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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
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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 people 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 data collected.12
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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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
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