Lung (2016) 194:249257
DOI 10.1007/s00408-015-9838-z
COPD AND ASTHMA
Muscular Dysfunction in COPD: Systemic Effect
or Deconditioning?
Eulogio Pleguezuelos1,2,3 Cristina Esquinas4 Eva Moreno5 Lluis Guirao1
Javier Ortiz6 Joan Garcia-Alsina6 Alex Mer2,3 Marc Miravitlles4
Received: 29 October 2015 / Accepted: 26 December 2015 / Published online: 7 January 2016
Springer Science+Business Media New York 2016
Abstract
Background Muscular dysfunction has been described as
one of the systemic manifestations of chronic obstructive
pulmonary disease (COPD).
Objective The aim of this study was to evaluate muscular
strength of the different anatomical compartments in
patients with severe COPD compared with healthy
controls.
Method We performed a cross-sectional study in patients
with severe COPD. We evaluated the muscular strength of
the respiratory muscles, flexors and extensors of the cer-
vical spine and knee, as well as handgrip force. The 6-min
walking test (6MWT) and serum inflammatory markers
were also analysed.
Electronic supplementary material The online version of this
article (doi:10.1007/s00408-015-9838-z) contains supplementary
material, which is available to authorized users.
& Eulogio Pleguezuelos
epleguezuelos@csdm.cat
1
Physical Medicine and Rehabilitation Department, Hospital
Mataro, C/Cirera s/n 08302, Mataro, Barcelona, Spain
2
Department of Experimental Science and Healthcare, Faculty
of Health Sciences, Universitat Pompeu Fabra, Barcelona,
Spain
3
Faculty of Health Sciences Blanquerna, Universitat Ramon
LLull, Barcelona, Spain
4
Pneumology Department, Hospital Universitari Vall
dHebron, Ciber de Enfermedades Respiratorias (CIBERES),
Barcelona, Spain
5
Physical Medicine and Rehabilitation Department, Hospitalet
General Hospital, LHospitalet de Llobregat, Barcelona, Spain
6
Biomechanics Laboratory, INVALCOR, Barcelona, Spain
Results Twenty-eight male patients with COPD (mean
age 67.8 years, mean FEV1 (%) 39 %) and 24 male heal-
thy controls (mean age 70.2 years) were studied. The
strength of the flexors and extensors of the knee was sig-
nificantly reduced in patients with COPD (p \ 0.001 and
p = 0.003). No differences were observed in the flexors
and extensors of the cervical spine and handgrip force
between groups. No correlation was observed between the
muscular strength in the different anatomic compartments
and the concentrations of blood inflammatory biomarkers
or the metres walked in the 6MWT in COPD patients.
However, a significant negative linear correlation was
observed between the 6MWT and IL-6 and IL-8 levels
(rho = -0.67, p = 0.001; rho = -0.57, p = 0.008). In
addition, we found a negative correlation between the
6MWT and inspiratory capacity (rho = -0.755,
p = 0.031).
Conclusions Our results suggest that muscular dysfunc-
tion in patients with COPD differs in different muscular
compartments. The main factor for a reduced exercise
capacity was a reduction in inspiratory capacity.
Keywords COPD
Muscle function
Deconditioning

Inflammatory markers
Introduction
Chronic obstructive pulmonary disease (COPD) is a res-
piratory disease with significant extrapulmonary effects
which may contribute to the severity of the disease [1].
Among the extrapulmonary manifestations, weakness of
the skeletal musculature and emaciation are frequent and
are associated with intolerance to exercise and deteriora-
tion in the state of health, independently of the level of
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obstruction of the respiratory tract [2]. Muscular dysfunc-
tion is one of the most commonly studied systemic mani-
festations of COPD and is characterized by a significant
reduction in muscle strength and resistance which may be
secondary to multiple mechanisms such as nutritional
alterations, systemic inflammation, alterations in muscle
repair, oxidative stress, drugs, ageing and deconditioning,
among others [2]. This muscular dysfunction may appear in
the first phases of the disease, significantly aggravating the
symptoms and having a direct effect on the quality of life
[2, 3].
However, functional deterioration of the muscles of the
upper and lower limbs may not be homogeneous [4].
Deterioration in the muscles of the lower limbs is largely
responsible for limitations in activities such as walking and
climbing stairs, and furthermore, a reduction in quadriceps
strength is a potent predictor of mortality in severe COPD
[5]. On the other hand, it is known that the basic activities
of daily life, which are mainly performed with the upper
limbs, are also poorly tolerated by patients with COPD [6].
Nonetheless, there are little data on the simultaneous
muscle involvement in different compartments in patients
with COPD.
The main objectives of the present study were to com-
pare the muscular strength of three different anatomical
regions of healthy subjects and patients with severe chronic
obstructive pulmonary disease (COPD), correlate the level
of systemic inflammation and muscular strength in these
three anatomical regions in COPD patients and lastly
determine what variables have a direct effect on limiting
exercise in these patients.
Method
Study Design
We performed a cross-sectional study in patients with severe
COPD. The inclusion criteria were age older than 40 years
and smokers or former smokers of at least 10 pack-years with
a post-bronchodilator spirometry showing a forced expira-
tory volume in 1 s/forced vital capacity (FEV1/FVC) \0.7
and FEV1 (% predicted) \50 %. The exclusion criteria
were: clinical instability defined as an acute exacerbation or a
change in regular medication in 3 months prior to recruit-
ment, other significant respiratory disease, severe cardio-
vascular, neurological and/or metabolic pathology that could
interfere with the results, treatment with systemic corticos-
teroids, total hip, knee or ankle arthroplasty, surgery at the
cervical spine, or of the anterior neck region, lower or upper
limb fractures, rhizarthrosis, severe alcoholism ([80 g/day)
and severe malnutrition (BMI \ 19 kg/m2).
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Lung (2016) 194:249257
Demographic, skeletal and clinical variables (blood
analysis and lung function test) were collected. The
skeletal force in the patients included was compared with a
control group of individuals older than 40 years who had
no respiratory symptoms, no previous diagnosis of any
chronic respiratory condition and who took no respiratory
medications.
Patients were informed about the nature of the study and
provided signed informed consent to participate. The Eth-
ics Committee of the Clinic Hospital of Barcelona
approved the study. The protocol was conducted in
accordance with the principles of the Declaration of Hel-
sinki, Good Clinical Practice and the applicable and local
regulatory requirements.
Measurements
Measurement of skeletal force was determined by 3 vari-
ables: (1) the maximum moment of force of flexion and
extension of the knee at low speed, (2) the isometric
strength of the flexor and extensor muscles of the cervical
spine, and (3) the maximum handgrip strength.
(1) The maximum moment of force of flexion and
extension of the knee at low speed was measured by
an isokinetic test in a concentricconcentric regime
at low speed (60/s) using the Biodex Advantage
system (Software V.4X). This test has been widely
validated and used in force evaluation, showing high
inter and intratest correlations in different patholo-
gies and healthy subjects [7, 8]. The study protocol
was as follows: (1) training, consisting of a 80 range
of mobility evaluation, 5 repetitions of 60/s, 20 s
rest and five repetitions; (2) the test which consisted
of two series of five repetitions of 60/s concentric
concentric regime, alternating with two series of five
repetitions, as described previously [9]. The variable
analysed in the study was the maximum moment of
force of flexion and extension of the knee at low
speed, recording the highest value of the different
repetitions.
(2) The isometric strength of the flexor and extensor
muscles of the cervical spine was determined by
three measurements for each of the two directions
(flexion and extension). The patient was placed in
the sitting position held by a pelvic belt and two belts
crossed at the chest. This support is essential to
minimize offsets from the body to the test. The
patient underwent prior training to become familiar
with the test, doing three repetitions of 3 s. There-
after, the evaluation was begun, performing 5
isometric contractions of the flexor and extensor
muscles of 3 s of duration with rest intervals of 10 s
Lung (2016) 194:249257 251

between each. The peak isometric strength (PIS) was normal distribution, interleukin values were analysed after
calculated in Newtons (N) [10]. logarithmic transformation. Trends were analysed by the
(3) Maximum handgrip strength was measured using a Spearman rank test or the Kendall Tau-c test for categorical
hydraulic hand dynamometer (Jamar dynamometer, variables. A p value \0.05 was considered significant. The
Saehan Corporation; Masan, Japan) with an SPSS version 19 software (SPSS Inc., Chicago, IL, USA)
adjustable handle and an analogous reproduction of was used for all analyses.
the power delivered in kilogramme-force. Partici-
pants sat on a chair while holding the dynamometer
in their dominant hand with the elbow flexed at 90 Results
and the forearm in neutral position. The analogue
screen was turned away from the participants so they Study Population
could not read the amount of force generated. They
were then instructed to grip the instrument as hard as A total of 28 patients with severe COPD were included in
possible on three consecutive attempts after which this study. All were males with a mean age of 67.8 (SD 9.4)
the highest score was recorded [11]. years; the mean BMI was 26.3 (SD 3.8) kg/m2, and the
mean FEV1 % was 39 % (SD 9.7 %). A total of 13 (43 %)
The 6-min walking test (6MWT) was used as an addi-
were treated with inhaled corticosteroids. The skeletal
tional variable to assess exercise capacity. This test has
force of these patients was compared with that of a control
been standardized following international recommenda-
group of 24 healthy males with a mean age of 69.2 (SD 7.2)
tions [12]. Oxygen saturation and heart rate were recorded
years (Table 1). Table 2 shows the lung function, exercise
throughout the test using a pulsioximeter (Digit Finger
capacity and inflammatory biomarker values of the patients
Oximeter, Smiths Medical PM, USA).
with COPD.
Cytokine Measurements
Skeletal Force in COPD Patients and Healthy
Controls
Blood samples were collected using standardized proce-
dures and stored frozen at -80 C until processing. Inter-
We observed a significant reduction in extension force of
leukin (IL)-1beta (b), IL-6, IL-8 and tumour necrosis
both knees in patients with COPD compared to the control
factor-alfa (TNF-a) were determined in duplicate with a
group (88.8 Nm (SD 29.3) vs. 116.1 Nm (SD 28.7)
high sensitivity enzyme-linked immunosorbent assay, and
p = 0.003; 86 Nm (SD 30) vs. 110.9 (SD 17.2) p = 0.003,
C-reactive protein (CRP) was assessed by latex-enhanced
respectively. Similarly, we found a significant decrease in
immunonephelometry as described previously [13].
the flexion force of both knees in COPD patients compared
Increased inflammation was defined as levels above the
to healthy subjects (43.7 Nm (SD 24.5) vs. 83.6 (SD 30.2
upper quartile of the distribution of concentrations of each
p \ 0.001; 39.8 Nm (SD 17) vs. 63.4 (SD 11.5) p \ 0.001,
of the biomarkers. We divided our population of COPD
respectively (Fig. 1). The flexion force of the cervical spine
patients into two subgroups: an inflamed group consisting
of COPD patients was 123.3 (SD 27.3), while that of the
of patients with 2 or more elevated inflammatory markers
control group was 130.3 (SD 23.4), with these differences
and a non-inflamed group with the remaining individuals
not being statistically significant (p = 0.255). The exten-
[14].
sion force of the cervical spine did not significantly differ
Statistical Analysis
Table 1 Baseline characteristics of patients with COPD and healthy
control group
Data are presented as mean (Standard Deviation, SD) or
median (interquartile range, IQR); categorical data are COPD (N = 28) Controls (N = 24) p
shown as percentage of positive patients. Age (years) 67.8 (9.4) 69.2 (7.2) 0.43
Unpaired non-parametric Mann-Whitney U tests were Gender, males (%) 28 (100) 24 (100)
used to compare the maximum moment of force of flexion BMI (kg/m2) 26.3 (3.8) 25.8 (4.2) 0.50
and extension of the knee at low speed according to the Retirement (%) 27 (96.4) 23 (95.8) 0.21
study group (COPD or healthy patients). A secondary Active smoker (%) 3 (11) 3 (12) 0.32
analysis was performed in COPD patients to study rela- Charlson index 1.3 (0.5) 1.2 (0.6) 0.11
tionships between clinical variables. Frequencies were
compared by the Chi squared test for categorical variables Data are presented as means (standard deviation) or valid percentage
(Fishers exact test with observed frequencies). Due to non- BMI body mass index

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Table 2 Functional and clinics characteristics in COPD patients between IL-6 and FVC(%) (rho = -0.444, p = 0.049),
Lung function COPD patients N = 28
FEV1(%) (rho = -0.484, p = 0.042), vital capacity %
(VC) (rho = -0.806, p = 0.039) and inspiratory capacity
FVC (ml) 3050 (934) (%) (IC) (rho = -0.781, p = 0.038). In addition, a mod-
FVC (%) 70.1 (18.1) erate negative linear relationship was found between serum
FEV1 (ml) 1260 (386) IL-6 and IL-8 concentrations and distance (m) in the
FEV1 (%) 39 (9.6) 6MWT (rho = -0.670, p = 0.001 and rho = -0.570,
FEV1/FVC (%) 48.0 (16.2) p = 0.008), respectively (Table 3).
IC (ml) 2413 (517) Two or more biomarkers were elevated in 8 patients
IC (%) 70.6 (16.6) (28 %). These patients presented a significantly lower IC
RV (ml) 3524 (1311) (mL and percentage) and a lower 6MWT distance com-
RV (%) 141.6 (31.4) pared with the remaining patients with COPD (Table 4). In
TLC (ml) 6924 (1189) contrast, no differences were observed in the clinical,
TLC (%) 87 (10) demographic characteristics or skeletal force variables.
RV/TLC (%) 59.3 (52.7)
DLCO/VA (%) 55.3 (38.7)
Exercise capacity and clinical parameters Discussion
6MWT (m) 383 (145)
Initial O2 saturations (6MWT) (%) 93.5 (2.7) The results of the present study suggest that muscular
Final O2 saturations (6MWT) (%) 89.7 (3.8) dysfunction in COPD varies depending on the anatomical
Number of exacerbations previous year 0 (01)a region studied. We observed a reduction in flexor and
Inflammatory markers extensor force of the knees in patients with COPD com-
IL-1b (pg/mL) 0.06 (0.0690.2)a pared to healthy volunteers. Nonetheless, these differences
IL-6 (pg/mL) 6.9 (2.57.8)a
were not found in flexor and extensor muscle force of the
IL-8 (pg/mL) 66.9 (9.8144.9)a
cervical spine or in handgrip strength. We also found no
TNF-a (pg/mL) 6.6 (4.37.3)a
relationship between muscle strength or exercise capacity
(evaluated with the 6MWT) with the levels of systemic
CRP (mg/dL) 33.3 (0.53.3)a
inflammatory markers. Likewise, neither did we find any
Data are expressed as mean (SD) correlation between exercise capacity and muscular force
FEV1 forced expiratory volume in 1 s; FVC forced vital capacity; IC in patients with severe COPD. We only found inspiratory
inspiratory capacity; RV residual volume; TLC total lung capacity;
KCO diffusion capacity of the lung for carbon monoxide; VA alveolar
capacity to be significantly related to exercise capacity in
volume; 6MWT 6-min walking test; O2 oxygen; IL interleukin; CRP these patients.
C-reactive protein; TNF tumour necrosis factor alpha One strength of our study is that three different
a
Median (interquartle range) anatomical regions were evaluated: lower limbs, upper
limbs and cervical spine. We found a very significant
reduction in flexor and extensor knee force (ischiocrural
between the two groups, being 193 (SD 54.1) in patients
and quadriceps) in patients with COPD compared to
with COPD and 213.4 (SD 35.1) in the control group
healthy volunteers. These results are similar to those
(p = 0.124) (Fig. 2). The average strength of the dominant
recently published by Evans et al. who described a
handgrip in the COPD patients was of 26.7 kg (SD 6.2)
reduction in quadriceps strength in patients with COPD
compared to 24 kg (SD 6.2) in the healthy controls
compared to healthy subjects [15]. Our study extends these
(p = 0.45) (Fig. 3).
results by also demonstrating a reduction in the force of the
flexor muscles. Interestingly, the reduction observed in
Relationship Between Inflammatory Biomarkers flexor musculature in our study was of 50 % in COPD
and Skeletal Force, Lung Function Variables patients compared to the controls, being much higher than
and Exercise Capacity in COPD Patients the 25 % reduction, which we observed in quadriceps
strength. To our knowledge, no other study has reported
No linear relationship was observed between the skeletal this predominant involvement of the ischiocrural muscu-
force and systemic inflammatory biomarkers in COPD lature compared to the quadriceps. This involvement may
patients (IL-1b, IL-6, IL-8, PCR and TNF-a) (Supplement be explained by the greater time which COPD patients
1). spend seated compared to healthy individuals [16, 17].
On comparing systemic inflammation with lung function While seated, the flexor muscles are in a shortened position
variables, we observed a negative linear relationship due to the knee being at 90, thereby reducing the number

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Fig. 1 Isokinetic knee testing (maximum force moment. Nm)

Fig. 2 The isometric neck (peak isometric strength. N)

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cervical spine of the patients with COPD did not differ

Fig. 3 Maximal Handgrip Strength Test (Maximum force moment.
Kg)
of sarcomeres in series and their muscular area to adapt to
this new longitude; furthermore, immobility increases the
production of connective tissue. From a neuromuscular
point of view, a muscle maintained in a passive shortened
position has less proprioceptive input dynamic muscle
spindle fibres, which plays an important role in reflexion
and tone [1820]. Thus, prolonged seated could justify the
predominant involvement of the flexor musculature in
patients with COPD.
This involvement of muscles of the lower limbs was not
observed in the remaining anatomical regions studied; this
is consistent with the observed benefits of pulmonary
rehabilitation. Aerobic lower extremity training is of ben-
efit in several areas of importance to patients with COPD,
including exercise endurance, perception of dyspnea and
quality of life, whereas upper extremity training has not
conclusively demonstrated to have the same benefits. The
strength of the flexor and extensor musculature of the
from that observed in the control group. No previous study
has evaluated cervical muscular strength in COPD. The
cervical musculature is essential for the maintenance of
head posture while upright and balanced. Fundamental
movements are coordinated by vestibulospinal pathways,
which, on one hand, link the vestibular system with the
spinal muscles to maintain balance, and on the other hand,
the tectospinal tract which links vision with the cervical
vasculature to follow moving objects. Therefore, our
results may be explained by the continuous muscular
activity of the flexor and extensor musculature of the cer-
vical spine, which maintains the head in an upheld position
[21].
No differences were found between the two groups in
relation to handgrip force, which was even slightly greater,
albeit not significantly, in COPD patients. Our results
coincide with those obtained by Heijdra et al. who com-
pared the handgrip strength of 32 patients with COPD with
a mean FEV1 (%) of 38 % with 36 healthy volunteers and
found no differences in handgrip strength of the dominant
hand [22]. However, other authors have described a
reduction in handgrip strength in COPD patients [23, 24].
These contradictory results may be explained in that the
muscular function of the upper limbs is more related to the
daily life activities carried out by patients than to the
presence and severity of the COPD.
Considered globally, our results of the three anatomical
regions support the theory of muscular deconditioning due
to disuse as the main cause of muscular dysfunction in
COPD rather than an effect caused by systemic
inflammation.
The results obtained on relating the concentrations of
markers of systemic inflammation to muscular strength
also support this hypothesis. Systemic inflammatory
markers are usually increased in patients with COPD

Table 3 Correlations between

IL-1 (pg/mL) IL-6 (pg/mL) IL-8 (pg/mL) TNF- a (pg/mL) CRP (mg/dL)
biomarkers and lung function
and walking test variables Lung function variables
FVC (%) 0.118 (0.55) -0.444 (0.04) -0.40 (0.83) 0.037 (0.85) -0.441 (0.09)
FEV1 % 0.326 (0.09) -0.484 (0.04) -0.09 (0.66) 0.057 (0.77) -0.254 (0.36)
FVC/FEV1 % 0.325 (0.09) 0.133 (0.50) -0.05 (0.79) -0.02 (0.92) -0.041 (0.88)
VC % -0.114 (0.56) -0.806 (0.04) -0.36 (0.06) -0.107 (0.58) 0.254 (0.06)
IC % -0.148 (0.42) -0.781 (0.04) -0.33 (0.08) 0.035 (0.84) -0.234 (0.07)

6MWT variables
Distance (m) -0.151 (0.44) - 0.670 (0.001) -0.58 (0.008) -0.160 (0.42) -0.231 (0.06)
Values of r (p value). Concentrations of inflammatory biomarkers were transformed logarithmically
IL-1 interleukin-1; IL-6 interleukin-6; IL-8 interleukin-8; TNF tumour necrosis factor alpha; CRP C-re-
active protein; FEV1 forced expiratory volume in 1 s; FVC forced vital capacity; IC inspiratory capacity;
VC vital capacity; 6MWT 6-min walking test

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Table 4 Characteristics of patients according to the presence of elevated inflammatory biomarkers

Variables Patients without 2 or more elevated biomarkers Patients with 2 or more elevated biomarkers p value
N = 20 N=8

Age (years) 66.4 (9.6) 71.4 (7.5) 0.244

Active smoker; number (%) 0 (0) 2 (28.6) 0.078
Number of exacerbations last 0.4 (0.6) 0.9 (0.7) 0.141
year
Charlson index 1.3 (0.6) 1.2 (0.4) 0.820
BMI (kg/m2) 25.8 (2.6) 27.7 (5.9) 0.912
Inhaled steroids; number (%) 16 (81.9) 6 (75) 0.637
FEV1 (ml) 1240 (356.4) 1311 (421.2) 0.601
FEV1 (%) 38.3 (9.2) 41 (7.5) 0.402
FVC (ml) 3101 (824.4) 3035 (958.4) 0.812
FVC (%) 70.5 (16) 69 (18) 0.800
FEV1/FVC (%) 46.8 (11) 51 (7.5) 0.101
IC (ml) 2470 (326.5) 2280 (286.5) 0.032
IC (%) 80.3 (19.6) 61 (3.7) 0.049
6MWT (metres) 477.9 (131) 296.4 (155.3) 0.048
Isokinetic knee testing
Maximum force moment (Nm)
60 right knee extension 89.99 (30.6) 85.26 (28.92) 0.781
60 left knee extension 84.83 (30.16) 89.78 (30.70) 0.791
60 right knee flexion 45.50 (27.6) 38.31 (8.9) 0.970
60 left knee flexion 38.92 (18.23) 42.80 (13.4) 0.482
Maximum handgrip strength 26.68 (6.74) 26.76 (4.9) 0.873
test
Maximum force moment (kg)
The isometric neck
Peak isometric strength (N)
Isometric neck flexion 114.7 (28.9) 109.1 (23.3) 0.820
Isometric neck extension 190.94 (54.6) 199.21 (56.9) 0.642
Data are expressed as Mean (SD) or percentage
BMI body mass index; FEV1 forced expiratory volume in 1 s; FVC forced vital capacity; IC inspiratory capacity; 6MWT 6-min walking test; IL
interleukin; CRP C-reactive protein; TNF tumour necrosis factor alpha

compared to healthy subjects [25]. Nevertheless, we did
not observe a relationship between inflammatory marker
levels and muscular strength in any of the three anatomical
regions studied. Our results contradict the findings of
Yende et al. who observed a significant relationship
between quadriceps strength and IL-6 and TNFa levels,
although their study population was very different and
consisted in well-functioning individuals from 70 to
79 years of age with obstructive lung disease irrespective
of smoking habits [26]. Similar to our study, Gagnon et al.
recently reported that they did not find any relationship
between plasma IL-6 levels and the force of maximum
voluntary contraction of the quadriceps in patients with
moderate COPD [27]. The absence of a correlation
between systemic markers of inflammation and muscular
dysfunction in COPD is supported by the finding of an
important increase in oxidative stress in the musculature of
the lower limbs in COPD, but this increase is not positively
correlated with cytokine levels in the muscle [28].
To the contrary, we did find an association between
FEV1 % and IL-6 levels. Likewise, we observed a negative
linear correlation between exercise capacity measured by
the 6MWT and IL-6 and IL-8 levels. These results coincide
with those obtained by other authors who have described a
relationship between greater plasma concentrations of
inflammatory markers and worse pulmonary function and
exercise capacity in patients with COPD [29, 30].
In addition, we found a strong negative correlation
between inspiratory capacity and IL-6 levels suggesting a
relationship between systemic inflammation and

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pulmonary hyperinflation. In a previous study, Gatta et al.
also observed that CRP levels were significantly higher in
patients with COPD with an IC less than 80 % compared to
those with a normal IC [31]. The relationship between
hyperinflation and inflammation is an interesting hypothe-
sis which requires further investigation.
Similar to the ECLIPSE [14] study, we defined patients
presenting an elevation of two or more inflammatory
markers as having inflammation, with 28 % of our patients
fulfilling this criterion. These individuals presented a sig-
nificant reduction in inspiratory capacity and in the metres
walked in the 6MWT compared to those without inflam-
mation; however, no differences were found in muscular
strength in any of the 3 anatomical regions studied. These
results also support the absence of a relationship between
muscular strength and systemic inflammation, although
greater inflammation is associated with worse exercise
capacity, which is explained by other phenomenon.
The most important limitation related to exercise
capacity was the IC. It is known that dynamic hyperinfla-
tion is the main conditioner of the reduction of physical
capacity in COPD [32, 33]. In contrast to other previous
studies, we did not find a relationship between the results of
the 6MWT and strength in the 3 anatomical regions stud-
ied. This lack of relationship may be due to the small
number of patients studied, and that all had severe COPD
with a FEV1 (%) less than 50 %.
As limitations of the study, the small number of patients
included is one, and our results would have had greater
relevance if we had been able to collect the level of
physical activity of the patients included. We only included
men due to the epidemiological characteristics of COPD in
Spain [34], and extrapolation of the results to women
should be made with caution. Lastly, the study only
included patients with severe COPD, thereby limiting the
possibility of investigating differences according to the
level of COPD severity.
In conclusion, the results of our study demonstrate that
muscular involvement is not homogeneous in the different
anatomical regions of patients with severe COPD, with the
extensor and flexor musculature of the knee being the most
affected. This finding, together with a lack of correlation
between the systemic inflammatory markers and functional
capacity and the strength of the anatomical regions studied,
indicates that the main cause of muscular dysfunction in
severe COPD may be due to deconditioning secondary to
physical inactivity. Likewise, we observed that the main
limiting factor of functional capacity was reduced inspi-
ratory capacity in COPD patients. This result is important
because assessment of pulmonary hyperinflation should be
performed in order to follow the response of therapeutic
interventions related to tolerance to exercise in patients
with COPD. Future larger studies are needed to confirm our
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Lung (2016) 194:249257
findings and evaluate and monitor muscular strength in
COPD patients regardless of the severity of the obstruction
and to determine predisposing factors for the development
of muscular dysfunction taking into account the presence
of pulmonary hyperinflation as one of the main variables.
Compliance with Ethical standards
Conflicts of interest The authors have no conflicts of interest in
relation to this work.
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