Comorbidities according to airflow limitation severity: data from comprehensive health examination in Japan
Masuda et al. Environmental Health and Preventive Medicine
Comorbidities according to airflow limitation severity: data from comprehensive health examination in Japan
Shota Masuda 1
Hisamitsu Omori 0 1
Ayumi Onoue 0
Xi Lu 1
Takahiko Katoh 1
0 Department of Biomedical Laboratory Sciences, Faculty of Life Sciences, Kumamoto University , 4-24-1 Kuhonji, Chuo-ku, Kumamoto 862-0976 , Japan
1 Department of Public Health, Faculty of Life Sciences, Kumamoto University , 1-1-1 Honjou, Chuo-ku, Kumamoto 860-8556 , Japan
Objectives: The present study aimed to investigate the relationship between airflow limitation (AL) severity and comorbidities in comprehensive health examination. Methods: This cross-sectional study included 6661 men and 6044 women aged 40-89 who underwent a lung function test during medical checkups. AL was defined as forced expiratory volume in 1 s/forced vital capacity of < 0.7. Logistic regression analysis was used to assess the association between AL severity and the presence of comorbidities. Results: When compared with the normal lung function group, subjects with AL had a higher prevalence of lung cancer (odd ratio (OR) 9.88, 95% confidence interval (CI) 3.88-25.14) in men, hypertension (OR 1.63, 95% CI 1.26-2.10) in women, diabetes and hyperglycemia (OR 1.23, 95% CI 1.02-1.49 in men, OR 1.61, 95% CI 1.18-2.20 in women) in men and women after adjusting for potential confounders. In men, lung cancer and MetS (the Joint Interim Statement: JIS) were significantly associated with moderate-to-very severe AL after adjustment. In women, hypertension, diabetes and hyperglycemia, MetS (JIS), and MetS (the Japanese Committee of the Criteria for MetS: JCCMS) were significantly associated with mild AL after adjustment. Hypertension was significantly associated with moderate-to-very severe AL after adjustment in women. Conclusions: Significant relationships were found between AL severity and the presence of comorbid lung cancer in men, hypertension in women, diabetes and hyperglycemia, and MetS in men and women. Knowledge of comorbidities associated with AL should be widely publicized to raise the awareness of chronic obstructive pulmonary disease (COPD).
COPD; Comorbidity; Airflow limitation; Lung function; Health checkup
Chronic obstructive pulmonary disease (COPD), a
common preventable and treatable disease, is characterized
by persistent airflow limitation that is usually progressive
and associated with an enhanced chronic inflammatory
response in the airways and the lung to noxious particles
or gases [1, 2]. Exacerbations and comorbidities
contribute to the overall severity in individual patients [1, 2].
COPD is a leading cause of morbidity and mortality
worldwide and results in an economic and social burden
that is both substantial and increasing [1, 2]. The World
Health Organization (WHO) reported that COPD is the
3rd leading cause of death in the world and is presently
the 5th leading cause of death among high-income
countries, with a rate of 31 deaths per 10,000 people .
Furthermore, the burden of COPD is still expected to
continue increasing .
COPD frequently coexists with other conditions often
known as comorbidities that may have a significant impact
on prognosis [1, 2]. Most common comorbidities are
cardiovascular disease, hypertension, metabolic syndrome
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and diabetes, osteoporosis, musculoskeletal disease, lung
cancer, and anxiety and depression . These
comorbidities have a significant impact on health status, health care,
hospital admission and eventually death in patients with
COPD [1, 2, 4–7]. The prevalence of individual
comorbidities varies widely between different studies.
There are limited data available regarding the severity
of airflow limitation (AL) and comorbidities, especially
among subjects undergoing medical health checkups, in
Japan. Therefore, the aim of the present study was to
determine the relationship between AL and the common,
chronic comorbid conditions of cardiovascular disease,
hypertension, metabolic syndrome and diabetes, osteoporosis,
lung cancer, and anxiety and depression.
Materials and methods
Figure 1 shows the flow chart for selecting the subjects
with either AL or a normal lung function. A total of 25,879
people visited the Japanese Red Cross Kumamoto Health
Care Center for medical health checkups between April
2009 and March 2010. Of these, 16,901 subjects aged
40–89 years underwent comprehensive health examination
that included spirometry, as previously described .
The comprehensive health examination included
interview questionnaires, a physical examination, blood
sampling, and spirometry, as previously described [8, 9].
The interview questionnaires were conducted by a trained
public health nurse to obtain data regarding medical
history including the use of medications, and smoking status.
The never smokers consisted of those who denied any
past or current smoking. The former smokers were those
who reported smoking cessation prior to the examination.
The current smokers were those who reported smoking
at least one cigarette a day. Pack-years were calculated
by multiplying the number of years of smoking by the
average number of cigarettes smoked per day and
dividing it by 20. All the participants were evaluated by
The subjects with asthma (number (n) = 597),
tuberculosis and pleurisy (n = 300), bronchiectasis (n = 28),
pneumothorax (n = 57), bronchitis (n = 171), and other
respiratory diseases (n = 288) were excluded. In the
present study, the subjects with lung cancer were included
because lung cancer is an important comorbidity and a
leading cause of death in COPD patients . None of the
subjects were diagnosed with COPD with acute
exacerbation. The subjects with FEV1/FVC > 70% and %FEV1 <
80% (n = 2,755) were also excluded from this study. Data
from a total of 12,705 subjects (6661 men and 6044
women) were including in the final analyses (Fig. 1,
Table 1). None of the subjects had a history of exposure to
workplace dust. Subjects were divided by lung function
(11,785 subjects (6010 men and 5775 women)) had
normal lung function, 469 subjects (257 men and 212
women) had mild AL, and 451 subjects (394 men and 57
women) had moderate-to-very severe AL) (Table 1).
All study subjects gave their informed consent to
undergo a screening examination. Our research protocol
was approved by the Human Ethics Committee of
Fig. 1 Flow chart for selecting the subjects with AL or normal lung function. AL airflow limitation, FEV1 forced expiratory volume in 1 s
Table 1 The characteristics of the study subjects based on lung function
Total (n = 12,705) Normal
(n = 11,785)
Abdominal circumference, cm
Systolic blood pressure, mmHg
Diastolic blood pressure, mmHg
Smoking status, n (%)
FEV1 % predicted, %
Fasting glucose, mg/dL
HDL cholesterol, mg/dL
LDL cholesterol, mg/dL
Kumamoto University (Numbers 84) and the Japanese
Red Cross Kumamoto Health Care Center.
Lung function tests
Spirometry was performed with an electronic spirometer
(DISCOM-21 FX: CHEST MI, Tokyo, Japan) as previously
described [8–13], using equipment and quality criteria that
complied with international recommendations .
Reversibility tests were not performed for this study, and the
classifications were based on pre-bronchodilator levels.
According to Global Initiative for Chronic Obstructive
Pulmonary Disease (GOLD) guidelines, we defined AL as
an FEV1/FVC ratio of < 70% . The predicted values were
determined from the prediction equations published by the
Japanese Respiratory Society (JRS) : men, 0.036 × height
(cm)-0.028 × age-1.178; women, 0.022 × height (cm)-0.022
× age-0.005. The criteria used for the AL staging were also
developed according to GOLD guidelines, as follows: Stage
I (mild AL): FEV1/FVC < 70% and %FEV1 > 80%; Stage II
(moderate AL): FEV1/FVC < 70% and 50% < %FEV1 < 80%;
Stage III (severe AL): FEV1/FVC < 70% and 30% < %FEV1 <
50%; and Stage IV (very severe AL): FEV1/FVC < 70% and
%FEV1 < 30%. The subjects were divided into three groups:
a control group (normal lung function), GOLD Stage I
(mild AL), and GOLD Stages II–IV (moderate-to-very
severe AL). The subjects with normal lung function were
defined as having a FEV1/FVC > 70% and %FEV1 > 80%.
Following an overnight fast, blood samples were
obtained to measure the serum levels of routine medical
checkup indicators, including triglycerides, high-density
lipoprotein cholesterol (HDL-C), low-density lipoprotein
cholesterol (LDL-C), fasting glucose, and white blood
cell count, as previously described .
The following comorbidities were evaluated according to
the severity of AL in this study: lung cancer,
hypertension, diabetes mellitus and hyperglycemia, dyslipidemia,
metabolic syndrome, ischemic heart disease,
osteoporosis, and depression and mental disease.
We ascertained the presence of lung cancer, ischemic
heart disease, osteoporosis, and depression and mental
disease by means of an interview. The presence of each
comorbidity was confirmed by a physician. We defined
hypertension as antihypertensive medication use, a systolic
blood pressure of 130 mmHg or more, or a diastolic blood
pressure of 85 mmHg or more. Dyslipidemia was defined
as medication use, a triglyceride level of 150 mg/dL or
more, an LDL cholesterol level of 140 mg/dL or more, or
an HDL cholesterol level of less than 40 mg/dL, as
described previously . Diabetes and hyperglycemia were
defined as medication use or a fasting glucose level of
110 mg/dL or more. We defined the presence of metabolic
syndrome (MetS) using the following two criteria: the Joint
Interim Statement (JIS)  and the Japanese Committee
of the Criteria for MetS (JCCMS) . MetS was diagnosed
according to the JIS  when three or more of following
components were present: 1) central obesity (waist
circumference ≥ 90 cm in men and ≥ 80 cm in women); 2) high
blood pressure (systolic blood pressure ≥ 130 mmHg and/
or diastolic blood pressure ≥ 85 mmHg and/or current use
of medication for hypertension); 3) high triglyceride
(triglyceride > 150 mg/dL and/or current use of medication for
triglyceride); 4) low HDL cholesterol (HDL cholesterol <
40 mg/dL in men or < 50 mg/dL in women and/or current
use of medication for HDL cholesterol); and 5) impaired
fasting glucose (fasting glucose ≥ 100 mg/dL and/or current
use of medication for diabetes mellitus).
Furthermore, we diagnosed metabolic syndrome
according to Japanese diagnostic criteria : a waist
circumference of at least 85 cm for men and 90 cm for women, and
2 or more of the following components: 1) a triglyceride
level of 150 mg/dL and/or current use of medication for
triglyceride or more and/or an HDL cholesterol level of less
than 40 mg/dL and/or current use of medication for HDL
cholesterol; 2) a systolic blood pressure of 130 mmHg or
more and/or a diastolic blood pressure of 85 mmHg or
more and/or current use of medication for hypertension;
and 3) a fasting glucose of 110 mg/dL or more and/or
current use of medication for diabetes mellitus.
Data were presented as number of cases, mean (standard
deviation), or median with interquartile range. Differences
among normal lung function, mild AL, and
moderate-tovery severe AL were compared using a one-way analysis of
variance or Kruskal-Wallis test in case of not normally
distributed data followed by Scheffe’s post-hoc tests for
continuous variables and a chi-squared test for categorical
variables. A multivariate logistic regression model adjusted
for age, BMI, and smoking was used to assess the
relationship between severity of AL and comorbidities, with
“normal lung function” as the reference. All statistical analyses
were performed with IBM SPSS Statistics 22.0 software.
Whether the data showed normal distribution was assessed
by Shapiro-Wilk test. Values of p < 0.05 were considered to
be statistically significant. There are no missing data in the
Study population characteristics
Table 1 shows the characteristics of the study subjects based
on their lung function status. The prevalence of AL in this
study population for the GOLD stages “mild” and
“moderate-to-very severe” AL were 3.7% (n = 469) and 3.5% (n =
451), respectively. Overall prevalence of AL was 7.2%. In
men, 3.9% (n = 257) had mild airflow limitation and 5.9% (n
= 394) had moderate-to-very severe airflow limitation. In
women, 3.5% (n = 212) had mild airflow limitation and 1.0%
(n = 57) had moderate-to-very severe airflow limitation.
Among 394 men with moderate-to-very severe AL, most of
the subjects were at moderate (n = 343, 5.15%) compared to
severe (n = 45, 0.68%) and very severe (n = 6, 0.09%). In 57
women with moderate-to-very severe AL, prevalence of the
subjects with moderate, severe and very severe AL were
0.83% (n = 50), 0.12% (n = 7), and 0% (n = 0), respectively.
In this study, 6.6% (n = 31) of subjects with mild AL and
1.6% (n = 7) of subjects with moderate-to-very severe AL
had been diagnosed with COPD/emphysema. Remaining
had not been diagnosed with COPD/emphysema.
Significant differences in the lung function status were
found with regard to age in men and women, height,
weight, smoking status, pack-years in men, abdominal
circumference, fasting glucose, triglyceride, and
HDLcholesterol in women. White blood cell count was
significantly higher in the subjects with mild and
moderate-to-very severe AL than in those with normal
lung function in men.
Table 2 shows the prevalence of comorbidities between
subjects with mild AL, moderate-to-very severe AL, and
normal lung function. Hypertension was the most
prevalent comorbidity in men and women in the subjects with
AL. The present study shows a low ratio of ischemic
heart disease, osteoporosis, and depression and mental
disease. When compared with the normal lung function
group, subjects in AL group had a significantly higher
prevalence of lung cancer and diabetes and hyperglycemia
in men and lung cancer, hypertension, diabetes and
hyperglycemia and osteoporosis in women. No significant
difference were found in dyslipidemia, Mets (JIS), Mets
(JCCMS), ischemic heart disease, osteoporosis, and
depression and mental disease in the different groups of
Table 3 displays the relationship between AL and
comorbidities according to lung function. In logistic
regression models adjusting for sex, age, BMI, and
smoking status, the risks of lung cancer (odd ratio (OR): 9.88;
95% confidence interval (CI): 3.88–25.14), and diabetes
and hyperglycemia (OR: 1.23; 95% CI: 1.02–1.49) were
higher in subjects with AL compared to those with
normal lung function and in logistic regression models
adjusting for age and smoking status, the risk of MetS
(JIS) (OR: 1.32; 95% CI: 1.02–1.69) was higher in
subjects with moderate-to-very severe airflow limitation
in men. However, hypertension, dyslipidemia, MetS
(JCCMS) and ischemic heart diseases were not
significantly associated with AL in men in the present study.
In women, the risks of hypertension were significantly
higher in subjects with AL (OR: 1.63; 95% CI: 1.26–
2.10), mild AL (OR: 1.59; 95% CI: 1.20–2.11), and
moderate-to-very severe AL (OR: 1.79; 95% CI: 1.04–
3.10) compared to those with normal lung function after
adjusting for age, BMI, smoking status. The risks of
diabetes and hyperglycemia were significantly higher in
subjects with AL (OR: 1.61; 95% CI: 1.18–2.20) and mild
AL (OR: 1.68; 95% CI: 1.19–2.37) compared to those
with normal lung function after adjusting for age, BMI,
smoking status. The risks of MetS (JIS) (OR: 1.43; 95%
CI: 1.04–1.98) and MetS (JCCMS) (OR: 1.83; 95% CI:
Table 2 Prevalence of comorbidites between subjects with mild AL, moderate-to-severe AL, and normal lung function
Men (n = 6,661)
Diabetes and hyperglycemia
Ischemic heart disease
Depression and mental disease
Women (n = 6,044)
Diabetes and hyperglycemia
Ischemic heart disease
Depression and mental disease
n = 6,010
n = 5,775
n = 212
n = 57
Data presented are number (percent)
Ischemic heart disease; including angina pectoris and myocardial infarction Airflow limitation (AL) was dfined as FEV1/FVC < 0.7
Hypertension; antihypertensive medication use or systolic blood pressure ≧ 130 mmHg or diastolc blood pressure ≧ 85 mmHg Diabetes and hypergfycemia; blood
glucose-lowerning medication use or elevated fasting glucose ≧ 110 Dyslipidemia; medication use or triglycerides ≧ 150 mg/dl, HDL-C < 40 mg/dl or LDL-C
≧ 140 mg/dl
AL airflow limitation, MetS metabolic syndrome, JIS Joint Interim Statement, JCCMS Japanese Committee of Criteria for MetS
Table 3 Relationship between AL and comorbidities according to lung function (Continued)
Crude OR (95% CI)
Adjusted OR (95% CI)
Adjusted for age, body mass index, smoking status, * adjusted for age and smoking status
Airflow limitation (AL) was difined as FEV1/FVC < 0.7
Hypertension; antihypertensive medication use or systolic blood pressure ≧130 mmHg or diastolic blood pressure ≧85 mmHg Diabetes and hyperglycemia; blood
glucose-lowerning medication use or elevated fasting glucose ≧110 Dyslipidemia; medication use or triglycerides ≧150 mg/dl, HDL-C < 40 mg/dl or
LDLC≧140 mg/dl MetS (JCCMS) Dyslipidemia
AL airflow limitation, MetS metabolic syndrome, JIS Joint Interim Statement, JCCMS Japanese Committee of Criteria for MetS, OR odds ratio, CI confidence interval
1.04–3.21) were significantly higher in subjects with mild
airflow limitation compared to those with normal lung
function after adjusting for age and smoking status in
women. However, the risks of lung cancer, dyslipidemia
and osteoporosis were not significantly higher in
subjects with AL after adjusting for age, BMI, smoking
status in women in the present study.
This study focused on the prevalence and risks of
comorbidities in those who received comprehensive
health examination according to their lung function.
The currently available data regarding the severity of AL
and comorbidities, especially among subjects undergoing
medical health checkups, are limited.
The main findings of this study are that the prevalence
of lung cancer, diabetes and hyperglycemia, and MetS
(JIS) were significantly higher in subjects with
moderateto-very severe AL. In men, the risks of lung cancer,
diabetes and hyperglycemia, and MetS (JIS) were
significantly higher in subjects with AL compared to those with
normal lung function. In women, the risks of
hypertension, diabetes and hyperglycemia, MetS (JIS) and MetS
(JCCMS) were higher in subjects with AL compared to
those with normal lung function.
The document of Global Initiative for Chronic
Obstructive Pulmonary Disease (GOLD) reported that lung
cancer is frequently seen in patients with COPD and has
been found to be the most frequent cause of death in
patients with mild to moderate COPD [1, 2]. In this study,
we demonstrated that the odds ratio for having lung
cancer compared to those with normal lung function
was 6.52 in subjects with mild AL and 12.58 in subjects
with moderate-to-very severe AL in men, whereas there
was no significant difference in women. In this study, we
could not obtain the information about the histologic
type of lung cancer from interview questionnaires.
Several longitudinal studies demonstrated the relationship
between COPD and lung cancer [18–20]. Mannino et al.
demonstrated a hazard ratio of 2.8 (adjusted for
smoking, age, sex, race, and education) in patients with
moderate to severe COPD and a risk proportional to the
severity of the AL in an analysis of 22-years follow-up
data . De Torres et al. showed that mild and
moderate stages of COPD are associated with a greater
risk for developing lung cancer . COPD has been
identified as an independent risk factor for lung cancer
[18–20]. In the present cross-sectional study, we
observed an association between airflow limitation severity
and lung cancer in men. As with any cross-sectional
study, there may be a potential reverse causation between
airflow limitation and lung cancer.
Our findings could have implications in the
management of subjects with AL encountered in the setting of
medical health checkups and in lung cancer screening
The exact reason why some smokers develop COPD,
some develop cancer and some develop both diseases is
not known . The presence of chronic smoldering
inflammation has been postulated as the possible
underlying mechanism linking cancer and COPD caused by
cigarette smoke exposure [19, 21]. Recent studies have
proposed chromosomal loci and/or candidate genes
associated with lung function, COPD and lung cancer
. It would be very useful to further understand the
overlapping pathways of COPD and lung cancer .
Sex differences have raised some controversy in the
literature regarding COPD and lung cancer . Loganathan
et al. showed a significantly lower prevalence of COPD in
females diagnosed with lung cancer than in males . Our
findings are in line with the previous study. They suggested
that sex-based differences should be taken into account
when building up strategies for lung cancer screening.
Larger epidemiological studies are needed in this area.
Hypertension is consistently one of the most prevalent
comorbid diagnosis in COPD patients reported in 40–
60%  and has implications for prognosis . Mannino
et al. reported a prevalence of hypertension of 34% in
normal subjects, rising to 40% in GOLD stage I patients,
44% in GOLD stageIIand 51% in GOLD stage III and IV
. In the multivariate analysis, the odds ratio for having
hypertension compared with normal subjects was 1.4 in
GOLD stage I and 1.6 in GOLD stages II and IV . In
this study, hypertension (OR: 1.63; 95% CI: 1.26–2.10) is
higher in subjects with AL compared to those with
normal lung function in women, whereas there was no
significant difference in men. Larger epidemiological
studies are needed regarding gender-based difference.
The OR having diabetes and hyperglycemia compared
with normal lung function was 1.23 for men and 1.61
for women in total AL, and 1.68 in mild AL for women.
The pathophysiological link between COPD and diabetes
is not entirely understood, although thought to involve
systemic inflammation with central roles for IL-6 and
TNF-α . We found that the prevalence of MetS was
higher when using JIS criteria than when using JCCMS
criteria, especially in women, which were consistent with
the study by Hu H. et al. . Hu H et al. demonstrated
that the JIS criteria can detect more people who later
develop diabetes mellitus than does the JCCMS criteria
. In men, MetS (JIS) (OR, 1.32; 95% CI, 1.02–1.69)
were significantly associated with moderate-to-very
severe AL, after adjusting for sex, age, and smoking status.
However, we found that MetS (JCCMS) was not
significantly associated with moderate-to-very severe AL after
adjusting for sex, age, and smoking status. In women,
MetS (JIS) (OR, 1.68; 95% CI, 1.19–2.37) and MetS
(JCCMS) (OR, 1.83; 95% CI, 1.04–3.21) were
significantly associated with mild AL, after adjusting for sex,
age, and smoking status. Previous studies have reported
that diabetes and Mets are more frequent in COPD
patients who are at the earlier stages of COPD [25–27].
The reason of the gender-difference is not clear. Further
studies are needed to better understand the
genderdifference. Our findings in men are consistent with our
previous study . These criteria differ in several
aspects, including the cut-off points of waist circumference
(WC), handling of the WC component (prerequisite or
optional for the diagnosis of MetS), and the criteria of
hyperglycemia and dyslipidemia . These differences
have led to confusion regarding the choice of the criteria
to diagnose MetS . Hu H. et al. very recently
demonstrated that waist circumference cut-offs of 85 cm for
men and 80 cm for women are appropriate in the
Japanese population . Additional research is needed
to clarify this aspect of criteria.
Dyslipidemia is one of several parameters employed to
diagnose metabolic syndrome [16, 17]. However, most
studies have not demonstrated significant differences in
the prevalence of dyslipidemia between COPD patients
and control subjects [23, 28]. Our findings are consistent
with these previous studies.
Compared with the previous study by Smith et al., our
study demonstrated a low ratio of ischemic heart disease
. According to the document of Global Initiative for
Chronic Obstructive Lung Disease (GOLD),
cardiovascular disease is a major comorbidity in COPD and probably
both the most frequent and most important [1, 2].
However, we found that ischemic heart disease is less prevalent
in this study. In addition, ischemic heart disease was not
significantly associated with AL after adjusting for sex,
age, BMI, and smoking status in the present study. There
are conflicting results regarding the association between
COPD severity and the risk of cardiovascular comorbidity
. A review by Takahashi S et al.  demonstrated that
the comorbidity spectrum of Japanese COPD patients
seems to differ from that of Westerners. For example, they
reported that cardiovascular disease is less prevalent
Japanese COPD patients. The fact that the prevalence of
cardiovascular comorbidities in Japanese COPD patients
differs from that in Western patients may arise from
ethnic or genetic differences, or from environmental
differences including lifestyle and socioeconomic factors .
Studies have shown that osteoporosis, anxiety and
depression are major comorbidities in COPD [1, 2, 29]. In
this study, we observed a low ratio of osteoporosis, anxiety
and depression. Further research is needed to elucidate
the relationship between AL and these comorbidities.
COPD is characterized by persistent systemic
inflammation [1, 6]. Previous research found that the group of
patients with severe COPD had significantly higher
circulating leukocyte . Our results are in line with this
study. Systemic inflammation has been widely reported
to be a key link between COPD and some comorbidities
. The source of systemic inflammation in COPD
may be the results of a spill-over of airway and lung
parenchymal processes . While the causal
relationship between COPD and comorbidities is not entirely
clear, inactivity and systemic inflammation have been
suggested as part of the mechanism for the
comorbidities associated with COPD and may relate to the natural
course of the disease [30, 31].
The strength of this study is estimating the prevalence
of AL and comorbidities among subjects undergoing
medical checkup. In this study, the prevalence of
diagnosed COPD/emphysema among subjects with AL
was only 6.6% in mild AL and 1.6% in moderate-to-very
severe AL. Remaining had not been diagnosed with any
respiratory diseases, suggesting a high degree of
underdiagnosis of COPD. Conclusively, earlier diagnosis and
intervention of COPD and its comorbidities could
improve the prognosis of COPD for individual patients and
reduce the disease burden of COPD on the society.
There are several limitations associated with the present
study. First, we did not employ reversibility testing, since
our Institutional Review Board considered it unacceptable
in the absence of a high suspicion of disease. For this
reason, the subjects with AL may have included subjects with
a post-bronchodilator FEV1/FVC ratio greater than 70%.
Our study excluded any subjects who had ever received a
diagnosis of asthma or other respiratory diseases except
for lung cancer. Therefore, these individuals could
possibly have COPD, and they may have even had asthma;
thus, we expressed “AL” instead of COPD. This limitation
has also been reported in the previous studies [8, 9]. A
modified GOLD definition that omits bronchodilation has
become widely adopted by population-based
epidemiological studies . Second, the presence of lung cancer,
ischemic heart disease, osteoporosis, and depression and
mental disease was confirmed by the interview by a
trained public health nurse and a physician. The
methodology used to report the presence of a comorbidity that is
not completely objective because it was not based on
confirmatory tests for each disease.
Third, because of the cross-sectional design, we cannot
rule out the possibility that reverse causation may explain
our results. Further larger-scale prospective studies are
needed to further confirm our findings. Fourth, the
present study was a single-center study performed with
subjects who underwent a medical health checkup. This
may limit applicability across different centers.
Despite these limitations, we consider the present
study to be worthwhile because it is the first to reveal
the relationship between AL severity and various
comorbidities in comprehensive health examination, as far as
the authors know.
In conclusion, a significant relationship was found
between AL and the presence of comorbid lung cancer in
men, hypertension in women, diabetes and
hyperglycemia, and MetS in men and women. Further research
investigating gender-based difference of comorbidity is
needed. Similarly, further research is required to fully
understand the relationships and underlying
mechanisms between airflow limitation and the comorbidities.
Our findings could have implications in the management
of subjects with AL on medical health checkups. Efforts
aimed at the earlier detection of AL and the
identification of comorbidities may become integral for the
reduction of the disease burden of COPD on the society.
Knowledge of comorbidities associated with AL should
be widely publicized to raise the awareness of COPD.
The authors would like to thank the technicians at the Japanese Red Cross
Kumamoto Health Care Center for their excellent technical assistance.
All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
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