Physiology Of Breathing Research Articles

Modern Methods for the Description of Complex Couplings in the Neurophysiology of Respiration

Breathing is a fundamental physiological process produced by movements generated and controlled by efferent signals from the nervous system. Improving our understanding of the mechanisms underlying breathing in humans is of particular interest. Another important practical issue is the design of noninvasive procedures for the diagnosis, prediction, and control of the respiratory system, which works as a subsystem embedded in the complex physiological environment of the human organism and its external environment. This paper provides a concise review of a selected set of modern techniques dedicated to the exploration of complex and varying systems and sets of time-series data. These methods are based on an 1D entropic tool (approximate and sample entropy, i.e., ApEn and SampEn, respectively), which is effective for assessing the regularity and complexity of information contained in data sets, as well as complex network theory, recurrence plot (RP) strategy, and the joint complex network-recurrence analysis mode. Exemplary results are given for real physiological data recorded in patients with symptoms of central sleep apnea syndrome. Although ApEn and SampEn are shown to be sensitive methods for the detection of pathological mechanisms affecting breathing patterns during sleep, qualitative and quantitative studies based on the RP strategy reveal even better efficiency for this task. In addition, the second mode of analysis enables multi-dimensional correlation of accessible data, which is important for studying the couplings between numerous physiological subsystems. Further work in this area is proposed to map the scheme of breathing physiology during sleep.

CT-Rhinometrie

Otorhinolaryngologists require new diagnostic methods to give further insight into the physiology of nasal breathing. The functional aspects of radiological data in the field of ENT have rarely been examined. This study compares computed tomography (CT) scan area measurements of the paranasal sinuses with physiological data from rhinomanometry. In a retrospective study, paranasal CT scans from 36 patients were analysed for volume, width and hydraulic diameter of the five key regions of the nasal cavity (CT rhinometry) and compared to the active anterior rhinomanometric (RMM) results representing the gold standard in nasal flow description. The highest correlation between the rhinomanometric results and CT rhinometry was found at the internal ostium, followed by the diffuser region. The structures important for regulating nasal flow could thus be identified in the CT area data. CT rhinometry revealed structures important for nasal breathing, in addition to providing anatomical and topographical data. CT rhinometry measured volumes, width and hydraulic diameters of the nasal cavity correlated with measurements of transnasal flow.

Editor's Introduction: Winter Issue 2012

The cover of this Winter 2012 issue of Biofeedback shows a woman in a biofeedback session, displaying a pulse oximeter on her left hand. An article in this issue, by Christopher Gilbert, PhD, introduces the use of the pulse oximeter in clinical biofeedback practice. Our thanks to the photographer, Eric Willmarth, PhD, and the model, Tonya Jackson, for this photograph.Fred Shaffer, Judy Crawford, and Donald Moss provide an article reviewing the expanded role of the Biofeedback Certification International Alliance (BCIA) in global biofeedback and neurofeedback certification. The BCIA mission is as follows: “BCIA certifies individuals who meet education and training standards in biofeedback and neurofeedback, and progressively recertifies those who advance their knowledge through continuing education.” The BCIA provides a number of supports for professional education, including a “blueprint of knowledge” describing essential knowledge in each certification area, guidelines for a mentoring process assuring that certified practitioners will possess a basic repertoire of skills, and an expanding number of webinars on topics in biofeedback and neurofeedback.Christopher Gilbert provides an article on the use of the pulse oximeter in breath training. A pulse oximeter measures the level of oxygen in the bloodstream, using a noninvasive and inexpensive sensor applied to the finger or earlobe. The oximeter uses photoplethysmography, which is an infrared sensor to measure oxygen saturation in the bloodstream, as well as current heart rate. Gilbert overviews the physiology of breathing and oxygen saturation, and describes how the oximeter can be used as an educational tool and as a safety measure.Richard Harvey, Erin Thorne, and Jourdan McPhetridge provide a report on a recent study of “dysponesis awareness training.” Dysponesis is a term first developed by George Whatmore and Daniel Kohli (1968) to describe unnecessary muscular effort that does not contribute functionally to a task. Whatmore and Kohli originally applied this concept to clinical patients suffering pathological pain. The Harvey et al. article utilizes healthy undergraduates and examines how biofeedback can be utilized to enhance awareness and control of misplaced muscle effort, and reduce inefficient muscle use.Leah Lagos, Thomas Bottiglieri, Bronya Vaschillo, and Evgeny Vaschillo provide an introduction to a new application area for heart rate variability (HRV) biofeedback—the treatment of postconcussion syndrome. They review the physiological dysfunction that typically follows a concussion, especially altered autonomic function and impairments in cerebral autoregulation. They examine the known therapeutic effects of HRV training and provide a physiological rationale for clinical trials applying HRV to postconcussion syndrome patients. Lagos and her colleagues will follow up in a future issue of Biofeedback with a case study of a patient with postconcussion syndrome with a positive therapeutic response to HRV training.Erik Peper, Dianne Schumay, and Donald Moss provide a discussion of the importance of a patient's illness beliefs or illness attributions in shaping that patient's willingness to pursue self-regulation oriented treatment programs. Patients who are strongly external in their locus of control and who believe that their illness is curable only by such external interventions as surgery or medication are less likely to undertake treatments based on skill acquisition, lifestyle change, and self-regulation. The authors discuss strategies for the use of both biofeedback and somatic education to increase internal locus of control and to introduce corresponding changes in illness beliefs. A case history illustrates a biofeedback intervention to positively change illness beliefs, and a somatic awareness exercise is used to illustrate a somatic education approach.

The physiological legacy of the Fenn, Rahn, and Otis school

Extraordinary advances in respiratory physiology occurred between 1941 and 1956 in the Department of Physiology, University of Rochester. These were principally the result of a collaboration between Wallace Fenn, Hermann Rahn, and Arthur Otis. Remarkably, all three scientists had worked in very dissimilar areas of physiology before and, by their own admission, were largely ignorant of respiratory physiology. However, because of the exigencies of war they were brought together to study the physiology of pressure breathing. The result was that they laid much of the foundations of pulmonary gas exchange and pulmonary mechanics and some of their work is still cited today. In pulmonary gas exchange they exploited the new oxygen-carbon dioxide diagram; clarified the effects of changes of altitude, hyperventilation, and pressure breathing; and pioneered the analysis of ventilation-perfusion relationships. In respiratory mechanics, they carried out groundbreaking work on the pressure-volume behavior of the lung and chest wall and went on to analyze aspects of gas flow and work of breathing. This explosion of ideas from what initially appeared to be a poorly prepared group has lessons for us today.

Mathematical model of the human lungs during phonation

To create the model of the lungs, their anatomic structure and physiology should be considered. The maximum attention should be given to consideration of physiology of breathing, since speech is the process accompanying the exhalation. Furthermore, the important features of human speech formation are neurobiological processes. When considering the lungs, attention must be paid to the function of the lungs as a part of the human respiratory system. According to [1–5], the lungs have the cone shape whose apex is turned up and the basis lies on the diaphragm. The external, forward, and backward surfaces of the lungs adjoin the internal surface of the thorax. The internal surface of the lungs is turned to mediastinum and adjoins its organs. The right lung is divided into three lobes, and the left lung is divided into two lobes. The lungs lie in the chest cavity on both sides of the heart. Each lung is enclosed in a thin-walled bag formed by thin, damp, and lustrous membranes – pleurae – continuously transforming one into another: visceral into parietal one. The pleural cavity which is a slit-like contains a small amount of the pleural fluid that plays the role of a lubricant during continuous respiratory motion of the lungs. Each lung contains bronchial ducts forming the original skeleton of the body – the bronchial tree – and the system of pulmonary sacks, or alveoli, which are respiratory (gas-exchange) organs of the respiratory system. Air freely passes through the respiratory tract, since walls of the respiratory ducts do not collapse due to the hyaline cartilage presented in them. The lungs are the main organs of the respiratory system. The volume of the lungs is changed by the thorax with muscles and the diaphragm. The thorax is a bony-muscular armor protecting the trachea, bronchial ducts, lungs, and heart from external damages. In addition, pectoral muscles actively participate in breathing. Rhythmical movements of the thorax provide ventilation of the lungs, that is, filling them by atmospheric air during the inhalation and expiring from them the alveolar air enriched with carbonic gas and poor with oxygen during the exhalation. The most part of the ventilation is provided by the main respiratory muscle – the diaphragm. The cycle of breathing consisting of inhalation and exhalation of the adult human at rest is repeated 14–18 times per 1 min. During sleeping, breathing is less often, and during hard working, it becomes much more frequent. The processes of breathing are regulated by the special organ of the central nervous system – the respiratory center. The paired respiratory center comprises two centers: inspiratory and expiratory ones. Nervous impulses arising in the respiratory center every 4 s cause the contraction of the diaphragm and other respiratory muscles. It is expedient to adjust the respiratory inhalation–exhalation cycle to the muscular activity of the human body (for example, with its

Breathwork in body psychotherapy: Towards a more unified theory and practice

The use of conscious breathing practices for the purpose of physical, psychological, emotional, and spiritual healing has a long and extremely varied history, yet little work has been done to see if these practices can be brought into a coherent and unified form that contributes to the field of body psychotherapy. This article attempts to meta-analyse the literature and research on breathwork in psychotherapy, with an emphasis on body psychotherapy, and to find common themes so that a general theory of breathwork and guidelines for practice might be developed. This paper provides an overview of the physiology of breathing, a review of the literature on breathwork.

Special populations: Do we need evidence from randomized controlled trials to support the need for respiratory syncytial virus prophylaxis?

Congenital abnormalities and impaired mechanisms that govern the normal coordinated physiology of breathing, sucking, swallowing and airway clearance, place infants with underlying medical disorders at high risk for respiratory morbidity following respiratory syncytial virus (RSV) lower respiratory tract infection. The use of RSV prophylaxis in premature infants' ≤ 35 weeks gestational age, infants with chronic lung and hemodynamically significant heart disease is firmly established through randomized controlled clinical trials (RCT's). RSV prophylaxis in infants with serious medical illnesses must be justified based on emerging scientific literature and the overriding concept of achieving a balance between benefit and harm with treatment. This article will explore the current evidence for palivizumab prophylaxis in a variety of disorders and examine existing differences between pediatric advisory body recommendations and real world practice.

Lung Function Testing in Infants

The neonatal period and the first year of life are times in which a significant amount of disease is caused by lung disorders related to a number of age-related factors. These include the lack of lung development due to preterm birth, the effects of intensive care treatment on the immature lung and early life infections with highly pathogenic agents including respiratory syncytial virus. Prenatal factors such as impaired foetal growth and maternal smoking in pregnancy can also have significant effects on lung function both in the immediate neonatal period but also throughout the first year of life and beyond. It has become increasingly recognised that lung pathology in infancy and early childhood is an important predisposing factor in the aetiology of long-term lung diseases in later childhood and possibly into adult life. The measurement of lung function in the neonatal period and during infancy has required the development of equipment specially adapted to the physical size of the patient and the unique physiology of breathing throughout this early phase of life. During the latter part of the 20th century specific tests to measure respiratory mechanics and to enable forced expiratory manoeuvres using the forced expiratory technique were developed. In more recent times forced inspiration to maximal lung capacity has also been developed. Some lung function tests can be performed reliably and reproducibly in unsedated preterm neonates. An important factor in measuring lung function after this period and especially during the first year of life is the need to sedate the patient in order to obtain cooperation during the specific respiratory manoeuvres mentioned above. Currently, chloral hydrate is the most frequently used agent. It has been shown to be safe and effective and also not to affect the results obtained as compared to unsedated infants. Standardisation of techniques and the establishment of normal values has been another major area of work in this field. The establishment several years ago of a joint European Respiratory Society/American Thoracic Society (ERS/ATS) task force on infant lung function has been responsible for many publications in this field and also the setting of standards for manufacturers of lung function equipment for this age group. Anatomical aspects are also important in this age group. During infancy, nasal breathing is predominant and can account for as much as 50% of total airway resistance, this may be especially important if measuring lung function 3–4 weeks after an upper respiratory tract infection. Another important anatomical aspect in infancy is that the chest wall is much more compliant than in later life. This means that during normal passive expiration the inward pull of the intrinsic elastic properties of the lung parenchyma will result in a lower level of overall lung capacity as compared to that of older children and adults. The result of this is that in some infants small airway closure occurs very close to the end of normal tidal breathing.

WS8-3 Physiology of breathing during sleep

WS8-3 Physiology of breathing during sleep

Numerical Study of High-Frequency Oscillatory Air Flow and Convective Mixing in a CT-Based Human Airway Model

High-frequency oscillatory ventilation (HFOV) is considered an efficient and safe respiratory technique to ventilate neonates and patients with acute respiratory distress syndrome. HFOV has very different characteristics from normal breathing physiology, with a much smaller tidal volume and a higher breathing frequency. In this study, the high-frequency oscillatory flow is studied using a computational fluid dynamics analysis in three different geometrical models with increasing complexity: a straight tube, a single-bifurcation tube model, and a computed tomography (CT)-based human airway model of up to seven generations. We aim to understand the counter-flow phenomenon at flow reversal and its role in convective mixing in these models using sinusoidal waveforms of different frequencies and Reynolds (Re) numbers. Mixing is quantified by the stretch rate analysis. In the straight-tube model, coaxial counter flow with opposing fluid streams is formed around flow reversal, agreeing with an analytical Womersley solution. However, counter flow yields no net convective mixing at end cycle. In the single-bifurcation model, counter flow at high Re is intervened with secondary vortices in the parent (child) branch at end expiration (inspiration), resulting in an irreversible mixing process. For the CT-based airway model three cases are considered, consisting of the normal breathing case, the high-frequency-normal-Re (HFNR) case, and the HFOV case. The counter-flow structure is more evident in the HFNR case than the HFOV case. The instantaneous and time-averaged stretch rates at the end of two breathing cycles and in the vicinity of flow reversal are computed. It is found that counter flow contributes about 20% to mixing in HFOV.

Sci-Fri AM: Imaging - 02: Regional Ventilation Mapping of the Rat Lung Using Hyperpolarized 3 He Magnetic Resonance Imaging

With the addition of inhaled contrast agents, namely hyperpolarized 3He and 129Xe, Magnetic Resonance (MR) imaging has the ability to measure anatomical and functional changes associated with disease progression in the rodent lung. Hyperpolarized 3He MR imaging has been used to measure regional ventilation in the normal rat lung using the dynamic gas signal from inside the lungs. This method employs a variable flip angle approach (FAVOR) to mitigate the effects of RF pulses and relaxation both in the ventilator system and in the rat lung. Theoretical models are used to fit signal enhancement curves to generate two-dimensional maps of the ventilation parameter, r, which is defined as the percent refreshment of gas per unit volume per breath. Healthy Sprague-Dawley rats (∼525 g) were anesthetized and ventilated with hyperpolarized 3He using a custom ventilator system. Imaging experiments were performed at 3.0 T and 2D projection images were acquired. The average r value obtained for the whole lung (r = 0.30 ± 0.02) agreed with expected values based on geometrical calculations. The ventilation gradient calculated in the anterior/posterior direction agreed with previously published xenon-enhanced CT results; however, there is no significant precedent for known ventilation gradients in the superior/inferior direction. In the future, these imaging techniques will be extended to measure ventilation gradients in all three dimensions using hyperpolarized 129Xe. The development of imaging tools to regionally quantify ventilation is expected to improve our understanding of breathing physiology in both normal rat lungs as well as rat models of asthma.

Thermistor at a Distance: Unobtrusive Measurement of Breathing

This paper unveils a thermal imaging methodology to recover the breathing waveform from the subject's nostrils. The resulting functionality is equivalent to that of a thermistor, but it is materialized in a contact-free manner. First, the nostril region is segmented and tracked over time through a network of cooperating probabilistic trackers. The mean thermal signal of the nostril region carries the breathing information. This information is extracted through wavelet analysis. The method has been tested on 20 healthy individuals. The breathing waveforms determined via the imaging computation were compared with the corresponding ones extracted from thermistors. The high degree of agreement between the two measurement methods confirms the validity of the proposed approach and opens the way for clinical applications. Furthermore, thermal imaging can be potentially used as an investigative tool to understand breathing physiology in ways not possible with contact sensors.

Reflective practice in practice

Reflective practice in practice

Are opioids associated with sleep apnea? A review of the evidence

Chronic opioid use for nonmalignant pain has increased dramatically; nonillicit unintentional deaths have also increased. This article reviews the physiology of breathing, effects of sleep on respiration, effects of opioids on respiration, potential interactions between sleep and opioids on respiration, and current evidence that chronic opioid use is associated with sleep-disordered breathing.

Physiology of breathing II

This contribution is the second part of a series discussing the basic science of the physiology of breathing. It focuses on inspired and alveolar gases, diffusion across the alveolar–capillary membrane, carriage of oxygen and carbon dioxide in the blood, right-to-left shunts and ventilation–perfusion matching, and the control of breathing.

Physiology of breathing I

The main function of the respiratory system is gas exchange. The lungs also break down microthrombi arriving from the veins, and have several metabolic actions, including the activation of angiotensin I to angiotensin II and the breakdown or deactivation of substances (e.g. 5-hydroxytryptamine, bradykinin, noradrenaline, acetylcholine, some drugs). This contribution discusses lung volumes and ventilation, respiratory muscles and the mechanism of breathing, and resistance to breathing.

Air versus oxygen for resuscitation of infants at birth

100% oxygen is the commonly recommended gas for the resuscitation of infants at birth. There is growing evidence from both animal and human studies that room air is as effective as 100% oxygen and that 100% oxygen may have adverse effects on breathing physiology and cerebral circulation. There is also the theoretical risk of tissue damage due to free oxygen radicals when 100% oxygen is given. The use of room air has, therefore, been suggested as a safer and possibly more effective alternative. In newborn infants requiring resuscitation, does the use of room air reduce the incidence of death, neurological disability and short term morbidity when compared with the use of 100% oxygen? This included searches of the Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004) and MEDLINE PubMed 1966 to December 2003, and handsearches of reference lists of relevant articles and conference proceedings. All randomised and quasi-randomised studies comparing the use of room air or any other concentration of oxygen versus 100% oxygen in the resuscitation of infants at birth. Three authors assessed the methodological quality of eligible trials and extracted data independently. When appropriate, meta-analysis was conducted to provide a pooled estimate of effect. For categorical data the relative risk (RR), risk difference (RD) and number needed to treat (NNT) with 95% confidence intervals (CI) were calculated. Continuous data were analysed using weighted mean difference (WMD). Five studies were identified which enrolled a total of 1302 infants. In two studies allocation was randomised and the caregivers were blinded to intervention group. In the other three studies, allocation was quasi-randomised and the caregivers were not blinded. Pooled analysis of the four trials reporting effect on death showed a significant reduction in the rate of death in the group resuscitated with room air [typical RR 0.71 (0.54, 0.94), typical RD -0.05 (-0.08, -0.01), NNT 20 (12, 100)]. There were no significant differences between the groups with respect to rates of grade 2 or 3 hypoxic ischaemic encephalopathy. One of the four trials reported a statistically significant difference in median 5 minute Apgar scores, favouring the group allocated to room air. However, the absolute difference between the medians was small and there were no significant differences in the median 10 minute Apgar scores in the three trials reporting this outcome. One trial followed up a selected subgroup of survivors to 18-24 months. There were no significant differences in rates of adverse neurodevelopmental outcomes including cerebral palsy and failure to achieve various milestones; however, the proportion of eligible patients seen was less than 70%. Analyses that were planned for this review, but not able to be carried out because of lack of published data, included a sub-analysis stratified by gestational age and assessments of the effect on bronchopulmonary dysplasia and retinopathy of prematurity. There is insufficient evidence at present on which to recommend a policy of using room air over 100% oxygen, or vice versa, for newborn resuscitation. A reduction in mortality has been seen in infants resuscitated with room air, and no evidence of harm has been demonstrated. However, the small number of identified studies and their methodologic limitations dictate caution in interpreting and applying these results. We note the use of back-up 100% oxygen in more than a quarter of infants randomised to room air. Therefore, on the basis of currently available evidence, if one chooses room air as the initial gas for resuscitation, supplementary oxygen should continue to be made available.

BONY BIRDS BREATHE BETTER

A fascination with dinosaur skeletons has led Jonathan Codd of Bonn University to new insights into birds' breathing physiology. Codd was puzzled by the role of velociraptors' uncinate processes, `small ossified structures projecting like little handles from their ribs.' Reflecting on the evolutionary link between dinosaurs and extant birds, he hoped that our feathered friends might provide him with some clues regarding the function of these strange structures. When Codd investigated the muscles associated with the uncinate processes of giant Canada geese, he found that these bony projections are integral to bird breathing mechanics(p. 849).Codd explains that vertebrate respiratory and locomotor systems are mechanically linked, so muscles attached to the rib cage could either help an animal breathe or stabilise it during walking. Together with Steve Perry he headed across the Atlantic to team up with Dave Carrier, a vertebrate morphologist at the University of Utah who studies the relationship between respiratory and locomotor systems. To determine whether the three muscles associated with birds' uncinate processes primarily assist during breathing or walking, they decided to measure muscle activity and breathing in standing,sitting and running geese.Muscle activity is normally recorded by sticking needle electrodes into muscles. `But you can't be sure that the needle is in the right place' Codd says. So he surgically implanted patch electrodes directly onto the three muscles, a technique that `allows you to be 100% certain that you have the right muscle.' To record the birds' breathing, Codd needed to measure pressure differences in their air sacs, `bags that act as bellows to pump air in and out of the birds' lungs.' Dona Boggs, a bird respiration expert, helped Codd insert differential pressure transducers into the birds' air sacs. Geese can have nasty tempers, but the team used this to their advantage: they measured the large inspirations and expirations associated with the birds' threatening hisses. If the three muscles were involved in breathing, the team reasoned they should see muscle activity during hissing.Sure enough, just before the birds hissed, the team noticed a burst of electrical activity from the appendicocostal muscle and larger inspiration,indicating that this muscle has an inspiratory function. And they saw bursts of activity from the external oblique muscle during the large expirations associated with hissing, suggesting that this muscle plays a role in expiration. But they only saw short bursts of activity in the external intercostal muscle while the geese were running, not when the birds were hissing, so the team concluded that this muscle has a locomotor function. Clearly, only two of the three muscles associated with birds' uncinate processes help the animals breathe.The team were particularly intrigued to see increased appendicocostal activity in sitting geese. Codd explains that when birds sit, their sternum movement is restricted, making breathing difficult. `The increased appendicocostal activity we noticed suggests that when the sternum's movements are restricted, like when birds are sitting on their nests, this muscle causes the rib cage to flare sideways and draw air into the birds' lungs' he says. So thanks to this muscle, birds can breathe easy during those long periods of egg incubation.

Physiology of Breathing and Respiratory Control during Sleep

Studies of respiratory control during sleep have revealed that multiple sites of central CO (2) chemosensitivity exist within the brainstem, and different chemosensory sites may function only during certain sleep states. In general, chemical control of respiratory function, related to both hypercapnia and hypoxia, appears to be blunted during sleep. The decline in respiratory activity during sleep is particularly marked in the muscles of the upper airway. A variety of neuromechanical factors originating in the lungs, chest wall, and upper airway also modify respiratory function during sleep. Cardiorespiratory function seems to be less stable during sleep, and arousal responses represent a final element in the control system that preserves cardiorespiratory function by terminating the sleep state and restoring more effective control mechanisms.

Physiology of breathing II

Stressors such as exercise, ascent to altitude and sleep present complex challenges to ventilatory ( ▪ E) control and the regulation of arterial PO 2 (PaO 2), PCO 2 (PaCO 2) and pH (pHa). This is because the primary humoral sensors (central and peripheral chemoreceptors) operate in a ‘closed-loop’ fashion. With ascent to altitude, for example, the initial hypoxic-induced hyperventilation causes a respiratory alkalosis (low PCO 2, high pH), which constrains the initial hyperventilation. However, as the metabolic compensations for the alkalosis (bicarbonate loss) develop, pH declines towards baseline, offsetting such constraints. In contrast, with long-term hypoxia, there is a hypoventilation and ‘blunting’ of hypoxic ventilatory responsiveness. For moderate exercise, ▪ E is closely matched to pulmonary CO 2 output, effecting regulation of PaCO 2 and pHa. The exact mechanisms underlying this coupling are unclear. It is largely unaffected by selective inactivation of central neural and muscle reflex drives, and also central chemoreflex and peripheral chemoreflex drives. This suggests that the ventilatory control system during exercise possesses considerable redundancy: a deficit in ventilatory drive being readily ‘picked up’ by other mechanisms. At higher work rates associated with a lactic acidosis, ▪ E control is further challenged by the requirement of respiratory compensation for the low pHa; i.e. hyperventilation. This additional response is mediated by the carotid chemoreceptors. In sleep, there is a tendency towards progressive hypoventilation and reduction of chemosensitivity, reflecting in part the progressive withdrawal of waking influences on ▪ E. Furthermore, congenitally impaired chemoreflex responsiveness in the awake state can precipitate profound hypoventilation during sleep.