LIRN PAPER: Discriminative Validity of Metabolic and Workload Measurements for Identifying People With Chronic Fatigue Syndrome 

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PTA 1501 Tests and Measurements with Lab
L.I.R.N. Evidenced Based Practice Assignment ​Grading Rubric

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CATEGORY 4 3 2 1

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in correct format
with no errors
(AMA style)

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with 1 or 2 errors

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errors

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SABER College
PTA Program

PTA 1501 Tests and Measurements with Lab

L.I.R.N. Evidence-based Practice Assignment

Assignment​: ​Write a minimum of 150-200 word clinical application summary of a research
article. Students will be assigned a body region. Each student will then be responsible for
choosing one article from a peer-reviewed journal using the virtual library or APTA website in
relation to assigned body region. Students must have the article approved by the instructor prior
to submission of the clinical application summary. The instructor will approve the article based
on a peer reviewed journal not content or relevance to topic.

Due Date​: ​Students need to turn in a copy of their research article for approval on ​Thursday
02/18/21​. If the article is not turned in for approval by allotted time then student will not be able
to turn in assignment and will receive a ZERO. The student must turn in the article and the LIRN

assignment on Google Classroom. This assignment is ​DUE ON March 30, 2021.

Instructions​:
The paper should be a minimum of 150-200 words, typed, double spaced, Times New Roman 12
font, 1” margin. The assignment should be written in whole complete sentences in the third
person.

Write the paper in the following order:
I. Citation: AMA style MUST BE USED

II. Clinical Application:
a. Describe why was the research done
b. Describe any and all test and measurements used in the study
c. Describe why this research is important to PTA’s in the clinic
d. Discuss the strength / weakness of the research conducted

Example: ​Use the following format.

I. Citation in AMA syle.

II. Clinical Application:
a. Introduction: The purpose (why the research was done) of this research was to

determine………Describe the tests and measurements used in the study to prove
the purpose of the research…….describe why this research is important (how can
it be used) to the PTA’s in the clinic…..finally discuss strength and weaknesses of
the research conducted.

Salwachter AR, Freischlag JA, Sawyer RG, Sanfey HA. The training needs and priorities of male and
female surgeons and their trainees. J Am Coll Surg. 2005; 201: 199-205.  

Discriminative Validity of Metabolic
and Workload Measurements for
Identifying People With Chronic
Fatigue Syndrome
Christopher R. Snell, Staci R. Stevens, Todd E. Davenport, J. Mark Van Ness

Background. Reduced functional capacity and postexertion fatigue after physical
activity are hallmark symptoms of chronic fatigue syndrome (CFS) and may even
qualify for biomarker status. That these symptoms are often delayed may explain the
equivocal results for clinical cardiopulmonary exercise testing in people with CFS

.

Test reproducibility in people who are healthy is well documented. Test reproduc-
ibility may not be achievable in people with CFS because of delayed symptoms.

Objective. The objective of this study was to determine the discriminative validity
of objective measurements obtained during cardiopulmonary exercise testing to
distinguish participants with CFS from participants who did not have a disability but
were sedentary.

Design. A prospective cohort study was conducted.

Methods. Gas exchange data, workloads, and related physiological parameters
were compared in 51 participants with CFS and 10 control participants, all women,
for 2 maximal exercise tests separated by 24 hours.

Results. Multivariate analysis showed no significant differences between control
participants and participants with CFS for test 1. However, for test 2, participants
with CFS achieved significantly lower values for oxygen consumption and workload
at peak exercise and at the ventilatory or anaerobic threshold. Follow-up classification
analysis differentiated between groups with an overall accuracy of 95.1%.

Limitations. Only individuals with CFS who were able to undergo exercise
testing were included in this study. Individuals who were unable to meet the criteria
for maximal effort during both tests, were unable to complete the 2-day protocol, or
displayed overt cardiovascular abnormalities were excluded from the analysis.

Conclusions. The lack of any significant differences between groups for the first
exercise test would appear to support a deconditioning hypothesis for CFS symp-
toms. However, the results from the second test indicated the presence of CFS-related
postexertion fatigue. It might be concluded that a single exercise test is insufficient
to reliably demonstrate functional impairment in people with CFS. A second test
might be necessary to document the atypical recovery response and protracted
fatigue possibly unique to CFS, which can severely limit productivity in the home and
workplace.

C.R. Snell, PhD, Department of
Sport Sciences, University of the
Pacific, Stockton, California, and
Workwell Foundation, Ripon,
California.

S.R. Stevens, MA, Workwell
Foundation.

T.E. Davenport, PT, DPT, OCS,
Department of Physical Therapy,
University of the Pacific, 3601
Pacific Ave, Stockton, CA 95211
(USA), and Workwell Foundation.
Address all correspondence to
Dr Davenport at: tdavenport@
pacific.edu.

J.M. Van Ness, PhD, Department
of Sport Sciences, University of the
Pacific, and Workwell Foundation.

[Snell CR, Stevens SR, Davenport
TE, Van Ness JM. Discriminative
validity of metabolic and workload
measurements for identifying
people with chronic fatigue syn-
drome. Phys Ther. 2013;93:
1484 –1492.]

© 2013 American Physical Therapy
Association

Published Ahead of Print:
June 27, 2013

Accepted: June 23, 2013
Submitted: October 27, 2011

Research Report

Post a Rapid Response to
this article at:
ptjournal.apta.org

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mailto:tdavenport@pacific.edu

mailto:tdavenport@pacific.edu

The absence of reliable diagnos-tic laboratory tests or biomark-ers often presents significant
problems for people with chronic
fatigue syndrome (CFS), treating cli-
nicians, and the CFS research com-
munity. The nature of conditions
characterized by chronic fatigue and
pain, such as CFS and fibromyalgia, a
common comorbidity, poses a spe-
cial challenge for physical thera-
pists,1 in part because fatigue is often
associated with deconditioning.
Exercise, the logical prescription for
physical therapists to use in treating
fatigue related to deconditioning,
often is not well tolerated by peop

le

with CFS. In addition, CFS may be
undiagnosed or misdiagnosed by a
physician before referral for physical
therapy, which places physical ther-
apists at the forefront of recognition
and management of individuals with
CFS.2 Although extreme fatigue is a
primary symptom in the 3 most
commonly used CFS case definitions
(the International Chronic Fatigue
Syndrome Study Group case defini-
tion,3 the 2003 Canadian clinical
case definition,4 and the Oxford cri-
teria5), none operationalizes fatigue
or indicates how it should be
assessed. It is clear that the develop-
ment of objective measurements that
can delineate symptoms, assist in
clinical evaluation, and provide an
estimate of prognosis should be of
paramount importance.

As a corollary to extreme fatigue in
CFS, postexertion malaise (PEM), or
exacerbation of symptoms after
physical exertion, is considered one
of the most common and recogniz-
able aspects of the illness.6,7 The
Canadian consensus document on
CFS goes so far as to mandate evi-
dence of symptom expression after
physical activity.4 The presence of
postexertion symptoms in the clini-
cal presentation of CFS suggests that
cardiopulmonary exercise testing
(CPET) can be reliably used to elicit
symptoms of CFS while also serving

as both an indicator of clinical status
and a quantifiable model of physical
exertion. Physical therapists are
trained to administer and interpret
CPET, in which objective measure-
ments are used for the clinical eval-
uation of undiagnosed exercise intol-
erance and the determination of
functional capacity and impairment.
Data obtained from CPET can pro-
vide valuable diagnostic and prog-
nostic information regarding out-
comes of disease.8 If physiological
parameters that correlate with CFS
can be identified through CPET,
physical therapists may be able to
use them to attempt to diagnose the
illness. Because CPET is used to
assess function, it may be particu-
larly helpful for physical therapists
who evaluate and treat people with
illnesses that limit their abilities to
perform functional activities

.9

Previous research comparing exer-
cise test performance in people with
CFS and people who do not have a
disability is equivocal, with some
studies showing lower performance
in people with CFS10 and others
showing no difference between the
groups.11 In addition to the patient
heterogeneity and small sample sizes
that are issues in much CFS research,
exercise studies are highly variable
in both the protocols and the mea-
surements used. A recent systematic
review of the available literature in
this area concluded that, on balance,
the evidence suggested a reduced
physiological exercise capacity in
people with CFS.12 However, in only
a few studies were maximal exercise
tests used and gas exchange da

ta

collected.1

2

The reproducibility of both meta-
bolic and work intensity measure-
ments obtained during CPET is well
documented in people who do not
have a disability,8 whereas test-retest
decrements in metabolic and work-
load measurements have been
obtained in people with CFS.13–15

Among all fatiguing conditions, CFS
is thought to be unique because of a
limited ability to reproduce meta-
bolic and workload measurements
on repeat maximal CPET.15,16

Indeed, most people who are seden-
tary but otherwise healthy recover
from a maximal exercise test within
24 hours. However, for people with
CFS, fatigue persists at levels close to
those reported immediately after
exercise for 24 hours and
beyond.15,17,18 Taken together, these
observations suggest the potential
importance of metabolic and work-
load measurements obtained during
serial CPET for differentiating people
with CFS from people who do not
have a disability. However, the dis-
criminative validity of metabolic and
workload measurements obtained
during serial CPET for such differen-
tiation remains unknown.

The purpose of this study was to
establish the discriminative validity
of objective measurements obtained
during CPET for distinguishing peo-
ple with CFS from people who do
not have a disability but are seden-
tary. To control for potential individ-
ual differences in preparation for
testing and the cyclical nature of CFS
symptoms, we used a dual-test para-
digm comprising 2 CPET sessions
separated by 24 hours. We hypothe-
sized that an exacerbation of symp-
toms after the first test would be
reflected in physiological responses
to the second test.

Method
Participants
A sample of convenience consisting
of 51 women with CFS and 10
women who served as a control
group participated in this study.
Most exercise test data have indi-
cated that gas exchange measure-
ments are highly reproducible
within a given individual if testing
methods are consistent.8 Given these
data and with CFS as the focus of the
study, the disparity in sample size

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was deemed acceptable. The women
were either recruited specifically as
research participants or referred by a
treating physician for functional
assessment. Efforts were made to
match participants with CFS with
control participants for age and body
mass index. All participants with CFS
met the criteria established by
Fukuda et al3 for the diagnosis of
CFS. In addition, all participants with
CFS reported exacerbation of symp-
toms after physical activity as a spe-
cific aspect of their diagnoses. Both
participants with CFS and control
participants were sedentary, as
defined by the American College of
Sports Medicine/American Heart
Association (ie, not participating in a
regular exercise program or not
accumulating 30 minutes or more of
moderate physical activity on most
days of the week).19,20

Procedure
After informed consent was obtained,
the entire procedure for exercise
testing was explained in detail to
each participant. Aerobic capacity
was assessed by use of an electroni-
cally braked Ergoline 800 stationary
cycle ergometer (CareFusion Corp,
San Diego, California) with a ramp-
ing protocol designed to reach peak
work rates in 8 to 12 minutes.

The protocol included 3 minutes of
rest followed by 1 minute of
unloaded cycling before the exercise
test. Participants were asked to main-
tain a pedaling cadence of 60 to 80
rpm throughout the test. For the
test, workload was increased pro-
gressively at a rate of 5 W/20 s
(15 W/min), and participants were
encouraged to pedal for as long as
possible. Breath-by-breath gas sam-
ples were collected with a comfort-
ably fitted Hans Rudolph face mask
(Hans Rudolph Inc, Shawnee, Kan-
sas) and analyzed throughout the test
with a Jaeger Oxycon Alpha meta-
bolic cart (CareFusion Corp). Partic-
ipants remained seated on the

ergometer, and recovery was moni-
tored for 2 to 5 minutes. Care was
taken to ensure complete safety dur-
ing the entire procedure. Continu-
ous electrocardiographic monitoring
of heart rate (12 lead) and measure-
ment of blood pressure every 2 min-
utes took place during the test.

Gas exchange data at peak exercise
were recorded. All participants
achieved a respiratory exchange
ratio (RER) of greater than or equal
to 1.1, indicating excellent effort
during testing.8 In addition to an RER
of greater than or equal to 1.1, all
participants met at least 1 other cri-
terion for determining peak effort
(ie, a plateau in oxygen consump-
tion, a rating of perceived exertion
of �17, or a heart rate of �85% of
the age-predicted maximum),
according to standard CPET interpre-
tation procedures.21 Submaximal
responses at the ventilatory thresh-
old (VT) were determined with the
V-slope method.*,22 In addition to the
value identified automatically by the
equipment, 2 experienced reviewers
validated the VT visually. The second
reviewer was unaware of participant
status. Subsequent to the initial exer-
cise test, all procedures were
repeated 24 hours later.

Data Analysis
To determine whether exercise per-
formance variables could be used to
reliably and accurately discriminate
between participants with CFS and
control participants who were sed-
entary, we entered peak oxygen con-
sumption, oxygen consumption at
the VT, peak workload, and work-
load at the VT as the dependent vari-
ables in a factorial multivariate anal-
ysis of variance (group � test). Post
hoc, descriptive discriminant func-
tion analyses were then used to

determine the variables that best dif-
ferentiated between groups at each
level of the test (ie, test 1 and test 2).
On the basis of the test-retest effect
shown in previous research,
between-group differences across
tests may be diagnostically rele-
vant.13,14 Thus, in the present study,
if a positive group � test interaction
was identified by a multivariate anal-
ysis of variance, an additional inves-
tigation, with separate discriminant
function analyses for test 1 and test
2, was undertaken to determine the
source of the difference. This level of
analysis would provide the opportu-
nity to establish the clinical impor-
tance of between-group differences
in each test that could be diagnosti-
cally relevant. Discriminant function
analyses can be sensitive to sample
size, but both the ratio of total sam-
ple to discriminator variables (15:1)
and the ratio of group samples to
discriminator variables for the small-
est group (3:1) were within accept-
able ranges.23

To aid in the interpretation of
results, we conducted post hoc F
tests for each exercise performance
variable.24 A Bonferroni-type adjust-
ment was made to the test alpha
level (alpha�.0125) to counteract
the potential for an inflated error rate
due to multiple F tests. All statistical
analyses were performed with SPSS
13.0 software for Windows operat-
ing systems (SPSS Inc, Chicago,
Illinois).

Role of the Funding Source
This study was funded, in part, by a
grant from the Chronic Fatigue and
Immune Dysfunction Association of
America.

Results
No significant differences were
found between participants with
CFS and control participants for age,
height, weight, or body mass index
(P�.05). Descriptive statistics for
physical variables are shown in Table

* The VT is generally accepted as being syn-
onymous with the anaerobic threshold, or the
point at which energy production transitions
from primarily aerobic to increasingly anaero-
bic glycolysis.

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1. The duration of illness for partici-
pants with CFS ranged from 6
months to 30 years (mean dura-
tion�11.06 years). Not all partici-
pants with CFS were able to recall
how they first began to experience
symptoms, but 25 participants
reported a sudden onset and 13 par-
ticipants reported a gradual onset.

The duration of testing was limited
by extreme fatigue,22 but all tests
were within the optimum range of 8
to 12 minutes for fatigue-limited
exercise.8 All participants cited leg
pain and muscle fatigue as the reason
for ending the tests, regardless of
group. Correlations among the
dependent variables ranged from
R�.427 to R�.699, fulfilling the
requirement for correlations that are
moderate or lower in magnitude.23

A significant Box’s M test result
(P�.001) indicated that homogene-
ity could not be assumed for the
variance-covariance matrixes across
cells formed by the between-subject
effects. Therefore, the Pillai trace
test statistic was used to interpret
significance because it is considered
the most conservative and robust in
the presence of unequal multivariate
distributions.

The results of a multivariate analysis
of variance showed a significant
group � test interaction (Pillai
trace�.113; F�3.47; df�4,115;
P�.010; power�.847) for the com-
bined dependent variables peak oxy-
gen consumption, oxygen consump-
tion at the VT, peak workload, and
workload at the VT. The test effect
was not significant (Pillai
trace�.086; F�2.09; df�4,115;
P�.086; power�.606) (Tab. 2).

Test 1
A nonsignificant Box’s M test (P�
.103) indicated that homogeneity
of variance-covariance could be
assumed; therefore, the Wilks � test
statistic was used to interpret signif-
icance. No variables from the first

test qualified for discriminant analy-
sis (Wilks ��.856, �2�8.84, df�4,
N�61, P�.065). Univariate compar-
isons of group means indicated a
significant group difference for
peak workload (F�6.11; df�1,59;
P�.005). There were no other signif-
icant group differences (P�.0125)
(Figs. 1 and 2).

Test 2
A nonsignificant Box’s M test (P�
.252) indicated that homogeneity
of variance-covariance could be
assumed; therefore, the Wilks � test
statistic was used to interpret signif-
icance. Discriminant analysis gener-
ated 1 significant function that differ-
entiated between participants with
CFS and control participants (Wilks
��.516, �2�37.71, df�4, N�61,
P�.001). The diagnosis of CFS was
found to account for 48% of the func-
tion variance. Standardized function
coefficients and correlation coeffi-
cients showed that workload at the
VT contributed the most to the dif-
ference between groups; peak work-
load made the next largest contribu-
tion. Classification results revealed
that 49 of 51 participants with CFS
and 9 of 10 control participants were
correctly classified. For the total sam-
ple, 95.1% were correctly classified.
Cross-validation derived 90.2% accu-
racy for the total sample. The means
of the discriminant functions were
consistent with these results. For
control participants, the function
mean was 2.15, whereas for partici-
pants with CFS, the function mean

was �0.422. Univariate analyses
comparing group means for each
variable generally concurred with
this interpretation, although the
group means for peak oxygen con-
sumption were not significantly dif-
ferent at the Bonferroni-adjusted
alpha level (P�.026) (Tab. 3).

Discussion
Optimal physical therapist examina-
tion, evaluation, and intervention for
people with CFS remain challenged
by a lack of validated diagnostic mea-
surements and a limited understand-
ing of the underlying pathophysiol-
ogy of the condition. The present
study was designed to examine the
validity of oxygen consumption and
workload measurements to differen-
tiate between participants with CFS
and matched control participants
(who did not have a disability).
Unlike control participants and con-
sistent with previous research,25,26

participants with CFS were unable to
reproduce their test 1 performance
on test 2.13,14,18,19 The decreased test
2 performance for participants with
CFS could be used diagnostically as
an objective indicator of an abnor-
mal postexertion response and pos-
sibly even a biomarker for the con-
dition. The performance decrement
between tests for participants with
CFS was most apparent for work-
load, particularly workload at the
VT. Attainment of the VT was a fur-
ther indication (in addition to an RER
of �1.1) that group differences were
not due to a lack of effort. The VT

Table 1.
Physical Data by Group

Characteristic

X (SD) for:

P
CFSa Group

(n�51)
Control Group

(n�10)

Age, y 46.29 (8.01) 40.80 (7.69) .053

Height, m 1.65 (0.09) 1.61 (0.10) .174

Weight, kg 70.66 (14.33) 74.39 (9.03) .433

Body mass index, kg/m2 25.96 (4.95) 28.99 (4.24) .076

a CFS�chronic fatigue syndrome.

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represents the point at which energy
derived from anaerobic metabolism
becomes the predominant metabolic
pathway. It is an important measure
in CPET because it represents the
onset of fatigue. Because of an
increased reliance on glycolytic
metabolism and an increased pro-
duction of lactic acid, work intensity
cannot be maintained, resulting in
the reduction or cessation of activity.

The VT is also an important measure
for understanding the activity limita-
tions in CFS.27 Under normal circum-
stances, most activities of daily living
require energy levels below the VT.
However, if the VT occurs at very
low levels of oxygen consumption,
very low workloads, or both, even
normal activities of daily living may
exceed the VT. Therefore, it is pos-
sible that in CFS the increased stress
of requiring anaerobic energy even
for normal activities of daily living
precipitates the symptom exacerba-
tion seen in PEM. The results of the
present study, in context with those
of earlier studies, add to a growing
body of literature that provides a
rationale for physical therapists to
use CPET to identify and character-
ize CFS.

Cardiopulmonary exercise testing, a
testing modality that can be applied
and interpreted in a skilled manner
by physical therapists, permits a
thorough assessment of the inte-
grated response to exercise through
a comprehensive evaluation of the
pulmonary, cardiovascular, hemato-
poietic, neuropsychological, and
musculoskeletal systems.26 To date,
however, few studies have used
maximal CPET with gas exchange
data collection in people with CFS,
and fewer still have used a dual-test
paradigm. Thus, the body of litera-
ture to guide physical therapists in
applying and interpreting CPET for
people with CFS is limited. In a
recent study in which CPET was
combined with gas exchange data

collection, people with CFS reached
the VT and peak exercise at much
lower levels of oxygen consumption
than people who served as controls
in both tests. The differences were
magnified in the second test.14 Con-
sistent with earlier research,25 no
abnormalities in muscular mitochon-
drial oxidative phosphorylation
were identified. This result led to the
conclusion that the poorer perfor-
mance of people with CFS may have
been due to limited oxygen-carrying
capacity. This explanation is also via-
ble for the results obtained in the
present study and emphasizes the
value of physical therapists using a
multisystem measurement tool, such
as CPET, to understand exercise per-
formance and functional decrements
in people with CFS.26

Despite being regarded as the most
accurate method for assessing func-
tion,21 maximal exercise testing with
the measurement of expired gases
can be problematic from both pro-
cedural and ethical perspectives.
When fatigue and pain are primary
symptoms, as in both CFS and fibro-
myalgia syndrome, patients may not
be capable of performing a maximal
test.28,29 The ethics of requiring
patients to undertake a test likely to
exacerbate pain and symptoms also
can be questioned.7

In light of these significant concerns,
several investigators have attempted
to develop appropriate submaximal
exercise tests for people with CFS.
The results of a standardized sub-
maximal ergometer test (the aerobic
power test) were found to be subject
to high error rates when used to pre-
dict peak exercise performance;
therefore, this test was deemed to be
inappropriate for clinical purposes.
Several participants were unable to
reach 75% of the age-predicted max-
imal target heart rate. This finding
was cited as a major limiting factor in
that study.29 These results raise con-
cerns about the external validity ofT

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Metabolic and Workload Measurements in Chronic Fatigue Syndrome

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other research using the same proto-
col to measure physiological
responses in people with CFS.30,31 A
more recent study in which the aer-
obic power test was used as an exer-
cise challenge to study pain and PEM
in people with CFS revealed signifi-
cant differences in the peak RER

between the CFS group (X�1.25)
and the control group (X�0.98).7

On the basis of accepted criteria for
evaluating effort during CPET, a peak
RER of greater than 1.10 indicates
excellent effort, and a peak RER of
less than 1.0 reflects submaximal
effort.8,21 The indication is that the

CFS group was working at or close to
maximal exertion, whereas the con-
trol group was not. These data have
important implications for physical
therapists because even low-level
exercise assessments and interven-
tions can involve nearly maximal
exertion by people with CFS.

Figure 1.
Measurements of oxygen consumption (V̇O2) at peak exercise (A) and at the ventilatory threshold (B) in participants with chronic
fatigue syndrome (CFS) and control participants during cardiopulmonary exercise test 1 (blue bars) and cardiopulmonary exercise
test 2 (gold bars). Error bars represent 1 standard deviation.

Figure 2.
Measurements of workload at peak exercise (A) and at the ventilatory threshold (B) in participants with chronic fatigue syndrome
(CFS) and control participants during cardiopulmonary exercise test 1 (blue bars) and cardiopulmonary exercise test 2 (gold bars).
Error bars represent 1 standard deviation.

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The attainment of RERs exceeding
1.1 by all participants in the present
study indicated comparable effort by
both groups. In addition, all partici-
pants met at least 1 other criterion
for peak effort. However, problems
of subjectivity and interindividual
variability suggest that caution
should be exercised when interpret-
ing the highest values obtained as
maximal.21 In this respect, submaxi-
mal data may allow more valid com-
parisons between groups. The anal-
yses indicated that a lower level of
oxygen consumption at the VT in
test 2 for participants with CFS con-
tributed significantly to the multivar-
iate differences between the groups.
Although statistically significant, the
mean values did not distinguish
between the groups clinically. Both
groups would be classified as having
moderate to severe impairments on
the basis of these data32 because
peak oxygen consumption values for
both groups were below the 10th
percentile for equivalent population
data.21 A more telling difference was
the workload at which each group
attained the VT; in test 2, the output
for the CFS group was approxi-
mately 40 W lower. The deficit in the
between-group workload at the VT
in test 1 was only approximately 8
W. Physical therapists should be

aware that the postexertion state in
patients with CFS is characterized by
objectively measurable deficits in
submaximal metabolism and work-
load that would be nearly impossible
for patients to fabricate.

The etiology of the postexertion
reduction in work efficiency
observed in the present study
remains unclear and warrants further
research, especially given that the
variables measured in the present
study explained almost half of the
discriminative function variance. It is
possible that synergy of small effects
across multiple systems was respon-
sible for the poor exercise perfor-
mance of participants with CFS in
the present study. Lower workloads
and levels of oxygen consumption at
peak exercise and at the VT are con-
sistent with a reduced oxygen-
carrying capacity hypothesis.26 Pos-
sible explanations for this finding
include low blood volume33 and car-
diac abnormalities, such as small
heart syndrome.34,35 In the absence
of respiratory disease, low oxygen
consumption also could result from
autonomic dysfunction and reduced
ventilation.36 This symptomatology
has been linked to immune dysregu-
lation, like that seen in illnesses such
as Guillain-Barré syndrome and mul-

tiple sclerosis.37 It also has been sug-
gested that the choice of an exercise
testing protocol can influence the
mechanical efficiency of people with
CFS.29 Future studies should exam-
ine variables affecting mechanical
efficiency across 2 identically admin-
istered maximal CPET sessions.

The present study would have bene-
fited from the inclusion of further
measurements to minimize the het-
erogeneity of participants. Current
CFS case definitions are suitably
vague, such that individual diagnoses
can show many clinical differences.
The problems of participant hetero-
geneity in CFS research were dis-
cussed in a recent article recom-
mending minimum standards for
data elements in CFS studies and
consideration of measurements that
allow for subgrouping.38 Functional
outcome measures such as those
obtained in the present study could
provide a way to subgroup study par-
ticipants. As in much CFS research,
participation in the present study
was limited to women. Although this
is a common approach to controlling
for gender bias,12 it does limit the
generalizability of study findings.
Tester bias is another potential prob-
lem for the present study because 1
of the testers was not unaware of
participant status. In an attempt to
control for any confounding effects,
objective criteria were used to deter-
mine data points used in the analy-
ses. For selecting VT data, in addition
to the tester, an experienced
reviewer unaware of participant sta-
tus was used to validate the selected
values. Lactate measurements would
have provided additional validation
of the VT and should be considered
in future research of this type.

As a quantifiable stressor, CPET has
the capacity to reveal abnormalities
across multiple systems that may not
be apparent at rest. Therefore, it can
be of tremendous value to physical
therapists for differential diagnosis,

Table 3.
Canonical Correlation Coefficients, Standardized Function Coefficients, F Values, and
P Values for Test 2a

Variable

Canonical
Correlation
Coefficient

With
Discriminant

Function

Standardized
Function

Coefficient Fb P

V̇O2peak, mL/kg/min .308 �.308 5.23 .026

VTO2, mL/kg/min .254 .375 7.78 .007
c

WLpeak, W .559 .563 17.54 �.001d

VTWL, W .781 .877 42.57 �.001d

a V̇O2peak�volume of oxygen consumed at peak exertion, VTO2�volume of oxygen consumed at
ventilatory threshold, WLpeak�workload at peak exertion, VTWL�workload at ventilatory threshold.
b df�1,59.
c Statistically significant at P�.01.
d Statistically significant at P�.001.

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for clinical and functional assess-
ments, and as an indicator of treat-
ment effectiveness. The RER, a mea-
sure exclusive to the analysis of
expired gases, provides the most
accurate and reliable gauge of an
individual’s effort. The use of this
measure avoids problems associated
with the use of the age-predicted
maximal heart rate, which varies sig-
nificantly in the general population
and can be affected by both medica-
tion and pathology.8 A blunted heart
rate response to exercise has been
shown in both CFS39 and fibromyal-
gia syndrome.40 Issues of response
bias in self-report indictors of effort
also are avoided when CPET and RER
are used.

For these reasons, it has been recom-
mended that CPET should be a pri-
mary consideration in the design of
clinical trials with functional end-
points.8 This recommendation not-
withstanding, the value of exercise
testing for evaluating therapeutic
treatments in people with CFS has
been questioned on the basis of a
single study in which exercise capac-
ity measurements were used to
evaluate cognitive behavioral and
graded-exercise–based strategies.41

Because of their association with
psychological hypotheses, decondi-
tioning hypotheses, or both for
CFS symptoms, these treatment
approaches are subject to consider-
able controversy within the commu-
nity of people with CFS. Suffice it to
say that if neither of these hypothe-
ses adequately explains the phenom-
enon of CFS, one would hardly
expect to see improved cardiovascu-
lar functioning subsequent to such
therapies. As the authors of that
study indicated, many improvements
in health-related quality of life for
people with CFS can be achieved
without increases in exercise capac-
ity.41 For example, pacing has been
effective in reducing the exertion-
related symptoms of CFS in patients
unable to exercise because of PEM.42

These findings do not preclude the
use of data obtained through CPET as
endpoints in other therapeutic trials
or for the purposes of diagnosis and
prognosis.

In conclusion, a serial CPET protocol
with the measurement of expired
gases was efficacious in distinguish-
ing between people with CFS and
people who were sedentary but oth-
erwise healthy. As in the only other
identified studies in which a dual
CPET paradigm with the measure-
ment of expired gases was used,14,15

participants with CFS showed a
decrease in performance on the sec-
ond test that was not seen in control
participants. This functional deficit
may provide an objective indication
of PEM. Despite considerable patient
heterogeneity with respect to illness
duration and type of onset, analysis
of data from the second test was able
to correctly classify 49 of 51 partici-
pants with CFS and 9 of 10 control
participants. Noninvasive biomark-
ers for CFS do not currently exist.
Physical therapists may consider the
use of CPET performance measure-
ments to differentiate between peo-
ple with CFS and people who do not
have a disability but are sedentary.
Work efficiency (ie, oxygen con-
sumption and work output) at the
VT or anaerobic threshold appears to
have diagnostic potential for CFS.
Cardiopulmonary exercise testing is
a test modality compatible with
physical therapist practice patterns
and provides a way for the profes-
sion to make strong contributions to
the diagnosis, treatment, and
research of CFS.

All authors provided concept/idea/research
design and data collection and analysis. Dr
Snell, Dr Davenport, and Dr Van Ness pro-
vided writing. Dr Snell and Dr Van Ness pro-
vided fund procurement. Dr Snell and Ms
Stevens provided facilities/equipment. Dr
Davenport provided clerical support. Dr
Snell, Ms Stevens, and Dr Davenport pro-
vided project management, institutional liai-
sons, and consultation (including review of

manuscript before submission). The authors
thank Daniel Peterson, MD, and Jose
Montoya, MD, for referring potential study
participants. They also gratefully acknowl-
edge all study participants for their valuable
contribution.

This study received exempt review approval
from the Institutional Review Board at the
University of the Pacific, Stockton, California.

Portions of the data were presented at the
Combined Sections Meeting of the Ameri-
can Physical Therapy Association; February
8 –11, 2012; Chicago, Illinois.

This study was funded, in part, by a grant
from the Chronic Fatigue and Immune Dys-
function Association of America.

DOI: 10.2522/ptj.20110368

References
1 Schachter CL, Busch AJ, Peloso PM, Shep-

pard MS. Effects of short versus long bouts
of aerobic exercise in sedentary women
with fibromyalgia: a randomized con-
trolled trial. Phys Ther. 2003;83:340 –358.

2 Griffith JP, Zarrouf FA. A systematic
review of chronic fatigue syndrome: don’t
assume it’s depression. J Clin Psychiatry.
2008;10:120 –128.

3 Fukuda K, Straus SE, Hickie I, et al; Inter-
national Chronic Fatigue Syndrome Study
Group. The chronic fatigue syndrome: a
comprehensive approach to its definition
and study. Ann Intern Med. 1994;121:
953–959.

4 Carruthers BM, Jain AK, De Meirleir KL,
et al. Myalgic encephalomyelitis/chronic
fatigue syndrome: clinical working case
definition, diagnostic and treatment proto-
cols. Journal of Chronic Fatigue Syn-
drome. 2003;11:7–115.

5 Sharpe MC, Archard LC, Banatvala JE, et al.
A report: chronic fatigue syndrome—
guidelines for research. J R Soc Med. 1991;
84:118 –121.

6 Nijs J, Van Oosterwijck J, Meeus M, et al.
Unravelling the nature of postexertional
malaise in myalgic encephalomyelitis/
chronic fatigue syndrome: the role of elas-
tase, complement C4a and interleukin-
1beta. J Intern Med. 2010;267:418 – 435.

7 Van Oosterwijck J, Nijs J, Meeus M, et al.
Pain inhibition and postexertional malaise
in myalgic encephalomyelitis/chronic
fatigue syndrome: an experimental study.
J Intern Med. 2010;268:265–278.

8 Balady GJ, Arena R, Sietsema K, et al. Cli-
nician’s guide to cardiopulmonary exer-
cise testing in adults: a scientific statement
from the American Heart Association. Cir-
culation. 2010;122:191–225.

9 American Physical Therapy Association.
Today’s physical therapist: a comprehen-
sive review of a 21st-century health care
profession. Move Forward website. Avail-
able at: http://www.moveforwardpt.com.
2012. Accessed March 7, 2012.

Metabolic and Workload Measurements in Chronic Fatigue Syndrome

November 2013 Volume 93 Number 11 Physical Therapy f 1491

D
ow
nloaded from
https://academ
ic.oup.com
/ptj/article/93/11/1484/2735315 by guest on 10 February 2021

10 De Becker P, Roeykens J, Reynders M,
et al. Exercise capacity in chronic fatigue
syndrome. Arch Intern Med. 2000;160:
3270 –3277.

11 Sargent C, Scroop GC, Nemeth PM, et al.
Maximal oxygen uptake and lactate metab-
olism are normal in chronic fatigue syn-
drome. Med Sci Sports Exerc. 2002;34:51–
56.

12 Nijs J, Aelbrecht S, Meeus M, et al. Tired of
being inactive: a systematic literature
review of physical activity, physiological
exercise capacity and muscle strength in
patients with chronic fatigue syndrome.
Disabil Rehabil. 2011;33:1493–1500.

13 Van Ness JM, Snell CR, Strayer DR, et al.
Subclassifying chronic fatigue syndrome
through exercise testing. Med Sci Sports
Exerc. 2003;35:908 –913.

14 Vermeulen RC, Kurk RM, Visser FC, et al.
Patients with chronic fatigue syndrome
performed worse than controls in a con-
trolled repeated exercise study despite a
normal oxidative phosphorylation capac-
ity. J Transl Med. 2010;8:93.

15 Van Ness JM, Stevens SR, Bateman L, et al.
Postexertional malaise in women with
chronic fatigue syndrome. J Womens
Health (Larchmt). 2009;19:239 –244.

16 Davenport TE, Stevens SR, Van Ness MJ,
et al. Conceptual model for physical ther-
apist management of chronic fatigue syn-
drome/myalgic encephalomyelitis. Phys
Ther. 2010;90:602– 614.

17 Davenport TE, Stevens SR, Baroni K, et al.
Reliability and validity of Short Form 36
Version 2 to measure health perceptions
in a sub-group of individuals with fatigue.
Disabil Rehabil. 2011;33:2596 –2604.

18 Davenport TE, Stevens SR, Baroni K, et al.
Diagnostic accuracy of symptoms charac-
terising chronic fatigue syndrome. Disabil
Rehabil. 2011;33:1768 –1775.

19 Haskell WL, Lee IM, Pate RR, et al. Physical
activity and public health: updated recom-
mendation for adults from the American
College of Sports Medicine and the Amer-
ican Heart Association. Med Sci Sports
Exerc. 2007;39:1423–1434.

20 Haskell WL, Lee IM, Pate RR, et al. Physical
activity and public health: updated recom-
mendation for adults from the American
College of Sports Medicine and the Amer-
ican Heart Association. Circulation. 2007;
116:1081–1093.

21 American College of Sports Medicine.
ACSM’s Guidelines for Exercise Testing
and Prescription. 8th ed. Ambler, PA: Lip-
pincott Williams & Wilkins; 2009.

22 Wasserman K, Hansen JE, Sue DY, et al.
Principles of Exercise Testing and Inter-
pretation: Including Pathophysiology
and Clinical Applications. 2nd ed. Phila-
delphia, PA: Lippincott Williams &
Wilkins; 2004.

23 Tinsley H, Brown S. Handbook of Applied
Multivariate Statistics and Mathematical
Modeling. Philadelphia, PA: Academic
Press; 2000.

24 Enders CK. Performing multivariate group
comparisons following a statistically signif-
icant MANOVA. Measurement and Eval-
uation in Counseling and Development.
2003;36:40 –56.

25 McCully KK, Natelson BH. Impaired oxy-
gen delivery to muscle in chronic fatigue
syndrome. Clin Sci. 1999;97:603– 608.

26 Forman DE, Myers J, Lavie CJ, et al. Car-
diopulmonary exercise testing: relevant
but underused. Postgrad Med. 2010;122:
68 – 86.

27 Jones DE, Hollingsworth KG, Jakovljevic
DG, et al. Loss of capacity to recover from
acidosis on repeat exercise in chronic
fatigue syndrome: a case-control study.
Eur J Clin Investig. 2012;42:186 –194.

28 Noonan V, Dean E. Submaximal exercise
testing: clinical application and interpreta-
tion. Phys Ther. 2000;80:782– 807.

29 Nijs J, Zwinnen K, Meeusen R, et al. Com-
parison of two exercise testing protocols
in patients with chronic fatigue syndrome.
J Rehabil Res Dev. 2007;44:553–559.

30 Wallman K, Goodman C, Morton A, et al.
Test-retest reliability of the Aerobic Power
Index test in patients with chronic fatigue
syndrome. Journal of Chronic Fatigue
Syndrome. 2003;11:19 –32.

31 Wallman KE, Morton AR, Goodman C,
Grove R. Physiological responses during a
submaximal cycle test in chronic fatigue
syndrome. Med Sci Sports Exerc. 2004;36:
1682–1688.

32 Weber KT, Janicki JS, Likoff MJ. Exercise
testing in the evaluation of cardiopulmo-
nary disease: a cardiologist’s point of view.
Clinics Chest Med. 1984;5:173–180.

33 Hurwitz BE, Coryell VT, Parker M, et al.
Chronic fatigue syndrome: illness severity,
sedentary lifestyle, blood volume and evi-
dence of diminished cardiac function. Clin
Sci. 2010;118:125–135.

34 Miwa K, Fujita M. Cardiovascular dysfunc-
tion with low cardiac output due to a small
heart in patients with chronic fatigue syn-
drome. Intern Med. 2009;48:1849 –1854.

35 Miwa K, Fujita M. Small heart syndrome in
patients with chronic fatigue syndrome.
Clin Cardiol. 2008;31:328 –333.

36 Newton JL, Okonkwo O, Sutcliffe K, et al.
Symptoms of autonomic dysfunction in
chronic fatigue syndrome. QJM. 2007;100:
519 –526.

37 Flachenecker P. Autonomic dysfunction in
Guillain-Barré syndrome and multiple scle-
rosis. J Neurol. 2007;254(suppl 2):II96 –
II101.

38 Jason LA, Unger ER, Dimitrakoff JD, et al.
Minimum data elements for research
reports on CFS. Brain Behav Immun.
2012;26:401– 406.

39 Van Ness JM, Snell CR, Stevens SR. Dimin-
ished cardiopulmonary capacity during
post-exertional malaise in chronic fatigue
syndrome. Journal of Chronic Fatigue
Syndrome. 2008;14:77– 85.

40 da Cunha Ribeiro RP, Roschel H, Artioli
GG, et al. Cardiac autonomic impairment
and chronotropic incompetence in fibro-
myalgia. Arthritis Res Ther. 2011;13:R190.

41 Pardaens K, Haagdorens L, Van Wambeke
P, et al. How relevant are exercise capac-
ity measures for evaluating treatment
effects in chronic fatigue syndrome?
Results from a prospective, multidisci-
plinary outcome study. Clin Rehabil.
2006;20:56 – 66.

42 Goudsmit EM, Nijs J, Jason LA, Wallman
KE. Pacing as a strategy to improve energy
management in myalgic encephalomyeli-
tis/chronic fatigue syndrome: a consensus
document. Disabil Rehabil. 2012;34:
1140 –1147.

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