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OSAHS Phenotypes : More
Understanding
BY
DR: MOHMMAD EL DESOUKY ABOU
SHEHATA
Prof of: PULMONOLOGY MASOURA
UNIVERSITY
Obstructive Sleep Apnea /Hypopnea
Syndrome (OSAHS)
The syndrome is characterised by obstruction of the
upper airway during sleep, resulting in repetitive
breathing pauses accompanied by oxygen desaturation
and arousal from sleep. This may result in diurnal
sleepiness and may lead to cognitive impairment and
cardiovascular morbidity
Riha R L et al Eur Respir J 2009; 33: 646–655
OSAHS AASM Definition
Sleep Apnea
• Obstructive apnea is the cessation of airflow for at least
10 seconds with persistent respiratory effort. .
• Central apnea is the cessation of airflow for at least 10
seconds with no respiratory effort
• Mixed apnea is an apnea that begins as a central apnea
and ends as an obstructive apnea
OSAHS AASM Definition
Sleep Hypopnea
• The recommended definition of a hypopnea is a 30%
or greater decrease in flow lasting at least 10
seconds and associated with a 4% or greater
oxyhemoglobin desaturation.
• An alternative definition is a 50% or greater
reduction in flow lasting at least 10 seconds and
associated with either a 3% or greater
oxyhemoglobin desaturation or an arousal.
Clinical Manifestation of OSAHS
Nocturnal symptoms
• Snoring,
• Witnessed apneas
• Gasping and choking sensations that arouse the patient from sleep
• Restless sleep, with patients often experiencing frequent arousals a
Daytime symptoms
• Not feeling refreshed upon awakening
• Morning headache, dry or sore throat
• EDS that usually begins during quiet activities (e g, reading,
watching television)
• Fatigue
Prevalence Of ( OSAHS)
•
•
OSAHS is the third most common respiratory condition after asthma
and chronic obstructive airway disease
2-4% of the middle-aged population is affected by OSAHS
• Up to 20% of the population is thought to have SDB at any one time
Bixler EO, et al. Am J Respir Crit Care Med 1998
Young T et al .N Engl J Med 1993; 328: 1230–1235
SEQULUE OF Untreated OSAHS
• OSAHS is an independent risk factor for diurnal hypertension
• epidemiologically, has been implicated as a risk factor for stroke and
other cardiovascular events
• OSAHS may contribute to the expression of metabolic syndrome,
increased insulin resistance and a higher inflammatory state.
Faccenda JF,et al (2001) Am J Respir Crit Care Med 2001; 163: 344–348
Shahar E ,et al (2001) Am J Respir Crit Care Med 2001; 163: 19–25.
CLINICO-PHYSIOLOGICAL PHENOTYPES OF
OSAHS
• A phenotype is any detectable characteristic of an organism
determined by an interaction between its genotype and environment
• Phenotypic plasticity, is the ability of an organism with a given
genotype to change its phenotype in response to changes in the
environment, may be applicable to OSAHS.
• Thus, a particular genotype may express itself as a different
phenotype at different times and in response to different
environmental circumstances .
Ernande B, Dieckmann U. J Evol Biol 2004; 17:
Riha R L et al Eur Respir J 2009; 33: 646–655
Risk Factors Implicated In OSAHS
Phenotype Expression
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Obesity and Ageing
Gender : Male > Female ; postmenopausal female
craniofacial abnormalities,
race and certain congenital conditions, such as Marfan’s syndrome,
Enviromental risk factors e g Alcohol ; sedative use, sleep
deprivation,tobacco use and sleeping in the supine posture
• Reduced nasal patency, due to a variety of causes, can contribute to
OSAHS
Strohl KP,et al, Am J Respir Crit Care Med 1996; 154: 279–289.
The Phenotypic Complexity of OSAHS
• Upper airway obstruction during sleep is the key
pathophysiological feature in OSAHS.
• dysfunction of upper airway muscles alone is unlikely to
be the sole cause of OSAHS
• A number of interrelated pathologies and risk factors
interact to produce the OSAHS phenotype
• The strongest risk factor is obesity and ageing
Riha R L et al Eur Respir J 2009; 33: 646–655
Impact of Normal Ageing in OSAHS
Phenotypic Expression
• A changes in parapharyngeal fat pad deposition
• serotonergic disregulation of brainstem respiratory control (wear and
tear )
• age-related changes in bony structures such as edentulism
• Variations in neuromuscular control of the upper airway may gain
greater importance in the elderly
• Increased prevalence of cardiac and cerebrovascular disease
• Older subjects may report less daytime sleepiness for a given level
of OSAHS
• OSAHS in the elderly is less likely to be equivalent to the same
disorders that develop in middle or young age.
OSAS From Genotype To Phenotype
• Hereditary factors are thought to invoke 40% of the
variance in the occurrence of OSAHS in the general
population;
• the rest is attributable to environmental factors
• It is likely that genetic factors associated with craniofacial
structure, body fat distribution and neural control of the
upper airway muscles interact to produce the OSAS
phenotype
Redline S, Tishler PV: The genetics of sleep apnea. Sleep Med Rev 2000; 4: 583–602.
M Casale et al . Curr Genomics .2009 ; April 10(2): 119-126
Intermediate Phenotypes of OSAHS
Due to the considerable clinical heterogeneity of the
OSAHS phenotype, the current paradigm of OSAHS was
considered as the product of intermediate phenotypes
which interact to produce the overall phenotype
OSAHS Intermediate Phenotypes
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•
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Craniofacial phenotype
Obesity phenotype
susceptibility to sleepiness phenotype
ventilatory and upper airway control.
Intermediate Craniofacial Phenotype
Morphological features
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cranial base dimensions being more obtuse,
inferior displacement of the hyoid bone,
increase in lower facial height,
a retroposed maxilla and a short mandible
macroglossia, adenotonsillar hypertrophy,
Intermediate Craniofacial Phenotype
Factors Linked To Expression Of Craniofacial Phenotype
• Environmental mechanisms play a strong role in determining
cranioskeletal growth. These include bad habits such as thumbsucking and abnormal tongue posturing, nasopharyngeal disease,
disturbed respiratory function (e.g. mouth breathing),
tumours, loss of teeth, malnutrition and endocrinopathy .
•
Gene involved in the embryogenesis, growth, development and
expression of the craniofacial complex are subject to very
complex gene–gene and gene–environmental effects and their
pathways are yet to be fully elucidated
genes controlling final adult height and
stature may affect craniofacial growth.
These include the vitamin D receptor, beta-2adrenergic receptor, growth hormone,
insulin-like growth factor (IGF-1), insulin-like
growth factor receptor and growth hormone
receptor (GHR). Specifically,
IGF-1 has been shown to be an important and
independent regulator of maxillofacial and
Mandibular growth postnatally
Latral cephalometric radiograph showing the Cervico-craniofacial skeletal
reference points and lines used for linear and angular measurements.( A:
subspinale =the most posterior midline point in the concavity between the
anterior nasal spine and the lowest point on the alveolar bone overlying
the maxillary incisors ,B: Supramentale = the most posterior medline point
on the anterior concavity of the mandibular symphysis
a midsagittal MRI image show the nasopharynx and
retroplatale narrowing
midsagittal MRI image show surface area of the tongue
midsagittal MRI image show surface area of the soft palate and
retroplatal obstruction
Airway of normal subject ( increase lateral dimension than AP)
Axial MRI of the velopharynx show the parapharyngeal muscular
thickness
Intermediate Obesity Phenotype
Link between obesity OSAHS
• Morbid obesity defined as a body mass index (BMI) of > 30 is
present in 60–90% of patients with OSAHS
• Central obesity, characterised by a high waist:hip ratio or increased
neck circumference, is probably better correlated with OSAHS.
• not all obese subjects will snore or have SDB .
Pathogenesis of OSAHS
• In obesity, fat deposition results in a reduction in nasopharyngeal
calibre
• Adipokines, such as leptin, may affect the regulation of the
respiratory centre
Axial MRI show parapharyngeal pad of fat
susceptibility to sleepiness
Link between sleepiness & OSAHS
• Sleepiness, as a consequence of SDB, is required to define
OSAHS but does not necessarily correlate with it.
• There appears to be a differential susceptibility to somnolence among
individuals.
Pathogenesis
• Sleep is regulated by neuronal and humoral mechanisms that are
interdependent
• Interleukin (IL)-1; TNF-a ; appear central to the sleep activation pathways,
and other sleep-inducing cytokines include IL-10, IL-6, interferon, IL-2, IL-4,
• Many of these cytokines are pleiotropic and also implicated in initiating or
propagating the sequelae of OSAHS, particularly inflammation
ventilatory and upper airway control.
Ventilatory control
•
There is a high degree of heritability of peripheral chemoreceptor
responses to hypoxia and hyperoxia in monozygotic twins
•
Although several studies have shown abnormalities of respiratory control It
is debatable whether respiratory control problems are implicated in the
pathogenesis of OSAHS
OSAHS Phenotype --- Home Message
• At present OSAHS has no distinct phenotype definition
• OSAHS appears to be a complex polygenic disease.
• Intermediate phenotypes interact in different dimensions to produce
a single phenotype at a given point in time.
• The degree of environmental influence is difficult to gauge but is
likely to be considerable.
• Progress in determining the genotype of OSAHS is affected by the
lack of a consistent definition of phenotype.