Exercise and sleep deprivation do not change cytokine expression levels in patients with chronic fatigue syndrome.

A major hypothesis regarding the cause of chronic fatigue syndrome (CFS) is immune dysregulation, thought to be reflected in upregulated proinflammatory cytokines leading to the symptoms that are characteristic of this illness. Because the symptoms worsen with physical exertion or sleep loss, we hypothesized that we could use these stressors to magnify the underlying potential pathogenic abnormalities in the cytokine systems of people with CFS. We conducted repeat blood sampling for cytokine levels from healthy subjects and CFS patients during both postexercise and total sleep deprivation nights and assayed for protein levels in the blood samples, mRNA activity in peripheral blood lymphocytes (PBLs), and function in resting and stimulated PBLs. We found that these environmental manipulations did not produce clinically significant upregulation of proinflammatory cytokines. These data do not support an important role of immune dysregulation in the genesis of stress-induced worsening of CFS.

Respiratory and Cardiovascular Response during Electronic Control Device Exposure in Law Enforcement Trainees.

OBJECTIVE: Law enforcement represents a large population of workers who may be exposed to electronic control devices (ECDs). Little is known about the potential effect of exposure to these devices on respiration or cardiovascular response during current discharge. METHODS: Participants (N = 23) were trainees exposed to 5 s of an ECD (Taser X26(®)) as a component of training. Trainees were asked to volitionally inhale during exposure. Respiratory recordings involved a continuous waveform recorded throughout the session including during the exposure period. Heart rate was calculated from a continuous pulse oximetry recording. RESULTS: The exposure period resulted in the cessation of normal breathing patterns in all participants and in particular a decrease in inspiratory activity. No significant changes in heart rate during ECD exposure were found. CONCLUSION: This is the first study to examine breathing patterns during ECD exposure with the resolution to detect changes over this discrete period of time. In contrast to reports suggesting respiration is unaffected by ECDs, present evidence suggests that voluntary inspiration is severely compromised. There is no evidence of cardiac disruption during ECD exposure.

Historical perspectives on the control of breathing.

Among the several topics included in respiratory studies investigators have focused on the control of breathing for a relatively few number of years, perhaps only the last 75 to 80. For a very long time, the phenomenon of respiration presented a great mystery. The Chinese had suggestions for proper breathing, and later the Egyptians sought to understand its purpose. But in the western world, the early Greeks made the more significant observations. Centuries passed before the anatomical structures pertinent to respiration were properly visualized and located. There followed efforts to understand if lung movement was necessary for life and what happened in the lung. The rise of chemistry in the 18th century eventually clarified the roles of the gases significant in respiratory behavior. More time was needed to understand what gases provoked increases in breathing and where those gases worked. At this point, control of breathing became a significant focus of respiratory investigators. Studies included identifying the structures and functions of central and peripheral chemoreceptors, and airway receptors, sources of respiratory rhythm and pattern generation, the impact of the organism's status on its breathing including environment and disease/trauma. At this same time, mid- to late-20th century, efforts to mathematicize the variables in the control of breathing appeared. So though wonderment about the mysterious phenomenon of respiration began over two millennia ago, serious physiological investigation into its control is by comparison very young.

Obstructive sleep apnea, metabolic syndrome, and age: will geriatricians be caught asleep on the job?

Obstructive sleep apnea (OSA) is increasingly recognized in older persons as an important cause of morbidity and mortality, resulting in cardiovascular disease, cognitive dysfunction, and disturbed sleep. It has been cited as an independent risk factor for the metabolic syndrome (MS). The elevated levels of cytokines, such as interleukin-6 and tumor necrosis factor-alpha, which also increase with age, are a common feature of both OSA and MS. Intermittent hypoxia caused by the recurring episodes of apnea and near-apnea in OSA is a major cause of its systemic effects. Mathematical models of OSA show how obesity and anatomic changes in the upper airways, which may be age-related, interact with the networks responsible for the chemical and neural control of breathing to cause the recurrent intermittent hypoxia of sleep apnea. Treatment of OSA with continuous positive airway pressure improves some aspects of the metabolic syndrome, reduces cardiovascular morbidity, and improves domains of cognitive function. OSA is more difficult to identify in the elderly because many of its symptoms can be caused by other disorders which are common in the elderly. Clinicians who encounter OSA may be advised to search for the presence of MS, and vice versa.

Paradoxical potentiation of exercise hyperpnea in congestive heart failure contradicts Sherrington chemoreflex model and supports a respiratory optimization model.

Congestive heart failure (CHF) patients suffer decreased exercise tolerance, yet they demonstrate an augmented ventilatory response to exercise such that P(aCO2) remains normal (isocapnic) from rest to maximal exercise in the face of increased pulmonary dead space (Fig. 1). On the other hand, the effect of a large external dead space is hypercapnic instead of isocapnic. This discrepancy suggests that external dead space and pulmonary dead space may exert distinct influences on control of breathing. These paradoxical clinical phenomena are at variance with the conventional chemoreflex model (Johnson 2001), but appear to be consistent with the predictions of the optimization model (Poon 2001; Poon, Tin et al. 2007).

Cardiovascular evaluation of electronic control device exposure in law enforcement trainees: a multisite study.

OBJECTIVE: Occupational health risk with regard to training exercises is a relatively under studied domain for law enforcement officers. One potential health risk is exposure to electronic control devices (ECDs). METHODS: Seven different training facilities in six states participated. Law enforcement trainees (N = 118) were exposed to Taser International's (Scottsdale, AZ) X26 for up to 5 seconds. RESULTS: There was no evidence of cardiac or skeletal muscle breakdown. Exposure did not adversely affect electrocardiogram (ECG) morphology obtained 24 hours after exposure in 99 trainees. For two trainees with preexisting ECG abnormalities, ECG morphology differed in the post-ECD samples. CONCLUSIONS: The results from this large, multisite study suggest that, for most trainees, ECD exposure does not represent a significant health risk. Further investigation is warranted for cardiac vulnerability and potential interactions with ECD exposure.

Cytokines across the night in chronic fatigue syndrome with and without fibromyalgia.

The symptoms of chronic fatigue syndrome (CFS) are consistent with cytokine dysregulation. This has led to the hypothesis of immune dysregulation as the cause of this illness. To further test this hypothesis, we did repeated blood sampling for cytokines while patients and matched healthy controls slept in the sleep lab. Because no one method for assaying cytokines is acknowledged to be better than another, we assayed for protein in serum, message in peripheral blood lymphocytes (PBLs), and function in resting and stimulated PBLs. We found no evidence of proinflammatory cytokine upregulation. Instead, in line with some of our earlier studies, we did find some evidence to support a role for an increase in interleukin-10, an anti-inflammatory cytokine. Although the changes were small, they may contribute to the common complaint in CFS patients of disrupted sleep.

Sleep is not disrupted by exercise in patients with chronic fatigue syndromes.

PURPOSE: Patients with chronic fatigue syndrome (CFS) report that exertion produces dramatic symptom worsening. We hypothesized this might be due to the exacerbation of an underlying sleep disorder, which we have previously demonstrated to exist. METHODS: Female patients with CFS and matched healthy controls with no evidence of major depressive disorder were studied with overnight polysomnography on a baseline night and on a night after their performance of a maximal exercise test. RESULTS: CFS patients as a group had evidence for disturbed sleep compared with controls. Although exercise improved sleep for healthy subjects, it did not do this for the group as a whole. When we stratified the sample on the basis of self-reported sleepiness after a night's sleep, the patient group with reduced morning sleepiness showed improvement in sleep structure, whereas those with increased morning sleepiness continued to show evidence for sleep disruption. CONCLUSIONS: Sleep is disturbed in CFS patients as a group, but exercise does not exacerbate this sleep disturbance. Approximately half the patients studied actually sleep better after exercise. Therefore, activity-related symptom worsening is not caused by worsened sleep.

Sleep structure and sleepiness in chronic fatigue syndrome with or without coexisting fibromyalgia.

INTRODUCTION: We evaluated polysomnograms of chronic fatigue syndrome (CFS) patients with and without fibromyalgia to determine whether patients in either group had elevated rates of sleep-disturbed breathing (obstructive sleep apnea or upper airway resistance syndrome) or periodic leg movement disorder. We also determined whether feelings of unrefreshing sleep were associated with differences in sleep architecture from normal. METHODS: We compared sleep structures and subjective scores on visual analog scales for sleepiness and fatigue in CFS patients with or without coexisting fibromyalgia (n = 12 and 14, respectively) with 26 healthy subjects. None had current major depressive disorder, and all were studied at the same menstrual phase. RESULTS: CFS patients had significant differences in polysomnograpic findings from healthy controls and felt sleepier and more fatigued than controls after a night's sleep. CFS patients as a group had less total sleep time, lower sleep efficiency, and less rapid eye movement sleep than controls. A possible explanation for the unrefreshing quality of sleep in CFS patients was revealed by stratification of patients into those who reported more or less sleepiness after a night's sleep (a.m. sleepier or a.m. less sleepy, respectively). Those in the sleepier group reported that sleep did not improve their symptoms and had poorer sleep efficiencies and shorter runs of sleep than both controls and patients in the less sleepy group; patients in the less sleepy group reported reduced fatigue and pain after sleep and had relatively normal sleep structures. This difference in sleep effects was due primarily to a decrease in the length of periods of uninterrupted sleep in the a.m. sleepier group. CONCLUSION: CFS patients had significant differences in polysomnographic findings from healthy controls and felt sleepier and more fatigued than controls after a night's sleep. This difference was due neither to diagnosable sleep disorders nor to coexisting fibromyalgia but primarily to a decrease in the length of periods of uninterrupted sleep in the patients with more sleepiness in the morning than on the night before. This sleep disruption may explain the overwhelming fatigue, report of unrefreshing sleep, and pain in this subgroup of patients.

Dyspnea and symptom amplification in asthma.

BACKGROUND: The severity of a patient's asthma and the intensity with which he describes his dyspnea do not correlate. OBJECTIVES: There is an indirect relationship between airway function in asthma and the intensity of dyspnea; this relationship is found only when the measure of a patient's general tendency to exaggerate the intensity of any somatic symptom is considered simultaneously. METHODS: Lung function, including spirometry (forced expiratory volume in 1 s, FEV(1)) and plethysmography (airway resistance, R(aw)), dyspnea (Borg scale score) and the tendency to exaggerate (the somatosensory amplification scale score, SSAS) have been quantified in 42 stable asthmatic patients. RESULTS: There was no correlation between the Borg score and any spirometric or plethysmographic measure in these subjects. By contrast, there was a moderate correlation between the Borg score and the SSAS (r = 0.36, p = 0.03). However, when FEV(1) or R(aw) (abscissa) and Borg scores (ordinate) were converted to residuals, there was a moderate correlation between the residuals and the SSAS score (for FEV(1), r = 0.33 and p = 0.05; for R(aw), r = -0.36 and p = 0.03). CONCLUSION: A physician may make a reasonable estimate of an asthmatic patient's lung function from the intensity of his complaint only if he - the physician - considers the patient's tendency to symptom amplify as well.

Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome.

CONTEXT: Patients with chronic fatigue syndrome and those with orthostatic intolerance share many symptoms, yet questions exist as to whether CFS patients have physiological evidence of orthostatic intolerance. OBJECTIVE: To determine if some CFS patients have increased rates of orthostatic hypotension, hypertension, tachycardia, or hypocapnia relative to age-matched controls. DESIGN: Assess blood pressure, heart rate, respiratory rate, end tidal CO2 and visual analog scales for orthostatic symptoms when supine and when standing for 8 minutes without moving legs. SETTING: Referral practice and research center. PARTICIPANTS: 60 women and 15 men with CFS and 36 women and 4 men serving as age matched controls with analyses confined to 62 patients and 35 controls showing either normal orthostatic testing or a physiological abnormal test. MAIN OUTCOME MEASURES: Orthostatic tachycardia; orthostatic hypotension; orthostatic hypertension; orthostatic hypocapnia or combinations thereof. RESULTS: CFS patients had higher rates of abnormal tests than controls (53% vs 20%, p < .002), but rates of orthostatic tachycardia, orthostatic hypotension, and orthostatic hypertension did not differ significantly between patients and controls (11.3% vs 5.7%, 6.5% vs 2.9%, 19.4% vs 11.4%, respectively). In contrast, rates of orthostatic hypocapnia were significantly higher in CFS than in controls (20.6% vs 2.9%, p < .02). This CFS group reported significantly more feelings of illness and shortness of breath than either controls or CFS patients with normal physiological tests. CONCLUSION: A substantial number of CFS patients have orthostatic intolerance in the form of orthostatic hypocapnia. This allows subgrouping of patients with CFS and thus reduces patient pool heterogeneity engendered by use of a clinical case definition.

Electroencephalogram characteristics of autonomic arousals during sleep in healthy men.

OBJECTIVE: Many sleep disorders involve frequent, brief arousals, not appreciated during conventional sleep stage scoring due to lack of electroencephalogram (EEG) desynchronization. We evaluated the temporal relation between heart rate (HR) changes, an index of autonomic activation, and EEG in seven healthy subjects during sleep. METHODS: We identified bouts of tachycardia-bradycardia and performed spectral analysis of EEG during these. We also identified cortical arousals by the appearance of EEG alpha activity. This allowed us to dichotomize bouts of tachycardia-bradycardia by presence or absence of cortical arousal. RESULTS: During non-rapid eye movement (REM) sleep, bouts with or without cortical arousal occurred with approximately equal frequency. Those with cortical arousals usually preceded onset of EEG changes. Those without cortical arousals were followed by increases in delta but not alpha power. EEG did not change during bouts in REM sleep. CONCLUSIONS: Capturing bouts of tachycardia-bradycardia is relatively easy via computerized algorithm. Bouts occur with cortical arousal or with slow wave synchronization suggestive of subcortical arousal. Thus, changes in HR may be useful index of arousal. SIGNIFICANCE: These brief bursts of tachycardia-bradycardia are consistent with autonomic arousal. Such a measure may be among the first in a continuum of arousal ending with frank awakening.