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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. [ABSTRACT FROM AUTHOR]

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.

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.

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., (© 2012 American Physiological Society. Compr Physiol 2:933-996, 2012.)

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.

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.

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.

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).

We examined the effect of arousals (shifts from sleep to wakefulness) on breathing during sleep using a mathematical model. The model consisted of a description of the fluid dynamics and mechanical properties of the upper airways and lungs, as well as a controller sensitive to arterial and brain changes in CO(2), changes in arterial oxygen, and a neural input, alertness. The body was divided into multiple gas store compartments connected by the circulation. Cardiac output was constant, and cerebral blood flows were sensitive to changes in O(2) and CO(2) levels. Arousal was considered to occur instantaneously when afferent respiratory chemical and neural stimulation reached a threshold value, while sleep occurred when stimulation fell below that value. In the case of rigid and nearly incompressible upper airways, lowering arousal threshold decreased the stability of breathing and led to the occurrence of repeated apnoeas. In more compressible upper airways, to maintain stability, increasing arousal thresholds and decreasing elasticity were linked approximately linearly, until at low elastances arousal thresholds had no effect on stability. Increased controller gain promoted instability. The architecture of apnoeas during unstable sleep changed with the arousal threshold and decreases in elasticity. With rigid airways, apnoeas were central. With lower elastances, apnoeas were mixed even with higher arousal thresholds. With very low elastances and still higher arousal thresholds, sleep consisted totally of obstructed apnoeas. Cycle lengths shortened as the sleep architecture changed from mixed apnoeas to total obstruction. Deeper sleep also tended to promote instability by increasing plant gain. These instabilities could be countered by arousal threshold increases which were tied to deeper sleep or accumulated aroused time, or by decreased controller gains.

Increased loop gain (a function of both controller gain and plant gain), which results in instability in feedback control, is of major importance in producing recurrent central apnoeas during sleep but its role in causing obstructive apnoeas is not clear. The purpose of this study was to investigate the role of loop gain in producing obstructive sleep apnoeas. Owing to the complexity of factors that may operate to produce obstruction during sleep, we used a mathematical model to sort them out. The model used was based on our previous model of neurochemical control of breathing, which included the effects of chemical stimuli and changes in alertness on respiratory pattern generator activity. To this we added a model of the upper airways that contained a narrowed section which behaved as a compressible elastic tube and was tethered during inspiration by the contraction of the upper airway dilator muscles. These muscles in the model, as in life, responded to changes in hypoxia, hypercapnia and alertness in a manner similar to the action of the chest wall muscles, opposing the compressive action caused by the negative intraluminal pressure generated during inspiration which was magnified by the Bernoulli Effect. As the velocity of inspiratory airflow increased, with sufficiently large increase in airflow velocity, obstruction occurred. Changes in breathing after sleep onset were simulated. The simulations showed that increases in controller gain caused the more rapid onset of obstructive apnoeas. Apnoea episodes were terminated by arousal. With a constant controller gain, as stiffness decreased, obstructed breaths appeared and periods of obstruction recurred longer after sleep onset before disappearing. Decreased controller gain produced, for example, by breathing oxygen eliminated the obstructive apnoeas resulting from moderate reductions in constricted segment stiffness. This became less effective as stiffness was reduced more. Contraction of the upper airway muscles with hypercapnia and hypoxia could prevent obstructed apnoeas with moderate but not with severe reductions in stiffness. Increases in controller gain, as might occur with hypoxia, converted obstructive to central apnoeas. Breathing CO2 eliminated apnoeas when the activity of the upper airway muscles was considered to change as a function of CO2 to some exponent. Low arousal thresholds and increased upper airway resistance are two factors that promoted the occurrence and persistence of obstructive sleep apnoeas.

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., (Copyright (c) 2008 S. Karger AG, Basel)

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.

The carotid body is essential to detecting levels of oxygen in the blood and initiating the compensatory response. Increasing evidence suggests that the purines ATP and adenosine make a key contribution to this signaling by the carotid body. The glomus cells release ATP in response to hypoxia. This released ATP can stimulate P2X receptors on the carotid body to elevate intracellular Ca(2+) and to produce an excitatory response. This released ATP can be dephosphorylated to adenosine by a series of extracellular enzymes, which in turn can stimulate A(1), A(2A) and A(2B) adenosine receptors. Levels of extracellular adenosine can also be altered by membrane transporters. Endogenous adenosine stimulates these receptors to increase the ventilation rate and may modulate the catecholamine release from the carotid sinus nerve. Prolonged hypoxic challenge can alter the expression of purinergic receptors, suggesting a role in the adaptation. This review discusses evidence for a key role of ATP and adenosine in the hypoxic response of the carotid body, and emphasizes areas of new contributions likely to be important in the future.

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.

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.

Previous investigations have demonstrated a subset of postural tachycardia syndrome (POTS) patients characterized by normal peripheral resistance and blood volume while supine but thoracic hypovolemia and splanchnic blood pooling while upright secondary to splanchnic hyperemia. Such "normal-flow" POTS patients often demonstrate hypocapnia during orthostatic stress. We studied 20 POTS patients (14-23 yr of age) and compared them with 10 comparably aged healthy volunteers. We measured changes in heart rate, blood pressure, heart rate and blood pressure variability, arm and leg strain-gauge occlusion plethysmography, respiratory impedance plethysmography calibrated against pneumotachography, end-tidal partial pressure of carbon dioxide (Pet(CO2)), and impedance plethysmographic indexes of blood volume and blood flow within the thoracic, splanchnic, pelvic (upper leg), and lower leg regional circulations while supine and during upright tilt to 70 degrees. Ten POTS patients demonstrated significant hyperventilation and hypocapnia (POTS(HC)) while 10 were normocapnic with minimal increase in postural ventilation, comparable to control. While relative splanchnic hypervolemia and hyperemia occurred in both POTS groups compared with controls, marked enhancement in peripheral vasoconstriction occurred only in POTS(HC) and was related to thoracic blood flow. Variability indexes suggested enhanced sympathetic activation in POTS(HC) compared with other subjects. The data suggest enhanced cardiac and peripheral sympathetic excitation in POTS(HC).

Periodic breathing is an unusual form of breathing with oscillations in minute ventilations and with repetitive apnoeas or near apnoeas. Reported initially in patients with heart failure or stroke, it was later recognized to occur especially during sleep. The recurrent hypoxia and surges of sympathetic activity that often occur during the apnoeas have serious health consequences. Mathematical models have helped greatly in the understanding of the causes of recurrent apnoeas. It is unlikely that every instance of periodic breathing has the same cause, but many result from instability in the feedback control involved in the chemical regulation of breathing caused by increased controller and plant gains and delays in information transfer. Even when it is not the main cause of the periodic breathing, unstable control modifies the ventilatory pattern and sometimes intensifies the recurrent apnoeas. The characteristics of disturbances to breathing and their interaction with the control system can be critical in determining ventilation responses and the occurrence of periodic breathing. Large abrupt changes in ventilation produced, for example, in the transition from waking to sleep and vice versa, or in the transition from breathing to apnoea, are potent factors causing periodic breathing. Mathematical models show that periodic breathing is a 'systems disorder' produced by the interplay of multiple factors. Multiple factors contribute to the occurrence of periodic breathing in congestive heart failure and cerebrovascular disease, increasing treatment options.

We have adapted two models previously proposed as respiratory pattern generators (RPGs) into a neurochemical feed back control model of ventilation. The RPG models, non-dimensional as originally presented, consisted of oscillating circuits of either two or five interconnected neurons [Matsugu, M., Duffin, J., Poon, C.-S., 1998. Entrainment, instability, quasi-periodicity, and chaos in a compound neural oscillator. J. Comput. Neurosci. 5, 35-51; Botros, S.M., Bruce, E.N., 1990. Neural network implementation of a three-phase model of respiratory rhythm generation. Biol. Cybern. 63, 143-153]. The neurochemical model into which they were integrated [Longobardo, G., Evangelisti, C.J., Cherniack, N.S., 2002. Effects of neural drives on breathing in the awake state in humans. Respir. Physiol. 129, 317-333] included the effects of cerebral blood flow variation with CO2, vagal stretch receptors input and a multicompartment model of carbon dioxide stores. The methodology is described whereby these neuronal oscillator networks were quantified, a necessary step for their inclusion as RPGs in broader models of the overall control of respiration. Subsequent simulations of the ventilation response to carbon dioxide with either respiratory pattern generator model exhibited only a limited range in which tidal volume and frequency increased with increasing respiratory drive. With both models, frequency peaked and then declined, as did ventilation when P CO2 was greater than normal. The range of the models was extended if the respiratory pattern generators were considered to be composed of multiple neuronal oscillators or a single oscillator in which there was increasing phasic input that was gated or pacemaker driven.

Cheyne-Stokes respiration (CSR) is one of several types of unusual breathing with recurrent apneas (dysrhythmias). Reported initially in patients with heart failure or stroke, it was then recognized both in other diseases and as a component of the sleep apnea syndrome. CSR is potentiated and perpetuated by changing states of arousal that occur during sleep. The recurrent hypoxia and surges of sympathetic activity that often occur during the apneas may have serious health consequences. Heart failure and stroke are risk factors for sleep apnea. The recurrent apneas and intermittent hypoxia occurring with sleep apnea further damage the heart and brain. Although all breathing dysrhythmias do not have the same cause, instability in the feedback control involved in the chemical regulation of breathing is the leading cause of CSR. Mathematical models have helped greatly in the understanding of the causes of recurrent apneas.

Objectives: To test the hypothesis that patients with well-documented diastolic dysfunction (DD) in the setting of normal systolic function will have inspiratory muscle weakness when compared to normal control subjects, and will experience dyspnea and tachypnea during exercise., Background: Respiratory muscle weakness has been described in patients with (systolic) congestive heart failure; however, whether or not patients with DD may present with the findings of congestive heart failure is not known., Methods: We selected for study 14 patients with DD previously referred for cardiopulmonary evaluation whose diagnosis had been confirmed by data obtained at cardiac catheterization. Seven control subjects matched for age, sex, and weight were recruited from the hospital community. Subjects performed both basic pulmonary function tests and tests of muscle strength: handgrip strength (Hgr), and maximal subatmospheric static inspiratory muscle pressure (Pimax). Subjects then performed a graded exercise test on a bicycle ergometer. Minute ventilation, oxygen consumption, carbon dioxide production, and heart rate were monitored continuously. Echocardiography was performed three times: before exercise, at a selected submaximal exercise level (20% of a predicted maximal workload), and at maximal exercise. Subjects rated their degree of dyspnea using the Borg scale at the same three time intervals., Results: Pimax was - 102 +/- 17 cm H(2)O in control subjects, and - 77 +/- 19 cm H(2)O in patients with DD (p = 0.013) [mean +/- SD]. Hgr was similar between the groups. At the selected submaximal exercise level, patients with DD rated dyspnea to be 2.6 +/- 2.2 Borg scale units (control subjects, 0.5 +/- 0.8 Borg scale units). Hey plots described a rapid, shallow breathing pattern in patients with DD during exercise. Patients with DD and control subjects achieved similar maximal work loads., Conclusion: Patients with DD have diminished Pimax, adopt a rapid, shallow breathing pattern during exercise, and experience dyspnea at low work loads when compared to matched control subjects.

Our concepts of oxygen sensing have been transformed over the years. We now appreciate that oxygen sensing is not a unique property limited to "chemoreceptors" but is a common property of tissues and that responses to changes in oxygen levels are not static but can change over time. Respiratory responses initiated at the carotid body are modified by the excitatory and depressant effects of hypoxia at the brain and on the pathways connecting the carotid body to the brain. Equally important is that we are beginning to use our understanding of the cellular and molecular pathways triggered by hypoxia and hyperoxia to identify therapeutic targets to treat diseases such as cancer. We also have a better understanding of the complexities of the human respiratory responses to hypoxia; however, major deficiencies remain in our ability to alter or even measure human ventilatory responses to oxygen deficiency.

We have developed a mathematical model of the regulation of ventilation that successfully simulates breathing in the awake as well as in sleeping states. In previous models, which were used to simulate Cheyne-Stokes breathing and respiration during sleep, the controller was only responsive to chemical stimuli, and allowed no ventilation at sub-normal carbon dioxide levels. The current model includes several new features. The chemical controller responds continuously to changes in P(CO(2)) with a lower sensitivity during hypocapnia than in the hypercapnic ranges. Hypoxia interacts multiplicatively with P(CO(2)) over the entire range of activity. The controller in the current model, besides the chemical drive, includes also a neural component. This neural drive increases and decreases as the level of alertness changes, and adds or subtracts from ventilation levels demanded by the chemical controller. The model also includes the effects of post-stimulus potentiation (PSP) and hypoxic ventilatory depression (HVD). While PSP eliminates apneas after a disturbance and also dampens the subsequent dynamics of the respiration, it is not a major factor in the damping of the response. Another finding is that HVD is destabilizing. The model is the first to reproduce results reported in conscious humans after hyperventilation and after acute and longer-term hypoxia. It also reproduces the effects of NREM sleep.

Background: Airway function, as assessed by standard spirometry, and the intensity of dyspnea reported by asthmatic patients correlate poorly., Objective: This study tests the following two hypotheses: (1) that measures of the tendency of a patient to somatize will reduce the variation in the report of dyspnea not explained by airway function; and (2) that plethysmography is a better tool with which to estimate the degree of dyspnea associated with asthma., Design: A prospective laboratory study carried out over one study session., Participants: Forty asthmatic subjects who had withheld bronchodilator (BD) therapy overnight., Interventions: We performed spirometry, plethysmography, and an assessment of dyspnea (ie, modified Borg scale) on all subjects before and after they received BD therapy. Standard questionnaires pertaining to psychological state and trait were administered as well., Results: The change in specific airway conductance with BD therapy correlated with a decline in the Borg score (r = 0.47; p = 0.007). By contrast, neither spirographic measures nor measures of static lung volumes correlated. Correlation with the Borg scale score was not improved by adding indexes of either somatization or psychological state or trait., Conclusion: The relief of dyspnea reported by patients with mild asthma after BD therapy is related to dilatation of the central airways.