflow; rigid airways; spherical noninteracting particles; and particle deposition
upon contact with the wall. However, based on medical imaging [e.g., computed tomography (CT)
scans, magnetic resonance imaging (MRI), positron emission tomography, ultrasound, and their
multimodal combinations] with the proper geometry-file conversion, researchers can perform
more comprehensive and detailed computer simulations, at least for representative airway seg-
ments. With the advent of petascale computing (i.e., 1015 calculations per second), future simula-
tion results will cover the most important transport phenomena in the nasal-oral-tracheobronchial
airways, as well as part of the alveolar region. Parallel to advances in computer modeling, high-
definition imaging [e.g., scans beyond airway generation 6 (G6) and radio-labeled particle tracking
in the lung] and high-resolution experimental measurements will contribute significantly to solv-
ing the problem of both dosimetry and the health effects of inhaled toxic particulate matter and
optimal drug-aerosol targeting to predetermined lung sites.
Several aspects of respiratory biomechanics have been recently reviewed in a special issue
of Respiratory Physiology and Neurobiology (Elad & Schroter 2008). The impact of toxic particle
inhalation has been reviewed by Phalen (2009), whereas targeted drug-aerosol delivery in the
human respiratory system has been discussed by Kleinstreuer et al. (2008).
2. AIRWAY MODELS
Accurate and realistic airway models compose the necessary precursor for experimental or com-
putational airflow and particle transport/deposition analyses. In optimal drug-aerosol delivery,
once an experimentally validated computer-simulation model has been developed, operational
parameters for a smart inhaler system, for instance, can be computed to conduct patient-specific
therapy. In any case, the nasal plus oral airways are referred to as the extrathoracic region, which,
along with the tracheobronchial and alveolar regions, forms the respiratory system (Figure 1).
From a functional viewpoint, the respiratory tract is divided into the conducting zone (i.e., G0 to
G16) and the respiratory zone (G17 to G23), where O2 -CO2 gas exchange takes place (Silverthorn
2004). An alternative geometric division would include the extrathoracic, upper bronchial, lower
bronchial, and alveolar region.
There are two modern approaches for generating geometric lung models for computa-
tional/experimental analyses: via algorithms that specify inhaled, volume-based rules for the
302 Kleinstreuer · Zhang

Nasal Posterior
passages Anterior
Generation Generation
number Nasal number (G)
(G) Pharynx
Oral
0 Trachea
1 Main
bronchus
Conducting zone
2 Bronchus G1
3 G2
4 G3
Bronchiolus G4
5
G5
G6
16 Terminal
bronchiolus G7
17 G8
18 Respiratory
bronchiolus
Respiratory zone
19
20
21 Alveolar
duct
22
23 Alveolus
Figure 1
Schematics of the human respiratory system. Figure from Kleinstreuer et al. 2008.
relationships between parent and daughter airways (e.g., Burrowes et al. 2008, Ma & Lutchen
2009) and lung replicas digitally reconstructed from CT scans or MRI data (e.g., Luo & Liu 2008,
van Ertbruggen et al. 2005). Using the first approach, Tebockhorst et al. (2007) also included air-
way morphogenesis due to development in children or triggered by lung diseases in their computer
model.
As mentioned above, the ultimate goal of these models is patient-specific modeling, which
one day will be applicable to relevant problem areas in biomedical engineering. Specifically, em-
ploying computer simulations supported by experimental tests, patient-specific modeling would
gain quantitative results and valuable physical insight for the best possible medical management
(e.g., Taylor & Draney 2004), including optimal drug delivery, but also organ replacement, by-
pass grafting, and/or implant design (see Kleinstreuer 2006, chapter 5, for sample applications).
The first step is to generate patient-specific airway (or blood-vessel) geometry data files. The
generic procedure is as follows. CT-scan images or enhanced MRI results of a subject’s body
part (i.e., DiCom files) are obtained from a radiologist or surgeon. Notably, the determination
of airway or vessel-wall thicknesses is still rather difficult. MRI, which measures the amount of
hydrogen, is a good technique for distinguishing different tissues and thus may help estimate
variable wall thickness. The DiCom files are loaded into geometric-file-conversion software, such
as Mimics/Geomagic (Materialise, Belgium) or Simpleware (Simpleware Ltd., Exeter, UK). This
software enables the modeler to edit the images, isolate the structures of interest, and generate 3D
www.annualreviews.org • Airflow and Particle Transport 303

geometry models. The CAD-like geometry files are then exported in suitable formats, typically
to computational fluid dynamics (CFD) software for mesh generation, and for numerical fluid
flow and solid structure analysis (e.g., see Shi et al. 2006, Wolters et al. 2005). Alternatively, the
3D finite-element computer model can be exported as an STL (stereolithography) file to a rapid
prototyping machine to build a physical model for laboratory studies (e.g., Kratzberg et al. 2005).
Of course, still images and dynamic imaging of human physiology extend well beyond the needs
of modelers in biomedical engineering into diagnostics, surgery planning, implant placement,
functional analysis, and follow-up studies (see Cinquin & Troccaz 2003, Perchet et al. 2004).
As mentioned above, realistic 3D imaging, and hence modeling, of the entire human lung is
unrealistic because of four major obstacles: (a) Presently, CT/MRI resolutions do not exceed G6
(or G8). (b) The lung consists of 23 generations (see Figure 1), encompassing 223 airways plus
millions of alveoli of different shapes with effective diameters of the order of 300 μm. (c) Given
the larynx (with its vocal cords plus the epiglottis) and the rather rigid airways in the conducting
zone, the geometry of the respiratory tract is time dependent, especially the alveoli. (d ) All lung
morphologies differ, and exact patient-specific modeling is still cost prohibitive.

For modeling purposes, the basic regions of the human respiratory system (see Figure 1) are
the extrathoracic region (i.e., nose, mouth, and throat), the tracheobronchial part (i.e., trachea,
or wind pipe, and bronchial tree), and the alveolar region (i.e., alveolar ducts and sacs). The
tracheobronchial airways are covered with a mucus layer that overlays fine hairs, the cilia, attached
to the walls. The oscillatory motion of the cilia propels the mucus layer, which may capture inhaled
particles, which leads to upward transport to the throat and ultimately clearance. Cartilaginous
rings are present in the trachea and upper bronchi for airway stabilization, forming an uneven
surface that may influence airflow and particle deposition (Li et al. 2007a, Zhang & Finlay 2005).
In the alveolar (or pulmonary) region (i.e., after G16), O2 -CO2 gas exchange takes place.
2.1. Basic Bifurcations

Basically, realistic (or for the most part idealized) respiratory segments include the nasal cavities
(Doorly et al. 2008a,b; Schroeter et al. 2006; Shi et al. 2008; Xi & Longest 2008c; Zamankhan
et al. 2006), the oral airways (Ball et al. 2008a,b; Cheng et al. 1997b; Lin et al. 2007; Xi &
Longest 2007; Zhang et al. 2002c), triple bifurcation of the bronchial tree (Kleinstreuer & Zhang
2009; Theunissen & Riethmuller 2008; Zhang et al. 2002a,b), and alveolated ducts (Balashazy
et al. 2008, Dailey & Ghadiali 2007, Harrington et al. 2006). Such basic airway components
allow for focused studies of both the respiratory-system geometry and the associated air-particle
transport phenomena. For example, Zhang et al. (2002a,b) analyzed cyclic airflow patterns and
micron-particle deposition in a triple bifurcation with different geometric features. Of interest
were the effects of smooth and sharp carinal ridges, as well as in-plane and out-of-plane daughter
tube configurations, on airflow and particle deposition. They also found a steady-state equivalent
Reynolds number,
Reeq uiv. = 0.5(Remax + Remean ), (1)
which matches deposition results under transient flow conditions, as long as the inhalation wave-
form is relatively smooth and the flow is laminar. More elementary, but most important for
computer-model validation, is the single bifurcation for which Lieber & Zhao (1998) measured
air-velocity profiles in space and time, whereas Kim & Fisher (1999) provided experimental aerosol
deposition characteristics.

2.2. Idealized Lung Configurations

Over the years several geometric lung models have been proposed. The enduring Weibel Type
A model (Weibel 1963) is still used worldwide by experimentalists and CFD analysts because
of its simplicity. It assumes that each lung generation branches symmetrically into two identical
daughter branches. This is not realistic, and even the individual tube effective diameters and
lengths are not quite correct (see Finlay 2001 for a discussion and the data comparison in his
table 5.1). In addition, the configuration and geometric data are for normal adult lungs. Clearly,
children and adult patients with asthma, chronic obstructive pulmonary disease, and other lung
ailments may feature unusual airway geometries. Therefore, various geometric improvements and
extensions have been proposed (e.g., Finlay 2001, Haefeli-Bleuer & Weibel 1988, Horsfield et al.
1971, Phalen et al. 1985, Raabe et al. 1976).
Although it is recognized that specific features of airway geometry have a major influence
on the local airflow structures and hence the particle-deposition pattern, idealized lung-airway
models perform quite adequately for the estimation of global deposition values (Kleinstreuer &
Zhang 2009). The most extreme example is the trumpet model (Choi & Kim 2007, Park & Wexler
2007), which geometrically converts the entire respiratory tract into a 1D expanding airway for
single-path transport modeling. Other examples for cost-effective global-lung modeling include
stochastic lung models (NCRP 1997, RIVM 2002) and deterministic semiempirical correlations
(ICRP 1994). Recently, Kleinstreuer & Zhang (2009) simulated air-particle flow in 16 generations
of the tracheobronchial tree, which were repeated in series and parallel, based on adjustable triple-
bifurcation units following the Weibel Type A model. The computed tracheobronchial deposition
fractions (DFs) were in line with experimental data sets for all available particle diameters (50 nm ≤
dp ≤ 10 μm) and two inhalation flow rates (Q = 15 and 30 liters min−1 ). However, two questions
remain: Can this 16-generation network be statistically representative for large population groups
after the necessary modifications, and are the local particle DFs accurate? Nonetheless, as long as
restrictions on computer (and laboratory) resources prevail, simplified modeling approaches are
necessary.
2.3. Realistic Airway Models

Because of the shortcomings of idealized lung-airway geometries and the dire need for accu-
rately predicting toxic or therapeutic aerosol depositions, researchers now focus on anatomically
based human airway models. Specifically, modern imaging techniques and geometry-file con-
version software allow for the representation of patient-specific airway configurations (e.g., see
http://www.i-clic.uihc.uiowa.edu). For example, Ma & Lutchen (2006, 2009) described meth-
ods for medical imaging and computer mesh generation for the upper airways of a healthy adult.
The impact of airway geometry on micron-particle deposition was demonstrated by Xi & Longest
(2007), who compared deposition results for a subject-specific and three idealized oral airway
models. Burrowes et al. (2008) reviewed work in the development of anatomically based models
on both the lung organ level and the associated tissue level. Perchet et al. (2004) provided the
necessary information for linking medical images (e.g., those obtained via multidetector computed
tomography) to mesh generation for simulation studies. In many applications, commercial soft-
ware packages, such as SimpleWare (Simpleware Ltd, UK) or Mimics (Materialise, Belgium), are
being employed for MRI/CT scan geometric file conversion to finite-volume or finite-element
meshes.
In contrast to the large number of lung airways (if spread out, they would cover a tennis court),
the two asymmetric nasal airways are always modeled based on anatomy. Recent examples include

contributions by Doorly et al. (2008a,b), Kelly et al. (2004a,b), Shi et al. (2006, 2007, 2008), and
Xi & Longest (2008c).
3. AIRFLOW STRUCTURES
As mentioned above, within the restriction of incompressible subsonic flow, most textbook fluid
flow phenomena appear in the human respiratory system. This is especially true for the nasal
airways; however, typically people breathe through the nose only at low flow rates, which preclude
turbulence and interactions between the airflow and cavity wall. In any case, specific air velocity and
pressure fields largely depend on the individual’s inhalation/exhalation waveform, the local airway
geometry, and temporary changes in airway geometry, such as speaking, swallowing, sleep apnea,
and asthma attacks. In turn, airflow structures and pressure levels determine aerosol transport and
deposition, mucus clearance, gas exchange, and wall movement.
Examples of governing equations for transient (or quasi-steady) laminar/turbulent airflows are
listed in Ball et al. (2008b), Luo et al. (2004), and Zhang & Kleinstreuer (2003a,b), among oth-
ers. Specifically, Zhang & Kleinstreuer (2003a,b) provided isothermal and nonisothermal airflow
equations for laminar and Reynolds-averaged Navier-Stokes (RANS) turbulence models, whereas
Luo et al. (2004) and Ball et al. (2008b) described the approaches of large-eddy simulation (LES)
and the lattice Boltzmann method, respectively.
3.1. Nasal Airways

Airflow in human nasal cavities has been measured for decades, starting with Swift & Proctor
(1977) who used a mini-Pitot tube to estimate the different flow rates in individual airways. Hahn
et al. (1993), Kim & Chung (2004), Churchill et al. (2004), and Doorly et al. (2008a) built replica
models from computerized axial tomography scans and used particle image velocimetry (PIV) to
study airflow patterns at different inhalation flow rates. Although the experimental results did not
reveal detailed flow fields, the observations indicated that the majority of airflows through the
middle-to-inferior main passage were laminar, which supposedly prevails up to Qin = 24 liters
min−1 on average. Furthermore, quasi-steady airflow may be a reasonable assumption.
In terms of computational investigations, Keyhani et al. (1995) and Subramaniam et al. (1998)
simulated a steady laminar airflow pattern and validated their simulations with experimental data
by Hahn et al. (1993). Horschler et al. (2003) employed a structured mesh solver with an advective
upstream splitting method to solve for the airflow field; however, only streamlines were presented.
Most recently, Shi et al. (2008) and Xi & Longest (2008b) simulated the detailed, local airflow
structures in the narrow and complex nasal passages, employing high-resolution hybrid meshes
(e.g., tetrahexdral meshes with multilayered prismatic wall elements).
Figure 2 shows a typical inspiratory airflow structure in the human nasal cavity, assuming
steady laminar flow under resting conditions (Q = 7.5 liters min−1 ). After the airflow enters a
nasal cavity, the majority of flow passes through the middle-to-low portion of the main passage-
way between the middle and inferior meatuses (see Figure 2d–f ). In particular, two high-speed
regions are located under the middle and inferior meatuses. The narrow olfactory region and
the upper part of the middle and inferior regions receive only small amounts of air, which is
believed to protect the cells for the sense of smell. Although airflow enters the nose almost ver-
tically, the quasi-funnel shape of the vestibule redirects the airflow horizontally after the nasal
valve (i.e., toward the lower nasal passageway). Then, most of the inhaled air flows through the
wider middle-to-low portion of the main passageway, which is free of obstacles. The secondary
flow fields are quite strong in the middle part of the nasal cavities (e.g., slices 3-3 and 5-5 in

a d e
Speed/Uinlet Q = 7.5 liters min–1, Uinlet = 1.263 m s–1 Normal velocity (u/uinlet) Normal velocity (u/uinlet)
1.30 Reinlet = 640 0.75 0.75
1.16 Y 0.67 0.67
1.01 3 4 Z 0.58 0.58
0.87 5 0.50 0.50
0.72 2 X 0.42 0.42
0.58 0.33 0.33
0.25 0.25
0.43 Normal velocity 0.17 0.17
0.29 1 u = u2 0.08
0
0.08
0
0.14
0
6
3' 4'
Nostril 1' 2' 5' 3–3' 4–4'
6'
b c f g
Normal velocity (u/uinlet) Normal velocity (u/uinlet) Normal velocity (u/uinlet) Normal velocity (u/uinlet)
1.00 1.00 0.75 0.75
0.89 0.89 0.67 0.67
0.58 0.58
0.78 0.78
0.67 0.67 0.50 0.50
0.56 0.56 0.42 0.42
0.44 0.44 0.33 0.33
0.33 0.33 0.25 0.25
0.22 0.22 0.17 0.17
0.11 0.11 0.08 0.08
0 0 0 0
1–1' 2–2' 5–5' 6–6'
h i
Q = 7.5 liters min–1 Q = 7.5 liters min–1
uinlet = 1.263 m s–1 uinlet = 1.263 m s–1
Reinlet = 640 uref = 1.0 uinlet Reinlet = 640 uref = 1.0 uinlet
Slice 3–3' Slice 5–5'
Figure 2
Examples of airflow structures in human nasal cavities at a constant inlet flow rate of 7.5 liters min−1 : (a) 3D
streamlines and velocity contours, (b–g) velocity fields in six selected slices, and (h,i ) secondary velocity fields
in slices 3-3 and 5-5 . Figure adapted from Shi et al. 2008.
Figure 2h,i ) because of the locally complex geometric features and the airflow-direction changes
in the vestibule. As the air flows into the anterior portion of the two meatuses, normal or axial
flow is dominant (see slice 3-3 ) while the secondary air passes into the meatus regions. In con-
trast, in the posterior areas of the meatuses (see slice 5-5 ), secondary flow is directed out of the
meatuses. As a result, secondary flow may also be a factor in delivering nanoparticles into the
meatuses.

The flow in the nasal cavity may also be influenced by the inflow condition and airway geometry,
as well as the size and orientation of the internal nasal valve (Doorly et al. 2008b). For example, Shi
et al. (2008) demonstrated that the local airflow rate increases notably in the olfactory region and
drops slightly in the meatus regions as the inspiratory flow rate increases from 7.5 liters min−1 to
20 liters min−1 . In general, the various flow-rate percentages are a function of local area dividers,
protrusions into the individual passageways, and flow momentum. At higher flow rates, more air
may detour the meatus regions because of the stronger momentum, which helps relatively more
airflow to bypass the geometric protrusions, such as the meatuses. Doorly et al. (2008b) reported
that significant differences (e.g., airflow to the olfactory clef ) can be observed between simulations
employing a blunt profile and a more realistic physiological inflow incorporating the external face
as part of modeled domain. The effects of nasal-cavity geometry may be inferred from different
computational studies conducted by different research groups. For example, the distributions of
flow about the turbinates vary in the different studies. However, the model techniques used (e.g.,
mesh generation approach, physical model and solver) are different in these studies as well. So far,
specific studies on nasal geometry effects have not been reported.
3.2. Lung Airways

Recently, steady and transient airflows in human lung airways (starting from the mouth and
proceeding through the pharynx, larynx, and trachea to the bronchial tree and alveolar regions)
have been extensively investigated both experimentally and theoretically (e.g., Adler & Brucker
2007; Ball et al. 2008a,b; Fresconi & Prasad 2007; Gemci et al. 2008; Grosse et al. 2007; Johnstone
et al. 2004; Lieber & Zhao 1998; Lin et al. 2007; Luo & Liu 2008; Ma & Lutchen 2006; Nowak
et al. 2003; Theunissen & Riethmuller 2008; van Ertbruggen et al. 2005, 2008; Yang 2006; Zhang
& Kleinstreuer 2002, 2004; Zhang et al. 2008). The effects of geometric airway changes are most
pronounced during inhalation. Experimental and computational analyses have focused mainly on
isolated sections of the human airways, such as the oral airways (or oral airway plus the first few
generations), multigeneration bronchial airways, and alveolated ducts or sacs.
Similar to the experimental studies for nasal airflow structures, PIV and hot-wire measurements
were also employed to measure velocity profiles in models of human lung airways. For example,
Heenan et al. (2003) and Johnstone et al. (2004) measured velocity profiles in an idealized human
extrathoracic airway using PIV and hot wire, respectively. Grosse et al. (2007) measured steady
and unsteady flow fields in the first bifurcation of a realistic silicone lung model G0 to G6 em-
ploying PIV. Theunissen & Riethmuller (2008) reviewed the PIV measurements of flow fields for
multibifurcation lung airways, and Fresconi & Prasad (2007) measured secondary velocity pro-
files in models of multigeneration conducting airways. These experimental studies may provide
validation and confirmation for more detailed computer simulations. However, some studies also
demonstrated that PIV and hot-wire measurements are not completely accurate (Ball et al. 2008a,
Heenan et al. 2003, Johnstone et al. 2004). Specifically, hot-wire measurements are not reliable
in zones with recirculation and secondary flows, whereas PIV measurements are influenced by
optical access and seeding limitations.
As for the computational studies, the use of appropriate CFD techniques is most important
for obtaining corrected airflow structures in the lung airways. Airflow in human lung airways may
undergo different flow regimes (i.e., laminar, transitional, and turbulent flows) in different airway
segments. Specifically, the flow may be laminar in the oral cavity and become transitional and
turbulent after the constriction formed by the soft palate and throat, but it may eventually turn
into laminar flow again after several generations in the bronchial tree because the local Reynolds
number gradually decreases. Hence, an appropriate low–Reynolds number (LRN) turbulence

model should be employed to simulate such flows. Clearly, such a model should not only predict the
transitional to fully turbulent flow behaviors, but should also capture the laminar velocity profiles
and pressure drops at lower Reynolds numbers. In the traditional RANS turbulence models, the
standard k-ε and k-ω models [including the renormalization group (RNG) k-ε and Menter k-ω
models] amplify flow instabilities after tubular constrictions and hence fail to capture laminar flow
behavior at LRNs, whereas the LRN k-ε model fails to simulate the transition to turbulent flow
(Varghese & Frankel 2003, Zhang & Kleinstreuer 2003a). On the contrary, the LRN k-ω model
has been proven to be one of the best RNAS models for modeling laminar-transitional-turbulent
airflows in constricted upper airways (Zhang & Kleinstreuer 2003a). However, Ball et al. (2008a)
demonstrated that the LRN k-ω model may still have large discrepancies in some regions (e.g.,
mid-stream locations) when compared with measurements, possibly because of both experimental
uncertainties and model approximations. Still, a tenfold increase in mesh refinement may greatly
improve the airflow accuracy when compared with the results of earlier CFD simulations (Ball
et al. 2008a).
Recently, LES and the lattice Boltzmann method have become alternative approaches for
modeling laminar-turbulent airflows in lung airways (Ball et al. 2008b, Freitas & Schroder 2008,
Lin et al. 2007, Luo et al. 2004). Luo et al. (2004) also demonstrated that LES may better predict
transitional airflows in constricted airways when compared with the LRN k-ε model. However,
no comparisons between the LRN k-ω model and LES have been published. Our ongoing studies
show that LES may predict similar mean flow structures as the LRN k-ω model.
3.2.1. Oral airways. Here we describe some of the main flow features in the oral airway mod-
els (Ball et al. 2008a,b; Kleinstreuer & Zhang 2003; Lin et al. 2007; Nithiarasu et al. 2008; Xi
& Longest 2008a; Zhang & Kleinstreuer 2004). Skewed velocity profiles generated by centrifu-
gal force can be observed in the curved portion of the oral airway, from the oral cavity to the
pharynx/larynx. Recirculated flows are created in regions with abrupt geometric changes (e.g.,
contraction and expansion). Such regions include the tongue and upper portion of the oral cavity,
the narrow portion of the pharynx, the epiglottis, and the entrance to the trachea (see Figure 3).
Asymmetric laryngeal jets and impinging flows are formed due to acceleration around the struc-
tures of the larynx. Large pressure drops and wall shear stress may be observed close to the narrow
portion of the pharynx (Nithiarasu et al. 2008). Secondary motions are set up when the flow
turns a bend from the mouth to the pharynx because of the centrifugally induced pressure gradi-
ent (Kleinstreuer & Zhang 2003). Secondary flows become more complicated downstream from
the mouth when the airstream expands or constricts with the varying cross-sectional areas and
continues to turn a bend from the pharynx to the larynx (Figure 3). In addition, the interaction
between secondary and axial motions also causes more complicated flows (e.g., six distinct vortices;
see Kleinstreuer & Zhang 2003). Turbulence may occur locally during normal inhalation (e.g.,
Q > 15 liters min−1 ). Usually, the turbulence intensity in the oral airway rises rapidly after the
constriction caused by the soft palate and then decreases until the disturbance is activated again
by the throat (glottis) (Lin et al. 2007, Zhang et al. 2002c). Turbulence levels, in terms of kinetic
energy k, seem to increase quickly through the strong varying-diameter zone after the glottis and
then decay, approaching an asymptotic level of approximately 0.2–0.3 (k/uin 2 ) at the six-diameter
station from the throat (Corcoran & Chigier 2000). With further redistribution of the flow’s ki-
netic energy over most of the cross section, accompanied by the onset of turbulence, the velocity
profiles may become more blunt (Kleinstreuer & Zhang 2003). The apparent effects of unsteadi-
ness can be observed in the oral airways during the decelerating phase of the inspiratory cycle
at normal breathing (Qin = 30 liters min−1 ) (Zhang & Kleinstreuer 2004). Specifically, airflow
during the decelerating phase exhibits apparent turbulent features and resembles those at peak

1'
Recirculating flows
Speed (m s–1)
3.0
2.6
2.2
1.8
1.4 2 2'
1.0
0.6 Laryngeal jet
0.2
1–1' 2–2'
–0.05 0.10 0.25 0.40 0.55 0.70 2.6

2.0
1.4
0.8
0.2
–0.4
Selected axial velocity contours and secondary velocity vectors
Figure 3
Examples of flow patterns in an idealized oral airway model at a constant inlet flow rate of 15 liters min−1 .
Results were obtained using large-eddy simulation with geometry data from Prof. A. Pollard (Queen’s
University, Canada) by permission.
inspiration. The onset of turbulence may take place during acceleration when Retrachea ≈ 2400,
but turbulent fluctuations may not weaken until Retrachea < 800 during deceleration. Moreover,
the difference in pressure drops between the transient case and quasi-steady case is relatively large
during deceleration.
Flow inside the oral airways may be further complicated by geometric features, such as the
compound curved expansion in the oral cavity or the epiglottis with its 3D curved sharp, leading
edge (Ball et al. 2008a). For instance, the location of the laryngeal jet, its deceleration, and the
overall pressure drop may be influenced by the shapes of the glottic aperture (Brouns et al. 2007).
Lin et al. (2007) predicted a laryngeal jet biased toward the rear wall of the trachea, whereas

Xi & Longest (2007), Ball et al. (2008a,b), and Zhang & Kleinstreuer (2004) found it biased
toward the front wall, employing different geometries.
One common conclusion of all these modeling effects concerning oral airway flows is that the
complex flows developed in the oral airways propagate subsequently into the tracheobronchial
airways. Hence, the realistic inlet conditions obtained from the upper head airways should be
applied to the bronchial airways, rather than using idealized inlet conditions (such as uniform,
fully developed laminar, or turbulent velocity profiles).
3.2.2. Bronchial airways. As mentioned above, single bifurcation models were the first employed
to understand flow behavior in bronchial airways. However, later studies confirmed that the first
bifurcation in large, multigeneration airways influences the flow in subsequent bifurcations (e.g.,
the second and third bifurcations) because the length of daughter tubes is not sufficiently long
for flow development (Theunissen & Riethmuller 2008, Zhang et al. 2001). Hence, realistic,
multigeneration lung bifurcation models were recently employed to study lung airway flows (see
Figure 1). Because of the limitation of geometric resolutions or computer resources, the most
popular bifurcation models in both experiments and simulations do not exceed six generations.
Most recently, Gemci et al. (2008) attempted to simulate airflows from the trachea to airway
generation 17. However, the computational mesh employed was very coarse and lacked a grid-
independence test due to limitations in computer resources, even with a tetra-scale computing
platform. For example, they used only approximately 4600 cells for each bronchus (6.744 × 106
for 1453 bronchi) for LES turbulence modeling, which is far less than the required resolution for
the convergence of velocity fields, even for laminar flows (usually >50,000 cells for a bronchus)
(Longest & Vinchurkar 2007a).
Although the turbulence levels appear to decay in the trachea of oral airway models, new flow
instabilities may be induced again at the bifurcation region due to the severe geometric transition
from the parent tube to the two daughter tubes (Kleinstreuer & Zhang 2009). Specifically, strong
turbulence fluctuations occur just around the flow dividers because of the contraction of the top
and bottom surface in the carinal ridges; moreover, the closer the airflow is to the divider, the
higher is the turbulence level. The turbulence intensities may be different at different dividers
owing to the different upstream effects and contraction ratios. In addition, turbulence decays
rapidly in the straight segment of the bifurcating tubes. Generally, turbulence occurring after the
throat can propagate to at least a few generations (e.g., generation G6) even at a low local Reynolds
number (e.g., Re = 700) because of the enhancement of flow instabilities just upstream of the
flow divider (Kleinstreuer & Zhang 2009, Olson et al. 1973).
In the inspiratory flow fields in the bifurcating bronchial airways upstream of generation G10,
the airstream in the branching airways splits at each flow divider, and new boundary layers are
generated at the inner walls of the daughter tubes. The velocity profiles are naturally skewed in
each daughter tube; hence, each daughter tube (or generation) may experience a different flow
rate. Secondary flows are set up due to the upstream flow histories, as well as the centrifugal-
force-induced pressure gradient when the flow turns in bends. The critical Dean number for
the onset of appreciable secondary vortices is approximately 10 (Fresconi & Prasad 2007). The
structures and magnitudes of secondary flow fields depend on the flow direction, Reynolds number,
geometric features, and axial location with respect to the flow divider (carinal ridge), as well as the
Womersley number for oscillatory flows (Comer et al. 2001, Fresconi & Prasad 2007, Zhang &
Kleinstreuer 2002). Different distinct secondary vortices may be observed in different generations
(Figure 4). In some cases, two distinct secondary vortices (typical Dean flow) appear in the
branching tube. Two additional corotating vortices (i.e., quadruple vortices) can be observed
in the second bifurcation of multibifurcated tubes or realistic lung models (Comer et al. 2001,

a b
c d
Figure 4
Examples of cross-sectional views of axial velocity contours and secondary velocity vectors in the bronchial
airways: (a) typical Dean flow in symmetric multibifurcation models (Zhang et al. 2001), (b) typical
four-vortex secondary flow in symmetric multibifurcation models (Zhang et al. 2001), (c) flow structures in
an asymmetric airway model (Li et al. 2007b), and (d ) flow structures in a computed tomography–scanned
airway model (Luo & Liu 2008).
van Ertbruggen et al. 2005, Zhang et al. 2001) owing to further development of upstream secondary
vortices. Specifically, Leong et al. (2009) demonstrated that four-vortex secondary flows were
generated because of vortex line extension upstream from the second bifurcation. The quadruple
vortices can further develop and merge again into double vortices in the subsequent bifurcations
(Zhang et al. 2001). In addition, the length of some bronchi in the CT-scanned lung model
is too short to form a typical Dean-flow pattern (Luo & Liu 2008); in other words, subsequent
bifurcations constantly interrupt the development of secondary flows (see Figure 4). The intensity
of secondary flows (i.e., the ratio of the mean secondary velocities to the amplitude of the mean
axial velocity) may not exceed 20% throughout the conducting airways (Fresconi & Prasad 2007,
Zhang & Kleinstreuer 2002). In general, the secondary currents may persist through generations
G10–G13, as measured by Fresconi & Prasad (2007) and predicted by Zhang et al. (2008). In
addition, the flow may become fully developed after generation G12 with the reduced Reynolds
number.
Some different flow phenomena may also be observed as a result of other significant geometry
changes. For example, in obstructed airways (i.e., in patients with chronic obstructive pulmonary
disease or with tumors), the obstruction may generate recirculation zones both upstream and
downstream (Yang 2006, Zhang et al. 2002d). Wall & Rabczuk (2008) also demonstrated that the
airflow patterns, including both axial and secondary velocity profiles, were quite different when

considering the fluid-structure interaction. But the influence of this interaction with respect to
flow distributions and secondary flow intensities is moderate (i.e., the differences are within 15%).
Bifurcating airflow during the expiratory phase is quite different from that during inspiratory
flow (Zhang & Kleinstreuer 2002). Instead of the airstreams being split at each flow divider,
two streams come together from the daughter tubes, so that near the flow divider, the velocity
profiles in the bifurcation plane may have indentations at the centers, so-called M profiles. Velocity
profiles with double peaks may appear after the flow dividers, but they soon transform into marked
centerline velocity peaks because of merging boundary layers. Especially in the high–Reynolds
number case, a distinct velocity spike at the centerline can be generated. As for inspiratory flow,
the airstream is curved, and therefore secondary motions develop when it turns a bend from the
daughter tube to the upstream tube. However, the secondary vortical structures may be quite
different as they merge in the parent tube. Two pairs of helical vortices can be generated by
the converging flow streams from parent tubes (Fresconi & Prasad 2007, Pedley 1977, Zhang &
Kleinstreuer 2002). The secondary motion is important during exhalation because it is the primary
factor governing aerosol transport and deposition. In addition, the inlet has less of an effect on the
expiratory flow than it does during inspiration. With increasing flow rates, the basic flow features
remain; however, the merging length for the high-axial velocity zone increases, which is the result
of the interplay of convective acceleration and near-wall viscous forces (i.e., the boundary-layer
effect on the central-axial velocity decreases with increasing Reynolds number). Generally, in
contrast to inhalation flow, expiratory flow features vary only slowly with axial distance.
The relative importance of unsteadiness in laminar oscillatory flow can be expressed with the
√
Womersley number (α = r0 ω0 /ν), which represents the ratio of unsteady inertial forces to viscous
forces. Many studies have confirmed that transient phenomena associated with boundary-layer
growth may be negligible for α ≤ 1 (Fresconi & Prasad 2007, Theunissen & Riethmuller 2008,
Zhang & Kleinstreuer 2002). The effect of unsteadiness on turbulent flow can be assessed roughly
by evaluating a turbulent counterpart of the Womersley number α ∗ as proposed by Pedley (1977).
Specifically, α ∗ can be computed by replacing ν in α with the eddy viscosity νT . Now, considering
light-activity breathing (e.g., Q = 30 liters min−1 ), α is approximately 2.25, whereas α ∗ cannot
exceed 0.7 in the trachea (with a diameter of approximately 1.6 cm). The relatively small α ∗
value implies that the presence of turbulent flow may reduce locally the effects of unsteadiness.
Generally speaking, the transient effects on both inspiratory and expiratory flow structures under
normal breathing conditions (e.g., Q = 15 ∼ 30 liters min−1 , f ∼ 15 cycles min−1 ) are not
pronounced, especially for airway generation beyond G3. For example, Zhang & Kleinstreuer
(2002) demonstrated that both the peak inspiratory and expiratory velocity profiles for the low
Womersley case (α = 0.93) agree well with those of instantaneously equivalent steady-state cases,
whereas some differences can be observed between flow acceleration and deceleration at off-peak
periods or near flow reversal, especially during inspiratory flow. Li et al. (2007b) showed that the
flow fields in generations G0 to G3 are similar to those obtained with equivalent Reynolds numbers
at steady state. Stronger axial and secondary velocities occur at all upper-branch locations during
flow deceleration because of the dynamic lingering effect (Li et al. 2007b). However, the situations
for high-frequency ventilation flows may be quite different because of a dramatically increasing
Womersley number and its resulting impact (Adler & Brucker 2007, Zhang & Kleinstreuer 2002).
3.2.3. Alveolar region. Although the Reynolds number of the flow in the alveolated ducts is
very low (Re < 1), the flow is still complex because of complicated geometric features as well as
the rhythmic expansion and contraction of the alveoli (see Figure 1). Several types of simplified
and idealized geometry models have been employed to study acinar flow. These configurations
include 2D long central channels surrounded by alveoli with circular shapes (Dailey & Ghadiali

a b
Vx (mm s–1)
2 2
7.44
6.61
5.78
y (mm)
y (mm)
4.95
4.11
1 1 3.28
2.45
1.62
0.78
–0.05
0 0
0 1 2 3 0 1 2 3
x (mm) x (mm)
Figure 5
Axial velocity contours and streamlines of steady airflow (Re = 0.046) in asymmetric alveolated ducts with (a) circular alveoli and
(b) smooth polygonal alveoli (units: Vx , mm s−1 ) (Li 2007).
2007; Tsuda et al. 1995, 2008), 2D multigeneration alveolated bifurcations (Darquenne 2002,
Darquenne & Paiva 1996), a 3D straight tube with hemispherical alveoli (Haber & Tsuda 2006,
Henry et al. 2009, Karl et al. 2004), 3D alveolated bends (van Ertbruggen et al. 2008), and
3D alveolated bifurcations (Harrington et al. 2006). Both the Womersley number and Strouhal
number are small in the pulmonary acinus (e.g., Wo < 1, Str ≈ 0.0015); hence the flow in the
alveolar region is quasi-steady. The typical alveolar flow patterns exhibit Poiseuille-like profiles
in the lumenal flow with recirculating structures inside the alveoli (see Figure 5). The streamline
pattern of the flow is sensitive to the ratio of the alveolar flow to the ductal flow (Tsuda et al.
1995). In some cases, the flow is complicated and exhibits chaotic behavior. For example, Haber
& Tsuda (2006) and Henry et al. (2009) demonstrated that oscillating, recirculating flows in
both rigid and expanded/contracted alveolated ducts were not revisable, but were chaotic, which
produces convective mixing. Karl et al. (2004) studied both experimentally and numerically LRN
viscous flow in a straight alveolated duct and showed that the type of flow developing in the
alveoli, or cavities, was controlled by the ratio of the depth to the width of the cavity and by
the ratio of cavity volume to duct volume. With different ratios, the cavities were filled with one
large recirculating region that was separated from the ductal flow by a streamline spanning the
cavity opening, or two recirculating flow regions, one in each lower corner of the cavity, and the
main flow penetrating deep into the cavity. Most recently, Theunissen & Riethmuller (2008), van
Ertbruggen et al. (2008), and Ma et al. (2009) measured with PIV, or simulated numerically, the
flow fields in a cylindrical bend surrounded by tortoidal alveoli, or a three-generation symmetric
bifurcation surrounded by circular rings. They obtained typical LRN flow patterns similar to
many of the previous studies. They demonstrated that the flow became fully developed within a
very short entrance length. Whereas streamlines were parallel to the axial direction in most of the
central duct, they became curvilinear near the alveolar opening. Recirculation zones appeared in
each alveolar cavity, and velocities inside the cavities were about two orders of magnitude smaller
than the mean lumen velocity. In addition, velocity profiles in the alvolated bifurcation model may
deviate from a parabolic shape in the bifurcation areas due to abrupt geometry changes, whereas
tubular vortices can be observed in the alveolated bend. However, all their models were rigid.
Sznitman et al. (2007) showed that alveolar patterns under rhythmic wall motion contrasted sharply

with results obtained in a rigid alveolus. Radial flows induced by wall displacement may interact
with recirculation in the cavity induced by the ductal shear flow over the alveolar opening, which
largely influences the alveolar flow patterns. Specifically, flows are dominated by recirculation
patterns for alveoli located in the proximal acinar generations. Flows may become largely radial
in the deeper acinar generations because of rhythmic wall motion and an increasing alveolus
volume, when the recirculation region gradually decreases until it vanishes in the distal region.
In general, understanding the flow structures in realistic alveolar structures with physiologically
correct fluid-structure interactions is still a great challenge.
4. DILUTE PARTICLE SUSPENSIONS

When studying inhaled particulate matter, one uses the common simplifications that the aerosols
are spherical, noninteracting, and monodisperse. These underlying assumptions allow for decou-
pling of the fluid phase from the particle phase. In reality, inhaled particles are nonspherical (i.e.,
ranging from carbon nanotubes to nonrigid micron fibers), all colliding and possibly aggregating.
To overcome the complexities of simulating actual particles of different shapes and loadings, cor-
relations for the drag coefficient of nonspherical particles (Holzer & Sommerfeld 2008) as well as
multisphere collisions (Crowe et al. 1998) and two-phase interactions (Michaelides 1997) have been
proposed. In any case, a possible criterion for dilute suspensions of spheres is ρd p vrel /(3μ) < 1,
where ρ and μ are the fluid’s density and viscosity, respectively, whereas dp and vrel are the particle
diameter and relative particle velocity, respectively (see example 2.2 in Kleinstreuer 2003).
When considering dilute particle suspensions, two separate sets of equations are necessary.
Specifically, for micron particles, dp > 1 μm, the Euler-Lagrange modeling approach is employed;
i.e., the flow field (Eulerian frame) is not influenced by the particle trajectories (Lagrangian frame).
In particular, solid, nonrotating spheres with a high ρ particle /ρ fluid ratio simplify the analysis signif-
icantly when the flow is laminar. In contrast, nanomaterial transport, in the effective diameter
range 1 < dp < 150 nm, can be modeled with the Euler-Euler approach; i.e., the fluid flow field is
solved separately from the convection-diffusion equation describing nanoparticle dispersion.
4.1. Nanomaterial and Vapor Transport

Alternatively to the Euler-Lagrange particle-tracking approach, the Euler-Euler mass-transfer
equation is typically employed for quasi-spherical nanoparticles. For Brownian particles in dilute
suspensions, the aerosol general dynamics equation (including convection, diffusion, coagulation,
surface growth, nucleation, and other internal/external forces) may be written as
∂Y ∂I
+ ∇ · ( vY ) + = ∇ · (Dp ∇Y ) − ∇ · ( cY )
∂t ∂v
∞
1 v
+ β(ṽ, v − ṽ)n(ṽ)n(v − ṽ)d ṽ − β(v, ṽ)n(v)n(ṽ)d ṽ, (2)
2 0 0
where Y is the particle concentration; I is the nucleation rate; Dp is the particle diffusion tensor;
f with
v is the velocity vector; and c is the migration or drift velocity in the field, given as c = F/

F being the external force vector and f the friction coefficient (Friedlander 2000). The external
forces usually considered in nanoparticle deposition are inertial, gravitational, and van der Waals
forces. The last two terms on the right-hand side of Equation 2 represent the coagulation rate,
where n(ṽ) is the number of particles of volume ṽ and β is the collision frequency function
for coagulation. Assuming the diffusion is isotropic and that turbulent dispersion is present, the

diffusion coefficient (Dp ) can be written as
Dp = D̃ + νT /σY , (3)
where νT is the eddy viscosity, σY = 0.9 is the turbulent Schmidt number, and D̃ is the effective
aerosol diffusion coefficient. For spherical nanoparticles, D̃ is calculated based on kinetic theory
(Finlay 2001); i.e.,
D̃ = (k B TCslip )/(3πμd p ), (4)
−23 −1
where kB is the Boltzmann constant (1.38 × 10 J K ), and Cslip is the Cunningham slip cor-
rection factor (Clift et al. 1978) The diffusion coefficient for nonspherical nanoparticles (e.g.,
ellipsoids) is less than that of a sphere (Friedlander 2000).
Clearly, if particle coagulation, surface growth, nucleation, and external forces are negligible,
Equation 2 reduces to the standard convection-diffusion equation; i.e.,

∂Y ∂ ∂ νT ∂Y
+ ujY = D̃ + . (5)
∂t ∂xj ∂xj σY ∂ x j
Equation 5 is suitable for the accurate modeling of vapor transport as well as dilute, noninteracting,
spherical nanoparticles with dp ≤ 100 nm (Shi et al. 2004, Zhang & Kleinstreuer 2004).
For relatively large nanoparticles (e.g., dp > 100 nm) or in flow fields with St > 5 × 10−5 ,
diffusional nanoparticle deposition may have to be augmented by particle convection to the wall
due to inertial effects (Longest & Oldham 2008, Longest & Xi 2007). Here, the Stokes number
is defined as St = ρ p d 2p U/(18μD), where ρ p is the particle density, dp is the particle diameter, U is
the mean velocity, μ is the fluid viscosity, and D is the tube diameter (see Equation 8).
Assuming that the airway wall is a perfect sink for vapors or nanoparticles upon contact,
the steady-state boundary condition on the wall is Yw = 0. This assumption is reasonable for
fast aerosol-wall reaction kinetics and also suitable for estimating conservatively the maximum
deposition of particles or toxic vapors in airways. Nanoparticles larger than approximately 10 nm
generally stick when they make contact with the airway surface; i.e., the perfectly absorbing wall
condition (Ywall = 0) can be employed. Conversely, nanoparticles less than or equal to 1 nm in
diameter behave more like a vapor, and have some probability of being absorbed instead of sticking
to the mucus layer.
For less soluble vapors, the wall concentration would be greater than zero, so that transport in
tissue and in airways must be considered simultaneously when simulating vapor uptake. Keyhani
et al. (1997) and Zhang et al. (2006b) modeled the flux condition at the airway boundary and
discussed the impact of wall absorption (i.e., Ywall = 0) on the deposition of gas/vapors or tiny
nanoparticles.
The regional deposition of vapors or nanoparticles in human airways can be quantified in terms
of the DF or deposition efficiency (DE) in a specific region (e.g., oral and nasal airways, first, second,
and third bifurcations) (Zhang et al. 2008). These parameters are defined as the ratio of deposited
nanoparticle mass to the inhaled amount entering the mouth/nose or a specific region. The DF
or DE of nanoparticles can also be calculated with the regional mass balance or the sum of local
wall mass flux with the Eulerian-Eulerian modeling technique (Zhang et al. 2008). Furthermore,
calculation of the respiratory mass-transfer coefficient, h m , or nondimensional Sherwood number
[Sh = (h m D)/ D̃ with D as the characteristic diameter] is also helpful in quantitatively predicting
the regional uptake of inhaled vapors or nanosize particles (Cheng et al. 1997b, Xi & Longest
2008a, Zhang et al. 2006b).
In addition to the traditional deposition parameters DE and DF, a deposition enhancement
factor (DEF) is useful to quantify local particle-deposition patterns (Zhang et al. 2005). The DEF

is defined as the ratio of local to average deposition densities; i.e.,

DFi /Ai
DEF = , (6)

n
n
DFi / Ai
i=1 i=1
where DFi is the local DF in the local wall cell (i ), Ai is the area of the local wall cell (i ), and n is
the number of wall cells in one certain airway region (e.g., oral airway, first airway bifurcation).
Clearly, maximum DEF values indicate particle deposition hot spots in certain regions.
In a series of papers, Cheng et al. (1995; 1996; 1997a,b) and Smith et al. (2001) published
their measurements of mass transfer and deposition of nanoparticles (3.6 nm < dp < 150 nm) in
casts of human nasal, oral, and upper tracheobronchial airways. Cohen et al. (1990) reported their
experimental work on nanoparticle deposition in an upper tracheobronchial airway cast, and Kelly
et al. (2004b) measured the nasal DEs of nanoparticles with diameters between 5 and 150 nm.
Daigle et al. (2003) and Kim & Jaques (2000, 2004) measured total respiratory tract DFs of
nanoparticles (8–100 nm) in healthy adults. Kim & Jaques (2004) also measured regional DFs of
nanoparticles (dp = 40–100 nm) in tracheobronchial and alveolar regions of healthy adult subjects.
Thus far, there are no in vivo data for tracheobronchial and alveolar depositions of nanoparticles
with mean diameters less than 40 nm. Clearly, subject-specific deposition measurements are time-
and cost-consuming and, of course, impossible for toxic aerosols. In this case, validated correlations
and computer modeling have become alternative tools to obtain the approximate regional or
accurate local deposition data sets for inhaled nanosize aerosols.
Examples of numerical simulations for nanoparticle deposition include Hofmann et al. (2003),
Kelly et al. (2004b), Shi et al. (2004, 2008), Xi & Longest (2008a,c), Xi et al. (2008), Yu et al.
(1996, 1998), Zamankhan et al. (2006), Zhang & Kleinstreuer (2004), and Zhang et al. (2006b,
2008). These studies focused on the nasal, oral, and upper tracheobronchial airways (e.g., from
trachea to generation G6), with the exception of Zhang et al. (2008), who simulated both local and
regional nanoparticle transport and deposition from the oral airway to generation G15, repeatedly
employing adjustable triple-bifurcation units. Little information is available about modeling and
measurements of vapor or ultrafine particle (dp < 100 nm) depositions in the alveolar region. There
have been simulations of 1-nm to 10-μm particle transport in a model alveolus, represented by
a rhythmically expanding and contracting hemisphere (Balashazy et al. 2008). It should be noted
that the large uptake of less soluble vapors (e.g., tetradecane) may occur in the pulmonary region.
In addition, the low surface tension produced by a surfactant film in the deeper parts of the lung,
including the alveolar region, may aid the transfer of ultrafine particles through the liquid wall layer
(Geiser et al. 2000) so that the toxicity effect of deposited particles in these regions is enhanced.
Below we give a brief summary of the studies cited above in terms of vapor and nanoparticle
distributions, deposition patterns, DFs, and DEs, focusing on aerosol inhalation to the conducting
airways, including oral and nasal airways, as well as tracheobronchial airways from the trachea to
generation G15.
4.1.1. Vapor or nanoparticle distributions. The diffusivities for vapors of most species (espe-
cially for the components of fuels) are approximately 0.05∼0.2 cm2 s−1 , which are at the same
order or approximately that of 1-nm particles ( D̃ = 0.054 cm2 s−1 ); hence, their transport and
deposition may behave similarly if nanoparticles are considered to be noninteracting and nonco-
agulating. The relationship between flow fields and vapor (or nanoparticle distributions) at a fixed
flow rate can be qualitatively described in terms of the Schmidt number (Sc = ν/D), which is the
ratio of momentum diffusivity to mass diffusivity. For vapors or tiny particles (e.g., dp = 1 nm),
the Schmidt number is small (e.g., Sc < 3), and the axial velocity field is a good indicator of particle

distributions (i.e., high-velocity regions imply high-concentration regions for particles and vice
versa) (Shi et al. 2008; Xi & Longest 2008a,c; Zhang & Kleinstreuer 2004; Zhang et al. 2008). This
is because convection mass transfer is relatively high in these regions, and particles can rapidly
convect, diffuse, and mix. However, with an increase in particle size, the situation changes. The
particle concentrations tend to be more uniform because of the decrease in diffusivity with parti-
cle diameter (Equation 4). For example, the larger-sized nanoparticles (e.g., dp = 10 nm with
Sc ≈ 294) cannot diffuse as rapidly and hence do not deposit as much as the tiny particles
(dp = 1 nm), leaving high particle concentrations mostly in the lumenal areas. However, in some
low-velocity and measurable secondary flow regions, the diffusion-convection interaction causes
nanoparticles to establish depleted concentration zones (Zhang et al. 2008). The general maps of
nanoparticle distributions in the nasal, oral, and tracheobronchial airways can be found in Shi et al.
(2008), Xi & Longest (2008a,c), Zhang & Kleinstreuer (2004), and Zhang et al. (2008). In the nasal
airways, most particles, or equivalent vapors, of dp = 1 nm pass through the middle-to-low main
passageway convected by the main airflow portion. In particular, a high particle concentration is
observed in the main passageway below the middle meatus. However, as the flow rate increases, a
larger portion passes through the olfactory region. When the suspension approaches the meatuses,
some nanoparticles enter the meatuses owing to both diffusion and secondary flow effects. Zhang
et al. (2008) found that a uniform nanoparticle distribution is a reasonable assumption at the inlets
of small airways (e.g., after G12).
4.1.2. Deposition patterns. The local deposition patterns of nanoparticles can be described in
terms of the distribution of the DEF as given in Equation 6. With complicated variations in flow
and concentration fields in the human airways, the deposition patterns are also inhomogeneous.
In the oral and nasal airways, the deposition patterns (i.e., DEF distributions) are complicated
functions of flow rate, particle size, and geometric features. For example, Zhang & Kleinstreuer
(2004) showed that the distributions of DEF in the trachea for a low (laminar) inhalation flow
rate (e.g., Qin < 15 liters min−1 ) are measurably different when compared with those for higher
flow-rate cases (Qin = 60 liters min−1 ) because turbulent flow appears after the throat contracts.
An increase in inhalation flow rate reduces the particle residence time and the chance for de-
position. The decrease in wall deposition may cause more uniform concentration profiles in the
conduits; as a result, deposition patterns do not vary as much for higher inhalation flow rates (e.g.,
Qin = 60 liters min−1 ) than for lower flow rates (Qin = 30 liters min−1 and 15 liters min−1 ). As the
particle size increases, wall depositions decrease, and the air-particle mixtures become much more
uniform, featuring flat similar particle distribution profiles and hence wall gradients, which also
reduce the differences in local wall deposition rates. Interestingly, Xi & Longest (2008a) showed
that the overall pattern of nanoparticle-deposition enhancement appears similar for different oral
airway geometries, ranging from the simplified, circular model to the realistic CT-scanned model.
Shi et al. (2008) and Xi & Longest (2008b) depicted local nanoparticle-deposition patterns in
nasal airways. Specifically, for dp = 1 nm, the majority of deposition occurs in the anterior part of
the nasal cavity because of high diffusivity. The meatus regions experience only small deposition
fluxes because most particles are taken up before they can reach the deeper regions of the meatuses.
High DEF values can be seen around the nasal valve region due to the locally narrowing airway.
For dp = 5 nm, deposition fluxes are a bit more evenly distributed because of the somewhat
uniform particle concentrations in the airways. Nonetheless, the locations of deposition hot spots
are basically the same; i.e., the nasal valve region and middle-meatus zones feature the highest
DEF values.
The situation in the tracheobronchial airways is different. Clearly, the local nanoparticle-
deposition patterns tend to be similar when advancing from large to small bronchial airways

(Zhang et al. 2008). Enhanced depositions occur at the carinal ridges due to the large particle
concentration gradients in these regions (Cohen et al. 1990, Zhang et al. 2005). Specifically, the
high concentration just upstream of the carina and zero concentration at the carinal ridge (i.e.,
generating high-concentration gradients) lead to high diffusional depositions. The location of
a bifurcation unit and airway rotation have a minor effect on the maximum DEF (DEFmax ) for
nanoparticles (Zhang et al. 2008).
Interestingly, the maximum DEF values reported in the nasal, oral, and tracheobronchial air-
ways are of the order of 1 to 10 when dp ≤ 40 nm. This implies that the deposited nanoparticles are
quite uniformly coating the airway surfaces when compared with micron-particle deposition, in
which the maximum DEF values can be of the order of 103 (Zhang et al. 2009). These values may
go up by an order of magnitude when dp > 100 nm, due to the effects of inertial force (Longest &
Xi 2007).
4.1.3. Deposition fractions and efficiencies. Different modeling methodology and approaches
may result in different accuracies in predicting particle deposition when compared with measured
data. Figure 6 shows computer-simulation results for nanoparticle deposition in a nasal airway
model compared with different experimental data. Whereas Zamankhan et al. (2006) employed
the Eulerian-Lagrangian approach, Shi et al. (2008) and Xi & Longest (2008c) used the Eulerian-
Eulerian approach. In Xi & Longest’s (2008c) particle transport model, they also included a
modified drift flux velocity to consider the simultaneous effects of diffusion and inertial impaction.
Notably, the nasal geometries of all three computer simulations were based on the same MRI data of
a 53-year-old male, which was also similar to the geometry employed in the experimental studies by
Kelly et al. (2004b) and Cheng et al. (1995). Clearly, Xi & Longest’s (2008c) results underestimate
the particle deposition for dp < 20 nm, whereas Zamankhan et al. (2006) largely overpredict
the deposition for dp > 20 nm. Shi et al.’s (2008) results match well with Cheng et al.’s (1995)
ANOT1 and ANOT2 data. This may be attributed to the combined effects of different modeling
approaches, mesh topologies, numerical methods, and even different commercial software [Fluent
100
Simulation (Shi et al. 2008)
Simulation (Xi & Longest 2008c)
Simulation (Zamankhan et al. 2006)
80 ANOT1(Cheng et al.1995)
ANOT2 (Cheng et al.1995)
Deposition fraction (%)
SLA (Kelly et al. 2004b)

60 Viper (Kelly et al. 2004b)
Swift et al. (1992)
40
20
0
100 101 102
Particle diameter (nm)
Figure 6
Comparisons of nanoparticle depositions in human nasal airways. SLA and Viper refer to nasal replicas
manufactured with different rapid prototype machines. ANOT, adult-nasal-oral-tracheal.

was employed by Xi & Longest (2008c) and Zamankhan et al. (2006), and CFX was used by Shi
et al. (2008)].
Zhang et al. (2008) and Xi & Longest (2008a) indicated that the geometric effect is minor
for nanoparticle deposition when compared with micron-particle deposition. For example, Zhang
et al. (2008) showed that the maximum variation of local DFs due to nonplanar geometry effects
in the bronchial tree is 3% to 26%, and is only pronounced for particles with dp ≤ 3 nm. This is
because the diffusional nanoparticle deposition is mainly dependent on the particle concentration
gradient near the airway wall, which is less influenced by the tube geometry features, except for
the carinal ridges. The flow and particle transport/deposition history (i.e., upstream, asymmetric
velocity profiles and particle distributions) has a more significant effect on particle deposition in
one specific airway segment when compared to the effect of nonplanar geometric features of this
segment. Specifically, maximum variations of DFs among the parallel, individual bifurcations with
the same number in series can be as large as 100%, caused by the difference among air/particle
distributions at the inlets of these bifurcations (Zhang et al. 2008).

Combining the effects of geometric features, inhalation flow conditions, and particle diffusion
capacity, we can develop some deposition equations for quick reliable health-effect analysis. In
different studies and different airways regions, the DEs were correlated with different equations
as functions of particle size (diffusivity), flow rate, and geometric features (see Table 1). It should
be mentioned that these equations were obtained under steady inspiratory flow conditions. Li
et al. (1998), Shi et al. (2006), and Zhang & Kleinstreuer (2004) discussed transient effects on
nanoparticle depositions in nasal, oral, and upper tracheobronchial airways. In general, cyclic
inspiratory flow patterns do not cause a statistically significant increase in total deposition because
the inhalation flow rate has a relatively minor effect on nanoparticle deposition when compared
with the particle size effect. Thus, as proposed by Zhang & Kleinstreuer (2004) and Shi et al.
(2006), deposition results for quasi-steady flow with matching Reynolds number provide a good
conservative estimate of the actual DF values. As mentioned above, the best matching flow rate was
determined to be the average between the mean and maximum flow rates [i.e., Qmatch = 0.5(Qmean +
Qmax )].
Airway wall absorption may influence the deposition of vapors or tiny nanoparticles in terms
of absorption parameter K (see Keyhani et al. 1997, Zhang et al. 2006b; and Table 1). Zhang
et al. (2006b) demonstrated that different sorption parameter K’s result in large variations of the
DFs. Specifically, when K is less than 1, the deposition is very low in the upper airways due to the
low solubility of species in the mucus layer. The DF is greatly dependent on K for cases in which
1 < K < 1000. If K > 1000, the DF is very close to that for the perfectly absorbing wall condition
(i.e., Ywall = 0). But K almost has no effect on the species mass-transfer coefficient for the same
diffusivity.
4.2. Solid Micron Particle and Droplet Dynamics

Micron-particle deposition in the lung may occur via impaction, including secondary airflow
convecting particles to the airway walls, diffusion, and/or sedimentation (i.e., the gravitational
effect). Clearly, inertial impaction is proportional to the airflow rate and the (aerodynamic) particle
diameter squared, as expressed with the impaction parameter; i.e.,
IP = Qd 2p or I P̂ = ρ Qd 2p . (7)
Diffusional and gravitational mechanisms are measurable at very low flow rates, i.e., typically in the
lower lung regions, with diffusion dominant for ultrafine particles in areas of high concentration
gradients, whereas gravity effects are significant for relatively large/heavy particles (Heyder 2004).

ANRV400-FL42-14
Table 1 Some correlations for inspiratory nanoparticle deposition efficiencies

ARI
Region Deposition equation Reference(s) Parameter definition

Nasal airways As 0.75 −0.45 −0.40 Cheng et al. 1996 As , total wall surface area of the
DE = 1 − exp −0.853 Re Sc airway segment
Āc
Āc , ū, average airway
Xi & Longest 2008c cross-section area and velocity
As St
DE = 1 − exp − Re−0.70 Sc−0.67 + 4.7 × 106 Ain , cross-section area of the inlet
ReSc
13 November 2009
Āc
Re = ū D/ν, Reynolds number
DE = 1 − 0.88 exp(−218Pe−0.75 ) Zamankhan et al. 2006 Sc = ν/ D̃, Schmidt number
18:18
DE = (0.568 − 0.69 ln
) ·
1/2 · Sc−1/6 Shi et al. 2008 ν, fluid kinematic viscosity
Oral airways DE = 1 − exp(−20.4 D̃0.66 Q −0.31 ) Cheng 2003 D, characteristic diameter
DE = 1 − exp[−0.1654(As /Ain )Re−0.339 Sc−0.661 ] Xi & Longest 2008a D̃, diffusion coefficient (see
Zhang & Kleinstreuer 2003b, Equation 4)
h m D̃K π Dm L
DE = 1 − exp · Zhang et al. 2006b St, Stokes number (see Equation
h m Din − D̃K Q
8)
with h m = Sh · D̃/Din = 0.852(ReSc)0.405 · D̃/Din Pe = Q/( D̃L), Peclect number
Bronchial airways DE(%) =
a exp(b − c
) with Zhang et al. 2008 Q, inspiratory flow rate
a = 0.78, b = 7.41, and c = 16,767 for 2 × 10−8 <
≤ 1 × 10−5 (B1–B6) L, length of the airway segment
a = 0.64, b = 5.73, and c = 2.62 for 1 × 10−5 <
≤ 2.5 × 10−2 (B1–B6)
= π D̃L/(4Q), diffusion
a = 0.636, b = 6.009, and c = 2.03 for 2 × 10−7 <
≤ 0.25 (B7–B15) parameter
Dm , Din , mean and inlet diameter
of the airway segment,
respectively
K, airway wall absorption
parameter is defined as
Din D̃m
K = ,
D̃a β Hm
where D̃a and D̃m are the vapor
www.annualreviews.org • Airflow and Particle Transport

diffusivity in the air and the
liquid mucus phase, respectively,
321
Hm is the thickness of the mucus
or surfactant layer, and β is the
species equilibrium partition
coefficient
In general, for particle-deposition studies, the Stokes number is used:
ρd 2p U
St = τ p : τ f = . (8)
18μD
It is the ratio of particle relaxation and flow characteristic times. Thus, St = fct. (particle diameter
squared, characteristic air velocity U, system length scale D, and fluid properties); hence, it is a
measure of the influence of inertial effects during a particle’s trajectory. However, in the (human)
respiratory system, the local airway geometries are rather complex or exhibit sudden changes,
while the airflow velocities are rapidly changing as well. Thus, the Stokes numbers as well as
Reynolds numbers have to be defined locally to capture more accurately the underlying physics
of micron-particle deposition.
Assuming noninteracting spherical micron particles, one can employ a Lagrangian frame of ref-
erence. In light of the large particle-to-air density ratio, dilute particle suspensions, and negligible
particle rotation, drag is the dominant force with additional forces relevant near the airway walls.
Thus, Newton’s second law of motion can be written for laminar and turbulent micron-particle
transport as
d p gravity
(m p ui ) = FD + Fi + ni (t) + Filubric atio n + FiP−Winterac t. , (9)
dt
where uiP and mp are the velocity and mass of the particle, respectively; and ni (t) is an interaction
force due to Brownian motion that results from collision of air molecules with particles of dp <
1 μm (Asgharian & Anjilvel 1994). The Brownian force can be modeled as a Gaussian white-noise
random process (He & Ahmadi 1999).
In Equation 9, FD is the drag force. Independent of particle shape, the drag force can be
formulated as
p p
FD = 12 C D ρ Ap (ui − ui )|u j − u j |, (10)
where ρ is the air density, Ap is the projected particle area, and CD is the particle drag coefficient.
The underlined forces in Equation 9 can be activated in the near-wall region. Specifically, the
lubrication (or wall drag) force as well as the Saffman-type lift force have been evaluated and
validated for a particle-hemodynamics system by Longest et al. (2004). For high aerosol loadings,
a particle-particle interaction (or collision) force is added.
In Equation 10, ui is the instantaneous fluid velocity with ui = ūi + ui , where ūi is the time-
averaged or bulk velocity of the fluid, and ui are its fluctuating components. Traditionally, turbu-
lence is assumed to consist of a collection of randomly directed eddies; hence, an eddy-interaction
model (EIM) is used to simulate the particle trajectories, and the fluctuating velocities ui are
obtained with a near-wall correction function (Gosman & Ioannides 1981, Matida et al. 2004).
Although the use of RANS equations with a two-equation k-ω turbulence model may not capture
anisotropic turbulent dispersion (Tian & Ahmadi 2007), a near-wall correction approach provides
a damping function for the component of fluctuating velocity normal to the wall (Matida et al.
2004). Numerous model validations demonstrated that the LRN k-ω model plus near-wall correc-
tion EIM produce good accuracies when simulating micron-particle deposition in human upper
airways (Longest & Vinchurkar 2007b, Xi & Longest 2007, Zhang et al. 2005). Recently, some
papers indicated that LES may predict particle deposition better when compared with standard
k-ε and standard k-ω models or the shear-stress-transport model (Breuer et al. 2006, Liu et al.
2007, Matida et al. 2006). However, the standard k-ε and standard k-ω models have failed in
capturing the laminar-transitional-turbulent airflows when compared with the present LRN k-ω
model (Zhang & Kleinstreuer 2003a). There are still no reports demonstrating that the use of LES

generates a major improvement in particle-deposition simulations when compared with the LRN
k-ω model plus near-wall correction EIM particle simulations. In any case, LES can directly obtain
the instantaneous fluctuating velocity to calculate the particle trajectories; hence, it should be a
better choice than the RANS plus EIM modeling if enough computer resources are available. In ad-
dition, Dehbi (2008) developed a Lagrangian continuous random-walk model to predict turbulent
particle dispersion considering the anisotropic and inhomogeneous characteristics of turbulence.
Droplet evaporation may occur in the upper airways associated with an unsaturated and non-
isothermal humid airstream. As vaporization reduces the droplet diameter, particle trajectories
and deposition are affected (Zhang et al. 2004). On the contrary, particle growth may also occur
in the moist airway conduits due to hygroscopicity. Recently, Zhang et al. (2004; 2006a,c) and
Longest & Xi (2008) modeled and discussed the effects of droplet vaporization or hygroscopic
particle growth on lung aerosol dynamics and deposition.
Similar to nanoparticles, the regional and local deposition of micron particles in human airways
can be quantified in terms of the DF, DE, or DEF in a specific region (e.g., nasal/oral airway, first,
second, and third bifurcation), as defined by Zhang et al. (2005).

Focusing mainly on the oral and bronchial airways, researchers have extensively investigated
micron-particle transport and deposition (e.g., Farkas & Balashazy 2008; Jayaraju et al. 2008; Kim
& Fisher 1999; Kleinstreuer et al. 2007; Li et al. 2007a; Ma & Lutchen 2009; Matida et al. 2004;
Nazridoust & Asgharian 2008; Robinson et al. 2007, 2008; Russo et al. 2008; Sosnowski 2007;
Stapleton et al. 2000; van Ertbruggen et al. 2005; Xi & Longest 2007; Xi et al. 2008; Zhang & Finlay
2005; Zhang et al. 2005, 2009). Recently, micron-particle transport and deposition in human nasal
airways have gained attention due to advancements in new nasal drug-delivery technologies and
computer simulations (Cheng 2003, Kelly et al. 2004a, Liu et al. 2007, Shi et al. 2007). However,
little information is available regarding the transport and deposition of vaporizing droplets in
human nasal airways (Shi et al. 2007).
Similar to alveolar flow studies, particle deposition in respiratory zones has also been investi-
gated over the past 15 years through 2D and 3D CFD methods based on simplified alveolar ducts,
alveolar sacs, and single alveoli (Balashazy et al. 2008, Dailey & Ghadiali 2007, Darquenne & Paiva
1996, Haber & Tsuda 2006, Haber et al. 2003, Harrington et al. 2006, Ma et al. 2009). These
results showed that micron-particle deposition in the alveolar regions was governed primarily by
gravitational settling. As a result, micron-particle deposition on the alveolar walls is inhomoge-
nous. Furthermore, the orientation and presence of bifurcation zones significantly affect particle
deposition. In addition, gravitational deposition processes and deposition sites in a rhythmically
expanding and contracting alveoli differed from conventional predictions that treat the acinar duct
as a straight pipe with rigid walls (Haber et al. 2003). Hence, fluid-structure interaction analysis
is important for micron-particle transport in deformable alveolus, considering that tissue forces
also influence the movement of the wall (Dailey & Ghadiali 2007).
4.2.1. Micron-particle distributions. Affected by the upstream deposition, local nonuniform

airflow, and particle motion, micron-particle distributions are nonhomogenous and concentrations
tend to be high in some areas. Specifically, at the nasal airways, the axial flow is a good indica-
tor of the particle concentration for small particles with a low impact parameter (IP) value (e.g.,
dp = 20 μm and Q = 20 liters min−1 ), whereas secondary flows may help particles move into the
meatus regions. As particle size and/or flow rate increases, deviations between particle pathlines
and air streamlines increase owing to higher particle inertia (i.e., impaction parameter value); as a
result, the amount of particles entrapped in the nasal cavity increases. However, the regions with
higher airflow velocity still carry more particles, especially in the main passageway beneath the

middle meatus. In the oral and upper airways (e.g., from G0 to G3), turbulent dispersion may
randomize the cross-sectional particle distributions (Kleinstreuer & Zhang 2003, Xi & Longest
2007, Xi et al. 2008, Zhang et al. 2009). In the large airways (e.g., G3 to G6), secondary flow mainly
influences the cross-sectional particle distribution, and again inertial impaction is the dominant
deposition mechanism. The distinct particle swirl motion associated with the corresponding sec-
ondary vortices can be observed in these regions (Zhang & Kleinstreuer 2002, Zhang et al. 2009).
In the small airways, the gravity angle may play a significant role in particle distribution owing to
the mechanism of sedimentation (e.g., beyond generation G12). Both gravitational settling and
secondary motion lead to micron-particle deposition in medium-sized airways (e.g., G6 to G12)
(Kleinstreuer et al. 2007, Zhang et al. 2009).
4.2.2. Deposition patterns. Microparticle deposition in large airways (e.g., nasal, oral, and up-
per tracheobronchial airways) during inhalation results mainly from impaction, secondary flow
convection, and turbulent dispersion. Thus, these particles largely deposit at stagnation points,
disrupting axial particle motion. For example, there are basically three major deposition hot spots
in nasal airways (Shi et al. 2007). The first one is near the nasal valve, where a narrow and 90◦
funnel-shaped bend forms the stagnant point for many particles. The second one is the top of the
middle meatus wall. With a steep geometry change, the particles intend to hit the middle meatus
wall or middle turbinate because of direct impaction and secondary flows. The third site is near the
nasopharynx, where the nasal airways experience a third 90◦ bend after a constriction so that parti-
cles hit the wall because of the combined effects of centrifugal force, jet flow, and inertial impaction.
For particles with very high IP values (e.g., IP > 8000 μm2 liters min−1 ), they cannot travel greatly
beyond the nasal valve region and hence a 100% DE can be achieved. In addition, wall roughness
possibly produced by manufacturing in experiments and nasal hairs in vivo may significantly affect
the deposition of large micron particles (e.g., dp > 5 μm) in nasal cavities (Shi et al. 2007).
In the oral airways, micron-particle deposition may occur at the tongue portion of the oral
cavity, the outer bend of the pharynx/larynx, and the regions just upstream of the glottis and the
straight tracheal tube. However, enhanced deposition can be observed mostly around the glottis
and the sidewalls of the upper trachea due to inertial impaction arising from the laryngeal jet
and secondary motion (Xi & Longest 2007, Zhang et al. 2005). Another region of intensified
deposition is the sidewall of the pharynx immediately upstream of the glottis (Xi & Longest
2007). Inspiratory flow rate, inhaled particle size, and geometric characteristics (including rings
at trachea) may significantly affect deposition patterns (Li et al. 2007a, Russo et al. 2008, Zhang
& Finlay 2005).
In large bronchial airways (e.g., from generation G0 to G6), micron-particle depositions mainly
occur around the carinal ridges (see Figure 7). However, in medium- to small-sized airways
(e.g., from G0 to G15), sedimentation cannot be neglected, and the deposition patterns change
somewhat. In this case, many particles essentially settle on the tube wall that is normal to the
direction of gravity. At the same time, the presence of gravity and its direction affect the deposition
patterns. In general, some particles that may land directly on the carinal ridges when considering
impaction only can be diverted. As a result, the maximum DEF values may decrease owing to
gravitational sedimentation. Specifically, Zhang et al. (2009) demonstrated that the maximum DEF
values may reduce one order of magnitude [e.g., from O(103 ) in G0–G3 to O(102 ) in G12–G15]
with a much broader distribution of micron particles due to gravitational settling. Furthermore,
the carinal ridges are not the unique deposition hot spots anymore; in fact, the entire airway
surfaces that are normal to the direction of gravity may become high-deposition regions. The

Mouth
Pharynx
Larynx DEF DEF

5.45 73.00
4.67 20.48
3.89 5.75
3.11 1.61
Trachea 2.34 0.45
1.56 0.13
0.01
0.78
0.01
0
DEF DEF
309.60
70.67
Upper 0 1.5 2.9 4.4 5.9 7.4 8.8 10.3 16.13
3.68
bronchial tree 0.84
0.19
0.04
0.01
Vapor/Nanoparticles Microparticles
Figure 7
Comparisons of micron- and nanoparticle deposition in an idealized upper airway model. Figure adapted
from Zhang et al. 2005. DEF, deposition enhancement factor.
location of bifurcation units, airway rotation, and particle size may have significant effects on the
maximum DEF values for micron particles.
In general, the maximum DEF values range from the order of 102 to 103 for micron particles
(see Figure 7 and Xi & Longest 2007; Xi et al. 2008; Zhang et al. 2005, 2009), indicating that
some local cells may receive doses more than 100 ∼ 1000 times higher than average values. This
is completely different from vapor or nanoparticle deposition, in which the DEFmax essentially
ranges from 1 to 10 (see Figure 7 and Shi et al. 2008; Xi & Longest 2008a,c; Xi et al. 2008; Zhang
et al. 2005, 2008). A more uniform distribution of deposited vapors or nanoparticles may relate to a
different toxicity effect when compared with fine aerosols made of the same materials. Specifically,
not only can the larger surface areas relative to the particle mass generate a higher probability
of interaction with cell membranes, but also, more importantly, can the larger surface areas with
a near-uniform deposition. Hence, this may result in a greater capacity to absorb and transport
toxic substances into tissue, blood, and the entire body and the enhanced possibility of systematic
diseases, such as cardiovascular diseases (Hoet et al. 2004, Oberdörster et al. 2005). In contrast, the
extremely high local DEF values for micron aerosols indicate the possibility of local pathological
changes in bronchial airways, such as the formation of lung tumors (Balashazy et al. 2003).
4.2.3. Deposition fractions and efficiencies. As reviewed by Finlay & Martin (2008), a se-
ries of correlation equations have been developed to predict total, extrathoracic, and lung DFs
over a broad range of parameters. Total DFs of micron particles can be correlated as a func-
tion of Stokes number, sedimentation parameter, and dimensionless inhalation volume. Whereas
micron-particle DFs in oral airways can be predicted by the Stokes and Reynolds numbers, iner-
tial deposition in the nasal cavity may be simply a function of Stokes number. An ICRP (1994)
model provided semiempirical equations to calculate the DFs in regions of the entire bronchial

tree and respiratory zone. As for the prediction of averaged generation-by-generation lung DFs,
mathematical models (e.g., single- or multipath models) with analytical equations based on de-
position calculations were usually employed (Asgharian et al. 2001, Choi & Kim 2007, NCRP
1997, RIVM 2002). However, Zhang et al. (2009) demonstrated that computer-simulated DFs
for the entire tracheobronchial region (e.g., G0–G15) agree well with those calculated or mea-
sured, i.e., employing analytical and semiempirical expressions or in vivo measurements. However,
the predicted DFs of micron particles using analytical formulas for most local bifurcations differ
greatly from simulation results, owing to the effects of local geometry and the resulting local
flow features and particle distributions (see Table 2). Clearly, the analytical deposition equa-
tions were developed for simple geometries (e.g., straight circular tubes) with idealized flow and
particle distributions (e.g., Poiseuille flow and uniform inlet concentrations), which do not con-
sider complex geometric features, realistic inlet conditions, and air-particle flow characteristics.
In addition, both Zhang et al. (2009) and Xi & Longest (2007, 2008a) indicated that geome-
try and upstream effects on micron-particle deposition are more significant than for nanoparti-
cles. In this case, the development of a single correlation similar to the analytical equation for
micron-particle DE in individual bifurcations is difficult. Therefore, more accurate and local de-
position equations are required to predict generation-by-generation depositions in human lung
airways.
5. CONCLUSIONS AND FUTURE DIRECTIONS

Accurate and realistic simulations of airflow structures and depositions of inhaled particles in the
human respiratory tract are most important for the understanding of basic transport phenomena
and dosimetry and health-effect studies, considering toxic or therapeutic particles. Although the
present trend is toward subject-specific imaging and modeling of air-particle flow, most simulation
results are for simplified segments of the human respiratory tract due to limitations in both medical
image resolution and computer resources.
Airflows in the nasal cavities and oral airways are rather complex, possibly featuring transition
to turbulent jet-like flow, recirculating flow, Dean’s flow, vortical flows, large pressure drops,
prevailing secondary flows, and merging streams in the case of exhalation. Such complex flows
propagate subsequently into the tracheobronchial airways. Secondary flows may disappear, and
fully developed flows may approach the lower conducting airways (e.g., after generation G12).
But flows in the alveolar regions may be further complicated by the complex shapes of alveoli, as
well as fluid-structure interactions.
The underlying assumptions for particle transport and deposition are that the aerosols are
spherical, noninteracting, and monodisperse and deposit upon contact with the airway surface.
Such dilute particle suspensions are typically modeled with the Euler-Lagrange approach for
micron particles and in the Euler-Euler framework for nanoparticles. Micron particles deposit
nonuniformly with very high concentrations at some local sites (e.g., the carinal ridges of large
bronchial airways). In contrast, nanomaterial almost coats the airway surfaces, which has implica-
tions for detrimental health effects in the case of inhaled toxic nanoparticles. Geometric airway
features, as well as histories of airflow fields and particle distributions, may significantly affect
particle deposition. However, the geometric effect on nanoparticle deposition is relatively minor
when compared with that of micron particles.
Future work should focus on air-particle flow simulations in patient-specific airways (i.e., from
the nose/mouth to generation G6 and beyond), as well as representative segments of the alveo-
lar region. In addition to analyses of nonspherical particle dynamics, three-phase flow, realistic
surrogates of toxic droplets, and fluid-structure interactions present challenging tasks.

ANRV400-FL42-14
ARI
Table 2 Bifurcation-by-bifurcation comparisons of micron-particle depositions between analytical models and computational fluid-particle dynamics
(CFPD) simulations in a 16-generation tracheobronchial airway model
13 November 2009
dp Bifurcation 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Total
Simulation 0.55 0.46 0.48 1.05 0.89 0.83 0.76 0.75 1.60 0.60 0.88 0.65 0.38 0.62 0.54 11.03
3 μm Math. Modela 0.26 0.37 0.54 0.78 0.67 0.97 0.91 0.80 1.35 1.02 0.91 1.48 1.17 1.06 1.64 13.93
18:18
Error (%) 53.3 19.3 11.8 25.4 24.2 16.7 19.7 6.8 15.5 71.7 3.0 128.3 205.8 72.5 202.0 26.3
1D modelb 0.08 0.31 0.55 0.55 0.63 0.55 0.63 0.63 0.71 0.71 0.86 0.79 0.86 1.26 1.65 10.76
Error (%) 85.7 32.0 13.6 47.7 29.0 33.9 17.3 15.7 55.8 18.8 2.1 21.4 126.1 104.3 203.8 2.5
Simulation 3.49 0.96 1.57 4.57 3.12 4.21 9.91 3.14 6.77 3.78 3.80 4.27 0.48 0.43 0.30 50.79
10 μm Math. Modela 1.74 2.45 3.41 4.63 3.60 4.80 3.96 3.09 3.99 3.10 2.41 2.98 2.31 1.78 2.08 46.34
Error (%) 50.2 155.4 116.3 1.3 15.5 14.2 60.0 1.6 41.1 18.0 36.6 30.1 384.0 314.9 600.4 8.8
Table adapted from Kleinstreuer & Zhang 2009.

a
The commonly used analytical deposition equations given in the NCRP model are employed to calculate the deposition efficiency (see Kleinstreuer & Zhang 2009).
b
Data for 1D trumpet model are from Choi & Kim (2007).
www.annualreviews.org • Airflow and Particle Transport

327
DISCLOSURE STATEMENT
The authors are not aware of any affiliations, memberships, funding, or financial holdings that
might be perceived as affecting the objectivity of this review.
ACKNOWLEDGMENTS
This effort was sponsored by the Air Force Office of Scientific Research, Air Force Material Com-
mand, USAF, under grant number FA9550-07-1-0461 (Dr. Walt Kozumbo, Program Manager),
NSF Grant CBET-0834054 (Dr. Marc S. Ingber, Program Director). The U.S. Government is
authorized to reproduce and distribute reprints for governmental purposes notwithstanding any
copyright notation thereon. The use of both CFX software from ANSYS Inc. (Canonsburg, PA)
and IBM Linux Cluster at the High Performance Computing Center at North Carolina State
University (Raleigh, NC) is gratefully acknowledged as well. The authors also thank Professor
Andrew Pollard and Mr. Christopher Ball of Queen’s University at Kingston for supplying their
idealized geometry of the extrathoracic airway (see Figure 3), which is a variation of the one
described in Stapleton et al. (2000).
LITERATURE CITED
Adler K, Brucker C. 2007. Dynamic flow in a realistic model of the upper human lung airways. Exp. Fluids
43:411–23
Asgharian B, Anjilvel S. 1994. A Monte-Carlo calculation of the deposition efficiency of inhaled particles in
lower airways. J. Aerosol Sci. 25:711–21
Asgharian B, Hofman W, Bergmann R. 2001. Particle deposition in a multiple-path model of the human lung.
Aerosol Sci. Technol. 34:332–39
Balashazy I, Hofmann W, Farkas A, Madas BG. 2008. Three-dimensional model for aerosol transport and
deposition in expanding and contracting alveoli. Inhal. Toxicol. 20:611–21
Balashazy I, Hofmann W, Heistracher T. 2003. Local particle deposition patterns may play a key role in the
development of lung cancer. J. Appl. Physiol. 94:1719–25
Ball CG, Uddin M, Pollard A. 2008a. High resolution turbulence modelling of airflow in an idealised human
extrathoracic airway. Comput. Fluids 37:943–64
Ball CG, Uddin M, Pollard A. 2008b. Mean flow structures inside the human upper airway. Flow Turbul.
Combust. 81:155–88
Breuer M, Baytekin HT, Matida EA. 2006. Prediction of aerosol deposition in 90◦ bends using LES and an
efficient Lagrangian tracking method. J. Aerosol Sci. 37:1407–28
Brouns M, Verbanck S, Lacor C. 2007. Influence of glottic aperture on the tracheal flow. J. Biomech. 40:165–72
Burrowes KS, Swan AJ, Warren NJ, Tawhai MH. 2008. Towards a virtual lung: multi-scale, multi-physics
modelling of the pulmonary system. Philos. Trans. R. Soc. A Math. Phys. Eng. Sci. 366:3247–63
Cheng KH, Cheng YS, Yeh HC, Swift DL. 1995. Deposition of ultrafine aerosols in the head airways during
natural breathing and during simulated breath-holding using replicate human upper airway casts. Aerosol
Sci. Technol. 23:465–74
Cheng KH, Cheng YS, Yeh HC, Swift DL. 1997a. An experimental method for measuring aerosol deposition
efficiency in the human oral airway. Am. Ind. Hyg. Assoc. J. 58:207–13
Cheng KH, Cheng YS, Yeh HC, Swift DL. 1997b. Measurements of airway dimensions and calculation of
mass transfer characteristics of the human oral passage. J. Biomech. Eng. Trans. ASME 119:476–82
Cheng YS. 2003. Aerosol deposition in the extrathoracic region. Aerosol Sci. Technol. 37:659–71
Cheng YS, Yeh HC, Guilmette RA, Simpson SQ, Cheng KH, Swift DL. 1996. Nasal deposition of ultrafine
particles in human volunteers and its relationship to airway geometry. Aerosol Sci. Technol. 25:274–91
Choi JI, Kim CS. 2007. Mathematical analysis of particle deposition in human lungs: an improved single path
transport model. Inhal. Toxicol. 19:925–39

Churchill SE, Shackelford LL, Georgi JN, Black MT. 2004. Morphological variation and airflow dynamics
in the human nose. Am. J. Hum. Biol. 16:625–38
Cinquin P, Troccaz I. 2003. Model driven therapy: the instance of computer assisted medical interventions.
Methods Inf. Med. 42:169–76
Clift R, Grace JR, Weber ME. 1978. Bubbles, Drops, and Particles. New York: Academic
Cohen BS, Sussman RG, Lippmann M. 1990. Ultrafine particle deposition in a human tracheobronchial cast.
Comer JK, Kleinstreuer C, Zhang Z. 2001. Flow structures and particle deposition patterns in double-
bifurcation airway models. Part 1: air flow fields. J. Fluid Mech. 435:25–54
Corcoran TE, Chigier N. 2000. Characterization of the laryngeal jet using phase Doppler interferometry.
J. Aerosol Med. Depos. Clear. Effects Lung 13:125–37
Crowe C, Sommerfeld M, Tsuji Y. 1998. Multiphase Flows with Droplets and Particles. New York: CRC Press
Daigle CC, Chalupa DC, Gibb FR, Morrow PE, Oberdorster G, et al. 2003. Ultrafine particle deposition in
humans during rest and exercise. Inhal. Toxicol. 15:539–52
Dailey HL, Ghadiali SN. 2007. Fluid-structure analysis of microparticle transport in deformable pulmonary
alveoli. J. Aerosol Sci. 38:269–88

Darquenne C. 2002. Heterogeneity of aerosol deposition in a two-dimensional model of human alveolated
ducts. J. Aerosol Sci. 33:1261–78
Darquenne C, Paiva N. 1996. Two- and three-dimensional simulations of aerosol transport and deposition in
alveolar zone of human lung. J. Appl. Physiol. 80:1401–14
Dehbi A. 2008. Turbulent particle dispersion in arbitrary wall-bounded geometries: a coupled CFD-Langevin-
equation based approach. Int. J. Multiphase Flow 34:819–28
Doorly DJ, Taylor DJ, Gambaruto AM, Schroter RC, Tolley N. 2008a. Nasal architecture: form and flow.
Philos. Trans. R. Soc. A Math. Phys. Eng. Sci. 366:3225–46
Doorly DJ, Taylor DJ, Schroter RC. 2008b. Mechanics of airflow in the human nasal airways. Respir. Physiol.
Neurobiol. 163:100–10
Elad D, Schroter RC, eds. 2008. Respiratory Physiology and Neurobiology: Special Issue for Respiratory Mechanics,
Vol. 163. Elsevier
Farkas A, Balashazy I. 2008. Quantification of particle deposition in asymmetrical tracheobronchial model
geometry. Comput. Biol. Med. 38:508–18
Finlay WH. 2001. The Mechanics of Inhaled Pharmaceutical Aerosols: An Introduction. London: Academic
Finlay WH, Martin AR. 2008. Recent advances in predictive understanding of respiratory tract deposition.
J. Aerosol Med. Pulm. Drug Deliv. 21:189–205
Freitas RK, Schroder W. 2008. Numerical investigation of the three-dimensional flow in a human lung model.
J. Biomech. 41:2446–57
Fresconi FE, Prasad AK. 2007. Secondary velocity fields in the conducting airways of the human lung.
J. Biomech. Eng. Trans. ASME 129:722–32
Friedlander SK. 2000. Smoke, Dust, and Haze: Fundamentals of Aerosol Dynamics. New York: Oxford Univ. Press
Geiser M, Schurch S, Im Hof V, Gehr P. 2000. Structural and interfacial aspects of particle retention. In
Particle-Lung Interaction, ed. P Gehr, J Heyder, pp. 291–321. New York: Marcel Dekker
Gemci T, Ponyavin V, Chen Y, Chen H, Collins R. 2008. Computational model of airflow in upper 17
generations of human respiratory tract. J. Biomech. 41:2047–54
Gosman AD, Ioannides E. 1981. Aspects of computer simulation of liquid-fueled combustors. J. Energy 7:482–
90
Grosse S, Schroder W, Klaas M, Klockner A, Roggenkamp J. 2007. Time resolved analysis of steady and
oscillating flow in the upper human airways. Exp. Fluids 42:955–70
Haber S, Tsuda A. 2006. A cyclic model for particle motion in the pulmonary acinus. J. Fluid Mech. 567:157–84
Haber S, Yitzhak D, Tsuda A. 2003. Gravitational deposition in a rhythmically expanding and contracting
alveolus. J. Appl. Physiol. 95:657–71
Haefelibleuer B, Weibel ER. 1988. Morphometry of the human pulmonary acinus. Anat. Rec. 220:401–14
Hahn I, Scherer PW, Mozell MM. 1993. Velocity profiles measured for air-flow through a large-scale model
of the human nasal cavity. J. Appl. Physiol. 75:2273–87

Harrington L, Prisk GK, Darquenne C. 2006. Importance of the bifurcation zone and branch orientation in
simulated aerosol deposition in the alveolar zone of the human lung. J. Aerosol Sci. 37:37–62
He CH, Ahmadi G. 1999. Particle deposition in a nearly developed turbulent duct flow with electrophoresis.
J. Aerosol Sci. 30:739–58
Heenan AF, Matida E, Pollard A, Finlay WH. 2003. Experimental measurements and computational modeling
of the flow field in an idealized human oropharynx. Exp. Fluids 35:70–84
Henry FS, Laine-Pearson FE, Tsuda A. 2009. Hamiltonian chaos in a model alveolus. J. Biomech. Eng. Trans.
ASME 131:011006
Heyder J. 2004. Deposition of inhaled particles in the human respiratory tract and consequences for regional
targeting in respiratory drug delivery. Proc. Am. Thorac. Soc. 1:315–20
Hoet P, Brueske-Hohlfeld I, Salata O. 2004. Nanoparticles: known and unknown health risks. J. Nanobiotechnol.
2:12
Hofmann W, Golser R, Balashazy I. 2003. Inspiratory deposition efficiency of ultrafine particles in a human
airway bifurcation model. Aerosol Sci. Technol. 37:988–94
Holzer A, Sommerfeld M. 2008. New simple correlation formula for the drag coefficient of nonspherical
particles. Powder Technol. 184:361–65

Horschler I, Meinke M, Schroder W. 2003. Numerical simulation of the flow field in a model of the nasal
cavity. Comput. Fluids 32:39–45
Horsfield K, Dart G, Olson DE, Filley GF, Cumming G. 1971. Models of the human bronchial tree. J. Appl.
Physiol. 31:207–17
Int. Comm. Radiol. Prot. (ICRP). 1994. Human respiratory tract model for radiological protection. In Annals
of the ICRP, pp. 1–468. New York: Elsevier
Jayaraju ST, Brouns M, Lacor C, Belkassem B, Verbanck S. 2008. Large eddy and detached eddy simulations
of fluid flow and particle deposition in a human mouth-throat. J. Aerosol Sci. 39:862–75
Johnstone A, Uddin M, Pollard A, Heenan A, Finlay WH. 2004. The flow inside an idealised form of the
human extrathoracic airway. Exp. Fluids 37:673–89
Karl A, Henry FS, Tsuda A. 2004. Low Reynolds number viscous flow in an alveolated duct. J. Biomech. Eng.
Trans. ASME 126:420–29
Kelly JT, Asgharian B, Kimbell JS, Wong BA. 2004a. Particle deposition in human nasal airway replicas
manufactured by different methods. Part I: inertial regime particles. Aerosol Sci. Technol. 38:1063–71
Kelly JT, Asgharian B, Kimbell JS, Wong BA. 2004b. Particle deposition in human nasal airway replicas
manufactured by different methods. Part II: ultrafine particles. Aerosol Sci. Technol. 38:1072–79
Keyhani K, Scherer PW, Mozell MM. 1995. Numerical simulation of airflow in the human nasal cavity.
J. Biomech. Eng. Trans. ASME 117:429–41
Keyhani K, Scherer PW, Mozell MM. 1997. A numerical model of nasal odorant transport for the analysis of
human olfaction. J. Theor. Biol. 186:279–301
Kim CS, Fisher DM. 1999. Deposition characteristics of aerosol particles in sequentially bifurcating airway
models. Aerosol Sci. Technol. 31:198–220
Kim CS, Jaques PA. 2000. Respiratory dose of inhaled ultrafine particles in healthy adults. Philos. Trans. R. Soc.
Lond. A Math. Phys. Eng. Sci. 358:2693–705
Kim CS, Jaques PA. 2004. Analysis of total respiratory deposition of inhaled ultrafine particles in adult subjects
as various breathing patterns. Aerosol Sci. Technol. 38:525–40
Kim SK, Chung SK. 2004. An investigation on airflow in disordered nasal cavity and its corrected models by
tomographic PIV. Meas. Sci. Technol. 15:1090–96
Kleinstreuer C. 2003. Two-Phase Flow: Theory and Applications. New York: Taylor & Francis
Kleinstreuer C. 2006. Biofluid Dynamics: Principles and Selected Applications. Boca Raton, FL: CRC Press
Kleinstreuer C, Zhang Z. 2003. Laminar-to-turbulent fluid-particle flows in a human airway model. Int. J.
Multiphase Flow 29:271–89
Kleinstreuer C, Zhang Z. 2009. An adjustable triple-bifurcation unit (TBU) model for air-particle flow sim-
ulations in human tracheobronchial airways. J. Biomech. Eng. Trans. ASME 131:021007
Kleinstreuer C, Zhang Z, Donohue JF. 2008. Targeted drug-aerosol delivery in the human respiratory system.
Annu. Rev. Biomed. Eng. 10:195–220

Kleinstreuer C, Zhang Z, Kim CS. 2007. Combined inertial and gravitational deposition of microparticles in
small model airways of human respiratory system. J. Aerosol Sci. 38:1047–61
Kratzberg JL, Greifzu S, Larson K, Dittman J, McCormick M, et al. 2005. Fabrication of a patient-specific
replica of abdominal aortic aneurysm with realistic compliance and translucency. Int.l J. Cardiovasc. Med.
5:33–38
Leong FY, Smith KA, Wang CH. 2009. Secondary flow behavior in a double bifurcation. Phys. Fluids 21:043601
Li W, Xiong JQ, Cohen BS. 1998. The deposition of unattached radon progeny in a tracheobronchial cast as
measured with iodine vapor. Aerosol Sci. Technol. 28:502–10
Li Z. 2007. Airflow and micro-particle transport and deposition in realistic lung airways including the alveolar region.
PhD thesis. North Carolina State Univ., Raleigh. 212 pp.
Li Z, Kleinstreuer C, Zhang Z. 2007a. Particle deposition in the human tracheobronchial airways due to
transient inspiratory flow patterns. J. Aerosol Sci. 38:625–44
Li Z, Kleinstreuer C, Zhang Z. 2007b. Simulation of airflow fields and microparticle deposition in realistic
human lung airway models. Part I: airflow patterns. Eur. J. Mech. B Fluids 26:632–49
Lieber BB, Zhao Y. 1998. Oscillatory flow in a symmetric bifurcation airway model. Ann. Biomed. Eng. 26:821–
30
Lin CL, Tawhai MH, McLennan G, Hoffman EA. 2007. Characteristics of the turbulent laryngeal jet and its
effect on airflow in the human intrathoracic airways. Respir. Physiol. Neurobiol. 157:295–309
Liu Y, Matida EA, Gu J, Johnson MR. 2007. Numerical simulation of aerosol deposition in a 3-D human
nasal cavity using RANS, RANS/EIM, and LES. J. Aerosol Sci. 38:683–700
Longest PW, Kleinstreuer C, Buchanan JR. 2004. Efficient computation of microparticle dynamics including
wall effects. Comput. Fluids 33:577–601
Longest PW, Oldham MJ. 2008. Numerical and experimental deposition of fine respiratory aerosols: devel-
opment of a two-phase drift flux model with near-wall velocity corrections. J. Aerosol Sci. 39:48–70
Longest PW, Vinchurkar S. 2007a. Effects of mesh style and grid convergence on particle deposition in
bifurcating airway models with comparisons to experimental data. Med. Eng. Phys. 29:350–66
Longest PW, Vinchurkar S. 2007b. Validating CFD predictions of respiratory aerosol deposition: effects of
upstream transition and turbulence. J. Biomech. 40:305–16
Longest PW, Xi JX. 2007. Computational investigation of particle inertia effects on submicron aerosol depo-
sition in the respiratory tract. J. Aerosol Sci. 38:111–30
Longest PW, Xi JX. 2008. Condensational growth may contribute to the enhanced deposition of cigarette
smoke particles in the upper respiratory tract. Aerosol Sci. Technol. 42:579–602
Luo HY, Liu Y. 2008. Modeling the bifurcating flow in a CT-scanned human lung airway. J. Biomech. 41:2681–
88
Luo XY, Hinton JS, Liew TT, Tan KK. 2004. LES modelling of flow in a simple airway model. Med. Eng.
Phys. 26:403–13
Ma B, Lutchen K. 2006. An anatomically based hybrid computational model of the human lung and its
application to low frequency oscillatory mechanics. Ann. Biomed. Eng. 34:1691–704
Ma B, Lutchen K. 2009. CFD simulation of aerosol deposition in an anatomically based human large-medium
airway model. Ann. Biomed. Eng. 37:271–85
Ma B, Ruwet V, Corieri P, Theunissen R, Riethmuller M, Darquenne C. 2009. CFD simulation and experi-
mental validation of fluid flow and particle transport in a model of alveolated airways. J. Aerosol Sci. 40:
403–14
Matida EA, Finlay WH, Breuer M, Lange CF. 2006. Improving prediction of aerosol deposition in an idealized
mouth using large-eddy simulation. J. Aerosol Med. 19:290–300
Matida EA, Finlay WH, Lange CF, Grgic B. 2004. Improved numerical simulation of aerosol deposition in
an idealized mouth-throat. J. Aerosol Sci. 35:1–19
Michaelides EE. 1997. Review: the transient equation of motion for particles, bubbles, and droplets. J. Fluids
Eng. Trans. ASME 119:233–47
Nazridoust K, Asgharian B. 2008. Unsteady-state airflow and particle deposition in a three-generation human
lung geometry. Inhal. Toxicol. 20:595–610
Natl. Council Radiat. Protect. Meas. (NCRP). 1997. Deposition, retention, and dosimetry of inhaled radioac-
tive substances. Report No. 125, Bethesda, MD

Nithiarasu P, Hassan O, Morgan K, Weatherill NP, Fielder C, et al. 2008. Steady flow through a realistic
human upper airway geometry. Int. J. Numer. Methods Fluids 57:631–51
Nowak N, Kakade PP, Annapragada AV. 2003. Computational fluid dynamics simulation of airflow and aerosol
deposition in human lungs. Ann. Biomed. Eng. 31:374–90
Oberdörster G, Oberdörster E, Oberdörster J. 2005. Nanotoxicology: an emerging discipline evolving from
studies of ultrafine particles. Environ. Health Perspect. 113:823–39
Olson DE, Sudlow MF, Horsfiel K, Filley GF. 1973. Convective patterns of flow during inspiration. Arch.
Int. Med. 131:51–57
Park SS, Wexler AS. 2007. Particle deposition in the pulmonary region of the human lung: a semiempirical
model of single breath transport and deposition. J. Aerosol Sci. 38:228–45
Pedley TJ. 1977. Pulmonary fluid dynamics. Annu. Rev. Fluid Mech. 9:229–74
Perchet D, Fetita CI, Vial L, Preteux F, Caillibotte G, et al. 2004. Virtual investigation of pulmonary airways
in volumetric computed tomography. Comput. Anim. Virtual Worlds 15:361–76
Phalen RF. 2009. Inhalation Studies: Foundations and Techniques. New York: Informa Health Care. 2nd ed.
Phalen RF, Oldham MJ, Beaucage CB, Crocker TT, Mortensen JD. 1985. Postnatal enlargement of human
tracheo-bronchial airways and implications for particle deposition. Anat. Rec. 212:368–80
Raabe OG, Yeh HC, Schum GM, Phalen RF. 1976. Tracheobronchial geometry: human, dog, rat, hamster,
LF-53, Lovelace Found., Albuquerque, NM
RIVM (Natl. Inst. Public Health Environ.). 2002. Multiple path particle dosimetry model (MPPD v 1.0): a
model for human and rat airway particle dosimetry. RIVA Report 650010030, Bilthoven, The Netherlands.
Robinson RJ, Snyder P, Oldham MJ. 2007. Comparison of particle tracking algorithms in commercial CFD
packages: sedimentation and diffusion. Inhal. Toxicol. 19:517–31
Robinson RJ, Snyder P, Oldham MJ. 2008. Comparison of analytical and numerical particle deposition using
commercial CFD packages: impaction and sedimentation. Inhal. Toxicol. 20:485–97
Russo J, Robinson R, Oldham MJ. 2008. Effects of cartilage rings on airflow and particle deposition in the
trachea and main bronchi. Med. Eng. Phys. 30:581–89
Schroeter JD, Kimbell JS, Asgharian B. 2006. Analysis of particle deposition in the turbinate and olfactory
regions using a human nasal computational fluid dynamics model. J. Aerosol Med. Depos. Clear. Effects Lung
19:301–13
Shi H, Kleinstreuer C, Zhang Z. 2006. Laminar airflow and nanoparticle or vapor deposition in a human nasal
cavity model. J. Biomech. Eng. Trans. ASME 128:697–706
Shi H, Kleinstreuer C, Zhang Z. 2007. Modeling of inertial particle transport and deposition in human nasal
cavities with wall roughness. J. Aerosol Sci. 38:398–419
Shi H, Kleinstreuer C, Zhang Z. 2008. Dilute suspension flow with nanoparticle deposition in a representative
nasal airway model. Phys. Fluids 20:013301
Shi H, Kleinstreuer C, Zhang Z, Kim CS. 2004. Nanoparticle transport and deposition in bifurcating tubes
with different inlet conditions. Phys. Fluids 16:2199–213
Silverthorn DU. 2004. Human Physiology: An Integrated Approach. Upper Saddle River, NJ: Prentice Hall
Smith S, Cheng US, Yeh HC. 2001. Deposition of ultrafine particles in human tracheobronchial airways of
adults and children. Aerosol Sci. Technol. 35:697–709
Sosnowski TR. 2007. Mechanisms of aerosol particle deposition in the oro-pharynx under nonsteady airflow.
Ann. Occup. Hyg. 51:19–25
Stapleton KW, Guentsch E, Hoskinson MK, Finlay WH. 2000. On the suitability of k-epsilon turbulence
modeling for aerosol deposition in the mouth and throat: a comparison with experiment. J. Aerosol Sci.
31:739–49
Subramaniam RP, Richardson RB, Morgan KT, Kimbell JS, Guilmette RA. 1998. Computational fluid dy-
namics simulations of inspiratory airflow in the human nose and nasopharynx. Inhal. Toxicol. 10:473–502
Swift DL, Montassier N, Hopke PK, Karpenhayes K, Cheng YS, et al. 1992. Inspiratory deposition of ultrafine
particles in human nasal replicate cast. J. Aerosol Sci. 23:65–72
Swift DL, Proctor DF. 1977. Access of air to the respiratory tract. In Respiratory Defense Mechanisms: Part I,
ed. JD Brain, DF Proctor, LM Reid, pp. 63–93. New York: Dekker
Sznitman J, Heimsch F, Heimsch T, Rusch D, Rosgen T. 2007. Three-dimensional convective alveolar flow
induced by rhythmic breathing motion of the pulmonary acinus. J. Biomech. Eng. Trans. ASME 129:658–65

Taylor CA, Draney MT. 2004. Experimental and computational methods in cardiovascular fluid mechanics.
Annu. Rev. Fluid Mech. 36:197–231
Tebockhorst S, Lee D, Wexler AS, Oldham MJ. 2007. Interaction of epithelium with mesenchyme affects
global features of lung architecture: a computer model of development. J. Appl. Physiol. 102:294–305
Theunissen R, Riethmuller ML. 2008. Particle image velocimetry in lung bifurcation models. In Particle
Image Velocimetry: New Developments and Recent Applications, ed. A Schröder, CE Willert, pp. 73–101.
Berlin: Springer
Tian L, Ahmadi G. 2007. Particle deposition in turbulent duct flows: comparisons of different model predic-
tions. J. Aerosol Sci. 38:377–97
Tsuda A, Henry FS, Butler JP. 1995. Chaotic mixing of alveolated duct flow in rhythmically expanding
pulmonary acinus. J. Appl. Physiol. 79:1055–63
Tsuda A, Henry FS, Butler JP. 2008. Gas and aerosol mixing in the acinus. Respir. Physiol. Neurobiol. 163:139–49
van Ertbruggen C, Corieri P, Theunissen R, Riethmuller ML, Darquenne C. 2008. Validation of CFD
predictions of flow in a 3D alveolated bend with experimental data. J. Biomech. 41:399–405
van Ertbruggen C, Hirsch C, Paiva M. 2005. Anatomically based three-dimensional model of airways to
simulate flow and particle transport using computational fluid dynamics. J. Appl. Physiol. 98:970–80
Varghese SS, Frankel SH. 2003. Numerical modeling of pulsatile turbulent flow in stenotic vessels. J. Biomech.
Eng. Trans. ASME 125:445–60
Wall WA, Rabczuk T. 2008. Fluid-structure interaction in lower airways of CT-based lung geometries.
Int. J. Numer. Methods Fluids 57:653–75
Weibel ER. 1963. Morphometry of the Human Lung. New York: Academic
Wolters B, Rutten MCM, Schurink GWH, Kose U, de Hart J, van de Vosse FN. 2005. A patient-specific com-
putational model of fluid-structure interaction in abdominal aortic aneurysms. Med. Eng. Phys. 27:871–83
Xi JX, Longest PW. 2007. Transport and deposition of microaerosols in realistic and simplified models of the
oral airway. Ann. Biomed. Eng. 35:560–81
Xi JX, Longest PW. 2008a. Effects of oral airway geometry characteristics on the diffusional deposition of
inhaled nanoparticles. J. Biomech. Eng. Trans. ASME 130:011008
Xi JX, Longest PW. 2008b. Evaluation of a drift flux model for simulating submicrometer aerosol dynamics
in human upper tracheobronchial airways. Ann. Biomed. Eng. 36:1714–34
Xi JX, Longest PW. 2008c. Numerical predictions of submicrometer aerosol deposition in the nasal cavity
using a novel drift flux approach. Int. J. Heat Mass Transf. 51:5562–77
Xi JX, Longest PW, Martonen TB. 2008. Effects of the laryngeal jet on nano- and microparticle transport and
deposition in an approximate model of the upper tracheobronchial airways. J. Appl. Physiol. 104:1761–77
Yang XL. 2006. Respiratory flow in obstructed airways. J. Biomech. 39:2743–51
Yu G, Zhang Z, Lessmann R. 1996. Computer simulation of the flow field and particle deposition by diffusion
in a 3-D human airway bifurcation. Aerosol Sci. Technol. 25:338–52
Yu G, Zhang Z, Lessmann R. 1998. Fluid flow and particle diffusion in the human upper respiratory system.
Zamankhan P, Ahmadi G, Wang ZC, Hopke PK, Cheng YS, et al. 2006. Airflow and deposition of nano-
particles in a human nasal cavity. Aerosol Sci. Technol. 40:463–76
Zhang Y, Finlay WH. 2005. Measurement of the effect of cartilaginous rings on particle deposition in a
proximal lung bifurcation model. Aerosol Sci. Technol. 39:394–99
Zhang Z, Kleinstreuer C. 2002. Transient airflow structures and particle transport in a sequentially branching
lung airway model. Phys. Fluids 14:862–80
Zhang Z, Kleinstreuer C. 2003a. Low-Reynolds-number turbulent flows in locally constricted conduits: a
comparison study. AIAA J. 41:831–40
Zhang Z, Kleinstreuer C. 2003b. Species heat and mass transfer in a human upper airway model. Int. J. Heat
Mass Transf. 46:4755–68
Zhang Z, Kleinstreuer C. 2004. Airflow structures and nano-particle deposition in a human upper airway
model. J. Comput. Phys. 198:178–210
Zhang Z, Kleinstreuer C, Donohue JF, Kim CS. 2005. Comparison of micro- and nano-size particle deposi-
tions in a human upper airway model. J. Aerosol Sci. 36:211–33

Zhang Z, Kleinstreuer C, Kim CS. 2001. Flow structure and particle transport in a triple bifurcation airway
model. J. Fluids Eng. Trans. ASME 123:320–30
Zhang Z, Kleinstreuer C, Kim CS. 2002a. Cyclic micron-size particle inhalation and deposition in a triple
bifurcation lung airway model. J. Aerosol Sci. 33:257–81
Zhang Z, Kleinstreuer C, Kim CS. 2002b. Gas-solid two-phase flow in a triple bifurcation lung airway model.
Int. J. Multiphase Flow 28:1021–46
Zhang Z, Kleinstreuer C, Kim CS. 2002c. Micro-particle transport and deposition in a human oral airway
model. J. Aerosol Sci. 33:1635–52
Zhang Z, Kleinstreuer C, Kim CS. 2006a. Isotonic and hypertonic saline droplet deposition in a human upper
airway model. J. Aerosol Med. Depos. Clear. Effects Lung 19:184–98
Zhang Z, Kleinstreuer C, Kim CS. 2006b. Transport and uptake of MTBE and ethanol vapors in a human
upper airway model. Inhal. Toxicol. 18:169–84
Zhang Z, Kleinstreuer C, Kim CS. 2006c. Water vapor transport and its effects on the deposition of hygroscopic
droplets in a human upper airway model. Aerosol Sci. Technol. 40:1–16
Zhang Z, Kleinstreuer C, Kim CS. 2008. Airflow and nanoparticle deposition in a 16-generation tracheo-
bronchial airway model. Ann. Biomed. Eng. 36:2095–110

Zhang Z, Kleinstreuer C, Kim CS. 2009. Comparison of analytical and CFD models with regard to micron
particle deposition in a human 16-generation tracheobronchial airway model. J. Aerosol Sci. 40:16–28
Zhang Z, Kleinstreuer C, Kim CS, Cheng YS. 2004. Vaporizing microdroplet inhalation, transport, and
deposition in a human upper airway model. Aerosol Sci. Technol. 38:36–49
Zhang Z, Kleinstreuer C, Kim CS, Hickey AJ. 2002d. Aerosol transport and deposition in a triple bifurcation
bronchial airway model with local tumors. Inhal. Toxicol. 14:1111–33

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Volume 42, 2010
Singular Perturbation Theory: A Viscous Flow out of Göttingen

Robert E. O’Malley Jr. p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 1

Dynamics of Winds and Currents Coupled to Surface Waves

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Gas Injection
Steven L. Ceccio p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 183
Wave–Vortex Interactions in Fluids and Superfluids
Oliver Bühler p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 205
Laminar, Transitional, and Turbulent Flows in Rotor-Stator Cavities
Brian Launder, Sébastien Poncet, and Eric Serre p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 229
Scale-Dependent Models for Atmospheric Flows
Rupert Klein p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 249
Spike-Type Compressor Stall Inception, Detection, and Control
C.S. Tan, I. Day, S. Morris, and A. Wadia p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 275
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Airflow and Particle Transport in the Human Respiratory System

C. Kleinstreuer and Z. Zhang p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 301
Small-Scale Properties of Turbulent Rayleigh-Bénard Convection
Detlef Lohse and Ke-Qing Xia p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 335
Fluid Dynamics of Urban Atmospheres in Complex Terrain
H.J.S. Fernando p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 365
Turbulent Plumes in Nature
Andrew W. Woods p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 391
Fluid Mechanics of Microrheology
Todd M. Squires and Thomas G. Mason p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 413

Lattice-Boltzmann Method for Complex Flows

Cyrus K. Aidun and Jonathan R. Clausen p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 439
Wavelet Methods in Computational Fluid Dynamics
Kai Schneider and Oleg V. Vasilyev p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 473
Dielectric Barrier Discharge Plasma Actuators for Flow Control
Thomas C. Corke, C. Lon Enloe, and Stephen P. Wilkinson p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 505
Applications of Holography in Fluid Mechanics and Particle Dynamics
Joseph Katz and Jian Sheng p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 531
Recent Advances in Micro-Particle Image Velocimetry
Steven T. Wereley and Carl D. Meinhart p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 557
Indexes
Cumulative Index of Contributing Authors, Volumes 1–42 p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 577

Cumulative Index of Chapter Titles, Volumes 1–42 p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 585
Errata
An online log of corrections to Annual Review of Fluid Mechanics articles may be found
at http://fluid.annualreviews.org/errata.shtml
viii Contents

Articol 1 - Diffusion Microchannels - Balan Et Al.

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• Top downloaded articles

C. Kleinstreuer1,2 and Z. Zhang1

Annu. Rev. Fluid Mech. 2010. 42:301–34 Key Words

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morphologies differ, and exact patient-speciﬁc modeling is still cost prohibitive.

2.1. Basic Bifurcations

Reeq uiv. = 0.5(Remax + Remean ), (1)

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2.2. Idealized Lung Configurations

2.3. Realistic Airway Models

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3.1. Nasal Airways

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1–1' 2–2' 5–5' 6–6'

Slice 3–3' Slice 5–5'

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speciﬁc studies on nasal geometry effects have not been reported.

3.2. Lung Airways

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–0.05 0.10 0.25 0.40 0.55 0.70 2.6

Selected axial velocity contours and secondary velocity vectors

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4. DILUTE PARTICLE SUSPENSIONS

4.1. Nanomaterial and Vapor Transport

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diffusion coefﬁcient (Dp ) can be written as

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is deﬁned as the ratio of local to average deposition densities; i.e.,

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SLA (Kelly et al. 2004b)

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distributions at the inlets of these bifurcations (Zhang et al. 2008).

4.2. Solid Micron Particle and Droplet Dynamics

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Table 1 Some correlations for inspiratory nanoparticle deposition efficiencies

Region Deposition equation Reference(s) Parameter definition

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In general, for particle-deposition studies, the Stokes number is used:

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second, and third bifurcation), as deﬁned by Zhang et al. (2005).

4.2.1. Micron-particle distributions. Affected by the upstream deposition, local nonuniform

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Larynx DEF DEF

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5. CONCLUSIONS AND FUTURE DIRECTIONS

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Table adapted from Kleinstreuer & Zhang 2009.

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alveoli. J. Aerosol Sci. 38:269–88

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particles. Powder Technol. 184:361–65

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