Proceedings of the 2005 IEEE

Engineering in Medicine and Biology 27th Annual Conference

Shanghai, China, September 1-4, 2005

Simulation of Pulmonary Pathophysiology During Spontaneous

Breathing
Y. C. Zhao, S. E. Rees, S. Kjrgaard , S. Andreassen
Center

for Model-based Medical Decision Support, Alborg

University, Denmark
Department of Anaesthesiology, Alborg

Hospital, Denmark

Abstract This paper presents a functional model of lung

mechanics including a non-linear alveolar pressure volume
curve and representation of the work of respiratory muscles
during breathing. The model is used to simulate the response
to forced inspiration and expiration, and these simulations
compared to the standard results of lung function tests routinely
performed in departments of lung medicine. The model can
simulate the characteristics of inspiratory and expiratory flow
profiles seen in normal subjects, and in patients with obstructive
or restrictive diseases.

I. I NTRODUCTION
In clinical practice linear models of respiratory mechanics
can be used to estimate resistance and elastance parameters
of the respiratory system. These may provide an understanding of the pathogenesis of lung disease, and may be
used to optimize ventilator settings or adjust pharmacological
therapy. Whilst the parameters of these linear models can
be estimated in the clinical settings, the complexity of the
models is insufficient, meaning that these models often
provide a poor fit to measurements of flow and pressure, and
give parameter values which are physiologically implausible
[1]. To overcome these limitations, models have been built
using the so called functional approach [2][3][4][5][6]. These
models divide the airways into three sections: upper airways
described as a flow dependent resistance; central airways
described as a transmural pressure dependent resistance; and
lower airways described as a volume dependent resistance. In
this approach, alveoli are lumped into single a compartment
with a constant compliance. Models built using the functional
approach have been used to simulate flows and pressures
during mechanical ventilation. However, these models have
not been used to simulate spontaneous ventilation. In particular they have not been used to simulate the flow and
volume profile that occurs during forced breathing, where
these profiles are often used in the diagnosis of respiratory
disease.
This paper presents a modified version of the model
previously proposed by Barbini et al [6]. This model includes
a sigmoid [7] function to represent the nonlinear properties of
both airways and the alveoli space, and a pressure generator
to describe the work of the respiratory muscles. In doing so,
it will be tested whether this model can simulate spontaneous
breathing, including forced breathing patterns in normal
subjects and patients with lung diseases.
This work was supported by the IT committee under the Danish Technical
Research Council.

0-7803-8740-6/05/$20.00 2005 IEEE.

II. M ODEL OF RESPIRATORY MECHANICS

Mechanical and electrical analogues of respiratory mechanics are illustrated in figure 1. The derivation of a
mathematical description of these models and its detailed
physiological interpretation follows.
A. Alveoli and Thoracic Cage
Figure 1(a) illustrates the physiology included in the
model. Alveoli are surrounded the pleural space which is
connected with the thoracic cage. The pressure inside the
alveoli and pleural space are called alveolar gas pressure (Pa )
and the pleural pressure (Ppl ) respectively. During breathing
the work performed by the muscles of the chest wall and
diaphragm generate pressure (Pm ) in the pleural space,
whilst chest wall elasticity (Ecw ) exerts recoiling pressure
(Pcw ) against it. Ppl is therefore given by
Ppl = Pm + Pcw

(1)

The elastic recoil pressure of the chest wall is considered

having a linear relationship with the thoracic cage volume
(Vtc ) and describes as
Pcw = Ecw Vtc Pcw0

(2)

where Pcw0 is a parameter representing the outward pulling

pressure generated by chest wall at the relaxed state, at
which the opposite pull of the alveoli and the chest wall
reaches the equilibrium. Vtc is approximated equal to the
sum of alveolar volume (Va ) and central airway volume (Vc ),
assuming negligible pleural volume, i.e.
Vtc = Va + Vc

(3)

The pressure difference between Ppl and body surface

pressure (Pbs ) is termed as trans-chestwall pressure (Ptc ),
which drives Vtc and is described as
Ptc = Ppl Pbs

(4)

The pressure difference between the alveoli and the pleural

space is called transpulmonary pressure (Ptp ), which drives
Va change in a nonlinear relationship [8][9][10], and is
described as
(5)
Ptp = Pa Ppl
In this paper, the relationship between Ptp and Va is represented by a sigmoid equation (6) proposed by Venegas et al
[7]


(6)
Va = a + [b (1 + e(d/(Ptp c)) )]

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Pleural Space
c
Rc v&c

v&

Pc

Ptm

Vc

l
Rl

Alveoli

v&a

Va
Pa

Ppl

Rc

Pc v&a

Ecw
Pcw

Pm

Chest Wall
Diaphragm

Thoracic Cage (Vtc)

(a)

Pbs

Pm

Rl

Pa

v&c

Ptm
-

Ptp
Ptc

Pbs

Ru

+-

u
Ru

Vc

+
2

Va

Ptp

Vtc Ecw
-

+
Pcw

PPl

(b)

Fig. 1. (a) A mechanical analogue representing physiological interpretation of respiratory mechanics. Airways are lumped into three sections, i.e. upper
(u), central (c), and lower airways (l). The thoracic cage is represented as a solid and dashed line, which indicates its compression due to pressure applied
by the chest wall and muscle work. (b) Respiratory mechanics is modeled and calculated in an electric analogue. Body surface pressure is referred as
ground in circuit analysis. The direction of inflation flow v is assumed as the positive direction.

where a corresponds to the lower asymptote of the lung

volume; b corresponds to the difference between the upper
and the lower asymptote of the lung volume; c is the pressure
at the inflection point between the upper and the lower
asymptote of the sigmoid curve; d indicates a pressure range,
in which the most constant compliance occurs, i.e. the range
(c 2d) to (c + 2d).
B. Airways
The respiratory airways are divided into three sections,
upper, central and lower airways, according to their functional importance. Upper airways are assumed to consist of
airways from mouth to extrathoracic trachea; Central airways
are assumed from intrathoracic trachea to small bronchi
(11th generation of Weibel model [11]); Lower airways are
assumed to consist of bronchioles extending to the alveoli,
i.e. generations (12th-23th) [11].
a) Upper Airways: Upper airways are represented as
rigid pipes with considerable structural resistance to collapse,
and can be modeled as flow dependent resistance (Ru )
according to Rohrer [12]
Ru = k1 + k2 |v|

(7)

where k1 represents resistance due to laminar flow, and k2

represents resistance due to turbulent flow.
b) Central Airways: Central airways can be compressed and correspondingly cause expiratory flow limitation
(EFL) during forced expirations or during normal ventilation in patients with chronic obstructive pulmonary disease
(COPD) [13]. Modeling this compression is therefore necessary to represent EFL. Compression due to high transmural
pressure (Ptm ) can be represented as the difference between
intraluminal pressure (Pc ) and pleural pressure (Ppl )
Ptm = Pc Ppl

(8)

Golden et al [3] modeled resistance due to collapsible

airways as a compressible cylinder with a fixed length
and variable volume Vc , whose resistance Rc is assumed
proportional to 1/Vc2 , and represented as

2
Vcmax
(9)
Rc = k3
Vc

where Vcmax stands for the maximal volume of collapsible

airways when the airways are fully distended. Under fully
distended conditions, k3 represent a small viscose airway
resistance.
Previously the relationship between Vc and Ptm has been
modeled as a nonlinear sigmoid function [6], the slope of
which is the airway compliance.


Vcmax




Ptm = a b ln
1
(10)
Vc
where a
stands for the point of the maximal airway compliance; b
is the parameter standing for a range in which
the most constant airway compliance occurs, i.e. the range
(a
2b
) to (a
+ 2b
).
c) Lower Airways: Lower airways have no rigid structure and are embedded in the lung parenchyma. Due to
traction arising from parenchyma on the airway walls the airways dilate with lung volume expansion [14], and therefore
minimize the airway resistance. The lower airway resistance
(Rl ) is inversely proportional to alveolar volume (Va ) [15],
thereby giving
k4
Rl =
(11)
Va
where k4 is a model parameter describing different pathophysiological states of the lower airways.
C. Model Dynamics
To describe the dynamics of the respiratory system requires representation of the volumes of lung compartments
and dynamics of gas flow between these. State variables are
selected describing the volume of gas in each compartment
(Va 1 , Vc , Vtc ), and differential equations formulated as:
dVa
= v a
(12)
dt
dVtc
= v
(13)
dt
dVc
= v c
(14)
dt
v a describes the net air flow into the alveoli, which can be
calculated from the pressure drop over the lower airways

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1 where

lower airway volume is lumped into the alveolar compartment

(Pc Pa ) divided by the lower airway resistance (Rl ) as

illustrated in figure 1(b), i.e.
v a =

Pc Pa
Rl

TABLE I

(15)

v describes airflow into the respiratory system, which can be

calculated from pressure gradient over the upper and central
airways (P Pc ) divided by the sum of airway resistance
in the upper (Ru ) and central (Rc ) airways as illustrated in
figure 1(b), i.e.
P Pc
v =
(16)
Ru + Rc
v c describes flow bypass due to collapsible airways, which
can be calculated from the flow entering the respiratory
system minus the flow entering the alveolar compartment
(v v a ) as illustrated in figure 1(b), i.e.
v c = v v a

Chest wall elastance (Ecw ) is assumed to be normal in all

cases, i.e. 5 cmH2 O/L [16].

(17)

III. M ODEL SIMULATIONS

This model includes seventeen equations with three differential equations (12-14) describing changes in state variables (Va , Vtc , Vc ), three equations describing flows between
compartments (15-17) and the remaining (1-11) describing
the relationship between pressures, volumes and resistances.
All equations can be solved to simulate a dynamic response
of the respiratory system to changes in ventilation, and
the resultant steady state, given values of model parameters {k1 , k2 , k3 , a
, b
, Vcmax , k4 , a, b, c, d, Ecw }, initial conditions of state variables (Va (0), Vtc (0), Vc (0)), and model
For spontaneous respiration inspiratory
inputs (Pm , P , v).
flow (v)
is not required as an input to the model, and the
pressure at mouth P equals the body surface pressure Pbs .
The model is used here to simulate forced inspiration and
expiration in three cases: normal patients, obstructive lung
disease (OLD) and restrictive lung disease (RLD). OLD is
characterized by an increase in airway resistance, because of
thickening, partial blockage and narrowing of the airways,
as is commonly seen in COPD. RLD is characterized by a
reduction on vital capacity (VC), because of alternations in
the lung parenchyma, disease of the pleura or the chest wall,
or neuromuscular apparatus.
To perform these simulations, initial values of state variables are set as in Table I according to reported values of
functional residual capacity (FRC) in normal, obstructive and
restrictive lung disease [16]. Values of model parameters are
fixed to represent the three conditions (Table II). OLD is
assumed to be an isolated airway disease, so that model
parameters of the alveolar space are assumed to be normal.
RLD is assumed to be an isolated alveolar disease, so that the
model parameters of the airways are assumed to be normal.
Values of k1 , k2 , k3 , a
, b
, Vcmax , k4 for airway model parameters are taken from the reference [6]. Values of a, b, c, d
for normal subjects and OLD patients are set or estimated
from textbook values [16] using an average elastance of
alveolar space, i.e. 5 cmH2 O/L [16]. For patients with RLD
these values are obtained from the work of Pereira et al [17].

I NITIAL VALUES FOR STATE VARIABLES .

Normal
OLD
RLD

Va (0)(L)

Vtc (0)(L)

Vc (0)(L)

3.0000
3.5000
1.5000

3.0748
3.5689
1.5735

0.0748
0.0689
0.0735

For each case (normal, OLD, and RLD) the model is used
to simulate flow and volume curves during forced respiration.
Four simulations are performed for each case, inspiratory
muscle pressure is fixed at -25 cmH2 O and expiratory muscle
pressure is set to 0, 30, 40, and 50 cmH2 O, respectively. To
verify the model, these simulations can be compared to the
results of standard lung function tests.
Figure 2 illustrates model simulated flow volume curves
during forced inspiration and expiration. Forced inspiration
starts at the FRC (point A), and ends at total lung capacity
(TLC) (point B). Relaxed expiration returns to point A, and
forced expiration ends at the RC (point C). The volume
between point B and C is the forced vital capacity (FVC),
and the forced expired volume in the first second is labeled
FEV1 . In clinical practice, two measurements are often used
to characterize obstructive and restrictive lung disease. These
are a relative FEV1 (FEV1,r ) calculated as FEV1 divided by
FVC; and a relative FVC (FVCr ) calculated as FVC divided
by the normal value of FVC. Model simulated values of
FEV1,r and FVCr are given in table III. The value of FVC
in normal conditions used in calculating FVCr is assumed to
be that obtained from model simulation of forced expiration
in normal subject with expiratory muscle pressure (Pm ) equal
to 50 cmH2 O.
TABLE III
R ELATIVE FEV1 AND FVC AS FRACTION OF NORMAL

Normal
OLD
RLD

Pm = 30cmH2 O
FEV1,r FVCr

Pm = 40cmH2 O
FEV1,r FVCr

Pm = 50cmH2 O
FEV1,r FVCr

0.82
0.35
0.96

0.83
0.35
0.96

0.84
0.35
0.97

0.98
0.79
0.48

0.99
0.80
0.48

1.00
0.81
0.48

Figure 2(a) illustrates a flow-volume curve of forced

ventilation in a normal subject. The maximal expiratory flow
(MEF) is about 8 L/s, and is only achieved during forced
expiration. The peak expiratory flow obtained in each forced
expiration varies only slightly when increasing expiratory
effort, i.e. when increasing Pm from 30 to 50 cmH2 O, a
standard result of lung function tests on normal subjects.
The values of FEV1,r (Table III), 0.82-0.84, for the normal
subject are consistent with reported values [16]. Figure 2(b)
illustrates forced ventilation in a patient with OLD. The simulated value of MEF is about 1.8 L/s, substantially lower than
normal. MEF is almost achieved during passive expiration
(Pm = 0) simulating flow limitation in relaxed expiration,
a simulation which is consistent with clinical findings in
severe COPD patients [13]. The calculated value of FEV1,r

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TABLE II
M ODEL PARAMETER VALUES FOR NORMAL , OLD AND RLD.
k1

k2
2

cmH2 O s/L cmH2 O s /L

Normal
OLD
RLD

0.5
0.5
0.5

0.2
0.2
0.2

Vcmax

k4

cmH2 O s

0.35
1.05
0.35

0.1
0.1
0.1

9.5
47.5
9.5

2.0
6.0
2.0

MEF

Normal

Pm=30

Flow (L/s)

8.0
8.0
13.3

Ecw

4.0
4.0
5.84

5.0
5.0
5.0
MEF

RLD

Pm=50

Pm=40

Pm=30

Pm=0

Pm=0

Pm=30

0.5

1.3 5.2
1.3 5.2
1.0 2.6

MEF
Pm=50
Pm=40

Pm=40

cmH2 O cmH2 O cmH2 O/L

OLD
1.5

Pm=50

b

cmH2 O s/L cmH2 O cmH2 O

0.2
0.2
0.2

a

k3
2

B
0

0.5

Pm=0

2
1

1.5

Pm=25
1

1.5

2.5

3.5

4.5

5.5

Lung volume (L)

2
2.5

Pm=25
3

3.5

Pm=25

4.5

Lung volume (L)

(a)

(b)

5.5

6.5

1.5

2.5

Lung volume (L)

(c)

Fig. 2. Model simulated flow-volume profiles during forced inspiration and expiration. Inspiratory and expiratory flow are represented using negative and
positive values respectively. FEV1 for an expiratory muscle pressure of 40 cmH2 0 is indicated by a circle. Solid lines represent forced inspiration at Pm
= -25 cmH2 0 and forced expiration at Pm = 50 cmH2 O. Dotted lines represent forced expiration at Pm = 40 cmH2 O. Dashed lines represent forced
expiration at Pm = 30 cmH2 O. Dashed-dotted lines represent passive expiration. Subplots illustrate flow-volume curves for (a) a normal subject; (b) an
OLD patient; and (c) a RLD patient.

and FVCr (Table III) are around 0.35 and 0.80 respectively,
typical of OLD patients [16]. Figure 2(c) illustrates forced
ventilation in a patient with RLD. MEF is close to normal,
FEV1,r is higher than normal and FVCr is reduced to 0.48
(Table III), typical of OLD patients [16].
IV. C ONCLUSION
This paper has described a model of respiratory mechanics
modified from previous models built using the functional
approach. By including representation of nonlinear pressurevolume curve of alveolar space and muscle pressure, the
model can be used to simulate forced respiration. The results
of these simulations are consistent with the usual results of
lung function test in normal subjects and in patients with
OLD and RLD, illustrating that quite complex pathologies
can be simulated with relatively simple models. Further
work is required to determine whether unique values can
be obtained for all model parameters in the clinical setting,
enabling tuning of the model to the individual patient.
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