Computers in Biology and Medicine 43 (2013) 1606–1613

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Computers in Biology and Medicine

journal homepage: www.elsevier.com/locate/cbm

A new approach to modeling of selected human respiratory system

diseases, directed to computer simulations
Grzegorz Redlarski n, Jacek Jaworski
Department of Mechatronics and High Voltage Engineering, Gdansk University of Technology, Gdansk, Poland

art ic l e i nf o a b s t r a c t

Article history: This paper presents a new versatile approach to model severe human respiratory diseases via computer
Received 17 January 2013 simulation. The proposed approach enables one to predict the time histories of various diseases via
Accepted 5 July 2013 information accessible in medical publications. This knowledge is useful to bioengineers involved in the
design and construction of medical devices that are employed for monitoring of respiratory condition.
Keywords: The approach provides the data that are crucial for testing diagnostic systems. This can be achieved
Model without the necessity of probing the physiological details of the respiratory system as well as without
Diseases identification of parameters that are based on measurement data.
Respiratory system & 2013 Elsevier Ltd. All rights reserved.
Obstructive
Restrictive

1. Introduction pneumatic mechanical resistances, inertances and compliances of

The respiratory system is one of the most important systems of
the human body that secures proper functioning of other systems.
Hence, its functional or structural disorders cause real threats.
According to various studies [1–7] respiratory diseases are usually
defined as any exceptions to the normal state that is typically
defined based on 90% of the healthy population. It is represented
by a group of symptoms that reveal only in a specific population—
named as ill individuals [1,2].
It is well-known that the present medicine is powered by the
latest biomedical engineering technologies, which support various
types of treatments. Good examples of those achievements, lead-
ing to new solutions in the field of pulmonary diagnostics, are
models of different medical conditions [8–16]. However, a deeper
understanding of the respiratory system and its pathological
mechanisms are the main requirements for application of such
models. The present methodology to model respiratory diseases,
known from the extensive literature [8–10,17–21], is based on
combination of mathematical models and monitored biosignals
(pressure, flow, etc.). Parameters of the model are estimated by
appropriate optimization methods. Due to the physical analogies
between pneumatic and electrical systems, the structure of the
human respiratory tract is usually presented as analogous to an
electrical system. This electrical system contains the RLC elements
(R—resistors, L—inductors, and C—capacitors), which represent the
n
Corresponding author. Present address: Gdansk University of Technology,
Faculty of Electrical and Control Engineering, Narutowicza 11/1280233 Gdansk,
Poland. Tel.: +48583472317.
E-mail address: g.redlarski@ely.pg.gda.pl (G. Redlarski).
specific anatomical parts. Besides many advantages (simplicity,
no requirement for significant computing power etc.), these
models are not free from serious drawbacks such like:

inability to change the nature and the intensity of lesions
modeled, which significantly reduces their versatility and
applicability,

low identification reliability obtained for certain model para-
meters [22,23],

substantial influence of natural variations that complicates
estimation of model parameters [6],

great influence of optimization algorithms on the effectiveness
and accuracy of parameter identification [8,22,24].
Additionally, it can be noticed that information on model para-
meter values is significantly scattered in the literature.
Referring to the disadvantages mentioned above, the purpose
of this paper is to fill the gap present in the literature by proposing
a versatile method useful to model selected respiratory diseases.
The method is based only on the knowledge of sources and
physiological effects of considered lesions that is accessible in
medical publications. Moreover, the values of model parameters
representing healthy and ill individuals are presented in this paper
as a complement to the main paper objective. The ability to create
models of respiratory diseases with defined parameter values is
extremely valuable during various research stages (e.g. for verifi-
cation of proposed or developed new scientific solutions). More-
over, the results presented are additionally valuable because of
their potential applications in applied technical systems, employed
for monitoring of respiratory diseases or diagnosis. Furthermore,

0010-4825/$ - see front matter & 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.compbiomed.2013.07.003
 G. Redlarski, J. Jaworski / Computers in Biology and Medicine 43 (2013) 1606–1613 1607

3. Modeling of changes in respiratory mechanics

In order to model the obstruction and restriction, changes in

the parameter values of the combined model (Fig. 2) are required,
corresponding to changes in respiratory mechanics.

3.1. Effects of obstruction and restriction

The obstruction is a phenomenon that results in narrowing of

specific anatomical features of the respiratory system. The con-
sidered phenomenon is frequently caused by: increased secretion
of mucus, muscle cramps, swelling of the mucous membranes,
inflammation etc. A significant growth in the values of resistance
Fig. 1. Meeting stringent criteria and proper test results (diagnosis 1) for adopted and inertance occurs as a result of respiratory obstruction. Accord-
settings (Model B) guarantees increased diagnostic tool reliability and proper test
results (diagnosis 2) for measured settings (Model A).
ing to [32,36] changes in the resistance are proportional to the
fourth power of the radii of considered anatomical features, while
changes in the inertance to the second [36]. The final mechanical
the possibilities to change the nature and intensity of the modeled feature, the compliance C, is described by the formula:
lesions, as proposed by the Authors, may support diagnostic or
calibration processes of medical devices. As a result of that it is dV
C¼ ð1Þ
possible to impose requirements much more stringent than for dP
real cases. For instance, if Model A (Fig. 1) represents a measured where dV represents a volume change caused by a pressure change
signal, the adoption of Model B instead—enforces to meet strin- dP.
gent criteria (e.g. for the amplitude A, the steepness angle α, the The impact of volume reduction on the compliance C, resulted
settling time T, etc.). Meeting stringent requirements (diagnosis 1) from the obstruction, may be assessed on the basis of Formula (1).
also guarantees proper operation under mild and real conditions Assuming constant driving pressure affecting the bronchi and
(diagnosis 2). provided by static contraction of the respiratory muscles, a
Because of a great variety of respiratory diseases and numerous decrease in the compliance C is characterized by the ratio:
ways of their classification (in terms of physiological changes: obstruc-
CN dV N =dP dV N
tive and restrictive; in terms of localization: bronchial, pleural, tracheal ¼ ¼ ð2Þ
CS dV S =dP dV S
etc. [3]) it is impossible to tackle the problem in a single, comprehen-
sive publication. Therefore, the Authors have limited the quantity where the subscript N represents obstruction variables, while the
of considered diseases to a few that result directly from certain subscript S healthy ones.
lesions located in respective parts of the respiratory system. Both For a linearized system near its operating point it may be
obstructive and restrictive groups of disorders are taken into con- written:
sideration [3,4,25,26]. Those cases, for which the anatomical features CN ΔV N
are afflicted by both of them, have not been taken into consideration. ¼ ð3Þ
CS ΔV S
According to [25], the obstruction is the prime phenomenon in
relation to the restriction. Therefore, the following obstructive diseases The ratio, defined by Formula (3), is dependent on the length l
are considered: asthma, chronic obstructive pulmonary disease and and the radius r of an anatomical feature (e.g. bronchi) according
congenital tracheal stenosis. As the representation of restrictive condi- to Relation (4):
tions, idiopathic pulmonary fibrosis is selected. In addition, breathing ΔV N π  l  r 2N1 π  l  r 2N2 π  l  ðr 2N1 r 2N2 Þ r 2 r 2N2
difficulty mechanisms caused by neuromuscular disorder, myasthenia ¼ ¼ ¼ N1 ð4Þ
ΔV S π  l  r S1 π  l  r S2
2 2 π  l  ðr S1 r S2 Þ
2 2 r 2S1 r 2S2
gravis, are also investigated.
where the subscript 1 represents an expanded feature and the
subscript 2 stands for the original size of the feature considered.
Eq. (4) may also be expressed by the tissue stretch ratio k,
2. Versatile model of the human respiratory system as presented by Eq. (5). However, one must assume that the
expansion is linear and the obstruction does not alter the nature of
Several models of the human respiratory system may be the feature:
distinguished by their applicability as well as different levels of 2
r 2N1 r 2N2 ðk  r N2 Þ2 r 2N2 k  r 2N2 r 2N2
complexity—according to [5,6,8,15,20,27–30,32–35]. Among all of ¼ ¼ 2
them a 10-coefficient model, described in [27–30], is often used r S1 r S2
2 2 2
ðk  r S2 Þ r S2
2
k  r 2S2 r 2S2
2

for lower respiratory tract mapping. For the upper respiratory tract ðk 1Þ  r 2N2 r N2 2
the most typical is a 6-coefficient model described in [5,20,30]. ¼ 2 ¼ ð5Þ
ðk 1Þ  r 2 r S2
S2
The combination of both these models, presented in [30], repre-
sents all important anatomical parts by one comprehensive model This implies that the ratio of bronchial compliances is propor-
of the respiratory system (Fig. 2). This enables one to analyze the tional to the second power of the ratio of the relevant radii. More-
central and peripheral respiratory tract. Based on the extensive over, the ratio of alveolar compliances is dependent on the third
literature survey [27,30,32,35,36] typical values of the model power of that ratio, which may be derived in a similar manner. As
parameters for healthy individuals are presented in Table 1. an effect of all alterations described in the pulmonary mechanics
The values of Pt and Pg have been adopted from the literature. resulted from the obstruction, the time constant of alveolar filling
According to [3,30–32] the tissue tension in the chest wall Pt increases significantly [4,6,30].
reaches up to  5 cmH2O and the driving pressure Pg can be A change in the elastance E of lung tissues is related to all
represented by a periodic function. Its frequency and amplitude the phenomena described above. Frequently, remodeling of lung
can reach up to 0.2 Hz and 5.5 cmH2O, respectively. tissues is observed, which results in a decrease in the elastance E.
1608 G. Redlarski, J. Jaworski / Computers in Biology and Medicine 43 (2013) 1606–1613

Fig. 2. A comprehensive model of the respiratory system [30]: Ruaw—upper airway wall resistance, Rua—upper airway resistance, Rc—central airway resistance, Rp—peripheral
airway resistance, Rl—lung tissues resistance, Rt—chest wall resistance, Iuaw—upper airway wall inertance, Iua—upper airway inertance, Ic—central airway inertance, It—chest
wall inertance, Cgua—upper airway gas compliance, Cuaw—upper airway wall compliance, Caw—bronchial wall compliance, Cg—alveolar gas compliance, Cl—lung tissues
compliance, Ct—chest wall compliance, Pg—pressure of breath cycle [cmH2O], Pt—pressure of chest wall stress [cmH2O], Pao—airway output pressure [cmH2O], dVao/dt—airway
output flow [l/s].

Table 1
Mean values of model parameters (Fig. 2) representing healthy individual.

Resistance coefficient Value [cmH2O s l  1] Inertance coefficient Value [cmH2O2 s l  1] Compliance coefficient Value [cmH2O  1 l]

Ruaw 24 Iuaw 7  10  3 Cgua 0.68  10  4

Rua 0.69 Iua 0.01 Cuaw 10.9  10  4
Rc 0.75 Ic 0.011 Caw 5  10  3
Rp 0.0852 It 2  10  3 Cg 3.6  10  3
Rl 0.206 Cl 0.2
Rt 3 Ct 0.22

It is observed along with the growth in the alveolar radius and a

decrease in the surface area per unit volume [37]. Hence, Func-
tional Residual Capacity (FRC) is increased, as a result of the
disturbed balance between elastic recoil forces of the lungs and
chest wall. Moreover, the alteration in the elastance E affects the
degree of tension in peripheral airways. Lung tissues operate like a
stabilizer that tightens the bronchial walls. If the elastance E is
decreased the effect of the stabilization is reduced significantly
consequently enhancing the obstruction (mainly peripheral part).
The loss of the elastance E leads to a nonlinear increase in the
compliance C [25] according to Formula (6). In fact, an alteration in
the elastance E is accompanied by a smaller change in the
compliance C [25,38,39] than calculated from Relation (6).
1
E¼ ð6Þ
C

The restriction is a phenomenon that results in reduction in the

lung compliance associated with a decrease in Vital Capacity (VC).
As a result the time constant of alveolar filling is reduced. This
phenomenon is caused mainly by destruction of elastic fibers
(elastin) [4] and leads directly to a decrease in the compliance C in
certain lung areas. It is associated with an uneven distribution of
the lung volume that increases significantly the effort of respira-
tory muscles.
3.2. Examples of obstruction and restriction
In Fig. 3 functional disorders observed for individuals affected
by the phenomena described in Section 3.1 are presented. Time
histories of lung volume represent the alveolar filling during long
deep inhalation. The volume is described by following equation:
Z The time histories of lung volume in Fig. 3 are intended to
t
V ao ðtÞ ¼ V_ ao ðτÞdτ
0 localization and the intensity of every phenomenon depend on the
Fig. 3. Lung volumes of individuals: healthy and affected by obstructive and
restrictive diseases, simulated with an 16-coefficient model of the respiratory
system.
On the basis of [2,6,17,26,36,37,40,41–43] and simulation-
based research by the use of the model presented (Fig. 2) the
parameter values for the obstruction and the restriction have
been estimated by the Authors. In the case of obstruction the
central tract narrowing of 45% is considered (that leads to a 6-fold
increase in the value of Rc and a 4-fold increase in the value of Ic, as
discussed in Section 3.1). In the case of restriction a 2-fold increase
in the elastance of lung tissues E is assumed that determines the
decrease of 50% in the value of Cl.
ð7Þ present the impact of functional disorders in general terms. The
 G. Redlarski, J. Jaworski / Computers in Biology and Medicine 43 (2013) 1606–1613
considered medical conditions as presented in next section.
It should be noted that in practice a great number of factors may
disrupt the control of respiration [3,26,37,44]. As a result altera-
tions of the respiratory pattern occur. However, for the purpose
of simulation-based research, e.g. preliminary verification of
developed solutions, in the opinion of the Authors the approach
presented remains suitable.
4. Modeling of selected respiratory diseases
Precise modeling of respiratory diseases is very complex and
time-consuming because of many factors that determine dysfunc-
tions of examined individuals. Therefore in the case of any disease
the results obtained during the examination may differ signifi-
cantly. Multi-strain pathogens and natural variation in humans are
the main reasons of that variation. Probably, it is impossible to
model all those elements and factors that affect the condition
because of the extraordinary dynamic complexity of biological
systems. Therefore modeling of medical conditions is a technical
process that should be construed as an assessment of the phe-
nomena under consideration. Such an approach may be suitable
for computer-based research and hardware-in-the-loop simula-
tions that result in fast implementation and verification of new
solutions developed. Moreover, all information on modeling pro-
cesses is valuable to those scientists and engineers, who have
a broad knowledge of the scientific and technical solutions.
However, their competence in medical fields is not required,
where these solutions are expected to be applied.
Mathematical modeling of respiratory diseases presented in
this subsection is based on the comprehensive model of the
respiratory system (Fig. 2) and information accessible in medical
literature. All medical conditions considered are discussed below:

Asthma is a chronic inflammatory disease of the airways that
through the alteration in lung functions, blood gas abnormal-
ities and chronic bronchial inflammation leads to significant
changes in the breathing pattern and fierce respiratory res-
ponses to chemical stimulation. Among all symptoms of
asthma, bronchial hyperactivity and substantial reduction in
airway patency are dominant, induced frequently by muscle
contraction [3,4,8,17,25]. Obstruction occurs over the entire
length of the bronchial tree resulting in prolonged expiration
and leading to lung inflation. Due to bronchial obstruction, the
ratio of arterial-to-venous blood is changed that leads to
hypoxemia and increased respiratory rate [21]. In the case of
asthma the resistances of the central and distal airways are
increased comparably. Therefore, the narrowing of the trachea
and bronchi results in alteration of the values of the parameters
Rc, Ic and Rp. On the basis of the data available [8,21,36,45] it
may be assessed that severe asthma is accompanied by reduc-
tion in the airway patency of approx. 30% to 40%. Hence,
narrowing of 30% of the central and distal airways is assessed
causing more than a 4-fold increase in the resistances Rc and Rp,
and a 2-fold increase in the inertance Ic. Additionally, a stenosis
of the respiratory tract of 30%, leads to about 2-fold decrease
in the value of Caw based on Formula (5).

Chronic obstructive pulmonary disease (COPD) results from
pathological changes in the airways and incompletely reversi-
ble destruction of lung parenchyma. COPD is characterized
by simultaneous occurrence of: chronic bronchitis, chronic
bronchiolitis and emphysema. Alterations in respiratory control
are more complex than in the case of asthma and depend on
many factors related to the nature and severity of the disease
itself. Inflammation of the bronchi (peripheral part mainly)
leads to their structural disorders that as a consequence results
1609
in their untimely closure. The phenomenon of emphysema
is denoted as destruction of alveolar walls and loss of tissue
elastance [4,37,40,45–47]. As a result the value of expiratory
pressure is reduced causing a significant reduction in the
expiratory flow. The alterations in lung parenchyma increase
the tissue compliance and decrease its resistance (represented
by the parameters Cl and Rl). Destruction of alveolar walls
results in an increase in the gas volume of the respiratory tract
that increases the value of the parameter Cg. The bronchial
obstruction corresponds to a substantial increase in the values
of the parameters Rc, Rp and Ic- and this effect is much more
significant in peripheral parts. Hence, on the basis of the data
available [3,4,9,10,23,25,26,32,37,40,45–51] it can be assessed
that the stage of severe COPD is accompanied by central tract
stenosis of approx. 15%, distal airways narrowing of 40% the and
45% loss of tissue elastance. Such assumptions result in a 90%
increase in the resistance Rc and a 40% increase in the inertance
Ic. In distal airways almost a 8-fold increase in the resistance
Rp and nearly a 3-fold reduction in the value of Caw are
observed—according to Eq. (5). Moreover, according to Eq. (6),
an approx. 1.8-fold increase in the compliance Cl occurs due to
changes in the value of tissue elastance. Based on [52] the loss
of tissue elastance is associated with a linear decrease in the
resistance, hence a decrease in the value of Rl of approx. 45% is
observed. Moreover, an increase in the value of the alveolar gas
compliance Cg of 14% is assessed, based on [47]. It results from a
significant growth in FRC.

Idiopathic pulmonary fibrosis is classified as an interstitial
pneumonia. It is characterized by dilation of the distal airways
and connective tissue deposition in the lung parenchyma that
leads to scarring. That results in the loss of oxygen diffusion
capacity and an increase in elastance preceded with the
diameter expansion and stiffening of bronchi. Moreover a
slight increase in the respiratory airflow and reduction in Tidal
Volume (TV) is observed. The pathogenesis of pulmonary
fibrosis has not been fully elucidated [43,53]. Thus a group of
diseases that are accompanied by fibrosis is characterized by
reduced compliance and increased tissue resistance—repre-
sented by the parameters Cl and Rl. According to [41,42,52,53]
it may be noticed that for severe idiopathic pulmonary fibrosis
an increase in the lung elastance is significant—reaching 200%.
Hence, based on Formula (6) and results presented in [52],
nearly a 3-fold decrease in the value of the lung tissues
compliance and a 3-fold increase in the value of the resistance
is observed. Distal airways are stiffer, so the value of Rp
decreases slightly—in [52] this decline is almost imperceptible
and it usually drops down to a few percent [41]. Moreover,
based on [41,42] it may be stated that severe pulmonary
fibrosis corresponds to an approx. 2-fold reduction in the value
of Caw (due to the reconstruction of the bronchial wall) and
a decrease in FRC of 30%, represented by the parameter Cg.

Myasthenia gravis is classified as a neuromuscular disease,
for which lung functions are not impaired, however a muscle
activity disorder is observed. As an effect, muscles cannot
support proper ventilation. The reason for that may be either
damage to nerve or neuromuscular transmission or muscle
pathology [54,55]. The selection of myasthenia gravis as a
representative respiratory disease is conditioned by its extra-
ordinary impact on the effectiveness of respiration. In this
paper, damage to acetylcholine receptors in the neuromuscular
transmission system is assumed. Modeling of severe myasthe-
nia gravis (stage 3 and 4 [54,55]) results in a significant change
in the value of Pg that represents the driving pressure. Accord-
ing to [54], for the third stage of myasthenia gravis the drop
of inspiratory pressure of 30–50% is observed. In this paper this
drop was assumed as equal to 30%.
1610 G. Redlarski, J. Jaworski / Computers in Biology and Medicine 43 (2013) 1606–1613

Table 2
A list of changes in parameter values.

Respiratory state Central airways Peripheral airways Bronchi Alveoli Lung tissues Respiratory muscles

Healthy Rc Ic Rp Caw Cg Cl Rl |Pg|

Asthma 4.2  Rc 2  Ic 4.2  Rp 0.5  Caw Cg Cl Rl |Pg|
COPD 1.9  Rc 1.4  Ic 7.7  Rp 0.36  Caw 1.14  Cg 1.8  Cl 0.55  Rl |Pg|
Fibrosis Rc Ic 0.9  Rp 0.5  Caw 0.7  Cg 0.3  Cl 3  Rl |Pg|
Myasthenia Rc Ic Rp Caw Cg Cl Rl 0.7  |Pg|
Tracheal stenosis 4.5  Rc 1,7  Ic Rp Caw Cg Cl Rl |Pg|

Congenital tracheal stenosis is a pathological phenomenon

caused by underdevelopment of cartilage and fibrous mem-
brane of the trachea. Tracheal stenosis of less than 50%
is asymptomatic, however repeated airway inflammations
may occur [37]. Modeling of relevant medical conditions results
in changes in the values of the central airways resistance Rc and
the inertance Ic. It should be noted that the trachea constitutes
nearly 50% of the total resistance of the lower respiratory tract
and about 60% of the central airways [37]. According to these
facts [3] the stenosis of the initial diameter of 60% is assessed.
That results in a significant increase in the values of central
airways parameters: the resistance Rc (more than 4.5-fold) and
the inertance Ic (1.7-fold).

The list of the necessary model parameters required for

computational evaluation of the conditions described above, and
based on the versatile model of the respiratory system (Fig. 2),
is presented in Table 2.
Fig. 4. Pulmonary volumes of individuals: healthy and affected by investigated
diseases.
5. Simulation results and discussion

Results of simulation-based research, based on the values of the

parameters presented in Table 2, and representing tidal breathing
of medical cases considered by the Authors, are presented in
Figs. 4–6 as a steady-state. Time histories of pulmonary volumes
are illustrated in Fig. 4, while expiratory airflows in Fig. 5 and
initial parts of inspiratory airflows in Fig. 6. The values of TV were
calculated, as presented in Table 3, based on expiratory airflows.
Furthermore, the results of dynamic spirometry are presented
in Fig. 7. The diseases were also described in details by forced
expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and
FEV1/FVC ratio, all well presented in Table 4.
The time histories of the pulmonary volume, presented in
Fig. 4, illustrate considerable functional differences. The waveform
of the COPD is unexpected—the peak value of the pulmonary
volume is increased in relation to healthy individuals. However,
that growth is not beneficial as it results from two factors. The first
is the loss of parenchyma elastance causing the emphysema, while
the second comes from the influence of the nervous system that is
not considered in this paper. Due to emphysema, greater volume Fig. 5. Expiratory airflows of individuals: healthy and affected by investigated
oscillations may be noticed. However, they are counterbalanced by diseases.
an increased value of FRC. As a result TV is only slightly increased.
The increased value of FRC results from the growth in airway
resistance only and may be seen in the final phase of expiration all medical conditions the flow considered is limited and greatly
(Fig. 4). The remaining obstructive diseases are also characterized hinders gas exchange. Generally, both amplitude and inclination of
by an increase in FRC. However, in the absence of elastance the expiratory flow are changed. Among the presented time
loss, reductions in peak values of the pulmonary volumes are histories only idiopathic fibrosis causes no significant alteration
noticed. The fibrosis, as a restrictive disease, results in a significant in the rate of growth/descent because of changes in the value of
reduction in TV by a decrease in the inspiratory volume. Further- airway resistance. However, the amplitude is changed as a result
more, in the case of myasthenia gravis, diminution of muscle of TV reduction, what corresponds directly to a smaller quantity
strength elucidates the reduction in TV that may be misdiagnosed of gas accumulated in the alveoli. In the case of COPD expiratory
as a restrictive disorder. airflow limitation is smaller than in the case of other obstruc-
Great differences are observed between individuals, based on tive diseases. It results from the loss of parenchyma elastance
waveforms of expiratory airflows presented in Fig. 5. In the case of that counterbalances the influence of increased resistance. The
 G. Redlarski, J. Jaworski / Computers in Biology and Medicine 43 (2013) 1606–1613 1611

Table 4
Values of considered parameters for considered clinical cases.

Respiratory state FEV1 [l] FVC [l] FEV1/FVC [%]

Healthy 3.48 4.54 77

Asthma 2.80 4.43 63
COPD 3.42 5.28 65
Fibrosis 2.01 2.14 94
Myasthenia 2.42 3.17 76
Tracheal stenosis 2.79 4.44 63

where t1 and t2 denote time instances representing the start and

end of the expiration. As expected, COPD leads to a slight increase
in the value of TV consistent with [26]. The remaining respiratory
diseases result in a considerable or great decrease in the values of
TV [4,5,10,23,26,43,49,54].
The time histories of inspiratory airflows, presented in Fig. 6,
illustrate considerable differences between the time constants of
Fig. 6. Initial parts of inspiratory airflows of individuals: healthy and affected by
investigated diseases.
alveolar filling. In the case of obstructive diseases their nature can
be expressed by an increase in the time constant T of alveolar
filling. It is obviously caused by a significant growth in the airway
Table 3 resistance. As expected, pulmonary fibrosis results in a small
Values of tidal volumes for considered reduction in the time constant T. The only disease with no change
clinical cases. in the considered parameter is myasthenia gravis. It affects the
respiratory muscles and reduces the value of driving pressure,
Respiratory state TV [l]
however the respiratory mechanics is not affected. Because of that
Healthy 0.463 the inspiratory airflow is reduced proportionally, however its
Asthma 0.403 shape is identical to the original one, as presented in Fig. 4.
COPD 0.479 The assessment of the respiratory mechanics solely based
Fibrosis 0.235
on tidal breathing is problematic and questionable [3,6,32,36].
Myasthenia 0.323
Tracheal stenosis 0.406 A much more convenient form of examination is dynamic spiro-
metry. The research on dynamic tests was simulated, preceded by
a deep expiration [25]. However, significant patient commitment
is required during considered examination. Stronger contraction of
the respiratory muscles was simulated by an increased amplitude
and reduced frequency of the driving pressure. The amplitude was
adjusted to reach both maximum and minimum volume of the
lungs. Obviously, through the use of linear models, the reliability
of the respiratory system mapping is insufficient. This principle
applies especially to the highly nonlinear edges of pressure–
volume characteristics of respiratory organs [3]. However, research
on dynamic spirometry is aimed only to generate qualitative data.
Significant differences between the results of dynamic spiro-
metry appear in the time histories presented in Fig. 7. Most of
them correspond with the results obtained by data presented in
Figs. 4 and 5. The values of FEV1, FVC and FEV1/FVC presented
in Table 4 describe the results of examination in details. However,
in the case of COPD, the results obtained do not correspond
completely with those expected, based on medical literature. The
value of FVC is much greater than the value obtained for healthy
individuals, while the value of FEV1 is only slightly reduced. This
behavior results from the application of a linear model, which
misrepresents phenomena of the respiratory tract. A significant
Fig. 7. Pulmonary volumes of individuals obtained from dynamic spirometry. decrease in the lung elastance leads to greater volume oscillations
(Fig. 7). This reduces the negative effect of flow limitation, which
remaining medical conditions manifest themselves as changes in on the other hand results from an increase in the airway resis-
both amplitude and shape of the flow curves. In the case of tance. Due to these facts at the end of expiration the alveoli
obstructive diseases, the changes are caused by an increase in become almost empty. In practice, the premature closing of the
airway resistance and in the case of neuromuscular diseases by peripheral airways, as described in Section 4, increases signifi-
diminution of the muscle strength. cantly the respiratory resistance during expiration. Therefore,
Based on expiratory airflows presented in Fig. 5 tidal volumes at the end of expiration the alveoli still contain a great amount
were calculated according to Formula (8) and are presented in of breathing gas, however in Fig. 7, they are almost empty.
Table 3: In practice, both FEV1 and FVC are reduced significantly.

Z  Nevertheless, all FEV1/FVC values clearly indicate the airway
t2
TV ¼ abs V_ ao ðtÞdt ð8Þ obstruction (values smaller than for healthy individuals) and lung
t1 restriction (values bigger than for healthy individuals). As none of
1612 G. Redlarski, J. Jaworski / Computers in Biology and Medicine 43 (2013) 1606–1613
these phenomena are observed in myasthenia, no change in FEV1/
FVC ratio value is noted. In the case of COPD the obstruction
is found despite incorrect values of the components of this ratio.
All these facts result from the absence of non-linear resistance in
each component. It should be noted that despite correct test
results obtained by the Authors, significant errors in respiratory
mapping resulting from miscalculations of the ratio components
should be considered. Therefore the final results of dynamic spiro-
metry for COPD are not always reliable.
6. Summary
All selected medical conditions affect significantly patient′s
comfort. The proposed method supporting modeling of various
diseases via information accessible in medical publications may be
helpful to many scientists. Simulation-based research on various
medical conditions result in fast implementation and verification
of new solutions developed. Moreover, it may be helpful in simpli-
fying or strengthening some medical procedures. In addition,
information about modeling of medical conditions is valuable to
many scientists, who have a broad knowledge of technical solu-
tions, but usually no competence in medical fields, where these
solutions are expected to be applied.
The proposed method seems to be very promising. The pre-
sented results are consistent with the information available in
medical literature [4,5,10,23,26,43,49,54]. Analysis of the results
selected by the Authors indicates that most of them correspond
with the data obtained by specialists during clinical research.
Furthermore, breathing patterns obtained by the Authors can
reveal disorders of the respiratory muscles that may be found
helpful to physiotherapists.
It was proven that modeling of respiratory diseases via elec-
trical analogues and knowledge available is possible, promising
and of high applicability. However, neglecting nonlinear effects
may lead to significant errors, especially during forced breathing –
as presented in Section 5 – making results of COPD unreliable. Due
to that fact, at least certain nonlinear effects should be taken into
account in respiratory mapping. Nevertheless, the presented
method provides great time saving and acceptable results, with
no tedious and time-consuming identification of model para-
meters [6,8,22–24,30]. Moreover, it should be noted that a slight
overestimation of parameters considered results in much more
stringent requirements than in reality. That may be valuable in
design of various medical devices or diagnostic systems, such
as spirometry, plethysmography, forced oscillation technique etc.
In conclusion it can be said that the approach proposed by the
Authors may become an extremely valuable tool for streamlining
and accelerating research on the development of new diagnostic
method treatments. However, it should be reminded that even
excellent models are only limited-scope representation of reality.
A conflict of interest statement
None declared.
References
[1] Standarized lung function testing, Official statement of the European Respira-
tory Society, Eur. Respir. J. Suppl. 16 (1993) 1–100.
[2] Standarization of Spirometry, 1994 Update. American thoracic society,
Am. J. Respir. Crit. Care Med. 152 (1995) 1107-1136.
[3] S.E. Weinberger, B.A. Cockrill, J. Mandel, Principles of Pulmonary Medicine,
(fifth ed.), Saunders Elsevier, Philadelphia, 2008.
[4] P. Śliwiński, Współistnienie astmy i POChP, Alergia 2 (2009) 13–18.
[5] M. Cauberghs, K.P. Van de Woestijne, Mechanical properties of the upper
airway, J. Appl. Physiol. 55 (1983) 335–342.
[6] W. Tomalak, Wybrane aspekty badania mechaniki oddychania i modelowania
systemu oddechowego przy użyciu techniki oscylacji wymuszonych, Sc.D.
Dissertation, 1998, IGiCP.ZP; Rabka.
[7] E. Wiatr, E. Rowińska-Zakrzewska, M. Pirożyński, Choroby śródmiąższowe płuc,
Alfa Medica Press, Bielsko-biala, 2012.
[8] A. Rajagiri, B. Diong, M. Goldman, H. Nazeran, Can asthma in children be
detected by the estimated parameter values of the augmented RIC model?
Conf. Proc. IEEE Eng. Med. Biol. Soc. 28 (2006) 5595–5598.
[9] C. Ionescu, E. Derom, R. De Keyser, Assessment of respiratory mechanical
properties with constant-phase models in healthy and COPD lungs, Comput.
Methods Programs Biomed. 97 (2010) 78–85.
[10] A.M. Di Mango, A.J. Lopes, J.M. Jansen, P.L. Melo, Changes in respiratory
mechanics with increasing degrees of airway obstruction in COPD: detection
by forced oscillation technique, Respir Med. 100 (2006) 399–410.
[11] J. Chmielecki, et al., Optimization of dosing for EGFR-mutant non-small cell
lung cancer with evolutionary cancer modeling, Sci. Transl. Med. 3 (2011)
90ra59, http://dx.doi.org/10.1126/scitranslmed.3002356.
[12] H. Koc, et al., The role of mathematical modeling in VOC analysis using
isoprene as a prototypic example, J. Breath Res. 5 (2011) 037102, http://dx.doi.
org/10.1088/1752-7155/5/3/037102.
[13] K.J. Cios, H. Mamitsuka, T. Nagashima, R. Tadeusiewicz, Computational
intelligence in solving bioinformatics problems, Artif. Intell. Med. 35 (2005)
1–8.
[14] J. Szaleniec, J. Składzień, R. Tadeusiewicz, K. Oleś, M. Konior, R. Przeklasa, How
can an otolaryngologist benefit from artificial neural networks? Otolaryngol.
Pol. 66 (2012) 241–248.
[15] J. Dolensek, F. Runovc, M. Kordas, Simulation of pulmonary ventilation and its
control by negative feedback, Comput. Biol. Med. 35 (2005) 217–228.
[16] R. Sturm, A computer model for the simulation of fiber–cell interaction
in the alveolar region of the respiratory tract, Comput. Biol. Med. 41 (2011)
565–573.
[17] D.W. Kaczka, E.P. Ingenito, E. Israel, K.R. Lutchen, Airway and lung tissue
mechanics in asthma, effects of Albuterol, Am. J. Respir. Crit. Care Med. 159
(1999) 169–178.
[18] M. Bahoura, Pattern recognition methods applied to respiratory sounds
classification into normal and wheeze classes, Comput. Biol. Med. 39 (2009)
824–843.
[19] D. Kaczka, E. Ingenito, K. Lutchen, Technique to determine inspiratory
impedance during mechanical ventilation: implications for flow limited
patients, Ann. Biomed. Eng. 27 (1999) 340–355.
[20] R. Peslin, C. Duvivier, P. Jardin, Upper airway walls impedance measured with
head plethysmograph, J. Appl. Physiol. 57 (1984) 596–600.
[21] R. Peslin, C. Duvivier, Partioning of respiratory mechanical impedance by
absolute and differential body plethysmograph, IEEE Trans. Biomed. Eng. 46
(1990) 1339–1345.
[22] J. Eyles, R. Pimmel, Estimating respiratory mechanical parameters in parallel
compartment models, IEEE Trans. Biomed. Eng. 4 (1981) 313–317.
[23] B. Diong, M. Goldman, H. Nazeran, Respiratory impedance values in adults are
relatively insensitive to mead model lung compliance and chest wall com-
pliance parameters, IFMBE Proc. 32 (2010) 201–203.
[24] G. Avanzolini, et al., A new approach for tracking respiratory mechanical
parameters in real-time, Ann. Biomed. Eng. 25 (1997) 154–163.
[25] J. Kowalski, A. Koziorowski, L. Radwan, Ocena czynności płuc w chorobach
układu oddechowego, 2004, Borgis; Warsaw.
[26] J. Milic-Emili, Recent advances in clinical assessment of control of breathing,
Lung 160 (1982) 1–17.
[27] R. Peslin, Computer simulation of respiratory impedance and flow transfer
functions during high frequency oscillations, Br. J. Anaesth. 63 (1989) 91–94.
[28] M. Rotger, R. Peslin, C. Duvivier, D. Navajas, C. Gallina, Density dependence of
respiratory input and transfer impedances in humans, J. Appl. Physiol. 65
(1988) 928–933.
[29] P. Piwowar, Diagnosing human′s airduct disease by negative pressure impulse
method, Conf. Proc. IEEE IMTC 23 (2006) 695–699.
[30] P. Piwowar, Pomiar mechanicznych parametrów dróg oddechowych metodą
wymuszania krótkotrwałych, ujemnych impulsów ciśnienia, Sc.D. Disserta-
tion, 2006, wyd. AGH; Cracow.
[31] E.R. Weibel, Morphometry of the Human Lung, Springer Verlag, Berlin, 1963.
[32] A.R. Carvalho, W.A. Zin, Respiratory mechanics: principles, utility and advances, in:
A. Gullo (Ed.), Anaesthesia, Pharmacology, Intensive Care and Emergency Medicine
A.P.I.C.E, Springer-Verlag Italia, Milan, 2011, pp. 33–46.
[33] J. Kretschmer, A. Wahl, K. Moller, Dynamically generated models for medical
decision support systems, Comput. Biol. Med. 41 (2011) 899–907.
[34] A.G. Polak, J. Mroczka, Nonlinear model for mechanical ventilation of human
lungs, Comput. Biol. Med. 36 (2006) 41–58.
[35] W. Tomalak, R. Peslin, C. Duvivier, Respiratory tissue properties derived
from flow transfer function in healthy humans, J. Appl. Physiol. 82 (1997)
1098–1106.
[36] T. Ritz, et al., Guidelines for mechanical lung function measurements in
psychophysiology, Psychophysiol 39 (2002) 546–567.
[37] D. Dziedzic, Choroby układu oddechowego, 2004, Wydawnictwo Lekarskie
PZWL; Warsaw.
[38] J. Pillow, et al., Variable ventilation improves ventilation and lung compliance
in preterm lambs, Intensive Care Med. 37 (2011) 1352–1359.
[39] A. Chatterjee, et al., Heat shock protein 90 inhibitors prolong survival,
attenuate inflammation, and reduce lung injury in Murine sepsis, Am J. Respir
Crit. Care Med. 176 (2007) 667–675.
 G. Redlarski, J. Jaworski / Computers in Biology and Medicine 43 (2013) 1606–1613 1613

[40] T. Similowski, POChP Przewlekła Obturacyjna Choroba płuc, Elsevier [54] A.K. Lefvert, K. Bergstrom, G. Matell, P.O. Osterman, R. Pirskanen, Determina-
Urban&Partner, Wroclaw, 2011. tion of acetylcholine receptor antibody in myasthenia gravis: clinical useful-
[41] S. Nava, F. Rubini, Lung and chest wall mechanics in ventilated patients with ness and pathogenic implications, J. Neurol. Neurosurg. Psychiatry 41 (1978)
end stage idiopathic pulmonary fibrosis, Thorax 54 (1999) 390–395. 394–403.
[42] M. Demedts, et al., High-dose acetylcysteine in idiopathic pulmonary fibrosis, [55] A. Jaretzki, et al., Myasthenia gravis: recommendations for clinical research
N. Engl. J. Med. 353 (2005) 2229–2242. standards, Neurology 55 (2000) 16–23.
[43] T. Gross, G. Hunninghake, Idiopathic pulmonary fibrosis, N. Engl. J. Med. 345
(2001) 517–525.
[44] A. Topeli, F. Laghi, M. Tobin, The voluntary drive to breathe is not decreased in
hypercapnic patients with severe COPD, Eur. Respir. J. 18 (2001) 53–60.
[45] P.J. Barnes, S. Godfrey, Astma Oskrzelowa, Elsevier Urban&Partner, Wroclaw,
Grzegorz Redlarski, PhD, DSc, Eng. Headmaster of the Department of Mecha-
2001.
tronics and High Voltage Engineering at the Electrical and Control Engineering
[46] J. Lehnen, B. Panaszek, J. Pluta, P. Bohater, Choroby Dróg Oddechowych,
Faculty at Gdansk University of Technology. He received his M.Sc. in 2000 within
MedPharm, Wroclaw, 2011.
the specialization of control engineering and advanced in the specialization of
[47] D. Massaro, G. Massaro, Estrogen regulates pulmonary alveolar formation, loss,
electrical engineering. As a result, he received his Ph.D. in 2003 and D.Sc. in 2011.
and regeneration in mice, Am. J. Physiol. Lung Cell Mol. Physiol. 287 (2004)
From 2011 he is also employed as a Associate Professor at the Faculty of Technical
L1154–L1159.
Sciences at the University of Warmia and Mazury in Olsztyn. His main fields of
[48] T. Officer, M. Pellegrino, V. Brusasco, J. Rodarte, Measurement of pulmonary
interest are power electronics, power engineering and, recently, biomedical
resistance and dynamic compliance with airway obstruction, J. Appl. Physiol.
engineering.
85 (1998) 1982–1988.
[49] E. Tschernko, et al., Changes in ventilatory mechanics and diaphragmatic
function after lung volume reduction surgery in patients with COPD, Thorax
52 (1997) 545–550.
[50] J. Ora, et al., Effect of obesity on respiratory mechanics during rest and exercise
in COPD, J. Appl. Physiol. 111 (2011) 10–19. Jacek Jaworski, MSc, Eng. Lecturer in the Department of Mechatronics and High
[51] G. Zosky, et al., Vitamin D deficiency causes deficits in lung function and alters Voltage Engineering at the Electrical and Control Engineering Faculty at Gdansk
lung structure, Am. J. Respir. Crit. Care Med. 183 (2011) 1336–1343. University of Technology. He received his M.Sc in 2011 in the major of Control
[52] H. Bachofen, M. Scherrer, Lung tissue resistance in diffuse interstitial Engineering and Robotics, specialization Control Engineering. Main fields of
pulmonary fibrosis, J. Clin Invest. 46 (1967) 133–140. interests are: biomedical engineering and application of control and signal
[53] B. Suki, J. Bates, Lung tissue mechanics as an emergent phenomenon, J. Appl. processing systems in medical sciences.
Physiol. 110 (2011) 1111–1118.