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Physiological Responses to Arm and Leg
Exercise in Women Patients
with Chronic Fatigue Syndrome
Casimiro Javierre, MD, PhD
José Alegre, MD, PhD
José Luis Ventura, MD, PhD
Ana García-Quintana, MD, PhD
Ramon Segura, MD, PhD
Andrea Suarez, MD
Alberto Morales, MD
Agusti Comella, MD, PhD
Kenny De Meirleir, MD, PhD
ABSTRACT. Patients affected by chronic fatigue syndrome (CFS)
characteristically show easy and unexplained fatigue after minimal exertion that does
not resolve with rest and is associated with specific symp-
Casimiro Javierre, Ramon Segura, Andrea Suarez, Alberto Morales, and Agusti Comella
are affiliated with the Department of Physiological Sciences II, Medical School. IDIBELL
(Campus of Bellvitge), University of Barcelona, Spain.
José Alegre is affiliated with the Department of Internal Medicine, Hospital of Vall
d'Hebrón, Barcelona, Spain.
José Luis Ventura is affiliated with the Department of Physiological Sciences II, Medical
School. IDIBELL (Campus of Bellvitge), University of Barcelona, Spain. He is also affiliated
with the Department of Intensive Care, University Hospital of Bellvitge, L'Hospitalet
(Barcelona), Spain.
Ana García-Quintana is affiliated with Delfos Medic Center, Chronic Fatigue Syndrome
Unit, Barcelona, Spain.
Kenny De Meirleir is affiliated with the Department of Human Physiology, Faculty of
Physical Education and Physical Therapy, Vrije University, Belgium.
Address correspondence to: Casimiro Javierre, Department of Physiological Sciences II,
Medical School. IDIBELL (Campus of Bellvitge), University of Barcelona, Ctra. Feixa Llarga
s/n
08.907, L'Hospitalet de Llobregat, Barcelona, Spain (E-mail: cjavierre@ub.edu).
Journal of Chronic Fatigue Syndrome, Vol. 14(1) 2007
Available online at http://jcfs.haworthpress.com
© 2007 by The Haworth Press, Inc. All rights reserved.
doi: 10.1300/J092v14nOl_05 43
44
JOURNAL OF CHRONIC FATIGUE SYNDROME
toms lasting for more than six months. Cardiopulmonary exercise testing is a
valid procedure for determining functional capacity in patients with CFS. We
compare cardioventilatory adaptation to exercise between a group of eighty-
five consecutive women patients affected by CFS and a group of fifteen
healthy women extremely sedentary individuals, with the use of maximum
incremental exercise testing on a cycle ergometer and arm ergometer,
assessing possible differences. The majority of values achieved at peak
exhaustive exercise were significantly lower in CFS patients than controls,
including the percentage of maximum oxygen uptake in arm physical test
(37.4 ± 10.0% in CFS vs. 58.9 ± 15.8% in controls) and leg physical test
(53.4
±
15.0% in CFS patients vs. 76.2
±
18.0% in controls).
In conclusion, the CFS group shows a lower work capacity in arm or leg
exercise that would not be justified exclusively by their personal charac-
teristics or deconditioning. doi: 10.1300/J092v14n01_05 {Article copies avail-
able for a fee from The Haworth Document Delivery Service: 1-800HAWORTH. E-
mail address:<docdelivery@haworthpress.com> Website:
<http://www.HaworthPress.com> © 2007 by The Haworth Press, Inc. All rights
reserved.}
KEYWORDS. Chronic fatigue syndrome, maximal oxygen uptake, lactate
INTRODUCTION
Patients affected by Chronic Fatigue Syndrome (CFS) characteristically
show easy and unexplained fatigue after minimal exertion (I) that does not
resolve with rest and is associated with specific symptoms lasting for more
than six months. Various peripheral physiological mechanisms (2), immune
deregulations (3,4) or central disorders (5) have been proposed to explain
this syndrome.
Several authors have reported decreased aerobic capacity relative to
normal subjects in these patients, with reductions in maximum oxygen
uptake (V02max), peak heart rate and peak power output (6,7,8,9), whereas
others describe aerobic capacity at the lower end of the normal range (10).
These differences could be due to the fact that the CFS population is very
heterogeneous, or to the small populations studied.
Cardiopulmonary exercise testing is a valid procedure for determining
functional capacity, the maximum oxygen uptake being a standard pa-
rameter to estimate a person's functional reserve. Exercise on a cycle
ergometer or treadmill, where performance involves the lower extremities,
is typically used to assess aerobic capacity. Exercise testing results
Original Research
45
can be used to differentiate between groups of patients who present
symptoms consistent with CFS, classifying impairment as none, mild,
moderate, or severe (11), although the association between exercise capacity
and activity limitation is moderate (12).
This study compares cardioventilatory adaptation to exercise between a
group of patients affected by CFS and a group of extremely sedentary
individuals, with the use of maximum incremental exercise testing on a
cycle ergometer and arm ergometer.
MATERIALS AND METHODS
The CFS group comprised 85 consecutive women patients with a mean
weight of 64.4
±
11.9 kg and height of 1.61
±
0.06 m referred to the
Department of Physiological Sciences II of the University of Barcelona for
a battery of examinations. All met the CDC criteria for CFS (13) and
diagnoses were confirmed in all patients by consensus of two physicians.
No alternative diagnoses were established in any patient over a minimum of
six months of additional observations. Fifteen healthy women with a mean
weight of 57.5
±
5,1 kg and height of 1.59
±
0.05 m served as the control
group and sex-, age-, height- and weight-matched CFS group. The controls
were considered to be extremely sedentary subjects on the following basis:
their occupation did not require physical effort, they did not perform
physical activity and all their other activities (hobbies, etc.) were sedentary
activities.
All participants were fully informed of the procedures, discomfort, and
the risks involved in performing the examinations. The study was approved
by the Ethics Committee of the Research Institute of Bellvitge Hospital
(IDIBELL-Bellvitge Campus, Barcelona). Written consent was obtained
from all subjects after informing them of the procedures to be used and the
risks entailed.
Laboratory Exercise Tests
Exercise testing was done in the Department of Physiological Sciences II
laboratory at a room temperature of22-24°C and relative humidity of 55-
65%. The subjects were instructed not to perform 'intensive physical activity
during the 72 hours prior to the evaluations. Tests were always conducted in
the morning after a light breakfast.
Each subject was firsttested on an arm ergometer (model Angio, Lode,
Groningen, The Netherlands) at a frequency of 40-50 rev·min-1. The
46
JOURNAL OF CHRONIC FATIGUE SYNDROME
initial load was l0 w; with consecutive increases of l0 w every one minute
until the subject could no longer maintain the target power output despite
strong vocal encouragement. After a recovery period of 10 min, the
participants were tested on a precalibrated Monark cycle ergometer (model
818E, Varberg, Sweden), starting with 0 watt at 50 rev·min-1 for 2 min, with
consecutive increases of 12.5 watt everyone minute until exhaustion.
O2 uptake and CO2 production were measured by an automatic gas
analysis system (model Metasys TR-plus, Brainware S.A., La Valette,
France) equipped with a pneumotacograph and making use of a two-way
mask (Hans Rudolph, Kansas, USA). Age-based predicted values for
VO2max were calculated from regression equations derived from maximal
testing in a cohort of healthy sedentary women (VO2max in mL·kg-1 . min-l
=
42.3 - [0.356· age in years]) (14).
Heart rate (HR) was monitored continuously using a pulsometer (model
Polar Accurex Plus, Polar Electro OY, Finland). The age-predicted maxi-
mum heart rate was calculated with the following formula: [208 - (0.7· age
in years)] (15).
Arm blood pressure (BP) was taken manually using a clinical sphyg-
momanometer. Blood lactate concentration was measured after the arm
ergometer test and the cycle ergometer test (YSI 1500 SPORT, YSI
Incorporated, Ohio, USA).
The rating of perceived exertion (RPE) (16) was recorded after all
workloads.
Statistical Analysis
Analysis of variance for repeated measures was performed to assess
group differences for the various samples. An independent student t-test was
performed to assess group differences for resting parameters. The level of
significance was set at P
<
0.05 for all the statistical tests. All data are
expressed as the mean ± SD.
RESULTS
Resting Parameters
There were no significant differences in the resting physiological
parameters between the CFS patients and the controls, except for the fol-
lowing: systolic BP, 120A± 5.3 mmHg in CFS vs.105.6 ± 15.1 mmHg
Original Research
47
in controls (P < 0.01); diastolic BP, 79.9 ± 12.0 mmHg in CFS vs. 69.2± 8.2
mmHg in controls (P < 0.05); and RPE 10.3 ± 2.3 in CFS vs. 6.0 ± 0.0 in
controls (P
<
0.001).
Arm and Cycle Ergometer Test Differences
Values at peak exercise in the arm ergometer test are shown in Table 1.
The majority of values achieved at peak exhaustive exercise were significantly
lower in CFS patients than controls, including the percentage of maximum
oxygen uptake (37.4 ± 10.0% in CFS vs. 58.9 ± 15.8% in controls).
For the peak workload, linear regression analysis determined the line of best
fit, defined as:
VO2theoretical peak = 0.370 + (workload· 0.01043)
Where VO2theo!etical peak (theoretical oxygen uptake pea~) is in 1· min-1
and workload IS given In watts (95% CI=0.272-0.469 l'mIn-1, r=0.548, P <
0.001).
Peak exercise values in the leg ergometer test are also shown in Table 1.
Again, most of the values achieved at peak exhaustive exercise were sig-
nificantly lower in the CFS patients as compared with the control group,
including the percentage of maximum oxygen uptake (53.4± 15.0% in CFS
patients vs. 76.2 ± 18.0% in controls).
Comparison Between Arm and Leg Performance
There were no significant differences between the groups in arm/leg ratio for
V02max' workload, or HR (Table 2).
DISCUSSION
The first aim of the present study was to assess the potential differences in
physiological adaptation to exercise between women patients with CFS and the
normal population. To prevent a gender-related influence, our patient
population was 90% women, a percentage consistent with the control group
(88%), and higher than the ratio reported in other study of approximately three
women diagnosed for every man (17). As potential factors that could influence
the results, some authors have suggested that maximum oxygen consumption
may not be achieved by the exercise protocol used or that the endpoint fo~'
maximum effort may not
50
JOURNAL OFCHRONIC FATIGUE SYNDROME
TABLE 2. Comparison between arm and leg exercise for different physiological
variables between the CFS and the control groups.
Variable
Arm/Leg VO2max (%)
Arm/Leg Work load (%)
Arm/Leg
HRmax
(%)
CFS group
71.9
±
20.3
55.5
±
18.1
93.4
±
9.3
Control group
75.2
±
13.0
45.7
±
9.1
88.2
±
7.5
Significance
>0.05
>0.05
>0.05
be well-established
(J
8, 19,7,9). To avoid this influence, a protocol was
designed for the arm and cycle ergometer testing using small increases in
workload that could be completed by physically inactive persons. The criteria
identifying maximum effort were the same for both the patient and control
groups. In CFS group, ]
1
% of the patients reached maximal effort using the
American College of Sports Medicine Guide to Exercise Testing. This subgroup
of CFS patients show similar differences respect the control group with a
decrease of 35.2% in maximal oxygen uptake and of 37.8% in the maximal
workload.
A factor to explain the fatigability and low exercise tolerance of CFS patients
is the "hypoactivity syndrome" and its deconditioning-related effects on
physiological responses and exercise capacity (8). These characteristics make it
particularly difficult to obtain a control group with similar activity levels.
Selection for our control group required more than one year of extremely
sedentary lifestyle, that is, very sedentary work, not walking to work, no
hobby/leisure activities requiring any physical effort, no physical activity, and
no obligations that would increase physical activity, such as owning a pet that
needed walking. These requirements are different
from
the term "sedentary" as
it is used to define normal, healthy individuals who are not engaged in regular,
structured physical activity, which describes most individuals (20).
Strict selection of the control group meant that the resting parameters were
comparable for weight, height, or ventilatory function. In contrast, the rating of
perceived exertion was high with respect to the controls who, in all cases
indicated an absence of fatigue. These findings are consistent with the concept
that CFS symptoms include fatigability at rest, according to various diagnostic
criteria
(1).
Blood pressure was higher in the CFS group, which could be related
to the fact that patients with CFS show alterations in measures of sympathetic
and parasympathetic nervous system function (21), with a more stressful
response at rest during the test.
Original Research
51
The arm ergometer testing showed an important difference in the work
capacity done in the specific physical test. The CFS group reached only
53.4% of the power output obtained by the controls, while the two groups
showed similar ratings of perceived exertion. All parameters related to the
load achieved demonstrated significant differences, with oxygen con-
sumption 78.4% higher in the control group, and lactate production 76.3%
higher.
The cycle ergometer test showed an even more important difference in
the work capacity done in the specific physical test. The CFS group reached
only 45.9% of the power output obtained by the control group, at a similar
rating of perceived exertion. All parameters related to the load achieved
showed significant differences, with 63.5% higher oxygen consumption in
the control group and 94.3% higher lactate production.
When the arm ergometry data were related to the cycle ergometry data,
the results were analogous for both groups, with 73.6% oxygen consumption
observed in the arms as compared to the legs. These findings are similar to
those reported by other authors (22) and would imply the same decrease in
work capacity regardless of the various muscle groups used.
In the group with an extremely sedentary life style for more than one year
(virtually the entire group had a similar lifestyle throughout their entire adult
life), there was a 24% decrease in
02
uptake with respect to predicted
values. This could result from a "hypoactivity syndrome" and its
deconditioning-related effects on physiological responses and exercise
capacity. In contrast, the CFS patients showed a decrease of 47% in
02
uptake with respect to predicted values which, although partly explained by
the above reasons, should be considered along with the CFS diagnosis to
justify a 23% higher decrease with respect to predicted values than in the
control group. It should be considered that there is a CFS-dependent
decrease in performance.
The maximum parameters obtained by our CFS group were lower than
those found by other authors (23,24). The ratio between the predicted values
of peak oxygen uptake by specific formulas for CFS patients showed a
moderate correlation with the data measured in our group. Indirect
calculation of peak oxygen uptake using the formula proposed by Mullis et
al. (23) showed a difference of -2.2% (95% CI = -7.9,3.4). Respect to the
formula proposed by Nijs and De Meirleir (24) a deviation of 12.1 %
occurred (95% CI=6.8-17.4), within the mean error of the prediction for the
formula submitted by these authors. Nevertheless, the comparison between
the different groups is difficult because in some of them, the percentage of
men/women is different (23) and, in the other, the maximum load reached is
significantly greater (49.7
±
24.8 vs.
5
2
JOURNAL OF CHRONIC FATIGUE SYNDROME
85.5
±
28.9) (24). Something similar could occur with the formula proposed
in our paper for indirect calculation of peak oxygen uptake in arm exercise,
which, although a good tool for our population. group, would need specific
modifications depending on the group studied or an increase in the number
of patients studied, based on a multicenter design.
In
summary, it appears that the decrease in the peak workload achieved in
arm or leg exercise by CFS patients would not be justified exclusively by
their personal characteristics or deconditioning.
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RECEIVED: 03/31/05
ACCEPTED: 09/26/05
doi: 10.1300/J092vI4n01_05