Egyptian Journal of Chest Diseases and Tuberculosis (2014) 63, 313–319

The Egyptian Society of Chest Diseases and Tuberculosis

Egyptian Journal of Chest Diseases and Tuberculosis

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ORIGINAL ARTICLE

Serum adiponectin level in obese and non-obese COPD

patients during acute exacerbation and stable conditions
Magdy Mohammad Omar a,1, Hesham Ali Issa b,2, Ahmad Abdelsadek
Mohammad a,*, Moustafa Abd-Elaty Abd-Elhamid c,3

a
Chest Department, Benha University, Egypt
b
Clinical & Chemical Pathology Department, Benha University, Egypt
c
Tanta Chest Hospital, Egypt

Received 23 December 2013; accepted 5 January 2014

Available online 5 February 2014

KEYWORDS Abstract Aim: To assess serum adiponectin in obese & non obese COPD during exacerbation and
Obesity; stable conditions and its relation to ventilatory functions.
Serum adiponectin level; Subjects and methods: The study was conducted on 40 male COPD patients during exacerbation
Body mass index; and stable conditions with 15 age matched healthy control subjects. Patients and control were
Exacerbation & stable COPD divided into non-obese and obese according to their body mass index. Subjects were submitted
to full history taking, Complete physical examination, plain chest X-ray, Complete blood count,
Erythrocyte sedimentation rate, Liver and kidney functions, Fasting and post prandial blood sugar,
Ventilatory functions, and Venous blood samples for Adiponectin measurement.
Results: There was Significant difference in serum adiponectin between exacerbated nonobese
COPD and nonobese controls (P < 0.005) and significant difference in serum adiponectin between
exacerbated obese COPD patients and obese controls (P < 0.05). Significant difference was
observed in serum adiponectin between nonobese stable COPD and nonobese controls
(P < 0.005). Significant difference was observed in serum adiponectin between exacerbated
nonobese COPD and stable nonobese COPD (P < 0.05). Significant difference was observed in
serum adiponectin between nonobese COPD and obese COPD patients during exacerbation and
stable states (P < 0.001). Non significant correlation was found between changes in serum
adiponectin in nonobese COPD and obese COPD (exacerbation and stable conditions) and

* Corresponding author. +20 1222758380/96563090628.

E-mail address: ahmadabdelsadek@yahoo.com (A.A. Mohammad).
1
Mobile: +20 1062226103.
2
Mobile: +20 1009120363.
3
Mobile: +20 1008391759.
Peer review under responsibility of The Egyptian Society of Chest
Diseases and Tuberculosis.

Production and hosting by Elsevier

0422-7638 ª 2014 Production and hosting by Elsevier B.V. on behalf of The Egyptian Society of Chest Diseases and Tuberculosis.
http://dx.doi.org/10.1016/j.ejcdt.2014.01.004
314
following ventilatory functions, FVC (% pred), FEV1 (% pred), FEV1/FVC and FEF25-75
(% pred).
Conclusion: Serum adiponectin was significantly higher in obese and nonobese COPD than con-
trols, the rising is more during exacerbation than stable condition and more in non obese than obese
COPD and non significant correlation between changes in adiponectin and ventilatory functions
was found.
ª 2014 Production and hosting by Elsevier B.V. on behalf of The Egyptian Society of Chest Diseases and
Introduction
Chronic Obstructive Pulmonary Disease (COPD) is a pre-
ventable and treatable disease with some significant extra pul-
monary effects that may contribute to the severity in
individual patients. Its pulmonary component is characterized
by airflow limitation that is not fully reversible. The airflow
limitation is usually both progressive and associated with
an abnormal inflammatory response of the lung to noxious
particles or gases [10]. An exacerbation of COPD is defined
as an event in the natural course of the disease characterized
by a change in the patient’s baseline dyspnea, cough, and/or
sputum that is beyond normal day-to-day variation, is acute
in onset, and may warrant a change in regular medication in
a patient with underlying COPD [4]. COPD affects about
10% of the general population, but its prevalence among hea-
vy smokers can reach 50% [6]. Adiponectin is a secretory
protein synthesized by adipocytes and has important anti-
inflammatory, anti-atherosclerotic and antiobesity effects
[28]. Adiponectin is a mediator with possible association with
the development and exacerbation of COPD that has recently
gained the spotlight (5–10). Adiponectin as a cytokine has
both pro-inflammatory and anti-inflammatory properties
and by stimulating the release of other cytokines particularly
interleukins plays a part in the development of exacerbation
or control of inflammation [5]. Due to this property,
researchers suspected that adiponectin may have a role in
the development and exacerbation of COPD and investigated
this issue in several studies [13].
Aim of the work
Was to assess the level of serum adiponectin in obese & non
obese chronic obstructive pulmonary disease patients (COPD)
during acute exacerbation and in stable conditions and to
determine whether changes in its level correlate with changes
in the ventilatory functions or not.
Subjects and methods
This study was conducted on 40 male patients with COPD
and 15 age matched healthy subjects as controls (all COPD
& controls are smokers). All COPD patients were in acute
exacerbation as defined by [7]. All COPD patients and the
control group were divided into non-obese and obese accord-
ing to their body mass index (BMI). Those with BMI < 25
& > 18.5 were considered non-obese. Those with
M.M. Omar et al.
Tuberculosis.
BMI > 30 were considered obese .Those with BMI between
25 and 30 were considered overweight and were not included
in this study [19]. They were admitted to the chest depart-
ment in Benha University hospital in the period between July
2010 and July 2011. The diagnosis of COPD had been estab-
lished on the basis of the Global Initiative for Chronic
Obstructive Lung Disease [10]. All patients for acute exacer-
bation COPD received adequate treatment until reach stable
state with disappearance of symptoms and signs of exacerba-
tion such as increased dyspnea, increased sputum purulence,
increased sputum volume, increased cough, increased wheeze,
chest tightness, increased fatigue, increased respiratory rate
more than 25 breath/minute and increased heart rate by
20% above baseline. All subjects were submitted to:
(1) Full history taking (including smoking history) and clin-
ical examination.
(2) Body mass index (BMI).
(3) Radiological examination (plain chest X ray postero-
anterior and lateral views)
(4) Ventilatory function tests (spirometry) done to all cases
during exacerbation and stable condition before and
after bronchodilatation by using a Sensor-medics V
max series, 2130 spirometer, V6200 Autobox, and 6200
DL.
(5) Laboratory tests: complete blood count, liver functions,
kidney functions, ESR and fasting, postprandial blood
sugar.
(6) Blood samples for adiponectin measurement: Venous
blood samples were obtained between 8:00 am and 9:00
am after an overnight fast. After clotting at 48 C, the
serum was separated by centrifugation at 1000g for
5 min at room temperature and stored at 70 C until
analysis. The serum levels of adiponectin were quantified
using a sandwich enzyme–linked immunosorbent assay
kit according to manufacturer’s protocol.
Principle of the assay
Adiponectin, also referred to as Acrp30, AdipoQ and GBP-
28, is an 244 aminoacids protein, which is physiologically
active, specifically and highly expressed in adipose cells
(adipokine). Adiponectin forms homotrimers, which are the
building blocks for higher order complexes found circulating
in serum. This Enzyme Linked Immuno Sorbent Assay (ELI-
SA) is based on the competition between free adiponectin and
Adiponectin level in obese and non-obese COPD patients
coated adiponectin, in the presence of a known quantity of
HRP labeled adiponectin antibody (tracer).
Measurement of serum adiponectin concentration
The serum adiponectin concentration was measured by the
double antibody sandwich ELISA method with an antibody
specific for human adiponectin (R&D systems).
Exclusion criteria
(1) History of any other co-morbidities that may raise the
adiponectin as, malignancy, hepatic cirrhosis, end-stage
renal disease, rheumatoid arthritis and any systemic
infection or inflammation [15].
(2) By spirometry: reversibility in post bronchodilator
FEV1 (% pred) more than 12% or 200 ml.
Statistical presentation and analysis of the present study
were conducted, using the mean, standard deviation, linear
correlation coefficient, analysis of variance [ANOVA] test
and chi-square test by SPSSV [29].
Results
See Tables 1–9.
Discussion
COPD is considered as a multicomponent disease including
weight loss, nutritional abnormalities, skeletal muscle dysfunc-
tion, risk of myocardial infarction, angina, osteoporosis, bone
fracture, depression and sleep disorders [26]. Adiponectin is an
adipocyte-specific protein secreted by visceral fat tissue that
has anti-inflammatory as well as anti-obesity effects [17]. In pa-
tients with metabolic syndrome, adiponectin levels in plasma
decreased in proportion with the increase in body weight [2].
Hypoadiponectinemia correlated with both insulin resistance
[24], and atherosclerosis resulting in cardiovascular disease
[14]. Adiponectin is a predominantly anti-inflammatory adipo-
kine. Adiponectin inhibits proinflammatory cytokines, such as
TNF-a, IL-6, and nuclear factor k B [16], as well as induces
anti-inflammatory cytokines, such as IL-10 and IL-1receptor
antagonist [14].
Table 1 Demographic data of studied subjects as regards, number, sex, age, & body mass index.
Obese
Control
No. 7 (100%)
Age/years 48.75 ± 5.4 R:43–59
BMI (kg/m2) 34 ± 1.3 R:31.7–35.8
COPD
No. 20 (100%)
Age/year 53.13 ± 5.08 R:45–60
BMI (kg/m2) 32.9 ± 1.9 R:30.2–35.9
315
The demographic data of the studied groups are illustrated
in Table 1. The study included 55 subjects (7 control obese, 8
control nonobese, 20 obese COPD patients and 20 nonobese
COPD patients) in this study the range of age in obese control
subjects was from 43 to 59 years with the mean age
48.75 ± 5.4 years while in nonobese control subjects from 43
to 60 years with the mean age 47.75 ± 6.43 years while in ob-
ese COPD patients the range was from 45 to 60 years with the
mean age 53.13 ± 5.08 years and in nonobese COPD patients
the range was from 47 to 63 years with the mean age
54.88 ± 5.25 years. The range of body mass index (kg/m2) in
obese control subjects was from 31.7 to 35.8 (kg/m2) with
the mean body mass index 34 ± 1.3(kg/m2). While in
nonobese control subjects from 22.6 to 24.9 (kg/m2) with the
mean body mass index 23.5 ± 2 (kg/m2) and, in obese COPD
patients the range was from 30.2 to 35.9 (kg/m2) with the mean
body mass index 32.9 ± 1.9(kg/m2) and in nonobese COPD
patients the range was from 19.2 to 24.9 (kg/m2) with the mean
body mass index 22 ± 1.7 (kg/m2).These demographic data re-
vealed no significant difference between control obese and non
obese as regarding age while there was significant difference in
body mass index between both of them. Also, there was no sig-
nificant difference between obese COPD patients and non ob-
ese COPD patients as regarding age while there was significant
difference in body mass index between both of them. In this
study, there was significant difference in serum adiponectin le-
vel between nonobese COPD patients during exacerbation and
nonobese controls (P < 0.005) and significant difference in
serum adiponectin level between obese COPD patients during
exacerbation and obese controls (P < 0.05) (Table 2). And
there was a significant difference in serum adiponectin between
nonobese stable COPD cases and nonobese controls
(P 6 0.005) (Table 3). Also there was a significant difference
in serum adiponectin between nonobese COPD cases during
exacerbation and nonobese stable COPD cases (P 6 0.05)
(Table 4). These results were in agreement with the work done
by Tomoda et al. [25] who made their study on 31 male COPD
patients in stable states, they were classified according to their
body mass index into groups under weight (BMI 6 20 kg/m.
n = 19), normal weight (BMI P 25 kg/m. n = 12) and age
matched healthy male control subjects (n = 12). Adiponectin
was measured by ELIZA. They found that the adiponectin le-
vel was significantly higher in COPD cases (under weight and
normal weight) than control subjects (P 6 0.01). Tomoda et al.
[25] study was done only on stable COPD patients but this
study was done during exacerbation and during stable states.
This study was in agreement with the work done by Kirdar
et al. [13] who made their study on 36 male patients with
Non Obese t-test p-value
8 (100%) 3.4 >0.05
47.75 ± 6.43 R:43–60 0.093 >0.05
23.5 ± 2 R:22.6–24.9 12.6 <0.005
20(100%) 3.8 >0.05
54.88 ± 5.25 R:47–63 0.677 >0.05
22 ± 1.7 R:19.2–24.9 11.9 <0.005
316 M.M. Omar et al.

Table 2 Statistical comparison of serum adiponectin (mcg/ Table 6 Correlation between changes in serum adiponectin
ml) between nonobese, Obese COPD cases during exacerbation (mcg/ml) and changes in FVC (%pred) in nonobese and obese
in comparison with the control groups. COPD cases from exacerbation to stable states.
Nonobese (n = 33) Obese (n = 22) r p
Control COPD Control COPD Non obese 0.241 >0.05
(n = 8) (n = 25) (n = 7) (n = 15) Obese 0.198 >0.05
Mean 5.51 19.4 1.37 5.38
±SD 1.51 1.58 0.91 1.15
t. test 13.895 3.253
p. Value <0.005 <0.05 Table 7 Correlation between changes in serum adiponectin
(mcg/ml) and changes in FEV1 (% pred) in nonobese and obese
COPD cases from exacerbation to stable states.
R P
Table 3 Statistical comparison of serum adiponectin (mcg/
ml) between nonobese, obese stable COPD cases in comparison Non obese 0.241 >0.05
Obese 0.282 >0.05
with the control groups.
Non obese (n = 33) Obese (n = 22)
Control COPD Control COPD
(n = 8) (n = 25) (n = 7) (n = 15)
Table 8 Correlation between changes in serum adiponec-
Mean 5.51 14.8 1.37 4.52
tin(mcg/ml) and changes in FEV1/FVC in nonobese and obese
±SD 1.99 2.76 0.53 1.36
COPD cases from exacerbation to stable states.
t. test 5.258 4.523
p. Value <0.005 <0.05 r p
Non obese 0.230 >0.05
Obese 0.099 >0.05

Table 4 Statistical comparison of serum adiponectin (mcg/ department of respiratory disease, and 30 healthy non smoking
ml) between nonobese, obese COPD cases during exacerbation male controls. All cases had normal weight (BMI range
and during stable states. 18.5–24.9 kg/m) the serum and induced sputum were collected
Non obese (n = 25) Obese (n = 15) from each case. They found that the concentration of adipo-
Exacerbation Stable Exacerbation Stable nectin in the serum or induced sputum in AECOPD was signif-
icantly higher than those in stable COPD or healthy non
Mean 19.4 14.8 6.38 5.5
smoking controls (P 6 0.01).The concentration of adiponectin
±SD 1.58 2.76 1.97 1.91
in stable COPD was significantly higher than that in healthy
t. test 2.856 1.241
p. Value <0.05 >0.05 non smoking controls (P 6 0.01). The inflammation in the air-
way leads to pathological process of COPD. In this process, a
large number of inflammatory cells accumulate in the airway
including neutrophils and macrophage. They release various
COPD (15 stable and 21 in exacerbation) and 17 age and sex inflammatory mediators, causing pulmonary damage [23].
matched healthy subjects .They found that the serum level of COPD is also a kind of systemic inflammatory disease [28]
adiponectin was significantly higher in COPD cases than those and is characterized with abnormal activation of inflammatory
in control subjects (P 6 0.001) and it was significantly higher cells and the abnormal increase of circulating cytokines,
in COPD during exacerbation as compared to stable states. including CRP, IL-8, TNF-a, IL-6 and Leptin. Adiponectin
This study was also in agreement with work done by Xie is a newly discovered cytokines [13]. Neutrophils are the main
et al. [12] who made prospective study from October 2008 to inflammatory cells in the airway of COPD patients, especially
October 2009, including 30 male AECOPD patients from the in AECOPD patients. By the action of various inflammatory
emergency department, 30 male stable COPD cases from the factors, neutrophils rapidly move to the airway through trans-

Table 5 Statistical comparison of serum adiponectin (mcg/ml) between nonobese and obese COPD cases during exacerbation and
during stable states.
COPD (exacerbation) COPD (stable)
Non obese (N = 25) Obese (N = 15) Non obese (N = 25) Obese (N = 15)
Mean 19.4 6.38 14.8 5.5
+SD 1.58 1.97 2.76 1.91
t. test 6.325 5.856
p. Value <0.005 <0.005
Adiponectin level in obese and non-obese COPD patients
Table 9 Correlation between changes in serum adiponectin
(mcg/ml) and changes in FEF 25–75 (% pred) in nonobese and
obese COPD cases from exacerbation to stable states.
r p
Non obese -0.241 >0.05
Obese 0.241 >0.05
epithelial transport and cause degranulation [9]. Various
inflammatory mediators are released in degranulation, pro-
moting inflammatory reaction. Epithelial cells in the airway
will stimulate expression of IL-8 under APN [20]. Adiponectin
is able to inhibit macrophages producing TNF-a and reduce its
synthesis and biological activity, suggesting that APN has
some anti inflammatory effects [18]. So adiponectin could play
both pro inflammatory and anti-inflammatory roles, APN
could be a new marker of COPD inflammation. A further rise
in serum adiponectin in the exacerbation period denotes that it
may be a biomarker of inflammation in COPD patients during
exacerbation. In this study, there was a significant difference in
serum adiponectin between obese COPD cases during exacer-
bation and obese control (P 6 0.05) (Table 2). And there
was a significant difference between obese stable COPD cases
and obese control (P 6 0.05) (Table 3). But there was no
significant difference between obese COPD cases during exac-
erbation and during stable state (Table 4). Very little
researches were found discussing the role of serum adiponectin
in obese COPD patients during exacerbation and during stable
conditions. So, this study tried to find out if adiponectin plays
a role in such patients. In healthy subjects, adiponectin carries
out its roles for preventing development of vascular changes
and the impairment of glucose and lipid metabolism, which
may be induced by a variety of attacking factors, such as
chemical subjects, mechanical stress, or nutritional loading.
A large amount of adiponectin flows with the blood stream
in the inside of vascular walls, it would be interesting to know
whether adiponectin can enter the vascular walls. Adiponectin
has potential inhibitory activities of these atherogenic cellular
phenomena. Adiponectin was shown to inhibit the TNF-a-in-
duced nuclear factor-KB activation through the inhibition of I
Kb phosphorylation, which might be a major molecular mech-
anism for the inhibition of monocyte adhesion to endothelial
cells [25]. Adiponectin also inhibits the expression of the scav-
enger receptor type A-1 of macrophages, resulting in markedly
decreased uptake of oxidized LDL and inhibition of foam cell
formation [1]. In addition, adiponectin inhibits the prolifera-
tion and migration of smooth muscle cells, from these vascular
cellular functions, adiponectin may have a potential antiath-
erogenicity. So, based on the above mentioned, serum levels
of adiponectin may play a role in obese COPD patients, it is
known that acute exacerbations of COPD (most often in
response to bacterial infection) are associated with increased
serum of CRP, IL-6, TNF-a, leptin, and adiponectin, as well
as with increases in other factors associated with bacterial
inflammation and infection. This suggests that the elevation
of plasma adiponectin level in obese COPD may be associated
with other pathophysiological findings beside body weight in
COPD. Tomoda et al. [25] detected that adiponectin was
317
approximately 2-fold higher in normal weight, stable COPD
cases than in controls, Kirdar et al. [13] also detected approx-
imately 2-fold higher adiponectin levels in COPD cases with
normal BMI than controls. In addition they reported higher
adiponectin levels in the exacerbation period compared to
those in stable patients, indicating augmented inflammatory
response. It was concluded from the above studies that serum
level of antiobesity adipokine adiponectin was significantly
higher even in COPD cases with normal BMI than the level
in healthy subjects indicating that serum level of adiponectin
rises earlier than body weight loss as a component of systemic
inflammatory response. Many studies reported elevated serum
of adiponectin in underweight COPD cases and in normal
weight but there was no direct comparison between nonobese
and obese COPD cases as in such studies. In Table 5 serum
adiponectin was compared between nonobese and obese
COPD cases during exacerbation and during stable states. It
was found that, there was a statistically highly significant dif-
ference in serum adiponectin (mcg/ml) between nonobese
COPD cases and obese COPD cases during exacerbation and
also during stable states (P 6 0.001). It was previously demon-
strated that in obese patients, adiponectin levels significantly
decreased. Adiponectin is an adipocyte-specific protein se-
creted by visceral fat tissue that has anti-inflammatory as well
as antiobesity effects [17]. In patients with anorexia nervosa
and cachexia, plasma adiponectin levels were elevated
[27].COPD is a syndrome rather than a single disease because
there are two major phenotypes in COPD. One is the emphy-
sema-dominant type, so-called ‘‘pink puffers,’’ who are fre-
quently cachectic. Another is the airway disease-dominant
type, so-called ‘‘blue bloaters,’’ who are frequently obese. It
was demonstrated that BMI might be one of the determinants
of COPD phenotype [11]. In the present study serum levels of
adiponectin remarkably elevated in nonobese COPD cases
rather than obese COPD cases. And this may be explained
by hyperinflation, one of the physiologic characteristics of
COPD, is caused by air trapping. Hyperinflation is known to
cause diaphragm dysfunction [21] which results in an increase
in respiratory effort [22]. The increase in respiratory effort cor-
relates with overload of respiratory muscles and excess respira-
tory exercise [8]. Some studies reported changes in plasma
adiponectin levels by exercise in different populations, these
studies generally revealed that chronic exercise, but not
short-time exercise, increased plasma adiponectin levels and
enhanced expression adiponectin receptor I in skeletal muscles.
Adiponectin receptor I promotes glucose uptake and lipid oxi-
dation in the muscle [3,30]. Hyperinflation is associated with
hypermetabolism and malnutrition in COPD [8]. The present
study demonstrated that even in obese patients with COPD,
plasma adiponectin levels elevated. These results suggest that
persistent excess respiratory exercise caused by hyperinflation
elevates plasma adiponectin levels before body weight loss
and that the elevated adiponectin may contribute to the devel-
opment of malnutrition in COPD. In the present study, corre-
lations of changes in ventilatory function tests with changes in
serum adiponectin were done in all COPD cases (nonobese and
obese) during exacerbation and during stable conditions.
There were lack of correlation between changes in serum
adiponectin and changes in FVC (% pred) in nonobese COPD
and obese COPD cases from exacerbation to stable state
318
(Table 6). There were also lack of correlation between changes
in serum adiponectin and changes in FEV1 (% pred) in nonob-
ese COPD and obese COPD cases from exacerbation to stable
state (Table 7). There were also lack of correlation between
changes in serum adiponectin and changes in FEV1/FVC ratio
in nonobese COPD and obese COPD cases from exacerbation
to stable state (Table 8). And there were also lack of correla-
tion between changes in serum adiponectin and changes in
FEF25-75 (% pred) in nonobese COPD and obese COPD
cases from exacerbation to stable state (Table 9). So, no corre-
lations were observed between changes in ventilatory function
tests and changes in serum adiponectin level. These results
were in agreement with the work done by Tomoda et al. [25]
in which FEV1 did not correlate with plasma adiponectin lev-
els but this study was done in nonobese. Also, this study was in
agreement with the work done by Kirdar et al. [13] in which
there was no correlation between FEV1 and plasma adiponec-
tin levels during exacerbation or during stable conditions.
Conclusions
(1) Serum adiponectin level is raised in nonobese COPD
cases and the rising is more during exacerbation.
(2) Serum adiponectin level is raised in obese COPD cases
during exacerbation and during stable conditions.
(3) Serum adiponectin level is raised in nonobese COPD
cases more than in obese COPD cases.
(4) There was lack of correlation between changes in serum
adiponectin and ventilatory functions.
Conflict of interest
None declared.
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