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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
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
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]
considered medical conditions as presented in next section. in their untimely closure. The phenomenon of emphysema
It should be noted that in practice a great number of factors may is denoted as destruction of alveolar walls and loss of tissue
disrupt the control of respiration [3,26,37,44]. As a result altera- elastance [4,37,40,45–47]. As a result the value of expiratory
tions of the respiratory pattern occur. However, for the purpose pressure is reduced causing a significant reduction in the
of simulation-based research, e.g. preliminary verification of expiratory flow. The alterations in lung parenchyma increase
developed solutions, in the opinion of the Authors the approach the tissue compliance and decrease its resistance (represented
presented remains suitable. 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
4. Modeling of selected respiratory diseases obstruction corresponds to a substantial increase in the values
of the parameters Rc, Rp and Ic- and this effect is much more
Precise modeling of respiratory diseases is very complex and significant in peripheral parts. Hence, on the basis of the data
time-consuming because of many factors that determine dysfunc- available [3,4,9,10,23,25,26,32,37,40,45–51] it can be assessed
tions of examined individuals. Therefore in the case of any disease that the stage of severe COPD is accompanied by central tract
the results obtained during the examination may differ signifi- stenosis of approx. 15%, distal airways narrowing of 40% the and
cantly. Multi-strain pathogens and natural variation in humans are 45% loss of tissue elastance. Such assumptions result in a 90%
the main reasons of that variation. Probably, it is impossible to increase in the resistance Rc and a 40% increase in the inertance
model all those elements and factors that affect the condition Ic. In distal airways almost a 8-fold increase in the resistance
because of the extraordinary dynamic complexity of biological Rp and nearly a 3-fold reduction in the value of Caw are
systems. Therefore modeling of medical conditions is a technical observed—according to Eq. (5). Moreover, according to Eq. (6),
process that should be construed as an assessment of the phe- an approx. 1.8-fold increase in the compliance Cl occurs due to
nomena under consideration. Such an approach may be suitable changes in the value of tissue elastance. Based on [52] the loss
for computer-based research and hardware-in-the-loop simula- of tissue elastance is associated with a linear decrease in the
tions that result in fast implementation and verification of new resistance, hence a decrease in the value of Rl of approx. 45% is
solutions developed. Moreover, all information on modeling pro- observed. Moreover, an increase in the value of the alveolar gas
cesses is valuable to those scientists and engineers, who have compliance Cg of 14% is assessed, based on [47]. It results from a
a broad knowledge of the scientific and technical solutions. significant growth in FRC.
However, their competence in medical fields is not required, Idiopathic pulmonary fibrosis is classified as an interstitial
where these solutions are expected to be applied. pneumonia. It is characterized by dilation of the distal airways
Mathematical modeling of respiratory diseases presented in and connective tissue deposition in the lung parenchyma that
this subsection is based on the comprehensive model of the leads to scarring. That results in the loss of oxygen diffusion
respiratory system (Fig. 2) and information accessible in medical capacity and an increase in elastance preceded with the
literature. All medical conditions considered are discussed below: diameter expansion and stiffening of bronchi. Moreover a
slight increase in the respiratory airflow and reduction in Tidal
Asthma is a chronic inflammatory disease of the airways that Volume (TV) is observed. The pathogenesis of pulmonary
through the alteration in lung functions, blood gas abnormal- fibrosis has not been fully elucidated [43,53]. Thus a group of
ities and chronic bronchial inflammation leads to significant diseases that are accompanied by fibrosis is characterized by
changes in the breathing pattern and fierce respiratory res- reduced compliance and increased tissue resistance—repre-
ponses to chemical stimulation. Among all symptoms of sented by the parameters Cl and Rl. According to [41,42,52,53]
asthma, bronchial hyperactivity and substantial reduction in it may be noticed that for severe idiopathic pulmonary fibrosis
airway patency are dominant, induced frequently by muscle an increase in the lung elastance is significant—reaching 200%.
contraction [3,4,8,17,25]. Obstruction occurs over the entire Hence, based on Formula (6) and results presented in [52],
length of the bronchial tree resulting in prolonged expiration nearly a 3-fold decrease in the value of the lung tissues
and leading to lung inflation. Due to bronchial obstruction, the compliance and a 3-fold increase in the value of the resistance
ratio of arterial-to-venous blood is changed that leads to is observed. Distal airways are stiffer, so the value of Rp
hypoxemia and increased respiratory rate [21]. In the case of decreases slightly—in [52] this decline is almost imperceptible
asthma the resistances of the central and distal airways are and it usually drops down to a few percent [41]. Moreover,
increased comparably. Therefore, the narrowing of the trachea based on [41,42] it may be stated that severe pulmonary
and bronchi results in alteration of the values of the parameters fibrosis corresponds to an approx. 2-fold reduction in the value
Rc, Ic and Rp. On the basis of the data available [8,21,36,45] it of Caw (due to the reconstruction of the bronchial wall) and
may be assessed that severe asthma is accompanied by reduc- a decrease in FRC of 30%, represented by the parameter Cg.
tion in the airway patency of approx. 30% to 40%. Hence, Myasthenia gravis is classified as a neuromuscular disease,
narrowing of 30% of the central and distal airways is assessed for which lung functions are not impaired, however a muscle
causing more than a 4-fold increase in the resistances Rc and Rp, activity disorder is observed. As an effect, muscles cannot
and a 2-fold increase in the inertance Ic. Additionally, a stenosis support proper ventilation. The reason for that may be either
of the respiratory tract of 30%, leads to about 2-fold decrease damage to nerve or neuromuscular transmission or muscle
in the value of Caw based on Formula (5). pathology [54,55]. The selection of myasthenia gravis as a
Chronic obstructive pulmonary disease (COPD) results from representative respiratory disease is conditioned by its extra-
pathological changes in the airways and incompletely reversi- ordinary impact on the effectiveness of respiration. In this
ble destruction of lung parenchyma. COPD is characterized paper, damage to acetylcholine receptors in the neuromuscular
by simultaneous occurrence of: chronic bronchitis, chronic transmission system is assumed. Modeling of severe myasthe-
bronchiolitis and emphysema. Alterations in respiratory control nia gravis (stage 3 and 4 [54,55]) results in a significant change
are more complex than in the case of asthma and depend on in the value of Pg that represents the driving pressure. Accord-
many factors related to the nature and severity of the disease ing to [54], for the third stage of myasthenia gravis the drop
itself. Inflammation of the bronchi (peripheral part mainly) of inspiratory pressure of 30–50% is observed. In this paper this
leads to their structural disorders that as a consequence results 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
Table 4
Values of considered parameters for considered clinical cases.
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