Santhosh Jayaraju

!!!!!!!!!!!!!!
!
!
!
FACULTY OF ENGINEERING
Department of Mechanical Engineering
!
!
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Thesis submitted in fulfilment of the requirements for the
award of the degree of Doctor in de ingenieurswetenschappen
(Doctor in Engineering) by
"12#)'3)!4'>,21?*-*!@1&1-1A$
April 2009
Advisor(s):
Prof. Dr. Ir. Chris Lacor

Prof. Dr. Sylvia Verbanck
Outline
Inhaled pharmaceutical aerosols have been playing a crucial role in the
health and wellbeing of millions of people throughout the world for several
years. Since the mid 1950s, aerosol forms of medication have been significant in treating the most common respiratory illnesses such as asthma
and chronic obstructive pulmonary disease (COPD). However, administration of drugs by the pulmonary route is technically challenging and our
understanding of the aerosol transport in the lungs is far from complete.
The main contributing factors are:
Variable filtering effects of the upper and central airways before the
medication can reach the alveolar region of the lungs where they are
eventually taken up by blood.
Considerable inter-subject variations in the airway morphology.
Variations in inhalation techniques.
For the above reasons, devising an efficient aerosol delivery system requires a systematic understanding of the effect of aforementioned variables on aerosol behavior in the human airways. Indeed, performing such
systematic in-vivo measurements is not feasible. Alternatively, the use of
Computational Fluid Dynamics (CFD) has emerged as an effective tool for
methodical analysis of various parameters affecting the airflow as well as
aerosol dynamics in the human airways.
As will be seen in the introduction chapter of this thesis, the human airway is mainly divided into three regions, namely the extra-thoracic (upper
airway), the tracheo-bronchial, and the alveolar region. The present thesis is focused on the study of air-breathing patterns and medical aerosol
transport-deposition in the upper airways. From CFD simulation point of
view, the upper airway region is the most challenging due to transitional
nature of the airflow. The present thesis is broadly divided into eight chapters. The contents and relevant significance of each chapter is briefly described below.
Chapter 1 gives a brief introduction to the human respiratory system.

Physical features of each part of the airway are highlighted. Particular
attention is given to the upper airway region due to its relevance in the
present thesis. A brief introduction is given as to how the aerosols and
the human airways are linked, followed by some details of the factors and
mechanisms affecting the aerosol transport-deposition in the upper airways.
The literature survey on the existing study of flow patterns and particle
transport in the upper airway constitutes Chapter 2. The upper airway geometries with varying degrees of geometrical complexities used in literature are drawn out. The airway geometries are presented in the ascending
order of their complexity, i.e., from simplest to the more complex. The modeling methods used for the CFD study of fluid as well as particle phase are
reported. The fluid flow patterns as well as the aerosol deposition characteristics observed by various researchers in different upper airway geometries are discussed. By combining various in-vivo and in-vitro deposition
data in the human upper airways, several authors have devised relatively
simple mathematical models for predicting the amount of inhaled aerosol
that may deposit in the upper airways. All such correlations pertaining to
the upper airways and their particular limitations are discussed. In addition to this chapter of literature survey which provides a brief summary of
the most important observations, the introduction section of each chapter
in this thesis also discusses the relevant literature pertaining to the concerned chapter.
In Chapter 3, the governing equations for the fluid phase, pertaining to the
modeling methods employed in the present thesis, are discussed. The modeling methods include Reynolds Averaged Navier Stokes (RANS), Large
Eddy Simulation (LES) as well as Detached Eddy Simulation (DES). Finally, the feasibility of using each of these methodologies to study the fluidparticle dynamics in the upper airways is discussed.
Chapter 4 describes the governing equations for the particle phase followed
by the main aspects of Lagrangian modeling methods employed for handling unstructured grids. Even though the concept of unstructured grids
exists since long, the practical applicability is still under budding stage,
especially for two-phase simulations. In this view, the modeling methods
described in this chapter can be seen as the first step towards applicability of unstructured grids for biomedical applications, which is by far the
only option to avoid expensive experiments for realistic geometry configurations. The next three chapters, i.e., Chapter 5, 6 and 7 are applications of
RANS methodology to study the fluid flow and particle deposition characteristics, convective mixing, and the effect of tracheal stenosis in the upper
airways.
ii
In Chapter 5, the fluid flow and particle deposition in a realistic CT-extracted

upper airway model is studied. RANS k turbulence model is used
for the fluid phase, and the Lagrangian particle solver module developed
in the previous chapter is used to study the aerosol deposition. Typical
steady inhalation modes of slow (15 l/min), normal (30 l/min) and heavy
(60 l/min) breathing are simulated. Micro-particle (1-20 m) transport and
deposition is investigated. Extensive quality control tests are performed to
study the effect of grid on fluid and particle phase; the effect of number of
aerosols on total upper airway deposition. The sensitivity of flow transition on the airway complexity is demonstrated. The pronounced effect of
sedimentation at very low flow rates on the deposition of heavy particles is
observed. Based on the enhanced oral airway deposition, the need for considering more realistic CT-based geometries is highlighted. The contents
of Chapter 4 and 5 are published in Jayaraju et al. [76].
In Chapter 6, the degree of volumetric dispersion undergone by a bolus
while passing through the upper airway passage is studied, both experimentally and numerically. In addition to aerosol bolus deposition study,
which was the main focus in the previous chapter, the study of volumetric dispersion also offers a sensitive tool to characterize aerosol transport.
Whether it is for the study of convective mixing or for medication targeting, an aerosol bolus inhaled to any given lung depth must transit the
upper airway, and it is crucial to quantitatively predict its dispersive effect, which was lacking in the literature. In this chapter, the dispersive
effects in both inhalation and exhalation modes are studied. Experiments
showed that the upper airway induces a relatively mild dispersion on the
traversing aerosol bolus and that the dispersive coefficients during inhalation and exhalation modes were very similar. The experimental dispersion
is found to be only 1/10th of the relatively arbitrary axial dispersion value
that is currently being used to characterize the upper airway transit for
simulations of aerosol transport in the deeper lung. Hence this quantification of upper airway dispersion is a considerable advancement in the field.
For the CFD simulations, RANS k methodology is used. The inability
of this model in accurately predicting the dispersive effects during expiratory mode has been observed, highlighting the need to critically assess
the most commonly used RANS k turbulence methodology. The work
corresponding to Chapter 6 is published in Jayaraju et al. [78].
Chapter 7 deals with the effect of tracheal stenosis on the flow dynamics
as well as the ensuing aerosol dispersion and deposition. The potential of
using aerosol boluses inhaled at normal breathing of 30 l/min to detect tracheal stenosis ranging 50-90% obstruction of tracheal cross sectional area
iii
is investigated. The aerosol bolus deposition efficiency and bolus dispersion, in terms of bolus half-width (HW) or bolus standard deviation (SD),
were numerically simulated as a function of the degree of stenotic obstruction. The effect of aerosol particle size on bolus deposition efficiency was
also considered. While the particle dispersion is seen to be quite insensitive to the stenotic constriction, 5 m particle deposition seemed to exhibit
considerable sensitivity, making it a probable non-invasive diagnostic tool
for the detection of tracheal stenosis. Detailed fluid flow characteristics in
the presence of stenosis is published in Brouns et al. [19].
The main objective of Chapter 8 is to test the validity of RANS, LES and
DES for the description of fluid/particle behavior in an upper airway model.
It was observed in Chapter 5 that the deposition percentage for the medical
aerosols which generally lie in the respirable range (1-5 m) were consistently over-predicted by RANS methodology. In Chapter 6, it was also seen
that RANS was inaccurate in predicting the dispersive effects during expiration mode. Based on these observations, the need to switch towards more
advanced numerical methodologies such as LES and DES is recognized.
To validate the fluid phase simulations, we performed PIV measurements
in a central sagittal plane of a simplified upper airway model cast. The
same airway model and fluid flow conditions are considered for the simulations. The transport and deposition of 1-10 m particles is investigated.
Extensive quality control tests have been performed. The superiority of
both LES and DES when compared to RANS in accurately predicting fluid
phase and the deposition of micro-particles pertaining to medical aerosols
(1-5 m) is demonstrated. The work presented in this chapter is published
in Jayaraju et al. [77].
iv
Acknowledgments
First and foremost, I would like to gratefully acknowledge the enthusiastic supervision of my promoter Prof. Chris Lacor. I particularity thank
him for our weekly technical discussions, which had a major influence on
this thesis. I am indebted to him for showing great confidence in me and
always pushing me to achieve greater heights. I can say for sure that the
past four years at VUB have been the most productive days of my learning.
The present thesis was simply not possible without the consistent guidance of my co-promoter Prof. Sylvia Verbanck. She virtually taught me everything; from making me understand the physiological aspects of human
breathing, to having those perfect final draft of articles we published together. Her leadership, attention to details, urge for perfection and downto-earth nature have set an example that I would like to match some day.
I warmly thank our system administrator Alain Wery, for his tremendous
support from my day one at VUB. I am yet to meet someone who is so patient and always ready to help others.
The support of our secretary Jenny Dhaes started even before I arrived in
Belgium. She was there for me, starting from filling down my admission
forms in Dutch, to organizing my PhD defense. Thanks a lot Jenny, you
truly have been great!
It is my pleasure to acknowledge my seniors, Mark Brouns and Ghader
Ghorbaniasl, for their valuable guidance through different phases of my
PhD. While Mark taught me his tried-and-tested practical ways of approaching a PhD, Ghader was like a walking handbook of Mathematics
whom I referred for various problems of mine.
I am also grateful to Kris Van den Abeele, firstly for guiding me through
various teaching assignments we carried out together, and secondly for gov
ing through my thesis and giving his valuable inputs. On the same note, I
would like to thank Patryk Widera for sharing the office space and for the
numerous constructive discussions we had over four years.
I am very pleased to acknowledge my present and former colleagues Sergey
Smirnov, Matteo Parsani, Mahdi Zakyani, Willem Deconinck, Khairy Elsayed, Dean Vucinic, Nikolay Ivanov, Cristian Dinescu, Jan Ramboer, Tim
Broeckhoven, and Vijay Kumar Verma, for their constant support and encouragement in all my professional endeavors.
Lastly, and most importantly, my utmost gratitude is reserved to my parents and family members for always being there through my good and bad
times.
vi
Jury Members
President
Prof. Johan DECONINCK

Vrije Universiteit Brussel
Vice-President
Prof. Rik PINTELON

Secretary
Prof. Patrick KOOL

External Members
Prof. Jan VIERENDEELS

Universiteit Gent
Prof. G
erard DEGREZ
Universit
e Libre de Bruxelles
Promoters
Prof. Chris LACOR

Prof. Sylvia VERBANCK
Universitair Ziekenhuis Brussel
vii
viii
Contents
1 Introduction
1.1 The respiratory system . . . . . . . . . . . . . . . .
1.1.1 Extra-thoracic region . . . . . . . . . . . . .
1.1.2 Tracheo-bronchial region . . . . . . . . . . .
1.1.3 Alveolar region . . . . . . . . . . . . . . . .
1.2 Aerosols and the respiratory system . . . . . . . .
1.3 Factors affecting pharmaceutical aerosol targeting
1.4 Mechanisms of particle deposition . . . . . . . . .
1.5 Clinical aerosol measurements (bolus tests) . . . .
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2 Literature Survey
2.1 Airway geometries . . . . . . . . . . . . . . . . . . . .
2.2 Modeling methods . . . . . . . . . . . . . . . . . . . .
2.2.1 Fluid phase . . . . . . . . . . . . . . . . . . .
2.2.2 Particle phase . . . . . . . . . . . . . . . . . .
2.3 Fluid flow characteristics in upper airways . . . . .
2.4 Particle deposition characteristics in upper airways
2.5 Empirical deposition relationships . . . . . . . . . .
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3 The Fluid Phase

3.1 Governing Equations . . . . . . . . . . . . . . . . .
3.1.1 Reynolds Averaged Navier Stokes (RANS)
3.1.2 Large Eddy Simulation (LES) . . . . . . . .
3.1.3 Detached Eddy Simulation (DES) . . . . . .
3.2 RANS, LES or DES ? . . . . . . . . . . . . . . . . .
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4 The Particle Phase

4.1 Governing Equations . . . . . . .
4.2 Modeling the particle phase . . .
4.3 Stochastic trajectory approach . .
4.4 Aspects of Lagrangian modeling .
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4.5
4.6
4.7
4.8
4.9
4.10
4.4.1 Time integration . . . . . . . . . . . . . .

4.4.2 Locating particles inside a control volume
4.4.3 Cell search algorithm . . . . . . . . . . . .
4.4.4 Interpolation of flow variables . . . . . . .
Boundary conditions . . . . . . . . . . . . . . . .
4.5.1 Inlet boundary condition . . . . . . . . . .
4.5.2 Wall and Outlet boundary condition . . .
Uncoupled and coupled calculations . . . . . . .
Programming language . . . . . . . . . . . . . . .
Data structures . . . . . . . . . . . . . . . . . . .
Flow chart of particle solver module . . . . . . .
Testcases . . . . . . . . . . . . . . . . . . . . . . .
4.10.1 Analytical solution . . . . . . . . . . . . .
4.10.2 2D Planar mixing layer . . . . . . . . . . .
5 Application I: Fluid Flow and Particle

Airways
5.1 Introduction . . . . . . . . . . . . . . .
5.2 Model preparation . . . . . . . . . . . .
5.3 Numerical methods . . . . . . . . . . .
5.3.1 Fluid phase . . . . . . . . . . .
5.3.2 Particle phase . . . . . . . . . .
5.4 Quality control . . . . . . . . . . . . . .
5.5 Results and discussion . . . . . . . . .
5.5.1 Fluid phase . . . . . . . . . . .
5.5.2 Particle phase . . . . . . . . . .
5.6 Conclusions . . . . . . . . . . . . . . .
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Deposition in Upper
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6 Application II: Convective Mixing in Upper Airways

6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . .
6.2 Materials and methods . . . . . . . . . . . . . . . . . .
6.2.1 Experimental methods . . . . . . . . . . . . . .
6.2.2 Numerical methods and quality control . . . .
6.3 Theoretical axial dispersion coefficient . . . . . . . . .
6.4 Results . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.4.1 Experimental results . . . . . . . . . . . . . . .
6.4.2 CFD results . . . . . . . . . . . . . . . . . . . .
6.5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . .
6.6 Limitations . . . . . . . . . . . . . . . . . . . . . . . . .
6.7 Conclusions . . . . . . . . . . . . . . . . . . . . . . . .
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7 Application III: Tracheal Stenosis

7.1 Introduction . . . . . . . . . . . . . . .
7.2 Numerical methods & quality control
7.3 Results . . . . . . . . . . . . . . . . . .
7.3.1 Fluid phase . . . . . . . . . . .
7.3.2 Particle phase . . . . . . . . . .
7.4 Conclusions . . . . . . . . . . . . . . .
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8 Fluid Flow and Particle Deposition in Upper Airways: LES

and DES
137
8.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
8.2 Model preparation & experimental methods . . . . . . . . . . 139
8.3 Numerical methods . . . . . . . . . . . . . . . . . . . . . . . . 141
8.4 Quality control . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
8.5 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
8.5.1 Fluid phase . . . . . . . . . . . . . . . . . . . . . . . . 147
8.5.2 Particle phase . . . . . . . . . . . . . . . . . . . . . . . 150
8.6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
9 Conclusions and Perspectives
9.1 Conclusions . . . . . . . . . . . . . . . . . .
9.2 Perspectives . . . . . . . . . . . . . . . . . .
9.2.1 Future CFD developments . . . . . .
9.2.2 Future Airway model developments
9.2.3 Future applications . . . . . . . . . .
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List of Publications
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Bibliography
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xi
xii
Nomenclature
Roman Symbols
(u up ) Slip velocity, m/s
Fd (u up ) Drag force per unit particle mass
Gravitational acceleration, m/s2
gx
up
Velocity of the particle, m/s
Position of the particle
xp
! !
ui uj
Reynolds stress tensor, m2 /s2
Ui , Uj Averaged or filtered velocity components, m/s
d
Length scale in DES model, m
A
Van Driest constant
C
Particle number concentration
WALE model constant
C
Drag coefficient
Cd
Cs
Smagorinsky model constant
D
Dispersion coefficient, cm 2 /s
Hydraulic diameter of the geometry, m
dh
dae
Aerodynamic diameter of the particle, m
dmean Mean diameter of the geometry, m
HW Half-width of an aerosol bolus, ml
L
Length of the geometry, m
Length scale for the smallest eddy, m
l
le
Length scale of an eddy, m
Ls
Length scale for sub-grid scales, m
p
Static pressure, pa
Static pressure at model inlet, pa
pin
Static pressure at model exit, pa
pout
Q
Flow rate, l/min
sij
Instantaneous strain-rate tensor
SD
Standard deviation of an aerosol bolus, ml
Crossing time of a particle in an eddy, s
tc
te
Time scale of an eddy, s
xiii
tint
Interaction time of a particle with an eddy, s
Velocity scale for the smallest eddy, m/s
u
u
Frictional velocity, m/s
ui , uj Instantaneous velocity vector components, m/s
!
!
ui , uj Fluctuating component of the instantaneous velocity, m/s
Interpolated flow variable at any vertex p
Up
Umean Mean velocity of the flow, m/s
V
Volume of the geometry, m 3
Vp
Penetration volume of an inhaled bolus, ml
Greek Symbols
Grid spacing, m
Deposition efficiency
Dynamic viscosity of the fluid, kg/m s
Kinematic viscosity of the fluid, m 2 /s

t
Eddy viscosity, m2 /s
Specific dissipation, 1/s

Weighting function
i
Conservative variable
Density of the fluid, kg/m 3

p
Density of the particle, kg/m3
Time scale for smallest eddy, s

p
Relaxation time of the particle, s
Viscous stresses, N/m2
ij
sgs
ij
Sub-grid scale stresses
Turbulent kinetic energy dissipation, m2 /s3
Random number
Dimensionless Numbers
Re = Umean dmean / Reynolds number
Rep = dp | u up |/ Reynolds number of the particle
Stk = p d2ae U/9dh Stokes number
y + = u d/ Non-dimensional distance to wall
Acronyms
COPD Chronic Obstructive Pulmonary Disease
DE
Deposition efficiency
DES Detached Eddy Simulation
DNS Direct Numerical Simulation
LES Large Eddy Simulation
LRN Low Reynolds Number
OOP Object Oriented Programming
RANS Reynolds Averaged Navier Stokes
S-A
Spalart Allmaras
SGS Sub Grid Scale
xiv
SST Shear Stress Transport

UAM Upper Airway Model
WALE Wall Adapting Local Eddy Viscosity
xv
xvi
Chapter 1
Introduction
Contents
1.1 The respiratory system . . . . . . . . . . . . . . . . . . 1
1.1.1 Extra-thoracic region . . . . . . . . . . . . . . . . . 1
1.1.2 Tracheo-bronchial region . . . . . . . . . . . . . . . 5
1.1.3 Alveolar region . . . . . . . . . . . . . . . . . . . . . 5
1.2 Aerosols and the respiratory system . . . . . . . . . . 5
1.3 Factors affecting pharmaceutical aerosol targeting
6
1.4 Mechanisms of particle deposition . . . . . . . . . . . 9
1.5 Clinical aerosol measurements (bolus tests) . . . . . 11
1.1 The respiratory system

Breathing is the process by which oxygen in the air is brought into the
gas exchanging part of the lungs and into close contact with the blood.
Blood absorbs oxygen and simultaneously gives up carbon-dioxide, which
is carried out of the lungs when air is breathed out. Fig. 1.1 shows a
schematic representation of the human respiratory system as well as the
respiratory pathway. The respiratory system is basically divided into three
categories namely the extra-thoracic region, the tracheo-bronchial region
and the alveolar region.
1.1.1
Extra-thoracic region
Fig. 1.2 shows a schematic representation of the extra-thoracic region

which consists of the nasal cavity, the mouth cavity, pharynx, larynx and
1
CHAPTER 1. INTRODUCTION
Air!enters!from!
Nose or Mouth
Passes!through!
Nasopharynx!or!
Oropharynx
Extra!thoracic"
Region"
Through!the!
Larynx!(glottis)!
Into!the!Trachea!
Into!the!left!and!
right!Bronchi!
Tracheo!bronchial"
Region"
Bronchi!further!
branches!into!
Bronchioles
Terminates!in!a!
cluster of Alveoli
Alveolar"Region
Figure 1.1: Left: Schematic representation of the human respiratory system [1];
Right: The respiratory pathway.
trachea. The extra-thoracic region is also most often referred to as the

upper airway region or the nose, mouth and throat region.
Nasal cavity
The nose (nasal cavity) is the preferred entrance for outside air into the
respiratory system. The nasal passage serves as a moistener, a filter, and
a warm up before the air intake. While the hairs in the nostrils act as a
filter for the foreign particles, the mucus and cilia (tail like projections on
the surface) collect dust, bacteria and other particles in the air. The mucus
membrane also helps in moistening the air. The blood in the capillaries
just below the mucus membrane help warm up the inspired air.
Mouth cavity
Mouth becomes the preferred method of air intake for the people who have
a mouth-breathing habit or whose nasal passage may be temporarily obstructed, as by a cold or during heavy exercise. Mouth is also the preferred
passage for the intake of aerosol medication in treating lung diseases such
as asthma. The shape of the mouth cavity varies considerably depending
2
Figure 1.2: Schematic representation of the extra-thoracic (upper) airway [46].
on the position of tongue and jaws.

Pharynx
The main function of pharynx (throat) is to collect the air coming from the
nose and mouth, and pass it downstream towards trachea. The pharynx
is further subdivided into nasopharynx and oropharynx. In subjects with
oral allergy syndrome and related allergies, the pharynx is often a reaction
site to allergens, with common symptoms including burning and itching.
Epiglottis
The epiglottis guards the entrance to the trachea by blocking it during
swallowing so that the swallowed material is guided towards the esophagus and stomach.
Larynx
The larynx (glottis, voice box) houses the vocal chords and as the air is
expired, the vocal chords vibrate. Humans can control these vibrations
which enables us to make sound. The vocal folds affect the shape and
magnitude of glottic cross-section depending on the flow rate and is seen
to be a crucial geometric feature to be considered in the air-flow dynamics study [20]. Brancatisano et al. [12] studied the movements of the
3
Figure 1.3: Electron scanning micrograph of cilia and mucus generating cells.
vocal cords during large lung volume changes in 12 normal subjects and
reported substantially different glottic width and glottic area between subjects. The glottic width and area increased during inhalation to 10.15.6
mm and 1268 mm2 respectively, whereas during exhalation the lowest
values were 5.70.5 mm and 707 mm2 .
Trachea
The trachea is a tube-like structure which acts as a passage from the pharynx to the lungs. The trachea is kept open by cartilage rings within its
walls. The presence of cartilage rings can have a considerable effect on
the flow dynamics [122]. Trachea roughly measures 10-14 cm in length
and 16-20 mm in diameter. Similar to nasal cavity, trachea is covered with
ciliated mucous membrane which acts as a filter for foreign particles. Fig.
1.3 shows the electron scanning micrograph of cilia and mucus generating
cells on the surface of the airway passage. Cilia extends approximately
5-10 m from the airway surface.
1.1.2
Tracheo-bronchial region
The trachea further divides into two cartilage-ringed and ciliated tubes
called the main bronchi. The bronchi enter the lungs and spread into a
tree-like structure by further subdividing itself into the lobar bronchi, segmental bronchi and finally ends up becoming tiny terminal bronchioles
(approximately 30,000) leading into the gas exchanging (alveolated) zone.
The tracheo-bronchial region is also referred to as the lower airways. The
extra-thoracic and tracheo-bronchial airways taken together are called the
conducting airways as they transport air to the gas-exchange region of the
lungs. The term central airways is sometimes used to refer to the upper
regions of the tracheo-bronchial airways [46].
1.1.3
Alveolar region
Each terminal bronchiole subtends an air chamber that could be likened

to a bunch of grapes. Each chamber contains many cup-shaped cavities
known as alveoli. The walls of the alveoli, which are only about one cell
thick, are the respiratory surface. They are thin, moist, and are surrounded by several numbers of capillaries. The estimation is that lungs
contain about 300 million alveoli and that the thin barrier with a large
surface makes it ideal for the exchange of oxygen and carbon dioxide between blood and through these walls. Their total surface area is roughly
about 70 m2 .
1.2 Aerosols and the respiratory system

Aerosol is defined as a suspension of fine solid particles or liquid droplets
in a gas. Examples are smoke, air pollution, smog etc. The aerosols are
related to human respiratory system in two ways:
Aerosol pollutants
The effects of inhaling particulate matter has been widely studied in humans and animals and include asthma, lung cancer, cardiovascular disease, and premature death. Particulate matter pollution is estimated to
cause 22,000 to 52,000 deaths per year in the United States (from 2000)
and 200,000 deaths per year in Europe.
The size of the particle is a main determinant of where in the respiratory tract the particle will deposit when inhaled. Larger particles (> 10
5
m) are generally filtered in the nose and throat and do not cause adverse
problems, but particulate matter smaller than about 10 m can settle in
the bronchi and lungs and cause health problems. The 10 m size does not
represent a strict boundary between respirable and non-respirable particles, but has been agreed upon for monitoring of airborne particulate
matter by most regulatory agencies. Similarly, particles smaller than approximately 2 m tend to penetrate into the gas-exchange regions of the
lung, and very small particles (< 100 nanometers) may pass through the
lungs to affect other organs.
Inhaled pharmaceutical aerosols

According to World Health Organization (WHO), around 300 million people suffer from asthma and around 255,000 people died of asthma in 2005.
It is predicted that the asthma deaths will increase by 20% in the coming
10 years if proper care is not taken.
Inhaled medication is the preferred method of drug administration to the
lung for the first-line therapy of asthma and chronic obstructive pulmonary
diseases. Asthma is a chronic condition in which the airways occasionally
constrict, become inflamed, and are lined with excessive amounts of mucus. Symptomatic control of episodes of wheezing and shortness of breath
due to asthma is generally achieved with fast acting broncho-dilators, which
are basically pocket-sized pharmaceutical aerosol inhalers. While targeting a delivery dose of inhaled pharmaceutical aerosol to the lower airways,
a high percentage of it is lost due to deposition and clearance in the upper airways. Furthermore, adverse health effects such as cellular damage,
inflammation and tumor formation can occur in the upper airways potentially as a result of local deposition and absorption patterns [161].
For the above reasons, it is of utmost importance to understand the fluidparticle dynamics in the upper airways. The present thesis is a step forward
in our attempts to better understand this important and very interesting aspect of biomechanics.
1.3
Factors affecting pharmaceutical aerosol

targeting
The effective targeting of the inhaled pharmaceutical aerosols to the alveolar regions of the respiratory system depends on the following factors:
6
Geometrical complexity
The inhaled aerosol particles need to negotiate the mouth-throat structure and the branching airway structures before reaching the alveolar lung
zone that could benefit from aerosol therapy. The complexity of the extrathoracic portion of the oral airway, which includes bends and sudden crosssectional changes potentially induces considerable local medication deposition. The angles of branching and the diameter and lengths of different
elements of the tracheo-bronchial region further influences deposition of
the medical aerosols. Also, the geometry of the respiratory tract is time
dependent and varies during the inhalation-exhalation cycle. Considerable differences in geometrical details exist between individuals.
Particle parameters
To reach the alveolar region of the lungs, the aerosol particles need to be in
certain optimal size range called the respirable range (0.5 - 5 m). While
the particles > 5 m range tend to deposit in the extra-thoracic region, particles < 0.5 m get inhaled without depositing and exhaled right back out.
The principal approach used in the existing pharmaceutical inhalation devices, particularly when targeting the alveolar region, is by using particle
sizes near 1-5 m, assuming that the density of the particle is close to that
of water ( 1000 kg/m3 ) [2].
Fig. 1.4 shows typical deposition patterns of inhaled droplets in different
regions of the respiratory tract. It should however be mentioned that the
graph should only be viewed to get a qualitative picture of the deposition
patterns in different regions of the airway tract. The actual deposition
percentages may vary depending on the inhalation flow rate and the complexity of the airway geometry under consideration.
Breathing flow rate

Breathing flow rates directly affect the aerosol transport/deposition. Based
on the activity of an individual, the inhalation flow rates are roughly classified as: slow breathing (15 l/min), normal breathing (30 l/min) and heavy
breathing (60 l/min).
Inhalation devices
Based on the working mechanism, there are three types of inhalation devices presently available in the market. a) metered dose inhaler, b) dry
powder inhaler, and c) nebulizers. Each of these devices have their own
7
0.9
extra-thoracic region
0.8
tracheo-bronchial region
deposition probability
0.7
alveolar region
0.6
0.5
0.4
0.3
0.2
0.1
0
0
10
12
14
16
diameter (micrometer)
Figure 1.4: The probability that inhaled droplets of different diameters will deposit on different regions of respiratory tract as predicted by a two-way coupled
hygroscopic model for a Ventolin aerosol with mass median diameter of 4 m and
geometric standard deviation of 1.7 with 100,000 droplets/cc and room temperature
ambient air of 50% RH is shown [2].
Figure 1.5: Different types of inhalers.
advantages/disadvantages based on the needs of individual patients.
a) Metered Dose Inhalers: It is also referred to as the pressurized metered
dose inhaler (pMDI) or propellant metered dose inhaler. Fig. 1.5(a) shows
a typical hand held pMDI. Pressing down the canister releases a mist of
medicine that is breathed into the lungs. pMDIs are currently the most
commonly used delivery device. Like most inhalation devices, only 10%20% of the nominal per puff dose reaches the targeted airways [109].
Most recommendations suggest that patients should slowly and fully inhale while firing the pMDI dose. The most common difficulties with pMDIs
are failure to coordinate actuation of the device with inhalation and an involuntary cessation of inhalation when cold aerosol particles reach the soft
palate. A means to avoid this problem is to place a spacer (ranging 50750 ml in volume) in between pMDI and patient, such that the aerosol can
be inhaled from the spacer immediately after the pMDI is actuated. The
spacer also filters out large particles that would otherwise stick to the upper airways.
b) Dry Powder Inhalers: Dry powder inhalers (DPIs) are breath-actuated
devices which eliminate the co-ordination problem seen with the pMDIs.
Fig. 1.5(b) shows one such DPI. It is very similar to PMDI, except for the
reduced surface area of the mouthpiece exit. DPIs are among the most recent delivery devices and generally adult patients find it to be more userfriendly than pMDIs. With DPIs, the rate of inspiratory flow is critical
and generally, a forceful and deep breath is required for optimum output
from this device. This flow is also necessary to desegregate the drug particles from their carrier (usually lactose).
c) Nebulizers: Nebulizers are among the oldest of inhalation devices. A
typical jet nebulizer is shown in Fig. 1.5(c). High pressure air from the
compressor is passed through nebulizer which houses a nozzle and a baffle. While nozzle helps in primary droplet production, the baffle filters
out larger particles before the mist of drug-containing droplets reach the
mouthpiece for inhalation. Nebulizers are employed chiefly for the delivery
of large bronchodilator doses during acute asthma attacks and for patients
unable to use other inhalation devices [3].
1.4
Mechanisms of particle deposition
The three main transport mechanisms acting on the particles in the respiratory system are impaction due to inertia of the particles, sedimenta9
Figure 1.6: Total and regional (extrathoracic, upper bronchial, lower bronchial,
and alveolar) deposition of unit-density spheres in the human respiratory tract
predicted by the semi-empirical model proposed by the International Commission
on Radiological Protection (ICRP) [6]. Density of sphere is 1000 kg/m 3 and the
flow rate is 18 l/min [65].
tion due to gravitational acceleration, and diffusion due to Brownian motion. Fig. 1.6 illustrates the different mechanisms influencing total as well
as regional deposition of unit density spheres orally inhaled at the mean
breathing pattern of an adult male in the sitting position.
Inertial Impaction: Deposition due to impaction is directly proportional

to the mass of the individual particle, ie., the size and the density of the
particle. The flow velocity also has an influence on the inertial deposition.
While deposition occurs throughout the airways, inertial impaction usually occurs in the first few generations of the lung, where the air velocity
is high and the airflow is generally turbulent [96].
Sedimentation: Deposition due to sedimentation is mainly due to large
particle size and relatively long residence times of the particles which is
10
Figure 1.7: Inhaled and exhaled bolus concentration curves for a given penetration
volume. Typical bolus characteristics such as mode and half-width are shown for
both inhaled and exhaled boluses [31].
usually the case in the last five to six generations of airways (smaller
bronchi and bronchioles) and in the alveolated region of the lung, where
the air velocity is low [90].
Diffusion: The random movement of the particles is represented by diffusion. The distance a particle travels by diffusional transport increases with
decreasing particle size and flow rate. The highest probability of aerosol
deposition due to diffusional displacement occurs for very small particles
inhaled into the lung periphery where the airway dimensions are small.
1.5 Clinical aerosol measurements (bolus tests)

Bolus dispersion technique is a widely used non-invasive experimental tool
to characterize the convective gas transport which can be altered in diseased lungs (e.g., [13, 21, 36, 35, 121, 125, 149]). It requires the subject to
be in the inhalation mode, while a small aerosol volume (typically 50 - 70
11
Figure 1.8: Exhaled bolus concentration curves at different penetration volumes.

At each penetration volume, there is a comparison between a normal patient and
a patient with cystic fibrosis [11].
ml) is inspired at a predetermined moment during inhalation [152] (Fig.

1.7). The penetration depth of the bolus, i.e., how deep it is transported
into the lungs is given by the volume of air following the bolus peak (Fig.
1.7). The distribution of the concentrations of aerosol during the subsequent exhalation is then plotted as a function of penetration volume. An
example plot of aerosol dispersion at different penetration volumes for a
normal subject and a patient with cystic fibrosis is shown in Fig. 1.8. As
can be seen, the deeper we probe into the lungs, the more broader (disperse) the exhaled curve becomes. It is also interesting to see that the
exhaled concentration curve for the patient with cystic fibrosis is more dispersed when compared to the normal patient at all lungs depths. In this
way, aerosol bolus behavior becomes a non-invasive diagnostic tool.
Since we will be dealing only with the extrathoracic portion of the airway
in the present thesis, the aerosol bolus is to be inhaled only to a very small
lung depth (shallow bolus). For the extrathoracic region (oral and laryngeal part), 49.3 ml was used as the penetration volume for the numerical
simulations of aerosol transport [32].
12
The inhaled and exhaled boluses are characterized by their half-width (H)
and deposition efficiency (DE). Half-width is the bolus width at one-half
of the bolus peak. The change in half-width (H) reflects the aerosol dispersion that has occurred to the bolus transit in the airways. H is defined
as,
"
! 2
2 1/2
H = Hex
Hin
(1.1)
where Hin and Hex are the inspired and expired half-widths respectively.
The deposition efficiency (DE) is obtained by,
$
#
Np,ex
DE = 1
Np,in
(1.2)
where Np,in and Np,ex are the number of inspired and expired aerosols
respectively. The ratio N p,ex /Np,in is obtained by comparing the areas of
the inspired and expired boluses on the plot of aerosol concentration vs.
volume.
13
14
Chapter 2
Literature Survey
Contents
2.1 Airway geometries . . . . . . . . . . . . . . . . . . . . . 15
2.2 Modeling methods . . . . . . . . . . . . . . . . . . . . . . 19
2.2.1 Fluid phase . . . . . . . . . . . . . . . . . . . . . . . 19
2.2.2 Particle phase . . . . . . . . . . . . . . . . . . . . . 21
2.3 Fluid flow characteristics in upper airways . . . . . 23
2.4 Particle deposition characteristics in upper airways 27
2.5 Empirical deposition relationships . . . . . . . . . . . 28
2.1 Airway geometries

The overall complexity of the upper pathway between the mouth and the
trachea, with its bends and cross-sectional changes, poses serious challenges for both experimental and computational studies. Previous studies
have used the upper airway models with varying degrees of geometrical
complexity.
Katz and Martonen [84] created a simple three-dimensional model of the
larynx (Fig. 2.1) based on morphometric measurements of replica human
casts and Weibel morphology of the tracheal dimensions. The larynx was
modeled as a 6 cm long cylinder with a circular entrance and exit crosssections. The apertures created by ventricular and vocal cords were modeled as ellipse.
15
CHAPTER 2. LITERATURE SURVEY
Figure 2.1: Simplified three-dimensional model of larynx [84].
Figure 2.2: Simplified three-dimensional model of larynx [28].
Corcoran and Chigier [28] measured the axial velocity and turbulence intensity, using Phase Doppler Interferometry (PDI) in a cadaver-based simple larynx-trachea model (Fig. 2.2). The model consisted of a polyurethane
casting of the human larynx, connected to a glass tube with an inside diameter matching the tracheal diameter of the cadaver.
Even though the models of Katz and Martonen [84] and Corcoran and
Chigier [28] are able to provide basic information about the flow patterns,
they are often too simplistic and not complete, particularly with respect to
the flow inlet conditions.
Zhang et al. [171] simulated air flow and micro-particle transport in a simplified, but more complete model of the upper human airways (Fig. 2.3),
incorporating a bend between mouth and trachea. The model consists of
a single circular tube with local diameter variations, based on data sets
provided by Cheng et al. [25].
Stapleton et al. [143] created an average geometrical model (Fig. 2.4) of
the extra-thoracic airways based on data from computed tomography (CT)
16
Figure 2.3: Simplified three-dimensional mouth-throat model [171].
scans, magnetic resonance imaging (MRI) scans, and direct observation

of living subjects. By using these characteristic dimensions, a model of
the extra-thoracic airways is constructed using simple geometric shapes.
One advantage of this approach over using a model based on an airway
cast is that extremely high grid resolutions are not needed at the walls to
resolve any small airway irregularity. However, the oral cavity region is
too simplistically modeled as a long tube-like structure with an unrealistically large airspace in the mouth cavity (see also the realistic cavity due to
tongue position in Fig. 1.2).
Yu et al. [165] constructed an upper airway including nasal, oral, laryngeal and the first two generations of tracheobronchial airway (Fig. 2.5).
The geometry was a simplified teaching model used by the medical school
students. While the nasal airways did not duplicate the exact nasal morphology, the oral airway was too simplistically represented. The trachea
and first two bifurcations were modeled as circular tubes.
Recognizing the need for more realistic representation of the oral cavity region, Brouns et al. [19] at the Vrije Universiteit Brussel performed a multislice CT imaging study in five otherwise healthy never-smoker male subjects and constructed a more realistic representation of the airway model
(Fig. 2.6).
Experimental aerosol deposition data obtained by Grgic et al. [58] on var17
Figure 2.5: Simplified three-dimensional upper airway model including nasal, oral,
laryngeal and first two generations of tracheobronchial airways [165].
18
ious realistic upper airway casts indicate considerable intra- and intersubject variability of the extra-thoracic airway deposition. The influence
of the inlet of the aerosol device, as well as individual mouth and trachea
morphology on local and total aerosol deposition suggests that individualized computation of extra-thoracic deposition would result in more accurate estimation of the amount of aerosol available to the deeper lung for a
given patient or for a given aerosol device. Xi and Longest [161] studied the
micro-particle deposition in a) CT based realistic mouth-throat model; b)
Simplified model based on the CT scans. It was concluded that the realistic
geometry provided the best predictions of regional deposition in comparison to experimental data and hence are needed for accurate evaluation of
localized deposition patterns. Recognizing this, Jayaraju et al. [76] at the
Vrije Universiteit Brussel performed RANS simulations on a truly realistic upper airway model (Fig. 2.7) obtained from the CT scan data.
2.2 Modeling methods

2.2.1
Fluid phase
There are rapidly growing works in the literature describing the use of
CFD for studying the fluid flow and particle deposition in the upper air19
Figure 2.7: Three-dimensional mouth-throat model as extracted from CT scan data

[76].
ways. The numerical methods are broadly classified based on the nature
of flow, i.e., laminar or turbulent. When dealing with turbulent flows, the
whole range of turbulence models and their ability in accurately predicting
the physics of turbulence comes into picture.
There is an extensive literature focused on the regions of respiratory tract
where the flows are predominantly laminar. This is mainly to avoid the
complications that come with turbulence modeling. Laminar fluid flow and
particle depositions in tubes and bifurcations where the Reynolds number
is only few hundred have been previously studied [69, 27, 93, 88]. Reynolds
number is a dimensionless number that gives a measure of the ratio of inertial forces to the viscous forces. In case of tubular flows, it is given by
ud/, where u is inlet velocity, d is the diameter of the pipe, and is the
kinematic viscosity. At a low flow rate of 15 l/min, Yu et al. [165] studied
the fluid flow and ultra-fine (0.001-0.01 m) particle diffusion in the oral
and nasal passages followed by larynx, trachea and main bronchi. Good
agreement with experiments were reported. Martonen et al. [100] performed laminar flow simulations in a larynx, trachea, and main bronchi
model to provide some insights into the basic flow features. As Stapleton
et al. [143] points out, the flows in larynx and trachea are normally turbulent or at least transitional and hence the results of Martonen et al. [100]
must be interpreted with caution.
20
Two equation RANS models are the most commonly used turbulence models for predicting the fluid-particle dynamics in the upper airways. Katz
et al. [83] used the standard k model to understand the effect of flow
rate on the flow patterns and the particle trajectories in a geometry based
on laryngeal casts (Fig. 2.1). Stapleton et al. [143] further tested the
performance of standard k model in a human mouth throat geometry
at a turbulent flow rate of 28.3 l/min. Significant deviations in simulated
versus experimental pressure drop were reported. Several studies, e.g.,
[51, 84, 85, 120] have used standard k to analyze flow patterns in the
larynx.
The poor performance of the k model clearly highlighted the need for an
experimentally validated, low-Reynolds-number (LRN) turbulence model,
which can represent laminar, transitional and turbulent flows for the computational analysis of transport phenomena in upper airways covering realistic inhalation rates (ranging 10 and 60 l/min). In an attempt to address
this problem, Zhang and Kleinstreuer [169] tested the performance of LRN
k model of Wilcox [160] in a test conduit with local constriction, at a
transitional Reynolds number of 2000. Good agreement with the experiments were seen when comparing velocity and kinetic energy levels across
the geometry.
2.2.2
Particle phase
Stochastic modeling of the particle phase involves direct simulation of

particle motion through a random turbulent flow field. There are several approaches in developing stochastic models. Few examples in literature include models based on the Langevin equation [97], random Fourier
modes [103] and pdf models [118]. However, one of the most widely used
model is the Eddy Interaction Model (EIM) first introduced by Hutchinson et al. [73] and further developed by Gosman and Ioannides [53]. Even
though several variants of EIM model have been proposed in the literature
[134, 57, 54, 55, 56], the originally proposed EIM of Gosman and Ioannides
[53] remains the most widely used, mainly because of its simplicity.
Katz and Martonen [83] were one of the first to study the effect of turbulence on particle motion within the human larynx and trachea using
k turbulence model coupled with EIM of Gosman and Ioannides [53].
However, no quantitative validations (e.g., comparison with experiments)
were provided. Stapleton et al. [143] further tested the performance of
standard k model coupled with EIM in a human mouth throat geom21

etry at a turbulent flow rate of 28.3 l/min. The transport of polydisperse
aerosol particles of 4.8 m were simulated and a huge over-prediction in
deposition was seen in the computations as opposed to the experiments.
This was mainly attributed to the poor fluid flow predictions by k model.
Riding on the confidence of good performance by LRN k model of Wilcox
[160] in a constricted tube at transitional Reynolds number [169], Zhang
et al. [171] performed transitional flow simulations (15, 30 and 60 l/min)
in a simplified upper airway model (Fig. 2.3) using LRN k turbulence
model coupled with EIM of Gosman and Ioannides [53]. Good agreement
of the simulated micro-particle (0.001 < Stk < 1) deposition were reported
when compared to experimental deposition correlation function. In most
of the works that followed [87, 167, 8, 102, 170, 60, 76, 77], it has become a
norm to use LRN k model in predicting the fluid-particle dynamics in
the upper airways.
Matida et al. [102] studied the deposition of monodisperse particles (126 m) in an idealized mouth-throat geometry (Fig. 2.4) at inhalation flow
rates of 30 and 90 l/min. LRN k turbulence model along with EIM based
on Gosman and Ioannides [53] was used. Contrary to the good performance
of LRN k model reported by Zhang et al. [171], the simulations of
Matida et al. [102] showed huge over-prediction in deposition percentages
(>50%), even for the lowest Stokes number particles. The reason according to the authors was the assumption of isotropy in the EIM model and
once the anisotropy effects next to the walls were modeled, a better overall
deposition prediction was obtained. However, recent attempts [161, 76, 77]
in predicting the micro-particle deposition in simplified as well as realistic
upper airways do not reproduce such behavior. All these recent works used
LRN k model along with an isotropic EIM model and the results were
comparable to those obtained by Matida et al. [102] using LRN k model
along with an anisotropic EIM model. Whether the near-wall anisotropy is
taken care or not, the main observation that can be made in all the above
discussed works is that there still remained a considerable over-prediction
in deposition at smaller Stokes number range, and the particles in these
Stokes number range are the ones pertaining to inhaled medication (1-5
m).
Several authors have started to explore the possibility of using large eddy
simulation (LES) methods for the study of particle deposition in the upper airway, by applying LES in relatively simple structures such as a 90 0
bend [16] or a constricted tube [99]. Together with LES simulations of
deposition in a simplified mouth cavity model [101], and in a simplified
upper airway model [79, 77], the potential of more accurately simulating
22
Figure 2.8: Lengthwise velocity vector lines for 15, 30 and 60 l/min respectively
[85].
aerosol transport in the upper airways has been recognized. Jayaraju et

al. [77] also explored the possibility of using DES instead of LES, as it is
computationally less expensive.
2.3
Fluid flow characteristics in upper airways
Katz and Martonen [84] were among the first to create a three-dimensional
simplified larynx model (Fig. 2.1) to understand the basic flow patterns at
15, 30 and 60 l/min. Swirling circumferential flows through the larynx due
to changes in cross-sectional area was observed. Katz et al. [85] further
extended this preliminary work to study the effect of glottal aperture modulation on inhalatory laryngeal fluid dynamics. Similar to their previous
work, three flow rates of 15, 30 and 60 l/min were considered. It was found
that the complex geometry produces jets, recirculation zones, and circumferential flows which may have a profound influence on particle deposition
near the larynx. Fig. 2.8 shows the recirculation zones formed at 15, 30
and 60 l/min, due to the presence of laryngeal constriction. It is a known
fact that the glottis has different shapes and cross-sectional areas at different moments during the respiratory cycle. In order to access this effect,
Renotte et al. [120] have studied the effect of pseudo-time-varying glottic aperture on the flow conditions at quiet breathing. In particular, two
23

glottic shapes were considered: one representing the glottal opening during inhalation and the other during exhalation. The geometry used was a
very simplified larynx-trachea model that closely resembled the one used
by Katz and Martonen [84] (Fig. 2.1). Minor differences were outlined between inhalatory and exhalatory flow profiles. This perhaps is due to simplistic representation of larynx-trachea (which is basically a constriction
in a straight tube). Brouns et al. [20] studied the influence of a circular,
elliptical and triangular shape glottis on the flow dynamics in a simplified
upper airway (Fig. 2.4) at a quiet breathing rate of 15 l/min. Even though
considerable variations in the flow patterns downstream of glottis were
observed, the total pressure drop was seen to be more dominated by the
cross-sectional area than by its shape.
Corcoran and Chigier [28] used Phase Doppler Interferometry to characterize axial velocity and turbulence intensity contours in the tracheal section of a cadaver-based larynx-trachea model (Fig. 2.2). The flow was characterized for steady state flow at three Reynolds numbers (1250, 1700, and
2800). Reverse flows with significant velocities were noted in the anterior
trachea within one diameter downstream of the larynx, for all three flow
cases. The cross-sectional area of the reverse flow regions was larger for
the lower Reynolds number cases. High levels of axial turbulence intensity were noted near the anterior/left tracheal walls within one diameter
downstream of the larynx. Turbulence levels were still significant after
four downstream diameters, indicating the potential for turbulent deposition at positions further downstream, including the bronchial tree where
passage diameters are smaller.
Laminar-to-turbulent air flow for typical inhalation modes (15, 30 and 60
l/min) in a representative human upper airway model (Fig. 2.3) have been
simulated by Zhang et al. [171]. At normal breathing of 30 l/min, the
velocity profiles (Fig. 2.9) were seen to become skewed in the curved portion of the oral cavity and pharynx/larynx due to centrifugal force effects.
Flow separation was seen due to abrupt geometric changes. While a uniform flow was observed in the glottis, an asymmetric laryngeal jet was
seen to be generated after the glottis. The turbulence kinetic energy (Fig.
2.9) was seen to become strong after the constriction of soft palate, to rise
rapidly after the glottis and to eventually decay more slowly, approaching
an asymptotic level. It was concluded that the turbulence that occurs after
the glottic constriction in the upper airways for moderate and high-level
breathing can enhance particle deposition in the trachea near the larynx.
Johnstone et al. [80] experimentally (hot wire anemometry) studied the
24
Figure 2.9: Left: Mid-plane velocity contours at a flow rate of 30 l/min; Right:
Variations of cross-sectional area-averaged turbulence kinetic energy [171].
Figure 2.10: Left: 2-D streaklines from PIV at a mid-plane and a normal inhalation
flow rate of 30 l/min [64].
25

mean and RMS axial velocity field in the central sagittal plane of an idealized representation of the human extra-thoracic airway (Fig. 2.4) during
steady inhalation flow rates of 10, 15, 30, 45, 60, 90 and 120 l/min. Regions
of separated and recirculating flow downstream of the mouth inlet, uvula,
and larynx were seen. Circumferential secondary flow patterns have been
reported in the oral cavity (Fig. 2.10). Normalized mean hot-wire axial velocity profiles across the first five model traverse sections (i.e. from the oral
inlet to the oropharynx) were typically found to increase as Reynolds number decreases, demonstrating the presence of stronger viscous effects at
lower inhalation flow rates. RMS velocities seemed to be least for the first
three flow rates, but were found to converge closely onto a similar curve at
the higher flow rates. Both mean and RMS axial velocity profiles distal to
the oropharynx region appear to be primarily shaped by the geometry of
the airways, since the basic features of these profiles were discovered to be
essentially independent of the Reynolds number of the flow.
Yu et al. [165] numerically simulated the human breath patterns at 15
l/min, in an idealized model (Fig. 2.5) that also incorporated the nasal
airway in additions to the mouth-throat geometry. It was seen that the inhalation patterns (i.e., nasal inhalation, oral inhalation and simultaneous
nasal-oral inhalation) had significant effects on the velocity profiles within
laryngeal airways. The larynx was seen to be the key morphological factor
affecting the character of air stream motion within the upper lung. During exhalation, the effects of reversing laryngeal jet were reported to be
insignificant.
The fluid flow patterns in the simplified geometry of Brouns et al. [19] (Fig.
2.6) at 15, 30 and 60 l/min are discussed in detail by Brouns [18]. Using
LES methodology, Jayaraju et al. [77] (Chapter 8) also describes the flow
patterns at a normal breathing flow rate of 30 l/min. The flow features
in the realistic geometry of Jayaraju et al. [76] (Fig. 2.7) at 15, 30 and
60 l/min are discussed in Chapter 5. For the sake of completeness, a brief
overview of velocity vector lines in both simplified and realistic geometries
is shown in Fig. 2.11 .
In summary, the consistent observation among different studies was that

the velocity profiles were seen to become skewed in the curved portions of
the mouth, pharynx and larynx in general. Also, major amplification in
kinetic energy is reported to take place downstream of larynx. However,
soon after the larynx, the skewness of the flow profile as well as the severity of the recirculation zone vary from one airway model to the other. As
can be seen from all the velocity profiles presented before, this mainly de26
Figure 2.11: Mid-plane velocity vector lines at a normal breathing rate of 30 l/min,
in a simplified model (left) and a realistic model (right) that were created in the
framework of the present thesis [77, 76].
pends on the orientation of larynx as well as the upstream flow conditions

while approaching the larynx. Hence, pharynx as well as larynx should be
considered as the key morphological factor affecting the flow characteristics.
2.4
Particle deposition characteristics in upper airways
Katz et al. [83] studied the particle deposition in one of the simplest
larynx-trachea model (Fig. 2.1) in order to understand the effect of larynx on the particle deposition. The key quantitative observation was that
the turbulence can have a profound effect on particle deposition in the larynx and trachea. It was concluded that any calculation for the deposition
of inhaled aerosols must consider the turbulence phenomenon.
Zhang et al. [171] studied the micro-particle (0.001 < Stk < 1) transport and deposition in a simplified oral airway model (Fig. 2.3) at 15,
30 and 60 l/min. The turbulence that occurs after the constriction in the
27

oral airways for 30 and 60 l/min led to enhanced particle deposition in the
larynx-trachea region, and the turbulence enhanced deposition was seen
to be more profound for smaller particles (Stk < 0.05) in particular. The
particles that were released around top and bottom part of the inlet plane
were seen to deposit more easily on the curved oral airway surfaces. Kleinstreuer and Zhang [87] further extended this work with the same model
and boundary conditions to demonstrate that the particles nicely follow
the airflow stream at 15 l/min, whereas the particle motion seemed to be
more random and disperse, i.e., influenced by flow fluctuations in case of
60 l/min. The particle size and inhalation flow rate were reported to be
the main factors influencing particle deposition when compared with the
turbulent dispersion alone.
In order to understand the effects of particle size, flow rate and flow Reynolds
number on the regional particle deposition, Grgic et al. [59] used gamma
scintigraphy and gravimetry to measure the deposition of radioactive monodisperse sebacate oil particles of diameter 3, 5 and 6.5 m at two constant flow
rates of 30 and 90 l/min. In addition to particle size and flow rate, another
Reynolds number effect on deposition was identified which is related to
varying flow cross-sectional velocity profiles. The aerosols were seen to deposit mostly in the laryngeal area and the upper part of the trachea. The
regional deposition profiles depended only weakly on different flow and
particle conditions. The pharyngeal and glottal constrictions were seen to
be the key morphological factors affecting downstream aerosol deposition.
Most of the above physical phenomena have also been numerically reproduced in the LES simulations of Jin et al. [79] in the same upper airway
model.
In summary, it was seen across different studies that the turbulence induced by the larynx has a profound effect on the particle deposition in
larynx/trachea region. The particle size, the fluid flow rate, and the fluid
Reynolds number were reported to have an influence on the particle deposition. The detailed analysis of aerosol transport and deposition patterns
in more complex geometries such as the ones shown in Fig. 2.7 and 2.6 are
discussed in Chapter 5 and 8 respectively.
2.5 Empirical deposition relationships

By combining various in-vivo and in-vitro deposition data in the human
upper airways available in the literature, it is possible to establish a relatively simple empirical relationship for predicting the amount of inhaled
28
Figure 2.12: Upper airway deposition efficiency in human subjects measured during mouth breathing shown as a function of impaction parameter d 2ae Q. Solid curve
is an empirical fit (Eq. 2.1) to the average of all of the data points while the dashed
lines indicate the approximate range of the data from Lippmann [95] and Chan
and Lippmann [23]. The above figure is taken from Stahlhofen et al. [142].
aerosol that may deposit in the upper airways. One of the most widely
used empirical relationship was proposed by Stahlhofen et al. [142] (Fig.
2.12) by using regional deposition data in oral airway of human volunteers
which were measured using mono-disperse particles tagged with radiolabel [95, 47, 23, 43, 139, 140, 141]. The measured deposition fractions
were a combination of both inhalatory and exhalatory deposition. Stahlhofen
et al. [142] defined the following empirical fit,
=1
1
3.5 108 (d2ae Q)1.7 + 1
(2.1)
where dae is the aerodynamic diameter (m) and Q is the inhalation flow
rate (cm3 /s). Please note that dae and Q are normalized by unit diameter and unit flow rate respectively, so that we have a non-dimensionalized
impaction parameter on the x-axis and a non-dimensionalized deposition
29

efficiency on the y-axis.
Cheng et al. [25] derived a new empirical fit for the inhalatory deposition
efficiency assuming that the inhalatory and exhalatory depositions were
identical. The empirical fit is given by,
= 1 exp(ad2ae Q)
(2.2)
dae is the aerodynamic diameter (m) and Q is the inhalation flow rate
(l/min). Same as before, both dae and Q are normalized by unit diameter
and unit flow rate respectively, to have a non-dimensionalized impaction
parameter on the x-axis and a non-dimensionalized deposition efficiency
on the y-axis. a =0.0002760.000188 (meanSE) is a best-fitted nondimensional parameter obtained by using a nonlinear regression program.
The empirical fit of Cheng et al. [25] is shown in the Fig. 2.13. The data
points represented by filled circles in Fig. 2.13 are experimental measurements obtained by Cheng et al. [25] at three different flow rates of 15, 30
and 60 l/min. In an attempt to account for the geometry specific length and
velocity scales, Cheng et al. [25] also represented the measured deposition
efficiency as a function of Stokes number (Fig. 2.14) which was defined
here as Stk = p d2ae U/9dh . U is a measure of the mean velocity defined
as Q/A, A is the mean cross-sectional diameter, and dh is the minimum
hydraulic diameter. A new empirical fit was derived based on the Stokes
number which is given by,
= 1 exp(6.66Stk)
(2.3)
It is apparent from Fig. 2.14 that the experimental data tend to fall into
a single curve even though there were three different flow rates considered. This was not the case when the deposition efficiency was simply
represented as a function of impaction parameter (Fig. 2.13). A similar
approach was adopted by Grgic et al. [58] who measured regional as well
as total depositions in seven realistic upper airway geometries that span
the range of key dimensions of a larger set of 80 geometries. Representing
the deposition efficiency as a function of inertial parameter showed large
scatter which was attributed to inter-subject variations and different inlet
diameter conditions. Representing the deposition efficiency as a function
of Stokes number showed better collapse of data, but significant scatter remained due to different geometric configurations downstream of inlet. In
order to account for this, Grgic et al. [58] replaced the hydraulic diameter
dh in the definition of Stokes number with a mean diameter d mean calculated simply by dividing cast volume V by the path length L of the central
sagittal line of the model to obtain a measure of area. A corresponding ve30
Figure 2.13: Upper airway deposition efficiency in human subjects measured during mouth breathing shown as a function of impaction parameter d 2ae Q [25].
Figure 2.14: Experimentally measured deposition efficiency as a function of Stokes

number [25].
31
100
Deposition Efficiency, %
90
S5b
S5a
80
S4
70
S3
S2
60
50
40
S1a
S1b
idealized
100-100/(11.5Stk1.912Re0.707+1)
30
20
10
0
0.01
0.1
10
Stk Re0.37
Figure 2.15: Experimentally measured deposition for 8 different models plotted as

a function of Stokes and Reynolds number correlation. Error bars are standard
deviations.
locity scale Umean was calculated from the volume flow rate and the mean
cross-sectional area. The Stokes number then looks like,
Stk
dmean
Umean
p d2p Umean
18dmean
%
V
2
L
QL
V
(2.4)
(2.5)
(2.6)
Using this Stokes number, the scatter among the data was markedly reduced. In their previous deposition tests on an idealized upper airway
geometry, Grgic et al. [59] had noticed that the deposition experiments
with constant Stokes number showed a Reynolds number dependence, due
to changes in flow field with Reynolds number. Therefore, Grgic et al. [59]
proposed the following empirical relationship where the Stokes number is
multiplied by Reynolds number to the power of 0.37.
32
100
11.5(Stk Re0.37 )1.912 + 1
%
Umean dmean
2Q
L
Re =
=
V
%
p d2p Umean
d2p Q L3
Stk =
=
18dmean
36
V3
= 100
(2.7)
(2.8)
(2.9)
An excellent collapse of data measured on various subjects (Fig. 2.15), on

to a single curve indicates that the above defined correlation is indeed an
adequate tool to compare and validate upper airway deposition values simulated on any given upper airway geometry. In the present thesis, Eq. 2.7
has been consistently used to represent the total deposition in the upper
airway.
33
34
Chapter 3
The Fluid Phase

Contents
3.1 Governing Equations . . . . . . . . . . . . . . . . . . . . 37
3.1.1 Reynolds Averaged Navier Stokes (RANS) . . . . . 40
3.1.2 Large Eddy Simulation (LES) . . . . . . . . . . . . 44
3.1.3 Detached Eddy Simulation (DES) . . . . . . . . . . 49
3.2 RANS, LES or DES ? . . . . . . . . . . . . . . . . . . . . 52
Before writing down the governing equations and different modeling approaches for the fluid phase, it is worth giving an introduction to the most
important flow phenomenon called Turbulence.
Turbulence is that state of fluid motion which is characterized by its randomness, increased diffusivity, relatively high Reynolds number, threedimensionality, and dissipativeness. In terms of energy cascade, turbulence is considered to be composed of various sizes of eddies. Developing a
mathematical model to mimic the physics of turbulence requires very good
understanding of the roles played by the largest and the smallest scales of
eddies in the transport of properties.
The energy cascade
Fig. 3.1 shows a schematic representation of the energy cascade. The large
scales are of the order of the flow geometry. If l and u are the length and
velocity scales of the largest eddy, the time scale is derived as,
=
35
l
u
(3.1)
CHAPTER 3. THE FLUID PHASE
Energy
from
mean flow
Large scales
Small scales
where dissipation
takes place
Figure 3.1: Schematic representation of the energy cascade [37].
Figure 3.2: Energy spectrum for a turbulent flow [160].
36

The large energy containing eddies give away their kinetic energy to slightly
smaller scale eddies with which the large scales interact. The process of
kinetic energy transfer continues in the similar fashion until we reach the
smallest scale eddies, where the frictional forces become so large that the
kinetic energy is converted into internal energy. This process of energy
transfer and dissipation is referred to as the cascade process. The dissipation () which takes place at the smallest scales, also referred to as the
Kolmogorov scales, can be estimated from the large scale properties as follows,
=
u2
u3
=
(3.2)
Since the process of dissipation in the smallest scales are due to viscous
forces, we can estimate the properties of smallest eddies using flow kinematic viscosity () and the dissipation () itself. The length, velocity and
time scales are given by:
l =
$1/4
(3.3)
1/4
(3.4)
u = ()
=
& '1/2
(3.5)
The turbulent length scale l is related to the wavenumber as = 2/l.

The energy spectrum E() for a turbulent flow is as shown in Fig. 3.2.
From dimensional analysis, the Kolmogorov -5/3 law characterizes the inertial subrange which is given by,
E() = C 2/3 5/3
(3.6)
C is the Kolmogorov constant.
3.1 Governing Equations

All fluid motions (laminar or turbulent) are governed by a set of dynamical
equations namely the continuity, momentum and the energy equation,
37
+
(ui ) =
t
xi
(ui ) +
(ui uj ) =
t
xj
p
ij
+
xi
xj
(3.8)
(E) +
(Hui ) =
t
xi
(ji uj qi )
xi
(3.9)
(3.7)
ui (+x, t) represents the i-th component of the fluid velocity at a point in

space +x and time t.
p(+x, t) is the static pressure.
ij (+x, t) are the viscous stresses.
(+x, t) is the fluid density.
E and H are the total energy and total enthalpy per unit mass.
qi in Eq. 3.9 is the heat flux which is proportional to the temperature
gradient.
T
(3.10)
qi =
xi
where is the thermal conductivity.
The Mach numbers associated with air breathing are very nominal which
allows the flow to be treated as incompressible. Furthermore, the air
breathed in and out behaves as a Newtonian fluid, in which case the viscous stresses are related to the incompressible fluid motion using a property of fluid, viscosity.
#
$
1
ij = 2 sij skk ij
(3.11)
3
sij is the instantaneous strain rate tensor given by,
$
#
1 ui
uj
+
sij =
2 xj
xi
(3.12)
For incompressible flows, Eqs. 3.7 & 3.8 are simplified to the following
form,
38
uj
xj
ui
ui
+ uj
t
xj
(3.13)
1 p
2 ui
+
xi
xj xj
(3.14)
The inhaled air is heated and humidified from the airway walls, which is
largely complete within the first few generations of the conductive airways
depending on the inhalation rate as well as on the temperature and humidity of the air being inhaled [46]. However, due to the difficulties in
measuring the actual temperature and humidity in the airways, only few
mathematical modeling is available in the literature. In the present thesis,
the temperature effects are ignored and hence Eq. 3.9 is uncoupled from
the continuity and momentum equations.
The four main numerical procedures for solving the Navier-Stokes are
Direct Numerical Simulation (DNS), Large Eddy Simulation (LES), Detached Eddy Simulation (DES) and Reynolds Averaged Navier Stokes (RANS)
approach. The most accurate approach is DNS where the whole range of
spatial and temporal scales of turbulence are resolved. Since all the spatial scales, from the smallest dissipative Kolmogorov scales (l ) up to the
energy containing integral scales (l), are needed to be resolved by the computational mesh, the number of points required in one direction is of the
order,
N=
l
l
(3.15)
The number of points required for a resolved DNS in three dimensions can
be estimated as,
# $3 # $9/4
l
ul
N=
= Re9/4
(3.16)
l
The number of grid points required for fully resolved DNS is enormously
large, especially for high Reynolds number flows, and hence DNS is restricted to relatively low Reynolds number flows. DNS is generally used
as a research tool for analyzing the mechanics of turbulence, such as turbulence production, energy cascade, energy dissipation, noise production,
drag reduction etc. The next three sections explain the RANS, LES and
DES methodologies in detail.
39
3.1.1
Reynolds Averaged Navier Stokes (RANS)
When the flow is turbulent, it is convenient to analyze the flow in two

parts, a mean (time-averaged) component and a fluctuating component,
!
Ui
= U i + ui
= P +p
Tij
!
!
= T ij + ij
Overline is a shorthand for the time average and in case of RANS, U i Ui

!
and ui =0. The above technique of decomposing is referred to as Reynolds
Decomposition. Inserting these decomposition into the instantaneous equations and time averaging results in the Reynolds Averaged Navier Stokes
equations.
U j
xj
U i
U i
+ Uj
t
xj
(3.17)
1 P
2U i
& ! !'
+
ui uj
xi
xj xj
xj
(3.18)
ui uj in the last term of Eq. 3.18 represents the correlation between fluctuating velocities and is called as Reynolds stress tensor. All the effects
of turbulent fluid motion on the mean flow are lumped in to this single
term by the process of averaging. This will enable great savings in terms
of computational requirements. On the other hand, the process of averaging generated six new unknown variables. Now, in total we have ten
unknowns (3-velocity, 1-pressure, 6-Reynolds stresses) and only four equations (1-continuity, 3 components of momentum equation). Hence we are
six equations too few. This is referred to as the Closure problem.
!
Based on the way we close the Reynolds stress tensor, there are two main
categories, namely the eddy viscosity models and Reynolds stress models.
The Reynolds stress tensor resulting from time averaging of Navier Stokes
is closed by replacing it with an eddy viscosity multiplied by velocity gradients. This is referred to as the Boussinesq assumption.
ui uj = t
!
U i
U j
+
xj
xi
40
(3.19)

In order to make Eq. 3.19 valid upon contraction because of Eq. 3.17, it
should be rewritten as,
#
$
U i
U j
2
! !
ui uj = t
+
(3.20)
+ ij k
xj
xi
3
k is the turbulent kinetic energy given by,
k=
1 ! !
uu
2 i i
(3.21)
The eddy viscosity is treated as a scalar quantity and is determined using

a turbulent velocity scale v and a length scale l, based on the dimensional
analysis.
t = vl
(3.22)
There are different types of Eddy Viscosity Models (EVM) based on the way
we close the eddy viscosity. Algebraic or zero equation EVMs normally use
a geometric relation to compute the eddy viscosity. In one equation EVMs
we solve for one turbulence quantity and a second turbulent quantity is
obtained from algebraic expression. These two quantities are used to describe the eddy viscosity. In two equation EVMs the two turbulent quantities are solved to describe the eddy viscosity.
In Reynolds Stress Models (RSM) we solve an equation for the Reynolds
stress and one length scale determining equation. Since we solve for Reynolds
stress, we dont need any model to close it. However RSMs are computationally much more demanding when compared to EVMs.
Two-equation k model
Two equation eddy viscosity models have served as the foundation for
much of turbulence research in the past two decades. The main reason for
their popularity is that they are complete, i.e., they can predict properties
of a given turbulent flow with no prior knowledge of turbulent structures.
All two equation eddy viscosity models use turbulent kinetic energy (k)
as one of the solved turbulent quantities. Along with the transport equation for k, another transport equation is solved for a second turbulent
quantity. The only difference in all two equation models is the choice
of this second quantity we solve for. The two most widely used turbulent quantity which is linked to the kinetic energy are the dissipation
rate at smallest scales (as defined in Eq. 3.2) or the specific dissipation . is related to as = /k . k turbulence model is the
41

most widely used in simulating the transitional fluid flow in the respiratory tract [87, 167, 8, 102, 170, 60, 76, 77]. There are two variants of the
k turbulence model, namely the standard k model of Wilcox [160]
(also called the high-Reynolds-number model) and shear-stress-transport
(SST) k proposed by Menter [105] (also called the low-Reynolds-number
model). The major ways in which the SST model differs from the standard
model are as follows:
Gradual change from the standard k model in the inner region
of the boundary layer to a high-Reynolds-number version of the k
model in the outer part of the boundary layer. The reason for this
switch is that the k model has a very strong sensitivity to the
(quite arbitrary) free-stream values of f outside the boundary layer
[105].
The definition of the eddy viscosity is modified to account for the
transport effects of the principal turbulent shear stress.
The above modifications make the SST k model more accurate and reliable when compared to the standard k model.
The modeled k and equations read,
(k) +
(kui ) =
t
xi
() +
(ui ) =
t
xi
#
$
k
k
+ Pk Dk
xj
#
$
w
+ Pw Dw + Cw
xj
xj
xj
(3.23)
(3.24)
The effective diffusivity for k and are given by,

k
t
k
(3.25)
(3.26)
The turbulent viscosity is related to magnitude of vorticity in the original

model [105]. Menter et al. [106] recently modified the definition of eddy
viscosity by relating it to the strain-rate magnitude. It is given by,
t =
1
k
'
&
max 1 , SF2
a1
42
(3.27)

where S is a strain-rate magnitude. is the turbulence Prandtl number
given by,
1
F1 /k,1 + (1 F1 ) /k,2
1
F1 /,1 + (1 F1 ) /,2
(3.28)
(3.29)
F1 and F2 are the blending functions. For further details on blending functions, the reader is referred to the Fluent manual [4]. is the damping
function for turbulent viscosity causing a low-Reynolds-number correction.
It is given by,
=
0.024 + Ret /6
1 + Ret /6
(3.30)
The production terms for k and are given by,
Pk
!
"
min t S 2 , 10 k
t S 2
t
(3.31)
(3.32)
The dissipation terms for k and are given by,
Dk
(3.33)
(3.34)
The cross-diffusion modification for equation is given by,

C = 2 (1 F1 ) ,2
1 k
xj xj
The values of constants are,

k,1 = 1.176
,1 = 2.0
a1 = 0.31
k,2 = 1.0
i,1 = 0.075
43
,2 = 1.168
i,2 = 0.0828
(3.35)

Advantages of low-Reynolds-number k- model
The two main attractive features of low-Reynolds-number k- model are,
1. It possesses a non-trivial solution for as k goes to zero. It is thus expected to capture flow characteristics which a low-Reynolds-number
k- model fails to handle.
2. It uses damping functions that only depend on turbulent Reynolds
number and hence it is convenient to apply this model to internal
flows with complex geometries, which is the case with the human
respiratory tract.
3.1.2
Large Eddy Simulation (LES)
In case of RANS, the most challenging aspect was to understand and model
the largest eddies, which account for most of the transport properties in a
turbulent flow. As we go closer towards the walls, the size of the eddies gets
smaller and RANS uses viscous damping functions in order to account for
these small dissipating scales. The RANS models often involve simplified
assumptions which makes it impossible for a single model to represent all
turbulent features. Furthermore, it may also require fine-tuning of model
constants to obtain better results for a given test-case.
The Large Eddy Simulation technique was developed based on an implication from Kolmogorovs theory of self similarity that the large eddies
of the flow are dependent on the geometry while the smaller scales are
more universal. Hence, the big three dimensional eddies which are dictated by the geometry and boundary conditions of the flow involved are
directly resolved whereas the small eddies which tend to be more isotropic
are modeled. Hence, the performance of LES as opposed to RANS will be
less problem dependent. An elaborate explanation on LES can be found in
several books such as [160, 123, 49, 117].
LES equations
In case of RANS, the instantaneous continuity and momentum equations
(Eq. 3.7 & 3.8) were time averaged to obtain steady form of averaged equations (Eq. 3.17 & 3.18).
In case of LES, instead of time-averaging, we filter the instantaneous timedependent equations. Filtering is a method that separates the resolvable
scales from the subgrid scales. Filtering can be performed in either wave
number space or the physical space. The filter cut-off should lie somewhere
44

in the inertial range of the spectrum (Fig. 3.2).
In finite volume methods, box filters are always used because the finite
volume discretization itself implicitly provides the filtering operation. One
of the earliest volume average box filters was given by Deardorff [38].
(X, t) =
1
3
x0.5x ( y0.5y
x0.5x
y0.5y
z0.5z
(, t)ddd
(3.36)
z0.5z
(3.37)
+ s
In the above equation, denotes the resolvable scale filtered variable and
s denotes the sub-grid scale fluctuation. is the filter width given by
= (xyz)1/3 .
Leonard [92] defined a generalized filter as a convolution integral which
is given by,
( ( (
(X, t) =
G(X ; ) (, t) d3
(3.38)
G is the filter function that determines the scale of resolved eddies. The
filter function is normalized by requiring that,
( ( (
(3.39)
G(X ; ) d3 = 1
The filter function in terms of the volume average box filter (Eq. 3.36) can
be written as,
1/3 , |x | < x/2

G(X ; ) =
0,
otherwise
Finally, the decomposition of the flow into a filtered part and a sub-grid
part looks like,
Ui
P
= U i + usi
= P + ps
Tij
s
= T ij + ij
The overline in the above equations represents the filtering operation as

opposed to the time-averaging in case of RANS. Also, contrary to RANS,
where the average of fluctuations is zero, in case of box filtering, we have
45

U i %= U i and us %= 0. Further details on the filtering methods can be found
in [117, 160, 37, 91].
Inserting the above decomposition into the instantaneous equations results in the following filtered Navier-Stokes equations,
U j
xj
,
U i
U i
+ Uj
t
xj
(3.40)
sgs
ij
2U i
1 P
+
xi
xj xj
xj
(3.41)
sgs
ij
are the sub-grid scale stresses.
SGS modeling
From the energy cascade, explained in the beginning of this chapter, it
is apparent that the energy transfer occurs from the bigger scales to the
smaller scales. Hence the main purpose of an SGS model is to represent
the energy sink. The representation of the energy cascade is an average
process. However, locally and instantaneously the transfer of energy can
be much larger or much smaller than the average [48]. Additionally, there
is also the phenomenon of energy backscatter in the opposite direction
[116]. Ideally speaking, SGS models should actually account for all these
phenomena. However, if the grid scale is much finer than the dominant
scales of the flow, even a crude SGS model will result in good predictions of
the behavior of the dominant scales [48]. Having this in mind, certain authors such as Tamura et al. [145] and Meinke et al. [104] even performed
LES without any explicit SGS model, but having refined grids to minimize
the importance of SGS stresses, and the energy drain was achieved by numerical schemes. Although this approach yields promising results in some
cases, this kind of modeling can hardly be evaluated or controlled [48].
Hence, in LES, central or spectral schemes are used and the SGS stresses
are explicitly modeled.
sgs
in Eq. 3.41 are given by,
The sub-grid scale stresses ij
sgs
= Ui Uj U i U j
ij
(3.42)
By using the definition of filtering as given by Eq. 3.37 we can further

sgs
work out ij
as,
46
sgs
ij
sgs
ij
&
'
Ui Uj (U i + usi )(U j + usj )
(3.43)
usi usj + (U i usj U j usi ) + U i U j U i U j

/0
1
. /0 1 .
/0
1 .
Reynolds
Crossterm
(3.44)
Leonard
Leonard [92] shows that the Leonard stresses can significantly drain energy from the resolvable scales and they can be directly computed. On the
other hand, Wilcox [160] mentions that Leonard stresses are of the same
order of magnitude as the truncation error when a finite-difference scheme
of second-order accuracy is used, and thus it is implicity represented.
The cross-term stresses are dispersive in nature and largely account for
the backscatter effects. Modeling them with a purely dissipative model
such as Smagorinsky would be in conflict because of its dispersive nature
[91]. In many applications, it is assumed that the Leonard and cross-term
stresses can be neglected and only the Reynolds stresses remain to be modeled. It is the same case in the present work.
A variety of SGS models have been used by different researchers, such as
two-point closures [89], scale-similar models [10], and one-equation models [129, 72, 22] to name a few among others. Please refer to the book of
Sagaut [123] for the detailed review of various SGS models available in
literature.
Smagorinsky model
One of the simplest SGS model is the Smagorinsky model [133]. The unknown subgrid-scale stresses are modeled employing the Boussinesq assumption as in the case of RANS. The subgrid-scale stress are related to
the eddy viscosity as follows,
#
$
U i
1
U j
(3.45)
+
ij kk ij = t
3
xj
xi
The eddy-viscosity is modeled as,
t = L2s
2
2S ij S ij
(3.46)
Ls is the length-scale for the sub-grid scale and is given by C s V 1/3 . V is the
computational cell volume. It is interesting to note that the length scale
is now the filter width rather than the distance to the closest wall as in
47

RANS. Cs is a constant which is taken to be 0.17. The only disadvantage
of the Smagorinsky model is the constant C s , which is not really a constant,
but is flow dependent. It is found to vary between 0.065 [107] and 0.3 [81].
In the dynamic version, which was first proposed by Germano et al. [52],
Cs is dynamically computed based on the information provided by the resolved scales of motion. However, the influence of the subgrid scale model
is expected to be small due to the low Reynolds numbers associated with
the upper airway flows we are dealing with in the present thesis [14, 15].
The specification of L s as Cs V 1/3 is not justifiable in the viscous wall region as it incorrectly leads to a non-zero shear-stress at the wall. In order
to rectify this, Moin and Kim [107] use a Van Driest damping function to
specify the length scale as,
,
# + $y
Ls = Cs V 1/3 1 exp
(3.47)
A+
where y + = u d/ is the non-dimensional distance from wall. u is the
wall shear stress velocity, d is the distance to the nearest wall and A=25 is
the Van Driest constant.
The above described SGS model is a standard version as defined in Smagorinsky [133]. The LES simulations in the present thesis are performed employing the Fluent flow solver. The Smagorinsky model implemented in
Fluent deviates slightly from the standard version in the following ways,
The length-scale for the sub-grid scale is computed as min(d, C s V 1/3 ).
is the von Karman constant (typically a value of 0.41 is used), d is
the distance to the closest wall. d is indeed one of the first mixing
length models in the literature to handle the turbulent viscosity and
was proposed by Prandtl [119]. Van Driest damping is basically an
improved version of Prandtls mixing length model. Both the Prandtl
and the Van Driest model are algebraic and from the zero-equation
models category.
The constant Cs in Fluent is taken to be 0.1 instead of 0.17 as was
originally proposed. The value of 0.17 for Cs was originally derived
for homogeneous isotropic turbulence in the inertial subrange. However, this value was found to cause excessive damping of large-scale
fluctuations in transitional flows near solid boundaries, and has to be
reduced in such regions [4]. A C s value of around 0.1 has been found
to yield the best results for a wide range of flows, and is the default
value in Fluent.
48

Wall-Adapting Local Eddy-Viscosity (WALE) model
The WALE model [110] is specifically designed to return correct wall-asymptotic
y 3 behavior of the SGS viscosity. The model is based on the square of the
velocity gradient tensor and accounts for the effect of both the strain and
the rotation rate to obtain the local eddy viscosity. The eddy viscosity is
modeled as,
= L2s
d
Sij
gij
d d 3/2
(Sij
Sij )
d S d )5/4
(S ij S ij )5/2 + (Sij
ij
" 1
1! 2
g + g 2ji ij g 2kk
2 ij
3
U i
xj
(3.48)
(3.49)
(3.50)
Ls is given by C V 1/3 . The main advantage of the WALE model is that

neither a damping function nor a dynamic procedure is required to account
for the no-slip condition. However, in Fluent, the length scale is still kept
to be min(d, C V 1/3 ). To the best of the authors knowledge, there is no
specific advantage of introducing the d in the length scale definition, as
the no-slip condition is already taken care of. The constant C in Fluent is
taken to be 0.325.
3.1.3
Detached Eddy Simulation (DES)
Detached Eddy Simulation was developed as a response to the computational and physical challenges associated with the reliable prediction of
massively separated turbulent flows in practical geometries at practical
Reynolds numbers. In most external aerodynamic computations such as
the flow around an airplane or an automobile, the boundary layers are
thin and populated with small attached eddies whose local length scale, l,
is much smaller than the boundary layer thickness, . LES, even with the
best wall-region treatment, is very far from affordable in aerodynamic calculations, and will be for decades [135]. The non-affordable computational
costs of LES in the attached boundary layers and the ability of a fine-tuned
RANS methodology in predicting the attached boundary layers lead to the
DES formulation.
DES was first expounded in 1997 together with its formulation based on
the Spalart-Allmaras turbulence model (S-A model) [138]. By definition,
DES is a three-dimensional unsteady numerical solution using a single
49

turbulence model, which functions as a subgrid-scale model in the regions
where the grid density is fine enough for an LES, and as a RANS model
in regions where it is not. The fine enough grid for LES is one where the
maximum spatial step, , is much smaller than the turbulent length-scale
t . Thus in the LES regions, little control is left to the model and the
larger, most geometry sensitive eddies are directly resolved. DES seems
to be most justified as the model adjusts itself to a lower level of mixing,
relative to RANS, in order to unlock the large-scale instabilities of the flow
and to let the energy cascade extend to length scales close to the grid spacing [144].
The most attractive feature of DES is that it is simply formulated unlike
most of the zonal methods where the RANS and LES regions are explicitly
tagged by the user. It provides a continuous velocity and eddy viscosity
field and there is no issue of smoothness between the RANS and LES regions.
S-A based DES formulation
The driving length scale in the standard RANS S-A model is the distance
to the closest wall d. This length scale plays an important role in the standard S-A model as it controls the destruction term [137]. The length scale
in the DES model is defined as,
d = min(d, Cdes )
(3.51)
d is the distance to closest wall and is the grid spacing based on the
largest grid space in the x, y or z directions forming the computational
cell. The empirical constant Cdes has a value of 0.65. The intention is that
in the boundary layers, far exceeds d and the standard S-A model rules
since d = d. Away from walls, d = Cdes and the model turns into a simple
one-equation subgrid-scale model, close to Smagorinskys in the sense that
both make the mixing length proportional to [130]. Grids with y + & 1
and a stretching ratio of 1.15 are generally used to resolve the log layer
[130, 111].
The S-A model, after inserting the length scale as given in Eq. 3.51 reduces to,
(
) +
(
U i) =
t
xi
#
,
$2 4

+ P Y
( +
)
+ Cb2
xj
xj
xj
(3.52)
50

P and Y are the production and destruction terms of turbulent viscosity
that occurs in the near-wall region due to wall blocking and viscous damping. and Cb2 are constants and is the molecular kinetic viscosity.
The turbulence production P is calculated as,
P = Cb1 S
(3.53)
where
S = S +
fv2
2 d2
(3.54)
fv2 = 1
1 + fv1
(3.55)
and
Cb1 and are constants. S is a scalar measure of the deformation tensor

based on the magnitude of the vorticity,
2
S = (2ij ij )
(3.56)
where ij is the mean rate-of-rotation tensor and is defined by,
$
#
1 U i
U j
ij =
2 xj
xi
(3.57)
The destruction term Y in Eq. 3.52 is given by,

Y = c1 f
where
,
# $2
(3.58)
-1/6
(3.59)
= r + C2 (r6 r)
(3.60)
fw
= g
6
1 + C3
6
6
g + C3
S2 d2
(3.61)
The turbulent viscosity t is computed from,

t
fv1
51
(3.62)

fv1 is the viscous damping function given by,
fv1 =
3
3
+ Cv1
(3.63)
(3.64)
and
=
The values of the constants are,
Cb1 = 0.1355
C1 =
Cb1
2
(1+Cb2 )
Cb2 = 0.622
C2 = 0.3
2
3
Cv1 = 7.1
C3 = 2.0
= 0.4187
As mentioned before, Eq. 3.52 implies that RANS is employed close to the
wall and one will switch to the LES model in the core-region. The switch
This causes the destruction term Y
to LES mode implies a reduction in d.
to increase, resulting in the decrease of turbulent viscosity t . The result
in turbulent viscosity reduction causes a drop in production P , so that
t further decreases [91]. Note that at equilibrium (meaning a balance of
production and destruction terms), the S-A model becomes a Smagornisky
like SGS model.
Over the years, there have been several potential improvements suggested
to the original procedure of DES. One such method is the Delayed DetachedEddy Simulation (DDES) which detects boundary layers and prolongs the
full RANS mode, even if the wall-parallel grid spacing would normally activate the DES limiter. This detection device depends on the eddy viscosity, so that the limiter now depends on the solution. Very recently [131],
further corrections are brought into the DDES method with the aim of resolving the log-layer mismatch and the models are named Improved DDES
(IDDES). The present thesis deals only with the original DES model and
for a detailed overview of the new trends in DES, the readers are referred
to Spalart [136].
3.2 RANS, LES or DES ?

Deciding between RANS, LES and DES for simulating the fluid-particle
dynamics in the respiratory tract needs the basic understanding of how
these models work. A few pros and cons of each of these models are briefly
described below.
52
Two equation RANS models are the very commonly used models for most
types of engineering problems and have become an industry standard.
If one is only interested in the averaged quantities, RANS is the best
choice. Since we are solving for time-averaged equations, the computational cost to perform a simulation is very reasonable. For example, a typical fluid-particle dynamics simulation (grid size - 550,000, injected particles - 15,000) in a realistic model of the extra-thoracic airway requires
about 14 hours on an AMD Opteron 2.4 MHz dual-core processor [77].
The main disadvantage of a RANS model is the modeling error that comes
while handling Reynolds stresses. The two-equation turbulence models often involve simplified assumptions which makes it impossible for a single
RANS model to represent all turbulent features. Furthermore, it may also
require fine-tuning of model constants to obtain better results for a given
testcase.
Since the large three-dimensional problem-dependent eddies are directly
resolved in LES, the accuracy of this method will generally be better than
that of RANS. However, LES still requires substantially finer meshes than
those typically used for RANS calculations. Also, the LES method is both
space and time dependent and needs to be run for a sufficiently long flowtime to obtain stable statistics of the flow being modeled. This results
in huge computational costs, which are typically few orders of magnitude
higher than those of RANS. For example, a typical fluid-particle dynamics
simulation (grid size - 1.9106 , injected particles - 5000) in a realistic model
of the extra-thoracic airway requires about 60 days on 4 AMD Opteron 2.4
MHz dual-core processors [77].
Detached eddy simulation (DES) is a modification of a RANS model in
which the model switches to a sub-grid scale formulation in regions fine
enough for LES calculations. Regions near solid boundaries where the turbulent length scale is less than the maximum grid dimension are assigned
for RANS mode of solution. As the turbulent length scale exceeds the grid
dimension, the regions are solved using the LES mode. Therefore the grid
resolution is not as demanding as pure LES, thereby cutting down the cost
of the computation to some extent. While the reduced mesh decreases computational effort, we need to solve the additional S-A equation which adds
to the computational cost. Also, due to the switch between RANS and LES,
generating an optimal cost-effective grid is more complicated.
In Chapter 8, the performance of RANS, LES as well as DES in simulating
the fluid-particle dynamics has been studied in detail. Hence, a definitive
53

answer for the preferred method between RANS, LES and DES can be
found in Chapter 8.
54
Chapter 4
The Particle Phase

Contents
4.1
4.2
4.3
4.4
Governing Equations . . . . . . . . . . . . . . .
Modeling the particle phase . . . . . . . . . .
Stochastic trajectory approach . . . . . . . .
Aspects of Lagrangian modeling . . . . . . . .
4.4.1 Time integration . . . . . . . . . . . . . . .
4.4.2 Locating particles inside a control volume
4.4.3 Cell search algorithm . . . . . . . . . . . .
4.4.4 Interpolation of flow variables . . . . . . .
4.5 Boundary conditions . . . . . . . . . . . . . . .
4.5.1 Inlet boundary condition . . . . . . . . . .
4.5.2 Wall and Outlet boundary condition . . . .
4.6 Uncoupled and coupled calculations . . . . .
4.7 Programming language . . . . . . . . . . . . .
4.8 Data structures . . . . . . . . . . . . . . . . . .
4.9 Flow chart of particle solver module . . . . .
4.10 Testcases . . . . . . . . . . . . . . . . . . . . . . .
4.10.1 Analytical solution . . . . . . . . . . . . . .
4.10.2 2D Planar mixing layer . . . . . . . . . . .
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55
60
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81
82
4.1 Governing Equations

Based partly on the physical properties of pharmaceutical aerosols and
partly on the mathematical modeling effort required, there are certain rea55
CHAPTER 4. THE PARTICLE PHASE

sonable assumptions made to describe the pharmaceutical aerosol transport in a fluid medium. The major simplifying assumptions are as follows,
The pharmaceutical aerosol is assumed to be spherical: This is a reasonable assumption, especially for the liquid based inhaled pharmaceutical droplets, since the small liquid droplets are spherical. The
aerosols generated from DPIs and pMDIs are not exactly spherical,
but it is still a reasonable assumption because the drag on these particles is very close to that on a sphere [46].
The ratio of particle to fluid density is very large: The density of pharmaceutical compounds are much higher when compared to the fluid
medium which is air. Typically, the density of aerosols is close to that
of water, which is 1000 kg/m3 as opposed to 1.2 kg/m3 for air
breathed in.
Drag force is the dominant point force: This is a direct result of the
previous assumption. Since the density of the aerosols are much
higher than the density of the fluid medium, several forces such as
the lift force, Basset force, Magnus force and buoyancy force can be
readily discarded as they have negligible effect on the aerosol transport.
The aerosol phase is dilute: A quantitative way of assessing a dilute
versus dense flow is by taking the ratio of the particle relaxation time
(tr ) to the particle collision time (tc ). The particle relaxation time is
defined as the time required by the particle to loose 63% of its initial
velocity. If tc > tr , the particle has enough time to respond to the
local fluid dynamic forces before collision occurs. Hence, a dilute flow
is one in which the particle motion is controlled by fluid forces such
as the drag force. In case of pharmaceutical aerosol transport, the
collision time is much larger than the relaxation time, making the
phase dilute.
One-way coupling: The phenomenon of mutual mass, momentum
and energy transfer between the phases is termed as coupling. Elghobashi [42] proposed a map of regimes of interactions between
particles and fluid turbulence as shown in Fig. 4.1. For values of
dispersed-phase volume fraction less than 10 6 , particles have negligible effects on turbulence and this is termed as one-way coupling.
The volume fraction of pharmaceutical aerosols we are dealing with
in the present thesis is much less than 106 and hence one-way coupling is assumed. In the second regime which lies between 10 6
103 , the existence of particles can augment the turbulence if the ratio of the particle response time to the turnover time of a large eddy
56
Figure 4.1: Map for particle-turbulence modulation [42].
is greater than unity, or can attenuate turbulence if the ratio is less

than unity. This interaction is called two-way coupling. In the third
regime where the volume fractions are greater than 10 3 , in addition to two-way coupling between particles and turbulence, particle
collisions take place and hence this regime is termed as four-way coupling.
Incorporating all the above assumptions, the Lagrangian equations governing the particle motion can be written as,
dxp
dt
= up
dup
dt
= Fd (u up ) + gx
(4.1)
(p )
p
(4.2)
xp is the particle position, gx is the gravitational force, and p are the

density of the fluid and the particle respectively.
Generally, the particle moves with a different velocity than the fluid at
any given point. The difference in fluid velocity (u) and the particle velocity (up ), termed as the slip velocity (uu p ), leads to an unbalanced pressure
57

distribution as well as viscous stresses on the particle surface which yields
a resulting force called drag force. In Eq. 4.2, the term F d (u up ) is the
drag force per unit particle mass. Fd is given by,
Fd =
1 Cd Rep
p 24
(4.3)
p is the particle relaxation time given by,

p =
p d2p
18
(4.4)
Laws of drag coefficient

The drag coefficient C d is a function of particle Reynolds number (Re p ).
Various experimentally based empirical correlations for the drag coefficient based on Rep are available in the literature. One such correlation
of Schiller and Neumann [126], which is employed in the present work, is
given below.
Cd =
24
(1 + 0.15Re0.687
)
p
Rep
(4.5)
The Reynolds number of the particle is defined as,

Rep = dp
|u up |
(4.6)
Fluent employs a different form of drag coefficient put forth by Morsi and
Alexander [108]. It is given by,
Cd = a1 +
a2
a3
+
Rep
Re2p
(4.7)
where a1 , a2 and a3 are constants that apply to smooth spherical particles

in a stipulated range of Rep as given in the table below,
58
Experimental data
Schlichting (1979)
Schiller and Neumann (1933)
Morsi and Alexander (1972)
10
Cd
10
10
10
10
10
10
10
Rep
10
10
10
10
Figure 4.2: Drag coefficient for spheres as a function of Re p .
Rep
< 0.1
a1
0
a2
24
a3
0
0.1 < 1.0
3.69
22.73
0.0903
1 < 10.0
1.222
29.1667
-3.8889
10.0 < 100.0
0.6167
46.5
-116.67
100.0 < 1000.0
0.3644
98.33
-2778
1000.0 < 5000.0
0.357
148.62
-4.75
5000.0 < 10000.0
0.46
-490.546
57.87
10000.0 < 50000.0
0.5191
-1662.5
5.4167
Fig. 4.2 shows the comparison of the above two formulations for C d with
respect to the experimental data of Schlichting [127]. As can be seen, both
models perform very well up until Re p =1000, after which, the model of
Morsi and Alexander [108] does a better job. However, the Re p encountered
in the present work are well below 1000 and both formulations are equally
suited.
59
4.2 Modeling the particle phase

Based on the recent experimental observations by Grgic et al. [58] on
inter-subject variability of the extra-thoracic airway deposition, the need
for considering realistic model for CFD study is recognized and an efficient
Lagrangian particle tracking module for unstructured grids to handle complex geometrical features is developed in the commercial C++ flow solver
of NUMECA. Even though the concept of unstructured grids exists since
long, the practical applicability is still under budding stage, especially for
two-phase simulations. In this view, the modeling methods described in
this chapter can be seen as the first step towards applicability of unstructured grids for biomedical applications, which is by far the only option to
remove expensive experiments for realistic geometry configurations.
Coming to the fundamental mathematical modeling of two-phase flow, the
two most widely used approaches are the Eulerian continuum approach
and the Lagrangian trajectory approach. For a detailed overview of the
modeling techniques for inhaled particle deposition, the readers are referred to Hofmann [68].
Eulerian continuum approach

In an Eulerian approach, the particles are treated as a second fluid which
behaves like a continuum and the equations are developed for average
properties of the particles. For example, the particle velocity is the average
velocity over an averaging volume. This approach is most suitable when
one requires a macroscopic field description of dispersed phase properties
such as pressure, mass flux, concentration, velocity and temperature. Eulerian approach is more suitable for simulating large-scale particle flow
processes. However, this approach requires sophisticated modeling in order to describe the key effects and phenomena found in industrial processes [30].
Lagrangian trajectory approach

A Lagrangian approach is useful when the particle phase is so dilute that
the description of particle behavior by continuum models is not feasible.
The motion of a particle is expressed by ordinary differential equations
in Lagrangian coordinates and are directly integrated to obtain individual tracks of particles. To solve the Lagrangian-equation for a particular moving particle, the dynamic behavior of the gas phase (generally obtained by an Eulerian approach) and other particles surrounding this moving particle should be pre-determined. Since the particle velocity and the
60

corresponding particle trajectory are calculated for each particle, this approach is more suitable to obtain the discrete nature of motion of particles.
However, to obtain statistical averages with reasonable accuracy, a large
number of particles will have to be tracked. An advantage of using the
Lagrangian approach is the ability to easily vary the physical properties
associated with individual particles such as diameter, density etc. Moreover, local physical phenomena related to the particle flow behavior can be
easily probed. Hence, the Lagrangian models can also be used for validation, testing and development of continuum models [30].
The Lagrangian approach is classified in to two types namely, Deterministic trajectory methods and Stochastic trajectory methods based on the effect
of turbulence. In a deterministic method, all the turbulent transport processes of the particle phase are neglected where as the stochastic method
takes in to account the effect of fluid turbulence on the particle motion by
considering instantaneous fluid velocity in the formulation of the equation
of particle motion. In the present thesis, the pharmaceutical aerosols are
modeled with a stochastic Lagrangian approach.
4.3
Stochastic trajectory approach
Stochastic modeling involves direct simulation of particle motion through

a random turbulent flow field. There are several approaches in developing stochastic models. Few examples in literature include models based on
the Langevin equation [97], random Fourier modes [103] and pdf models
[118]. However, one of the most frequently used model is the eddy interaction model (EIM) first introduced by Hutchinson et al. [73] and further
developed by Gosman and Ioannides [53].
The instantaneous motion of particles governed by Equations 4.1 and 4.2
can be written in a general form as given below,
dx
dt
dup
dt
up
(4.8)
1
(u up ) + g
p
(4.9)
The instantaneous fluid velocity u in the above equation is represented as

the sum of the mean and fluctuating velocity,
u=U +u
Assuming isotropic turbulence, we have,
61
(4.10)
u! 2 = v ! 2 = w ! 2 =
2
k
3
(4.11)
where k is the turbulent kinetic energy which may be determined from the
k model. Furthermore, it is assumed that the local velocity fluctuations of the fluid phase obey a Gaussian probability density distribution.
Most stochastic models in practical use are derived from the formulation
of Gosman and Ioannides [53], which is given by,
!
u =
2
k
3
(4.12)
where is a random number drawn from a normal probability distribution

with zero mean and unit standard deviation. The minimal random number generator of Park and Miller with Bays-Durham shuffle [5] is implemented. The random number generator returns a uniform random derivative with zero mean and unit standard deviation.
The chosen fluctuation is referred to a turbulent eddy whose size (length
scale) and life-time (time scale) is known. Sommerfeld et al. [134] proposed
the following relations for eddy parameters,
te
ct
le
te
(4.13)
2
k
3
(4.14)
where ct was taken to be 0.3.

Since we are using a k turbulence model, the dissipation rate is taken
to be = k. Fig. 4.3 shows a 2D schematic representation of an eddy inside a rectangular domain. At any given particle position (x p , yp ), the eddy
parameters are first evaluated based on the local fluid kinetic energy and
dissipation rate. The particle position (xp , yp ) is assumed to be located at
the center of this hypothetical eddy. It is accepted that each eddy has its
!
own fluctuation u , which remains constant until the particle leaves this
eddy. The particle leaving an eddy is based on a certain interaction time
of the particle with the eddy. Once this interaction time is reached while
time integration of particle equations, the particle is assumed to have left
the present eddy. Now, based on the new position of the particle, new eddy
!
parameters are calculated and a new fluctuation u is assigned to this eddy.
This procedure may be repeated for as many interaction times as required
62
(x , y )!
p
Figure 4.3: 2D illustration of a particle within an eddy.
for the particle to traverse the required distance. If a statistically significant number of particles are tracked in this way, the ensemble averaged
behavior should represent the turbulent dispersion induced by the prevailing fluid field [53].
The interaction time is the minimum of two time scales, one being a typical
turbulent eddy lifetime and the other the crossing-time of the particle in
the eddy [53].
(4.15)
tint = min(te , tc )
The crossing-time is defined as,
,
#
tc = p ln 1
le
p |u up |
$-
(4.16)
where p is the particle relaxation time, le the eddy length scale and |uu p |
the magnitude of slip velocity. In circumstances where l e /(p |u up |) > 1,
Eq. 4.16 has no solution. This can be interpreted as the particle trapped
by an eddy, in which case t int = te [53].
4.4
Aspects of Lagrangian modeling
Developing a Lagrangian module on unstructured hexahedral meshes which

is directly applicable for complex engineering configurations requires the
following key issues to be addressed,
(a) Time integration.
(b) Efficient search and location of particles on an unstructured grid.
63
(c) Interpolation of flow variables at particle location.
4.4.1
Time integration
Equations 4.8 and 4.9 are numerically integrated to obtain the updated
particle velocity and position. Two numerical schemes have been implemented, namely the trapezoidal discretization and Runge-Kutta scheme.
Trapezoidal discretization
The particle momentum and the displacement equations can be solved using a numerical discretization scheme. In the trapezoidal scheme, the variables up and u in Eq. 4.9 are taken as averages, while acceleration due to
gravity (g) is kept constant.
"
unp
un+1
1 !
p
=
u up + g
t
p
(4.17)
The averages u and up are given by

u
up
un+1
"
1! n
u + un+1
2
"
1! n
u + un+1
p
2 p
= un + tunp un
(4.18)
(4.19)
(4.20)
Inserting the above into Eq. 4.17 results in the particle velocity at new
time n + 1 which is,
=
un+1
p
&
unp 1
1 t
2 p
'
t
p
! n 1
"
u + 2 tunp un + tg
1+
1 t
2 p
(4.21)
The new particle location is computed by the trapezoidal discretization of

Eq. 4.8.
"
1 !
xn+1
= xnp + t unp + un+1
p
p
2
64
(4.22)

Runge-Kutta scheme
The governing equation for a single particle in a carrier flow can be expressed in a general form as,
dY
= L(Y, t)
(4.23)
dt
Y = f (r, u) is a vector of physical properties which include the particle
position, particle velocity etc. L = f (Fd , g) represents the rate of change of
particle properties with time dependent source terms like the drag force,
gravity etc. The above non-linear differential equation can be numerically
integrated using a Runge-Kutta method to obtain the solution at the next
time level through a number of intermediate steps (stages). A K-stage
explicit Runge-Kutta scheme to solve the above equation is given as,
+ (s)
Y
+ (1)
Y
=
=
+ (n+1)
Y
+ (s1) , s = 2...K
+ n + t k L
Y
n
+
Y
+ n + t L
+ (K)
Y
(4.24)
(4.25)
(4.26)
In specific, a 4-stage explicit Runge-Kutta scheme which is second order accurate was employed. The coefficients are 2 =0.25, 2 =0.33333, 2 =0.5.
Since the fluid field is calculated with second-order accuracy, it is reasonable to provide the same accuracy level for particle tracking [166]. Being a one-step method, the trapezoidal scheme has the advantage that the
movement of particles from one control volume to the next can easily be
controlled as opposed to a multi-stage Runge-Kutta. The details of the
cell-crossing of a particle are discussed in detail in the next sections.
The purpose of particle tracking is to obtain detailed information on particle parameters within all passed control volumes. To achieve this, the
particle should ideally make several time-steps within each control volume it passes through. Hence the integration time-step t should be of
the order of l/u p , l being the minimum edge length of the control volume. Please do note that the integration time-step has further constraints
from the eddy interaction model as described in the Stochastic modeling
approach.
4.4.2
Locating particles inside a control volume
Locating particles on a structured grid is straight-forward since physical

co-ordinates can be transformed into a uniform computational space. However, this is not the case in unstructured grids. Westermann [158] proposed several approaches to locate particles in particle-in-cell codes based
65
a3
xp
a4
a2
a1
Figure 4.4: 2D representation of a hexahedral cell and its respective partial areas
a1 to a4 .
on different requirements. Two such approaches which are suitable for the
present work are discussed below.
Computing partial volumes
First approach was based on computing partial volumes. The nodes of the
control volume are joined to the particle location and the volumes of the
resulting sub-volumes are compared with that of total cell volume. If the
volumes are exact, the particle lies in the control volume.
For example, consider a 2D representation of a hexahedral cell as shown
in Fig. 4.4. If xp is the position of a particle within the cell, partial areas
are created by connecting the nodes of the cell to the particle position. If
the summation of a1 , a2 , a3 , and a4 is equal to the total area of the cell,
then the particle lies within this cell.
Projection to cell faces
The second approach is to project the particle location onto the control volume faces. If the projection is positive for all faces of the control volume,
the particle lies within the control volume. In Fig. 4.5, x p is the particle
position within the cell, A, B, C and D are the faces of the cell, x is the
position of the cell face B, and f is the corresponding face-normal of cell
face B. Now, the projection for face B is computed as P B = (xp x) f . The
same procedure is repeated for faces A, C, and D. If P > 0 for all the faces,
it implies that the particle is within the cell.
Both these methods were implemented in the code, and it was seen that the
method of computing partial volumes fails dramatically for highly skewed
66
B
x
f
xp
A
Figure 4.5: 2D representation of a hexahedral cell showing the position of a particle

within a cell and a face-normal f i .
7
6
5
4
Figure 4.6: Typical 2D arrangement of unstructured hexahedral cells.
meshes due to round-off inaccuracies in computing partial volumes where

as the projection method was found to be accurate even for highly skewed
control volumes. Since skewed meshes are an integral part of complex
geometries, the projection method should clearly be the preferred choice.
4.4.3
Cell search algorithm
Efficient searching of the particle when it crosses the present control volume under consideration is the next challenge. The time step can be chosen to restrict the particle to remain in one of the neighboring cells of the
present control volume. One should also note that each control volume
may have a variable number of neighboring cells depending on the geometrical details.
67

For example, consider a typical 2D cell arrangement which can be expected
in an unstructured hexahedral grid as shown in Fig. 4.6, with the particle
position to be in cell p. It can be seen that the cell p has 9 neighboring
cells. The particle position is projected on to each of the control volume
faces of cell p. If the projection is negative for a face, the neighboring cell
sharing the face is chosen as a reference cell. Now the particle position is
projected on to the faces of reference cell. If all the distances are positive,
the reference cell is taken as the new cell with updated particle position.
However, this procedure works only when the particle moves from cell p to
cell 1, 3, 5, 6 or 8. Only in the case when the particle is not found in cell
1, 3, 5, 6 or 8 we consider the remaining neighboring cells of p (2, 4, 7 or
9), by checking each of the remaining cells in the same way of projecting to
faces.
As mentioned before, the chosen integration time-step t restricts the particle to remain in one the neighboring cells of the present control volume.
Once the projection is negative for a particular face, the neighboring cell
to which this face is common is identified using the face-cell connectivity.
The particle location is now projected to the faces of neighboring cell and
if all are positive, this neighboring cell is taken as the new control volume
inside which the particle lies. The procedure is repeated until the particle
reaches a wall or outlet.
4.4.4
Interpolation of flow variables
Since complex geometries with unstructured meshes always include highly

skewed meshes, a robust interpolation scheme is a requirement. The particleladen flows of Apte et al. [9] and Zaitsev [166] used a linear interpolation
scheme, with the flow solver being second-order accurate in space and concluded that linear interpolation is robust and also provides adequate accuracy for interpolating the flow parameters between nodes.
The viscous flux discretization in the flow solver of Numeca requires the
knowledge of flow variables at cell vertices. For irregular hexahedron
meshes, a linearity-preserving interpolation based on the formulation of
Holmes and Connell [70] is used to ensure accurate transfer of variables
from cell-centers to vertices. The flow variables are computed at individual particle locations within a control volume using the same generalized
linearity-preserving interpolation scheme which is described below,
To interpolate at any point p surrounded by n number of cells, the value of
68

flow variable U at vertex p is given by,
Up =
n
5
Ui i
i=0
n
5
(4.27)
i
i=0
Ui is the cell center value of a flow variable. i is the weighting function

which is defined as,
(4.28)
i = 1 + x xi + y yi + z zi
where xi , yi and zi are the coordinate differences between cell i and

vertex p (xi = xi xp , ...). The weighing coefficients x , y and z are
computed by assuming that Eq. 4.27 should be exact for linear evolution
of U . Hence we can write,
Ui = Up + xi
Up
Up
Up
+ yi
+ zi
x
y
z
(4.29)
Rewriting 4.27 in the following form,

n
5
i=0
(4.30)
i (Ui Up ) = 0
and inserting 4.29 in 4.30 results in,

#
$
Up
Up
Up
i xi
+ yi
+ zi
=0
x
y
z
i=0
n
5
(4.31)
For linear functions, this relation should remain valid for any value of
derivatives. Since there are three unknowns determining i , three particular sets of derivatives were chosen so that we obtain the following three
equations from Eq. 4.31, where i is replaced by Eq. 4.28.
n
5
xi + x
i=1
n
5
i=1
yi + x
i=1
n
5
i=1
n
5
n
5
x2i + y
n
5
i=1
xi yi + y
i=1
zi + x
n
5
i=1
xi yi + z
xi zi
= 0
yi zi
= 0 (4.32)
i=1
n
5
i=1
xi zi + y
n
5
n
5
i=1
69
yi2 + z
n
5
i=1
yi zi + z
n
5
i=1
zi2
= 0
Figure 4.7: One dimensional representations of A) One particle injection from face
center; B) Multiple particle injections from a single face; C) Multiple particle injections from face-center, but different fluctuations.
This linear algebraic system with three unknowns x , y and z are solved
using Cramers rule.
4.5 Boundary conditions

4.5.1
Inlet boundary condition
The particles are typically injected from the cell faces that mesh the inlet
surface. Depending on the number of particle injections required, there
are three different possibilities.
One particle per face

This is the simplest way, where one particle is injected from the face-center
of each cell face that forms the inlet surface. A one dimensional representation of this scenario is shown in Fig. 4.7A. The face-center is computed
based on the available face-vertex data. For example, consider a face in
physical space as shown in Fig. 4.8. The face center is now computed as,
70
xc
1
(x1 + x2 + x3 + x4 )
4
(4.33)
yc
1
(y1 + y2 + y3 + y4 )
4
(4.34)
Uniform distribution within a face

In Lagrangian modeling, it is required to track a huge number of particles
in order to obtain good statistical averaging. Most often, the number of
cell-faces available at the inlet are very nominal. Hence, we can inject multiple particles from each cell-face by uniformly distributing them within
each face. A one dimensional representation of this scenario is shown
in Fig. 4.7B. Uniform particle distribution is accomplished by Laplacian
transformation. The particles will first be distributed in isoparametric
space and then transformed into the physical space as described below,
In the isoparametric space as shown in Fig. 4.8, i = 1 : m, and j = 1 : n
and m n is the number of particles needed inside the face. The division
in and directions are given by,
=
2
max min
=
m+1
m+1
(4.35)
2
max min
=
n+1
n+1
(4.36)
and are defined as,

(i) =
1 + i
(4.37)
1 + j
(4.38)
(j)
The transformed locations on the physical space are calculated by,

xp (i, j) =
n1 (i, j)x1 + n2 (i, j)x2 + n3 (i, j)x3 + n4 (i, j)x4
(4.39)
yp (i, j) =
n1 (i, j)y1 + n2 (i, j)y2 + n3 (i, j)y3 + n4 (i, j)y4
(4.40)
x14 and y14 are the vertex co-ordinates in the physical space. n 14 are
defined as,
71
Laplacian transformation
" ( j)
(#1,1)
( x4 , y 4 )
(1,1)
( x3 , y3 )
! (i )
(#1,#1)
(1,#1)
( x2 , y 2 )
( x1 , y1 )
Isoparametric space
Physical space
Figure 4.8: Representation of the isoparametric space and the physical space.
n1 (i, j) =
(1 (i)) (1 (j))
4
(4.41)
n2 (i, j) =
(1 + (i)) (1 (j))
4
(4.42)
n3 (i, j) =
(1 + (i)) (1 + (j))
4
(4.43)
n4 (i, j) =
(1 (i)) (1 + (j))
4
(4.44)
One particle per face with random perturbation

In case of RANS simulations, we can take advantage of the way the eddy
interaction model works. We can inject multiple particles from the same
face-center position, but use a different random number in Eq. 4.12 during the first step of particle injection. In the case of unsteady RANS, LES
and DES, injecting a set of particles at different time levels automatically
ensures random fluctuations on the particles.
72
up
rp
Figure 4.9: Representation of the wall deposition of a particle.
Perform the fluid flow calculations to obtain a

converged mean-flow solution
Calculate the particle phase by using an eddy

interaction model
Figure 4.10: Uncoupled particle phase calculations.
4.5.2
Wall and Outlet boundary condition
The airway passage is normally wet and it is realistic to assume that the
particle sticks to the wall. As can be seen in Fig. 4.9, as soon as the
distance between the particle and the wall becomes equal to the radius of
the particle, it is taken to be deposited on the wall. The same procedure
applies to the outlet of the domain.
4.6
Uncoupled and coupled calculations
In case of uncoupled calculations, the solution procedure is as shown in

Fig. 4.10. The time-averaged fluid flow calculations are performed till the
required accuracy is achieved and then the particles are introduced in this
mean-flow solution and tracked using the eddy interaction model which
models the fluctuating part of the velocity.
73
Perform one fluid flow time-step calculation

to obtain instantaneous-flow solution
Update the particle phase for the above timestep, without any EIM
Figure 4.11: Coupled particle phase calculations.
Fig. 4.11 shows the solution procedure for coupled calculations. The instantaneous fluid flow solution is calculated for a given physical time-step,
and then the particle phase is updated in this instantaneous fluid field for
the same time-step duration. This fluid phase and particle phase calculations are repeated in a loop till the particles deposit on the walls or reach
the outlet of the domain.
4.7 Programming language

The present all-hexahedral unstructured flow solver of Numeca is based on
the object oriented programming (OOP) language C++ which has several
advantages when compared to traditional languages such as FORTRAN
which still dominates the scientific computing community. Rather than
trying to fit a problem to the procedural approach of a programming language, OOP attempts to fit the language to the problem. The basic organization of a C++ program is shown in Fig. 4.12.
Unlike structured programming where a problem is approached by dividing it into functions, in OOP, the problem is divided into objects. Thinking
in terms of objects rather than functions makes the designing and maintenance of a huge industrial code easier. The basic idea is to make the
data and the functions that operate on this data into a single unit. If one
wants to modify the data in an object, it can only be achieved by using
the member functions of that object. No other functions outside this object
can manipulate this data. This very feature simplifies the programming,
debugging, and maintenance of the code. A typical C++ program consists
of several objects which interact with each other by calling one anothers
member functions. A collection of objects together represents a class. A
class basically serves as a blueprint or a plan which holds specific information about what data and functions will be included in the objects of
74

OBJECT
Data
Member function
Member function
OBJECT
OBJECT
Data
Data
Member function
Member function
Member function
Member function
Figure 4.12: The organization of a C++ program [82].
its class. One of the most attractive feature of OOP is inheritance, which
allows one to build new classes based on the old ones. The new class is
referred to as the derived class, which can inherit the data structures and
functions of the original class, also referred as the base class. This allows
programmers to add new features to the existing ones, but without altering the base class. This indeed confines errors, if any, to the derived class,
which makes maintenance and debugging easier.
4.8 Data structures

Data structure is a way of storing data so that it can be used efficiently.
A well-designed data structure allows a variety of critical operations to be
performed using less resources, both in terms of computational time and
memory space required.
All computational grids are made up of basic entities that are cells, faces,
edges and vertices. The most complete data-structure showing all connectivities is shown in Fig. 4.13. The higher the available connectivities, the
less searching operations are needed during a computation. However, this
is at the expense of the memory cost required to store the connectivities.
75
Cell
Face
Vertex
Edge
Figure 4.13: All possible connectivities between cells, faces, edges and vertices
[114].
Cell
Face
Vertex
Figure 4.14: Connectivities used by flow solver module.
Flow solver connectivities

Since the implemented Lagrangian module is an extension of Numecas
flow solver module, understanding the data structure of the flow solver is
essential. In terms of connectivities, the flow solver module uses a light,
face-based data structure but stores more mesh related information such
as face-normals or cell-volumes in order to avoid expensive re-calculations.
Fig. 4.14 shows the connectivities built for the flow-solver module.
The choice of an appropriate data structure is mainly guided by the discretization methods used. The flow solver of Numeca uses a finite-volume
central scheme with artificial dissipation [75], which requires the knowledge of face-cell connectivity. The viscous fluxes, which are purely centrally discretized require the knowledge of velocity gradients at cell faces.
In order to obtain the velocity gradients at cell faces, the knowledge of flow
76
Cell
Face
Vertex
Figure 4.15: Connectivities used by particle solver module.
variables at the cell vertices is needed. To perform an interpolation from

the cell centers to the cell vertices, the face-vertex connectivity is needed
[114].
Particle solver connectivities

As explained in section 4.4.3, it is impossible to identify the cell to which
the particle moves when it travels from cell p to cell 2, 4, 7 or 9 unless we
know all the neighboring cells of p in advance. To identify the neighboring
cells of each control volume in a domain, we need to know the faces each
cell is associated with. In other words, we need the cell-face connectivity.
Once we have built this connectivity, the neighboring cells are identified
by looping over the faces of each cell and using the face-cell connectivity
which is built in the flow solver module.
It was concluded in section 4.4.1 that the integral time-step t should be
of the order of l/u p . l is the shortest edge of a cell in which the particle
travels. Each face of a cell is recognized using cell-face connectivity. Shortest edge of each face is constructed using the face-vertex connectivity which
is available from the flow solver module. A structured way of numbering
the face-vertex connectivity enables to construct the shortest edge of each
face. Finally, the shortest edge among all faces is taken as the shortest
edge of the cell.
Fig. 4.15 summarizes the connectivities needed for particle solver module. Please note that the cell-vertex connectivity was also built in order
to perform the cell-search by computing partial volumes. However, this
method was found to be inaccurate for highly skewed meshes as described
in section 4.4.3, and hence the cell-vertex connectivity can be skipped.
77
Data storage in particle solver module

In unstructured meshes, all mesh-related searching operations demand
huge amounts of computational resources. At the same time, it is not feasible to perform all the operations once and store them, due to memory
cost. Hence, there should be an ideal combination of what should be stored
and what can be computed dynamically during the simulation. All data
stored are in vectors or multi-dimensional arrays. Below is the list of data
which are stored or dynamically computed for the particle phase module.
Cell-face connectivity
The cell-face connectivity is required for the following two reasons,
a) To identify the surrounding cells of each cell.
b) To identify if a particle is inside the cell or not, by using the projection method.
Considering a maximum grid refinement of 4, 24 integers per control volume have to be stored. This connectivity is built at the beginning of particle solver module before the particle injection.
Surrounding cells connectivity
The surrounding cells are required for the following two reasons,
a) For interpolation at any point inside a cell.
b) For cell searching during particle tracking.
Considering a maximum refinement of 4, 56 integers per cell have to be
stored. Having such a huge storage in memory for each control volume is
not practical. Hence, the surrounding cells are dynamically calculated as
and when the particle travels through that control volume.
Shortest edge of a cell
This is required to define the time step for integrating the particle equations. One real variable has to be stored per cell. This is performed at the
beginning of the particle phase.
78

Boundary cells
The IDs of boundary cells are also stored in a single array. This is helpful
for two purposes.
a) For deciding if the particle has crossed a boundary face or not.
b) To consider the boundary values when interpolating the flow parameters at any point inside a boundary cell or inside any cell associated with
the boundary cell.
4.9
Flow chart of particle solver module
The flow chart in Fig. 4.16 gives a brief of the steps involved in tracking
a single injected particle using the present particle solver module implemented in the unstructured all-hexahedral C++ flow solver of Numeca.
Once the inlet particle distribution is decided, an array containing the x,
y, and z positions of the injections is generated. Now, the particles are
injected one by one by looping over the number of injections. Once the injection position is known in a given control volume, the surrounding cells
of this control volume are found using the cell-face and face-cell connectivities. The flow variables at the particle position are interpolated using
the variables available in the present control volume and its surrounding
cells. Once the flow variables are known, estimates of eddy length and time
scales are made based on the turbulence kinetic energy and its dissipation
rate. An estimate of the fluctuating velocity is also calculated based on the
kinetic energy level and employing a random number generator. Based
on the prescribed injection properties of the particle such as the density
(p ), diameter (dp ), injection velocity (u p ), and the interpolated fluid velocity at the injection position (u), the external forces acting on the particle
are calculated. As mentioned before, the two main forces considered in the
present study are the drag force and the gravitational acceleration. Once
the forces are computed, the physical time-step for integration of the particle equations is determined based on the cell size of the present as well
as the surrounding cells, and the eddy parameters. One time-step is performed to obtain the updated particle velocity and position. It is checked
if the new particle position is within the present control volume. If no, the
control is passed back to compute the surrounding cells of the new control volume. If yes, it is further checked if the current control volume is a
boundary cell. If it is not a boundary cell, the control is passed to interpolating the flow variables at the new location and continuing the particle
tracking until the distance between the particle center and the nearest
79
Determine the inject co-ordinates based on the

required inlet distribution and inject one particle
Compute the surrounding cells of the current
control volume where the particle lies
Interpolate the flow variables at the particle
position
Determine the eddy parameters and fluctuating
velocity using interpolated flow variables and the
random number generator
Compute the forces acting on the particle
Determine the integration time-step based on the
cell size & eddy parameters
Perform a time-step to obtain updated particle
position and velocity
NO
NO
If the particle is still in the current cell

If the current cell is a boundary cell
YES
YES
Check the distance between particle position &

the nearest wall/outlet
NO
If the distance to wall/outlet <= particle radius
YES
Particle is stuck on wall or reached outlet
Figure 4.16: Flow chart demonstrating the steps involved in tracking one injected
particle.
80

wall/outlet becomes equal to or less than the radius of the particle.
4.10
Testcases
4.10.1
Analytical solution
The mathematical implementation of the code can be checked by formulating a test-case for which the analytical solution exists. Consider the
following ordinary differential equation which governs the particle motion,
drp
d2 rp
= u(rp )
+
dt2
dt
drp
= upo
t = 0 : rp = rpo ;
dt
(4.45)
where u(rp ) is a linear function describing carrier flow velocity distribution. is the relaxation time due to drag force.
Considering the carrier flow velocity components, u x = xp , uy = yp , uz = 0
in Eq. 4.45 results in the following two independent equations,
dxp
d2 xp
xp = 0
+
dt2
dt
dxp
= upo
t = 0 : xp = xpo ;
dt
d2 yp
dyp
yp = 0
2 +
dt
dt
dyp
= vpo
t = 0 : yp = ypo ;
dt
(4.46)
(4.47)
The analytical solution for particle positions in time is given by,

xp (t) =
P1 =
2 xpo upo
; P2
2 1
yp (t) =
Q1 =
2 ypo vpo
; Q2
2 1
P1 exp(1 t) + P2 exp(2 t)
(4.48)
1 xpo upo
1 1 + 4
; 1,2 =
1 2
2
Q1 exp(1 t) + Q2 exp(2 t)
1 ypo vpo
1 1 4
; 1,2 =
1 2
2
81
(4.49)
Tau = 1
Tau = 0.1
Tau = 0.001
Computed trajectory
1.5
0.5
0.5
0
0.5
1.5
2.5
3.5
Figure 4.17: Comparison of simulated particle trajectories with analytical solution

for different relaxation times.
* : analytical solution for = 0.001; xo = 0.35

! : analytical solution for = 0.1; xo = 0.25
: analytical solution for = 1; xo = 0.15
: computed trajectory of the particles
Fig. 4.17 shows that the computed trajectories of particles are in very
good agreement with the analytical solution for a varied range of particle
relaxation times, which proves that the mathematical part is correctly implemented. Please note that drag force is the only considered part of the
interphase forces.
4.10.2
2D Planar mixing layer
Chang et al. [24] noted that very few measurements are available in relation to the polydispersed properties of two-phase flows and made it an
objective to provide well-defined benchmark quality data for model validation. The experimental setup is described below.
Measurements were made in a vertical tunnel which was split in to two
separate flow paths by a central splitting plate. The contraction ratio of
the tunnel was 16:1 with a 150 150 mm2 cross-sectional area at the
test section. The mean velocities at high and low-streams were 10.0 and
2.3 m/s respectively. The high speed stream was seeded by polydispersed
82
(a)
Figure 4.18: The computational domain.
water drops with diameters ranging from 3-100 m. Data was collected
at four stations in the streamwise direction, 5, 20, 40 and 80 mm from the
separation point of the splitting plate. The data obtained at 5 mm provided
all the required inlet boundary conditions for the flow simulation, except
for the rate of dissipation of turbulent kinetic energy. Additional measurements of turbulent shear stress and velocity gradients were performed at
5 mm and the rate of dissipation was estimated by using the Boussinesq
hypothesis.
The carrier flow field is simulated using Numecas flow solver for unstructured hexahedron grids, FINE-Hexa 2.1. The computational domain is
as shown in Fig. 4.18. It varies from 5 mm to 120 mm in the streamwise
direction and -35 mm to +35 mm in the transverse direction. Box adaptation was used to refine the mesh in the region of the mixing layer. Velocity,
kinetic energy and the dissipation profiles are specified at the inlet, static
pressure at the outlet and the mirror for boundaries.
Fig. 4.19 summarizes the fluid phase results. It can be seen that the
streamwise velocities are very well predicted whereas the transverse velocities are not. Increase in mesh size did not show any improvements. Zaitsev [166], who developed the Lagrangian module in the structured code
of Numeca performed the same test case for model validation and also reported the under-estimation of the transverse velocity field. It can be seen
that the peak values of kinetic energy move from the upstream side (high
velocity region) towards the downstream side (considerably low velocities).
Two k models were tested, namely the low-Reynolds number Yang-Shih
model [164] and an extended wall function model of Hakimi [61]. The LRN
83

model of Yang-Shih provided the best results.
Fig. 4.20 represents the streamwise velocity predictions of the particles.
The comparison between the predictions and measurements is favorable.
However, it is seen that the drop penetration depth into the low-speed
stream side considerably reduces with reduction in particle diameter. The
dispersion of particles is due to the combined effect of fluctuating velocities and inertia of the particle. It is known that the turbulent dispersion
of large particles is dominated by their inherent inertia. This explains the
deepest penetration depth predicted for large particles (80 m). The reason for reduction in penetration depth for smaller particles is prehaps due
to the fluctuating velocity. The fluctuating velocity is predicted using a
random number generator with zero mean and standard deviation of one,
but theoretically, we should choose a random number generator with zero
mean and standard deviation between - to +, which is impractical due
to limited computer capabilities.
The spanwise velocity predictions are given in Fig. 4.21. The underprediction of spanwise velocities for all particle sizes is understandably
due to under-prediction of transverse velocity of the flow. However, the extent of under-prediction reduces with increasing particle diameter, which
again highlights that the heavier particles are less sensitive to turbulent
dispersion effects.
84
Figure 4.19: Flow field velocity and kinetic energy profiles.
: experimental data [24].

: computed profiles.
85
Figure 4.20: Streamwise velocity profiles of the particles.

86
Figure 4.21: Spanwise velocity profiles of the particles.

87
88
Chapter 5
Application I: Fluid Flow

and Particle Deposition in
Upper Airways
Contents
5.1 Introduction . . . . . .
5.2 Model preparation . .
5.3 Numerical methods . .
5.3.1 Fluid phase . . . .
5.3.2 Particle phase . .
5.4 Quality control . . . . .
5.5 Results and discussion
5.5.1 Fluid phase . . . .
5.5.2 Particle phase . .
5.6 Conclusions . . . . . . .
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89
91
93
93
94
94
97
97
101
109
5.1 Introduction
Although inhaled medication is the preferred method of drug administration to the lungs, aerosol deposition in the extrathoracic airways constitutes a major obstacle to efficient aerosol drug delivery to the intrathoracic airways. The overall geometrical complexity of the extrathoracic
pathway, with its bends and sudden cross sectional changes, poses serious
challenges for both experimental and computational studies. In addition,
89
CHAPTER 5. APPLICATION I: FLUID FLOW AND PARTICLE

DEPOSITION IN UPPER AIRWAYS
experimental aerosol deposition data obtained on various realistic upper
airway casts indicate considerable intra- and inter-subject variability of
the extrathoracic airway deposition [58]. The influence of the inlet of the
aerosol device, as well as individual mouth and trachea morphology on local and total aerosol deposition suggests that individualized computation
of extrathoracic deposition would result in more accurate estimation of the
amount of aerosol available to the deeper lung for a given patient or for
a given aerosol device. Assuming that individualized imaging of the extrathoracic airway can be obtained, an individualized estimate of aerosol
deposition would require a computational fluid dynamics (CFD) simulation that can be performed on an unstructured mesh with an appropriate
particle tracking module. Indeed, the complexity of a realistic structure
and the distorted nature of its walls make it difficult to mesh with a structured grid.
Previous studies have used upper airway models with varying degrees of
geometrical simplification for simulation or experimental studies of deposition [167, 40, 87, 171, 102]. The deposition study undertaken by Grgic et al.
[58] in seven casts of realistic extrathoracic models, which were thought to
be representative of magnetic resonance imaging scans obtained in 80 subjects, showed pronounced inter-subject deposition variability attributed to
the variations in the morphological dimensions with individuals studied.
While acknowledging the necessity for individualized aerosol deposition
studies, these authors also developed an empirical deposition curve similar to the most widely used Stahlhofen curve [142], which could account
for geometrical differences such that different deposition curves would collapse onto one curve. This was done by incorporating a critical length
scale which is characteristic of the geometry, into the definition of the
Stokes number. In the case of total deposition, Grgic et al. [58] used a socalled equivalent diameter, computed on basis of the overall geometry volume and its total centerline path length. A supplementary dependence on
Re, observed experimentally, was also incorporated and the best fit curve
showed a dependence on the product Stk 1.91 Re0.707 . A similar approach
was used in the experimental study by DeHaan and Finlay[40] where inlet diameter was the crucial length introduced into the definition of Stokes
number to compute mouth deposition. In this case, the deposition curve
only contained Stk 1.91 .
Based on the recent experimental observations on inter-subject variability
of the extrathoracic airway deposition, the need for considering realistic
model for CFD study is recognized and an efficient Lagrangian particle
tracking module for unstructured grids is developed to handle complex ge90

ometrical features. The details of Lagrangian modeling are as explained in
Chapter 4. Even though the concept of unstructured grids exists since long,
the practical applicability is still under budding stage, especially for twophase simulations. In this view, the present work is the first step towards
applicability of unstructured grids for biomedical applications which is by
far the only option to remove expensive experiments for realistic geometry configurations. To the best of our knowledge, these are the first CFD
simulations of particle deposition in a truly realistic extrathoracic airway
geometry.
5.2 Model preparation

Local ethics approval was obtained for a multi-slice CT imaging study in
five otherwise healthy never-smoker male subjects who were referred for
lung imaging due to possible low concentration occupational asbestos exposure. CT images were acquired using a Sensation 16 CT-scanner with
following settings: acquisition 160.75 mm, reconstruction slice thickness
1mm, pitch 1.25, rotation time 0.5 seconds, Care dose, reference mAS 100,
KV 120, Medium filter B45f. An approximately oval shaped mouth-piece
was used with major axis 17.36 mm and the minor axis 11.68 mm. Nose
clamps were used to prevent nose breathing. Imaging was initiated above
the nasal cavity and synchronized to start with the subject slowly inhaling at about 15-20 l/min to near total lung capacity where a breath hold
was inserted to complete data acquisition just below the carina. An example of one such CT-scan is as shown in the Fig. 5.1. From the scans obtained on the five subjects, one representative image of upper and central
airway anatomy was selected by the pulmonary radiologist and pneumologist. The multi-slice CT images were imported in to a 3D reconstruction
software Amira 4.0 and a raw upper and central airway 3D geometry was
constructed by triangulation.
The highly irregular and complex nature of the model (Fig. 5.1) makes
the creation of a structured grid tedious and work-intensive. For such
complex geometries, unstructured meshes are more feasible. Using Numecas unstructured grid generator - Hexpress (2.2), an all-hexahedral
unstructured mesh is generated.
91

Figure 5.1: A: Sample of a CT-Scan; B: The reconstructed 3D airway geometry with

different angle views of mouth cavity.
92

5.3
5.3.1
Numerical methods
Fluid phase
The computational domain is imported into Numeca (Fine/Hexa 2.3-1) compressible Reynolds-Averaged-Navier-Stokes (RANS) solver. The basic RANS
equation in a cartesian frame of reference integrated over a control volume
V is expressed as,
( ( (
V
dV +
t
( (
+ =
F+ dS
( (
+
+ dS
Q
(5.1)
The conservative variables being density (), 3 components of velocity

(U, V, W ) or energy (E). F and Q represents inviscid and viscous flux
respectively. In the low subsonic Mach number regime, time-marching
algorithms designed for compressible flows show a pronounced lack of efficiency due to large disparity of acoustic wave speed u+c compared to shear
and entropy waves which are convected at fluid speed u. This problem
is overcome by bringing a correction to discretization of the conservation
equations called preconditioning. The preconditioning matrix used here is
a combination of those suggested by Turkel[147] and Choi and Merkle[26].
The central scheme with Jameson type dissipation [75] is used for spatial
discretization. A fourth order Runge-Kutta scheme is used for time integration. Multigrid V-cycle strategy [67] with three grid levels is used for
convergence acceleration. The flow is assumed to be converged when the
dimensionless mass and momentum residuals were less than 10 3 .
The flow is modeled using low-Reynolds-number shear-stress-transport k
turbulence model of Menter [105], with the recent modification brought
to the eddy viscosity by Menter et al. [106]. The value of turbulent kinetic
energy at the inlet is prescribed assuming 5% turbulence intensity. When
the air is inspired from still atmosphere, the turbulence intensity levels
will generally be very small, however, the mist of aerosols coming from the
inhaler may enhance the turbulence intensity at the inlet. Heenan et al.
[64] noted that varying turbulence boundary conditions had little effect on
the final results in their simulations on idealized mouth-throat geometry
with similar flow rates as in our simulations. We specifically carried out
three different simulations by plugging 1%, 5% and 10% turbulence intensities respectively at the inlet. The maximum difference in total deposition
of a mixture of five different particle diameters (2, 4, 6, 8 and 10 m) was
seen to be less than 1.9%, signifying the insensitivity of particle deposition on the inlet turbulence intensity. This is understandably so because
93

Figure 5.2: Left: Normalized Axial velocity contour; Right: Normalized kinetic
energy contour.
the increase in turbulent kinetic energy levels is mainly triggered by the

complex geometrical features of the mouth-throat geometry.
5.3.2
Particle phase
With a view of efficient particle tracking on unstructured grids, a stochastic Lagrangian trajectory model was implemented in the flow solver of Numeca. The details of Lagrangian modeling are as described in Chapter
4.
5.4
Quality control
The reliability of fluid flow solver using the present LRN SST k model
to simulate transitional flow is validated by performing a simulation in
an axisymmetric tubular flow with stenosis [7] at a transitional Reynolds
number of 2000. The normalized axial velocity contours and kinetic energy
contours are shown in Fig. 5.2. Two dimensional cross-sectional velocities at different diameters downstream of stenosis (Fig. 5.3) compare well
94

z = 0d
u/uin
3
2
1
0
0
5
3
Exp. data (Ahmed 1983)
LRN kw (Zhang &
Kleinstreuer 2002)
SST kw (present)
0.5
r/R
z = 2.5d
2
1
0
1
0
5
0
5
0.5
z = 5d
z = 1d
0.5
0.5
z = 4d
0.5
z = 6d
0.5
Figure 5.3: Comparison of normalized axial velocity (at different sections downstream of the glottis) for the constricted tube at Re = 2000 with the experimental data of Ahmed and Giddens[7] and the simulations of Zhang and
Kleinstreuer[168].
95

Figure 5.4: Velocity magnitude at section A-B near glottis for 3 different grid sizes
at an inhalation flow rate of 60 l/min.
with the experimental data of Ahmed and Giddens[7] and the LRN k
model simulations of Zhang and Kleinstreuer[168] which is suggested to
be the best readily available LRN turbulence model. The presently employed LRN SST model was able to adequately predict the uniform flow at
the glottis and the rapid decrease in velocity at z = 4d due to flow transition. The peak velocities in the center of the domain at z = 2.5d and z = 4d
are also comparatively well predicted.
As we are dealing with transitional flow, it is certain that few portions
of the flow will remain locally laminar. We performed both laminar and
turbulent simulations for a very low flow rate of 3 l/min which is certainly
laminar and compared the velocity profiles at different sections in the geometry. The present LRN k model was able to reproduce the laminar
flow behavior which gave further confidence in the turbulence model employed.
The adequacy of grid resolution is tested by verifying both fluid and particle results. The fluid results are checked on three different mesh sizes at
the maximum flow rate of 60 l/min. In Fig. 5.4 we see that the velocity
magnitudes taken at a cut-section near the glottis region agrees well for
550,000 and 950,000 meshes. Also, the total pressure drop from inlet to
outlet for both meshes varied only by 0.5 Pa.
The effect of grid-resolution on the particle deposition is tested by considering two different mesh sizes of 550,000 and 950,000. Three different
96

particle diameters (2, 8 and 14 m) and two different flow rates of 30 and
60 l/min were considered. The maximum difference in total deposition did
not exceed 4%. Hence the 550,000 mesh suffices for accurate flow and particle simulations.
The effect of total number of injected particles on the deposition percentage was also tested by considering 1500 and 3500 particle injections. Four
different particle diameters (2, 6, 10 and 20 m) at flow rates of 30 and 60
l/min were tested. The maximum difference in total deposition was seen to
be less than 2% and hence 1500 particles suffice for accurate prediction of
deposition percentage. This observation is consistent with that of Matida
et al. [102] who stated that their simulated deposition results on an idealized geometry didnt change when the number of particles injected were
changed from 1000 to 10,000.
5.5 Results and discussion

5.5.1
Fluid phase
Fig. 5.5 shows contours of the velocity magnitude for sedentary breathing
condition, i.e., 15 l/min. In addition to velocity magnitude contours, the
cross-sectional views also show the secondary velocity vector lines. The
cross-sections D1-D2, E1-E2 and F1-F2 are approximately one, three and
six diameters from C1-C2 which marks the larynx (glottis). We refer the
side towards C1 as posterior and the side towards C2 as anterior. The
axial-velocity profiles are highly skewed with many recirculation zones due
to the complex nature of the domain. The flow entering through mouthpiece impinges on the tongue and accelerates as it moves through the middle region of the mouth due to the reduction in cross-sectional area. The
axial velocity profile at section A1-A2 shows that the maximum velocity
is not at the center as in most of simplified geometries, but is inclined
towards anterior side. This feature may have considerable effect on the
particles and may result in higher mouth deposition compared to simplified geometries where the mouth region is symmetric. The presence of the
uvula just next to the soft palate at the end of mouth region (Fig. 5.1) forms
a huge restriction for the airway passage resulting in the flow entering the
pharynx in the form of a jet which is from hereon referred to as oropharyngeal jet. The streakline representation in Fig. 5.5 shows recirculation
regions in the epiglottis and upper part of pharynx region as a result of the
oropharyngeal jet. When the flow bends from the mouth to the pharynx,
it experiences complex secondary motions due to the pressure gradient.
Section B1-B2 shows three distinct secondary vortices as the flow moves
97

Figure 5.5: Velocity profiles (cm/s) in the oral airway model at 15 l/min. Above:
Mid plane velocity contour and 2-D streaklines. Below: Axial velocity contours and
secondary velocity vector lines at six different cross-sections.
98

Figure 5.6: Velocity profiles (cm/s) in the oral airway model at 60 l/min. Above:
Mid plane velocity contour and 2-D Streaklines. Below: Axial velocity contours
and secondary velocity vector lines at six different cross-sections.
99

downstream of the pharynx. A sharp step at the end of pharynx on the
posterior side results in a laryngeal jet beginning from the glottal region
and developing towards the anterior side of trachea. The secondary motions at the glottis region (C1-C2) are considerably damped out in a very
short span between B1-B2 and C1-C2. The posterior side peak velocity at
C1-C2 develops towards the anterior side as the flow moves downstream.
At three diameters downstream, secondary motions again become more
prevalent due to highly skewed laryngeal jet and partly also because of
the complex nature of trachea. It is interesting to note that the trachea
is at an inclination to the mouth inlet face, where as most of the simplified geometries assume a straight tube parallel to inlet face. This indeed
may also increase particle deposition, especially those with higher stokes
number due to inertial effects. As a result of laryngeal jet, there is a big
flow separation on the posterior side as seen in the streakline representation. Heenan et al. [64] observed that the development of the laryngeal
jet widely varies across studies and that it is essentially due to the variation in cross-sectional shapes used to model the glottis. Also, Brouns et
al. [20] studied the influence of glottic aperture on the tracheal flow in
an idealized mouth-throat geometry and showed how the interaction between glottis size and shape on the one hand, and the geometry of the
mouth-throat model on the other hand, is crucial to the laryngeal jet and
the overall fluid flow field.
The kinetic energy plot in Fig. 5.7 shows amplification and transition to
turbulence soon after the glottis region. In the previous simulations on
an idealized airway model, Kleinstreuer and Zhang[87] had indicated that
the turbulence intensity prescribed at inlet is damped out and laminar flow
prevails throughout the geometry under such low flow rate condition. By
contrast, Heenan et al. [64] studied the effect of inlet boundary condition
in an idealized oropharynx model and found transitional flow regimes at
similar flow rates. Stapleton et al. [143] refers to a previous experimental
study where turbulent structures were found in the flow of tracheal casts
for inhalation flow rates above 3 l/min. From these different observations,
we conclude that the degree of turbulence critically depends on the degree
of geometrical complexity of the extrathoracic airway model.
At 60 l/min (Fig. 5.6), the flow features in the mouth and the pharynx
remain very similar to those obtained for 15 l/min. However, the laryngeal jet which develops soon after the glottis region, expands more quickly
and transfers more momentum to the flow downstream. Corcoran and
Chigier[28] observed a similar behavior in their phase doppler study of the
laryngeal jet in a cast of larynx/trachea. The length of the separated flow
100

Figure 5.7: Turbulent kinetic energy profile (m 2 /s2 ) in the oral airway model for
15 l/min (left) and 60 l/min (right).
zone in the trachea due to the laryngeal jet reduces considerably compared
to 15 l/min due to faster expansion of the jet.
Fig. 5.8 shows the area-averaged pressure drop (p p in ) across the airway
model for 15, 30 and 60 l/min. The pressure drop remains very nominal
throughout the airway geometry for 15 l/min. For 30 and 60 l/min, we see
that the major losses are in the mouth and larynx region. The drop in the
second half of the mouth and the larynx region is a direct result of the flow
acceleration.
5.5.2
Particle phase
Total deposition
Since the flow velocities in the extrathoracic airways are relatively high
and the residence time of the particles are short, inertial impaction is the
dominant mechanism for particle deposition. Hence it is common to represent the extrathoracic deposition as a function of inertial impaction parameter p d2p Q. However, the experimental data available in literature show a
lot of scatter when plotted with respect to the inertial parameter and this
101

10
Mouth
Pharynx Larynx
Trachea
Pressure Drop (Pa)
10
20
15 l/min
30 l/min
60 l/min
30
40
50
60
70
0
50
100
150
200
Axial Length (mm)
250
300
Figure 5.8: Area average pressure drop (p pin ) (Pa) at every 5mm along the axial
direction.
100
Deposition (%)
80
Experimental fit (Grgic 2004)

Simulated deposition
60
40
20
0 3
10
10
10
Stk Re0.37
10
10
Figure 5.9: Simulated total deposition (open symbols) as a function of Stokes number and Reynolds as defined in Grgic et al. [58]. The experimental best fit curve is
also represented (solid line).
102

Oral Cavity Deposition (%)
100
80
Experimental fit (DeHaan 2004)

Simulated deposition
95% prediction limits
60
40
20
0
3
10
10
10
Stk
Figure 5.10: Simulated oral cavity deposition (%) as a function of Stokes number
as defined in DeHaan and Finlay[40]. The solid line represents the experimental
best fit curve.
scatter is generally attributed to inter-subject variations. In order to take

the geometry into account, Grgic et al. [58] proposed to plot the extrathoracic deposition as a function of Stokes number. First, the Stokes number
is defined as p d2p U/18D, where the mean diameter, D, is calculated using the cast volume
6 V and the path length L of the central sagittal line of
the model (D = 2 V /L). The corresponding velocity scale is calculated
as U = QL/V . Finally, a Reynolds number dependence is incorporated by
plotting deposition data against Stk 1.91 Re0.707 . Using this representation,
our CFD simulated total deposition data are plotted in Fig. 5.9, along with
the experimental based best fit curve of Grgic et al. [58]. While the overall
deposition prediction pattern agreed with the experimental fit, there still
remained considerable over-prediction in the low Stokes-number range.
This observation is consistent with that of Matida et al. [102] in their idealized model and, Xi and Longest [161] in their CT-based realistic model of
the upper airways.
For the specific purpose of aerosol deposition in the mouth cavity, we used
the method of DeHaan and Finlay[40], which in our application, consisted
of defining the Stokes number as p d2p Cc (U + 2k 0.5 )/18D, where U is the
average inlet velocity, D is the inlet diameter, and k is the inlet turbulent
kinetic energy. Using this representation, our CFD simulated mouth de103

Figure 5.11: Simulated deposition values (expressed as % of particles at model

inlet) in three model subparts.
position data are plotted in Fig. 5.10. Again, the good agreement between
simulated mouth deposition and the best fit curve lends further support to
the validity of our computational methods.
Particle deposition in model subparts
Fig. 5.11 shows that the total deposition increases with increase in particle diameter, suggesting that inertial impaction is the dominant deposition mechanism. The relative deposition in each model subpart, expressed
as a fraction of total aerosol entering the mouth, is largely unaffected by
change in flow rate or particle diameter. Note however that for particles
above 12 m in the case of 60 l/min, the mouth deposition becomes so high
that the subsequent pharynx and larynx-trachea deposition reduces with
further increase in particle diameter. Clearly, the mouth region acts as an
effective filter and is responsible for a major percentage of total deposition.
This agrees with the experimental observation of Grgic et al. [58] where
104

the oral cavity accounted for most intense deposition in six out of the seven
realistic upper airway casts studied. In contrast, studies on an idealized
oral airway model (e.g.,[171, 59]) show considerably smaller mouth depositions, which maybe an indication of the need for realistic models of the
mouth cavity to reliably estimate mouth deposition.
In addition to the deposition values in the model subparts, as represented
in Fig. 5.11, a more detailed description of the deposition patterns of individual particles is shown in Fig. 5.12. Since compendious representation of
3D deposition patters is often difficult, we project the particle coordinates
onto a 2D plane. Fig. 5.12 shows the particle deposition coordinates along
with a best possible 2D cutting plane that passes through the center of the
domain. Note that the geometry is not symmetric and the cutting plane
does not cover the outermost boundary of the domain, which explains why
some particles appear to be deposited outside this plane.
2 m: For sedentary breathing, there is almost no deposition in the oval
shaped mouth-piece where as for normal breathing, there is a concentrated
deposition. This can be attributed to increase in the magnitude of turbulent fluctuations (which is proportional to the flow kinetic energy) when
compared to sedentary breathing. For heavy breathing condition, in addition to mouth-piece deposition, inertial forces become important and we
observe a concentrated deposition at the beginning of tongue. Deposition
in pharynx remains low for all three flow rates showing that most of the
particles which escape deposition in the first half of mouth will reach the
outlet (end of trachea).
6 m: Relative deposition patterns remain almost the same as of 2 m
with slightly increased deposition in second half of the mouth and in the
pharynx region.
10 m: For both sedentary and and normal breathing condition, there
are some particles deposited at the end of the tongue region as the flow
bends from mouth to pharynx. As the particles move downstream of the
pharynx, they experience a sharp step at the end of pharynx (beginning
of larynx) resulting in some regional deposition which increases with increase in flow rate. In addition to these depositions, for heavy breathing,
we observe considerable deposition towards the end of the mouth in the
uvula region (Fig. 5.1) because the inertia of particles dominates and the
particles can no more follow the sudden bend in the flow from mouth to
pharynx. There is also a concentrated deposition on the outer wall of the
pharynx which is due to the direct impingement of oropharyngeal jet on to
105

30 l/min
60 l/min
18 m
14 m
10 m
6 m
2 m
15 l/min
Figure 5.12: Two-dimensional representation of individual particle deposition.
106

22
1 m
3 m
5 m
7 m
20
18
Deposition (%)
16
14
12
10
8
6
4
2
0
0
10
20
30
40
Flow rate (l/min)
50
60
(a)
22
1 m
3 m
5 m
7 m
20
Total deposition (%)
18
16
14
12
10
8
6
4
2
0
10
15
20
Flow rate (l/min)
25
30
(b)
Figure 5.13: (a) Simulated deposition percentage in the model as a function of

particle size and inhalatory mass flow. (b) Total deposition in the airway model
which is a sum of mouth-throat model deposition (present simulations) and the
lung model deposition extending from the trachea up to the segmental bronchi
[151]. Please note the different scales on x-axis between figures (a) and (b).
107

the outer surface of pharynx.
14 m: For sedentary and normal breathing, the relative deposition patterns remain same as that of 10 m. For heavy breathing we see additional
deposition region at the middle region of the mouth on its outer walls which
is clearly due to increased inertia forces.
18 m: For sedentary breathing, in addition to previous observations at
14 m, we see a chunk of particles trapped in the cavity region soon after
the mouth-piece where there is flow recirculation. The number of particles
trapped in this region decreases with increase in flow rate suggesting that
it is mostly the turbulence effect. For normal breathing, we observe few
small patches of deposition in the middle region of mouth which were not
seen for 14 m, suggesting the beginning of inertial effect in this region.
There is also a considerable concentration on the outer wall of pharynx
due to the oropharyngeal jet. For heavy breathing, the deposition patterns
are less scattered and more intensely concentrated at the mouth-piece, beginning of tongue and upper wall of the middle mouth region. When we
compare the mouth-piece deposition with that of 2 m, it is evident that
most of the particles are deposited on lower half of the mouth-piece, suggesting that inertia dominates and the turbulence effects are not at all felt.
Finally, Fig. 5.13(a) shows the simulated deposition as a function of flow
rate, for particle diameters between 1 and 7 m, including also a flow rate
as low as 3 l/min, to verify whether such a low flow rate generates greater
deposition as gravity becomes important. This was clearly the case, and as
expected, this gravitational effect at 3 l/min was amplified for the heavier
particles. For the range of flows between 3 and 30 l/min in Fig. 5.13(a), simulated deposition rates have been reported for a 10-generation bronchial
model by van Ertbruggen et al. [151]. When combining our own deposition
efficiencies obtained in mouth and trachea with those predicted from the
bronchial model [151], i.e., as if the latter were directly appended to the
end of our trachea, we can obtain a rough estimate of total deposition for
different combinations of flow and particle diameter which is shown in Fig.
5.13(b). These cumulated deposition data indicate that for normal breathing conditions, inhalatory deposition in the upper and central airways for
the particle size 5 m, which is usually referred to as the upper limit of
the respirable range for inhalation drugs, does not exceed 12% when the
aerosol is at rest before inhalation (e.g., inhaled from a spacer).
108

5.6
Conclusions
The original contributions of this work are:

1. The realistic airway flow simulations show that the laminar to turbulent transition, especially at low flow rates is sensitive to the complexity of the airway model. Flow transition was seen soon after the
glottis region for a low flow rate of 15 l/min, which are not reported
in the simplified geometry simulations found in the literature.
2. Mouth region acts as an effective filter and is responsible for major
percentage of total deposition, which again is not the case with simplified models. This indicates the need for more realistic representation of mouth cavity to reliably predict regional mouth deposition in
simplified models.
3. The deposition due to sedimentation becomes important for heavier
particles at very low flow rates resulting in higher depositions compared to the depositions at a considerably higher flow rate.
4. The cumulative depositions (upper airway + central bronchial tree)
indicate that for normal breathing conditions, inhalatory deposition
in the upper and central airway tree for the particle size 5 m, which
is usually referred to as the upper limit of the respirable range for
inhalation drugs, does not exceed 12%.
109

110
Chapter 6
Application II: Convective

Mixing in Upper Airways
Contents
6.1 Introduction . . . . . . . . . . . . . . . . . .
6.2 Materials and methods . . . . . . . . . . . .
6.2.1 Experimental methods . . . . . . . . .
6.2.2 Numerical methods and quality control
6.3 Theoretical axial dispersion coefficient .
6.4 Results . . . . . . . . . . . . . . . . . . . . . .
6.4.1 Experimental results . . . . . . . . . .
6.4.2 CFD results . . . . . . . . . . . . . . . .
6.5 Discussion . . . . . . . . . . . . . . . . . . . .
6.6 Limitations . . . . . . . . . . . . . . . . . . .
6.7 Conclusions . . . . . . . . . . . . . . . . . . .
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111
113
113
116
117
117
117
120
120
126
127
6.1 Introduction
The upper airway geometry with its glottic narrowing embedded in a tortuous oropharyngeal pathway, affects aerosol deposition and dispersion
on its way to the lungs. Previous experimental and numerical studies
have mainly concentrated on aerosol deposition, using realistic upper airway models with varying degrees of geometrical simplification [76, 102].
Aerosol transport is generally considered under steady flow conditions, except for a recent work by Grgic et al. [60], where small volumes of aerosols
111
CHAPTER 6. APPLICATION II: CONVECTIVE MIXING IN UPPER

AIRWAYS
(aerosol boluses) delivered in different stages of the inhalatory phase, were
used to study the effect of flow accelerations on aerosol deposition in the
upper airway. Besides the deposition of an aerosol bolus, its degree of volumetric dispersion also offers a sensitive tool to characterize aerosol transport. Indeed, aerosol boluses delivered to different lung depths are being
used to quantify all aerosol mixing processes, except for Brownian diffusion, that are collectively referred to as convective mixing [34]. Several
sources of convective mixing have been identified [32, 121], such as turbulent mixing, cardiogenic mixing, and asymmetry between inhalatory and
exhalatory flow patterns (e.g., secondary flows, ventilation heterogeneity).
These effects are operational to a different extent at different lung depths.
They can be quantified experimentally via their effect on aerosol boluses
(typically confined to an initial volume of 50-100 ml) inhaled to various
lung depths and recovered at the mouth during exhalation.
The degree to which aerosol boluses disperse in extra- and intrathoracic
airways has been the subject of several studies [36, 66, 121, 128, 149, 148].
It has been suggested that convective mixing of boluses inhaled to penetration volumes between 100 ml (past the carina) and 200 ml (end of
anatomical dead space) can be accounted for by empirical formulas for dispersion in a network of branching conductive airways, such as those proposed by Scherer et al. [125], Ultman [148] or van der Kooij et al. [150].
Rosenthal et al. [121] speculated that the larynx may elicit a degree of
bolus dispersion comparable to that in the conductive airways, and concluded their study with a call for a dedicated study of bolus dispersion in
the larynx. Simone et al. [132] studied the transport of He and SF 6 boluses through a larynx cast inserted in a straight tube. They pointed out
that the laryngeal jet would tend to increase dispersion and that the turbulence propagated from the high shear boundary of the jet would tend
to decrease dispersion. Ultman et al. [149] showed in 5 normal subjects,
that effective axial dispersion undergone by He and SF 6 boluses in the
first 80 ml of the upper airway ranged 290-390 cm 2 /s. This is in contrast
with the effective axial dispersion of 2400 cm 2 /s attributed to the orophraynx in order to match simulated and experimental values of aerosol bolus
dispersion for very shallow boluses [33]; the same study obtained excellent agreement between simulated and experimental bolus dispersion as
a function of volumetric depth in conductive and alveolated airways. In
recent years, sophisticated 3D computational fluid dynamic (CFD) simulation studies in realistic upper airway geometries (e.g., [94]) do provide
detailed predictions of flow patterns, including laryngeal jets, vortices and
turbulent intensities. However, the accuracy of these CFD simulations remains difficult to validate, and a relatively easy way to do so, would be to
112

AIRWAYS
predict the dispersive effect on an aerosol bolus. This simulated bolus then
represents a relevant physiological measure that can be obtained experimentally for comparison.
Whether it is for the study of convective mixing or for medication targeting, an aerosol bolus inhaled to any given lung depth must transit the
upper airway, and it is crucial to quantitatively predict its dispersive effect, which is currently lacking. We therefore aimed to quantify bolus dispersion by carrying out aerosol bolus experiments on a physical cast of a
realistic upper airway model [19] and by performing corresponding CFD
simulations in exactly the same 3D geometry. We tested the hypotheses
that bolus dispersion may be different in inhalatory and exhalatory flow
directions, and that bolus dispersion in either flow direction may deviate
from the one dictated by a simple Gaussian from which a 1D axial dispersion coefficient is derived. Irrespective of the exact experimental bolus
shape, it represents a physiological measure that can be used to test the
accuracy of CFD simulation methods currently employed to study aerosol
transport in the upper airway.
6.2 Materials and methods

6.2.1
Experimental methods
The 3D geometry of the upper airway model (UAM) was retrieved from
previous work [19] and cast into a silicone hollow model, assembled in
two halves (one half is depicted in Fig. 6.1). Briefly, the UAM geometry
had been previously derived from a smoothened representative upper airway geometry obtained with multi-slice CT imaging on five healthy neversmoking male subjects (average age 38 years; range 26-52 years). Importantly, CT imaging had been initiated above the nasal cavity and synchronized with inhalation in order to obtain a representative glottic area during slow inhalation. Glottic area was 125 mm2 in this UAM model, total
UAM volume was 90.6 cm3 and the average UAM cross section amounted
to 2.78 cm2 .
The aerosol generating system consisted of an ACORN II nebulizer (Marquest Medical Products, Englewood, CO) from which a diluted suspension
of polystyrene latex 1 m particles (Duke Scientific, Palo Alto CA) was
aerosolized and passed via a silica-gel drying tunnel, into a the 50 ml tube
between valves 1 and 2. The aerosol continuously entered the 50 ml tube
via one sliding valve (2) and was evacuated through a filter via another
sliding valve (1) so as to obtain a steady concentration of aerosol in the 50
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AIRWAYS
flow meter
aerosol
UAM cast
photometer
syringe
Figure 6.1: Schematic view of the experimental setup used for bolus dispersion
measurement in a 3D hollow cast of the upper airway model (UAM). A dry 1 m
aerosol contained in a 50 ml tube located between valves 1 and 2 is aspired through
the UAM, and the photometer beyond it, with a 2 liter syringe.
114

AIRWAYS
ml tube. In preparation of the 50 ml aerosol delivery to the UAM, valves
1 and 2 were then switched to obtain an open passage between the air
from behind the flow meter and the syringe. By having the syringe aspire a volume of 2 liters, the 50 ml aerosol was pulled through the UAM
and the photometer (PARI,Starnberg, Germany); the syringe was operated
manually using visual feedback from the flow meter. Throughout the experiment, the photometer continuously recorded the particle concentration
as a function of aspired volume; data acquisition was at 100 Hz.
Aerosol bolus tests were performed with the UAM in the inhalatory position (as depicted in Fig. 6.1) and alternating target flows between 250
ml/s and 500 ml/s in a series of 12 tests in total. At these two flows,
Reynolds numbers were about 1300 and 2600, respectively. A similar test
sequence was performed with the UAM in the exhalatory position, i.e., by
connecting the tracheal end to valve 1 and UAM mouthpiece end to the
photometer. In both in- and exhalatory UAM configuration, the aerosol
was made to enter the UAM via a 90 o bend beyond valve 1. Using a 90 o
bend has been shown to render the incoming aerosol profile flatter than
when delivered in a straight line [152], enabling a better comparison with
a CFD simulated uniform injection of particles at the model inlet. Also,
based on our previous experience with a similar setup where boluses could
be monitored during both inhalation and exhalation by placing the photometer in between valve 1 and an actively breathing subject [154, 155],
the bolus was seen to remain well contained within a 50 ml volume upon
entering the subject. Preliminary tests on the present setup confirmed
that this was also the case for a bolus entering the UAM.
Bolus dispersion was quantified in terms of its halfwidth, i.e., the volumetric width between concentrations at half peak height, and of its standard
deviation, i.e., the second moment of the volume dependent bolus concentration curve [13]. Halfwidths and standard deviations were indicated by
HWin and SDin for inhalation, and by HWex and SDex for exhalation; all
are obtained by a simple formula [121] for each flow direction. For instance, HWin is computed as,
2
2
2
HWin = HWendtrachea
HWmouth
(6.1)
with UAM in inhalatory configuration (i.e., bolus injected at the mouth and
recovered at end of trachea), and HW ex is computed as,
2
2
2
HWex = HWmouth
HWendtrachea
(6.2)
with UAM in exhalatory configuration (i.e., bolus injected at the end of the
115

AIRWAYS
trachea and recovered at the mouth). The same type of formulas are used
to obtain SDin and SDex .
6.2.2
Numerical methods and quality control
Fluid phase
Using the existing UAM 3D geometrical boundaries of Fig. 6.1, a preliminary grid resolution study was conducted. Comparing flow fields obtained
with unstructured hexahedral meshes of either 800,000 or 2,170,000 cells
(Hexpress, Numeca, Brussels, Belgium) had indicated that the differences
in velocity magnitude in a cross-section downstream of the larynx were
negligible. Therefore, the UAM with the hexahedral mesh containing 800,000
cells was used here. All flow field computations were performed using a
commercial CFD software package (Fluent 6.3, ANSYS, Canonsburg, PA).
An incompressible Reynolds Averaged Navier Stokes (RANS) solver was
employed to simulate the fluid flow, and a two equation shear stress transport k model was used to model the turbulence. The k model has
been previously proposed to be the most adequate turbulence model for
simulating transitional flows in the upper airways [102, 150]. For the spatial discretization, a second-order upwind scheme was used. A third-order
MUSCL scheme was used for the momentum and the k equation respectively. The SIMPLE algorithm was used for pressure-velocity coupling. A
typical simulation of the flow field to obtain a convergence level of three
orders of magnitude took approximately 11-12 hours on a 2.4 MHz dual
core processor (AMD Opteron, Sunnyvale, CA).
Particle phase
For the particle phase, we used an Eddy Interaction Model (EIM) where
the fluctuating part of the instantaneous velocity is modeled assuming
isotropic turbulence and assigned to an eddy with known life time and
length scale. More details on the EIM is described in Chapter 4. One micron particles were injected homogeneously at the UAM inlet cross section
so as to obtain a uniform particle number per surface area distribution over
the entire cross-section. A preliminary particle number study injecting either 10,000, 15,000 or 30,000 particles had indicated that the halfwidths
of particle concentration profiles obtained at the geometry outlet differed
by 0.7% between 10,000 and 30,000 particles and by 0.6% between 15,000
and 30,000 particles. For the present simulations, 15,000 particles were
considered and trapezoidal scheme for particle tracking was employed. Approximately 5 hours were required to track 15,000 particles.
116

AIRWAYS
6.3
Theoretical axial dispersion coefficient
In an attempt to find a one dimensional dispersion coefficient D to characterize the axial dispersion undergone by an aerosol bolus in the UAM, the
particle profile recovered at the model outlet was compared with the analytical solution of the 1D diffusion equation corresponding to an aerosol
profile initially confined between axial locations x = h and x = +h [29]
,
-$
#
,
1
h + x u0 t
h x + u0 t
C(x, t) =
+ erf
(6.3)
erf
2
2 Dt
2 Dt
where C is particle number concentration as a function of space and time,

x is axial pathway length; D is the axial dispersion coefficient and u 0 is
an average velocity defined as the ratio of flow rate (250 ml/s or 500 ml/s)
over average cross section (2.78 cm 2 ). With a homogeneous injection of the
15,000 particles at the UAM inlet surface, the injected aerosol bolus in the
CFD simulations effectively occupied an initial volume of 0.125 cm 3 , corresponding to an initial aerosol bolus slab thickness of 0.045 cm (= 2.h) at
the initial bolus position (x = 0). When considering such a bolus passing a
fixed location, for instance at x = 32.6 cm (i.e., UAM length), the transformation of the time-dependent concentration trace into a volume-dependent
one via flow rate, shows a halfwidth which increases as a function of D up
to approximately 2500 cm2 /s and then levels off (Fig. 6.2A). By contrast,
when considering the spatial dispersion of typical concentration curves obtained with Eq. 6.3 at a fixed point in time (t = 0.05 s here), and varying
D, a steady increase of spatial dispersion with D is observed (Fig. 6.2B).
In this case, the flow rate does not interfere with halfwidth, since it merely
translates the entire diffusing bolus along the x-direction at a faster pace.
6.4
6.4.1
Results
Experimental results
Actual flows corresponding to bolus tests with the UAM in the inhalatory and exhalatory configuration and with a target flow of 250 ml/s were
26012(SD) ml/s and 26214(SD) ml/s respectively. For the UAM tests
with a target flow of 500 ml/s, actual inhalatory and exhalatory flows were
49728(SD) ml/s and 49038(SD) ml/s respectively. Six typical photometer traces corresponding to a bolus test with the UAM in the inhalatory
configuration are presented in Fig. 6.3A. In Fig. 6.3B, the representative traces of Fig. 6.3A are normalized to peak height, and compared to
the corresponding analytical solution of Eq. 6.3 for D = 200 cm 2 /s and
D = 250 cm2 /s. While neither option perfectly captures the entire bolus
117

AIRWAYS
A
200
180
x=0
t=0
bolus halfwidth (ml) .
160
x=32.6cm
140
120
100
80
60
40
250ml/s
20
500ml/s
0
0
1000
2000
3000
4000
5000
D (cm /s)
30
x=0
t=0
bolus halfwidth (cm) .
25
t=0.05s
20
15
10
Eq(3)
!2Dt
0
0
1000
2000
3000
4000
5000
D (cm /s)
Figure 6.2: Panel A: Halfwidth computed from the 1D theoretical time dependent
concentration of a bolus recovered at x = 32.6 cm (i.e., the axial pathway length
between UAM in- and outlet), after being initially contained within a 0.045 cm
slab at x = 0 and transported towards x = 32.6 cm by diffusion and convective flow
(the latter is indicated by the block arrow). For each axial dispersion coefficient
D, the solution of Eq. 6.3 at x = 32.6 cm is transformed from a time-dependent
to a volume-dependent bolus (via flow rate), such that the volume difference at
half bolus peak height, i.e., the halfwidth, can be determined (circles:250 ml/s vs.
triangles:500 ml/s). Panel B: Halfwidth computed from the 1D theoretical spatial
concentration of a bolus at t = 0.05 s, after being initially contained within a 0.045
cm slab at x = 0 and transported by diffusion and convective flow (the latter is
indicated by the block arrow, but only introduces a spatial translation and does
not affect spatial halfwidth). For each axial dispersion coefficient D, halfwidth is
obtained as the x-difference at half peak height (in cm) of the solution of Eq. 6.3 for
a fixed t =0.05 s (solid circles); also represented is the axial bolus halfwidth given
by x = 2Dt with t = 0.05 s (dotted line) .
118

AIRWAYS
A
8
IN 250ml/s
IN 500ml/s
7
photometer signal (a.u.)
photometer signal (a.u.)
6
5
4
3
2
0
100
200
300
400
500
100
volume (ml)
200
300
400
500
volume (ml)
B
Experiment 250ml/s
Experiment 500ml/s
250ml/s; D=200cm2/s
500ml/s; D=200cm2/s
Experiment 250ml/s
Experiment 500ml/s
250ml/s; D=250cm2/s
500ml/s; D=250cm2/s
100%
concentration (%peak) .
concentration (%peak) .
100%
80%
60%
40%
20%
0%
80%
60%
40%
20%
0%
0
100
200
300
400
500
volume (ml)
100
200
300
400
500
volume (ml)
Figure 6.3: Panel A: Synchronized photometer traces with the UAM in the inhalatory configuration and a target flow of 250 or 500 ml/s (6 tests each); synchronization was arbitrarily set to have all bolus fronts aligned to 100 ml for clarity of representation. From each set of 6 curves, one representative photometer trace (solid
circles) is derived from which halfwidths are computed as indicated by the dotted
lines (HW = 89 ml and 84 ml for respective target flows of 250 or 500 ml/s). Panel
B: Combined representative photometer traces of Panel A for 250 and 500 ml/s
(solid circles), normalized to their peak bolus value, and set against corresponding
theoretical solutions of Eq. 6.3, considering an initial bolus volume of 50 ml (as in
experiments) with a effective axial dispersion coefficient D set to either 200 cm 2 /s
(left) or 250 cm2 /s (right); dotted and dashed lines refer to the theoretical traces
for 250 and 500 ml/s respectively.
119

AIRWAYS
curve, particularly in its tail portion, the analytical solution corresponding
to D = 200 cm2 /s best matches the initial part of the bolus, including its
halfwidth, while the D = 250 cm2 /s solution somewhat better captures the
bolus tail. This is particularly true for D = 250 cm2 /s at a flow of 250 ml/s
(dotted line in the right panel of Fig. 6.3B), yet, at the expense of an overestimated bolus halfwidth.
Fig. 6.4 summarizes the average (SE) values of the experimental bolus
dispersion indices. Overall, there were small decreases in HW in , HWex ,
SDin and SDex with increasing flow rate, but none of the post-hoc pair-wise
comparisons reached significance. There were no statistically significant
differences between HW in and HWex or between SD in and SDex .
6.4.2
CFD results
CFD simulated inhalatory and exhalatory aerosol deposition in the UAM

was 3% and 4%, respectively for 250 ml/s and 8% and 9%, respectively for
500 ml/s. Fig. 6.5 shows the CFD simulated particle concentration traces
at the model outlet, which were normalized to their respective bolus peaks,
for 250 ml/s (thick solid lines) and 500 ml/s (normal solid lines). The bolus halfwidths corresponding to the CFD simulated particle concentration
curves were much smaller for exhalation than for inhalation at both 250
ml/s (HWin = 69 ml; HWex = 20 ml) and 500 ml/s (HWin = 49 ml; HWex
= 20 ml). Also superimposed on the inhalatory traces of Fig. 6.5A are the
corresponding analytical solutions from Eq. 6.3 with D = 200 cm 2 /s, for
250 ml/s (dotted lines) and 500 ml/s (dashed lines). In Fig. 6.5B, the analytical solution with D = 25 cm2 /s is also displayed, merely to illustrate
the degree of underestimation of axial bolus dispersion for the exhalatory
UAM configuration. The marked difference in halfwidth between the CFD
generated boluses in panels A and B of Fig. 6.5 is in contrast to the very
similar halfwidths obtained in bolus experiments with the UAM in inhalatory and exhalatory configuration (Fig. 6.4).
6.5 Discussion
With respect to the primary aim of this study, we have found that the
dispersion of an experimental aerosol bolus transiting a realistic model of
the upper airway including the trachea can be reasonably approximated
by a Gaussian fit (Eq. 6.3). The remaining discrepancy was in the bolus
tail, where the experimental bolus showed a slightly greater skew than
the Gaussian fit, especially at flow rates exceeding quiet breathing (> 250
120

AIRWAYS
inspiration (HWin)
100
expiration (HWex)
98
Bolus HW (ml)
96
94
92
90
88
86
84
82
80
0
200
400
600
flow rate (ml/s)
B
inspiration (SDin)
50
expiration (SDex)
49
Bolus SD (ml)
48
47
46
45
44
43
42
41
40
0
200
400
600
flow rate (ml/s)
Figure 6.4: Panel A: Experimental bolus halfwidth (meanSE) for target flows
of 250 and 500 ml/s with the UAM in the inhalatory (open circles) and exhalatory (solid circles) configuration. Panel B: Experimental bolus standard deviation
(meanSE) for target flows of 250 and 500 ml/s with the UAM in the inhalatory
(open circles) and exhalatory (solid circles) configuration.
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AIRWAYS
A
INSPIRATION
100%
CFD 250ml/s
CFD 500ml/s
250ml/s; D=200cm2/s
500ml/s; D=200cm2/s
part conc (% peak)
80%
60%
40%
20%
0%
0
50
100
150
200
250
300
volume (ml)
EXPIRATION
100%
CFD 250ml/s
CFD 500ml/s
250ml/s; D=25cm2/s
part conc (%peak)
80%
500ml/s; D=25cm2/s
60%
40%
20%
0%
0
50
100
150
200
250
300
volume (ml)
Figure 6.5: Panel A: CFD simulated outlet profiles with the UAM geometry in inhalatory configuration for flows of 250 ml/s (thick solid lines) and 500 ml/s (normal
solid lines) and corresponding theoretical solutions of Eq. 6.3, using D = 200 cm 2 /s
for both flows. Panel B: CFD simulated outlet profiles with the UAM geometry
in exhalatory configuration for flows of 250 ml/s (thick solid lines) and 500 ml/s
(normal solid lines) and corresponding theoretical solutions of Eq. 6.3, using D =
25 cm2 /s for both flows.
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AIRWAYS
ml/s). Depending on the physiological application, and whether it requires
to better capture the bolus peak and halfwidth or its tail, an effective axial dispersion of 200-250 cm2 /s adequately characterizes the dispersion
process in this segment of the airway tree. Inhalatory and exhalatory
boluses showed roughly the same bolus dispersion, and bolus dispersion
only slightly decreased by increasing flow from 250 to 500 ml/s. The CFD
numerical simulations reproduced experimental results for inhalation but
not for exhalation, warranting further scrutiny on the part of the numerical methods (turbulence models and parameters) used to describe transitional flows in structures such as the UAM used here.
Our experiments show that the upper airway geometry leads to a 80-90
ml wide bolus at the model outlet, for a 50 ml bolus at model inlet under quiet breathing conditions (250-500 ml/s) and in either inhalatory or
exhalatory flow direction. When correcting an average 85 ml bolus at
UAM outlet for the non-zero initial aerosol bolus according to Eqs. 6.1
and6
6.2, the net dispersion halfwidth HWin or HWex amounts to 69 ml
(=
(85ml)2 (50ml)2 ). For medical aerosols, this implies that a typical aerosol from a pressurized metered dose inhaler, which is typically
fired into a 250 ml holding chamber prior to inhalation, will undergo a net
dispersion in the upper airway (including the trachea) such that its volumetric
6 dispersion beyond that point becomes no more than 260 ml (i.e.,
(= (260ml)2 (250ml)2) to obtain 69 ml net dispersion). With respect to
the target lung volume for aerosol medication, this degree of volumetric
dispersion induced by the upper airway is negligible from a clinical standpoint.
From a physiological standpoint, the degree of dispersion induced by the
upper airway concerns its contribution to the overall convective mixing
process at different lung penetration volumes (V p ) proximal to the gas exchanging zone. Only some laboratories have actually measured the halfwidth
of exhaled aerosol boluses after inhalation to very shallow penetration volumes (Vp < 100ml) [13, 149]. For instance, in 79 normal subjects, Brand
et al. [13] have measured an average HW (corrected for the 20 ml inhaled
bolus width) of 70 ml and 120 ml for aerosol boluses inhaled to a V p of 20
ml and 50 ml, respectively (respiratory flow was 250 ml/s). Assuming, on
basis of our experiments, that net UAM dispersion in each flow direction
amounts to 69 ml, the combined UAM dispersion of a 20 ml bolus during
inhalatory and exhalatory phases can be predicted according to Eqs. 6.1
and 6.2 as follows. At end of inhalation, a 20 ml bolus gets dispersed over
71.5 ml ( to obtain 69 ml net dispersion) and at end of exhalation, this 71.5
ml bolus gets dispersed over 99 ml (to obtain 69 ml net dispersion). Fi123

AIRWAYS
nally, when correcting this 99 ml bolus halfwidth at end of exhalation for
the initial 20 ml inhalatory bolus, the predicted cumulative HW for the inand exhalatory cycle amounts to 97 ml, falling in the 70-120 ml halfwidth
range obtained by Brand et al. [13] for V p ranging between 20 and 70 ml
in human subjects.
In five normal subjects, Ultman et al. [149] had previously obtained an
average SD value of 55 ml for SF 6 gas boluses inhaled to a penetration
volume corresponding to the UAM volume (91 ml). When cumulating SD
values from our UAM experiments in either flow direction according to
Eqs. 6.1 and 6.2, the corresponding SD value we obtain is 59 ml. This
excellent agreement can provide an answer to the open suggestion put forward by Ultman [148] that the dispersion obtained from a full in- and
exhalatory cycle, on basis of experiments which study inhalatory and exhalatory dispersive effects separately, may represent an overestimation of
the real cumulative dispersion. The comparison of our cumulative UAM
data to this relatively limited set of experimental data on human subjects
does suggest that in the upper airway segment, dispersion effects occurring during in- and exhalatory phases are approximately additive.
The present in vitro study shows that the impact of the upper airway
on aerosol dispersion is relatively small. A previous in vitro study by Simone et al. [132] had been concerned with the impact of the larynx on
mixing in various segments of a 3-generation branching model. These authors studied the standard deviation of 5 ml SF 6 gas boluses in a broad
range of Reynolds numbers and they normalized the SD 2 values they measured in various model segments by the corresponding segment volume
squared in order to obtain a dimensionless number for comparison with
other studies. Considering Reynolds number between 1,000 and 2,000,
their (SD/volume)2 ratio for the upper airway segment including a somewhat simplified larynx, amounted to 0.14 (= (20ml) 2 /(53ml)2 ); our corresponding value is 0.22 (= (43ml)2 /(91ml)2 ). Like Simone et al. [132], we
also found a decreasing dispersion with increasing flow, but the magnitude
of flow dependent changes seen here is much smaller than the 20% SD decrease found by Simone et al. [132] between Reynolds number 1,000 and
2,000. We can only speculate that this is due to geometrical differences,
in particular, the fact that the larynx cast in Simone et al. [132] was embedded in a straight tube directly leading to the tracheobronchial model.
With the upper airway structure studied here, a transiting aerosol is subjected to complex changes in both cross section and angle, all of which may
have an effect on the flow dependence of bolus dispersion. The present
study suggests that a realistic upper airway indeed induces poorly flow124

AIRWAYS
dependent bolus dispersion in the 250-500 ml/s flow range.
Another interesting finding by Simone et al. [132] in their in vitro branching plus larynx model was that the largest degree of dispersion originated
at the first bifurcation. Taken together with our finding of a relatively
limited dispersion induced by a more realistic model of the upper airway
and trachea, this could explain the broad range of halfwidths (70-150 ml)
obtained in human subjects for shallow volumetric depths (V p < 100 ml)
across different studies. Indeed, the exact penetration volume, i.e., the volume of air following the inhaled aerosol in any experimental setup, may
be subjected to some variability regarding the exact upper airway structures that have been crossed by the aerosol bolus under study. Therefore,
the outcome HW value in each experimental setup possibly depends on
whether a shallow bolus has actually passed the carina and whether a
markedly asymmetrical recombination of boluses at the first bifurcation
took place or not. Rosenthal et al. [121] had speculated that there may
be a faster increase of dispersion with V p in the upper airway structure
than in the conductive airways. The present study suggests that at least
the upper airway including the trachea has a relatively limited dispersive
effect.
The CFD simulations only partly confirmed the experimental observations
in that the HWin with UAM in the inhalatory configuration averaged 59
ml for flow rates 250 ml/s and 500 ml/s, but exhalatory HWex was just 20
ml in this flow range (versus 69 ml in experiments). Like the UAM experiments, the corresponding CFD simulations also produced slightly tighter
boluses at higher flows. However, the CFD simulations also predicted a
markedly different shape for exhalatory and inhalatory boluses, which was
not observed experimentally. In particular, the CFD simulated exhalatory
bolus peak was almost impossible to associate with a proper Gaussianderived solution (Eq. 6.3; Fig. 6.5B), given the sharp initial peak and the
long tail.
The above discrepancy between CFD simulations and experiments point
to a problem with the CFD methodology using RANS with a k turbulence model. RANS k simulations have been widely used in recent CFD
studies of gas and aerosol transport in the upper airway by us and others
[20, 76, 102, 171], and generally tend to overestimate aerosol deposition.
A recent comparison of experimental particle image velocimetry and simulated flow patterns of the carrier gas [77] has indicated that large eddy
simulation (LES) better capture the experimental patterns of turbulent
kinetic energy than RANS k . Given that turbulence is crucial to both
125

AIRWAYS
aerosol deposition and dispersion in the upper airway, it may be worthwhile pursuing the LES approach in the future, despite being far more
time-consuming than RANS. Given that CFD tools are currently finding
such a widespread use in the prediction of the fate of aerosols in the lungs,
and that the transitional laminar-turbulent flow regime in the upper airway poses a particular challenge, it is recommended that the bolus dispersion be used as a sensitive tool to validate emerging CFD approaches
such as LES. Indeed, it has been observed before [33] that total deposition
is a relatively crude measure of aerosol behavior. However, bolus dispersion may be a more adequate tool to validate CFD simulations of aerosol
transport in the human lung, and in particular, in the upper airway.
6.6
Limitations
In all its simplicity, the aerosol bolus dispersion experiment does present
some pitfalls and limitations. Firstly, the equipment used for bolus experiments monitors aerosol concentrations that are averaged over part or the
entirety of the tube cross section, thereby neglecting any non-uniformity
that may potentially develop within a given cross-section. Secondly, any
attempt to a simple quantification of aerosol dispersion usually relies on
a 1D Gaussian approach (Eq. 6.3) to extract one axial dispersion coefficient, which is ideally suited for describing concentrations of a dispersing gas by molecular diffusion. Since convective mixing of aerosol in the
UAM may be more complex, it is not surprising that a Gaussian does not
fully mimic the bolus shape. Indeed, the experimental bolus tail cannot
be fully captured by Eq. 6.3, and depending on the exact choice of fitting
criteria (either fitting the entire bolus curve or fitting its halfwidth), the
corresponding dispersion coefficient will slightly vary. We should bear in
mind that physiological bolus dispersion studies either consider bolus half
width (i.e., ignoring the bolus tail altogether) or exclude all bolus concentrations below 15% of the bolus peak value when computing bolus SD or
bolus skewness (i.e., effectively ignoring part of the bolus tail) [13]. Hence,
comparison between physiological bolus experiments will not suffer much
from the degree of discrepancy with the Gaussian characterization that we
observe here in the bolus tail. Thirdly, there is a limitation of using bolus
traces at the model outlet (Fig. 6.2A) to estimate spatial dispersion actually undergone by a bolus inside the model (Fig. 6.2B). For instance, a time
(or volume) dependent concentration trace at the outlet of a 32.6 cm tube
in a perfect 1D case of axial dispersion given by Eq. 6.3, shows a leveling
off of bolus halfwidth somewhere between D = 2500 and 5000 cm 2 /s (Fig.
6.2A), which in addition, partly depends on the flow rate. However, for D
values below 1000 cm2 /s, there is a monotonic increase of halfwidth with
126

AIRWAYS
D and a relatively limited dependence on flow rate. Given that the physiologically relevant D values indicated by the present study are well below
1000 cm2 /s, bolus halfwidth can indeed be considered a suitable parameter to quantitatively study aerosol transport in the upper airway under
normal breathing conditions.
On basis of experiments [132] or simulations [94], several authors have
duly argued that aerosol transport in the upper airway can have an impact
on airways downstream from it. Conversely, the presence of a bifurcation
at the tracheal end may affect bolus dispersion inside the trachea. This is
a limitation of studying any partial model of the respiratory system, as is
the case here. Yet, it must be recognized that realistic 3D experiments and
simulations in the entire lung are simply not feasible, and in some cases,
they are also not necessary. For instance, to test the effect on aerosol bolus dispersion or deposition of glottic area, it would suffice to consider only
this segment and compare numerical data with bolus experiments in exactly the same 3D geometry under exactly the same flow conditions, as was
done here. Also, CFD studies of aerosol transport in the alveolar space
(e.g., [62]) do not need more than a reasonable estimate of axial dispersion
of a bolus transiting the extra- and intrathoracic airways compartments,
for comparison with bolus experiments performed by human subjects. For
the conductive airways compartment, satisfactory empirical formula of axial dispersion already existed in the literature [125, 148, 150] and for the
oropharynx, an axial dispersion value of 2400 cm 2 /s was adopted [33]. The
present experiments provide a direct measure of axial dispersion in the
upper airway compartment, comprising oropharynx and trachea, which
ranges 200-250 cm2 /s. Some variations on this range may exist, depending on, for instance, inter-subject glottic aperture or intra-subject glottic
area variations during respiration [12]. However, we suspect these to have
a minor effect on bolus dispersion, for two reasons. First, there is a small
inter-subject variability of bolus dispersion of shallow boluses and absence
of correlation of any bolus parameter with gender [13]. Secondly, a numerical study in a laryngeal channel with pseudo-time varying glottis between
112 mm2 (peak inhalation) and 66 mm2 (peak inhalation), where Renotte
et al. [120] found minor differences in velocity profiles between in and
exhalation.
6.7 Conclusions
1. We have found experimentally that a realistic geometry of the upper
127

AIRWAYS
airway between mouth and end of the trachea induces a relatively
mild dispersion on a traversing aerosol bolus. For those studies of
aerosol bolus behavior in airways peripheral to the trachea, requiring
an estimate of bolus dispersion while trespassing the upper airway,
an axial dispersion coefficient of 200-250 cm 2 /s can be adopted under
normal breathing conditions.
2. Using a realistic UAM leads to unique dispersion curve patterns that
cannot be accurately captured by a simple 1D Gaussian, which is
usually employed to extract the axial dispersion coefficient.
3. For both inhalation and exhalation, the values of dispersion coefficient were found to be quite insensitive to the two flow rates considered.
4. The dispersion effects occurring during in- and exhalatory phases
were seen to be approximately additive.
5. CFD simulations matched the experimental results for inhalation,
but not for exhalation, indicating that the turbulence models should
be further scrutinized to adequately simulate all aspects of aerosol
transport in the upper airway.
128
Chapter 7
Application III: Tracheal

Stenosis
Contents
7.1 Introduction . . . . . . . . . . . . . . . .
7.3 Results . . . . . . . . . . . . . . . . . . . .
7.3.1 Fluid phase . . . . . . . . . . . . . .
7.3.2 Particle phase . . . . . . . . . . . .
7.4 Conclusions . . . . . . . . . . . . . . . . .
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129
130
130
130
133
135
7.1 Introduction
Air entering the mouth, passes through pharynx and flows into the trachea via the glottal region. As we saw in Chapter 5, flow in these regions is highly irregular owing to the complexity of the airway structure.
The presence of an obstructive lesion such as tracheal stenosis adds resistance to the flow due to changes in pressure and eventually results in
breathing problems. A common form of tracheal stenosis is the so-called
web-like stenosis, i.e., a marked tracheal narrowing that spans only a few
millimeters. Patients with tracheal airway stenosis often do not show any
breathing problems even when 50% of the airway lumen cross-section is obstructed, and then report a relatively sudden appearance of breathing impairment when over 75% obstruction is reached [19]. Considering 7 different stenotic constriction percentages ranging between 50 to 90%, we performed CFD simulations at a normal breathing flow rate of 30 l/min. The
129
CHAPTER 7. APPLICATION III: TRACHEAL STENOSIS

aim here was to investigate the potential of using the total fluid flow pressure drop (i.e., airway resistance), aerosol bolus deposition, and aerosol
bolus dispersion to detect tracheal stenosis at the earliest possible stage of
constriction.
Most of the CFD studies on the effect of local obstructions are focused on
the tracheobronchial region [44, 163, 98, 162, 172]. To the best of the authors knowledge, our recent work (Brouns et al. [19]) is the first attempt
to focus on the fluid flow dynamics in the presence of a web-like tracheal
stenosis. Pressure drops during normal breathing were analyzed and a
rule of thumb was derived from which pressure drops over the stenosis can
be estimated on the basis of breathing flow and stenosis cross-section. Experimental studies of stenosis include Wassermann et al. [157] who used
a newly developed bronchoscopic technique for the assessment of intratracheal pressures as a way to quantify tracheal resistance for use in diagnosis of patients with tracheal stenosis. Fasano et al. [45] used a noninvasive technique to propose specific airway resistance as a diagnostic
tool.

The numerical methods and quality control for the fluid and particle phase
are identical to the RANS methodologies described in Chapter 6.
7.3
7.3.1
Results
Fluid phase
In chapter 5, we analyzed the flow profiles in a healthy mouth-throat geometry. In this chapter, we will concentrate on the effect of stenosis on the
flow patterns. Fig. 7.1 shows the velocity contours and the velocity vector
lines in the central sagittal plane at a normal breathing flow rate of 30
l/min. We focus on the evolution of the flow downstream of the stenosis for
two different degrees of stenotic constriction. The flow coming from pharynx experiences a sharp step at the end of the pharynx which results in the
laryngeal jet developing towards the anterior side of the trachea. A little
downstream, the laryngeal jet which was developing towards the anterior
side encounters the tracheal stenosis which results in second jet like structure developing downstream of stenosis. This jet which has the tendency
of developing towards the posterior side is from now on referred to as the
stenotic jet. Due to the stenotic jet, there is a recirculation zone set on the
130
Figure 7.1: Mid-plane velocity contours and the velocity vector lines at a normal
breathing flow rate of 30 l/min. 50% and 75% constrictions are shown.
anterior side. As the stenotic constriction increases (from 50% to 75%), the
intensity of stenotic jet increases and results in a bigger recirculation zone
on the anterior side. This trend remains consistent for all constrictions
above 75%. The increase in absolute velocity and the recirculation zone
due to the jet will indeed have considerable effect on the particle deposition downstream of the stenosis.
Fig. 7.2 shows the area-averaged normalized velocity magnitude at every
2 mm after the stenotic constriction. Steady levels of velocity are seen up
to one diameters downstream of stenosis, after which there is a steep fall
between one and three diameters downstream.
Fig. 7.3 shows the area-averaged normalized kinetic energy at every 2 mm
after the stenotic constriction. For 50 and 60% constriction, the amplification levels are very small. For rest of the constrictions, there is a steep increase in the kinetic levels up to one, one and half diameters downstream,
after which a steady decrease is seen. It is interesting to note that the
maximum kinetic energy level at 90% stenosis is twice as much as the levels seen for 85% constriction. The higher levels of kinetic energy generally
131
Figure 7.2: Area-averaged normalized velocity magnitude (u/u in ) at every 2 millimeters after the stenotic constriction.
Figure 7.3: Area-averaged normalized kinetic energy (k/u2in ) at every 2 millimeters

after the stenotic constriction.
132

300
Pressure drop (pa)
250
200
150
100
50
0
40
50
60
70
80
90
100
Stenotic constriction (%)
Figure 7.4: Total pressure drop (p in pout ) as a function of stenotic constriction at

30 l/min.
enhances the turbulent mixing and this perhaps explains the faster fall of
velocity magnitude (Fig. 7.2) in case of 90% stenosis as opposed to the 85%
stenosis.
Fig. 7.4 shows the total pressure drop between inlet and outlet as a function of constriction percentage. We see a modest increase in pressure drop
up to about 75% stenotic constriction, beyond which it steeply rises. Such a
pattern agrees with the appearance of breathing symptoms with patients
who already show a very marked stenosis and explains why patients usually do not experience a major breathing impairment, or associated need
for a stenting procedure (mechanical dilation of the airway), until the constriction is well above 50%.
7.3.2
Particle phase
The aerosol bolus deposition efficiency and bolus dispersion, in terms of

bolus half-width (HW) and bolus standard deviation (SD), were simulated
as a function of the degree of stenotic obstruction (Table 7.1). It is interesting to note that the dispersion and deposition of 1 m particles with 50%
stenosis (40 ml dispersion and 4% deposition) are smaller when compared
to the case with no stenosis (49 ml dispersion and 8% deposition, as seen
133
Table 7.1: Dependence of dispersion and deposition on the percentage of stenotic

constriction.
Stenosis
(%)
Dispersion
(ml)
1 m
HW
Deposition
(%)
1 m
SD
5 m
10 m
50
40
22
10
62
60
45
25
11
64
70
50
28
12
67
80
60
31
20
70
85
65
37
28
78
90
80
39
15
51
86
134

in Chapter 6). This indeed is due to the presence of stenotic constriction
which restricts the free development of the laryngeal jet which was not
seen in the no-stenosis case (Fig. 7.1).
The CFD results show that the upper airway geometry with a maximum
stenotic constriction of 90% leads to a 80 ml wide bolus at the tracheal
outlet, for a 0.125 ml bolus at the model inlet under normal breathing condition of 500 ml/s during inhalation. Since the bolus volume at the model
inlet is very small, the non-zero initial bolus correction is not required. For
diagnostic aerosol boluses, this implies that a typical 50 ml aerosol bolus
will undergo a net dispersion in the upper airway (including the trachea)
such that its volumetric
6 dispersion beyond that point becomes no more
than 94.3 ml (i.e., = (94.3ml)2 (50ml)2 to obtain 80 ml net dispersion).
Such a mild dispersion increase for such a dramatic increase in constriction indicates that the bolus dispersion is not an adequate parameter to
detect tracheal stenosis.
The effect of airway stenosis on bolus deposition efficiency for different
particle sizes was also studied. Simulations predicted that shallow boluses
inhaled by subjects with a stenosis of 80% or more, would be affected most
in terms of bolus deposition of a 5 m aerosol, showing a high relative
change (a 2-3 fold deposition efficiency from 50% to 80-85% obstruction)
and a measurable absolute change (10-18% greater deposition for 80-85%
stenosis). Smaller (1m) and larger (10m) particles would require picking
up smaller absolute differences in bolus deposition efficiency, which could
be difficult to achieve experimentally. We can therefore conclude that shallow boluses of 5 m aerosols, and in particular their deposition efficiency,
could be a useful non-invasive diagnostic tool for the detection of tracheal
stenosis. It should however be noted that only inhalatory phase is considered in the present study due to the fact that CFD has been shown to be
unreliable for exhalatory bolus simulation (see previous chapter). In clinical setting, the cumulative dispersion during inhalation and exhalation
is considered, since the inhaled aerosol bolus is measured at the subjects
mouth upon exhalation. Hence bolus dispersion and deposition during exhalation will be needed to provide a definitive answer as to the potential
diagnostic tool.
7.4
Conclusions

1. The simulation results have shown a modest increase in pressure
135

drop up to 75% stenotic constriction, beyond which it steeply rises.
Such a pattern agrees with the appearance of breathing symptoms
with patients who already show a very marked stenosis and explains
why patients usually do not experience a major breathing impairment, or associated need for a stenting procedure (mechanical dilation of the airway), until the constriction is well above 50%.
2. Particle dispersion was found to be quite insensitive to the stenotic
constriction percentage during inhalatory phase and hence falls short
of being a sensitive tool to detect stenosis.
3. Deposition for 5 m particles was seen to exhibit a measurable sensitivity in relative deposition, making it a potential non-invasive diagnostic tool for the detection of tracheal stenosis.
136
Chapter 8
Fluid Flow and Particle

Deposition in Upper
Airways: LES and DES
Contents
8.1
8.2
8.3
8.4
8.5
Introduction . . . . . . . . . . . . . . . . . . . .
Model preparation & experimental methods
Numerical methods . . . . . . . . . . . . . . . .
Quality control . . . . . . . . . . . . . . . . . . .
Results . . . . . . . . . . . . . . . . . . . . . . . .
8.5.1 Fluid phase . . . . . . . . . . . . . . . . . .
8.5.2 Particle phase . . . . . . . . . . . . . . . .
8.6 Conclusions . . . . . . . . . . . . . . . . . . . . .
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137
139
141
143
147
147
150
154
8.1 Introduction
Inhaled medication is a preferred method of drug administration to the
lung for the first-line therapy of asthma and chronic obstructive pulmonary
diseases. The inhaled aerosol particles need to negotiate the mouth-throat
structure in order to reach the smaller airways and the alveolar lung zone
that could benefit from aerosol therapy. The complexity of the extrathoracic portion of the oral airway, which includes bends and sudden crosssectional changes, potentially induces considerable local medication deposition before actually reaching the lungs. A quantitative study of aerosol
137
CHAPTER 8. FLUID FLOW AND PARTICLE DEPOSITION IN UPPER

AIRWAYS: LES AND DES
transport and deposition in a realistic model of the mouth-throat poses
many challenges, both from an experimental and simulation standpoint.
Most previous experimental studies in mouth-throat geometries have focused on the characterization of fluid flow fields, with the ultimate aim of
predicting aerosol deposition patterns. For instance, Corcoran and Chigier
[28] used phase doppler interferometry to study the axial flow field in a
larynx/trachea cast, assessing the effects of the laryngeal jet on inhalation flow patterns. Gemci et al. [50] used laser doppler velocimetry to
characterize axial velocity fields and turbulent intensity levels in a simple
throat model (essentially a constricted tube). Heenan et al. [64] used endoscopic particle image velocimetry (PIV) to visualize the velocity fields in
distinct parts of the central sagittal plane of an idealized model of the human oropharynx. In specific locations of the same geometry, Johnstone et
al. [80] measured mean and RMS axial velocity using x-hot-wire anemometry. Heenan et al. [63] combined PIV and scintigraphic aerosol deposition
measurements in an attempt to relate time-averaged flow fields in the central sagittal plane to local aerosol deposition in two realistic extrathoracic
airway geometries. Finally, DeHaan and Finlay [39] employed ultraviolet
spectrophotometric assay to measure depositions in a mouth throat geometry for different inhalation devices, and DeHaan and Finlay [41] collected
aerosols from dry powder inhalers on disposable filters to determine oral
cavity deposition.
Most previous numerical studies have simulated the fluid/particle behavior in mouth-throat geometries by means of RANS simulations, mainly
using two equation turbulence models like k and k for the fluid
phase, sometimes coupled with Eddy Interaction Model (EIM) for the particle phase. Stapleton et al. [143] observed that even in a simplified
mouth-throat model, k turbulence model was not suitable for the accurate prediction of particle deposition. Matida et al. [102] obtained better
results with standard k model compared to standard k , yet, for
the particles in low Stokes number range (pertinent to medical aerosols),
the simulated total mouth-throat deposition was 50% in contrast to the
much lower depositions encountered experimentally (i.e., less than 5%).
When anisotropy effects close to the walls were taken into account in the
EIM, simulated deposition came down to 15%. On the other hand, Xi and
Longest [161] employed a low Reynolds number k model to assess the
effects of geometry simplifications on aerosol deposition, reporting deposition values of less than 20% (even without considering anisotropy near the
walls). The same behavior was also seen in our simulations presented in
Chapter 5. RANS models, which have been basically developed for fully
138

turbulent flows, may be inappropriate for the prediction of particle deposition in the mouth-throat, where flow is in fact transitional. Realizing this
problem, several authors have started to explore the possibility of using
large eddy simulation (LES) methods for the study of particle deposition
in the mouth-throat, by applying LES in relatively simple structures such
as turbulent duct flow [146], a 900 bend [16] or a constricted tube [99]. LES
simulations of deposition in a simplified mouth cavity model [101, 17, 74]
and in a simplified mouth-throat model [79] have indicated the potential
of LES to more accurately simulate aerosol transport in the extrathoracic
airways.
The aim of the present work was to test the validity of the most commonly
used modeling methods, namely the RANS, LES and detached eddy simulation (DES) for the description of fluid/particle behavior in the mouththroat model. The existing experimental data in literature either resulted
from intrusive measurement methods, or only provided partial data sets
on existing model geometries, making the comparison with present simulations difficult. Therefore, we performed PIV measurements in a 3D
mouth-throat cast and used exactly the same mouth-throat geometry for
CFD simulations, enabling direct comparison between simulations and experiments. On the part of CFD simulations, RANS employed SST k
turbulence model, DES was based on the Spalart-Allmaras model for the
near-wall region, and LES was based on two subgrid scale models, namely
the Smagorinsky and the WALE model. Alternatively, we considered the
frozen LES method proposed by Matida et al. [101] where the particles
are released in a frozen (static) instantaneous velocity field and tracked in
steady mode, without any EIM.
8.2 Model preparation & experimental methods

The mouth-throat geometry used for PIV measurements and CFD simulations is shown in Fig. 8.1. This geometry was previously used for the
CFD study of tracheal stenosis [19]. From the mouth-throat geometry, a
male model was generated by means of stereolithography, after which a
one block transparent female model of the mouth-throat was obtained by
following the procedures which are discussed in detail by Hopkins et al.
[71]. No geometric re-scaling was necessary for the present PIV measurements. A water-glycerin mixture was used with a viscosity of 5.88 10 6
m2 /s as determined with the AVS300 viscosimeter from Schott Gerate
at 25.2oC. Dynamic similarity was achieved for the liquid-based exper139

Figure 8.1: Simplified geometry reconstructed from CT-scan data showing different
cross-sections of the geometry.
140

iments by matching the Reynolds number. The PIV measurements were
performed in a central sagittal plane at a volumetric flow rate of 11.2 l/min,
corresponding to a Re number of 2527 (based on inlet diameter).
The water-glycerin mixture was pumped in a reservoir placed 1.5 meter above the model in order to create a developed velocity profile. The
reservoir had an inlet which was connected to the pump, an outlet connecting the model and an overflow exit which guaranteed a constant level
in the reservoir. The outlet of the reservoir was separated from the inlet and overflow exit by a fine maze to stabilize the level and to remove
any fluctuations caused by the pump. The flow rate was regulated by a
valve which was placed behind the flow meter (KOBOLD Instrumentation
NV/SA with accuracy of 4% f.s.).
A New Wave MinilaseII Nd-Yag laser (532 nm wavelength, 100mJ/pulse)
was synchronized with a pulse separation, depending on the flow rate. The
pulse separation was chosen in such a way that the reflection of the tracer
particles (10 m hollow glass spheres) shift 5 pixels between an image pair.
The laser beams were combined and formed into a sheet with cylindrical
optics. This pulsed sheet was passed through the model, parallel to the
flow, and the light scattered from the particles was recorded with a PCO
sensicam QE 5 Hz camera.
Approximately 4000 image pairs were recorded. The images were analyzed
using PIVview 2C software (PIVTEC GmbH, Germany). The vector fields
were generated using cross-correlation fast Fourier transform (FFT) with
a multi-grid procedure combined with a sub-pixel based image shifting or
image deformation with a third order interpolation scheme [124]. The final
interrogation region was 3232 pixels with an overlap of 50%. Spurious
vectors were detected by using the normalized median test, which eliminates a dependence of the detection criterion on the interrogation domain
size [159]. Only 0.1% of the vectors had to be interpolated. A least squares
3-point Gauss fit algorithm was used to recover the sub-pixel displacement
of the correlation.
8.3
Numerical methods
The fluid and particle phase were solved employing the incompressible
solver of FLUENT 6.3.
141

Fluid phase
RANS : The time averaged Navier Stokes equations are modeled employing low Reynolds number variant of SST k model [105], which requires
resolving the near-wall region with a fine mesh. This model has been selected based on its ability to accurately predict the particle depositions in
the models of mouth-throat geometries [87, 102, 161]. Second-order upwind scheme for momentum equation and third-order MUSCL scheme for
k equation were employed for spatial discretization. SIMPLE algorithm was used for pressure-velocity coupling.
DES : Detached Eddy Simulation is most often referred to as the hybrid
RANS/LES model where unsteady RANS is employed to model the nearwall region and LES in the core turbulent region. The present DES model
is based on the standard one equation Spalart-Allmaras model. Second
order implicit formulation for temporal discretization and central differencing for spatial discretization of momentum as well as the turbulent viscosity equation were employed. DES is computationally more expensive
than RANS but less expensive than LES since the near wall is modeled
using RANS approach. However, DES involves solving of an additional
turbulent viscosity equation.
LES : In the Large Eddy Simulations, the big three dimensional eddies
which are dictated by the geometry and boundary conditions of the flow
involved are directly resolved whereas the small eddies which tend to be
more isotropic and less dependent on the geometry are modeled. Two constant sub-grid scale models, namely the Smagorinsky model and the Wall
Adapting Local Eddy Viscosity (WALE) model were tested. Similar to DES,
second order implicit formulation is used for temporal discretization and
central differencing for spatial discretization of momentum equation.
The governing equations for RANS, DES and LES methodologies are as
described in Chapter 3.
Particle phase
RANS : The governing equations for the Lagrangian modeling of particle
phase are as described in Chapter 4. A trapezoidal scheme is used to update the particle position and particle velocity.
DES and LES : In the unsteady mode, each fluid phase iteration is followed by a particle phase iteration and the particles are tracked in real
time. Hence, the effect of resolved large-scale instantaneous velocity on
the particles are accounted for and there is no need for an eddy interaction
142

Table 8.1: Dependence of deposition percentage on the inlet condition.
Inlet
type
2 m
Dep. (%)
4 m
Dep.(%)
6 m
Dep. (%)
8 m
Dep. (%)
10 m
Dep. (%)
Profile
8.96
13.51
22.52
41.11
64.64
Blunt
8.39
12.95
20.61
39.21
63.12
model as in RANS. In case of frozen LES, the fluid flow is simulated for
certain number of through flow cycles followed by the injection of particles
in a stagnant (frozen) instantaneous velocity field and tracked as in RANS,
but without the EIM.
8.4
Quality control
The air flow in the mouth-throat geometry is investigated at a normal

breathing rate of 30 l/min. A steady top hat velocity profile along with
5% turbulence intensity at the inlet and static pressure at the outlet were
imposed. No-slip boundary condition was used at the walls.
We investigated Lagrangian particles with density p = 912 kg/m3 and
diameters 2, 4, 6, 8 and 10 m. Particular care was taken to obtain a uniform surface area distribution of particles at the model inlet. The particles
were injected with their initial velocity set equal to that of inlet fluid velocity. As we are dealing with dilute particulate flow, one-way coupling as
described by Elghobashi [42] is assumed. Since the airway passage is normally wet, it is assumed that a particle is taken to be deposited on the wall
as soon as it touches the wall.
The effect on inlet condition on the fluid flow and particle deposition was
investigated. Applying either a blunt inlet profile or a parabolic inlet profile showed negligible effect on the flow while comparing different crosssectional velocities in the central sagittal plane of the model (Fig. 8.2). A
total deposition variation of less than 2% was observed for all particle diameters considered in the present study (Table 8.1).
143

2
Profile inlet
Blunt inlet
u/u
in
1.5
1.5
0.5
0.5
0
0
0.5
x/d
0
0
0.5
2
D
C
1.5
1.5
0.5
0.5
0
0
0.5
0.5
0
0
Figure 8.2: Comparison of normalized 3 component velocity magnitude for different

inlet conditions. (A) Five millimeters above epiglottis; (B,C,D) One, two and three
tracheal diameters downstream of larynx respectively.
144

RANS : A recent study by Vinchurkar and Longest [156] has shown clear
advantages of using hexahedral meshes in respiratory aerosol transport
and deposition. The present mouth-throat model was meshed into 800,000
hexahedral cells with clustering in the vicinity of the wall and a stretching
ratio of 1.2. The y + of the first layer of cells next to the wall was about
1. For each particle diameter, 5,000 particles were injected at the model
inlet. Meshes of either 800,000 or 2,170,000 cells (essentially obtained by
doubling the number of grid points in each direction) had shown negligible
variation of cross-sectional velocity magnitude in the larynx region and a
deposition variation of less than 2% for all particle diameters. The difference in percentage deposition by injecting 5,000 or 15,000 particles at the
model inlet had been found to be less than 1%. Matida et al. [102] had previously reported that their simulated deposition results were unaffected
by increasing the number of injected particles from 1000 to 10,000. For
the particle transport, high order trapezoidal scheme was employed. The
typical simulation time of the flow field to obtain a convergence level of
three orders of magnitude and to subsequently track 5,000 particles took
14 hours on an AMD Opteron 2.4 MHz dual-core processor.
LES and DES : In case of LES, the mouth-throat model was meshed into
1.9 106 hexahedral cells with clustering towards the wall. The first cell
layer next to the wall had a y + 0.2 with a stretching ratio of 1.05, which
was sufficient to resolve the viscous sublayer. For the DES mesh, 1.2 10 6
hexahedral cells were employed with a y + 1 and a stretching ratio of 1.2.
The converged steady state solution based on SST k model was perturbed by adding random fluctuations and was used as an initial solution
for faster convergence of LES/DES computations. To get rid of any possible
initial condition effects, 3 through flow cycles were performed before starting the time-averaging. A through flow cycle is defined as the ratio of the
length of airway model to the average cross-sectional velocity in the central sagittal plane. For 30 l/min, it is 0.1 seconds. A through flow cycle
is much smaller compared to a typical inhalation period which is 2 seconds [93]. The time-step to advance the flow was chosen such that the CFL
number in the entire domain was less than 1. The typical time step was
1 105 sec when using 1.9 106 mesh points. To test mesh independence
of the solution, an additional simulation was performed for LES (WALE
model) with the same time step but on 2.9 10 6 cells. Essentially, no differences were found in the average velocity magnitude except for a slight
offset in the location of velocity profile on the anterior side at 5 mm above
epiglottis (Fig. 8.3(a)). For all LES and DES simulations, obtaining a time
145

2
A
1
1.5
u/u
in
0.8
0.6
0.4
LES 1.9*10
0.5
LES 2.9*10
0.2
DES 1.2*10
0
0
0.2
0.4
0.6
0.8
0
0
0.2
0.4
0.6
0.8
0.2
0.4
0.6
0.8
x/d
1.5
1.4
C
1.2
0.8
0.6
0.5
0.4
0.2
0
0
0.2
0.4
0.6
0.8
0
0
Figure 8.3: Comparison of normalized 2 component (ux and uz ) velocity magnitude

corresponding to the central sagittal plane. (A) Five millimeters above epiglottis
(corresponds to section C in Fig. 8.1); (B,C,D) One, two and three tracheal diameters downstream of larynx respectively (corresponds to section H, I, J in Fig. 8.1);
x/d = 1 corresponds to the anterior airway wall.
146

independent averaged solution took approximately 4 through flow cycles.
Each through flow cycle for LES and DES took approximately 160 hours
and 110 hours respectively, while running parallel on four AMD Opteron
2.4 MHz dual-core processors.
Once the time-independent average solution was obtained, Lagrangian
particles were introduced into the domain by injecting 5,000 particles for
each particle diameter uniformly over a time span of one through flow cycle. Previous LES studies [79, 101] had indicated that 3500 particles
were sufficient. Approximately 5 through flow cycles were required to get
all the particles to either deposit on the wall or reach the outlet. Once
the unsteady tracking was finished, the flow solution was also used for
the frozen LES simulations where the particles were injected in the frozen
instantaneous velocity field and tracked as in RANS, but without the EIM.
8.5 Results
8.5.1
Fluid phase
The flow patterns obtained with LES, DES and RANS are assessed by
comparing the two-component normalized velocity magnitude profiles with
experimental ones at various model cross-sections (Fig. 8.4). Both LES
subgrid scale models (Smagorinsky and WALE) perform well in all four
cross-sections, with a slightly better prediction of the velocity profile by
the Smagorinsky model in the pharynx region on the anterior side (close
to x/d = 1 in Fig. 8.4(a)). In all four cross-sections, DES and LES predictions of velocity profiles are very similar. By contrast, the widely used
k RANS model systematically overestimates velocity near the anterior
airway wall, particularly in the tracheal region (Fig. 8.4(b-d)).
In order to compare kinetic energy across the computations and experimental data, we first considered the 2 component kinetic-energy as measured by PIV. The experimental data were compared with the corresponding 2 component kinetic-energy obtained with LES and DES (left panels of
Fig. 8.5), showing a good agreement between simulations and experiments
and negligible variation across the LES/DES models . Since the kinetic energy in RANS implicitly comprises of all 3 components, direct comparison
! 2
! 2
with experimentally measured 2 component kinetic-energy (u x and uz )
is not possible. Considering the similarity of 2 component kinetic energy
profiles between LES/DES and the experiments, the corresponding 3 component kinetic energy profiles for LES Smagorinsky was compared with
RANS (right panels in Fig. 8.5). It can be observed that the kinetic energy
147

2
A
u/uin
1.5
Experiment
LES Smagorinsky
LES Wale
DES
RANS
B
1.5
0.5
0.5
0
0
0.5
x/d
0
0
0.5
2
C
1.5
1.5
0.5
0.5
0
0
0.5
0.5
0
0
Figure 8.4: Comparison of normalized 2 component (ux and uz ) velocity magnitude

corresponding to the central sagittal plane. (A) Five millimeters above epiglottis;
(B,C,D) One, two and three tracheal diameters downstream of larynx respectively.
148

A
Experiment
LES Smag
LES Wale
DES
k/u2in
0.3
0.2
0.1
0
0
B
0.3
0.2
0.1
0.5
x/d
0
0
0.3
0.3
0.2
0.2
0.1
0.1
0
0
LES Smag (3 comp)

RANS
0.5
0
0
0.5
0.5
0.5
0.5
C
0.3
0.3
0.2
0.2
0.1
0.1
0
0
0.5
0
0
D
0.3
0.3
0.2
0.2
0.1
0.1
0
0
0.5
0
0
Figure 8.5: Left: Comparison of normalized 2 component (ux and uz ) kinetic energy corresponding to the central sagittal plane between Experiments, LES and
DES; Right: Comparison of normalized 3 component kinetic energy between LES
and RANS; (A) Five millimeters above epiglottis, (B,C,D) One, two and three tracheal diameters downstream of larynx respectively.
149

profile obtained with the k model is very different from that of LES,
with both under- and overestimation of local kinetic energy depending on
the cross-section under study.
The time-averaged flow patterns and the secondary flow structures are
presented in Fig. 8.6 for the LES Smagorinsky model. The six crosssectional views show velocity magnitudes that are greater than 50% of the
maximum velocity in the airway model (i.e., 2.6 m/s and above). The flow
entering through the mouth piece impinges on the tongue and takes a bend
upwards. As it continues to move forward, it accelerates in the middle part
of the mouth due to reduction in cross-sectional area. As can be seen in section A1-A2, velocity in most of this cross-section is above 2.6 m/s. Also, two
distinct recirculation zones are seen. Towards the end of mouth region,
the flow takes a downward turn and enters the pharynx in the form of a
jet which undergoes an expansion due to increase in cross-sectional area.
Consequently, the velocity is reduced and complex secondary motions are
set as shown in slice B1-B2. Just beyond the epiglottis region, the flow
again accelerates due to reduction in cross-sectional area and a clear high
velocity zone develops on the posterior side of section C1-C2. At the end
of the pharynx, a step on the posterior side guides the flow towards the
anterior side of the trachea in the form of a laryngeal jet. As a result of
this laryngeal jet, two distinct recirculation zones originate at the posterior side at section E1-E2 and move towards the center as the flow moves
further downstream (section F1-F2).
The normalized velocity magnitude contours in Fig. 8.7 illustrate that
the shape of laryngeal jet for LES is much closer to what is observed in
experiments, and RANS predicts a more pronounced and longer laryngeal
jet compared to LES. It also shows that RANS leads to greater velocities at
the anterior tracheal wall, as previously observed at discrete model crosssections (Fig. 8.4(b-d)).
8.5.2
Particle phase
Fig. 8.8 summarizes the simulated total deposition percentages for different particle diameters along with the experimental curve fit of Grgic
et al. [58], obtained from deposition measurements in 7 different model
casts representative of over 80 image-based mouth-throat structures. For
the 2 and 4 m particles, LES and DES show particle depositions that
are much closer to the experimental curve than those obtained with RANS
k , while for the 8 and 10 m particles, RANS, LES and DES perform
equally well. Alternatively, RANS k with mean flow tracking, i.e. with150

Figure 8.6: Above: Time averaged central sagittal plane velocity magnitude and
corresponding streamlines; Below: Time averaged velocity magnitude (above 50%
of maximum velocity in the airway model) and corresponding secondary velocity
vector lines at six different cross-sections.
151

Figure 8.7: Time averaged 2 component normalized velocity magnitude contour (ux
and uz ) in (a) experiments; (b) LES; (c) RANS.
out EIM, consistently underestimates deposition for all particle diameters

greater than 2 m. The same is true for the frozen LES method, possibly because the under-relaxation parameter settings, which yielded good
results for LES (Fig. 8.8), are too dissipative for the frozen LES method.
Considering that 5 m is generally referred to as the upper limit of the respirable range for inhalation drugs (represented by the dash-dotted line in
Fig. 8.8), our findings suggest that in the mouth-throat geometry, the prediction of medication aerosol deposition inhaled at normal flow rates were
more accurate for LES and DES than for the RANS k model. At a first
glance, DES can then be seen as the preferred method over LES due to
reduced computational requirements. To be certain regarding DES being
better than LES on 1.2 106 mesh points, an additional LES simulation
was performed on the DES mesh. It is observed that LES did as good as
DES for both fluid and particle phase. This clearly means that LES would
remain the preferred method among the models tested, as it obviates solving an additional equation for t required for DES. For the description of
particle transport with diameters above 5 m (e.g., in the upper range of
air pollutant particle distributions) or for small diameters but inhaled at
greater inhalatory flows (e.g., dry powder inhalers), RANS with its vastly
152

100
90
Deposition Efficiency (%)
80
70
Experimental fit
(Grgic 2004)
RANSEIM
RANSMEAN
LES
Frozen LES
DES
60
50
40
30
20
10
0 2
10
10
10
10
Stk.Re0.37
Figure 8.8: Simulated total deposition (expressed as % of particles at model inlet)

as a function of Stokes and Reynolds number as defined by Grgic et al. [58]. The
solid line represents the experimental best fit curve. The dash-dotted line corresponds to a 5 m particle at 30 l/min. In case of RANS, + represents turbulent
tracking i.e. considering EIM; represents mean flow tracking i.e. without EIM.
lower computational requirements suffices to adequately predict aerosol

deposition.
In order to better understand the discrepancy in particle deposition between LES (Smagorinsky) and RANS (k ), deposition in the three model
sub-parts are shown for the five particle diameters (Fig. 8.9). It is seen that
RANS overestimates larynx/trachea deposition, showing relatively greater
discrepancy with LES for the smaller particles. This can be explained by
the profound and longer laryngeal jet in case of RANS compared to LES
(Fig. 8.7) and the velocity overestimation near the anterior airway wall
(Fig. 8.4(b-d)).
Even though LES and DES are more accurate among the models considered, they pose a limitation when attempting to simulate transient inhalation/exhalation cycles, partly because of the small sampling time requirements and partly due to relatively high time-cost associated with typical
153

70
trachea + larynx
pharynx
mouth
Deposition Efficiency (%)
60
50
40
30
20
10
RANS
LES
0
2
10
Diameter (m)
Figure 8.9: Simulated deposition values (expressed as % of particles at model inlet)

in three model subparts; Mouth deposition excludes deposition in the inlet tube.
transient waveforms. For example, to perform LES/DES simulation of a

2 second transient inhalation waveform as considered by Li et al. [93]
would require 5 times more computational time compared to the steady
inhalation case simulated in the present work. Alternative RANS models may therefore be worth considering. For instance, Matida et al. [102]
applied the near-wall anisotropic corrections to a RANS k model and
showed considerable improvement in deposition over the one obtained with
isotropic assumption. However, the fact that the basic fluid flow field is
not accurately predicted by RANS (Fig. 8.4, 8.5, 8.7) is a problem. Another
possibility is to consider a Reynolds Stress Model (RSM) which implicitly
accounts for near-wall anisotropy, and has been reported to outperform
RANS k model when predicting nano and micro-particle deposition in a
duct flow [146]. However, as pointed out by these authors, the performance
of the different modalities of the Reynolds stress model in a more complex
geometry warrants further investigation.
8.6
Conclusions

1. RANS, LES and DES simulations showed that for the fluid phase,
154

LES/DES lead to similar velocity and kinetic energy profiles and all
of which compare well with experimental data, as opposed to RANS.
2. 5 m is generally referred to as the upper limit of respirable range
for inhalation drugs. For the micro-particles below 5 m considered
in the present study, LES and DES more closely match experimental
aerosol deposition than RANS (without near-wall correction). Simulating LES on the DES mesh showed that LES would be the preferred
method among the models tested.
3. For the simulation of particles above 5 m at normal breathing condition, the similar performance of RANS and LES/DES makes RANS
the preferred method.
155

156
Chapter 9
Conclusions and
Perspectives
9.1 Conclusions
In order to account for inter-subject variability, the need for considering
realistic CT based airway models has been recognized and an efficient Lagrangian particle tracking module for unstructured grids to handle complex geometrical features has been implemented in the commercial C++
flow solver of NUMECA. The RANS methodology was used in the following three applications:
Application 1: Fluid flow and particle deposition in a CT based realistic

extra-thoracic airway model was studied. Inhalation flow rates of 15, 30
and 60 l/min were considered with particle diameters ranging between 2
and 20 m. The complex flow patterns with skewed velocity profiles and
flow separations are discussed. While most idealized mouth-throat models
predict no transition to turbulence for a flow rate of 15 l/min, we observe
increase in kinetic energy levels soon after glottis, indicating the sensitivity to geometrical complexity at low flow rates. Mouth cavity acts as
an effective filter and is responsible for the major deposition in the upper
airway for all three flow rates. Combining our model depositions with previous simulations in central bronchial tree depositions indicates that for
normal breathing conditions, inhalatory deposition for the particle size 5
m, which is usually referred to as the upper limit of the respirable range
for inhalation drugs, does not exceed 12%.
Application 2: The axial dispersive effect of the upper airway structure
157
CHAPTER 9. CONCLUSIONS AND PERSPECTIVES

(comprising mouth cavity, oropharynx and trachea) on a traversing aerosol
bolus was investigated. This was done by means of aerosol bolus experiments on a hollow cast of a realistic upper airway model (UAM) and 3D
computational fluid dynamics (CFD) simulations in the same UAM geometry. The experiments showed that 50 ml boluses injected into the UAM,
dispersed to boluses with a half-width ranging 80-90 ml at the UAM exit,
across both flow rates (250, 500 ml/s) and both flow directions (inhalation,
exhalation). These experimental results imply that the net half-width induced by the UAM typically was 69 ml. Comparison of experimental bolus
traces with a 1D Gaussian derived analytical solution resulted in an axial
dispersion coefficient of 200-250 cm 2 /s, depending on whether the bolus
peak and its half-width, or the bolus tail needed to be fully accounted for.
CFD simulations agreed well with experimental results for inhalatory boluses, and were compatible with an axial dispersion of 200 cm 2 /s. However, for exhalatory boluses, the CFD simulations showed a very tight bolus peak followed by an elongated tail, in sharp contrast to the exhalatory
bolus experiments. This indicates that CFD methods, which are widely
used to predict the fate of aerosols in the human upper airway, where flow
is transitional, need to be critically assessed, possibly via aerosol bolus
simulations. It is concluded that, with all its geometric complexity, the upper airway introduces a relatively mild dispersion on a traversing aerosol
bolus for normal breathing flow rates in inhalatory and exhalatory flow
directions.
Application 3: The potential of using aerosol boluses inhaled at 30 l/min

to detect tracheal stenosis ranging 50-90% obstruction of tracheal cross
sectional area was investigated. Computational fluid dynamic simulations
were performed in a realistic upper airway model of the mouth and trachea, using a two-equation RANS (with a k turbulence model). The
aerosol bolus deposition efficiency and bolus dispersion, in terms of bolus
half-width (HW) or bolus standard deviation (SD), were simulated as a
function of the degree of stenotic obstruction. The effect of aerosol particle
size on bolus deposition efficiency was also considered. Simulations predicted that shallow boluses inhaled by subjects with a stenosis of 80% or
more, would be affected most in terms of bolus deposition of a 5 m aerosol,
showing a high relative change (a 2-3 fold deposition efficiency from 50%
to 80-85% obstruction) and a measurable absolute change (10-18% greater
deposition for 80-85% stenosis). Smaller (1 m) and larger (10 m) particles would require picking up smaller absolute differences in bolus deposition efficiency, which could be difficult to achieve experimentally. It is
concluded that shallow boluses of 5 m aerosols, and in particular their
deposition efficiency, could be a useful non-invasive diagnostic tool for the
158

detection of tracheal stenosis.
Finally, fluid flow was simulated in a simplified human mouth-throat model
under normal breathing conditions (30 l/min) alternatively employing RANS,
DES and LES methods. To test the validity of the fluid phase simulations,
PIV measurements were carried out in a central sagittal plane of an identical model cast. Velocity and kinetic energy profiles showed good quantitative agreement of experiments with LES/DES, and less so with RANS
k . Mouth-throat deposition was simulated for particle diameters 2, 4,
6, 8 and 10 m. By comparison with existing experimental data, LES/DES
showed considerable improvement over the RANS k model in predicting deposition for particle sizes below 5 m. For the bigger particles, RANS
k and LES/DES methods produced similarly good predictions. It is concluded that for the simulation of medication aerosols inhaled at a steady
flow rate of 30 l/min, LES and DES provide more accurate results than the
RANS k model.
9.2 Perspectives
9.2.1
Future CFD developments
In case of LES/DES, concurrent simulation of fluid flow and particle motion

is indeed a lengthy computational process and one needs to look towards
other cost-effective ways to model the particle motion. Frozen LES as described and tested in Chapter 8 was already the first step, however, it was
seen to be inaccurate. In future, the following potential ways of particle
modeling should also be tested.
1. Instead of performing frozen LES simulation at just one instantaneous flow field, it could be useful to perform few such frozen LES
calculations separated by an integral time scale (Tint = length of the
model/average cross-sectional velocity). For example, say we perform
25 independent frozen LES calculations, each separated by T int in
time, and finally obtain the particle deposition characteristics by averaging the results of the 25 frozen LES calculations. Since we are
averaging the deposition results of 25 different realizations, the error
encountered is expected to be less when compared to performing just
one realization as in Chapter 8.
2. Store the time-dependent flow field in terms of three instantaneous
velocity components over a length of one integral time scale (T int ).
Perform particle tracking by repeatedly playing this stored flow field.
159

To avoid discontinuities in the flow field, the stored flow field should
be played in a periodic fashion. For example, if 100 instantaneous
flow fields are stored, we start the particle tracking using flow fields
1 to 100, and then back from 100 to 1.
3. Store the time-averaged three-dimensional flow field in terms of three
averaged velocity components, the turbulence kinetic energy (which
is the sum of resolved and modeled part), and the energy dissipation
rate. By using the time-averaged LES solution, perform the particle tracking as in case of RANS (using an eddy interaction model).
The time-averaged solution obtained from LES is indeed more accurate when compared to RANS fluid-flow solution. Also, the effect of
anisotropy can be considered in the eddy interaction model as the
Reynolds stresses are directly available from LES. Hence, the results
obtained from particle tracking are expected to be more accurate as
opposed to RANS.
In Chapter 6, it was seen that CFD simulations did not reproduce the exhalatory bolus measurement data. To resolve this issue, PIV measurements
of both fluid flow and bolus dispersion should be performed on the upper
airway model during the exhalation mode. The data should then be used
to validate/improve the turbulence models in CFD.
9.2.2
Future Airway model developments
Airway model extension

In the present thesis, we have been dealing with the upper airway model,
i.e., from mouth till end of trachea. However, the inhaled medical aerosols
have still a long way to go before reaching the alveolar regions of the lungs.
The present upper airway model can be extended to accommodate the tracheobronchial region. The first few generations of the tracheobronchial
region are still a challenging part in terms of CFD simulations. Since
the kinetic energy levels in trachea are generally high, it is expected that
the kinetic energy prevails even downstream of it, at least till first two or
three bifurcations. Most of the studies on the fluid flow and particle deposition in the tracheobronchial region assume the flow to be laminar. This
is generally not true, especially for normal (30 l/min) and heavy (60 l/min)
breathing conditions. Hence, performing turbulent simulations in the tracheobronchial region is required. Also, the flow entering into the tracheobroncial region is quite distorted due to the presence of larynx upstream.
This upstream effect should also be considered in future simulations.
160

Moving larynx
The larynx (glottis) area is seen to considerably vary during respiratory
cycle, even during quiet breathing. Renotte et al. [120] mentioned that
the glottis dimension may evolve between 5.70.5 and 10.10.5 mm during the respiratory cycle. Considering the dynamically varying geometries
during a flow simulation is completely a new and unexplored aspect, especially with applications to upper airways, and hence a preliminary study in
this direction is needed to provide insights towards the moving boundary
effects and the numerical complexities associated with it.
9.2.3
Future applications
Airway resistance measurement

In chapter 7, the potential of using the non-invasive techniques of dispersion/deposition in order to detect the tracheal stenosis was explored. A
possible additional non-invasive technique is to measure the airway resistance and relate the undue increase in resistance to the airway abnormality. There are several possible ways of measuring the airway resistance,
however, the most promising method, which is sensitive to the upper airway component is the forced oscillation technique. Recently, Verbanck et
al. [153] at VUB medical school has shown a promising use of forced oscillation technique in detecting fixed upper airway obstruction. This potential method should further be explored.
Ultrafine particles in healthy and diseased lungs
Submicron particles, i.e. particles with diameters smaller than 1 m, fall
into the category of fine respiratory aerosols (diameter ranging from 100
nm to 1 m) or the category of ultrafine particles (diameter <100 nm, also
referred as nanoparticles). In the ambient air, the ultrafine particles (<100
nm in diameter) are much greater in number than coarser particles. A
considerable fraction is emitted from combustion sources such as diesel
engines, where particle size ranges from 5 to 500 nm. Other sources are
tobacco smoke (18 nm to 1.6 m), viruses such as Avian flu and SARS
with sizes typically from 20 to 200 nm, and bacteria. Measured concentrations on roads in Minnesota are as high as 107 particles/cm3 [86]. Animal studies show that exposure to high doses of such particles can cause
lung injuries [112, 113]. Also, recent epidemiological studies have indicated that ultrafine particles may have greater adverse respiratory effects
than fine or coarse particles in urban air [115]. Due to all the above reasons, studying the deposition characteristics of ultrafine particles in the
161

tracheobronchial regions is important.
In a study of the World Health organization (2004), it is stated that the
most common cause of death in men and women is cancer-related. Lung
cancer is responsible for 1.3 million deaths worldwide annually. It is hypothesized that cancerous lesions may arise from a continuous insult from
toxic particles, creating hot spots in particular locations of the tracheobronchial tree. Hence, it is interesting to predict tumor location in any
given patient on basis of aerosol deposition hot spots simulated for this patients particular traceobronchial structure. This type of study has never
been done before. Obviously, such a study necessitates that a CT rendering of the lung structure of each individual patient, and the localization of
the tumor with respect to this patients particular structure. This indeed
requires an optimal coordination of medical interventions (examinations,
biopsies, CT) with the engineering staff, in order to be able to use these
medical data in a quantitative way (i.e., use the data for CFD computations).
162
List of Publications
Journal articles
1. S T Jayaraju, M Brouns, C Lacor, B Belkassem, S Verbanck. Large
eddy and detached eddy simulations of fluid flow and particle deposition in a human mouth-throat, Journal of Aerosol Science, 39:862875, 2008.
2. S T Jayaraju, M Paiva, M Brouns, C Lacor, S Verbanck. The contribution of upper airway geometry to convective mixing, Journal of
Applied Physiology, 105:1733-1740, 2008.
3. S T Jayaraju, M Brouns, S Verbanck, C Lacor. Fluid flow and particle deposition analysis in a realistic extrathoracic airway model using
unstructured grids, Journal of Aerosol Science, 30:494-508, 2007.
4. M Brouns, S T Jayaraju, C Lacor, J De Mey, M Noppen, W Vincken,
S Verbanck. Tracheal stenosis: A flow dynamics study, Journal of
Applied Physiology, 102:1178-1184, 2007.
Conference proceedings
1. S T Jayaraju, M Brouns, S Verbanck, C Lacor. Fluid-particle dynamics in human mouth-throat geometry, International Conference
of Turbulence and Interaction, Sainte-Luce, Martinique, 2009.
2. S T Jayaraju, M Paiva, C Lacor, W Vincken, S Verbanck. Shallow
aerosol bolus tests for detection of tracheal stenosis, American Thoracic Society Conference, San Diego, USA, 2009.
3. S T Jayaraju, M Brouns, S Verbanck, C Lacor. LES and DES study
of fluid-particle dynamics in human upper respiratory pathway, European Congress on Computational Methods in Applied Sciences and
Engineering, Venice, Italy, 2008.
163
4. S T Jayaraju, M Brouns, S Verbanck, C Lacor. Lagrangian particle

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Prof. Dr. Ir. Chris Lacor

Chapter 1 gives a brief introduction to the human respiratory system.

In Chapter 5, the fluid flow and particle deposition in a realistic CT-extracted

Prof. Johan DECONINCK

Prof. Rik PINTELON

Prof. Patrick KOOL

Prof. Jan VIERENDEELS

Prof. Chris LACOR

3 The Fluid Phase

4 The Particle Phase

4.4.1 Time integration . . . . . . . . . . . . . .

5 Application I: Fluid Flow and Particle

6 Application II: Convective Mixing in Upper Airways

7 Application III: Tracheal Stenosis

8 Fluid Flow and Particle Deposition in Upper Airways: LES

Dynamic viscosity of the fluid, kg/m s

Kinematic viscosity of the fluid, m 2 /s

Specific dissipation, 1/s

Density of the fluid, kg/m 3

Time scale for smallest eddy, s

Turbulent kinetic energy dissipation, m2 /s3

SST Shear Stress Transport

1.1 The respiratory system

Fig. 1.2 shows a schematic representation of the extra-thoracic region

trachea. The extra-thoracic region is also most often referred to as the

Figure 1.2: Schematic representation of the extra-thoracic (upper) airway [46].

on the position of tongue and jaws.

Each terminal bronchiole subtends an air chamber that could be likened

1.2 Aerosols and the respiratory system

Inhaled pharmaceutical aerosols

Factors affecting pharmaceutical aerosol

Breathing flow rate

Figure 1.5: Different types of inhalers.

Mechanisms of particle deposition

Inertial Impaction: Deposition due to impaction is directly proportional

1.5 Clinical aerosol measurements (bolus tests)

Figure 1.8: Exhaled bolus concentration curves at different penetration volumes.

ml) is inspired at a predetermined moment during inhalation [152] (Fig.

2.1 Airway geometries

CHAPTER 2. LITERATURE SURVEY

Figure 2.1: Simplified three-dimensional model of larynx [84].

Figure 2.2: Simplified three-dimensional model of larynx [28].

CHAPTER 2. LITERATURE SURVEY

Figure 2.3: Simplified three-dimensional mouth-throat model [171].

scans, magnetic resonance imaging (MRI) scans, and direct observation

CHAPTER 2. LITERATURE SURVEY

Figure 2.4: Simplified three-dimensional mouth-throat model [143].

CHAPTER 2. LITERATURE SURVEY

Figure 2.6: Simplified three-dimensional mouth-throat model [19].

2.2 Modeling methods

CHAPTER 2. LITERATURE SURVEY

Figure 2.7: Three-dimensional mouth-throat model as extracted from CT scan data

CHAPTER 2. LITERATURE SURVEY

Stochastic modeling of the particle phase involves direct simulation of

CHAPTER 2. LITERATURE SURVEY

CHAPTER 2. LITERATURE SURVEY

aerosol transport in the upper airways has been recognized. Jayaraju et

Fluid flow characteristics in upper airways

CHAPTER 2. LITERATURE SURVEY

CHAPTER 2. LITERATURE SURVEY

CHAPTER 2. LITERATURE SURVEY

In summary, the consistent observation among different studies was that