Sleep Disorders Human Sleep

ITS RECOGNITION AND MEDICAL CONSEQUENCES

Rommel D. Bayot, MD FPCP, FPCCP

Division of Pulmonary and Critical Care Medicine

What is sleep? FUNCTIONS OF SLEEP

• Reversible behavioral state of perceptual
• Body & brain tissue restoration
disengagement from and unresponsiveness to
the environment • Energy conservation
• Adaptation
• Memory reinforcement and consolidation
• Complex amalgam of physiological and
behavioral processes • Synaptic and neural network integrity
• Thermoregulation

Caiskador and Dement

Chokroverty, 2000

SLEEP REQUIREMENT

• Newborn → 16 hrs.
• 3-5 years → 10 hrs Stages of Sleep
• Adult → 8 hrs.
– Sleep < 4 hrs or > 9hrs → ↑ risk for CAD, stroke
and cancer

Chokroverty, 2000

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 Non-REM
• Non-rapid eye movement
• 75-80% of sleep time in adult humans
• Characterized by behavioral quiescence
with residual muscle tone and very
regular, deep breathing
Non-REM
• Stage I NREM
– 2-5% of sleep time; lightest stage of sleep
– alpha rhythm ↓ < 50% in an epoch
– theta rhythm & beta waves appear
– EMG activity ↓ slightly

Non-REM Non-REM
• Stage II NREM • Stage III NREM
– 45-55% of sleep time; intermediate sleep
–15-20% of sleep time; deep sleep
– begins after 10-12 minutes of Stage I NREM
– sleep spindles, K complexes, delta waves –delta waves = 20% of the epoch
<20%
– lasts 30-60 mins

REM REM
• Rapid Eye Movement • Tonic Stage
–20-25% of sleep time –desynchronized EEG, hypotonia & atonia of
–1st REM noted 60-90mins after onset major muscle groups
of NREM sleep • Phasic Stage
–EEG → fast rhythms and delta waves –characterized by rapid eye movements in all
directions
→ sawtooth appearance –phasic swings in BP, HR, RR
–frequently occur in early morning hours
Chokroverty 2000

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 CYCLES OF SLEEP
• Four or five 90-minute cycles of sequential stages
recur during the night
• REM stage episodes increase in duration
• Slow-wave sleep disappears beyond the second cycle
• Infants: large REM sleep up to 2 years
• Old: stage 3 diminishes or disappears, sleep
fragmentation
• REM : total sleep 25%
• Nocturnal sleep fluctuates between 5-9 hrs

Obstructive Sleep Apnea (OSA)

• Characterized by intermittent episodes of
complete or partial pharyngeal obstruction
during sleep
Obstructive Sleep
Apnea-Hypopnea Syndrome Obstructive Sleep Apnea –
Its Recognition and Medical Consequences
Hypopnea Syndrome (OSAHS)
 When apnea and hypopnea are combined with
symptoms such as daytime somnolence

Bassiri & Guilleminault. Sleep Medicine 2000

Incidence of OSAHS and OSA Risk Factors for OSAHS

OSAHS OSA • Obesity – 70% of patients
– BMI = 30 kg/m2
• Men = 4% 24%
– Neck Circumference
• Women = 2% 9% • Men > 17 inches
Chokroverty, Sleep Disorders Medicine 2000 • Women > 16 inches
• Male gender
 Adults with mean BMI of 25-28, 1 of every 5
• Menopausal women
has at least mild OSA and 1 of every 15 has at
least moderate to severe OSA • Increasing age - = 40 years old
• (+) Family History - ? risk 2-4x
 OSAHS estimated to occur in 1 of 20 adults
usually unrecognized and undiagnosed and • Alcohol
results in behavioral and cardiovascular • Smoking
morbidity • Increasing drug use
Young, AJRCCM 2002

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 *Respiratory Events in OSA Symptoms of OSAHS
• Narrowing at one or more sites along Nocturnal Symptoms Daytime Symptoms
the upper airway (retropalatal, • Snoring • Sleepiness
retroglossal or hypopharyngeal • Witnessed apnea • Fatigue
• Choking • Morning headache
region) snoring • Poor concentration
• Dyspnea
• Pharyngeal collapse apneas and • Restlessness
• Decreased libido or
impotence
hypopneas • Diaphoresis • Decreased attention
• Esophageal reflux • Depression
• Increased effort of breathing lead • Drooling • Personality changes
to arousals and fragmented sleep • Dry mouth

*Clinical Features Associated

Clinical Examination
with OSAHS
• Obesity and neck circumference • Obesity
– BMI • Neck circumference
> 40 cm
– Neck circumference • Enlarged nasal
• Upper Airway turbinates
• Deviated nasal
– Craniofacial dysmorphism septum
• Narrow mandible
– Tongue, uvula, soft palate (size, length,
• Narrow maxilla
height) • Dental overjet and
retrognathia
– Retroglossal area
– Nose
• Crossbite and dental
malocclusion
• High and narrow hard
palate
• Elongated and low lying
uvula
• Prominent tonsillar
pillars
• Enlarged tonsils and
adenoids
• Macroglossia

Philippine Journal of Chest Diseases

Vol 14 No 2 May-Aug 2008

Characteristics of Patients with Sleep-Disordered

Breathing Referred to the Philippine Heart
Center Sleep Clinic for Polysomnography

 Middle age group, snoring, obesity, increased neck

circumference and daytime sleepiness are
predictors of sleep-disordered breathing

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 POLYSOMNOGRAPHY

• The single MOST important laboratory

Laboratory Assessment of technique for assessment of sleep and its
OSAHS disorders

POLYSOMNOGRAPHY What does Polysomnography measure?

• Method of identifying and evaluating sleep- • It monitors the multiple physiological

state and several physiologic variable during
sleep
ATS 1989
• A multi-parametric test that is used to
study/record in detail all the biophysiological
changes that occur in the human body when
the person is asleep
characteristics simultaneously during sleep
at night.
• It allows assessment of sleep stages and
wakefulness, respiration, cardio-circulatory
functions and body movements.
• It monitors physiological or pathological
events in sleep.

When Is Sleep Laboratory

Evaluation in Order? What is monitored in PSG?
• Electroencephalogram (EEG) • Oximetry
• Serious excessive daytime sleepiness with no known
• Electrooculogram (EOG) • Leg electromyogram (EMG)
medical cause and not relieved by 2 weeks of
• Chin electromyogram (EMG) • Body position
significant increase of time in bed
• Electrocardiogram (ECG) • Snoring sensors
• Snoring with interrupted breathing or periodic limb • Nasal and/or oral airflow • Continuous audio/video
movements • Breathing effort (chest and monitoring & behavior
• Nocturnal seizures abdomen) observation

Hauri et al. Sleep Disorders, 1992

AASM Practice Parameters for Indications for Polysomnography 2005

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 Indications for Cardiopulmonary
Sleep Studies
• COPD patients with awake PaO2 > 55mmHg but with
cor pulmonale

• Patients with restrictive ventilatory impairment

secondary to chest wall and neuromuscular
disturbances and complicated by chronic
hypoventilation, polycythemia, pulmonary
hypertension, disturbed sleep, daytime somnolence
and fatigue
ATS 1989

Indications for Cardiopulmonary

Indications for Polysomnography
Sleep Studies

• Patients with disturbances of respiratory control • Polysomnography is routinely indicated for the
whose awake PaO2 > 45mmHg or with complications diagnosis of sleep related breathing disorders.
• Snoring and obesity (Standard)
• Patients with excessive daytime sleepiness
• Patients with nocturnal cyclic bradytachyarrhythmia, • Polysomnography is indicated for positive airway
pressure (PAP) titration in patients with sleep related
nocturnal abnormalities of atrioventricular
breathing disorders. (Standard)
conduction and ventricular ectopy during sleep

AASM Practice Parameters for Indications for Polysomnography 2005

ATS 1989

Indications for Polysomnography

• A preoperative clinical evaluation that includes

polysomnography or an attended cardiorespiratory
(Type 3) sleep study is routinely indicated to
evaluate for the presence of obstructive sleep apnea
in patients before they undergo upper airway
surgery for snoring or obstructive sleep apnea.
(Standard)

AASM Practice Parameters for Indications for Polysomnography 2005

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 Laboratory Assessment
of OSAHS
• Other Laboratory test
– Thyroid function test
– Pulmonary function test

SLEEP RELATED APNEA Obstructive Apnea

(Apnea 10 sec. & ≥ 5/hr of sleep)

• Central Apnea
– cessation of airflow with no respiratory effort • Cessation of airflow, usually for more than 10
seconds
• Obstructive sleep Apnea
– cessation of airflow through the nose or mouth • With abdominal and/or thoracic effort
with persistence of diaphragmatic & intercostal • Usually terminated by an arousal and/or
muscle activities associated with a desaturation
• Mixed Apnea
– initial cessation of airflow with no respiratory
effort followed by periods of upper airway OSA
ATS, 1989

Central Apnea

• Cessation of airflow, usually for more than 10

seconds
• Without abdominal and/or thoracic effort
• May be terminated by an arousal and/or
associated with a desaturation
• Very different type syndrome than OSA;
chemo-receptor irregularities

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 Mixed Apnea
– Cessation of airflow >10 s (in adults) with
respiratory effort
– Contains both central and obstructive
components, with each component lasting
at least one normal respiratory cycle
– Typically leads to a desaturation and an
arousal
– Is really just a type of obstructive event
with the same consequences

Hypopnea
• Reduced airflow, usually for more than 10
seconds
• Many labs require at least a 50% reduction in
flow; however, more and more labs do not
require a specific % reduction, but look at the
SaO2 and EEG to affect the decision
• May be terminated by an arousal and/or
associated with a desaturation

Scoring Definitions:
Apnoea Absence of or > 90% decrease in airflow
compared to baseline lasting > 10s
Classified as central, obstructive or mixed
apnea
Hypopnoea Any of the following respiratory events lasting
>10s are scored:
> 50% reduction of airflow
> 30% reduction of airflow (but <50%)
associated with > 4% oxygen desaturation

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 Clinical Event Parameters
• Apnea index (AI): number of apneas per hour of TST
• Hypopnea index (HI): number of hypopneas per
hour of TST
• Apnea/hypopnea index (AHI): number of combined
apneas and hypopneas per hour of TST
• Periodic limb movement index (PLMI): number of
periodic limb movements in sleep per hour of TST
• Isolated limb movements index: number of non-
periodic limb movements per hour of TST
Clinical Event Parameters
• Spontaneous arousal index: number of arousals that
occur which are not associated with any other
clinical event
• Arousal index (AI): number of all arousals per hour
of TST
• Periodic limb movement arousal index (PLMAI):
number of periodic limb movements associated with
arousal in sleep per hour of TST
• Mean Heart rate: the average heart rate during the
PSG evaluation which can also be reported by sleep
state, REM, non-REM, and wake.

Pathophysiological Effects of OSA on Cardiovascular Disease and Mechanisms of

the Cardiovascular System Association with Sleep-Disordered Breathing

OBSTRUCTIVE APNEA Endothelial dysfunction

Inflammation

Arousal ↓PaO2, ↑PaCO2 ↓ Intrathoracic pressure Reactive oxygen species

↑ SNA
↓ Myocardial O2 delivery
↑ Catecholamines
CARDIAC ISCHEMIA
CARDIAC ARRHYTHMIAS
Acute Chronic
CARDIAC HYPERTROPHY
CARDIAC FAILURE
Thrombosis Nitric oxide/superoxide Hypoxia
Sleep disorders and cardiovascular
disease; Potential mechanisms
↑ LV wall tension
Catecholamines
↑ Cardiac O2 demand Leptin
Alterations in lipid
metabolism Endothelin

↑ HR
↓ Stroke Volume
↑ BP Hypertension Metabolic syndrome
Obesity Abnormal
Insulin resistance vascular tone

*Proposed Pathophysiological Effects of Obstructive Apnea on the *Proposed Pathophysiological Effects of Obstructive
Cardiovascular System Apnea on the Cardiovascular System
Acute Effects Chronic Effects
• Reduced myocardial oxygen delivery • Autonomic cardiovascular derangements
– Intermittent hypoxia – Sympathetic nervous system activation
– Decreased cardiac output – Reduced heart rate variability
• Increased myocardial oxygen demand – Impaired baroreflex control of heart rate
– Arousals from sleep – Systemic hypertension-nocturnal and diurnal
– Sympathetic nervous system activation • Myocardial effects
– Increase in left ventricular afterload – Left ventricular hypertrophy
• Negative intrathoracic pressure – Left ventricular dysfunction and failure
• Increased blood pressure
• Increased platelet aggregability and blood coagulability
– Increased heart rate
– Increased susceptibility to thrombotic and embolic cardiac and
• Nocturnal myocardial ischemia cerebrovascular events
• Nocturnal pulmonary edema
• Cardiac arrhythmias

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 Acute Cardiovascular Morbidity Chronic Cardiovascular Morbidity
Associated with OSA Associated with OSA
• Myocardial infarction
• Arterial hypertension
• Cerebrovascular disease (stroke)
• Pulmonary hypertension
• Cardiac arrhythmia
• Congestive heart failure

Weiss, Sleep Medicine 2000 Weiss, Sleep Medicine 2000

Incidence of CVD in OSA Incidence of CVD in OSA

• At least one CVD observed in 22 of 60 • Sleep Heart Health Cohort Study

(36.7%) cases of OSA – Increased risk of HPN, cardiac failure, stroke
and IHD in patients with even mild OSA
• CVD incidence in OSA independent of age and BMI
– 21 of 37 (56.8%) – incompletely treated Doherty. CHEST 2005
– 1 of 15 (6.7%) – efficiently treated • OSA severity was not associated with
• OSA asso. with almost five fold increase mortality nor a risk factor for mortality
in risk for development of CVD
independent of age, BMI and smoking Rodriguez. CHEST 2005
Peker, AJRCCM 2002

OSA and Risk Factors for CVD OSA and Risk Factors for CVD
• Increased homocysteine level
• Increased leptin levels
– Endothelial dysfunction
– Wt gain in sleep apnea asso with leptin
– Increased oxidative stress
levels
– Promotes vascular smooth muscle growth
– Leptin is a promoter of platelet aggregation
• Insulin resistance syndrome
• Increased C-reactive protein
– IGT, HPN and/or central metabolic
– Asso with blunted endothelium-dependent
syndrome
vasodilation
– Sleep apnea – higher fasting glucose
– Induces increase in cell adhesion
molecules – IGT → asso with severity in oxygen
– Correlates with severity of sleep apnea desaturation during sleep apnea
Philipps. Curr Opin Pulm Med 2002

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 Obstructive Sleep Apnea and Mechanisms of
Myocardial Infarction Myocardial Infarction in OSA
• Increased sympathetic activity may contribute to myocardial
• Apnea index > 5.3 episodes/hour of sleep ischemia and coronary plague disruption
is an independent predictor of myocardial • Chronically elevated catecholamine levels may injure the
myocardium
infarction Dart. CHEST 2003
• Hypoxia triggers a generalized inflammatory response causing
Dart. CHEST 2003 systemic release of inflammatory mediators
• ST-segment depression during the night Quan. Circulation 2004
• Obstructive apnea can lead to myocardial ischemia even in the
occurred in 30% of patients with OSA absence of hypoxia
Scheuf. Am Rev Resp Dis. 1992
Hanly. Am J of Cardiol. 1997 • Main trigger of ischemia was an increase in oxygen demand
rather than oxygen desaturation
Pelial. J. Am Coll Cardiology

Obstructive Sleep Apnea and

Coronary Artery Disease and OSA
Cardiac Arrhythmias
• Mortality:
• Tachyarrhythmias and bradyarrhythmias reported in
– 38% - with OSA >75% of patients with sleep apnea
– 9% - without OSA • Sinus bradycardia – during apneic phase
• Atrial tachycardia, V-tach, PVC – due to
• OSA a poor prognostic indicator in catecholamine surges and hypoxemia at termination
CAD Peker. AJRCCM 2002 of apnea
Dart. CHEST 2003

• Individuals with severe SDB have two-to-fourfold

• Respiratory disturbance index, an higher odds of complex arrhythmias than those
independent predictor of mortality in without SDB even after adjustment for potential
CAD confounders
Yuksel. AJRCCM 2000 Mehra. AJRCCM 2006

Possible Mechanisms of OSA and Hypertension

Arrhythmias • 40% of patients with OSA have daytime HPN
• Obstructive events →↑ myocardial wall • 30% of middle – aged men with HPN have occult
tension and oxygen demand → myocardial sleep apnea
ischemia • Each additional episode of apnea/hypopnea per hour
of sleep was asso. with a two-fold increase in systolic
• Hypoxemia and hypercarbia → lead to blood pressure Young. AJRCCM 1997
cortical arousals, ↑ sympathetic tone and
• Only systolic BP increased with OSA and CPAP
catecholamine release significantly attenuated the increase in systolic BP
and no effect on diastolic BP
Tkacova. Circulation 1998
Quan. Circulation 2004

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 Possible Mechanisms Linking OSA
OSA and Hypertension and HPN
• OSA has a direct and disproportionate • Intermittent Hypoxia → stimulation of peripheral
effect on systolic BP that is difficult to chemoreceptors → stimulate brainstem
control with pharmacologic agents sympathetic vasoconstriction
• Increased activity of adrenal glands, renal
Logan , J of HPN 2001
sympathetic nerves and renin angiotensin
• HPN refractory to maximal medical
system
therapy, 87% had OSA
Leung. AJRCCM 2001
Leung, AJRCCM 2001 • Repeated arousals during sleep is asso. with
increased sympathetic activity

Nieto. JAMA 2000

Possible Mechanisms Linking OSA Possible Mechanisms Linking OSA

and HPN and HPN
• Nocturnal hypoxemia results in significant
elevation in plasma endothelin → sustained
daytime BP elevation
• ↑ Platelet activation → chronic hypertension
• Diminished endothelial cell production of nitric • OSA promotes atherogenesis through
oxide → impaired vasodilatation and higher recurrent exposure to hypoxemia
resting vascular tone
• Hypoxemia and sleep deprivation induce Shabarn. AJRCCM 2001
production of pro – inflammatory cytokines →
endothelial dysfunction

Quan. Circulation 2004

When should OSA be considered *Obstructive Sleep Apnea and

in a patient with systemic HPN? Congestive Heart Failure
• OSA was associated with a 2.38
• Signs and symptoms of OSA
relative odds for congestive heart
• Unexplained or worse cardiac disease
failure independent of other known
than expected based on the level of BP
risk factors
• Patients with resistant HPN Sleep Heart Health Study, AJRCCM 2001

Dart. CHEST 2003

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 Obstructive Sleep Apnea
Mechanisms of CHF in OSA
and Stroke
• Negative intrathoracic pressure • Patients who suffered a stroke, sleep
– Adverse ventricular contractions
– Increased ventricular wall stress
apnea is reported to occur in 43-91% of
– Reductions in cardiac output patients
– Increased PCWP
Leung. AJRCCM 2001
Sin. AJRCCM 1999
• Systemic HPN – most obvious mechanism • OSA after adjustment for age and sex is
• Ischemia and reduced contractility due to hypoxia related to significantly increased odds of
• Cardiac myocyte injury or necrosis due to increased suffering a stroke over the next 4 years
catecholamine stimulation

Arzt AJRCCM 2005

Leung. AJRCCM. 2001

Mechanisms of OSA and OSA & Stroke: Adverse

Cerebrovascular Events Prognostic Implications
• Systemic hypertension
• Increased platelet aggregability
• Blood coagulability
• Worse functional capacity
• Obstructive apnea cause a significant decline in cerebral • Longer period of post-stroke
blood flow due to ↓ in cardiac output rehabilitation
• Abrupt alterations in vascular shear forces and
acceleration of atherosclerosis • Higher death rate
• Hypoxia can lead to the elaboration of neuroinhibitory
peptide such as γ-aminobutyric acid → compromise Artz. AJRCCM 2005
cerebral function

Leung. AJRCCM 2001

Obstructive Sleep Apnea and Obstructive Sleep Apnea and

Pulmonary Hypertension (PH) Venous Thromboembolism (VTE)

• 17% of OSAHS had PH • Possible association between OSAHS

• PH is usually mild to moderate and VTE
• Due to thrombolytic coagulation
Mechanism :
abnormalities provided by recurrent
Chronic hypoxemia ? pulmonary episodes of hypoxemia
vasoconstriction and remodeling of the Arnulf, JAMA 2002
pulmonary vascular bed
Chaouat Chest 1976

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 *OSAHS and Impaired Glucose- *OSAHS and Impaired Glucose-
Insulin Metabolism Insulin Metabolism
• IGT and Type 2 DM are common in • Incidence
patients with AHI = 10. Type 2 DM was – 30.1% - Type 2 DM in OSAHS
newly diagnosed in 40% of the diabetic – 3.9 % - Type 2 DM in non-apneic snorers
patients – 20 % - IGT in OSAHS
– 13.9 % - IGT in non-apneic snorers
• AHI is independently related to glucose Meslier ERJ 2003
metabolism and insulin sensitivity after
adjusting for confounding variables • Snoring is independently associated with
impaired glucose tolerance and Type 2 DM
Punjab, AMJ Epidemiol 2004
Meslier. ERJ 2003

*OSAHS and Impaired Glucose- *OSAHS and Impaired Glucose-

Insulin Metabolism
• Mechanisms
• Mechanisms
– Cyclical hypoxia could lead to glucose
intolerance and insulin resistance by
promoting release of pro-inflammatory
cytokines (IL-6 and TNFα)
– Sleep fragmentation increases levels of
plasma cortisol ? ? glucose levels and
insulin concentration and increased
insulin secretion
Insulin Metabolism
– Sympathetic hyperactivity
• influences glucose homeostasis by increasing
glycogen breakdown and gluconeogenesis
• increases circulating free fatty acids via stimulation
of lipolysis and promotes insulin resistance
– Central obesity leads to insulin resistance via
? lipolysis and fatty acid availability
Punjab, AMJ Epidemiol 2004

*OSAHS and Impaired Glucose-

Insulin Metabolism *OSAHS & Hypothyroidism
• Even mild degrees of OSA would be
associated with glucose intolerance and insulin • 1-3% = prevalence of hypothyroidism
resistance in OSAHS
• Early metabolic dysfunction occurs with OSA
before overt clinical manifestation of underlying
• Screening for hypothyroidism in
disease OSAHS does not seem necessary
• Metabolic dysfunction associated with OSA unless patient is symptomatic of
may increase the risk of CVD morbidity and belongs to a risk group
mortality
Punjab AJRCCM 2002 Saaresenta ERJ 2003

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 *OSAHS and Growth Hormone
Deficiency
• 70% of nocturnal GH pulses are
associated with slow-wave sleep
• Mechanisms
– Sleep fragmentation results in
decreased amount of slow wave sleep
– Hypoxia inhibits growth hormone release
or biosynthesis
– Obesity decreases GH secretion
Saareseanta ERJ 2003

Effects of Treatment Effects of Treatment

• 10-15 % weight loss can reduce or
eliminate OSA
• Low levels of weight reduction may
curtail cardiovascular risk
Punjab, AJRCCM 2002
• Serum leptin levels decrease with CPAP
without weight loss
• Decrease in leptin levels already
observed after the first night of CPAP
• CPAP induced reduction in leptin level is
due to improved sleep and breathing
Saareseanta. ERJ 2003

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 Effects of Treatment
Effects of Treatment
• Treatment of OSA by CPAP for 1 month
caused dramatic improvements in LVEF (from • The effect of nocturnal CPAP carry over
37% to 49%) and cardiac functional status into wakefulness
Leung. AJRCCM 2001
• Effects of one month treatment
• 8 - year follow-up on rate of new onset IHD – 9% absolute and 35% relative rise in LVEF
– 14% = untreated group
– Decrease in systolic BP of 10 mmHg
– 5% = CPAP group
– Decrease in heart rates of 4 beats/ minute
• Long Term Effect of CPAP on Cardiovascular
Outcome (5 - year follow up)
– 31% = total CV events in the untreated group Kaneko. NEJM 2003
– 18% = CPAP group Doberty. CHEST 2005

Effects of Treatment Effects of Treatment

• CPAP treatment for 3 months improved
insulin responsiveness
• Insulin sensitivity significantly increased
after 2 days of CPAP especially in patients
with BMI < 30
Harsch ASRCCM 2003
5-year cumulative survival rate
• 96.4% = CPAP compliance >6 hrs/day
• 91.3% = CPAP compliance 1-6 hrs/day
• 85.5% = CPAP compliance <1hr/day
Rodriquez. CHEST 2005

Better understanding of sleep

“Laugh and the world laughs with you,
related breathing disorders can
improve health outcomes in patients snore and you sleep alone.”
suffering or at risk for its systemic Anthony Burgess
consequences. English novelist, critic

*What-eber?! 

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