European Respiratory Society
Sleep Apnoea (out of print)

This book has been superseded by a newer edition.

  • European Respiratory Society Monographs
  1. Page v
  2. Page vi
  3. Page vii
  4. Page 1
    Abstract
    Correspondence: A. Atalla, Unit of Sleep and Ventilation, Royal Brompton Hospital, Sydney Street, London, SW6 3NP, UK, E-mail a.atalla@imperial.ac.uk

    Sleep represents a period of vulnerability to ventilatory irregularities, even in healthy individuals. Moreover, the presence of disease magnifies both the risk and the consequences of sleep-disordered breathing. Respiratory disorders during sleep are highly prevalent in the population but despite this the underlying mechanisms leading to breathing instability remain poorly understood because of the limitations related to studying humans and the lack of non-mammalian models that can mimic the complexity of this integrated, physiological system. In this chapter we have reviewed the present understanding of brainstem respiratory control in non-mammalian models and how this control is modulated during sleep. Although much remains to be resolved, animal models are invaluable for the understanding of human respiratory control and vice versa.

    In humans, the onset of sleep brings about a number of physiological changes that have also been reviewed, such as a reduction in alveolar ventilation and chemosensitivity, as well as an increase in upper airway resistance. Moreover, the concept of loop gain has been used to predict the response of the respiratory control system to the sleep-related changes and hence, stability of breathing. It is hoped that combining evidence from these different models and methodologies will increase understanding of the respiratory control during sleep. Likewise, being aware of the pathophysiological mechanisms that lead to, or present as, sleep-disorderd breathing will result in improved clinical management and inform more targeted therapies.

  5. Page 17
    Abstract
    Correspondence: A. Iranzo, Neurology Service, Hospital Clinic de Barcelona, C/Villarroel 170, Barcelona 08036, Spain. E-mail: airanzo@clinic.ub.es

    Chronic excessive daytime sleepiness (EDS) is a disabling condition associated with an increased and exaggerated tendency to fall asleep, leading to reduced quality of life and other problems. A common cause of EDS is obstructive sleep apnoea syndrome (OSAS).

    Evaluating EDS is problematic as somnolence is not easily measured with the available subjective and objective tools.

    The Multiple Sleep Latency Test (MSLT) is the standard objective measure, evaluating the tendency to fall asleep without external alerting factors; however, it discriminates poorly between patients with EDS-linked sleep disorders (except narcolepsy) and normal population. Weak correlations have been found between the MSLT and subjective sleep scales (Stanford/Epworth Sleepiness Scales) and between the MSLT and treatment responses with CPAP. The weak correlation, suggests that these measures may be evaluating different aspects of a complex phenomenon.

    It is assumed, but not demonstrated, that the OSA severity correlates with the degree of sleepiness. Measures of EDS are not associated with the apnoea/hypopnoea and arousal indices, hypoxaemia or slow-wave sleep, suggesting a lack of understanding of either sleep disturbance in OSA or MSLT measures. The mechanisms of EDS in OSAS remain to be elucidated.

  6. Page 31
    Abstract
    Correspondence: R.J. Kimoff, McGill University Health Centre, Respiratory Division, Rm L4.08, 687 Pine Ave W, Montreal, QC, Canada, H3A 1A1. E-mail: john.kimoff@mcgill.ca

    The pathophysiology of obstructive sleep apnoea (OSA) is complex and the contributing factors may vary considerably between individuals. Reduced upper airway anatomic dimensions and altered tissue mechanics contribute to varying extents, but do not suffice to explain the upper airway collapse which occurs uniquely during sleep. Sleep-related changes in upper airway dilator muscle activation and reflex responsiveness play a key role. Varying degrees of impaired upper airway neuromuscular compensation during sleep are observed, and considerable work is still required to understand the basis of this impairment. Contributing factors may include upper airway neuropathy or impaired muscle function or mechanical coupling. Ventilatory control instability and alterations in the arousal threshold to respiratory stimuli appear to be important determinants of recurrent respiratory events in some patients. Innovative, broadly applicable approaches to “phenotyping” OSA are needed. More comprehensive characterisation of the specific contributing factors in individual subjects will facilitate both the study of genetic mechanisms in OSA and the development of therapies targeting specific pathophysiolgical factors in subsets of OSA patients.

  7. Page 51
    Abstract
    Correspondence: E. Lindberg, Dept of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Akademiska sjukhuset, SE-751 85 Uppsala, Sweden. E-mail: eva.lindberg@akademiska.se

    Approximately 3–7% of adult males and 2–5% of adult females inwestern countries and Asia suffer from symptomatic obstructive sleep apnoea syndrome (OSAS) and are therefore candidates for treatment. In addition, a large percentage of individuals suffer from either snoring in combination with sleepiness or OSA without overt daytime symptoms. The clinical significance of this is still controversial.

    Sex, obesity and age are all important risk factors for OSA. Moreover, smoking, alcohol consumption and physical inactivity appear to increase the occurrence of the disorder.

    The relationship between OSA and daytime hypersomnolence is not completely understood. Most subjects with verified OSA do not report daytime sleepiness and there is increasing evidence that snoring without apnoeas or hypopnoeas might also relate to sleepiness.

    Cross-sectional studies indicate an independent link between diabetes and OSA but this has not yet been confirmed in longitudinal surveys.

  8. Page 69
    Abstract
    Correspondence: R.L. Riha, Dept of Sleep Medicine, The Royal Infirmary of Edinburgh, 51 Little France Crescent, EH16 4SA, Edinburgh, UK. E-mail: rlriha@hotmail.com

    Obstructive sleep apnoea (OSA) is known to be hereditary but a number of environmental and developmental factors can affect its expression, e.g. obesity, hormonal changes, nasal occlusion and lymphoid tissue growth.

    For this reason, OSA is generally considered to be a sum of its component parts with relative contributions in each individual from craniofacial morphology, susceptibility to sleepiness, ventilatory control, obesity, upper airway control and lymphoid tissue overgrowth.

    The phenotypic complexity of OSA makes establishment of a single genetic basis elusive. Furthermore, unlike other polygenic disease models, such as chronic obstructive pulmonary disease, asthma and hypertension, funding for studies in OSA has been limited. A number of genetic approaches have been utilised, including genome-wide studies, case–control studies and genome-wide association studies. The results of these demonstrate our first tentative, but hopeful, steps of uncovering some of the markers of disease expression, as well as disease progression.

    Future efforts aimed at exploring the sequelae of OSA and possible genetic modulators of these are more likely to yield clinically useful data, which will ultimately result in improved patient care.

  9. Page 86
    Abstract
    Correspondence: R. Tkacova, Dept of Respiratory Medicine, Faculty of Medicine, P.J. Safarik University and L. Pasteur Teaching Hospital, Rastislavova 43, Kosice, 041 90, Slovakia. E-mail: ruzena.tkacova@upjs.sk

    Obstructive sleep apnoea (OSA) is a common disorder affecting 2–4% of the adult population. Cardiovascular, metabolic and neurocognitive consequences of OSA underline the need for early diagnosis and treatment of the disorder. The diagnosis of OSA is based upon the combined assessment of clinical features alongside the objective demonstration of sleep-disordered breathing, using an appropriate sleep study. The typical presentation of OSA is represented by an overweight male patient complaining of loud snoring, nocturnal choking, nocturia, excessive daytime sleepiness and mild cognitive impairment, with a history of witnessed apnoeas during sleep. The physical examination can suggest increased risk and should include the respiratory, cardiovascular and neurological systems. Particular attention should be given to the presence of obesity, signs of upper airway narrowing and arterial hypertension. Nevertheless, OSA is a heterogeneous disorder with a broad range of nocturnal and daytime symptoms that may not conform to the typical history and physical findings, particularly among females, the elderly, during pregnancy, or in the presence of other disorders that can contribute to the development of OSA or to the adverse consequences of OSA, such as congestive heart failure, end-stage renal disease, chronic obstructive pulmonary disease and certain endocrine disorders. Since OSA is associated with adverse cardiovascular outcomes, increased awareness of the atypical presentation of OSA in different patient populations is warranted.

  10. Page 104
    Abstract
    Correspondence: S.L. Verhulst, Dept of Paediatrics, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium. E-mail: stijn.verhulst@ua.ac.be

    Obstructive sleep apnoea (OSA) is frequently encountered in children, with an estimated prevalence of 1–4%. Childhood OSA is a different entity compared to OSA in adults.

    Adenotonsillar hypertrophy is the most common anatomical risk factor. Obesity is increasingly becoming an important risk factor for childhood OSA, although the exact risk mechanisms by which obesity results in an increased prevalence of OSA syndrome remain to be defined.

    Polysomnography remains the golden standard in the diagnosis of OSA syndrome. Complications include neurobehavioural effects, metabolic and cardiovascular complications and impaired growth. Adenotonsillectomy is the first-line treatment but is associated, especially in obese children, with a high failure rate and thus, there is a clear need for alternative treatment options.

  11. Page 121
    Abstract
    Correspondence: P.J. Strollo, UPMC Sleep Medicine Center, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. E-mail: strollopj@upmc.edu

    Since its emergence, half a century ago, sleep laboratory monitoring has revolutionised the evaluation and management of patients with sleep disorders. Throughout this period the sleep laboratory has been used for countless clinical and research purposes, with its most widespread application lying within the diagnosis and treatment of sleep-related breathing disorders.

    A comprehensive sleep history and physical examination remains at the cornerstone of the initial evaluation for any patient presenting with symptoms of sleep apnoea or any other sleep-related complaints. Nevertheless, at the present time, clinical symptoms and risk factors alone are insufficient to accurately diagnose and assess the severity of a sleep-related breathing disorder. Furthermore, despite the growing momentum of unattended diagnostic and therapeutic strategies for evaluating and managing sleep aponea outside of the laboratory, it is clear that attended polysomnography in the sleep laboratory will continue to play a prominent role in the care administered to millions of patients with sleep apnoea and other associated sleep disorders.

  12. Page 136
    Abstract
    Correspondence: T. Penzel, Sleep Center, Charité Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany. E-mail: thomas.penzel@charite.de

    The overview of ambulatory diagnosis for sleep-disordered breathing is preceded by a summary on cardiorespiratory polysomnography (PSG). This summary is based on evidence reviews and is the basis for the following overview on the ambulatory diagnosis of obstructive sleep apnoea. First, possibilities and limitations are given in detail, compiled from an evidence-based review. Categories of systems with four to six channels and one to three channels are introduced and presented. The importance of a high, pre-test probability is elucidated. Open research questions regarding these systems are mentioned.

    Ambulatory diagnosis of sleep apnoea is a challenging field for new technologies, which try to make devices simpler and more reliable. New technologies and concepts are presented here, based on current research papers. Electrocardiogram-derived respiration photoplethysmogram analysis, midsagittal jaw movements and respiratory sound analysis will also be reviewed. Systems and sensors become less disturbing for the patient and with some systems there is no contact with the subject at all. Not all techniques will survive a harsh review compared with cardiorespiratory PSG. However, this overview may inspire new developments and may trigger clinical studies using the technologies available today. Recommendations are made in order to initiate evidence-based diagnostic processes.

  13. Page 150
    Abstract
    Correspondence: M.R. Bonsignore, Dip. Biomedico Medicina Interna e Specialistica (DIBIMIS), University of Palermo, V Cervello Hospital, Via Trabucco 180, 90146 Palermo, Italy. E-mail: marisa@ibim.cnr.it

    Obstructive sleep apnoea (OSA) causes nocturnal hypertensive peaks at the end of apnoeas and is often associated with daytime systemic hypertension. A causal relationship between OSA and increased blood pressure (BP) during wakefulness has been shown in humans and experimental models, and recent guidelines on hypertension recognised OSA as a frequent cause of secondary hypertension.

    The pathogenesis of hypertension in OSA patients involves sympathetic hyperactivity secondary to intermittent hypoxia, decreased baroreflex sensitivity, endothelial dysfunction, neurohumoral mechanisms involving the hypothalamic-pituitary-adrenal axis, and increased platelet activation. Associated conditions such as obesity significantly contribute to the pathogenesis of both OSA and hypertension. Hypertension in OSA patients can affect target organs (heart, blood vessels and kidney), and may play a role in the increased cardiovascular risk found in untreated OSA.

    OSA is a frequent cause of “masked hypertension”, i.e. hypertension undetected by office BP measurements. Patients with resistant hypertension should be investigated for the presence of OSA.

    Treatment of OSA with continuous positive airway pressure (CPAP) decreases BP especially in severe OSA and hypertensive patients. Hypertensive OSA patients treated with CPAP usually also need anti-hypertensive treatment, as prevention of respiratory events during sleep may be insufficient to normalise BP.

  14. Page 174
    Abstract
    Correspondence: L. Grote, Sleep Disorders Center, Pulmonary Medicine, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden. E-mail: ludger.grote@lungall.gu.se

    There is a substantial body of evidence that obstructive sleep apnoea (OSA) causes vascular dysfunction, promotes early atherosclerosis and increases the incidence of cardiovascular (CV) events. However, this does not seem to be applicable for the population in general. Therefore, OSA may not be classified as a traditional risk factor for the development of CV disease but it can definitely be classified as an important comorbid condition. In studies performed in clinical populations with elevated CV risk profiles, the occurrence of moderate-to-severe OSA was very often accompanied by a worsened vascular function and increased prevalence of structural abnormalities. The use of continuous positive airway pressure treatment could provide significant improvements in vascular functionality and structure. In fact, the majority of data on incidences of CV disease and mortality suggest a disadvantage in patients with untreated OSA or ineffectively treated OSA. Furthermore, the consequences of OSA are more pronounced in patients who are male, young and obese, with some studies suggesting that consequences may be more pronounced in subjects with daytime hypersomnolence. Diagnosis and treatment of these subgroups appear to be very important. It is obvious that obesity, in this context, is a key comorbid condition and that future research may focus on areas where data currently are more sparse, i.e. in subjects without apparent comorbidities, pre- and post-menopausal females, children and adults. Finally, the “age paradox” claiming that OSA has a protective mechanism against CV mortality or CV dysfunctions, needs to be addressed with prospective, mechanistic, and epidemiological research.

  15. Page 189
    Abstract
    Correspondence: M. S-M. Ip, Room 409, 4/F., Professorial Block, Dept of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, SAR, China. E-mail: msmip@hkucc.hku.hk

    Obstructive sleep apnoea (OSA) is increasingly recognised as a risk factor for cardiometabolic dysfunction. Obesity is the most common risk factor in OSA, and various obesity-related cardiometabolic disorders, including a spectrum of glucose disorders from insulin resistance to overt type 2 diabetes mellitus, hypertension, dyslipidaemia and the metabolic syndrome, have all been found to be highly associated with sleep-disordered breathing.

    Current evidence on the magnitude of the impact on ultimate morbidity or mortality attributable to OSA-induced metabolic dysfunction is scarce. Given the known pathophysiology of intermittent hypoxia and sleep disturbance/loss in OSA, it is postulated that OSA independently contributes towards metabolic dysfunction through various downstream intermediary pathways of sympathetic activation, neurohumoral changes, inflammation and oxidative stress. Human and animal/cell experiments are providing clues to these mechanistic pathways. Regardless of any independent role in the causation of metabolic dysfunction, awareness of the concurrence of OSA and metabolic disorders, and the modifying roles of diet and lifestyle behaviour on metabolic function cannot be over emphasised.

  16. Page 216
    Abstract
    Correspondence: D. Rodenstein, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, 1200 Brussels, Belgium. E-mail: daniel.rodenstein@uclouvain.be

    Patients with obstructive sleep apnoea (OSA) have increased utilisation of health resources. Costs are related to the severity of the disease and the associated comorbidities. Patients with OSA have been shown to have more motor accidents than drivers in the general population and more accidents at the workplace.

    The application of an efficient treatment in OSA results in a significant reduction in healthcare costs in the months and years that follow. In fact, several studies have shown that the treatment of OSA is cost-effective. Despite the fact that OSA is a serious risk factor for motor accidents, there is no harmonisation among European countries in the way in which legislation regarding driving licence is applied. OSA is not mentioned in Annex III of the European Directive, which legislates the driving licence.

    This chapter highlights many aspects of OSA that are usually beyond the scope of the medical practitioner. It provides a much more complete picture of the implications of a disease on the individual patient, as well as on the economy, the safety of transportation and driving and, finally, society as a whole.

  17. Page 225
    Abstract
    Correspondence: P. Lévy, Exploration Fonctionnelle Cardio-Respiratoire, Pôle Rééducation et Physiologie, Centre Hospitalier Universitaire de Grenoble, BP 217 X, 38043 Grenoble, France. E-mail: PLevy@chu-grenoble.fr

    Outcomes of obstructive sleep apnoea (OSA) have been extensively studied since the late 1990s. There have been a large number of controlled studies evaluating the effects of continuous positive airway pressure (CPAP) on sleepiness and daytime functioning, blood pressure, cardiovascular outcomes and metabolic parameters.

    These better-identified outcomes may help in determining to what extent CPAP is able to fully reverse the chronic consequences of OSA. Although there is clearly a significant impact of CPAP on excessive daytime sleepiness (EDS) and blood pressure, EDS may persist in a significant proportion of patients and blood pressure may fall only modestly under CPAP, i.e. 1–3 mmHg. Other treatments, such as pharmacological treatment, weight loss, positional treatment, oral appliances and upper airway surgery, should be considered, although the degree of evidence, apart from that for oral appliances and weight loss, is rather limited.

    From these data, the aim was to define strategies according to OSA severity. Finally, we suggest that comparison and combination of treatment modalities, e.g. CPAP for OSA alleviation and specific cardiovascular or metabolic treatments, may be critical as regards the chronic consequences of sleep apnoea.

  18. Page 244
    Abstract
    Correspondence: J.M. Montserrat, Sleep Laboratory. Hospital Clinic, Villarroel 170. 08036 Barcelona, Spain. E-mail: jmmontserrat@ub.edu

    Obstructive sleep apnoea (OSA) is a common disorder that increases morbidity and even mortality. When the apnoea/hypopnoea index (AHI) is >30 and is accompanied by symptoms, OSA must be treated. Although continuous positive airway pressure (CPAP) is the most useful form of treatment, it should always be complemented by the prescription of the following: a weight loss programme, physical exercise, positional therapy, sufficient sleep time, and an avoidance of sedatives and alcohol. As each patient needs a different fixed CPAP, titration must be performed. When patients have no severe associated comorbidity the fixed CPAP can be obtained by using automatic devices. Training, educational sessions and close follow-up, especially during the first months, are crucial for obtaining adequate compliance. It is not clear whether non-sleepy OSA patients should be treated, although CPAP should probably be prescribed for those with severe cardiovascular disease or a very high AHI.

  19. Page 267
    Abstract
    Correspondence: J.A. Fleetham, The Lung Centre, 7th Floor, 2775 Laurel Street, Vancouver, BC V5Z 1M9, Canada. E-mail: John.Fleetham@vch.ca

    Oral appliances are commonly used for the treatment of snoring and obstructive sleep apnoea–hypopnoea (OSAH). Oral appliances increase the size of the upper airway. Mandibular advancement splints (MAS) are the most widely used type of oral appliance. There is increasing evidence that MAS improve sleepiness, blood pressure and indices of sleep-disordered breathing. Continuous positive airway pressure (CPAP) is more effective than MAS in improving sleepiness, health status and indices of sleep-disordered breathing. CPAP remains the primary treatment for severe OSAH. Current guidelines recommend oral appliances as a primary treatment for patients with mild-to-moderate OSAH. Oral appliances are the best alternative treatment for patients with OSAH who are unwilling or unable to comply with CPAP therapy. Oral appliance therapy may also be indicated as an adjuvant to CPAP when the patient is away from home or electrical power. Oral appliance therapy should be supervised by both medical and dental specialists. MAS should not be recommended for patients with major periodontal disease. Follow-up sleep monitoring is needed to verify the efficacy of oral appliance therapy. Patients treated with oral appliances require long-term medical and dental follow-up care.

  20. Page 286
    Abstract
    Correspondence: O. Marrone, Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia Molecolare, Via Ugo La Malfa, 153, 90146 Palermo, Italy. E-mail: marrone@ibim.cnr.it

    Surgical treatment of obstructive sleep apnoea (OSA) is mainly aimed at enlarging the upper airway and making it less susceptible to collapse during sleep in patients who do not want or cannot be treated by other means. Surgical success has commonly been defined as a ≥50% reduction in apnoea/hypopnoea index (AHI) associated with a post-operative AHI of <20 events·h−1. Subjective improvement ensues more often than resolution of respiratory disorders. Long-term relapse may occur.

    Pre-operatively, radiological and endoscopic tests may provide indications regarding the site of upper airway closure during sleep. Pharyngeal, hyoid and lingual surgery may show effectiveness when airway occlusion occurs at specific sites; their degree of success ranges 60–70%. In adults, radiofrequency volume reduction of the tongue and/or the soft palate is convenient for subjects with mild OSA. Maxillomandibular advancement and tracheostomy are almost always effective, irrespective of the site of obstruction and the severity of OSA. In children, adenotonsillectomy and maxillary distraction osteogenesis are often followed by favourable outcomes, at least in non-obese subjects.

  21. Page 302
    Abstract
    Correspondence: C.L. Chang, Woolcock Institute of Medical Research, PO Box M77 Missenden Rd, Camperdown NSW 2050, Sydney, Australia. E-mail: contact_cat@hotmail.com

    The public health impact of obstructive sleep apnoea (OSA) is increasingly recognised and will rise in conjunction with the obesity epidemic.

    Current clinical management of OSA focuses on device-based interventions, which do not correct underlying obesity. Various approaches to weight loss have been tested, including diet and behavioural modification programmes, pharmacological interventions and bariatric surgery.

    Emergent clinical trials demonstrate that intensive diet and behavioural interventions can reduce weight, and this will substantively reduce OSA severity. However, there is little long-term or subgroup data.

    Pharmacological interventions alone provide minimal weight loss and potentially unacceptable side-effect profiles as highlighted by the recent withdrawal of sibutramine. Bariatric surgery can markedly reduce obesity and is an effective OSA treatment but there is little good-quality long-term outcome data specific to OSA. The relative effectiveness and safety profiles of various bariatric surgeries, pharmacotherapies or behavioural/diet interventions either in combination or in comparison are unstudied.

    The multi-comorbidity of OSA lends itself to a multidisciplinary approach incorporating dieticians, physiotherapists, psychologists, exercise physiologists, sleep physicians and surgeons.

  22. Page 321
    Abstract
    Correspondence: J. Hedner, Sleep Disorders Centre, Dept of Pulmonary Medicine and Allergology, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden. E-mail: jan.hedner@lungall.gu.se

    Several attempts have been made to identify a uniformly effective pharmacological remedy in obstructive sleep apnoea (OSA). However, no currently described drug has consistently reduced the severity of the condition by more than 50% in controlled trials. Most of the data is based on testing of compounds used in other therapeutic areas and there are few examples of rational strategic drug development. OSA is frequently associated with considerable comorbidities, including: hypertension, obesity, metabolic derangement and hormonal dysfunction, beside the more or less consistent symptoms of daytime sleepiness and cognitive dysfunction. Hence, specific considerations, such as classification of phenotype, existing comorbidity etc., should be taken into account when explorative clinical trials are designed in patients with OSA. The clinician should be made aware that there is no systematically documented drug yet available for the treatment of sleep apnoea. Future drug development is likely to incorporate a more global approach to comorbid conditions and risk modification in OSA.

  23. Page 340
    Abstract
    Correspondence: Dept of Pulmonary and Sleep Disorders, St. Vincent's University Hospital, Elm Park, Dublin 4, , Ireland. E-mail: briankent@physicians.ie

    Obstructive sleep apnoea syndrome (OSAS) is associated with an increased risk of cardiovascular morbidity and mortality. Evidence from in vitro, animal, clinical and population studies supports an independent role for OSAS in the development of atherosclerosis. Intermittent hypoxia and OSAS cause low-grade systemic inflammation, oxidative stress and endothelial dysfunction, leading to a pro-atherogenic state. Concomitant sympathetic excitation promotes the development of systemic hypertension, while the haemodynamic effects of recurrent episodes of negative intrathoracic pressure contribute to ventricular remodelling.

    The effect of obesity and dysfunctional inflamed adipose tissue are, however, major confounding factors in trials exploring the effect of OSAS. In particular, it is unclear if OSAS plays an independent role in metabolic dysfunction or the development of white adipose tissue inflammation in obese individuals. Further carefully designed trials are required to explore this area.

  24. Page 360
    Abstract
    Correspondence: L. Lavie, Unit of Anatomy and Cell Biology. The Ruth and Bruce Rappaport Faculty of Medicine, Technion, POB 9649, 31096, Haifa, Israel. E-mail: lenal@tx.technion.ac.il

    Enormous progress has been made in the last decade in understanding the impact obstructive sleep apnoea syndrome (OSAS) has on the cardiovascular system and the associated comorbidities. However, the mechanisms governing these associations are poorly understood. The accumulated evidence implicates oxidative stress and inflammation as two basic mechanisms associated with OSAS and with various metabolic dysregulations. The recent development of various experimental models of intermittent hypoxia, based on animals and cultured cells, has helped to unveil some of these mechanisms and pathways affected by the intermittent hypoxia. It is likely that an improved understanding of these mechanisms may lead to the development of new and more effective treatment modalities to abort the cardiovascular risk, resulting from oxidative stress and inflammation.

  25. Page 381
    Abstract
    Correspondence: D.G. McSharry, Brigham and Women's Hospital and Harvard Medical School, Division of Sleep Medicine, Sleep Disorders Program, 221 Longwood Ave, Boston, MA 02115, USA. E-mail: macsearraigh@ireland.com

    Central sleep apnoea (CSA) encompasses a diverse group of conditions from periodic breathing at altitude to opiate-induced CSA. Considerable overlap exists between obstructive sleep apnoea and CSA in terms of pathogenesis and pathophysiology. CSA syndromes can be broadly classified into patients with high drive and those with low drive. Many forms of CSA can ultimately lead to adverse cardiovascular outcomes. Treatment can be challenging and varies according to the underlying aetiology of the CSA. Some exciting new therapeutic options (e.g. phasic administration of CO2) require further research, in particular with respect to safety and potential outcome benefits.

  26. Page 396
    Abstract
    Correspondence: M.T. Naughton, Alfred Hospital and Monash University, Commercial Road, Prahran, 3181, Victoria, Australia. E-mail: m.naughton@alfred.org.au

    Sleep-related breathing disorders are present in ∼50% of patients with chronic heart failure, with fairly equal prevalence of obstructive sleep apnoea (OSA) and central sleep apnoea (CSA) with Cheyne–Stokes respiration. While it is widely accepted that OSA exerts negative effects on the heart, controversy remains as to whether CSA contributes to morbidity and mortality in chronic heart failure patients or whether it is simply an epiphenomenon. The largest randomised trial to date, which involved patients with heart failure and CSA, did not demonstrate a convincing effect of continuous positive airway pressure on transplant-free survival. At least two large, long-term randomised trials examining the effect of ventilatory strategies on patients' survival with heart failure and sleep-related breathing disorders are in progress. To address the question of therapeutic benefit, suitable patients should be considered for enrolment in these studies.

  27. Page 421
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