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Marie Bruyneel
https://t.me/medicina_free
Department of Pneumology, CHU
Saint-Pierre and CHU Brugmann, and
Université Libre de Bruxelles, Brussels,
Belgium
marie.bruyneel@stpierre-bru.be
Bertien Buyse
Department of Respiratory Diseases, UZ
Leuven, Leuven, Belgium
bertien.buyse@uzleuven.be
Louise Byrne
Department of Respiratory Medicine, St
James’ Hospital, Dublin, Ireland
1byrnelouise@gmail.com
Francesca Casoni
Sleep Disorders Center, Vita-Salute San
Raaele University, Milan, Italy
casoni.francesca@hsr.it
Silvia V. Conde
Universidade Nova de Lisboa Faculdade
de Ciencias Medicas, Lisbon, Portugal
silvia.conde@nms.unl.pt
Sarah Cullivan
Department of Respiratory Medicine, St
James’ Hospital, Dublin, Ireland
sarahkcullivan@gmail.com
Sonia Deweerdt
Department of Pneumology, UZ Brussel,
and Vrije Universiteit Brussel, Brussels,
Belgium
Sonia.DeWeerdt@uzbrussel.be
Marijke Dieltjens
Department of ENT, Antwerp University
Hospital and University of Antwerp,
Antwerp, Belgium
marijke.dieltjens@uza.be
Marta Drummond
Faculty of Medicine, University of
Porto, and Centro de Responsabilida
de Integrada de Sono e VNI, Centro
Hospitalar Universitário de São João,
Porto, Portugal
marta.drummond@gmail.com
Marieke L. Duiverman
Department of Pulmonary Diseases/
Home Mechanical Ventilation, University
of Groningen, University Medical Center
Groningen, Groningen, and Groningen
Research Institute of Asthma and COPD,
University of Groningen, University
Medical Center Groningen, The
Netherlands
m.l.duiverman@umcg.nl
Refika Ersu
Division of Pediatric Respirology,
Children’s Hospital of Eastern Ontario,
University of Ottawa, Ottawa, ON,
Canada
rersu@yahoo.com
Francesco Fanfulla
Respiratory Function and Sleep Unit,
Scientific Institutes of Pavia and
Montescano IRCCS, Istituti Clinici
Scientifici Maugeri, Pavia, Italy
francesco.fanfulla@icsmaugeri.it
Brigitte Fauroux
Pediatric Noninvasive Ventilation and
Sleep Unit, AP-HP, Hôpital
Necker-Enfants malades, Paris, France
brigitte.fauroux@aphp.fr
Luigi Ferini-Strambi
Department of Clinical Neurosciences,
Neurology – Sleep Disorders Center,
IRCCS San Raaele Scientific Institute,
Milan, and “Vita-Salute” San Raaele
University, Milan, Italy
ferinistrambi.luigi@hsr.it
Andrea Galbiati
Department of Clinical Neurosciences,
Neurology – Sleep Disorders Center,
IRCCS San Raaele Scientific Institute,
Milan, and “Vita- Salute” San Raaele
University, Milan, Italy
andrea.galbiati.unisr@gmail.com
Sergio Garbarino
Department of Neuroscience,
Rehabilitation, Ophthalmology, Genetics
and Maternal/Child Sciences (DINOGMI),
University of Genoa, Genoa, Italy
sgarbarino.neuro@gmail.com
x
Robin Germany
Division of Cardiovascular Diseases,
University of Oklahoma, Oklahoma City,
OK, USA
robin-germany@ouhsc.edu
Maelle Guellerin
https://t.me/medicina_free
University Grenoble Alpes, Grenoble,
and Service Hospitalo-Universitaire
Pneumologie et Physiologie,
Grenoble, France
MGuellerin2@chu-grenoble.fr
Anna Heidbreder
Department of Neurology, Medical
University Innsbruck, Innsbruck, Austria
anna.heidbreder@i-med.ac.at
Shahrokh Javaheri
Montgomery Sleep Laboratory, Bethesda
North Hospital, Cincinnati, OH, and
University of Cincinnati, College of
Medicine, Cincinnati, OH, USA
shahrokhjavaheri@icloud.com
Athanasios Kaditis
Division of Pediatric Pulmonology, Sleep
Disorders Laboratory, First Department
of Pediatrics, University of Athens
School of Medicine and Agia Sofia
Children’s Hospital, Athens, Greece
kaditia@hotmail.com
Alexandros Kalkanis
Department of Respiratory Diseases, UZ
Leuven, Leuven, Belgium
alexandros.kalkanis@uzleuven.be
Ulf Kallweit
Clinic of Sleep and Neuroimmunology,
Institute of Immunology, and Center
for Biomedical Education and Research
(ZBAF), University Witten/Herdecke,
Witten, Germany
Ulf.Kallweit@uni-wh.de
Georgios Kaltsakas
Lane Fox Unit, Sleep Disorders Centre,
Guy’s & St Thomas’ NHS Foundation
Trust, and Centre for Human and
Applied Physiological Sciences
(CHAPS), School of Basic and Medical
Biosciences, Faculty of Life Sciences
& Medicine, King’s College London,
London, UK
georgios.kaltsakas@gstt.nhs.uk
Barry Kennedy
Department of Respiratory Medicine,
St James’ Hospital, Dublin, Ireland
Bkennedy@stjames.ie
Brian D. Kent
Department of Respiratory Medicine, St
James’ Hospital, Dublin, and School of
Medicine, Trinity College Dublin, Dublin,
Ireland
briankent@physicians.ie
Marie Marklund
Department of Orthodontics, Faculty
of Medicine, Umeå University, Umeå,
Sweden
marie.marklund@umu.se
Juan F. Masa Jiménez
CIBER of Respiratory Diseases
(CIBERES), Madrid, and Pneumology
Service, San Pedro de Alcántara
Hospital, Cáceres, Spain
fmasa@separ.es
Frederik Massie
ResMed Science Center, Leuven,
Belgium, and Department of
Engineering, Natural Interaction Lab,
University of Oxford, Oxford, UK
frederik.massie@eng.ox.ac.uk
Gisèle Maury
Department of Respiratory Diseases,
Université Catholique de Louvain, Yvoir,
Belgium
gisele.maury@chuuclnamur.uclouvain.
be
Walter T. McNicholas
School of Medicine, University College
Dublin, and Department of Respiratory
and Sleep Medicine, St. Vincent’s
Hospital Group, Dublin, Ireland
walter.mcnicholas@ucd.ie
Ludovico Messineo
Division of Sleep and Circadian
Disorders, Brigham and Women’s
Hospital and Harvard Medical School,
Boston, MA, USA
ludovico.messineo@yahoo.it
Imran Johan Meurling
Sleep Disorders Centre, Guy’s & St
Thomas’ NHS Foundation Trust,
London, UK
johan.meurling@gstt.nhs.uk
Maria Paola Mogavero
Sleep Disorders Center, Vita-Salute San
Raaele University, Milan, Italy
paola_mogavero@libero.it
xi
Emilia C. Monteiro
https://t.me/medicina_free
CEDOC, Chronic Diseases Research
Center, NOVA Medical School/
Faculdade de Ciências Médicas,
Universidade Nova de Lisboa, Lisbon,
Portugal
emilia.monteiro@nms.unl.pt
Timothy I. Morgenthaler
Center for Sleep Medicine, Division of
Pulmonary, Critical Care, and Sleep
Medicine, Mayo Clinic, Rochester, MN,
USA
tmorgenthaler@mayo.edu
Annabel H. Nickol
Oxford Centre for Respiratory Medicine,
Oxford University Hospital NHS
Foundation Trust, Oxford, UK
Annabel.nickol@ndm.ox.ac.uk
Dimitrios Papadopoulos
Department of Respiratory Diseases, UZ
Leuven, Leuven, Belgium
dimitrios.papadopoulos@uzleuven.be
Athanasia Pataka
Respiratory Failure Unit G Papanikolaou
Hospital Thessaloniki, Aristotle
University of Thessaloniki, Thessaloniki,
Greece
patakath@yahoo.gr
Jean-Louis Pépin
University Grenoble Alpes, Grenoble,
France
jpepin@chu-grenoble.fr
Elisa Perger
Istituto Auxologico Italiano, IRCCS,
Sleep Disorders Center & Department
of Cardiovascular, Neural and Metabolic
Sciences, San Luca Hospital, and
Department of Medicine and Surgery,
University of Milano-Bicocca, Milan,
Italy
elisaperger@hotmail.com
Dirk Pevernagie
Department of Respiratory Medicine,
Ghent University Hospital, and
Department of Internal Medicine and
Paediatrics, Faculty of Medicine and
Health Sciences, Ghent University,
Ghent, Belgium
Dirk.Pevernagie@UGent.be
xii
Victor R. Ramírez Molina
Hospital H+ Querétaro, Querétaro,
Mexico
victorraul_26@hotmail.com
Renata L. Riha
Department of Sleep Medicine, Royal
Infirmary of Edinburgh, and University of
Edinburgh, Edinburgh, UK
rlriha@hotmail.com
Ivana Rosenzweig
Sleep and Brain Plasticity Centre,
Neuroimaging, IoPPN, King’s College
London, London, UK
ivana.1.rosenzweig@kcl.ac.uk
Silke Ryan
School of Medicine, University College
Dublin, and Pulmonary and Sleep
Disorders Unit, St Vincent’s University
Hospital, Dublin, Ireland
silke.ryan@ucd.ie
Bernardo Selim
Respiratory Care Unit, Division of
Pulmonary, Critical Care, and Sleep
Medicine, Mayo Clinic, Rochester, MN,
USA
selim.bernardo@mayo.edu
Marco Sforza
Department of Clinical Neurosciences,
Neurology – Sleep Disorders Center,
IRCCS San Raaele Scientific Institute,
Milan, and “Vita- Salute” San Raaele
University, Milan, Italy
marco.sforza@gmail.com
Neeraj M. Shah
Lane Fox Unit, Sleep Disorders Centre,
Guy’s & St Thomas’ NHS Foundation
Trust, and Centre for Human and Applied
Physiological Sciences (CHAPS), School
of Basic and Medical Biosciences, Faculty
of Life Sciences & Medicine, King’s
College London, London, UK
neeraj.shah@gstt.nhs.uk
Ambra Stefani
Department of Neurology, Neurological
Clinical Research Institute,
Massachusetts General Hospital, Boston,
MA, USA, and Department of Neurology,
Sleep Disorders Clinic, Medical University
of Innsbruck, Innsbruck, Austria
astefani2@mgh.harvard.edu, ambra.
stefani@i-med.ac.at
Joerg Steier
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Lane Fox Unit, Sleep Disorders Centre,
Guy’s & St Thomas’ NHS Foundation
Trust, and Centre for Human and
Applied Physiological Sciences
(CHAPS), School of Basic and Medical
Biosciences, Faculty of Life Sciences
& Medicine, King’s College London,
London, UK
joerg.steier@kcl.ac.uk
Renaud Tamisier
University Grenoble Alpes, Grenoble,
and Service Hospitalo-Universitaire
Pneumologie et Physiologie,
Grenoble, France
rtamisier@chu-grenoble.fr
Hui-Leng Tan
Department of Pediatric Respiratory
Medicine, Royal Brompton Hospital,
London, UK
H.Tan@rbht.nhs.uk
Luigi Taranto-Montemurro
Division of Sleep and Circadian
Disorders, Brigham and Women’s
Hospital and Harvard Medical School,
Boston, MA, USA
ltarantomontemurro@bwh.harvard.edu
Dries Testelmans
Department of Respiratory Diseases, UZ
Leuven, Leuven, Belgium
dries.testelmans@uzleuven.be
Michel Toussaint
Centre de Référence Neuromusculaire,
Department of Neurology, Cliniques
Universitaires de Bruxelles, Hôpital
Erasme, Université libre de Bruxelles
(ULB), Brussels, Belgium
Michel.Toussaint@erasme.ulb.ac.be
Ha Trang
University of Paris; AP-HP, University
Hospital Robert Debré; Paediatric Sleep
Centre, Centre of reference for CCHS,
Paris, France
ha.trang@aphp.fr
Piet-Heijn van Mechelen
Stichting Apneu Research, Bentveld, the
Netherlands
phvanmechelen@gmail.com
Olivier Vanderveken
Multidisciplinary Sleep Disorders
Centre, Antwerp University Hospital
and University of Antwerp, Antwerp,
Belgium
olivier.vanderveken@uantwerp.be
Johan Verbraecken
Multidisciplinary Sleep Disorders
Centre, Antwerp University Hospital
and University of Antwerp, Antwerp,
Belgium
johan.verbraecken@uza.be
Stijn Verhulst
Department of Pediatrics, Antwerp
University Hospital and Lab of
Experimental Medicine and Pediatrics,
University of Antwerp, Antwerp,
Belgium
stijn.verhulst@uantwerpen.be
Maria Pia Villa
Department of Pediatrics, Sleep Disease
Centre, University of Rome
La Sapienza-Sant’Andrea Hospital,
Rome, Italy
mariapia.villa@fondazione.uniroma1.it
Steven Vits
Faculty of Medicine and Health
Sciences, University of Antwerp,
Antwerp, and ResMed Science Center,
Leuven, Belgium
Steven.Vits@student.uantwerpen.be
Peter J. Wijkstra
Department of Pulmonary Diseases/
Home Mechanical Ventilation,
University of Groningen, University
Medical Center Groningen, Groningen,
and Groningen Research Institute
of Asthma and COPD, University of
Groningen, University Medical Center
Groningen, The Netherlands
p.j.wijkstra@umcg.nl
Conflicts of interest
Disclosures for all authors are given at
https://doi.org/10.1183/9781849841641.coi
xiii
List of abbreviations
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AHI apnoea–hypopnoea index
ASV adaptive servo ventilation
BMI body mass index
BP blood pressure
BPAP bilevel positive airway
pressure
CHF congestive heart failure
CPAP continuous positive airway
pressure
CSA central sleep apnoea
CSR Cheyne–Stokes respiration
CVD cardiovascular disease
COPD chronic obstructive
pulmonary disease
DBP diastolic BP
EDS excessive daytime
sleepiness
EEG electroencephalography
EMG electromyography
ENT ear, nose and throat
EOG electrooculography
EPAP expiratory positive airway
pressure
ESS Epworth Sleepiness Scale
FVC forced vital capacity
FRC functional residual capacity
FEV1 forced expiratory volume
in 1 s
HF heart failure
ICSD International Classification
of Sleep Disorders
IPAP inspiratory positive airway
pressure
MRI magnetic resonance imaging
MSLT Multiple Sleep Latency Test
NIV noninvasive ventilation
NREM non-rapid eye movement
OHS obesity hypoventilation
syndrome
OSA obstructive sleep apnoea
OSAS OSA syndrome
OSLER Oxford Sleep Resistance Test
P
arterial carbon dioxide
aCO
2
tension
P
arterial oxygen tension
aO
2
PAP positive airway pressure
PSG polysomnography
P
transcutaneous carbon
tcCO
2
dioxide tension
REM rapid eye movement
SAHS sleep apnoea–hypopnoea
syndrome
S
arterial oxygen saturation
aO
2
SDB sleep disordered breathing
SBP systolic blood pressure
V'E minute ventilation
xiv
Preface
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Respiratory sleep medicine is a rapidly evolving discipline in pneumology.
Since the first edition of the ERS Handbook of Respiratory Sleep Medicine, we
have seen significant progress in the pathophysiological understanding of the
various endotypes of obstructive sleep apnoea, described distinct phenotypes
based on symptoms and comorbidities, and gained insights into the
limitations and potential of biomarkers. This helps us to reformulate a pure
mechanistic understanding of the disease. Moreover, we have proceeded from
a generic definition of the disease based on the apnoea–hypopnoea index to
its replacement by outcome-oriented or patient-related biomarkers. Similarly,
we are currently discovering important information about the dierent
phenotypes of central sleep apnoea and its optimal, personalised treatment.
Finally, large randomised controlled studies have produced unexpected
results, that underline the urgent need for a change in study design and use
of refined statistical analysis based on large number of patients. Therefore, an
update of the ERS Handbook of Respiratory Sleep Medicine is clearly necessary.
Sleep medicine is a true multidisciplinary field. Sleep physicians are referred
and treat patients from all specialties of medicine. Therefore, we are grateful
for the contributions from colleagues, not only from pulmonary medicine, but
also from neurology, paediatrics, psychiatry and ENT, among others.
We have worked to ensure the book provides a valuable update, not only for
experienced sleep specialists, but also for trainees, nurses and allied healthcare
professionals. Our aim is to focus on practical aspects, tips and advice based
on clinical practice and up-to-date guidelines.
We are really grateful to everyone who contributed to this edition.
Maria R. Bonsignore, Winfried Randerath,
Sophia E. Schiza and Anita K. Simonds
Chief editors
xv
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Neurobiology and
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physiology of sleep and
breathing
Ivana Rosenzweig, Silvia V. Conde and Emilia C. Monteiro
Sleep has been defined as a recurring, reversible neurobehavioural state of psychomotor
arrest with increased arousal threshold. This neurobehavioural state is facilitated by
relative perceptual disengagement and unresponsiveness to the environment. Sleep
involves sets of complex interactions in the central nervous system and all other body
systems that are still far from being fully understood. As humans, we spend up to
third of our lives in this universal neurobehavioural state that has been observed in
all species of animals and which is commonly accompanied by postural recumbence,
behavioural quiescence and closed eyes.
The neural regulation of the sleep–wake cycle
During sleep, the brain continues to be active in complex series of stages that repeat
itself in a characteristic pattern. Healthy human sleep comprises two states, REM
and NREM sleep, which alternate cyclically across a sleep episode. The timing and
quality of sleep are determined by intricate interplay of ultradian, homeostatic and
circadian factors.
Circadian and homeostatic signals are integrated in diencephalic brain structures.
Circadian sleep rhythm is among several intrinsic body rhythms modulated by the
hypothalamus. Its rhythmicity is based on an interlocking positive–negative feedback
mechanism that controls gene transcription in the suprachiasmatic nucleus (SCN) of
Key points
• Glutamatergic neurons in the parabrachial nucleus provide main ascending
arousal influence from the brainstem.
• Cycles of NREM and REM sleep alternate throughout the night in a predictable
manner.
• HRV varies with gender, age, previous hypoxic exposures and sustained CO2
tension, and can be modified if hypoxia is sustained or intermittent.
• Reductions in BP and heart rate occur during NREM sleep phase (dipping
phenomenon).
• Peaks in BP and heart rate variability are characteristic of REM and transitions
from NREM sleep, and associated to high cardiovascular morbidity in the early
morning.
1ERS Handbook: Respiratory Sleep Medicine
Neurobiology and physiology
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the hypothalamus. The physiological mechanism of the circadian rhythm is probably
initiated by light striking particular cells in the retina of the eye. These cells then
secrete a hormone that causes the SCN to signal the pineal body to stop secreting
melatonin. The SCN sets the body’s ‘clock’ to ∼24.2 h; light exposure and schedule
clues entrain this to the 24-h cycle. Circadian rhythm disruption can have severe
health implications in multiple organ systems. Recently, the presence of secondary
or peripheral oscillators has been demonstrated throughout the body. Whilst they
act independently, they are all nonetheless synchronised with the SCN, as well as
other external cues, such as temperature and timing of meals. The best method of
measuring the circadian rhythm includes monitoring the core body temperature and
salivary or plasma melatonin levels.
Previous models of brain circuitry controlling homeostatic wake–sleep focused on
monoaminergic and cholinergic arousal systems. However, recent evidence suggests
that these may play a modulatory role, and that the backbone of the wake–sleep
regulatory system depends upon glutamate and γ-aminobutyric acid (GABA) fast
neurotransmitters (figure 1).
The brain transitions from a slow-wave state to REM sleep (figure 2), the brain state
with a faster, low voltage EEG and loss of muscle tone (atonia), associated with
REMs. The REM sleep is likely generated by a population of glutamatergic neurons in
the region just ventral to the locus coeruleus, in the region oen referred to as the
subcoeruleus region. The ventrally based neurons from this region instigate motor
atonia due to activation of inhibitory interneurons in the medulla and the spinal
cord. REM sleep is associated with EEG desynchronisation, the source of which is
yet unknown. However, all the nearby regions that project to the forebrain, namely
the parabrachial nucleus, pedunculopontine and laterodorsal tegmental nucleus,
also contain REM-active neurons. Similarly, it is not known which circuitry underlies
the activation of eye movements but some studies suggest that they may be due to
short projections to the paramedian pontine reticular formation. A main control over
the REM generator is through inhibitory, mostly GABAergic neurons in the nearby
ventrolateral periaqueductal grey matter, at the level where the cerebral aqueduct
begins to open into the fourth ventricle.
Normal sleep architecture
Sleep has a unique structure with a cyclical pattern composed of dierent sleep stages
and transitions between them. Sleep architecture is traditionally represented by a
graph called a hypnogram (figure 3). Sleep architecture and stages can be evaluated
by PSG, which evaluates brain activity using specific scalp EEG channels and eye
movements with EOG electrodes. Other EMG electrodes, and respiratory and cardiac
monitoring are also required.
In 1968, Rechtschaen, Kales and a committee of experts established the rules for
the scoring of sleep in normal human adults, on which the current American Academy
of Sleep Medicine (AASM) scoring is based. The sleep scoring assesses data seen in
sequential 30-s images (epochs) of PSG.
The dierent sleep stages of NREM–REM cycling are associated with diverse
physiological changes. In adults, sleep is most oen initiated through NREM sleep and is
marked by synchronisation of EEG activity. NREM sleep has increased parasympathetic
tone with slow heart rate, low BP and decreased respiratory rate. Body temperature
is lowest during NREM sleep. During REM sleep, autonomic instability with bursts of
sympathetic activity causes irregular heart rate and transient increases in BP. Similarly,
2
ERS Handbook: Respiratory Sleep Medicine
Neurobiology and physiology
a) b)
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LH
GABA
BF
SUM
(ACh,
(Glu,
GABA)
GABA)
Hypothalamus
Pons
Medulla
Thalamus
LH
(ORX)
TMN
(Hist)
Raphe
(5HT)
vPAG
(DA)
LDT (ACh)
PPT (ACh)
PB, PPT (Glu)
LC (NA)
(GABA, Gal)
Hypothalamus
Cerebellum
Brainstem
MNPO
VLPO
Thalamus
MCH
TMN
SUM
(Hist,
Glu)
Pons
Medulla
ORX
Raphe
(5-HT)
(NA)
LC
(GABA)
PFZ
vPAG
(DA)
LDT (ACh)
PPT (ACh)
PB
Cerebellum
Brainstem
Figure 1. a) A schematic presentation of the fast neurotransmitter systems that have the largest
role in promoting wakefulness. The monoaminergic, cholinergic and peptidergic neurons in
the brainstem and hypothalamus, which were prominent in earlier models, are here shown in
brown. They play a modulatory role and lesions in these locations have little eect on wake–sleep
amounts. The backbone of the arousal system is shown here in red: this is the glutamatergic input
from the parabrachial nucleus (PB) and pedunculopontine tegmental nucleus (PPT) to the basal
forebrain, and the GABAergic and cholinergic neurons in the basal forebrain (BF) that diusely
innervate the cerebral cortex. Lesions at these sites result in loss of consciousness, whereas
lesions of supramammillary (SUM) glutamatergic or dopaminergic (DA) neurons in the ventral
periaqueductal grey matter (vPAG) near the dorsal raphe nucleus commonly cause ∼20% loss
of wake time. Additionally, two populations of GABAergic neurons in the lateral hypothalamus
(LH), shown in purple, may also promote wakefulness by inhibiting sleep promoting neurons in
the thalamus and preoptic area. b) A schematic presentation of the fast neurotransmitter systems
that contribute to sleep promotion (purple). Ventrolateral preoptic (VLPO) and median preoptic
(MnPO) GABAergic neurons send axons to most components of the arousal system (shown in
red, orange and green), and are thought to inhibit them in a coordinated fashion. Parafacial
zone (PFZ) GABAergic neurons in the medulla have a pro-hypnotic eect by inhibiting the
parabrachial glutamatergic arousal neurons. Melanin-concentrating hormone (MCH) neurons
in the lateral hypothalamus contain both GABA and glutamate (Glu), and may be able to release
them at dierent terminal sites, including neurons in the brainstem that control REM sleep. 5HT:
serotonin; ACh: acetylcholine; Hist: histamine; LC: locus coeruleus; LDT: laterodorsal tegmental
nucleus; NA: noradrenaline; ORX: orexin; TMN: tuberomammillary nucleus. Reproduced and
modified from Saper et al. (2017) with permission from the publisher.
during REM, respiratory rate increases, but the ventilatory drive responding to hypoxia
and hypercapnia decreases. A healthy nocturnal pattern of sleep (figure 3) commonly
includes several consistent features. It starts with NREM N1 and progresses through
deeper NREM stages (N2 and N3), before the first episode of REM sleep occurs
approximately 80–100 min later. Aer that, NREM and REM sleep cycle with a period
of ∼90 min. The 90-min NREM–REM cycle is repeated approximately three to six
times during the night, with N3 sleep stages being more concentrated in the early
NREM cycles, while REM sleep episodes lengthen through the night. The preferential
occurrence of NREM sleep (e.g. slow-wave sleep (SWS)) early in the night is coincidental
with sleep homeostasis, while the predominance of REM sleep later in the night is
thought to be associated with the circadian rhythm of core body temperature. The
transition from wake to sleep can be dicult to determine as there are typically brief
periods of drowsiness with transient bursts of wakefulness before sleep consolidation.
3ERS Handbook: Respiratory Sleep Medicine
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