Computers in Biology and Medicine 43 (2013) 914–921

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Computers in Biology and Medicine

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

Computerized analysis of respiratory sounds during

COPD exacerbations
Daniel Sánchez Morillo a,n, Sonia Astorga Moreno b, Miguel Ángel Fernández Granero a,
Antonio León Jiménez b
a
Biomedical Engineering and Telemedicine Researching Group, University of Cádiz, Cádiz 11003, Spain
b
Pulmonology and Allergy Unit. Puerta del Mar University Hospital, Cádiz, Spain

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

Article history: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a major event in the natural
Received 16 June 2012 course of the disease, and is associated with significant mortality and socioeconomic impact. Abnormal
Accepted 27 March 2013 respiratory sounds are commonly present in patients with AECOPD. Computerized analysis of these
sounds can assist in diagnosis and in evaluation during follow-up. Exploratory data analysis methods
Keywords: were applied to respiratory sounds in these patients when they were hospitalized because of
COPD exacerbation. Two different patterns of presentation and evolution of respiratory sounds in AECOPD
Respiratory sounds were found and described from the method of computerized respiratory sound analysis and unsuper-
Exacerbation vised clustering that was devised. Based on the findings of the study, remote monitoring of respiratory
Signal processing
sounds may be useful for the detection and/or follow-up of COPD exacerbation.
Clustering
& 2013 Elsevier Ltd. All rights reserved.

1. Introduction variations [1]. Normally, exacerbations appear about twice or three

Chronic obstructive pulmonary disease (COPD) is a major cause
of mortality and morbidity and an important factor accounting for
rising healthcare costs worldwide [1]. The overall prevalence of
COPD in adults is higher than 10% of population [2], and it is
estimated to be the fourth leading cause of death worldwide in
2030 [3]. This disorder is caused by long-term exposure to noxious
particles and gases and characterized by a non-fully reversible
chronic airflow limitation. Chronic inflammation leads to altera-
tions such as small-airway obstruction, remodelling and parench-
ymal destruction. COPD leads to markedly reduced exercise
capacity and, eventually, disability.
Acute exacerbation of COPD (AECOPD) is a major event in the
natural course of the disease characterized by a worsening of
respiratory symptoms. AECOPD is associated with significant
mortality, adversely affects patient's quality of life and represents
a huge socioeconomic burden mainly due to hospitalizations [4].
Key symptoms of exacerbations are increased breathlessness,
cough and sputum production that is beyond normal day-to-day
n
Correspondence to: Universidad de Cádiz – Escuela Superior de Ingeniería,
Dpto. de Ingeniería en Automática, Electrónica y Arquitectura y Redes de Compu-
tadores, CP 11003 Cádiz, Spain.
Tel.: +34 9560 15709.
E-mail addresses: daniel.morillo@uca.es (D. Sánchez Morillo), sonia.astorga.
moreno@gmail.com (S. Astorga Moreno), ma.fernandez@uca.es
(M.Á. Fernández Granero), anleji@hotmail.com (A. León Jiménez).
times per year, depending on COPD severity, causing a worsening
in the patient's health status [4]. Diagnosis of AECOPD is made
clinically when the patient presents acute worsening of dyspnea,
cough or sputum production. Although respiratory sounds such as
wheezes are reported by patient's self-assessment in 35% of
AECOPD [5], little attention has been given to such a sign.
The course of exacerbations is characterized by a significant
increase in airway obstruction and abnormal bronchial mucus
production [6]. Respiratory sounds such as wheezes and rhonchi
are a manifestation of airway narrowing and mucus secretion,
respectively [7,8], and are hallmark symptoms related to the
pathophysiology of AECOPD. The changes to the pulmonary
structure induced by an exacerbation affect sound transmission
to the surface of the chest wall [9]. Therefore, changes in
respiratory sounds are one of the clinical signs reported in
exacerbation episodes. It is generally accepted that normal vesi-
cular lung sounds are usually replaced by adventitious sounds like
wheezes or rhonchi in AECOPD. Monitoring changes in respiratory
sounds before, during and after a patient-specific therapy is seen
as a valuable clinical strategy on which physicians can rely to
confirm clinical improvement in patients.
Over the past decades, computational methods used for
recording and analyzing respiratory sounds have overcome the
many limitations of conventional auscultation. But despite being
one of the most distinguishing characteristics of episodes of
exacerbation, the changes and peculiarities of respiratory sounds
during an exacerbation have been barely studied. Computerized

0010-4825/$ - see front matter & 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.compbiomed.2013.03.011
 D. Sánchez Morillo et al. / Computers in Biology and Medicine 43 (2013) 914–921
analysis of relative differences in respiratory sound intensity has
been recently reported to be potentially useful in distinguishing
acute dyspnea caused by congestive heart failure (CHF), COPD or
asthma during acute exacerbations [10]. To our knowledge, there
are no significant studies that have examined the evolution of
respiratory sounds in patients hospitalized for AECOPD during the
period of hospital stay in order to generate clinical and diagnostic
applications.
The aim of this work is to examine respiratory sounds in
patients with COPD hospitalized for AECOPD and find substantial
differences in the sounds evolutionary behaviour that may allow
the establishment of exacerbation typologies with possible clinical
implications. Therefore, the purpose of this study is to provide an
answer to the hypothesis that a computerized system can detect
changes in respiratory sounds during COPD exacerbations and that
these changes are consistent with those assessed by physicians,
thereby aiding in the detection of AECOPD.
2. Methods and materials
2.1. Subjects
A group of patients hospitalized due to AECOPD in the
Pulmonology and Allergy Unit of the University Hospital Puerta
del Mar of Cádiz (Spain) were followed during their hospital stay.
An intentional, non-probabilistic sample of 53 individuals was
studied. Because the recruited participants had mild to very severe
airflow limitation, they represented a broad spectrum of COPD
patients. Respiratory sounds were recorded from admission to
discharge. The hospital's research ethics committee approved the
project, and signed informed consent was obtained from all
patients before enrolment.
Inclusion criteria were as follows: (a) a history of COPD and a
ratio of forced expiratory volume in one second (FEV1) to forced
vital capacity (FVC) less than 0.7 in a stable phase of disease; (b)
patients admitted for AECOPD. The only exclusion criterion was
the presence of any cognitive impairment that prevented active
participation in the study.
2.2. Data collection
2.2.1. Sounds recording
Sounds were recorded with an electret microphone with
coupling chamber and flat response between 50 and 18.000 Hz.
Electronics was embedded in a special housing tailored for self-use
(Fig. 1). Sensor was placed over the trachea on the suprasternal
notch and handled by the patients themselves. Sampling rate was
Fig. 1. Patient self-auscultation. Detail of the tailored sensor device.
915
8000 Hz. Analog to digital conversion was performed with 16-bit
quantization. Both clinical history and sound files were assigned to
a codified electronic patient record, especially designed for hospi-
talized COPD patients monitoring.
All recordings were made in bed, in a semi-recumbent position
(elevation of head of bed of 45 degrees). The first recording was
performed within the first 24-h of admission and the last one on
the day of discharge. At least three complete breathing cycles were
recorded after instructing the patients to breathe as deep as
possible. Recordings with background voice and/or high environ-
mental noise were discarded.
2.2.2. Auscultation emplacement
A close relation between airflow and tracheal respiratory
sounds spectrum has been reported [11]. The interest in tracheal
sounds as possible indicators of airway obstruction has been
documented [12]. The trachea has been proposed as a better
location than the lung for analysing wheezes [13]. In fact, previous
studies [14] have pointed out that lung tissues absorb high
frequency components. Additionally, the spectral pattern of tra-
cheal sounds is stable with low intra-subject variability [15]. When
compared to the thorax, the trachea is an easily accessible skin
surface and has lower noise interference caused by hair and
clothes, but it poses some drawbacks in children and some
short-neck adults.
2.2.3. Other clinical variables
Demographic and clinical data of the participants were col-
lected from the patients' clinical history or by face-to-face inter-
view during their hospital stay. Data included age, gender, weight,
height, body mass index (BMI), smoking habits (pack-years),
smoking history (current smoker, non-smoker or ex-smoker),
COPD severity stage according to GOLD and coexisting chronic
respiratory insufficiency (CRI). Predicted values of FEV1 were
calculated in accordance with accepted Spanish population values
[16]. Furthermore, on each admission, a chest radiograph of the
patient while in the emergency unit was obtained. Coexisting
pneumonia was assessed by a senior pulmonologist. Finally, the
respiratory sounds evolution (RSE) during hospitalization was
annotated. Two senior specialists studied each case independently
and classified each patient.
In order to facilitate the aforementioned task, a sensor and an
electronic stethoscope (Thinklabs ds32a) were used concurrently
to allow sounds recording in ten locations on the anterior, side and
posterior chest. Spectrogram of every recording was also provided
as an additional resource. A dichotomous classification was estab-
lished based on each case. The first group of patients, referred to as
RSE-G1, included patients with absence of abnormal sounds and
916 D. Sánchez Morillo et al. / Computers in Biology and Medicine 43 (2013) 914–921

diminished vesicular sounds upon admission, and increased vesi- Table 1

cular sounds accompanied by occasional adventitious sounds at
the time of discharge. The second one (RSE-G2) consisted of
patients with pronounced adventitious sounds on admission
(mainly wheezes and rhonchi), which decreased significantly or
even disappeared at the time of discharge.
Thirteen features were selected for respiratory sounds characterization. STFT was
applied to the respiratory sound signals and the changes in each spectral feature
were captured by the average (prefix ‘u’) and standard deviation (prefix ‘d’) of the
series. The final dataset was composed of 26 parameters. Further details can be
found in [17].
Feature Labels

2.3. Statistical analysis plan Characteristic frequencies

Mean frequency (MNF) uMNF, dMNF
Median frequency (MDF) uMDF, dMDF
The statistics plan began with the selection of relevant fre-
quency domain features. For each subject, the difference between Spectral parameters
each admission and discharge feature value was calculated to build Spectral crest factor (SFC) uSCF, dSCF

a dataset of continuous features. Correlations within the group of Entropies

selected variables were then studied by using cluster analysis to Shannon entropy (SE) uSE, dSE
Rényi entropy (RE) uRE, dRE
determine, in an unbiased way, whether the information provided
Tsallis entropy (TE) uTE, dTE
by each feature was independent from each other. Because
redundancy was found, principal component analysis (PCA) was Relative power (RP) factors in octave bands
RP in the 50–200 Hz band uΔfLF, dΔfLF
used for reducing high correlation between variables. Then, cluster RP in the 200–400 Hz band uΔf400, dΔf400
analysis based on the first principal components was applied. RP in the 400–800 Hz band uΔf800, dΔf800
Bivariate comparisons were performed to the resulting clusters RP in the 800–2000 Hz band uΔfHF, dΔfHF
using the χ2 test (RSE, GOLD stage and the coexistence of CRI or High order frequency moments
pneumonia) and Student t test (FEV1, BMI and pack-years). Second order moment (M2) uM2, dM2
Statistical significance was set at P o0.05. Statistical analyses were Skewness (SK) uSK, dSK
performed using SPSS statistical analysis software. In addition, PCA Kurtosis (KU) uKU, dKU

and clustering were also applied, and Matlabs was used for signal
processing.
2.4. Selection of features
Changes in respiratory sounds caused by diverse respiratory
disorders are reflected in a spectral content displacement from
some frequency bands to others [9]. Consequently, spectral con-
tent needs to be quantified. As lung sounds are non-stationary
signals, conventional methods of frequency analysis are not
recommended. In order to accurately characterize the spectral
time varying properties, it is necessary to use non-stationary
signal analysis techniques. Analysis of non-stationary signals
including sounds has been mainly carried out using short-time
Fourier transform (STFT) and wavelet transforms. STFT and wave-
lets provide means of analysing signals simultaneously in both
time and frequency domain. In this work, STFT was used for
respiratory sounds analysis. Features extracted from STFT can yield
physiologically meaningful information, helpful for results inter-
pretation. Furthermore, the proposed features, derived from STFT
have been successfully applied in the analysis of respiratory
sounds in COPD patients [17]. Thirteen features were selected
and computed. They provided a priori useful information for the
purpose of this study. Mean and standard deviation of each of the
spectral parameters were calculated to quantify the characteristics
of respiratory sounds, as displayed in Table 1.
2.5. Features estimation
Much of the tracheal sounds spectral energy is located in the
band from 100 to 1200 Hz, although some abnormal sounds may
present higher frequency content [13]. As heart sounds spectrum
is concentrated below 100 Hz, intelligent reduction of the
unwanted heart components is essential. To prevent aliasing and
to reduce the influence of heart, noise and muscle sounds, sound
signals were band-pass filtered after removal of the DC compo-
nents by using an equirriple band-pass finite impulse response
filter (FIR) from 100 to 2000 Hz with 80 dBs of attenuation out of
the band-pass.
A recursive least squares (RLS) adaptive filter [18] was used
to adaptively filter the respiratory signal by using a second
environment microphone and an estimated heart signal. The
objective was to enhance noise suppression.
STFT for each filtered auscultation was then calculated. Each
sound signal was divided into 25% overlapping segments of 64 ms
(Hamming window, 512 samples). The spectral content between
the cut-off frequencies f1 ¼ 100 Hz and f2 ¼ 2000 Hz was selected
and the power spectral density (PSD) was normalized to a scale
from 0 to 1. Finally, changes of each spectral feature were captured
by the average and standard deviation of the one-value
per segment series. Therefore, 26 features were extracted from
the admission and discharge recordings. The difference between
the discharge values and the admission ones was calculated for
each patient and used in further steps.
2.6. Dimensionality reduction and exploratory data analysis
Explorative data analysis techniques and unsupervised cluster-
ing methods were applied in order to study the resulting dataset
built from the 53 COPD patients. Due to the difficulty in under-
standing the underlying information of such a complex data
model, and to learn about its multidimensional structure and the
potential existence of subsets of patients with observable differ-
ences in clinical practice, the interrelationships among the attri-
butes were evaluated by applying a data-driven approach. Rather
than using statistical methods for classical hypothesis testing,
exploratory data analysis (EDA) tools were used [19]. Multivariate
statistical theory and cluster analysis were applied to discard
imposition of an a priori structure [20].
As a first approach to visual inspection of the data, the study of
hidden structures and dimensionality reduction were performed
without a priori hypotheses through PCA. The main goal was to
assess the presence of separated clusters. PCA was applied to the
features dataset. The results allowed reducing the space dimen-
sions. Second, a fuzzy C-means algorithm was used for unsuper-
vised clustering to characterize the subgroups observed. Finally,
the observed clusters were compared against variables like FEV1,
coexistent CRI and pneumonia, BMI, pack-years and RSE. The
objective was to verify possible correspondences between the
results and the clinical evidence.
 D. Sánchez Morillo et al. / Computers in Biology and Medicine 43 (2013) 914–921
2.6.1. Principal component analysis
Multidimensional data visualization is a typically challenging
task in biomedical multivariate problems. Since our dataset was
composed of a large number of variables operating in the same
domain, a high correlation between some of them was expected. It
was necessary to simplify the explorative analysis process by
considering a smaller number of linear combinations among the
original variables. Such dimensionality reduction can be achieved
by PCA [21]. Therefore, linear combinations of the twenty six
variables were used to build a new set of twenty six independent
components. The advantage of PCA is that the first few compo-
nents explain most of the variance in the dataset. Consequently,
dimensionality of the original dataset can be reduced with mini-
mal loss of information. Voronoi density plots [22] and special
graphs called biplots [23] were then used to explore the data, by
displaying information on both new components and original
variables and by allowing easy visual interpretation of the rela-
tionships among them.
2.6.2. Cluster analysis
PCA-based cluster analysis was performed to search for groups
in data. Clustering is a main task of explorative data mining and is
widely used in bioinformatics and many other fields. Clustering is
an unsupervised strategy that allows automatic assigning of
samples into relatively homogeneous groups. In this study,
fuzzy-C-means clustering (FCM) was used [24]. Because the
number of clusters cannot be defined a priori, a good cluster
validity criterion has to be found. Cross-validation is an approach
to estimate the number of clusters in the data. For cross-validation,
data are split into two or more parts. One part is used for
clustering and the remaining parts are used for validation. How-
ever, some authors have reported that cross-validation fails to
identify the optimal number of clusters, particularly when the
features are highly correlated [25], as it occurs in this study. In this
work, the partition coefficient (PC), a measure of the fuzziness of
the partition, and partition entropy (PE), which provides informa-
tion about the membership matrix, were used for internal valida-
tion [26].
3. Results
Patients' morphological, smoking and functional characteristics
are presented in Table 2. Application of PCA to the dataset led to
the conclusion that the three first components accounted for over
Table 2
Anthropometric, smoking and functional characteristics of the group of 53 patients
with COPD. Values are given as mean 7SD. BMI: body mass index; FEV1: forced
expiratory volume in 1 s; CRI: chronic respiratory insufficiency. Smoking habit was
not available for one patient.
Characteristic
Male gender
Age (years)
BMI (kg/m2)
FEV1 (%)
Smoking exposure pack–years
Active smoker
Ex-smoker
GOLD stage 1
GOLD stage 2
GOLD stage 3
GOLD stage 4
CRI
Pneumonia
917
90% of the sample variance, and the first two for more than 83%.
In order to perform a better discriminating visual exploratory
analysis, the first two components were considered for further
processing stages.
Biplots show inter-unit distances, variances and correlations of
variables of datasets. They can be used to reveal clustering and to
guide the interpretation of PCA [23]. A PCA biplot overlaps both
the original variables vectors and a scatter plot of the transformed
data. Fig. 2 shows the biplot related to the first two PCA
components (see Table 1 for details and labels). From the direc-
tions of the original variable vectors it is possible to derive a subset
of parameters with a better discriminating capacity. In particular,
Fig. 2 displays a set of features composed of uMNF, uMDF, dKU and
uKU along the two-cluster axis direction. The other parameters
seem not to be significant, either because they are orthogonal to
the possible cluster axis or because of their low modules. There-
fore, the aforementioned variables do not provide reliable infor-
mation for discriminating between the two clusters.
If the scatter plot of the transformed data is drawn using a color
scheme representing the data density, the presence of partially
overlapping subgroups or clusters in the underlying data structure
is revealed. Fig. 3 shows the density plot computed using the
Voronoi approach. Remarkably, the number of identified clusters
remained at two, as shown by the two high density structures that
are clearly distinguishable.
To sum up, the visual exploratory analysis of the functional
respiratory variables yielded the presence of a patient subgroup
(cluster I) characterized by lower values for uMNF and uMDF, and
simultaneous higher values for dKU and uKU. The analysis also
revealed a second subgroup characterized by higher values for
uMNF and uMDF, and simultaneous lower values for dKU and uKU
(cluster II).
Overlaid on Fig. 3 are the results of cluster analysis. Each point
corresponds to one patient. Two subgroups or clusters identified
by applying FCM are visible in this space. The two clusters show
slight overlaps. The values of the selected validity measures
depending on the number of clusters are plotted in Fig. 4. The
highest PC and the lowest PE values were obtained considering
two as the optimum number of clusters within the series of
patient’s data points. This estimation agreed with the exploratory
analysis performed through biplots and density plots.
The aim of the next steps in the analysis of data was to evaluate
the two clusters and the relationship between them and clinical
factors related to the condition like FEV1, CRI, GOLD stage and RSE
perceived by the pulmonologists. Statistical significance was
not found for the interaction between CRI (chi-square¼0.011,
Value
48 (90.6%)
74.3 77.7
28.8 7 5.9
42.1 714.2
75.2 7 41.4
13 (24.5%)
39 (73.6%)
1 (1.9%)
10 (18.9%)
14 (26.4%)
28 (52.8%)
27 (50.9%)
22 (41.5%) Fig. 2. PCA biplot. Samples are plotted in two dimensions using their projections
onto the first two principal components.
918 D. Sánchez Morillo et al. / Computers in Biology and Medicine 43 (2013) 914–921

Fig. 5. Frequency of cluster membership. The frequency of memberships for COPD

Fig. 3. Voronoi density plot shows the presence of two crescent-shaped clusters.
Voronoi cells determine data densities. Partitioning in two clusters of the whole
dataset is overlaid. Each patient is assigned a cluster membership by the clustering
algorithm. Black-filled circles represent cluster I and white-filled circles cluster II.
patients was stratified according to severity of disease (GOLD guidelines).
Table 3
Characteristics of the two revealed clusters. Values are given as mean7 SD. BMI:
body mass index; FEV1: forced expiratory volume in 1 s; uMNF, dMNF, uMDF,
dMDF, uM2, dM2, uKU and dKU represent the frequency features selected for
respiratory sounds evolution characterization.

Characteristic Cluster I (N¼ 19) Cluster II (N¼ 34) P*

Age (year) 73.84(7.09) 72.41(14.62) NS

BMI 31.40(6.25) 27.66(5.18) 0.0442
Pack/years 79.06(44.11) 73.79(40.87) NS
FEV1 48.00(15.34) 38.96(12.93) 0.0491
uMNF 0.34(0.10) 0.46(0.11) 0.0002
uMDF 0.32(0.09) 0.46(0.11) o 0.0001
uM2 0.43(0.08) 0.42(0.09) NS
uKU 0.43(0.03) 0.40(0.03) 0.013
dMNF 0.42(0.11) 0.41(0.04) NS
dMDF 0.43(0.11) 0.41(0.06) NS
dM2 0.42(0.06) 0.41(0.04) NS
dKU 0.43(0.04) 0.39(0.06) 0.0212

n
Significant at Po 0.05.
Fig. 4. Clustering validation indexes. Dashed line: partition coefficient (PC). PC
measures fuzziness. The closer to unity the index is, the “crisper” the clustering is.
Continuous line: partition entropy (PE). PE provides information about the Table 4
membership matrix. The closer the value of PE to 0, the “crisper” the clustering is. Confusion matrix between respiratory sounds evolution groups and cluster
memberships. RSE-G1: respiratory sounds evolution, group 1; RSE-G2: respiratory
sounds evolution, group 2.

P ¼0.9182) or pneumonia (chi-square¼ 0.127, P¼ 0.7215) and cluster RSE-G1 RSE-G2

memberships.
With regard to the FEV1, the two identified clusters cover two
different ranges of FEV1 values. Normality assumption for FEV1 was
accepted according to the D’Agostino–Pearson test (P ¼0.3189). As
the two-tailed probability from Student t test was P¼ 0.049, the
null hypothesis was rejected, and therefore, the two means seem
to differ significantly. The patients that belong to cluster I are
characterized by significantly higher FEV1 values than the patients
in cluster II.
Estimated GOLD stage-specific prevalence rates for the clusters
in the total COPD cohort are shown in Fig. 5. There was no a
significant association between COPD severity and clusters mem-
berships (significance level from χ2 test for trend was P¼ 0.3495).
Table 3 summarizes the statistical information about the
interaction between cluster membership and age, BMI, pack-years,
FEV1 and the most relevant features in the dataset.
A strong relationship between the identified clusters and the
RSE perceived by the specialists was revealed (chi-square¼ 12.934,
P ¼0.0003). The specialists classified their observations based on
the increase or decrease of vesicular and abnormal sounds. They
identified two groups (RSE-G1 and RSE-G2) according to the course
of the exacerbation assessed in terms of the sounds heard over the
trachea, as described earlier in the previous section. Therefore,
these two groups showed a significant association with the cluster
membership, as depicted in Table 4.
Cluster I 12 7 19 (35.8%)
Cluster II 4 30 34 (65.2%)
Total 16 (30.2%) 37 (69.8%) 53 (100%)
4. Discussion
The main finding of this study is that two distinct groups or
clusters of patients with AECOPD arose from the unsupervised
analysis of parameters derived from the respiratory sounds
processing.
While conventional auscultation with a stethoscope is subjec-
tive and hardly comparable [27], acoustic studies with computer
systems could provide objective aid, with better sensitivity
and reproducibility of the results. Respiratory acoustic analysis
allows quantifying changes in the respiratory sounds, storing
recordings and obtaining graphic representations that can help
in the diagnosis and management of patients with a respiratory
pathology.
It is widely accepted that a change in the characteristics of
normal respiratory sounds or the presence of adventitious sounds
reflect a pathological condition of the lungs. Different types of
adventitious sounds, which differ in terms of acoustic features
such as tone, amplitude, frequency, duration, among other fea-
tures, commonly occur in several diseases. The sensitivity of the
 D. Sánchez Morillo et al. / Computers in Biology and Medicine 43 (2013) 914–921
respiratory sounds and changes in airway diameter gets revealed
in routine auscultation of patients with varying degrees of airway
obstruction. The emergence or the increase in adventitious sounds
and/or decrease in normal sounds can be appreciated in these
cases.
There are many acoustic studies addressing recognition or
automatic analysis of respiratory sounds [28]. Different authors
have designed methods for automatic detection of wheezes
[29–31]. It has been shown that automated detection provides
earlier detection of wheezes than ordinary auscultation [32]. Other
authors have studied recognition methods to automatically differ-
entiate between normal and pathological respiratory sounds, and
even discriminate between different types of adventitious sounds
[33–35].
Efforts have been focused on the improvement of automatic
classification systems for certain adventitious sounds. The goal has
been to provide rates correlated to the degree of airway obstruc-
tion or severity of respiratory disorders.
However, such a strategy has some weak points. First of all, it is
well known that normal lung sounds show interpersonal varia-
tions. In addition to this, it is worth pointing out that there exist
both same-day variability and between-day variability in lung
sounds [36]. Second, even in the same subject, there is a correla-
tion between respiratory sounds and age, possibly due to the
change in tissue structure with age, which also leads to a change in
lung function [37]. Finally, the absence of wheezes in many
patients with significant airway obstruction is remarkable [38].
Therefore, automatic classification tools lose effectiveness in the
aforementioned cases. In these patients, other types of changes in
the respiratory sounds, such as the decrease in intensity of normal
breath sounds, can be perceived on auscultation.
A personalized approach should be then proposed. To this end,
this study has applied a different strategy that focused on the
estimation of spectral parameters and their changes over time
rather than applying automatic detection of adventitious sounds
or their ratios.
This study has delved into the aforementioned direction and
has tried to show the existence of two groups of patients
hospitalized for AECOPD. These groups showed significant differ-
ences, as it can be clearly seen in the exploratory visual analysis in
Fig. 2 and Fig. 3. As shown in Fig. 2 and confirmed in Table 3, the
uMNF, uMDF, uKU and dKU parameters have a discriminatory
capacity. uKU and dKU have greater mean values for cluster I,
whereas uMNF and uMDF present greater values for cluster II.
The implementation of PCA and FCM led to a space partition in
the dataset. The resulting space partition was capable of quantita-
tively summarizing the data characteristics. Visual inspection
confirmed the presence of two partially overlapping subsets of
aggregation. As Fig. 3 illustrates, cluster I has predominantly
negative values along principal coordinate I when compared to
cluster II, which has mainly positive values of this principal
coordinate. Unlike coordinate I, principal coordinate II is predo-
minantly positive for cluster I and negative for cluster II. The two
clusters are an optimum approach, according to the validity
indexes PC and PE, showing only slight overlaps.
After confirming and quantifying the existence of the afore-
mentioned two groups, the following step in the analysis was to
examine whether the two partitions correlated with the available
clinical variables. Table 3 summarizes the mean values and the
standard deviations of the most relevant parameters for each
group together with the results of the statistical analysis.
The study of the prevalence of each group of patients with
varying degrees of COPD severity yielded statistically non-
significant results (Fig. 5). However, the intentional non probabil-
istic sample is characterized by a high percentage of patients with
GOLD stage III or IV COPD, which makes it difficult to exclude the
919
effects of the progression of COPD and their direct influence on the
established classification. Another factor to bear in mind is the
inclusion of patients with pneumonia. Radiographic consolidation
commonly complicates acute exacerbations of COPD. Pulmonary
consolidation has not been considered an exclusion criterion in the
major UK national audits of COPD exacerbations [39] as well as in
relevant recent studies [40–41]. Therefore, AECOPD and coexisting
pneumonia were included in this work within the definition of
AECOPD. The analysis of the results suggests that the coexistence
of pneumonia does not reveal any significant relationship with
established partitions. These results are consistent with those
reported in [17], where discrimination between AECOPD and
pneumonic exacerbations using computerized analysis of respira-
tory sounds recorded at admission was performed with an
accuracy of 77.6%. In the study, since a fraction of patients
admitted because of exacerbation, regardless of its etiology, did
not present the characteristic sounds that enabled discrimination
(wheezing and/or crackles) the classifier failed in these cases. This
fraction could correspond to the patients in cluster I. These
patients have high values of FEV1 and present no clear adventi-
tious sounds at admission. These adventitious sounds may appear
after initiation of treatment.
No significant relationship with coexisting chronic respiratory
failure was either found. The most relevant finding was related to
the changes of respiratory sounds perceived by the specialists
(RSE). In this respect, the two groups or clusters characterized in
this study confirm the aforementioned statement concerning
intra-subject variability. According to Table 4, there was an overall
agreement of 79% between the clustering results and the RSE
score. 75% of RSE-G1 patients were assigned to cluster I, whereas
81% of patients classified as RSE-G2 were included in cluster II.
Therefore, the group of patients that makes up cluster I displays
the respiratory sounds progression described in the literature. In
the acute state of exacerbation, some patients do not have
adventitious sounds but decreased vesicular sounds. On the other
hand, the characteristics of the second group (cluster II) largely
correspond with the usual description in the literature, including
the presence of adventitious sounds as symptomatic AECOPD
indices.
Our study has some limitations: the sample size is relatively
small and thus further studies with a larger sample of patients
(different ages and disease severity) should be carried out to
confirm the findings. The results of our PCA-based cluster analysis
suggest that the relationship between the clusters and BMI and
FEV1 needs to be further researched. P values are bordering
statistical significance (0.0442 and 0.0491, respectively). The
sample of this study is biased to low FEV1 values (mainly GOLD
3 and 4 stages). A sample with a wider range of COPD severities is
required to shed some light on the aforementioned limitations.
On the other hand, there have been several attempts, most of
them based on biological markers, to define exacerbation pheno-
types [42]. Such phenotypes could correspond to different etiolo-
gies (bacterial, viral or eosinophilic). The markers used in such
studies are expensive and hardly applied in routine clinical
practice [43]. The existence of different respiratory sounds evolu-
tionary patterns in AECOPD opens up the possibility of considering
such patterns as the expression of different exacerbation etiolo-
gies, which makes it much more easily available in daily clinical
practice.
In recent years, the existence of different COPD phenotypes has
been suggested. Such an idea would entail the acceptance of
different groups of patient that share the same clinical, functional,
prognostic or evolutionary characteristics [44]. In fact, some of
the aforementioned phenotypes are being more clearly defined
[45–46], and it is possible that either of the clusters identified in
this study is related to certain phenotypes.
920 D. Sánchez Morillo et al. / Computers in Biology and Medicine 43 (2013) 914–921
In addition, if it is possible to characterize the course of
exacerbations to define two groups based on the variation of
certain parameters computed from respiratory sounds analysis,
and if there is a stable correlation between such groups and the
exacerbation profiles, what follows is that the follow-up of these
parameters and the detection of increasing or decreasing trends
may serve as the basis for the establishment of personalized alert
thresholds to determine the onset of exacerbations with a high
probability of success.
5. Conclusions
This study suggests that COPD population does not show a
homogeneous spectrum but two different respiratory sounds
patterns that can be differentiated in the course of AECOPD
through computerized analysis. To our knowledge, the aforemen-
tioned finding has not been described in other previous works,
and could enable the detection or follow-up of exacerbations
through remote monitoring of respiratory sounds. Furthermore,
the results of this study open the door to further studies that can
assess whether the different respiratory sounds patterns corre-
spond with different exacerbation etiologies, more or less
advanced stages of COPD or with auscultation patterns associated
to different COPD phenotypes. Such patterns could be much more
easily applied in clinical practice where auscultation is highly cost-
effective.
Summary
In computerized analysis of respiratory sounds, most efforts
have focused on the improvement of automatic detection systems
for certain adventitious sounds. However, this strategy has some
weak points, such as inter- and intra-subject variability. Some
exacerbated patients do not present relevant respiratory adventi-
tious sounds.
There have recently been several attempts to define COPD
exacerbation phenotypes. The attempts are being mainly based on
biological markers. These phenotypes could correspond with
different etiologies (bacterial, viral or eosinophilic). The markers
used in the aforementioned studies are expensive and hardly
applicable in routine clinical practice.
This study shows that COPD population does not show a
homogenous spectrum in terms of their respiratory sounds evolu-
tion. It is possible to characterize the course of COPD exacerbations
into two groups, based on the variation of certain parameters
calculated through computerized analysis of respiratory sounds.
The existence of different respiratory sounds evolutionary
patterns in AECOPD opens up the possibility of considering such
patterns as the expression of different exacerbation etiologies.
Such patterns could be much more easily applicable in daily
clinical practice because auscultation is a cost-effective solution
widely available in all clinical settings. Moreover, the findings of
this study could also contribute to automated remote detection or
follow-up of exacerbations.
Authors’ contributions
The work presented here was carried out in collaboration
between all authors: they all defined the research theme, read
abstracts, selected reviews for full text assessment, reviewed
related papers, designed, conducted the study, interpreted its
results, revised the manuscript and approved the final version.
DSM managed the review process. DSM and AL drafted the full
article and revised it critically for intellectual content. DSM carried
out the computerized processing of signals, and SA and MAF the
recording and annotations of data.
Conflict of interest statement
The authors declare no conflict of interest.
Acknowledgements
This work was supported in part by the Ambient Assisted Living
(AAL) E.U. Joint Programme, by grants from Ministerio de Educa-
ción y Ciencia (Ministry of Education and Science) of Spain and
Instituto de Salud Carlos III under Projects PI08/90946 and PI08/
90947.
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