Obstructive Sleep Apnea Diagnosis and Treatment - part 1 pps

Obstructive
Sleep Apnea
Diagnosis and Treatment
SLEEP DISORDERS
Advisory Board
Antonio Culebras, M.D.
Professor of Neurology
Upstate Medical University
Consultant, The Sleep Center
Community General Hospital
Syracuse, New York, U.S.A.
Anna Ivanenko, M.D., Ph.D.
Loyola University Medical Center
Department of Psychiatry and Behavioral Neuroscience
Maywood, Illinois, U.S.A.
Clete A. Kushida, M.D., Ph.D., RPSGT
Director, Stanford Center for Human Sleep Research
Associate Professor, Stanford University Medical Center
Stanford University Center of Excellence for Sleep Disorders
Stanford, California, U.S.A.
Nathaniel F. Watson, M.D.
University of Washington Sleep Disorders Center
Harborview Medical Center
Seattle, Washington, U.S.A.
1. Clinician’s Guide to Pediatric Sleep Disorders, edited by
Mark A. Richardson and Norman R. Friedman
2. Sleep Disorders and Neurologic Diseases, Second Edition,
edited by Antonio Culebras
3. Obstructive Sleep Apnea: Pathophysiology, Comorbidities, and
Consequences, edited by Clete A. Kushida

4. Obstructive Sleep Apnea: Diagnosis and Treatment,
edited by Clete A. Kushida

Edited by
Clete A. Kushida
Stanford University
Stanford, California, USA
Obstructive
Sleep Apnea
Diagnosis and Treatment
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Library of Congress Cataloging-in-Publication Data
Obstructive sleep apnea: Diagnosis and treatment / edited
by Clete A. Kushida.
p. ; cm. (Sleep disorders ; 4)
Includes bibliographical references and index.
ISBN-13: 978-0-8493-9182-8 (hb : alk. paper)
ISBN-10: 0-8493-9182-2 (hb : alk. paper) 1. Sleep apnea syndromes. I. Kushida,
Clete Anthony, 1960- II. Title: Diagnosis and treatment.
III. Series: Sleep disorders (New York, N.Y.) ; 4.
[DNLM: 1. Sleep Apnea, Obstructive diagnosis. 2. Sleep Apnea,
Obstructive therapy. WF 143 O139 2007]
RC737.5.O265 2007
616.2’09 dc22 2007000617
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iii
Preface
“When in doubt, pressurize the snout.”
—attributal to Philip R. Westbrook
I often thought of this mantra during my on-call nights when, as a Stanford sleep
medicine fellow, I was awakened from sleep by a technologist informing me that
one of the clinic patients had repetitive obstructive apneas with significant oxygen

desaturations. The technologist would typically ask, “can I start the patient on CPAP?”
Invariably, I would mutter a drowsy “yes,” often chiding myself that on the previous
day I should have clearly written the respiratory thresholds for starting continuous
positive airway pressure on the patient’s sleep-study order sheet. This anecdote
illustrates the fact that continuous positive airway pressure has become such an
important and ubiquitous treatment for obstructive sleep apnea since its develop-
ment over a quarter century ago. The modern sleep specialist has new diagnostic
tools and other treatments, such as upper airway surgery and oral appliances, for
patients with obstructive sleep apnea; nevertheless, our field is still in its adole-
scence with respect to the diagnosis and treatment of obstructive sleep apnea and
other sleep disorders.
The reader might wonder why a neurologist is editing a two-volume set of
books on obstructive sleep apnea, since it is a sleep-related breathing disorder and
would therefore appear to be within the domain of pulmonary physicians. However,
besides pulmonologists—neurologists, psychiatrists, internists, pediatricians, and
otolaryngologists have entered the field of sleep medicine. Many clinicians now
treat patients with sleep disorders on a full-time basis. Sleep medicine has truly
become multidisciplinary, and a sleep clinician is expected to diagnose and treat a
wide range of sleep disorders, from insomnia to restless legs syndrome, that were
previously referred by internists to other specialists.
It is indeed a testament to the ever-increasing knowledge base on obstructive
sleep apnea that there is a need for a two-volume set of books on this topic. The first
volume, Obstructive Sleep Apnea: Pathophysiology, Comorbidities, and Consequences
covers the pathophysiology, comorbidities, and consequences of obstructive sleep
apnea, with sections exploring the features, factors, and characteristics of this disor-
der as well as its associations and consequences. This volume focuses on the diag-
nosis and treatment of obstructive sleep apnea, and includes a section on special
conditions, disorders, and clinical issues. The authors and I have tried to conform
the conditions and disorders described in this book to the second edition of the
International Classification of Sleep Disorders: Diagnostic & Coding Manual published

by the American Academy of Sleep Medicine in 2006, although some terms, such as
obstructive sleep apnea syndrome and sleep-disordered breathing, have been
retained in a few statements when appropriate. We have also tried to discuss new
entities and findings such as complex sleep apnea, oxidative stress, cyclic alternat-
ing pattern, and adaptive servo-ventilation. However, given the rapidity with which
the area of sleep medicine is advancing, it is highly conceivable that two volumes
might not be sufficient to cover the topic of obstructive sleep apnea in just a few
short years!
These books could not exist without the excellent contributions of a talented
group of international authors; their detailed and comprehensive works are greatly
appreciated. I am deeply indebted to the renowned and true pioneers of our field of
sleep, William Dement, Christian Guilleminault, Sonia Ancoli-Israel, Chris Gillin,
and Allan Rechtschaffen, who served as my mentors through various stages of my
career. In all of my endeavors, I can always count on my parents, Samiko and Hiroshi
Kushida, to assist me; these books were no exception. I have been very fortunate to
serve, along with Dr. Dement, as Principal Investigator of the multicenter, rand-
omized, double-blind, placebo-controlled Apnea Positive Pressure Long-Term
Efficacy Study, sponsored by the National Heart, Lung, and Blood Institute of the
National Institutes of Health. To date, this is the largest controlled trial funded by
the National Institutes of Health in the field of sleep.
This book is dedicated not only to my parents but also to the marvelous core
team of the Apnea Positive Pressure Long-Term Efficacy Study, consisting of William
Dement, Pamela Hyde, Deborah Nichols, Eileen Leary, Tyson Holmes, Dan Bloch,
as well as National Heart, Lung, and Blood Institute officials (Michael Twery and
Gail Weinmann), site directors, coordinators, consultants, committee members, key
Stanford site personnel (Chia-Yu Cardell, Rhonda Wong, Pete Silva, Jennifer Blair),
Data and Safety Monitoring Board members, and other personnel without whom
this project could not have functioned in such a meticulous and efficient manner.
It is my sincere hope that the reader will strive to become expert in the field of
sleep. Although there is always room for improvement, awareness of sleep disor-

ders by patients, physicians, and the general public is at an all-time high. However,
available funding for sleep research and the number of young investigators inter-
ested in a career in basic or clinical sleep research are areas that need enhancement.
The interested reader can directly contribute to this field in several ways: applying
for membership in the American Academy of Sleep Medicine or Sleep Research
Society, serving on committees in these organizations, becoming board certified in
sleep medicine, submitting a sleep-related grant proposal to the National Institutes
of Health, and/or just simply learning more about sleep and its disorders.
Lastly, etched forever in my memory is a sticker posted on the door of Mary
Carskadon’s former office at Stanford that contained words to live by: “Be alert. The
world needs more lerts.”
Clete A. Kushida
iv Preface
v
Contents
Preface . . . . iii
Contributors . . . . vii
SECTION I: DIAGNOSIS
1. History and Physical Examination 1
Rory Ramsey, Amit Khanna, and Kingman P. Strohl
2. Screening and Case Finding 21
Charles F. P. George
3. Polysomnography and Cardiorespiratory Monitoring 35
Michael R. Littner
4. Upper Airway Imaging 61
Nirav P. Patel and Richard J. Schwab
5. Alertness and Sleepiness Assessment 89
Max Hirshkowitz
SECTION II: TREATMENT
6. Continuous Positive Airway Pressure 101

Peter R. Buchanan and Ronald R. Grunstein
7. Bilevel Pressure and Adaptive Servo-Ventilation for Obstructive
and Complex Sleep Apnea 125
Peter C. Gay
8. Auto-Positive Airway Pressure 137
Richard B. Berry
9. Critical Factors in Positive Pressure Therapy 151
Scott M. Leibowitz and Mark S. Aloia
10. Noninvasive Positive Ventilation 173
Dominique Robert and Laurent Argaud
11. Upper Airway Surgery in the Adult 191
Donald M. Sesso, Nelson B. Powell, Robert W. Riley, and Jerome E. Hester
12. Oral Appliances 217
Peter A. Cistulli and M. Ali Darendeliler
13. Adjunctive and Alternative Therapies 233
Alan T. Mulgrew, Krista Sigurdson, and Najib T. Ayas
SECTION III: SPECIAL CONDITIONS, DISORDERS, AND CLINICAL ISSUES
14. Gender Differences in Obstructive Sleep Apnea 247
Vidya Krishnan and Nancy A. Collop
15. Obstructive Sleep Apnea in Children 261
Rafael Pelayo and Kasey K. Li
16. Obstructive Sleep Apnea in the Elderly 281
Lavinia Fiorentino and Sonia Ancoli-Israel
17. Medication Effects 295
Julie A. Dopheide
18. Snoring and Upper Airway Resistance Syndrome 305
Riccardo A. Stoohs and Antoine Aschmann
19. Central Sleep Apnea 321
M. Safwan Badr
20. Other Respiratory Conditions and Disorders 333

Francesco Fanfulla
21. Other Sleep Disorders 347
Meeta H. Bhatt and Sudhansu Chokroverty
22. Neurological Disorders 367
Maha Alattar and Bradley V. Vaughn
23. Medical Disorders 389
Robert D. Ballard
24. Legal Implications of Obstructive Sleep Apnea 405
Daniel B. Brown
25. A Concluding Note and Future Directions 425
William C. Dement
Index . . . . 427
vi
Contents
vii
Contributors
Maha Alattar Department of Neurology, University of North Carolina, Chapel Hill,
North Carolina, U.S.A.
Mark S. Aloia Butler Hospital, Providence, Rhode Island, U.S.A.
Sonia Ancoli-Israel Department of Psychiatry, University of California, San Diego
and Veterans Affairs San Diego Healthcare System, San Diego, California, U.S.A.
Laurent Argaud Emergency and Intensive Care Department, Edouard Herriot
Hospital, Lyon, France
Antoine Aschmann Medica Surgical Private Clinics, Mülheim, Germany
Najib T. Ayas Sleep Disorders Program and Respiratory Division, University of
British Columbia, Vancouver, British Columbia, Canada
M. Safwan Badr Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine,
Wayne State University School of Medicine, Detroit, Michigan, U.S.A.
Robert D. Ballard Advanced Center for Sleep Medicine, Presbyterian/St. Luke’s
Medical Center, Denver, Colorado, U.S.A.

Richard B. Berry Division of Pulmonary, Critical Care, and Sleep Medicine,
University of Florida, Gainesville, Florida, U.S.A.
Meeta H. Bhatt New York University School of Medicine and New York Sleep
Institute, New York, New York, U.S.A.
Daniel B. Brown Greenberg Traurig, LLP, Atlanta, Georgia, U.S.A.
Peter R. Buchanan Royal Prince Alfred Hospital, Woolcock Institute of Medical
Research and The University of Sydney, Sydney, Australia
Sudhansu Chokroverty Department of Neurology, NJ Neuroscience Institute at JFK
Medical Center, Edison, New Jersey and Seton Hall University, South Orange,
New Jersey, U.S.A.
Peter A. Cistulli Centre for Sleep Health & Research, Royal North Shore Hospital and
The University of Sydney and Woolcock Institute of Medical Research, Sydney,
Australia
Nancy A. Collop Division of Pulmonary/Critical Care Medicine, Johns Hopkins
University, Baltimore, Maryland, U.S.A.
M. Ali Darendeliler Discipline of Orthodontics, Faculty of Dentistry, The University
of Sydney and Department of Orthodontics, Sydney Dental Hospital, Sydney, Australia
William C. Dement Stanford Sleep Research Center, Palo Alto, California, U.S.A.
Julie A. Dopheide Schools of Pharmacy and Medicine, University of Southern
California, Los Angeles, California, U.S.A.
Francesco Fanfulla Centro di Medicina del Sonno ad indirizzo cardio-respiratorio,
Istituto Scientifico di Montescano IRCCS, Fondazione Salvatore Maugeri, Montescano
(Pavia), Italy
Lavinia Fiorentino Department of Psychiatry, University of California, San Diego
and Veterans Affairs San Diego Healthcare System, San Diego, California, U.S.A.
Peter C. Gay Pulmonary, Critical Care, and Sleep Medicine, Mayo Clinic College
of Medicine, Rochester, Minnesota, U.S.A.
Charles F. P. George University of Western Ontario, London Health Sciences
Centre, London, Ontario, Canada
Ronald R. Grunstein Royal Prince Alfred Hospital, Woolcock Institute of Medical

Research and The University of Sydney, Sydney, Australia
Jerome E. Hester Department of Otolaryngology/Head and Neck Surgery,
Stanford University Medical Center, Palo Alto, California, U.S.A.
Max Hirshkowitz Sleep Center, VA Medical Center and Departments of Medicine
and Psychiatry, Baylor College of Medicine, Houston, Texas, U.S.A.
Amit Khanna Department of Family Medicine, Case Western Reserve University,
Cleveland, Ohio, U.S.A.
Vidya Krishnan Division of Pulmonary/Critical Care Medicine, Johns Hopkins
University, Baltimore, Maryland, U.S.A.
Scott M. Leibowitz The Sleep Disorders Center of Cardiac Disease Specialists,
Atlanta, Georgia, U.S.A.
Kasey K. Li Sleep Apnea Surgery Center, East Palo Alto, California, U.S.A.
Michael R. Littner VA Greater Los Angeles Healthcare System, Sulpulveda,
California and David Geffen School of Medicine, University of California, Los Angeles,
California, U.S.A.
Alan T. Mulgrew Sleep Disorders Program and Respiratory Division, University of
British Columbia, Vancouver, British Columbia, Canada
Nirav P. Patel Division of Pulmonary, Critical Care, and Allergy, Center for
Sleep & Respiratory Neurobiology, University of Pennsylvania Medical Center,
Philadelphia, Pennsylvania, U.S.A.
Rafael Pelayo Stanford University Center of Excellence for Sleep Disorders,
Stanford, California, U.S.A.
Nelson B. Powell Department of Otolaryngology/Head and Neck Surgery,
Stanford University Medical Center and Division of Sleep Medicine, Department of
Behavioral Sciences, Stanford School of Medicine, Palo Alto, California, U.S.A.
Rory Ramsey Division of Pulmonary and Critical Care Medicine, Department of
Medicine, Case Western Reserve University, Cleveland, Ohio, U.S.A.
viii
Contributors
Robert W. Riley Department of Otolaryngology/Head and Neck Surgery, Stanford

University Medical Center and Division of Sleep Medicine, Department of Behavioral
Sciences, Stanford School of Medicine, Palo Alto, California, U.S.A.
Dominique Robert University Claude Bernard and Edouard Herriot Hospital,
Lyon, France
Richard J. Schwab Division of Sleep Medicine, Pulmonary, Allergy, and Critical Care
Division; University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, U.S.A.
Donald M. Sesso Department of Otolaryngology/Head and Neck Surgery,
Stanford University Medical Center, Palo Alto, California, U.S.A.
Krista Sigurdson Sleep Disorders Program and Respiratory Division, University of
British Columbia, Vancouver, British Columbia, Canada
Riccardo A. Stoohs Somnolab Sleep Disorders Centers—Dortmund, Essen,
Dortmund, Germany
Kingman P. Strohl Division of Pulmonary and Critical Care Medicine, Department
of Medicine, Case Western Reserve University, Cleveland, Ohio, U.S.A.
Bradley V. Vaughn Department of Neurology, University of North Carolina, Chapel
Hill, North Carolina, U.S.A.
Contributors ix

1
History and Physical Examination
Rory Ramsey
Division of Pulmonary and Critical Care Medicine, Department of Medicine,
Case Western Reserve University, Cleveland, Ohio, U.S.A.
Amit Khanna
Department of Family Medicine, Case Western Reserve University, Cleveland,
Ohio, U.S.A.
Kingman P. Strohl
Division of Pulmonary and Critical Care Medicine, Department of Medicine,
Case Western Reserve University, Cleveland, Ohio, U.S.A.
INTRODUCTION

The patient-physician encounter is an inquiry designed to disclose and test disease
hypotheses. Physicians detect “cues” early in a patient interview and use them to
generate predictions about a disease presence or state. They then ask questions to
test the likelihood of hypothesized disease(s) and answers modify perceived proba-
bility. This process continues until a reasonable list of potential problems, a differential
diagnosis, is shaped and decisions become more explicit. Physicians rely on their
own experience, skill, and knowledge base to assign values to the presence or
absence of key clinical features.
The purpose of this chapter is to identify those features in sleep history taking
that are more likely to assign diagnostic value. The chapter will start by outlining
some of the cues that physicians use to direct a general sleep history and then detail
the contribution of other elements important in the consideration of obstructive
sleep apnea (OSA). A sleep-specific physical examination will then be discussed.
Adult and pediatric issues will be compared.
It is important to recognize that there are major limitations in the current
literature. To a considerable extent, the recommendations in this chapter result from
data from uncontrolled studies, case series, consensus guidelines, practice para-
meters, and other less rigorous forms of evidence like expert opinion; most of this
literature is not focused on how a history and physical help in patient management
or outcome. There is an enormous heterogeneity in study design, quality and in
populations studied, so that a concordance among studies on the history and physi-
cal is difficult to discuss at more than a superficial level. Finally, clinical studies
express associations in terms that are not always interchangeable, for example,
relative risk (RR), odds ratio (OR), correlation coefficient (r), positive predictive
value, likelihood ratio (LR), sensitivity, specificity, and so on. These features led to
challenges in producing this review.
Yet, there is value still present in a general medical examination. No features
or combination of features are ever fully sensitive and specific for sleep apnea or for
sleep problems. A physician–patient encounter should do more than just capture a
single suspected diagnosis. The process may involve not only a sleep outcome, but

1
Section I: Diagnosis
2 Ramsey et al.
can disclose comorbid conditions and personal issues that could optimize testing
and treatment.
MAIN CUES
Excessive Daytime Sleepiness
Excessive daytime sleepiness (EDS) is very common. Epidemiological studies
estimate the prevalence to be 8% to 30% in the general population (1–3) depending
on the definition of sleepiness and the population sampled. A primary care clinic-
based study found that 38.8% experienced wake time tiredness or fatigue at least
three to four times per week (4) and a study of sleep clinic patients found 50%
complaining of excess sleepiness (5).
EDS is a challenging symptom because of a significant overlap with features
of fatigue and the difficulty patients and physicians have in differentiating between
the two symptoms. Sleepiness is the tendency to fall asleep, whereas fatigue involves
a task context with musculoskeletal and/or neurasthenic qualities. For instance, one
author has described fatigue as a drive for rest, and daytime sleepiness as a drive for
sleep (6). Sleepiness may occur more often during “passive” conditions, such as
watching television or sitting as a passenger in a car; but in its most severe form,
sleepiness can intrude into “active” conditions, such as talking to someone or
driving a car.
Several instruments have been developed to identify and measure symptoms
of EDS (7). Currently, the most useful instrument may be the Epworth sleepiness
scale (8). It is a list of eight questions that measure the propensity to sleep in familiar
situations and has good test–retest reliability (9).
EDS is not particularly useful in directing one towards the consideration of
any one disease. It is, however, very important in the quantification of the problem
of sleepiness and should be described in regard to onset, situation, and chronicity.
Specifics about functional sleepiness are probably the most useful. It is also important

to note that people often underestimate their sleepiness (10). While the differential
diagnosis of EDS is wide, sleep-related disorders should be considered early on.
Snoring (See Also Chapter 18)
Community-based studies have estimated that as many 30% to 40% of the general
population (2,3,11) snores and others have shown that more than 50% of primary care
populations snore (4). Studies from community, primary care, and sleep clinics have
all shown a significant relationship between the presence of snoring and sleep apnea
(2,4,12–15), and some have incorporated snoring into clinical prediction rules for
sleep apnea (4,12–14). While snoring is clearly helpful in suggesting sleep apnea as
a diagnostic possibility, its high prevalence in widespread populations impairs its
ability to identify real disease. Nevertheless, this symptom should be described in
regard to onset, severity, frequency, quality, and chronicity.
Witnessed Apneas/Bed Partner’s Reports of Choking or Gasping
Polls have estimated that the prevalence of witnessed apneas in the general adult
population ranges from 3.8% to 6% (2,11,16). A primary care population survey
found that 11.1% of responders had observed breathing pauses at least one to two
times per month (4). Community-, primary care-, and sleep clinic-based studies
have all demonstrated a strong relationship between sleep apnea and witnessed
apneas or nocturnal choking and several have incorporated these reports into
multivariate prediction models for sleep apnea (12,14,17). One community-based
History and Physical Examination 3
study found that the report of apnea increased the odds of sleep apnea nine-fold (2)
and another sleep clinic-based study found that it increased the odds 19-fold (18). In
the Sleep Heart Health Study, witnessed apneas had the highest prevalence of all
collected demographic and predictor variables in patients with an apnea–hypopnea
index (AHI) ≥ 15 (15). However, the utility of this report is limited by a low sensitivity
as only 9% of these sleep apnea subjects reported this symptom (15). Two additional
limitations include the fact that not everyone has a bed partner and people may be
poor reporters when it comes to describing respiratory events at night (19).
Insomnia

Insomnia is a repeated difficulty with sleep initiation, duration, consolidation, or
quality that occurs despite adequate time and opportunity for sleep and results in
some form of daytime impairment (20). Collectively, insomnia encompasses:
adequate sleep opportunity, a persistent sleep difficulty, and associated daytime
dysfunction. Among adults, insomnia typically manifests as difficulty initiating sleep,
maintaining sleep, waking up too early, or sleep that is chronically nonrestorative or
poor in quality. When considering adults who experience daytime sleepiness a few
days a week versus those who do not, 73% complain of at least one symptom of
insomnia, while only 25% carry a diagnosis of a sleep disorder (21). Detailed inquiry
regarding the use of sleep aids is important when assessing patients for insomnia.
Sleep Hygiene
Addressing the sleep environment and associated behaviors that revolve around
sleep onset are crucial pieces of history when trying to understand the etiology
of one’s sleep complaints and potential confounding or contributing factors.
Understanding the location of one’s sleep environment, the nature of temperature,
light and sound exposure, and whether or not the bed is shared (i.e., number of persons,
pets, etc.) can help address a patient’s sleep complaints. Activities prior to bedtime
must also be discussed. Ingestions (food, caffeine, alcohol, medications, tobacco, illicit
substances) close to bedtime can have varied effects on one’s sleep. Stimulating activi-
ties prior to bedtime, such as exercise (within 6 hours), television watching, reading,
working, music listening, can all affect sleep quality. The location of where such
activities are occurring must also be appreciated. Bedtime rituals (i.e., bathing, clothing
worn to sleep, etc.) can also enhance one’s insight to a patient’s sleep complaints.
Sleep-Wake Schedule
Asking the patient for his/her Sleep-Wake schedule is important in demarcating a
sleep complaint. Schedule abnormalities in wake and sleep times are clues to the
more common sleep disorders (i.e., insomnia and circadian rhythm disorders) and
can also be useful in suggesting the presence of other sleep disorders (i.e., narcolepsy
and sleep apnea). It can be important to elicit prebedtime rituals, such as caffein-
ated/acidic foods, prescription/illicit/over-the-counter (OTC)/herbal pharmaceu-

ticals, tobacco, and presleep physical, emotional, or cognitive stimulations. Nocturnal
waking behaviors, especially nocturia, are proposed as a clue for sleep apnea (22).
An inquiry would include details on usual bedtime, time to falling asleep
(sleep latency), awakenings from sleep (frequency, length, identifiable causes), final
wake-up time (naturally; prompted by alarm, pet, or another person), and nap times
and nap length. A formal sleep log over several days to weeks can be useful, since
there can often be a discrepancy between remembrance reports on the first visit and
prospectively recorded events.
4 Ramsey et al.
Cataplexy
Cataplexy is specifically used in the diagnosis of narcolepsy. Cataplexy refers to a
sudden loss of postural tone that is precipitated by the experience of strong emotion.
Triggers include joy, sadness, anger, and hilarity. Laughter is the most common
trigger (23,24). Cataplexy can manifest in many ways including head nodding,
collapsing, dropping an item, and so on. The knees, face, and/or neck are the most
common muscle groups involved; oculomotor involvement can also occur, affecting
one’s vision. Respiratory muscles are not affected by cataplexy. Loss of conscious-
ness is rare (23). Cataplectic events are usually short, ranging from a few seconds to
at most several minutes, and recovery is immediate and complete (23). People found
to have narcolepsy, however, often carry a variety of other diagnoses such as peri-
odic paralysis, absence seizures, and fugue states, often because the trigger events
are not elicited or ignored. Other associated features of narcolepsy include sleep paral-
ysis, hypnagogic hallucinations, and reports of poorly consolidated sleep (described
below). These symptoms can however occur, albeit infrequently, in normal patients
and isolated symptoms may be present in those with other sleep disorders.
A curious correlation is reported with one’s month of birth and increased odds
of manifesting narcolepsy. Retrospectively, when 800 birthdates were reviewed
from confirmed narcoleptics with cataplexy in North America and Europe, the
monthly distribution of birth yielded a peak in March with a maximal OR at 1.45
and a trough in September with a minimal OR at 0.63 (24,25).

Sleep Paralysis
Sleep paralysis is a transient, generalized inability to move or to speak during the
transition between sleep and wakefulness. Such experiences can be frightening to
the patient, as muscle control is regained within a few minutes. The sensation of
being unable to breathe is sometimes perceived. Sleep paralysis is reported in
40% to 80% of narcoleptics, and may occur with sleep deprivation and can be
familial (20).
Hypnagogic Hallucinations
Hypnagogic hallucinations are vivid perceptual (visual, tactile, auditory) experi-
ences typically occurring at sleep onset. These experiences are often accompanied
by feelings of fear. Recurring themes include being caught in a fire, being attacked,
or flying through the air. Recurrent hypnagogic hallucinations are experienced by
40% to 80% of patients with narcolepsy and cataplexy (20).
Movements During Sleep
This class of symptoms can encompass a number of disparate but important entities
including restless leg syndrome (RLS), periodic limb movement disorder (PLMD),
and parasomnias. RLS is characterized by an irresistible urge to move the legs and
is usually accompanied by uncomfortable and unpleasant sensations in the legs
(dysesthesias). Spontaneous unpleasant sensations (e.g., “creepy-crawly,” “ants
marching up my legs”) of the limbs occur at rest and are usually relieved by move-
ment. This typical description is extremely suggestive if not diagnostic. RLS is
estimated to occur in approximately 2.5% to 15% of the population, with a female
predominance, occurring 1.5 to 2 times more commonly in women, and its preva-
lence increases with age (26–29). Other considerations include conditions such as
History and Physical Examination 5
muscle cramps and myotonic jerks, positional discomfort, hypotensive akathisias,
sleep starts (hypnic jerks), neuroleptic-induced akathisias, sleep-related leg cramps,
pain associated with arthritis, vascular conditions, injuries, and neuropathy can all
mimic RLS to a certain degree.
A majority of patients with RLS also have concomitant periodic limb move-

ments during sleep (PLMS). These PLMS primarily manifest by kicking or jerking
leg movements at night, but they can also affect the arms. PLMS can be mistaken as
leg kicks that occur around the time of arousal following an apnea or more rarely as
a seizure. The individual leg movements that comprise PLMS need to meet specific
polysomnographic criteria (i.e., 25% of baseline amplitude, 0.5–5 seconds duration,
separated by 4–90 seconds, train of four individual leg movements equals one
periodic leg movement) as well as resulting in a clinical sleep disturbance or day-
time fatigue in order to meet the criteria for PLMD (20).
For the most part, parasomnias involve complex, seemingly purposeful, and
goal-directed behaviors. There are 12 core categories of parasomnias, with only
rapid eye movement (REM) sleep behavior disorder (RBD) requiring polysomno-
graphic confirmation for diagnosis (20). Although the remaining 11 categories are
clinical diagnoses, coexisting polysomnographic collaboration findings can be very
helpful adjuncts at confirming or excluding certain diagnoses. OSA-induced arousals
from REM or non-REM (NREM) sleep with complex or violent behaviors may
trigger parasomnias, including: RBD, confusional arousals, sleepwalking, and sleep
terrors, and sleep-related eating disorder. The differential diagnosis would include
nocturnal complex seizures or nocturnal dissociative states. It is suggested that
rebound slow-wave sleep with initiation of therapy for sleep apnea could trigger
parasomnia phenomena.
SPECIFIC CUES FOR SLEEP APNEA WITH AN EMPHASIS
ON ADULT PRESENTATIONS
Demographics
Sleep apnea is a very prevalent disorder in important populations. Epidemiological
studies estimate the prevalence to be 2% to 4% in the general population (3,30,31),
while other, more selected population studies achieved a prevalence range of 7% to
16% (2,32). Prevalence estimates (and therefore pretest probability) increase in
clinical populations due to an enrichment of medical problems. Rates encountered
in the primary care or hospital settings are particularly high: primary care (high risk
37.5%) (4), obese 40% to 60% (33), bariatric surgery evaluation 71% to 87% (34,35),

hypertension 38% (36), stable outpatient congestive heart failure (CHF) > 50%
(37,38), coronary artery disease (CAD) > 50% (39), acute stroke > 70% (40,41), and
sleep clinic 67% (29).
In regards to the presentation of sleep apnea, studies show a strong relation-
ship between age and sleep apnea (see also Chapter 16) (15,30,42,43). Duran (2) found
that sleep apnea prevalence increased with age with an OR of 2.2 for each 10-year
increase. The Sleep Heart Health Study noted that prevalence rose steadily with age
up to 60 years at which point a plateau in prevalence occurs around 20% (15). It has
also been shown that the severity of sleep apnea (42) and the effect of body mass
index (BMI) seem to decrease with age (15,43) and that the magnitude of associations
for sleep apnea, snoring, and breathing pauses also decreases with age (15).
Men have a higher prevalence of sleep apnea than women across all ages in
epidemiological (3,31,44) and clinic-based studies (see also Chapter 14). This effect
6 Ramsey et al.
diminishes with time, however, and both sexes achieve a similar incidence by age 50
(43). A study of OSA incidence and its risk factors found the risk for sleep apnea in
men increased only marginally with age, while it increased very significantly in
women: the OR (confidence interval) for increased AHI per 10-year increase was 2.41
in women (1.78–3.26) and only 1.15 (0.78–1.68) in men (43). A study of Hong Kong
women found a 12-fold rise in the prevalence of sleep apnea in women between the
fourth and sixth decades (31). There is a large amount of literature to support the
role of menopause in modulating this increased risk for sleep apnea in women
around the age of 50 (44–46). In general, men and women are present with the
same constellation of sleep-related symptoms and complications (47). Women
with OSA may be slightly older, more obese, more likely to use sedatives, and
complain of insomnia and depression (48).
It is not clear if race can be categorically used to confer risk, or if race difference
is just a surrogate for a different risk profile. A study of sleep apnea risk factors in
the Sleep Heart Health Study did not show a significantly higher prevalence in
African-Americans (15) and another did not note any differences in respiratory

disturbance index (RDI) when adjusted for known confounders (49). In contrast,
a study of older community dwelling adults found that African-Americans had a
2.5 times greater odds of having an AHI > 30 (50), and the Cleveland Family Study
found the prevalence of sleep apnea in young African-Americans was higher than
that of Caucasians (51).
Studies in Asia estimate the prevalence of sleep apnea to be similar to that of
the West (30,31). This is an intriguing finding given that obesity, the risk factor
believed to modulate a large part of the risk for sleep apnea in the West, is less
common in Asia. Other factors must therefore act in the expression of this disorder.
Craniofacial morphology has been implicated as a modifier of risk in nonobese
populations but could also interact with obesity as well (52–54).
History of Present Illness
General issues in the presentation would be the age of onset of symptoms as well as
some consideration of the trajectory of illness severity. Some of these features are
listed in Table 1, and includes features important in both adult and pediatric popu-
lations. The pediatric examination is also discussed in a separate section below.
Sleepiness is very common in sleep apnea patients: 38% to 51% in one epide-
miological study (55) and 47% to 73% in a sleep clinic population (56). Despite this
it is not associated with sleep apnea in clinical studies. This is in large part due to
difficulty in differentiating sleep from fatigue. In a study of sleep apnea patients’
perception of their problems, lack of energy, tiredness, and fatigue were more prev-
alent complaints than sleepiness (56).
Snoring is extremely common in sleep apnea patients and its absence should
make OSA less likely (13). In one study only 6% of patients with OSA did not report
snoring. Keep in mind however, that many patients have misperceptions about their
snoring and tend to underestimate it (57). Some studies have shown that a report of
“loud” habitual snoring strengthens by seven-fold the statistical association with
sleep apnea and snoring (4,15,58). Witnessed apneas are relatively specific for sleep
apnea, but have a low sensitivity (15).
Insomnia complaints are highly prevalent in OSA. Fifty-five percent of patients

being referred for possible evaluation of OSA were noted to have complaints of
insomnia, with difficulties maintaining sleep (38.8%) being more common than
History and Physical Examination 7
difficulties initiating sleep (33.4%) or early morning awakenings (31.4%). Despite the
overall high prevalence of insomnia complaints in this study population, insomnia
was more common in patients without rather than with significant sleep-disordered
breathing (81.5% with AHI < 10 vs. 51.7% with AHI > 10) (59). The high prevalence of
insomnia complaints may be attributable to the fact that the sleep disruption associ-
ated with OSA may be perceived as insomnia, or perhaps such patients with insomnia
and OSA are more symptomatic, thus more likely to seek medical attention.
Weight gain increases the probability of sleep apnea. One large population-
based study found a 10% weight gain and predicted a 32% increase in AHI. This
translated to a six-fold increase in the odds of developing (moderate-to-severe)
sleep apnea (32). Inversely, a decrease in weight leads to an improvement in sleep
apnea. Studies in bariatric surgery patients show a dramatic improvement in RDI
after weight loss (35,60).
Frequent awakening from sleep to urinate is common in sleep apnea patients.
One retrospective study found a prevalence of 49% in sleep apnea patients (61) and
others have noted frequent nocturia is related to sleep apnea severity (61–63).
Nocturnal angina may be related to apneas in some patients with ischemic
heart disease and sleep-disordered breathing. Small series in patients with ischemic
heart disease and relatively severe sleep apnea suggested a link between myocardial
ischemia and apneas (64,65). However, these findings conflict with a larger study
that included patients with less severe sleep apnea and failed to appreciate a signifi-
cant association (66).
Past Medical History
OSA will coexist with other sleep disorders. A retrospective analysis of 643 OSA
patients found that 31% had another sleep disorder: 14.5% had poor sleep hygiene
and 8.1% had PLMD (67). In two other studies more than 50% of sleep apnea patients
complained of insomnia (59,68).

Sleep apnea is not only associated with cardiovascular disease but may directly
contribute to its pathogenesis. It was present in 38% of hypertensive subjects in one
TABLE 1 Features of Emphasis in the Adult and Pediatric Examination
Impact on daytime
functioning
Irritability, mood swings, hyperactivity, automatic behaviors, work
or academic performance, behavior of concern (inappropriate
napping, inattentiveness), absences from work or school
Sleep/wake schedules Usual bedtime, fall asleep time, wake time, napping habits,
weekday/weekend variations
Customs surrounding sleep Presleep routines and related transitional objects (television,
pacifier, toy, etc.)
Sleep environment Shared or private room, bed partners (including pets/toys/stuffed
animals); electronics or other toys that may impede sleep
routines; persistence or resolution of sleep complaints in other
environments (hotels, sleepovers, etc.)
Body position(s) during sleep Side sleeping and/or neck hyperextension to relieve obstruction
Exposures Caffeinated beverages, tobacco products, recreational drugs
Other sleep behaviors Snoring, witnessed apneas, paradoxical breathing, mouth
breathing with dry mouth and throat, morning headaches,
gastroesophageal reflux, sweating (may suggest increased
work of breathing), stereotypic movements/complaints
suggestive of seizure or movement disorders (including
parasomnias and restless legs syndrome)
8 Ramsey et al.
study (36). A dose–response relationship is present (69) and several trials found a small
but significant improvement in hypertension with sleep apnea treatment (70–72).
Others suggest that the prevalence of sleep apnea in patients with CAD, postmyo-
cardial infarction, CHF, and poststroke to be > 50% (37–41). Results from the Sleep
Heart Health Study show increasing odds of self-reported heart failure, stroke, and

CAD in subjects with a high AHI (73). Additionally, a pathogenic role is suggested
by observational studies that show fewer adverse cardiovascular outcomes in
treated versus untreated patients (74–76).
Several studies have found that sleep apnea is independently associated with
glucose intolerance and insulin resistance (33,77). The Sleep Heart Health Study
found that patients with mild and moderate/severe OSA had increased adjusted
ORs for fasting glucose intolerance: 1.27 (0.98, 1.64) and 1.46 (1.09, 1.97), respec-
tively (77). At least one treatment study has found improvement in glucose control
in patients treated for sleep apnea (78).
Depression is linked to sleep apnea in a number of correlation studies. Most
are small, use different instruments to measure depression, and indicate that 24% to
58% of sleep apnea patients have some measure of depression (79,80). In a larger
European telephonic survey, 17.6% with a Diagnostic and Statistical Manual of
Mental Disorders (DSM-IV) breathing-related sleep disorder also had a diagnosis of
a major depressive disorder (81).
Sleep apnea in the setting of pulmonary diseases is called the “overlap
syndrome.” Chronic obstructive pulmonary disease is the most common of these,
but has a prevalence in the sleep apnea population similar to that of the general
population (82). Pulmonary arterial hypertension is another disease but is much less
common and the prevalence of sleep apnea in these patients is not well studied (83).
Hypothyroidism symptoms of fatigue can overlap with those of sleep apnea.
Case series have reported improvement or resolution of sleep apnea in selected
patients treated with thyroxine alone (84). Nonetheless, the limited evidence
available suggests the prevalence of hypothyroidism in sleep apnea patients is no
different than that seen in the general population (85) and routine screening in the
absence of other signs of hypothyroidism is not cost-effective. Cases have also
described lingual thyroids causing airways obstruction at night (86).
Glaucoma (87), end-stage renal disease (88,89), and gastroesophageal reflux
disease (90,91) have been reported to occur with OSA, but the specificity of the asso-
ciations are not established.

The occurrence of sleep disturbances during pregnancy is well documented,
but the prevalence and incidence of specific sleep disorders is not confirmed in
large-scale population studies. A spectrum of association between pregnancy and
sleep disturbances ranges from an increased incidence of excessive sleepiness, insom-
nia, nocturnal awakenings, and parasomnias (especially restless legs syndrome) to
snoring, and both obstructive and central sleep apnea (92). Although specific sleep
disorders tend to emerge during different stages of pregnancy, the third trimester
appears to be the most vulnerable. Of special attention are those women who gain
excessive weight during pregnancy. Thus, during routine perinatal obstetrical care,
the sleep history should be periodically revisited.
Social History
Sleep apnea significantly worsens after heavy alcohol ingestion (93,94). The effect of
more moderate levels of alcohol ingestion on sleep apnea are not as clear and results
History and Physical Examination 9
are conflicting (95,96). Some proposed mechanisms include increased nasal resis-
tance due to edema, and reduced hypoglossus motor nerve activity.
Data from the Wisconsin Sleep Cohort Study found current smokers to have an
increased risk of having moderate sleep apnea compared to nonsmokers (OR 4.44).
Heavy smokers had the higher risk (OR 40.47) (97). One sleep clinic study found
current smokers to have increased adjusted odds of sleep apnea [OR 2.5, confidence
interval (CI) 1.3–4.7, p = 0.0049] (98).
Family History
The Cleveland Family Study found that there is a familial aggregation to sleep
apnea. Families with an index case of sleep apnea had a higher prevalence of sleep
apnea than in those without (21% vs. 9%, p = 0.02) and risk increased with addi-
tional affected members (99). Ongoing genetic studies are trying to find the relative
role of different anatomical risk factors in mediating this increased risk. At the
present time routine assessment and testing of family members is not advocated in
the absence of clinical illness.
The sleepiness and lack of concentration that accompanies sleep apnea impair

work performance, driving ability (100,101) and have deleterious effects on family
relationships. Commercial drivers are a special group that is receiving an increasing
amount of attention, as driving risk becomes a public safety issue. Moreno et al.
(102) administered the Berlin questionnaire to a large group of truck drivers and
found that 26% were at high risk for sleep apnea; however, the presence of inactivity
and obesity were also strongly implicated in this pretest probability estimate.
Medication History
There is an accounting of medication use for sleep apnea in Chapter 17. In general,
medications to note during the history and physical fall into three categories:
(i) those that are associated with OSA, (ii) those that sedate and/or decrease respira-
tory drive, and (iii) those that impair sleep onset or maintenance (Table 2).
Drug-induced sleepiness is the most commonly reported side effect of central
nervous system active pharmacological agents; the 1990 Drug Interactions and Side
Effects Index of the Physicians’ Desk Reference lists drowsiness as a side effect of
584 prescription or OTC preparations (103).
Allergies
Nasal obstruction contributes to the worsening of sleep-disordered breathing, but
the extent to which this might be related to allergic rhinitis is not known. One case-
control study did show that sleep apnea patients had a higher rate of perennial
allergic rhinitis and atopy than controls (104).
THE PHYSICAL EXAMINATION FOR ADULT SLEEP APNEA
A sleep physical examination is directed at modifying the probability of sleep-
disordered breathing based on the history, looking for evidence of associated or
complicating disease, and excluding other potential causes for neurologic or cardio-
vascular symptoms. A broader examination incorporating many of the other organ
systems should be employed when considering other sleep disorders that may be
caused by or confounded by other diagnoses.
10 Ramsey et al.
TABLE 2 Medications as Clues to Predisposing Factors
Medications associated

with OSA
Medications that sedate and/or
reduce respiratory drive
Medications that impair sleep
onset or maintenance
Barbiturates
Benzodiazepines
Ethanol, illicit narcotics
Hypertensive and diabetic
treatments
Alpha-blockers
Anticonvulsants
Antidiarrheal agents
Antiemtics
Antihistamines
Antimuscarinic
Antipsychotics
Antispasmotics
Antitussives
Anxiolytics
Atypical antidepressants
Barbituates
Benzodiazepines
Beta-blockers
Dopaminergics
Diphenhydramine, phenylhydramine
Ethanol, illicit narcotics
Genitourinary smooth muscle
relaxants
Hydantoins

Melatonin receptor agonists
Monoamine oxidase inhibitors
Muscle relaxants
Nonbenzodiazepine hypnotics
Opiate agonists
Selective serotonin reuptake
inhibitors
Succinimides
Tricyclic antidepressants
Valerian root, kava kava, melatonin,
chamomile, passiflora
Adrenocorticotropin and
corticosteroids
Alpha-agonists
Anticholesterol agents
Anticonvulsants
Antineoplastic agents
Appetite suppressants
Atypical antidepressants
Benzodiazepines
Beta-blockers
Caffeine, nicotine, ethanol,
illicit narcotics
Decongestants
Diuretics
Dopaminergics
Monoamine oxidase inhibitors
NSAIDs
Opiates
Oral contraceptives

Pemoline, dextroampheta-
mines, methylphenidates
Progesterone
Pseudoephedrine, ephedrine,
phenylpropanolamine
Quinidine
Quinolone antibiotics
Theophylline, albuterol,
ipratropium, terbutaline,
salmeterol, metaproterenol,
xanthine derivatives
Thyroid supplements
Tranquilizers
Abbreviations: NSAIDs, nonsteroidal anti-inflammatory drugs; OSA, obstructive sleep apnea.
Blood Pressure
Many population-based studies have shown that hypertension is independently
associated with sleep-disordered breathing studies (105–110). Blood pressure has
been integrated into several clinical prediction rules for sleep apnea (4,12,17,18).
One study found hypertension to have an adjusted OR of 11.9 for an AHI ≥ 30 (17).
More recently, a causal relationship has been suggested by a number of studies that
have shown an improvement in hypertension with sleep apnea treatment (70–72).
Obesity
Although a number of different measures of obesity have been used in clinical studies
the BMI is probably the best and certainly the most practical. It has been found to be
strongly associated with the presence of sleep apnea (4,12–15,18,108,111–115) and
has been incorporated into a number of clinical prediction rules (4,13,14,18) for this
disorder (see also Chapter 2).