Chronic fatigue syndrome (CFS) is a medically unexplained illness characterized by severe fatigue lasting at least 6 months and accompanied by numerous symptoms including impaired memory or concentration, sore throat, tender lymph nodes, muscle and/or multi-joint pain, headaches, unrefreshing sleep, and postexertional malaise (11). The symptoms associated with CFS could potentially affect how exercise is perceived and undoubtedly contribute to the patient’s sedentary lifestyle. In fact, previous research has reported that RPE during exercise are elevated in CFS (10,12,13,18,21) and that central dysregulation of the perception of effort leads to increased fatigue and a decreased exercise capacity (10,18). However, we previously reported that although ratings of perceived exertion during maximal treadmill exercise were higher at absolute exercise intensities, these differences were eliminated when the data were expressed relative to peak aerobic capacity (part 1 of this series). That study challenged the widely held notion that the perception of exertion is dysregulated in CFS and highlighted the importance of using a standardized approach and making appropriate comparisons when examining RPE in fatiguing illness.
Apart from the civilian population, there exists another distinct group of CFS sufferers, namely Gulf War veterans (GV). Military personnel deployed to the Persian Gulf War reported medically unexplained symptoms twice as frequently as personnel who were not deployed (7,14,16). It is estimated that approximately 16% of the ∼68,000 GV who volunteered for the Veterans Affairs Gulf War Registry, a comprehensive medical evaluation offered to all GV, met case criteria for CFS (17). Data describing perceptual responses to exercise in GV with CFS are limited and could provide important information toward understanding how exercise may be used in treating those veterans with unexplained fatigue.
Despite their diagnostic similarity, GV with CFS differ substantially from their civilian counterparts. First, GV with CFS are predominantly male, whereas CFS in civilians tends to occur most often in females (8:1) (11). With regard to disease presentation, GV were diagnosed with CFS after service during the Gulf War, thus representing a quasi-epidemic episode. CFS in American civilians normally presents endemically. Finally, it has been reported that compared with civilians with CFS, GV with CFS represent a less severe group in terms of symptoms, activity level, and ability to work (20). These differences suggest that divergent pathophysiological processes may be producing the same clinical syndrome. It is unknown to what degree CFS in GV affects their perception of exercise. Therefore, the purpose of the present investigation was to determine whether perceived exertion is altered during exercise in GV with CFS compared with healthy GV controls. Based on our previous work in civilians with CFS, we hypothesized that GV with CFS would report higher RPE at absolute exercise intensities compared with healthy veteran controls, but that these differences would not occur when RPE were expressed relative to peak exercise capacity.
Our sample included 34 GV (N = 15 CFS, 12 males and 3 females;N = 19 healthy controls, 16 males and 3 females; see Table 1). Fourteen subjects per group provided statistical power of 0.80 to detect a moderate to large effect (Cohen’s SD = 0.7) between groups for six repeated measures given a two-tailed alpha of 0.05 and a high correlation (r = 0.7–0.9) between repeated measures (25). These participants were enrolled in the VA NJ Center for Environmental Hazards Research. A diagnosis of CFS was given if the subject met the current Centers for Disease Control case definition (11). One of the 15 GV in the CFS group did not completely fulfill criteria for CFS (i.e., symptom duration of 4 months) and was diagnosed with idiopathic chronic fatigue (11), a slightly less severe form of CFS. Analyses done with and without this individual did not produce different results. For purposes of statistical power, this subject’s data were included in all analyses as part of the CFS group. Control subjects were GV in good health, reporting no history of cardiovascular, respiratory, or neurological disorder and having used no medications with central or peripheral adrenergic activity.
Prospective subjects were mailed a health survey package including a screening questionnaire designed to identify GV with and without CFS who would be suitable for participation. Veterans meeting eligibility criteria and willing to participate were brought to the East Orange, NJ VA Medical Center for more thorough medical evaluation by a physician trained in the diagnosis of CFS (20). On-site evaluation included a medical history, physical examination, standard laboratory tests, and a computerized diagnostic psychiatric interview (Q-DIS) (WSU School of Medicine, St. Louis, MO). Before participation, all veteran participants signed a consent form approved by the review board at the VA hospital of East Orange, NJ.
Subjects reported to the human performance laboratory having abstained from nicotine for at least 2 h and from caffeine for 4 h. Experimenters were kept blind to the subject’s clinical status throughout the entire evaluation process. The Baecke physical activity questionnaire (1) was administered to determine the amount of self-reported physical activity during a routine week. This instrument has been shown to be a valid and reliable tool for measuring regular physical activity in men and women (15).
Before testing, the subjects were instrumented for monitoring of blood pressure (BP), heart rate (HR), and metabolic responses to exercise. BP was monitored using an automated system (CardioDyne NBP 2000, Worcester, MA) and verified with concurrent mercury sphygmomanometry. HR was monitored by ECG using the Quinton Q4000 (Quinton Instruments, Seattle, WA). Expired air was collected from the mouth via a two-way nonrebreathing valve (Hans-Rudolph, Kansas City, MO) and was analyzed with the Max-1 metabolic measurement system (Physio-Dyne Instruments, Quoge, NY). Before each test, the Max-1 system was calibrated for ambient conditions. Exercise testing was done on a regularly calibrated, mechanically braked cycle ergometer (Monark 818, Varberg, Sweden).
Perceived exertion assessment.
RPE were obtained during exercise by using a standardized 0–10 category ratio scale (3). Before exercise, subjects were given standard instructions for the proper use of the 0–10 scale. Briefly, subjects were instructed that the 0–10 scale would be used to determine: 1) “the intensity of effort, stress, or discomfort felt during exercise”; 2) that all feelings and physiological cues should be integrated into an overall feeling of effort; 3) that each number represents a category of sensation that is ordered according to its intensity; and 4) that the verbal anchors should be used to help determine the level of effort at that particular moment. Subjects were also provided cognitive anchors at the high and low ends of the perceptual continuum. Specifically, consistent with Borg’s range model, participants were instructed the number 0 represents the lowest exertion imaginable and that the number 10 should be reserved for maximal effort or the greatest effort they could imagine (2). During the exercise test, RPE were obtained during the last 15 s of each stage of exercise.
Maximal exercise testing.
Subjects were seated on a cycle ergometer (Monark 818E) with seat and handlebars adjusted for optimal performance, and allowed a few minutes to habituate to the cycle and various monitoring devices. The exercise test began with three min of unloaded pedaling. Subjects were instructed to maintain a pedaling cadence of 60 rpm. After this warm-up period, work intensity was increased 30 W·min−1 until volitional exhaustion or a point where the subject could no longer maintain the prescribed pedal rate. HR was continuously monitored and BP was recorded in the last 15 s of each exercise stage.
During the exercise test, cardiorespiratory and metabolic variables including oxygen consumption (V̇O2), carbon dioxide production (V̇CO2), ventilation (V̇E), and respiratory rate (RR) were measured breath by breath. Respiratory exchange ratio (RER) was determined by the ratio of V̇CO2 produced to V̇O2 consumed. Maximum effort was determined based on meeting at least two of the following criteria: 1) respiratory exchange ratio ≥ 1.1, 2) attainment of 85% of age-predicted maximum HR (220 − age), and 3) plateau or decline of V̇O2 despite increasing workload.
The gas exchange threshold (GET), a noninvasive index of the onset of exercise-induced metabolic acidosis, was determined using the V-slope method as described by Sue et al. (24). V̇O2 and V̇CO2 data were averaged for each 20-s period of exercise. Using plots of V̇O2 versus V̇CO2, two independent blinded researchers determined the first point of V̇CO2 to depart from linearity. The average corresponding V̇O2 was designated the GET. In the event of a >200 mL discrepancy, the average V̇O2 was calculated including a third researcher’s evaluation.
Subject characteristics, variables at the GET, and peak exercise variables were analyzed using independent samples t-tests. Ratings of perceived exertion during exercise were analyzed between groups using ANOVA with repeated measures for exercise intensity. Self-reported fatigue (23) collected at the time of entry into the VA NJ Center for Environmental Hazards Research was entered as a covariate to determine the influence of general fatigue on RPE. On average, this occurred within 6 months of study participation, except for five of the CFS patients where collection occurred more than 1 yr before the exercise test. However, it should be pointed out these subjects were all continuing Center participants and all subjects were reevaluated the day before participation to ensure that CFS patients continued to meet case criteria and that controls were still in good health. The data sets for both groups were complete for the first six submaximal intensities (i.e., 0–150 W), as most subjects could not continue exercise above this intensity. Therefore, the repeated measures analyses for absolute exercise intensities represent values up to 150 W. For relative exercise intensities, RPE were available for both groups at 40%, 50%, 60%, 70%, 80%, and 100% of peak exercise intensity. Therefore, the repeated measures analysis was conducted on these six intensities. Independent samples t-tests with Bonferroni corrections were used to determine differences in the event of a significant interaction term. Given the relatively small number of female veteran participants, sex comparisons could not be made. However, analyses done with and without the female subjects included in the data sets did not change the results. Thus, we chose to include the three females from each group in all analyses. Power functions for each subjects’ complete exercise test were determined by linear regression of log transformed (log10) perceived exertion versus log transformed exercise intensity. According to Borg’s modification of Steven’s power law [R = a + c(S − b)n], a resting value was determined for each subject based on their RPE during warm-up and this value was used as the constant “a” in determining the power function [R − a = c(S)n]. One sample t-tests were performed to examine whether the exponents were significantly different than a linear value of 1. Independent samples t-tests were used to examine group differences in the regression derived exponents. Pearson correlations were used to examine the relationship between RPE and select exercise variables.
Demographic information can be seen in Table 1. GV with CFS did not differ from the healthy GV in age, height, weight, or regular physical activity (physical activity total: GV CFS = 7.5 ± 2.4 vs GV control = 7.3 ± 2.1, P = 0.87).
Gas exchange threshold.
Select variables measured at the GET can be seen in Table 2. Subjects with CFS rated the exercise as more effortful than their respective controls (GV:P = 0.002). There were no significant differences in oxygen consumption at the GET; however, GV with CFS were exercising at a significantly higher percent of peak oxygen consumption than healthy GV controls (P = 0.04).
Perceived exertion during exercise.
Ratings of perceived exertion at selected absolute exercise intensities are presented in Figure 1a. The data are limited to 0–150 W of cycling exercise, which represents the intensities that all subjects in our sample were able to complete. ANOVA revealed significant main effects for group [F (1,32) = 16.4, P < 0.001] and exercise intensity [F (5,160) = 173.7, P < 0.001], as well as a group × exercise intensity interaction [F (5,160) = 3.0, P = 0.01]. Figure 1a illustrates that RPE increased as a function of increasing exercise intensity for both groups; however, GV with CFS reported higher RPE. Post hoc analysis revealed that CFS patient’s reported significantly higher RPE at each absolute exercise intensity (P < 0.008). Covariate analysis with the general fatigue score from the multidimensional fatigue inventory (MFI) entered into the model eliminated both the group main effect [F (1,31) = 0.1, P = 0.7] and the group × exercise intensity interaction [F (5,155) = 0.1, P = 0.9].
Log transformed plots of RPE and W can be seen in Figure 2a. The average exponents, based on the data from each individuals complete exercise test, were 1.0 ± 0.2 and 1.0 ± 0.1 for the CFS and healthy control groups, respectively. There was no significant group difference, and the exponents were not significantly different than a linear value of one.
Ratings of perceived exertion at relative exercise intensities are presented in Figure 1b. RPE data for our sample were complete for 40%, 50%, 60%, 70%, 80%, and 100% of peak oxygen consumption. ANOVA revealed significant main effects for group [F (1,32) = 7.2, P = 0.01] and exercise intensity [F (5,160) = 290.9, P < 0.001], but no interaction [F (5,160) = 1.07, P = 0.38]. When the data were expressed relative to peak oxygen consumption, GV with CFS reported exercise as more effortful than healthy GV controls (Fig. 1b). Covariate analysis with the general fatigue score from the MFI entered into the model eliminated the group main effect [F (1,31) = 3.5, P = 0.07].
Log-transformed plots of RPE and percent peak oxygen consumption can be seen in Figure 2b. The average exponents, based on data from each individuals complete exercise test, were 1.6 ± 0.3 and 1.6 ± 0.3 for the CFS and healthy control groups, respectively. There was no significant group difference and both exponents were significantly greater than a linear value of one (P < 0.02).
Peak data and correlations.
Peak exercise variables can be seen in Table 3. GV with CFS had significantly lower peak V̇E (P = 0.013). There were no other significant differences in any of the peak exercise variables examined for the GV sample. There was no significant relationship between physical activity, as measured by the Baecke (1), and RPE during exercise in our GV sample.
The purpose of the present investigation was to examine RPE during exercise in GV with CFS. This study was an extension of our previous work (companion paper in this issue) involving civilians with CFS. Our aim was to further determine whether perceived exertion is altered in fatiguing illness by examining a unique and understudied CFS patient population. Consistent with our hypothesis, GV with CFS reported greater RPE at absolute exercise intensities compared with healthy GV controls. Contrary to our hypothesis, when the data were expressed relative to peak oxygen consumption, differences in RPE remained significantly elevated for GV with CFS. Further, the group differences were eliminated when we controlled for self-reported fatigue, suggesting that symptoms of CFS in GV are important in determining perceived effort during exercise.
We are not aware of any research that has examined perceived exertion in GV with CFS. Based on our results, RPE are elevated during maximal cycle ergometry whether expressed in terms of either absolute work or relative physiological reference criteria. The differences cannot be explained by cardiovascular fitness, exercise capacity, or physical activity level. In fact, data from these same subjects (separate manuscript currently in review) indicated that cardiorespiratory responses to exercise were in fact normal in GV with CFS and were not different from healthy GV controls. A normal metabolic response to exercise further suggests that fatigue associated with CFS in GV is an important determinant underlying the differences in perceived exertion observed in the present investigation.
Determination of psychophysical power functions for both groups indicated that when resting exertion is accounted for in the psychophysical model both groups had a linear increase (exponent = 1.0) in exertion as a function of absolute power output and a positively accelerating increase (exponent = 1.6) when expressed relative to peak oxygen consumption. These values are in agreement with previous values obtained for RPE during cycling exercise in healthy populations (4). This indicates that GV with CFS rated greater effort at each level of exercise but the rate of increase was similar compared with controls. Moreover, it indicates that both groups were using the CR-10 scale in a linear fashion when the data were expressed as a function of absolute W and in a curvilinear fashion when expressed as a function of relative exercise intensity. The exact reasons why we saw differences in scaling characteristics are not apparent; however, the lower values obtained for absolute W may be a result of the small increments (30 W) in exercise intensity and short exercise stages (1 min) used during the cycle test. Comparable results have been obtained by Borg (5), reporting exponents that averaged 1.2 for healthy men using a similar cycle ergometry protocol and expressing the data as a function of absolute W. Finally, the group differences in RPE were apparent only when fatigue was not accounted for, a different finding compared with our previous work with CFS in civilians’ where self-reported fatigue failed to account for differences in exertion.
GV with CFS exhibited an elevated RPE at the GET compared with GV controls, a result also found in our studies of civilians with CFS (part 1 of this series and 21). The differences observed in our sample may have been a function of exercise intensity. GV with CFS were exercising at a greater percentage of their peak aerobic power compared to GV controls. However, this difference should be viewed with caution. The 6% difference observed in the GV sample equated to less than 1 mL·kg−1·min−1, a value that is within the range of error of the metabolic testing system. It is more likely, that the results at the GET reflect the higher RPE observed at the relative exercise intensities (40–80% and 100%).
There are several potential explanations for the different results obtained for the GV in the present investigation versus our previous work in civilians. An obvious explanation is the difference in mode of exercise used in the two studies. Cycle ergometry, as employed in the GV sample, produces a much greater peripheral signal from the active musculature than treadmill exercise (6,9,19). It is possible that cycle ergometry produced a greater peripheral signal, and therefore a greater perceptual signal, in GV with CFS versus healthy GV. If this were the case, RPE would be greater in CFS during cycling even when expressed relative to peak exercise capacity. Most studies examining perceived exertion in CFS have used a maximal treadmill test (12,21,22). Future research examining differentiated ratings versus global ratings of exertion in CFS during cycle ergometry may help to address this question. Sex differences in CFS could also account for the RPE differences observed. To our knowledge, sex differences for RPE in CFS have not been addressed. However, sex differences in perceived exertion have been documented in healthy civilian groups. Cook et al. (8), using cycle ergometry, reported that women rated exercise as more effortful at absolute exercise intensities. However, women rated the exercise as less effortful when the data were expressed relative to peak power output. To generalize these results to groups with CFS requires a direct comparison between men and women with CFS. Finally, GV who have experienced numerous stressors associated with service during the Gulf War may represent a unique group of CFS sufferers. Therefore, at the present time, our findings must be limited to GV with CFS.
In summary, GV with CFS reported greater perceived exertion at both absolute and relative exercise intensities during graded cycle ergometry. These differences were eliminated when symptoms of fatigue were accounted for, suggesting that fatigue associated with having CFS influences the perception of exertion during exercise. The results indicate that GV with CFS are unique compared with their civilian counterparts. Future investigations directly comparing GV and civilians with CFS, including both male and female patients, and directly assessing the influence of preexercise symptoms of fatigue on RPE will be important toward assessing differences in perceived exertion, as well as determining to what degree perceived exertion can be used in designing and monitoring exercise programs for these patients.
The authors wish to thank Theresa Policastro and Pamela Flippin for their assistance in subject recruitment, data collection, and the preparation of this manuscript.
This work was supported by NIH Center grant no. U01 AI-32246 and the DVA NJ Center for Environmental Hazards Research no. 561-003.
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