1 Perspectives

References

Section I: Features, Factors, and Characteristics

2 History

Pretwentieth Century Literature

Burwell Et Al.’S Poker Player And The First Sleep Recordings Of Pickwickian Patients

First Treatment Attempts

Sleep Apnea In Thin Persons

First Major International Conference Of Respiratory Sleep Disorders

Sleep Apnea Over The Past Twenty-Five Years

Sleep Apnea In Children

Cornerstones Of Modern Treatment For Obstructive Sleep Apnea

Conclusions

References

3 Epidemiology

Introduction

Snoring

Obstructive Sleep Apnea Prevalence

Gender

Menopause

Pre-eclampsia

Ethnicity

Children

New Directions

Metabolic Syndrome

Conclusions

References

4 Ontogeny

Introduction

Infancy

Childhood And Adolescence

Adulthood And Old Age

Clinical Manifestations

Age Dependence

Risk Factors for Osa During Adulthood

Pathophysiology of Osa in Adults and the Elderly

Outcomes and Comorbidities of Osa in Adults and the Elderly

Conclusions

References

5 Phylogeny and Animal Models: An Uninhibited Survey

Introduction

Terrestriality And Evolution Of The Pharynx

Evolutionary Pressures Influence The Pharynx

Walking, Talking, and Breathing: What Is the Problem?

Changes in the Craniofacial Relationships

Changes in the Maxilla

Oropharyngeal Compression

Language, Speech, And Brain Growth

Altricial Brain Growth in Mammals

Cerebral Control Over Pharynx

Acquisition of Speech Predisposes to Obstructive Sleep Apnea

Life History and Emergence of Obstructive Sleep Apnea

Animal Models Of Obstructive Sleep Apnea

Obesity and Bony Abnormalities

Rhesus Monkey Model of Nasal Constriction

Descent of Hyoid: Chimpanzees Mirror Human Ontogeny

Conclusions

References

6 Upper Airway Anatomy

Introduction

Anatomy Of The Upper Airway

Overview

Nose

Anterior Nasal Cavity

Posterior Nasal Cavity/Nasopharynx

Mouth

Anterior Oral Cavity and Tongue

Posterior Oral Cavity/Oropharynx

Pharynx

Oropharynx: Retropalatal Region

Oropharynx: Retroglossal Region

Hypopharynx

Larynx

Conclusions

References

7 Physiology and Dynamics of the Upper Airway

Introduction

Embryology

Nonrespiratory Functions Of The Upper Airway

Speech

Swallowing

Physiologic Functions Of Selected Regions Of The Upper Airway

Physiology of the Nose

Upper Airway Muscles

Physiology of the Larynx

Dynamics Of The Upper Airway During Sleep

The Starling Resistor Model

Measurements in the Static Upper Airway

Limitations of Studies on Upper Airway Collapsibility

Determinants of Upper Airway Neuromotor Tone

Sleep State

Ventilatory Drive

Subatmospheric (Negative) Pressure

Lung Volume

Posture and Neck Position

Gender

Airway Length

Upper Airway Sensation

Development

Upper Airway Collapsibility in Osa

Conclusions

References

8 Upper Airway Pathology

Introduction

Nasal Obstruction

Choanal Atresia

Laryngomalacia

Tracheomalacia And Tracheal Stenosis

Congenital Pharyngeal Stenosis

Hurler’S And Hunter’S Syndromes

Hurler’s Syndrome

Hunter’s Syndrome

Maxillary Hypoplasia

Crouzon’s Syndrome

Apert’s Syndrome

Pfeiffer’s Syndrome

Antley-Bixler’s Syndrome

Stickler’s Syndrome

Down Syndrome

Cleft Palate Repair

Mandibular Hypoplasia

Pierre Robin Syndrome

Treacher Collins Syndrome

Goldenhar’s Syndrome

Tongue Enlargement

Beckwith-Wiedeman Syndrome

Conclusions

References

9 Control of Breathing in Sleep

Introduction

Hallmarks Of Sleep Apnea

Changes In The Control Of Breathing In Sleep

Reduced Respiratory Motor Output

Sleep Unmasks a Highly Sensitive Apneic Threshold

Importance of Reflex Inputs—Reduced Gain of Chemoreflexes

Concept of Loop Gain (See Also Chapter 11)

The Co2 Reserve and Apnea

The Co2 Reserve Is Labile

Which Chemoreceptors Are Responsible for Apnea?

Reduced Gain of Mechanoreflexes

Alterations in Cerebral Blood Flow and Vascular Responsiveness

The Special Problem Of Rem Sleep

Skeletal Muscle Atonia

Excitation of Central Rhythm Generator

Sleep Effects On Ventilatory Control And Sleep Apnea In Special Circumstances

Obstructive Sleep Apnea

Neurodegenerative Disease

Congestive Heart Failure

Hypoxia

Elderly

Conclusions

Acknowledgments

References

10 Arousal from Sleep

Introduction

What Is A Micro-Arousal And How Is It Related To The Course Of Sleep?

The Concept Of Cortical And Subcortical (Autonomic) Arousal

Arousals Preceded By Synchronization (Slow Waves, K-Complexes) Eeg Changes

Influence Of Sensory Stimulation On The Formation Of Both Types Of Arousals

State-Specific Reactivity In Sleep

Hierarchy Of Arousals—The Concept Of A Continuum

Pathologic Arousals, With Special Emphasis On Sleep-Related Breathing Disorders

Arousals Gating Pathological Events

Functions Of Arousal During Sleep

Conclusions

Acknowledgment

References

11 Pathogenesis

Introduction

Anatomy (See Also Chapter 6) Function

Structure

Upper Airway Lumen

Upper Airway Soft Tissue

Other Anatomical Factors

Upper Airway Shape

Upper Airway Length

Nasal Obstruction

Upper Airway Collapse

Sites of Collapse

Collapsibility in Obstructive Sleep Apnea

Mechanisms

Balance of Forces

Neuromuscular Compensation

Background

Awake

The Effect of Sleep

Theory Of Upper Airway Collapse

Newer Theories Of Upper Airway Collapse (Fig. 2)

Lung Volume

Ventilatory Control Instability

Respiratory Drive and Upper Airway Patency

Loop Gain

Loop Gain in Obstructive Sleep Apnea

Co2 Reserve and Loop Gain

Neuromuscular Compensation During Sleep

Arousal Threshold

Motor and Sensory Deficits

Other Mechanisms

Neurotransmitters And Sleep (Fig. 5)

Conclusions

References

12 Risk Factors

Introduction

Obesity (See Also Chapter 20)

Weight Gain and Obstructive Sleep Apnea

Weight Loss and Obstructive Sleep Apnea

Effect of Obesity on Obstructive Sleep Apnea

Fat Distribution

Neck Circumference

Summary on Obesity and Obstructive Sleep Apnea

Craniofacial Features (See Also Chapter 8)

Upper Airway Soft Tissues and Skeletal Features

Soft Tissues of the Pharynx

Nose

Gender

Weight and Gender

Upper Airway Mechanics and Gender

Control of Breathing and Gender

Menopause

Ethnicity

Age (See Also Chapter 4)

Smoking

Alcohol

Specific Diseases

Polycystic Ovarian Syndrome

Stroke

Other Neurologic Conditions

Snoring

Body Position

Conclusions

References

13 Familial and Genetic Factors

Introduction

Intermediate Phenotypes

Obesity (See Also Chapter 20)

Craniofacial Structure (See Also Chapter 12)

Ventilatory Control (See Also Chapters 7 and 9)

Disorders That Affect Sleep And Breathing

Sudden Infant Death Syndrome

Congenital Central Alveolar Hypoventilation Syndrome

Prader-Willi Syndrome

Other Congenital Syndromes

Obstructive Sleep Apnea Genetics

Phenotype Selection

Familial Aggregation

Linkage Analyses

Candidate Genes

Obstructive Sleep Apnea And Related Disorders

Pleiotropy

Obstructive Sleep Apnea Consequences

Conclusions

References

14 The Spectrum of Sleep-Disordered Breathing

Introduction

The Obstructive Sleep Apnea Syndromes

Overview

Pathophysiology of Airway Obstruction (See also Chapters 6–11)

Snoring

Upper Airway Resistance Syndrome

Obstructive Sleep Apnea

Quantifying the Severity of Obstructive Sleep Apnea

The Phenotype of Osa: Effects of Age and Gender

The Diagnostic Dilemma

The Central Sleep Apnea Syndromes

Sleep-Related Hypoventilation/Hypoxemic Syndromes

Conclusions

Glossary Of Terms And Abbreviations

References

Section II: Associations and Consequences

15 Morbidity and Mortality

Introduction

Obesity (See Also Chapter 20)

Insulin Resistance And Glucose Tolerance (See Also Chapter 19)

Cardiac And Cardiovascular Disease (See Also Chapters 17 And 18)

Hypertension

Stroke

Heart Failure

Arrhythmias

Coronary Artery Disease

Pulmonary Hypertension

Depression

Motor Vehicle Accidents (See Also Chapter 24)

Conclusions

References

16 Central and Autonomic Nervous Systems

Introduction

The Impact Of Obstructive Sleep Apnea On The Central Nervous System

Evoked Potentials During Wakefulness

Evoked Potentials During Sleep

Brain Morphology Using Magnetic Resonance Imaging

Functional Magnetic Resonance Imaging

Summary of Central Nervous System Effects

The Impact Of Obstructive Sleep Apnea On The Autonomic Nervous System

The Measurement of Autonomic Activity During Sleep: Methodological Comments

Autonomic Cardiovascular Activity Druing Sleep: Healthy Individuals

Autonomic Cardiovascular Activity in Obstructive Sleep Apnea

Summary of Autonomic Nervous System Effects

Conclusions

References

17 Cardiac Arrhythmias and Congestive Heart Failure

Introduction

Cardiovascular Autonomic System

Baroreceptors and Chemoreceptors

Cardiovascular Characteristics Of Normal Sleep

Pathophysiological Mechanisms In Obstructive Sleep Apnea

Immediate Effects of Variations in Intrathoracic Pressure

Immediate Effects of Hypoxia and Hypercapnia

Immediate Effects of Arousals

Chronic Effects of Obstructive Sleep Apnea

Inflammatory, Oxidative, and Vascular Endothelial Effects of Obstructive Sleep Apnea

Cardiac Arrhythmias And Obstructive Sleep Apnea

Bradyarrhythmias

Ventricular Arrhythmias

Ventricular Arrhythmias In Obstructive Sleep Apnea Patients With Normal Left Ventricular Systolic Function

Ventricular Arrhythmias In Obstructive Sleep Apnea Patients With Depressed Left Ventricular Systolic Function

Atrial Fibrillation

Congestive Heart Failure And Sleep-Disordered Breathing

Obsructive Sleep Apnea And Congestive Heart Failure

Central Sleep Apnea And Congestive Heart Failure

Conclusions

References

18 Hypertension and the Cardiovascular System

Introduction

Osa And Hypertension

Osa And Ischemic Heart Disease

Osa And Stroke

Osa And Ph

Pathogenesis

Conclusions

References

19 Endocrine Function and Glucose Metabolism

Introduction

The Somatotropic Axis

The Corticotropic Axis

The Thyrotropic Axis

The Prolactin System

The Gonadotropic Axis

Glucose Metabolism In Osa

Conclusions

References

20 Obesity

Introduction

Definition Of Obesity

Anatomy And Pathophysiology

Upper Airway Anatomy

Neck Circumference

Central Obesity

Age

Gender

Male Predominance

Menopause

Pregnancy

Genetics

Ethnicity

Genome Studies

Cause and Effect Considerations

Comorbidities

The Metabolic Syndrome

Leptin

Hypertension

Vascular Disease

Congestive Heart Failure

Stroke

Epidemiology

Mortality and Morbidity

Health Care Costs

Therapy

Weight Loss

Our Experience

Case Report

Conclusions

References

21 Mood and Behavior

Introduction

Osa And Mood

Depression and Osa

Consequences of Depression in Osa

Moderators of Depression in Osa

Mediators of Depression in Osa

Other Affective Disorders And Osa

Irritability, Anger, Anxiety, and Osa

Sexual Dysfunction And Osa

Osa And Neurobehavioral Function

Cognitive Functioning and Osa

Potential Mechanisms for Neurobehavioral Dysfunction

Mood, Behavior, And Treatment Of Osa

Conclusions

References

22 Sleepiness

Introduction

Prevalence Of Sleepiness In Obstructive Sleep Apnea

Evaluation Of Excessive Daytime Sleepiness In Obstructive Sleep Apnea

Assessment of Symptoms

Subjective Measurements

Objective Measurements

Causes Of Sleepiness In Obstructive Sleep Apnea

Management Of Sleepiness In Obstructive Sleep Apnea

Continuous Positive Airway Pressure

Oral Appliances

Surgical Intervention

Treating Nonsleepy Patients

Persistent Sleepiness After Treatment Of Obstructive Sleep Apnea

Sleepiness In Children With Obstructive Sleep Apnea

Conclusions

References

23 Health-Related Quality-of-Life

Introduction

Quality-Of-Life Assessment: What Is It, And Why Measure It?

What Is Hrqol?

How is Hrqol Measured?

Generic Instruments

Specific Instruments

Why Measure Hrqol?

How Does Osa Affect Quality-Of-Life?

Establishing a Causal Relationship

What Effect Does Treatment Have On Qol?

How Do I Incorporate Hrqol Assessments Into My Practice?

The Process of Measuring Hrqol

The Purpose of Hrqol Assessment

Generic vs. Specific Assessment

Choosing an Instrument

Instruments Used To Measure Hrqol In Osa Patients

Generic Instruments

Medical Outcome Study Short Form-36 (SF-36)

The Nottingham Health Profile (NHP)

The Sickness Impact Profile (SIP)

The Functional Limitations Profile (FLP)

The Euroqol (EQ-5D)

Specific Instruments

Calgary Sleep Apnea Quality-of-Life Instrument (SAQLI)

Functional Outcomes of Sleep Questionnaire (FOSQ)

Symptoms of Nocturnal Obstruction and Related Events Instrument (SNORE25)

Special Circumstances: Pediatric Hrqol Assessment

Pediatric Hrqol Instruments

The Child Health Questionnaire (CHQ)

Franco’s Pediatric Osa Instrument-18 (OSA-18)

Obstructive Sleep Disorders-6 (OSD-6)

Cohen’s Osa Surgery Qol Questionnaire

Tonsil and Adenoid Health Status Instrument

Issues to Consider in Pediatric Assessment

Logistical Considerations

Clinical Vs. Statistical Significance

Conclusions

References

24 Driving Risk and Accidents

Overview Of The Problem

Prevalence And Associated Risks

How To Evaluate The Driving Risk In Apneic Patients?

Impact Of Treatment On The Accidental Risk

Economic Impact Of Accident Reduction

Conclusions

References

25 Economic and Societal Impact

Introduction

Basic Notions In Health Economics

Typology Of Economic Evaluations

Cost-Effectiveness Analysis

Quality-of-life

Cost-Utility Analysis

Cost-Benefit Analysis

Obstructive Sleep Apnea

Costs Of Obstructive Sleep Apnea

Medical Costs of Sleep Apnea Before the Diagnosis

Indirect Costs Related to Sleep Apnea

Sleep Apnea and its Treatment: The Patient’s Point of View

Direct Medical Costs: The Diagnostic Tests for Sleep Apnea

Direct Medical Costs: Treatment Costs in Sleep Apnea

Conclusions

References

Index