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Subclassifying Chronic Fatigue Syndrome through Exercise Testing


Medicine & Science in Sports & Exercise: June 2003 - Volume 35 - Issue 6 - pp 908-913
CLINICAL SCIENCES: Clinically Relevant

VANNESS, J. M., C. R. SNELL, D. R. STRAYER, L. DEMPSEY IV, and S. R. STEVENS. Subclassifying Chronic Fatigue Syndrome through Exercise Testing. Med. Sci. Sports Exerc., Vol. 35, No. 6, pp. 908–913, 2003.

Purpose: The purpose of this study was to examine physiological responses of persons with chronic fatigue syndrome (CFS) to a graded exercise test.

Methods: Cardiopulmonary exercise tests were performed on 189 patients diagnosed with CFS. Based on values for peak oxygen consumption, patients were assigned to one of four impairment categories (none, mild, moderate, and severe), using American Medical Association (AMA) guidelines. A one-way MANOVA was used to determine differences between impairment categories for the dependent variables of age, body mass index, percentage of predicted V̇O2, resting and peak heart rates, resting and peak systolic blood pressure, respiratory quotient (RQ), and rating of perceived exertion.

Results: Significant differences were found between each impairment level for percentage of predicted V̇O2 and peak heart rate. Peak systolic blood pressure values for the “moderate,” and “severe” groups differed significantly from each other and both other groups. The more impaired groups had lower values. The no impairment group had a significantly higher peak RQ than each of the other impairment levels (all P < 0.001). Peak V̇O2 values were less than predicted for all groups. Compared with the males, the women achieved actual values for peak V̇O2 that were closer to their predicted values.

Conclusion: Despite a common diagnosis, the functional capacity of CFS patients varies greatly. Stratifying patients by function allows for a more meaningful interpretation of the responses to exercise and may enable differential diagnosis between subsets of CFS patients.

Chronic fatigue syndrome (CFS) is a complex illness characterized by pervasive fatigue, sleep disturbance, neurocognitive problems, joint and muscle pain, and numerous other symptoms. Researchers from DePaul University have estimated that as many as 836,000 Americans may be afflicted with CFS, with approximately 90% of patients yet to be diagnosed and provided appropriate treatments. Although CFS seems to afflict both males and females of various ethnic backgrounds from childhood to adulthood, the syndrome is most commonly diagnosed in females (18). However, this may be in part a function of women visiting doctors more often overall. In the population as a whole, CFS is probably just as prevalent among men (10). The corresponding economic impact resulting from the disability caused by CFS is becoming an important societal concern (24). Because CFS is an emerging illness, there are few guidelines for the evaluation of patients.

In 1988, the U.S. Centers for Disease Control and Prevention (CDC) established a case definition for CFS to assist clinicians and researchers in diagnosing patients in a more uniform manner (16). The CDC revised the case definition for CFS in 1994 (12). For a diagnosis to be made, any medical conditions that may explain the presence of fatigue must be ruled out. The fatigue associated with the syndrome is described as debilitating or easy fatigability in a person who has no previous history of similar symptoms, that does not resolve with bedrest, and that is severe enough to reduce or impair average daily activity below 50% of the patient’s premorbid activity level for a period of at least 6 months (16). Fukuda et al. (12) defines the fatigue inherent in CFS as clinically evaluated, unexplained persistent or relapsing chronic fatigue that is of new or definite onset (has not been lifelong), is not the result of ongoing exertion, is not substantially alleviated by rest, and results in substantial reduction in previous levels of occupational, educational, social, or personal activities. Additionally, an individual must exhibit four or more of the following symptoms; sore throat; tender cervical or axial lymph nodes; muscle pain; multi-joint pain without joint swelling or redness; headaches of a new type, pattern, or severity; unrefreshing sleep and postexertional malaise lasting more than 24 h.

The current diagnostic criteria for CFS (12) focus primarily on the subjective symptoms associated with the illness. Consequently, the etiology, pathophysiology, and pathogenesis of the disease are still not clearly understood (25). Researchers have documented immune (20) and central nervous system dysfunction (28) as well as metabolic (25–27) and endocrine (18) abnormalities in CFS patients. Although some progress has been made toward identifying a common cause underlying the symptoms of CFS (9), currently no single diagnostic test exists. The continued reliance on consensus of clinical description in the absence of measurable pathology has resulted in a heterogeneous patient population and inconsistency among research findings (35). Because the defining characteristics of this illness are fatigue and intolerance for physical activity, it might seem reasonable to use an index of physical functioning to more objectively quantify the level of patient dysfunction and help facilitate uniformity of patient samples. In disease states involving cardiovascular, pulmonary, or metabolic disorders, cardiopulmonary exercise tests (CPX) using maximal oxygen uptake (V̇O2max) as a measure of functional capacity are routinely administered to assess the degree of limitation in function and the level of impairment imposed by the disease. Recently CPX testing has been applied to CFS as it has classically been applied to other disease states. Studies evaluating the ability of CFS patients to perform physical work using standardized exercise tests have generated conflicting results. Some researchers report that the aerobic capacity of CFS patients is within the normal range (25,30,35), whereas others find a reduced aerobic capacity compared with healthy subjects (8,11,17,29). Possible explanations for these equivocal findings may include the heterogeneity of CFS patient populations and problems associated with the compromised exercise capacity of some patients. In rehabilitation studies involving exercise, patients are generally high functioning, able to attend outpatient workout sessions, and likely represent less than 10% of CFS cases (31). It is also the case that the exercise-induced pain experienced by many CFS patients can encourage a belief that physical activity is dangerous and possibly associated with organ damage (13). This may be one reason for the high dropout rates found in many exercise studies involving CFS patients (38). A number of cardiac abnormalities have also been identified in CFS patients that may not be apparent with standard 12-lead electrocardiograms (7,22,23). It is suggested that these may result from persistent herpes virus infections and that variations in herpes virus causality could explain the patient heterogeneity in CFS (21). Among the herpes viruses, Epstein-Barr virus (EBV) has been linked to both mild and severe cardiac dysfunction (37). It is possible that virally mediated cardiac abnormalities underlie the inability of some CFS patients to meet accepted criteria for maximal effort during exercise testing. Patients unable to meet these criteria are often excluded from research involving exercise tests (17).

One aspect of exercise testing notably absent from the CFS research literature is its potential for subclassifying CFS patients based upon their functional status. Such classification could provide for stratification of patients involved in research studies, helping to control for patient differences. Further, assessment of functional capacity may assist physicians when prescribing treatment for CFS. The purpose of this study is to examine the results of exercise testing from a large population of patients with CFS. These findings may provide insight to the mechanisms underlying fatigue, and aid in the treatment of CFS.

1University of the Pacific, Department of Sport Sciences, Stockton, CA;

2The Workwell Foundation, Ripon, CA; and

3Hemispherx Biopharma, Inc., Philadelphia, PA

Address for correspondence: J. Mark VanNess, Department of Sport Sciences, University of the Pacific, Stockton, CA 95211; E-mail:

Submitted for publication June 2002.

Accepted for publication December 2002.

©2003The American College of Sports Medicine