International Journal of Cardiology 119 (2007) 83 – 89

www.elsevier.com/locate/ijcard

Anorexia in chronic obstructive pulmonary disease — Association

to cachexia and hormonal derangement
Friedrich Koehler a , Wolfram Doehner b,⁎, Soeren Hoernig c , Christian Witt c ,
Stefan D. Anker b,d , Matthias John c
a
Department of Cardiology, Charité University Hospital, Campus Mitte, Berlin, Germany
b
Division of Applied Cachexia Research, Department of Cardiology, Charité University Hospital, Campus Virchow, Berlin, Germany
c
Department of Pneumology, Charité University Hospital, Campus Mitte, Berlin, Germany
d
Clinical Cardiology, National Heart and Lung Institute, Imperial College, London, United Kingdom
Received 10 April 2006; accepted 15 July 2006
Available online 24 October 2006

Abstract

Background: In patients with chronic obstructive pulmonary disease (COPD) weight loss frequently occurs that may ultimately lead to
cachexia as a serious co-morbidity, indicating severely impaired functional capacity, health status and increased mortality. Increased energy
expenditure due to mechanic and metabolic inefficiency and systemic inflammation are determinants of a hypermetabolic state that is not
balanced by dietary intake. Anorexia may importantly contribute to weight loss in COPD, however, the association between immune and
hormonal derangement and altered appetite has not been studied in detail.
Aim: The aim of the present study was to investigate whether anorexia in COPD is related to inflammation and hormonal derangement in
association to weight loss.
Methods: We prospectively enrolled 103 consecutive patients with COPD (age 59.8 ± 1.3 years, 35% female, mean FEV1 38.3 ± 1.7%) in
comparison to healthy controls of similar age (n = 15).
Results: In 34 patients (33%) cachexia was diagnosed (weight loss N 7.5%, BMI ≤ 24 kg/m2). Cachectic COPD patients had lower BMI
(19.0 ± 0.5 vs 25.6 ± 0.7 kg/m2) and impaired lung function (FEV1 31 ± 2% vs 42 ± 2%, FVC 51 ± 3 vs 59 ± 3%, both p b 0.001). Inflammatory
immune activation (IL-6 and IL-6/IL-10 ratio) was significantly higher in cachectic COPD patients. Analysis of the extent of anorexia (visual
analogue scale) revealed that cachectic COPD patients had significantly decreased subjective desire to eat compared to non-cachectic patients
(3.5 ± 0.3 vs 6.3 ± 0.2, p b 0.001). Patients with COPD and cachexia showed evidence of acquired GH resistance (decreased IGF-1/GH ratio)
and insulin resistance (HOMA). Anorexia showed a direct correlation with the IGF-1/GH ratio (r = 0.34, p b 0.05) and was further related to
BMI and % weight loss (both p b 0.001).
Conclusion: In COPD anorexia relates to hormonal derangement and inflammatory immune activation. Anorexia contributes to development
of cachexia. The concept of appetite stimulating therapy emerges as a novel therapeutic option in cachectic COPD patients.
© 2006 Elsevier Ireland Ltd. All rights reserved.

Keywords: COPD; Anorexia; Cachexia; Catabolic/anabolic imbalance

Abbreviations: AIDS, Acquired immune deficiency syndrome; BMI, Body mass index; CHF, Chronic heart failure; cCOPD, Cachectic COPD; CLIA,
Chemiluminescence Immunoassay; COPD, Chronic obstructive pulmonary disease; DHEA, Dehydroepiandrosterone; ELISA, Enzyme-linked immunosorbent
assay; FEV1, Forced expiratory volume in 1 s; FVC, Forced ventilatory capacity; GH, Growth hormone; HOMA, Homeostatic model assessment; IGF-1, Insulin-
like growth factor-1; IL-6, Interleukin-6; Log, Logarithm; ncCOPD, Non-cachectic COPD; SEM, Standard error of mean; TNF-α, Tumor necrosis factor-α; IQR,
Interquartile range.
⁎ Corresponding author. Div of Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow Hospital, Augustenburger
Platz 1, 13353 Berlin, Germany. Tel.: +49 30 450 553 507; fax: +49 450 553951.
E-mail address: wolfram.doehner@charite.de (W. Doehner).

0167-5273/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.ijcard.2006.07.088
84 F. Koehler et al. / International Journal of Cardiology 119 (2007) 83–89
1. Introduction
Chronic obstructive pulmonary disease (COPD) is an
inflammatory disease. In the chronic course of the disease,
the pathogenesis and clinical manifestations of COPD are
not restricted to pulmonary structural and functional im-
pairment but rather have multi-systemic implications includ-
ing metabolic, hormonal and organ dysfunction such as in
skeletal muscle, heart, brain and skeleton [1]. Weight loss
due to tissue wasting is frequent in COPD and may ul-
timately lead to cachexia as a serious co-morbidity in ad-
vanced disease state. Cachexia in COPD – as in other
chronic diseases – is associated with a greater susceptibility
to exacerbation of clinical symptoms, with severely im-
paired functional capacity [2], poor health status and quality
of life [3,4]. The loss of skeletal muscle tissue and, in
particular, of respiratory muscle is associated with a loss of
power and endurance leading to a further mechanical
impairment of lung function with consecutive hypoxia and
hypercapnia [5]. This may contribute to progression of the
disease. Accordingly, increasing evidence suggests that
weight loss and cachexia are independent prognostic factors
in COPD [6,7].
Weight loss in COPD is a consequence of increased
energy expenditure due to mechanic and metabolic ineffi-
ciency that is not balanced by adequately increased energy
supply. Inflammatory activation and hormonal derangements
may further add to a hypermetabolic state and an overall
catabolic/anabolic imbalance leading to depletion of endog-
enous energy storages and eventually to structural tissue
degradation.
The regulation of energy expenditure in association to
inflammatory activation and hormonal derangement in
COPD patients has widely been studied [8–12]. Anorexia
may importantly contribute to weight loss in COPD. The
therapeutic concept, however, of nutritional supplementa-
tion failed to show significant effects on anthropometric
measures and functional capacity in these patients [13] and
mechanisms of non-response to nutritional therapy have
been discussed [14]. In this context, the significance of
alteration in appetite as a central regulator of food intake has
not been studied in detail.
In the current study we prospectively assessed in a cohort
of COPD patients with and without weight loss the extent of
anorexia in relationship to alteration in body weight. The
specific association to hormonal and inflammatory para-
meters in order to identify potential factors that may in-
fluence appetite in COPD is taken into account.
2. Methods
2.1. Patient population
We recruited 103 consecutive patients (age 59.8 ±
1.3 years, 36 female [35%]) diagnosed with COPD by his-
tory, physical examination and pulmonary function test, ac-
cording to the guidelines of the American Thoracic Society
[15]. All patients showed a FEV1 reversibility of less than
15% in response to inhaled bronchodilators. At time of
investigation, all patients were clinically stable without signs
of acute exacerbation. No patient had required hospital ad-
mission or treatment change during the preceding 3 months.
Treatment was individually and included long acting β2
agonists (88%), ipratropium (20%), oxitropium bromide
(30%), tiotropium bromide (11%), theophylline (69%) and/
or inhaled steroids (32%) in varying combinations. Specific
exclusion criteria were current or past diagnosis of allergic
asthma and a respiratory tract infection in the previous
3 months. Patients with cancer, thyroid disease, severe liver
disease and chronic heart failure were also excluded. Healthy
subjects of similar age (n = 15) with no medical history
served as control group.
Body mass index (weight/height2) and weight loss were
assessed. Patients who reported to have had intentional
weight loss were excluded from the study. Patients where
divided into cachectic and non-cachectic subgroups. Ca-
chexia was diagnosed when non-intentional, non-oedema-
tous weight loss of ≥ 7.5% of the previous normal weight
over a period of N 6 months was documented [16]. 34
patients were diagnosed with cachexia (age 58 ± 2, 11 female
[32%]). The non-cachectic group consisted of 69 patients
(age 61 ± 2, 25 female [36%], p N 0.2 vs cachectic patients).
Appetite (the subjective desire to eat) was assessed using a
visual analogue scale ranging from 0–10 (0 no appetite at all,
10 always very good appetite) based on the current eating
behaviour during 14 days prior to the study. The study was
approved by the Local Ethics Committee of the University
Hospital Charite, Humboldt University, Berlin. All patients
gave informed consent.
2.2. Pulmonary function test
FVC and FEV1 were measured with standard spirometric
techniques (Masterlab, Jaeger, Wurzburg, Germany). All
values obtained were related to age and gender and expressed
as percentage of their predicted value.
2.3. Biochemical analyses
In patients with and without cachexia, insulin-like growth
factor-1 (IGF-1), insulin and human growth hormone (GH)
were measured by radioimmunossay (Biochem Immunsys-
tems, Freiburg, Germany, test kit sensitivity: 12 ng/ml for IGF-
1, 1.0 μU/ml for insulin, 10 ng/ml for GH). The inflammatory
parameters, tumor necrosis factor alpha (TNFα, sensitivity
0.1 pg/ml), Interleukin-6 (IL-6, sensitivity 5 pg/ml) and were
analysed by ELISA technique using commercially available
kits (R and D Systems Inc., Minneapolis MN, USA). Cortisol,
testosterone and DHEA (Dihydroepiandrosterone) were
analysed by chemilumineszenz immunoassay (CLIA) (sensi-
tivity: DHEA 0.054 μmol/l, cortisol 5,5 nmol/l, testosterone
0.35 nmol/l). Homeostasis model assessment (HOMA)
 F. Koehler et al. / International Journal of Cardiology 119 (2007) 83–89 85

represents a marker of insulin sensitivity and is defined as

insulin × glucose/22.5 [17]. The ratio of IGF-1/GH was
calculated as an estimate of GH resistance with a lower IGF-
1/GH ratio indicating presence of FH resistance. Further ratios
between catabolic and anabolic hormones and cytokines were
calculated to characterise metabolic imbalance.

2.4. Blood sampling

Blood samples from an anticubital vein were collected

under standardised conditions in the morning, between 9 and
10 am, after a fasting period of ≥ 12 h and after resting in a
supine position for at least 15 min. Samples were immedi-
ately processed using a cooled centrifuge and aliquots were
stored at − 70 °C until analysis.

2.5. Statistical analysis

Results are given as mean ± SEM. To analyse relationships

between variables, Student's t-test and simple regression
analyses were performed (StatView 4.5, Abacus Concepts
Inc., Berkley CA, USA). Parameters that are not normally
distributed were log-transformed to allow a parametric sta-
tistical approach. Median and inter-quartile range (IQR] are
reported for these variables. A p-value of b0.05 was con-
Fig. 1. A: Appetite score (visual analogue scale) in COPD patients with and
sidered to be significant. If blood results were below the limit
without cachexia in comparison to healthy control subjects. B: Weight loss
of detectability of a test, the lower limit of detection was in COPD patients with and without cachexia.
recorded.

3. Results
3.1. Patient characteristics
The main clinical characteristics of the study population
are presented in Table 1. COPD Patients and control subjects
were similar for age and global parameters of body com-
position but patients had impaired respiratory function
parameters. Comparing patient subgroups of cachectic and
non-cachectic patients, COPD patients with cachexia showed
further decreased respiratory (FEV1, FVC, and FEV1/FVC; all
p b 0.05). Age, height and drug therapy were similar between
subgroups (p N 0.2).
3.2. Analysis of anorexia
The analysis of the extent of anorexia using the visual
appetite score revealed that COPD patients in comparison to
healthy controls had a 36% lower appetite (p = 0.001). Ca-
chectic COPD patients showed a further significant reduc-
tion of appetite compared to non-cachectic patients (− 44%,
p b 0.001; Fig. 1A). Observed weight loss in the patient

Table 1
Clinical status and lung function test of cachectic and non-cachectic COPD patients in comparison to healthy controls
Healthy controls All COPD p, controls vs all ncCOPD p, ncCOPD vs cCOPD p, controls vs p, cCOPD
n = 15 n = 103 COPD n = 69 controls n = 34 cCOPD vs ncCOPD
Age, years 54.5 ± 1.4 59.8 ± 1.3 0.1 60.7 ± 1.6 0.08 58.0 ± 2.1 0.4 0.3
Weight, kg 71.4 ± 2.8 66.9 ± 1.7 0.3 72.8 ± 2.1 0.8 55.0 ± 1.7 b0.001 b0.001
Height, cm 169 ± 3.0 169 ± 1.0 0.9 169 ± 1.1 0.9 170 ± 1.7 0.7 0.5
Body mass index, 25.2 ± 1.1 23.4 ± 0.6 0.3 25.6 ± 0.7 0.8 19.0 ± 0.5 b0.001 b0.001
kg/m2
Weight loss, % 0.0 ± 0.0 5.2 ± 0.8 b0.02 0.3 ± 0.2 0.8 15.4 ± 1.2 b0.001 b0.001
Appetite 8.5 ± 0.1 5.4 ± 0.2 0.001 6.3 ± 0.2 b0.001 3.5 ± 0.3 b0.001 b0.001
FEV1, % 106.0 ± 3.2 38.3 ± 1.7 b0.001 42.0 ± 2.2 b0.001 30.7 ± 2.3 b0.001 b0.002
FVC, % 102.9 ± 2.5 56.1 ± 1.9 b0.001 58.7 ± 2.5 b0.001 50.5 ± 2.8 b0.001 b0.02
FEV1 / FVC, % 102.9 ± 1.7 60.7 ± 1.6 b0.001 65.0 ± 2.0 b0.001 52.0 ± 2.1 b0.001 b0.001
cCOPD indicates cachectic and ncCOPD non-cachectic COPD patients.
Data are mean ± SEM.
86 F. Koehler et al. / International Journal of Cardiology 119 (2007) 83–89

Table 2
Hormonal and inflammatory parameters of cachectic and non-cachectic COPD Patients
Healthy controls All COPD patients p, controls ncCOPD p, ncCOPD cCOPD p, controls p, cCOPD
N = 15 vs COPD vs controls vs cCOPD vs ncCOPD
GH, μg/ml 383 ± 213 1154 ± 174 n=80 b0.001 912 ± 158 n=54 b0.005 1658 ± 412 n=26 b0.001 0.16
IGF-1, ng/ml 132 ± 11 130 ± 7 n=75 0.9 133 ± 9 n=53 0.9 118 ± 11 n=22 0.5 0.3
Glucose (mg/dl) 94 ± 5.0 122 ± 3.9 b0.01 125 ± 4.8 b0.1 115 ± 5.9 0.058 0.2
Insulin, μIU/ml 24.8 ± 6.6 36.1 ± 4.4 n=80 0.3 40.3 ± 5.6 n=55 0.1 26.9 ± 6.7 n=25 0.8 b0.02
HOMA 6.1 ± 1.6 10.4 ± 1.3 n=80 0.18 12.2 ± 1.7 n=55 0.06 6.4 ± 1.9 n=25 0.9 b0.05
Cortisol, nmol/l 216.8 ± 27.4 399.1 ± 25.3 n=95 b0.01 391.0 ± 32.8 n=63 =0.01 415.1 ± 39.1 n=32 b0.01 0.7
Testosterone, nmol/l 5.13 ± 1.41 8.55 ± 1.0 n=80 0.2 8.0 ± 1.2 n=53 0.3 9.72 ± 1.8 n=27 0.1 0.4
DHEA, μmol/l n.a. 11.08 ± 2.83 n=44 12.41 ± 4.32 n=26 9.17 ± 3.05 n=18 0.6
TNF-α, pg/ml n.a. 4.8 ± 0.7 n=76 3.9 ± 0.6 n=50 6.5 ± 1.5 n=26 0.06
IL-6, pg/ml 2.0 ± 0.0 12.24 ± 2.4 n=76 b0.001 8.26 ± 1.51 n=49 b0.001 19.5 ± 6.0 n=27 b0.001 b0.05
IL-10, pg/ml 5.0 ± 0.0 4.35 ± 0.42 n=66 b0.05 4.45 ± 0.40 n=44 0.2 4.15 ± 1.0 n=22 b0.01 0.1
cCOPD indicates cachectic and ncCOPD non-cachectic COPD patients.
Data are shown as mean ± SEM.

population was significantly more severe than in control
subjects (p b 0.02), however, this was driven by a significant
weight loss (− 10.3 ± 1.0 kg) in the cachectic population only
(− 15.4%; vs controls: p b 0.001) while no significant weight
reduction (0.2 ± 0.1 kg) was seen in non-cachectic patients
(− 0.3%; vs controls: p N 0.5; Fig. 1B). This accords with a
decreased BMI in cachectic vs non-cachectic COPD patients
(19.0 ± 0.5 vs 25.6 ± 0.7, p b 0.001) whereas BMI was not
different between ncCOPD and controls (p N 0.5).
(cortisol, DHEA, testosterone) were not different between
cachectic and non-cachectic COPD patients.
Cachectic COPD patients presented with increased ratios
of IL-6/IGF-1 (p b 0.05), IL-6/insulin (p b 0.01), IL-6/IL-10
(p b 0.05), and TNF/insulin (p b 0.01) compared to non-
cachectic COPD patients.
3.4. Relation between appetite and catabolic/anabolic
imbalance

3.3. Hormonal imbalance and inflammatory parameters
Data on hormonal balance in controls vs patients and in
cachectic/non-cachectic patient subgroups are shown in
Table 2. Hormonal derangement was observed in COPD
patients compared to controls but metabolic balance was
further impaired in cachectic vs non-cachectic COPD. Indi-
cation of acquired GH resistance was seen in COPD patients
compared to controls and was most pronounced in cachectic
COPD. GH levels were highest in cachectic COPD (p b 0.05
for ANOVA, Table 2) with no significant differences in IGF-
1 levels. Accordingly, the IGF-1/GH ratio was lowest in
cachectic COPD (p b 0.002 for ANOVA, Table 3).
Non-cachectic COPD Patients presented elevated levels
of fasting insulin. HOMA insulin sensitivity was similar in
cachectic COPD compared to controls but impaired in non-
cachectic COPD (Table 2). Plasma levels of steroid hormones
In the total patient population of COPD patients
significant correlations between appetite and parameters of
body composition were revealed (appetite vs BMI [r = 0.48,
p b 0.0001] and vs weight loss [r = − 0.58, p b 0.0001,
n = 103]; (Fig. 2). Furthermore, significant correlations
between appetite and measures of catabolic anabolic
imbalance were observed as indicated by the IGF-1/GH
ratio (r = 0.34, p b 0.005, n = 75), the IL-6/insulin ratio (r =
− 0.46, p b 0.0001, n = 73), TNF/insulin ratio (r = − 0.33,
p = 0.01, n = 54) and IL-6/IGF-1 ratio (r = −0.29, p b 0.02,
n = 69; Fig. 3).
4. Discussion
This study demonstrates a significant prevalence of
cachexia occurring in COPD and shows that anorexia is
frequently present in patients with COPD and cachexia. The

Table 3
Ratios of catabolic and anabolic hormones
Healthy controls n = 15 All COPD patients p, controls ncCOPD p, ncCOPD cCOPD p, controls p, cCOPD
vs all COPD vs controls vs cCOPD vs ncCOPD
IGF-1/GH 1560 ± 342 543 ± 74 n=73 b0.001 570 ± 85 n=53 b0.01 474 ± 154 n=20 b0.001 0.09
IL-6/IGF-1 0.017 ± 0.001 0.116 ± 0.027 n=69 b0.001 0.074 ± 0.014 n=47 0.3 0.206 ± 0.077 n=22 b0.01 0.01
IL-6/insulin 0.17 ± 0.03 1.26 ± 0.36 n=73 0.17 0.60 ± 0.18 n=55 0.6 2.60 ± 0.98 n=25 b0.01 b0.01
IL-6/IL-10 0.4 ± 0.0 5.91 ± 1.69 n=62 b0.001 3.62 ± 1.25 n=41 b0.001 10.4 ± 4.27n=21 b0.001 b0.02
TNF/IGF-1 n.a. 0.048 ± 0.007 n=50 0.037 ± 0.006 n=34 0.074 ± 0.015 n=16 b0.01
TNF/Insulin n.a. 0.29 ± 0.038 n=54 0.24 ± 0.47 n=36 0.39 ± 0.06 n=18 b0.01
cCOPD indicates cachectic and ncCOPD non-cachectic COPD patients.
Data are shown as mean ± SEM.
 F. Koehler et al. / International Journal of Cardiology 119 (2007) 83–89 87

strength and endurance, decreased diaphragmatic size [22]

with increased work of breathing, and predisposition to death
due to heart failure play an important role triggering weight
loss in COPD. The lean tissue mass in COPD patients is
influenced by a number of interacting factors such as aging,
medication, tissue hypoxia and inactivity [23]. Therefore the
development of cachexia in COPD is a multifactorial process
including tissue hypoxia, systemic inflammation, physical
inactivity, neurohormonal activation and hypermetabolism
[24,25].

Fig. 2. The relationship of the appetite score (visual analogue scale) to

clinical/humoral parameters in COPD: A: Appetite vs % weight loss
(n = 103), B: Appetite vs BMI (n = 103), C: Appetite vs IGF-1/GH ratio
(n = 75).

degree of appetite in COPD patients is related to body mass

index, inflammation and catabolic/anabolic imbalance.
The pathogenesis and clinical manifestations of COPD
are not restricted to pulmonary inflammation and airway
remodelling [18]. Involuntary weight loss occurs frequently
in a significant number of patients, particularly in those
Fig. 3. The relationship of the appetite score (visual analogue scale) to ratios
suffering from emphysema [19,20], and presents an of catabolic and anabolic parameters in COPD. A: Appetite vs IL-6/insulin
independent risk factor of impaired prognosis [21]. Several ratio (n = 73), B: Appetite vs TNF/insulin ratio (n = 54), C: Appetite vs IL-6/
studies have shown that decreased respiratory muscle IGF-1 ratio (n = 69).
88 F. Koehler et al. / International Journal of Cardiology 119 (2007) 83–89
Further hypotheses for the development of cachexia in-
clude inadequate dietary intake, increased resting energy
expenditure and diet induced thermogenesis [2,3]. Anorexia
with loss of appetite might be one reason for an inadequate
food intake [2]. The results of the present study demonstrate
that appetite is low in general in COPD patients and espe-
cially in those who are cachectic. The appetite was quantified
by a visual analogue scale that assesses the subjective desire
to eat. This test is widely used for assessment of appetite and
has been evaluated as a reliable method with good re-
producibility and feasibility [26,27]. In another study, we
have applied the same test to healthy subjects (mean appetite
score 8) and chronic heart failure patients with and without
cachexia (mean appetite score 6.5 and 7.5, respectively
(Anker et al, unpublished observation). The results of the
present study show that appetite is reduced by 45% in ca-
chectic vs non-cachectic COPD patients (p b 0.001). Strong
correlations of the appetite score with body mass index,
weight loss, and measurements of GH resistance, catabolic/
anabolic imbalance and immune activation were observed.
These data suggest that impaired appetite might be involved
in the complex regulation of body composition in chronic
inflammatory disease and the development of cachexia.
The observed relationships are in line with the pathophys-
iologic understanding of cachexia in COPD, resulting not
only from increased energy expenditure but also from reduced
dietary intake due to loss of appetite. These data indicate that
treatment of anorexia itself may be beneficial in COPD
cachexia. The use of appetite stimulants (like megastrol
acetate [28]) has been shown to be beneficial in cancer
cachexia and AIDS cachexia. This could be tested in COPD as
well.
Furthermore, our findings support the hypothesis that the
protein catabolic state in pulmonary cachexia is related to an
increased host inflammatory response and a hormonal
derangement. This phenomenon may be due to a hypoxia
related alteration in intermediary metabolism shifting the
body composition towards wasting of fat free mass.
Finally, increased levels of growth hormone were de-
tected in cachectic COPD patients indicating a growth hor-
mone resistance. This is suggestive of presence of acquired
GH resistance, which is also seen in CHF patients [29].
Anabolic therapy with higher doses of GH should therefore
be tested in cachectic COPD patients [30]. Alternatively,
novel therapeutic options such as the growth hormone
releasing peptide ghrelin might provide additional benefit to
those patients with severely impaired body composition.
Preliminary data from an open label pilot study show pro-
mising results as muscle wasting, functional capacity, and
sympathetic status have all been improved following a
3 week iv administration of ghrelin in seven cachectic COPD
patients [31]. Further studies are required to verify whether
this concept may indeed translate into meaningful benefit for
cachectic COPD patients.
In summary, cachexia in COPD is a multifactorial disease
process characterised by loss of appetite, growth hormone
resistance and proinflammatory immune activation. Reduced
appetite is part of the catabolic/anabolic imbalance in the
process of wasting in COPD. More pathophysiological
studies are needed to confirm the role of anorexia in the
pathogenesis of pulmonary cachexia and to develop therapies
that impact on this systemic manifestation of COPD.
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