Journal of

Clinical Medicine

Article
The Clinical Profile of Patients with COPD Is Conditioned
by Age
Diego Morena 1,2, *, José Luis Izquierdo 1,3 , Juan Rodríguez 4 , Jesús Cuesta 3 , María Benavent 5 ,
Alejandro Perralejo 5 and José Miguel Rodríguez 3,6

1 Pulmonology Department, Respiratory Medicine, Hospital Universitario de Guadalajara,

19002 Guadalajara, Spain; [email protected]
2 Doctoral Program in Health Sciences, University of Alcalá, 28871 Alcalá de Henares, Spain
3 Department of Medicine and Medical Specialties, University of Alcalá, 28871 Alcalá de Henares, Spain;
[email protected] (J.C.); [email protected] (J.M.R.)
4 Geriatric Medicine, Hospital Universitario de Guadalajara, 19002 Guadalajara, Spain;
[email protected]
5 SAVANA, 28013 Madrid, Spain; [email protected] (M.B.); [email protected] (A.P.)
6 Respiratory Medicine, Hospital Universitario Príncipe de Asturias, 28805 Alcalá de Henares, Spain
* Correspondence: [email protected]; Tel.: +34-627889489

Abstract: In recent years, many studies have analyzed the importance of integrating time, or aging,
into the equation that relates genetics and the environment to the development and origin of COPD.
Under conditions of daily clinical practice, our study attempts to identify the differences in the clinical
profile of patients with COPD according to age and the impact on the global burden of the disease.
This study is non-interventional and observational, using artificial intelligence and data captured
from electronic medical records. The study population included patients who were diagnosed with
COPD between 2011 and 2021. A total of 73,901 patients had a diagnosis of COPD. The mean age
was 73 years (95% CI: 72.9–73.1), and 56,763 were men (76.8%). We observed a specific prevalence of
obesity, heart failure, depression, and hiatal hernia in women (p < 0.001), and ischemic heart disease
and obstructive sleep apnea (OSA) in men (p < 0.001). In the analysis by age ranges, a progressive
increase in cardiovascular risk factors was observed with age. In conclusion, in a real-life setting,
Citation: Morena, D.; Izquierdo, J.L.; COPD is a disease that primarily affects older subjects and frequently presents with comorbidities
Rodríguez, J.; Cuesta, J.; Benavent, that are decisive in the evolutionary course of the disease.
M.; Perralejo, A.; Rodríguez, J.M. The
Clinical Profile of Patients with Keywords: COPD; big data; artificial intelligence; age; comorbidities; daily clinical practice
COPD Is Conditioned by Age. J. Clin.
Med. 2023, 12, 7595. https://doi.org/
10.3390/jcm12247595

Academic Editors: Pierachille Santus 1. Introduction

and Ildiko Horvath Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mor-
Received: 28 October 2023
bidity and mortality worldwide. Symptoms usually appear after the age of 40, although the
Revised: 21 November 2023 clinical presentation varies greatly at the onset of the disease, during its progression, and in
Accepted: 7 December 2023 terms of its clinical impact at different stages of life. This variability requires an understand-
Published: 9 December 2023 ing of all the factors that determine the burden of the disease in any given patient [1,2]. The
current pharmacological treatment of COPD is based on the results of large clinical trials
that select subjects who represent the average patient, but they do not always analyze the
associated diseases that influence the clinical deterioration of these patients. Furthermore,
Copyright: © 2023 by the authors. the main clinical trials on which the evidence for the pharmacological treatment of COPD
Licensee MDPI, Basel, Switzerland.
is based is usually restricted to a mean patient age of 65 + 8 years [3–7]. In many cases, this
This article is an open access article
patient selection prevents the results from being adequately extrapolated to a large number
distributed under the terms and
of patients who may require personalized treatment due to their specific characteristics.
conditions of the Creative Commons
In order to correctly understand what happens in patients with COPD, we must
Attribution (CC BY) license (https://
consider that the patient’s clinical situation is often conditioned by other diseases that
creativecommons.org/licenses/by/
4.0/).
are not always related to the degree of limitation observed on spirometry and which also

J. Clin. Med. 2023, 12, 7595. https://doi.org/10.3390/jcm12247595 https://www.mdpi.com/journal/jcm

J. Clin. Med. 2023, 12, 7595 2 of 11

increasingly progress with age [8,9]. In fact, a common finding in patients with COPD
is that, even with similar forced expiratory volume in 1 s (FEV1) levels, we may observe
different patterns of functional impairment, dissimilar clinical manifestations, a variable
number of exacerbations, and varying degrees of quality of life. Part of this variability may
be related to the heterogeneity of the disease itself, which possibly originates in different
pathogenic mechanisms and is reflected in the clinical phenotypes. However, several
studies carried out in the general population have shown that, as the age of patients with
COPD increases, it is common for more than one chronic comorbidity to appear, which
contributes towards the accentuated clinical deterioration of these patients [10,11].
In addition to presenting a greater number of comorbidities, age itself has been de-
scribed as having a potential influence on the progression of COPD. Nonetheless, although
similarities have been described between lung aging (within the concept of “senile lung”)
and COPD, the physiological changes that occur with age cannot be interpreted as a
pathological process that requires intervention. There is currently not enough evidence to
establish whether lung aging alone is highly relevant in patients with COPD who require
medical care or hospitalization for exacerbation; in fact, it would only explain certain
associated pathological changes—mainly emphysema [12]. Regardless of the role that
aging may have in the pathogenesis of COPD, what is indisputable is that, as they age,
patients with COPD present different clinical characteristics that must be identified, as they
can decisively influence disease progression.
In recent years, many studies have analyzed the importance of integrating time, or
aging, into the equation that relates genetics and the environment to the development
and origin of COPD. The age of an individual when the interaction between genetics and
the environment occurs is important, as well as the previous exposures suffered by said
individual, or even their parents. A genetic–environmental–temporal approach will provide
not only more information on lung functionality, but also determine the heterogeneity of
clinical presentation in COPD [13].
Our hypothesis is that the clinical profile of COPD varies with patient age, resulting in
differences in the burden of the disease. This factor should be considered when designing
clinical studies and proposing specific treatment programs, thereby making it possible to
plan more personalized patient management focused on the main treatable traits, while
potentially reducing the current burden of COPD.
The application of big data techniques and artificial intelligence in healthcare enable
us to manage and extract value from complex data generated in large volumes from
electronic health records (EHR). Thanks to this technology, it is possible to evaluate the
main indicators of a certain clinical process, avoiding selection biases beyond the very
existence of the registry. Big data has emerged as a fundamental tool in the current era,
transforming the way we approach and understand complex phenomena in various fields,
including epidemiology. Its utility in the contemporary age is particularly highlighted in
the field of public health, where the massive collection and analysis of data have enabled the
early detection of diseases, the monitoring of epidemiological patterns, and the formulation
of more effective preventive strategies.
In the context of epidemiology, big data facilitates the integration of data from var-
ious sources, such as electronic health records, social media data, and wearable health
devices. Additionally, big data analysis allows for more precise customization of health
interventions and policies, tailoring them to the specific needs of different communities.
Moreover, the marriage of big data and artificial intelligence (AI) further enhances our
capabilities for health management. AI plays a crucial role in processing and analyzing
large datasets generated by big data. Advanced algorithms can identify patterns and
correlations in real time, enabling early disease detection and a faster response to critical
epidemiological situations. The machine learning capability of AI also contributes to the
continuous improvement of predictive models, refining their accuracy over time as new
data is incorporated. In this regard, the synergy between big data and AI emerges as a
J. Clin. Med. 2023, 12, 7595 3 of 11

fundamental pillar to strengthen epidemiological resilience and promote global health in

the present day.
The objective of this study is to identify, under conditions of normal clinical practice,
the differences in the clinical profile of patients with COPD according to age and their
impact on the global burden of the disease. In this way, we can obtain a better understand-
ing of these gene–environmental–temporal interactions in order to provide higher quality
treatments and prevention of this disease.

2. Materials and Methods

We designed an observational, retrospective and non-interventional study using
secondary data captured from the free text of electronic medical records (EMR). This study
was conducted in the Castilla-La Mancha region of Spain, whose healthcare administration
(SESCAM) utilizes the Savana Manager v.3.0 tool, making it possible to analyze data going
back to 1 January 2011. In doing so, we have followed the Strengthening the Reporting of
Observational Studies in Epidemiology (STROBE) guidelines [14]. The study population
included all patients over the age of 40 with a diagnosis of COPD who had been treated
between 1 January 2011 and 24 January 2021.
The methodology we used has been described in previous publications [15–18]. Sa-
vana Manager is a data extraction system based on artificial intelligence (natural language
processing, NLP) and big data techniques. This technology is able to extract unstructured
clinical information (natural language or free text) from electronic history records (EHR)
and transform it into reusable and organized information for research purposes, while
maintaining the anonymous nature of patients at all times. In addition, through the use
of computational linguistic techniques, comprehensive clinical content is scientifically de-
tected and validated by the SNOMED CT [19] tool using data from the EHR of the SESCAM
specialized care network (hospitalization, emergency, and outpatient consultations) and
primary care services.
Data management and protection: The hospital IT services are responsible for pro-
cessing the data and rendering it anonymous so that Savana subsequently receives non-
identifiable data. In addition, an algorithm is used during data extraction to randomly
insert confounding information per patient, while at the same time, only recovering part
of the individual information. The end result of this methodology is the creation of a
completely dissociated and anonymous patient database, so that all study reports contain
only aggregated data, and neither patients nor physicians can be identified. According to
the European Data Protection Authority, once an anonymous clinical record is cleared of
personal data, the General Data Protection Regulation no longer applies. This study was
approved by the Research Ethics Committee (Comité de Ética de la Investigación, or CEIm)
of the Guadalajara public healthcare area (ref 1/2023, date 17 January 2023).
Information extraction assessment: For the scope of this study, variable COPD was
detected in the free text using a named-entity recognition approach. As additional layers,
negation and temporality detection were applied. The machine learning model to detect
negation is a combination of a rule-based layer with a binary convolutional neural network
trained on real Spanish EHRs and evaluated against a rich set of reference standards. This
model classifies each clinical entity as being affirmative or non-affirmative, based on its
lexical and semantic context. The temporality detection is carried out by an NLP module
that consists of various layers that work in combination to assign dates to clinical entities.
The first layer is a named-entity detection engine responsible for the detection of any
mentioning of dates in the free text of the EHRs. Subsequently, a relationship model based
on a Bi-LSTM decides if a detected date is related to a detected clinical entity. In addition, a
normalization layer converts different date formats, as written in the EHRs’ free text, into
a normalized representation. The last step in NLP processing, the post-processing step,
carries out several quality control operations and combines the output from the different
NLP modules into a final database.
J. Clin. Med. 2023, 12, 7595 4 of 11

After the cNLP processing, three authors validated the results of the tool and the
performance of the technology. The purpose of this evaluation was to verify the validity of
the EHRead® technology in the identification of records containing mentions of “COPD”
and related variables. A set of 560 documents was manually verified, which ensured
the reliability of the manual annotation/review and constituted the gold standard. The
performance of Savana was calculated using a gold standard evaluation resource created
by the experts, i.e., the accuracy of Savana in identifying records in which the presence of
the disease under study, and the related variables detected, were measured with respect to
the gold standard. The performance was calculated by the standard metrics of precision
(P), recall (R), and the F-score, which is the harmonic mean of the two previous metrics.
Precision indicated the reliability of the information retrieved by the system and
was calculated as P = tp/(tp + fp). Recall, an indicator of the amount of information
retrieved by the system, was calculated as R = tp/(tp + fn). The F-score was calculated
as F = 2 × precision × recall/(precision + recall). This parameter provided an indicator of
overall information retrieval performance. In all cases, true positives (tp) were the sum of
correctly identified records, false negatives (fn) were the sum of unidentified records, and
false positives (fp) were the sum of incorrectly retrieved records.
We have previously described that the values for these metrics were greater than 0.9,
indicating that the diagnosis was adequate for identifying the study population. The F
values of the different terms included in the analyses ranged between 0.92 and 0.97.
Statistical analysis: All variables were evaluated using SPSS software (version 25.0;
IBM, Armonk, NY, USA) and OpenEpi (https://www.OpenEpi.com accessed on 6 February
2023). We used standard descriptive statistical analyses. Qualitative variables are expressed
as absolute frequencies and percentages, while quantitative variables are expressed as
means, 95% confidence intervals, and standard deviations. For the analysis of numerical
variables, the Student’s t-test for independent measures was used, while the Chi-squared
test was used to measure the association and compare proportions between qualitative
variables. To assess whether the variables analyzed were related with the population
selected, significance was assessed using a Chi-squared 2 × 2 contingency table, controlling
for sex and age biases. A p-value less than 0.05 was considered statistically significant.
Savana presents the events in order, according to the odds ratio (observed vs. expected
frequency). In all cases, differences whose p-value associated with the contrast test was less
than 0.05 were considered significant.

3. Results
During the study period (1 January 2011 to 14 January 2021), 73,901 patients diagnosed
with COPD were treated by Castilla-La Mancha Public Healthcare Services (SESCAM).
The mean age was 73 years (95% CI: 72.9–73.1), and 76.8% of patients were male (56,763).
Figure 1 presents the flowchart of the patients included in this study.
The main clinical and demographic characteristics of the study population are shown
in Table 1.
When we analyzed the patients by sex, we found that obesity, heart failure, depression,
and hiatal hernia were especially prevalent in women (p < 0.001), while ischemic heart
disease and obstructive sleep apnea (OSA) were more prevalent in men (p < 0.001).
In the analysis by age ranges, a progressive increase in cardiovascular risk factors is
observed with age. In addition, a progressive increase in associated diseases, especially
cardiovascular diseases, is also observed (Table 2).
In fact, in patients over the age of 70, heart failure is present in a high percentage of
patients (30.9% from 70–79 years of age, and 58.7% over 80 years of age). Compared to the
general 40+ population, patients with COPD have a statistically significantly higher inci-
dence of cardiovascular risk factors, cardiovascular disease, depression, and hiatal hernia.
J. Clin. Med. 2023, 12, 7595 5 of 11
J. Clin. Med. 2023, 12, x FOR PEER REVIEW 5 of 12

Figure 1.1.Flowchart
Figure Flowchartof patients included
of patients in thisinstudy.
included this study.

TableThe maincharacteristics
1. Basal clinical and demographic characteristics of the study population are
of the study population.
shown in Table 1.
Male COPD Female COPD
Population Population p
Table 1. Basal characteristics of the study population.
(n = 56,763) (n = 17,138)
Age, years (95% CI) 72.9 (72.8–73)
Male COPD 72.3 (72.1–72.5)
Female COPD <0.001
Comorbidities Population Population p
Arterial hypertension (%) (n = 56,763)
70.0 (n = 17,138)
72.3 <0.001
Age, years (95% CI) 72.9 (72.8–73) 72.3 (72.1–72.5) <0.001
Dyslipidemia (%) 49.6 52.5 <0.001
Comorbidities
Diabetes (%) 37.9 38.5 <0.001
Arterial hypertension (%) 70.0 72.3 <0.001
Smoking (%) (%)
Dyslipidemia 49.6 41.7 52.5 35.9 <0.001 <0.001
Obesity (%)
Diabetes (%) 37.9 23.9 38.5 32.7 <0.001 <0.001
Smoking (%) (%)
Heart failure 41.7 37.3 35.9 48.3 <0.001 <0.001
Obesity (%)
Atrial fibrillation (%) 23.9 19.4 32.7 18.4 <0.001 <0.01
Heart failure (%)
Ischemic cardiopathy
37.3 14.4
48.3 7.7
<0.001 <0.001
Atrial fibrillation (%) 19.4 18.4 <0.01
Obstructive sleep apnea (%) 13.5 10.8 <0.001
Ischemic cardiopathy 14.4 7.7 <0.001
Depression (%) 10.0 27.2 <0.001
Obstructive sleep apnea (%) 13.5 10.8 <0.001
Hiatal hernia
Depression (%)
(%) 10.0 12.7 27.2 17.3 <0.001 <0.001
Hiatal hernia (%) 12.7 17.3 <0.001
Table 2. Comorbidities in COPD by age.
When we analyzed the patients by sex, we found that obesity, heart failure, depres‐
sion, and Total
>40 without hiatal hernia were especially prevalent in women (p < 0.001), while
COPD COPDischemic
70–79 >COPD 80
Age Range, Years COPD 40–49 COPD 50–59 COPD 60–69
COPD Population
heart disease 40 p sleep apnea (OSA) were more prevalent in men (p <74.4
and >obstructive 0.001). 85.3
Mean (CI 95%) 45 (44.9–45.1) 54 (54.7–54.8) 64 (64.3–64.4)
62.1 (62–62.1) 73 (72.9–73.1) (74.4–74.5) (85.3–85.4)
In the analysis by age ranges, a progressive increase in cardiovascular risk factors is
Sex, male (%) 51.4 76.8 <0.001 66.7 71.2 79.4 82.1 77.1
observed with age. In addition, a progressive increase in associated diseases, especially
Comorbidities cardiovascular diseases, is also observed (Table 2).
Arterial hypertension (%) 29.9 70.5 <0.001 30.8 46.2 61.1 72.7 78.7
Dyslipidemia (%) 21.0 50.3 <0.001 27.4 39.9 47.8 51.0 47.2
Diabetes (%) 14.4 38.1 <0.001 19.6 28.2 35.3 40.0 37.2
Smoking (%) 11.2 40.3 <0.001 70.3 68.2 52.0 32.1 17.7
Obesity (%) 8.2 25.9 <0.001 22.8 25.5 26.2 25.7 20.4
Heart failure (%) 6.9 40.1 <0.001 5.1 8.0 10.6 30.9 58.7
Atrial fibrillation (%) 4.5 19.1 <0.001 1.9 4.5 9.2 17.4 27.5
Ischemic cardiopathy 2.7 12.9 <0.001 2.6 6.4 10.3 13.5 14.7
Obstructive sleep apnea (%) 2.5 12.9 <0.001 14.1 16.3 15.4 11.0 7.1
Depression (%) 6.9 14.0 <0.001 16.4 15.5 12.0 11.2 11.7
Hiatal hernia (%) 5.1 13.8 <0.001 9.1 10.2 10.8 12.4 14.3
 J. Clin. Med. 2023, 12, 7595 6 of 11

Table 3 shows the impact of age on the burden of disease, measured by hospital
admissions and mortality.

Table 3. Burden of the disease evaluated by hospitalizations and hospital mortality.

Age Range, Years 40–49 50–59 60–69 70–79 >80

% of total COPD population 3.2 11.9 20.8 28.0 36.1
% COPD patients that required
11.9 14.7 19.9 24.2 30.7
hospitalization for acute deterioration
Number of hospitalizations among
2.3 2.5 2.9 3.0 3.0
patients that required hospitalization
In-hospital death 3.7 2.6 3.2 4.3 6.2

This factor is relevant since the percentage of hospital admissions and mortality increases
significantly, but it also represents a very high percentage of the entire COPD population.
J. Clin. Med. 2023, 12, x FOR PEER REVIEW 7 of 12
The sex-related differences observed in the general population were maintained over
all age ranges (Figure 2).

(A)

(B)

Figure 2. Cont.
J.J.Clin.
Clin.Med.
Med.2023,
2023,12,
12,x 7595
FOR PEER REVIEW 8 of
7 of1211

(C)

(D)

(E)
Figure
Figure2.2.Differences
Differencesinincomorbidities
comorbiditiesby
bysex
sexinindifferent
differentage
ageranges
rangesabove
above40
40years.
years.(A)
(A)Population
Population
between 40–49 years; (B) population between 50–59 years; (C) population between 60–69
between 40–49 years; (B) population between 50–59 years; (C) population between 60–69 years; years; (D)
population between 70–79 years; (E) population over 80 years.
(D) population between 70–79 years; (E) population over 80 years.
J. Clin. Med. 2023, 12, 7595 8 of 11

4. Discussion
The data from this study confirm that most patients with COPD have an associated
complexity of conditions, which partly correlates with comorbidities and increases progres-
sively with age. As these patients age, changes in their profile are associated with a greater
consumption of healthcare resources (hospitalizations) and mortality.
COPD should not be seen as a single disease, but as a syndrome that encompasses
functional and structural alterations, causing recognizable chronic symptoms. This is
due to the interactions between the environment and genetics, but with time (aging) as a
direct collaborator. The final biological and clinical results that is produced by the genetic-
environmental interactions and those previous accumulated interactions—in regards to
the patient, as well as to their parents—present a crucial axis, which is time, or aging [13].
Knowledge about the usefulness of this factor in COPD could allow for the identification
of new early therapeutic and preventive targets for this disease.
Certain associated comorbidities (such as cardiovascular disease, especially heart
failure) can have a decisive effect on the clinical symptoms of patients. Using data from
the ECLIPSE study, Agustí et al. proposed a shared pathogenic mechanism [20]. However,
there are no data to confirm either a causal relationship or a mere association motivated by
a greater coincidence of risk factors. In any event, as clearly demonstrated by our study,
patients with COPD have a high prevalence of comorbidities, which can be decisive in
the clinical expression of COPD, some of which are significantly associated with increased
morbidity and mortality [21]. Several observational studies have previously described
the higher prevalence of comorbidities in patients with COPD compared to the general
population, and this is also noted in our setting [8,22]. However, the most important
achievement of this study is that it quantifies the importance of the problem in a real-life
setting, without the selection biases of most previous observational studies, identifying its
age-adjusted magnitude.
Several studies have shown an inverse correlation between the patient’s health status
and the existence of comorbidities, especially when three or more are associated, regardless
of lung function [23–25]. Additionally, the risk of exacerbation and hospitalization, mortal-
ity, and the economic impact of the disease on healthcare systems are related to the number
of comorbidities [26–28].
Some series have shown that, compared to the general population, patients with
COPD studied under real-life conditions have a higher frequency of obesity, depression,
obstructive sleep apnea (OSA), and hiatal hernias [29–31], whose frequency does not
intensify with the age of the patient. However, other comorbidities may have a greater
impact, depending on patient age. For instance, this age-related increase is highly significant
in cardiovascular diseases. Heart failure is common among patients with COPD, but it can
be decisive in certain patients over the age of 70, since its presence can not only deteriorate
the baseline clinical situation of the patient, but also simulate or aggravate exacerbations.
Based on our data, which are current and obtained from a real-life setting, we can
confirm that COPD is a disease that predominantly affects elderly patients, and that this
age group has a higher concentration of patients, as well as cases of more complex disease,
causing a greater impact on healthcare services. The use of big data methods and artificial
intelligence has allowed us to obtain a realistic overview of the treatment needs of patients
in a given region, indicating that more than 50% of patients with COPD in our setting were
over 70 years of age. These data are consistent with the results of the EPISCAN2 study,
which has recently demonstrated the prevalence of COPD in Spain [32]. In this study, only
6.03% of COPD patients were 40 to 49 years of age, while 30.08% were 70 to 79 years of age.
However, a particularly important group of patients, which is the over-80 age group, was
not analyzed. In our series, this group represents 36% of the total.
One limitation of this study is that it included patients whose diagnosis of COPD
had not always been confirmed with post-bronchodilator spirometry. This is especially
relevant in patients over the age of 80. However, as they are diagnosed and treated as
COPD patients, the great importance of this population in terms of treatment requirements
J. Clin. Med. 2023, 12, 7595 9 of 11

is evident. As most previous studies do not include this population, it seems reasonable
to assess specific strategies for these age groups, since only individualized treatment that
considers each patient’s particularities will allow us to correctly manage these patients.
Multimorbidity, or comorbidity, are aspects of complexity and may be factors that do
not fully explain the patient’s situation. Some patients with a single disease may require
complex management, while others may present with many diseases, but may be easy to
manage. For this reason, the assessment of comorbidity cannot replace functional evalu-
ation as a means of obtaining a diagnosis, prognostic markers, or therapeutic objectives,
and even less so in a type of population in which the specific weight of each disease is
diluted under the overall impact of the accumulation of multiple alterations in various
physiological systems. Despite that, the most remarkable and novel study presented here
is the use of the big data approach. We believe that it can end the long-term permanent
exclusion of the elderly from studies and models of chronicity and multimorbidity, despite
being the population group with the highest prevalence of pathologies and for which health
expenditures are concentrated. They are the real patients of our health system [33,34].

5. Conclusions
The main conclusion of this study, whose strength is that it has included a large
population in a real-life setting, is that COPD is currently a disease that primarily affects
patients of advanced age who frequently present with comorbidities that are decisive in
the evolutionary course of the disease. A comprehensive understanding of the patient,
and not merely of the disease alone, will be crucial for the correct management of most
patients with COPD, and the use of frailty assessment instruments developed by geriatric
specialists will allow for a better understanding of this group of patients and therefore, the
application of measures tailored to their needs. Meanwhile, the most advanced age group
comprises the greatest disease burden, both for the patient, as well as the public healthcare
system. Knowledge about the usefulness of the time factor in COPD (GETomicis [13]) could
allow for the identification of new early therapeutic and preventive targets for this disease,
adding to the previously determined genetic and environmental factors.

Author Contributions: D.M., J.L.I., J.R. and J.M.R. were responsible for the design, development,
data extraction, analysis, and preparation of the manuscript. The remaining authors, J.R., J.C., M.B.
and A.P., participated in the data extraction, analysis, and correction of the manuscript. All authors
have read and agreed to the published version of the manuscript.
Funding: This project was funded by the Chair of Inflammatory Diseases of the Airways, University
of Alcalá.
Institutional Review Board Statement: This study was conducted in accordance with the Decla-
ration of Helsinki and approved by the Ethics Committee of Guadalajara’s Hospital for studies
involving humans.
Informed Consent Statement: Informed consent was not required because the study is anonymous,
observational, and retrospective.
Data Availability Statement: The data presented in this study are available upon request from the
corresponding author. The data are not publicly available because they belong to the National Health
System of Castilla La Mancha.
Conflicts of Interest: We declare there are no real or perceived conflict of interests or financial
compensations related to this submission, and that we have no links to tobacco manufacturers and/or
the tobacco industry.
J. Clin. Med. 2023, 12, 7595 10 of 11

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