Aerobic capacity of Gulf War veterans with chronic fatigue syndrome

Military Medicine, Sep 2003 by Nagelkirk, Paul R, Cook, Dane B, Peckerman, Arnold, Kesil, William, Et al

A large overlap exists between the diagnosis of chronic fatigue syndrome (CFS) and the unexplained symptoms reported by many Gulf War veterans (GV). Previous investigations have reported reduced aerobic capacity in civilians with CFS. The present investigation examined metabolic responses to maximal exercise in GVs with CFS compared with healthy GVs. Cardiorespiratory and metabolic responses were recorded during a maximal exercise test on a cycle ergometer. The groups were not different in any demographic category (p > 0.05) or self-reported physical activity (p > 0.05). No differences were observed between groups for maximal oxygen uptake (28.9 or - 6.7 mL/kg/min for CFS vs. 30.8 or - 7.1 mL/kg/min for controls; p = 0.39), heart rate (155.8 or - 16.1 bpm for CFS vs. 163.3 or - 14.9 bpm for controls; p = 0.17), exercise time (9.6 or - 1.5 minutes for CFS vs. 10.2 or - 1.4 minutes for controls; p = 0.26), or workload achieved (208 or - 36.7 W for CFS vs. 224 or - 42.9 W for controls; p = 0.25). Likewise, no differences were observed at submaximal intensities (p > 0.05). Compared with healthy controls, GVs who report multiple medically unexplained symptoms and meet criteria for CFS do not show a decreased exercise capacity. Thus, it does not appear that the pathology of the GVs with CFS includes a deficiency with mobilizing the cardiopulmonary system for strenuous physical effort.

Introduction

Following the Persian Gulf War, many soldiers began reporting nonspecific symptoms that have no medical explanation. These symptoms in Gulf War veterans (GVs) occur twice as frequently as in soldiers who were not deployed to the Gulf.13 The wide diversity of the reported symptoms, collectively referred to as "Gulf War Illnesses," have made these complaints extremely difficult to study. To date, no unique syndrome has been conclusively identified and a widely accepted case definition does not exist.

Many theories regarding the underlying pathology of Gulf War Illnesses could manifest themselves as a reduction in exercise capacity. Toxic exposure could have produced a pathophysiological process that might affect metabolic function of cardiac or skeletal muscle.4 Previous work in our laboratory suggests that GVs with unexplained fatigue may exhibit abnormalities of the central nervous system as well as peripheral defects such as immune and cardiovascular dysfunction. Zhang et al.5 observed a general tendency toward up-regulation of markers of immune function in GVs with fatiguing illness compared with healthy veterans. Peckerman et al.6 reported that GVs with unexplained symptoms demonstrated elevated tactile thresholds, possibly related to a subtle neurological deficit. More recently, our group reported diminished blood pressure (BP) responses to cognitive Stressors such as speech presentation and mental arithmetic in GVs with chronic fatigue,7 suggesting dysfunction of central regulatory mechanisms. When metabolic and/or cardiovascular abnormalities exist, cardiorespiratory responses to exercise may be altered, thus limiting one's ability to perform at increasingly higher physical intensities.

No case definition in support of a "Gulf War Syndrome" has been identified; however, many of the symptoms associated with Gulf War Illnesses are also part of the complex of symptoms known as chronic fatigue syndrome (CFS). To strengthen the design of our study, we chose to investigate a well-defined subset of this GV population, specifically GVs diagnosed with CFS. CFS is defined as a minimum of 6 months of fatigue, which is severe enough to produce a substantial decrease in activity and is accompanied by four or more of the following symptoms: impaired memory or concentration, sore throat, tender lymph nodes, muscle and/or multijoint pain, headaches, unrefreshing sleep, and postexertional malaise.8 It is estimated that as much as 20% of the symptoms reported by GVs are unexplained.1,2,9 Additionally, Kipen et al.10 estimate that 15.7% of GVs who volunteered for the Veterans Affairs Gulf War Registry, a comprehensive medical evaluation offered to all GVs, meet case definition criteria for CFS. One advantage to studying only those GVs who meet criteria for CFS is that doing so may reduce the heterogeneity that has complicated research of Gulf War Illnesses.

There is a second advantage of only studying GVs who meet the criteria for CFS. Since they are syndromically the same as nonveterans, one can apply the state of knowledge gleaned from nonveteran studies to them. Current literature contains little information regarding the exercise ability of GVs suffering from unexplained symptoms. There is, however, a growing body of evidence describing aerobic capacity in civilian CFS populations. Since our GV sample meets the case definition criteria for CFS, we can compare and contrast our results with data from previous studies of civilian CFS patients.

Studies examining the ability of civilian CFS patients to perform maximal exercise have produced mixed results due to potential selection bias, lack of control for routine physical activity levels, and differences in exercise protocols. Some have described the aerobic capacities of civilian CFS patients as being in the "low normal" range,11,12 whereas others report a reduced aerobic capacity relative to healthy individuals.13-16 The present study attempted to improve on the design of previous civilian studies by controlling for variables that may have rendered some of these conclusions suspect.

The purpose of the present investigation was to examine respiratory and cardiovascular responses to maximal exercise in GVs with CFS compared with healthy GVs. We used an incremental exercise testing protocol on a cycle ergometer to evaluate the peak exercise capacity of GVs with unexplained symptoms and meeting case definition criteria for CFS. These results were compared with the exercise responses of a group of apparently healthy GVs of the same age, gender, regular physical activity, and military deployment status.

Methods

Subjects

Prospective subjects were mailed a health survey package, including a screening questionnaire designed to identify GVs with and without CFS who would be suitable for participation. Veterans meeting eligibility criteria and willing to participate were brought to the East Orange, New Jersey Veterans Affairs Medical Center for more thorough medical evaluation by a physician trained in the diagnosis of CFS.17 On-site evaluation included a medical history and physical examination and standard laboratory blood tests to rule out common medical causes of fatigue.18 The Quick Diagnostic Interview Schedule,19 a computerized interview, was used to diagnose axis I psychiatric disorders (i.e., all psychiatric diagnoses excluding personality disorder and mental retardation). A diagnosis of CFS was given if the subject met the current CDC case definition.8 Subjects with medical or psychiatric explanations for their fatigue were excluded from participation.