Introduction
Obstructive sleep apnea is defi ned as a breathing
disorder characterized by prolonged upper airway
partial and/or intermittent complete obstruction that
disrupts normal ventilation during sleep and normal
sleep patterns accompanied by associated signs and
symptoms characteristic of the disorder.1,2 (According
to American Academy of pediatrics clinical practice
guidelines)
Obstructive sleep apnea syndrome (OSAS) was fi rst
reported in children by Guilleminault et al (1976)
following which recognition of abnormal breathing
during sleep has progressed.3 The prevalence of OSA
in childhood is around 2-3% affecting all ages with
peak incidence between 2-8 years. 4Frequent snoring
is reported by parents in 3-15% of children while
prevalence of reported apneic events is 0.2-4%.4
OSA is a part of a complex of sleep disordered
breathing (SDB) with a spectrum of clinical
manifestations ranging from primary snoring to
OSAS with upper-airway resistance syndrome
(UARS) falling in between the extremes.5
Primary Snoring
Snoring during sleep without associated apneas, gas
exchange abnormalities or excessive arousals is defi ned
as primary snoring. This does not progress to OSAS in
young children and is known to resolve over time.6
Upper Airway Resistance Syndrome (UARS)
UARS is characterised by snoring, partial airway
obstruction leading to increasingly negative intrathoracic pressures during inspiration. This
causes arousals, sleep fragmentation but there is
preservation of airfl ow and oxygenation. Thus,
there is no evidence of apnea, hypopnea or gas
exchange abnormalities on polysomnography.
Polysomnography (PSG) shows snoring with marked
paradoxical breathing movements or repetitive
arousals. Increased respiratory effort with arousals
clinches the diagnosis of UARS on esophageal
pressure monitoring.7,2
Obstructive Sleep Apnea Syndrome
1-3% children have OSAS and 40% of children
referred to sleep medicine or an otolaryngologist may
have OSAS.Obstructive sleep apnea ischaracterised
by prolonged upper airway obstructionduring sleep
resulting in partial or complete cessation of breathing
associated with reduction of oxyhemoglobin
saturation or hypercarbia, or both. This may lead
to obstructive apnea or obstructive hypoventilation.
Obstructive hypoventilation is not seen in adults
usually. It leads to paradoxical respiratory efforts,
hypercarbia and occasionally hypoxemia.7,8
The obstructive events resulting in hypoxia
and multiple arousals contribute to metabolic,
cardiovascular and neurocognitive changes.
Pathophysiology
Upperairway is a collapsible tube, the patency of
which is determined by the tone of the pharyngeal
muscles causing dilatation as well as phasic
contractions of these muscles during inspiration.
7Pathophysiology can be arbitrarily divided into
anatomical factors, control of airway patency and
obesity.
Anatomical factors
Changes in the anatomical framework of the head
and neck, affects the calibre of pharyngeal airway,
which in turn contributes to increased risk of airway
obstruction. The most common cause for childhood
OSA is adenotonsillar hypertrophy. 8
Arens et al used MRI to study the airway of children
with OSAS. These children had signifi cantly enlarged
tonsils and adenoids leading to smaller upper airway
volumes as compared with controls.In addition
positive correlation was seen when percent difference
of combined tonsil and adenoid volume between each
subject and matched controls was plotted against
apnea-hypopnoea index.9Soft palate volume was also
found to be more in subjects with OSA.Children with
OSA have hyperplasia of lymphoid tissue in regions
other than waldeyers ring also.
Kun-Tai kang et al reviewed 495 children with OSA
and studied the contribution of adenoid and tonsil
size in childhood OSA and interactions between
adenotonsillar hypertrophy, age and obesity. They
found that the effect of adenoid size on OSA decreased
in adolescence. Moreover, both adenotonsillar
hypertrophy together increased OSA risk more than
tonsil or adenoid hypertrophy alone.10
Adenoidal- nasopharyngeal space is narrowest at
4.5 years of age and adenoidal mass reaches greatest
size at 7-10 years of age when facial framework
rapidly develops. This space gradually decreases
until 12 years of age. Thus the infl uence of adenoid
size decreases as the child reaches adolescence.
However,there is no such correlation between age,
tonsil size and OSA in children.10
Adenoidal- nasopharyngeal space is narrowest at
4.5 years of age and adenoidal mass reaches greatest
size at 7-10 years of age when facial framework
rapidly develops. This space gradually decreases
until 12 years of age. Thus the infl uence of adenoid
size decreases as the child reaches adolescence.
However,there is no such correlation between age,
tonsil size and OSA in children.10
Craniofacial factors includehypoplasia or retropositioning
of maxilla or mandible, large or retropositioned
tongue.(see box 1)Evaluation of children
with craniofacial anomalies is directed towards
assessing skull base shape, maxillary size and shape,
tongue size and support and mandibular size and
shape. OSAS in such children persists even after
adenotonsillectomy and additional surgical as well as
non-surgical therapies are generally required. Infants
usually require tracheostomy.9Skeletal dysplasias
such as achondroplasia may lead to ‘mixed apnea
syndrome’. Brainstem or cervico-medullary
compression results in abnormal ventilatory drive
and central apnea. Adenotonsillar enlargement and
craniofacial factors cause Obstructive sleep apnea.7
Control of airway patency
Anatomical factors are not the only determining
factor leading to OSA in pediatric age group. Children
with large tonsils may not have OSA. Since upper
airway is a collapsible tube, Marcus et al proposed
the ‘Starling Resistor Model’of the upper airway.
According to this model maximum inspiratory fl ow
through a collapsible upper airway is determined
by upstream (nasal) pressure changes and pressure
changes surrounding the collapsible segment. This
airfl ow is not dependent on the tracheal pressure
generated by the diaphragm. The pressure outside
the airway is determined by the activity of the airway
dilator muscles.7,9 The pressure at which airway
collapses is termed as critical closing pressure
(Pcrit) and this is a measure of airway collapsibility.
Children with OSA have more airway collapsibility
(Pcrit was higher or less negative) than children with
primary snoring.5
Obesity
With increasing epidemic of obesity in children
especially in developed countries and now in the
developing countries too, more and more children
presenting with OSA are observed to be obese.
Classical presentation of a child with adenotonsillar
hypertrophy and failure to thrive is now being
replaced with an obese child presenting with OSA.
These children may or may not have adenotonsillar
hypertrophy. They usually present at alater age and
the clinical profi le resembles adult OSA phenotype.
9A percentage of this group of children undergoing
adenotonsillectomy(AT), still have residual OSA
following surgery.
Possible mechanisms causing OSA in childhood
obesity are as follows.7,9
• There are alterations in mechanisms regulating
upper airway patency and increased airway
collapsibility in obese children.
• Central obesity reduces functional residual
capacity by limiting diaphragmatic descent,
more during supine position. Moreover, these children have decreased lung compliance leading
to hypoventilation, atelectasis and ventilationperfusion
mismatch.
• OSA can induce leptin resistance and increase
ghrelin levels both of which can increase
obesogenic behaviour .
Three subtypes of childhood OSA have been
identifi ed4,11:
Type I marked increased lymphoid tissue in upper
airways in absence of obesity
Type II milder lymphoid hypertrophy associated
with obesity
Type III Children with syndromic OSAS
OSA and Infl ammation
OSA leads to elevation of CRP. An animalmodel of
intermittent hypoxia and hypercapnia lead to elevation
of interleukin-6 (IL-6) level, which is a precursor of
CRP.12Some studies demonstrated increased levels
of proinfl ammatory cytokinesTNF-α, IL-6 and IL-
1α from OSA derived tonsils. They postulated that
recurrent vibrations of the upper airway during
snoring, promotes localized infl ammation. 8Goldbart
et al showed higher levels of leukotriene B4 and
cysteinyl leukotriene in children with OSA. Even
sputum from children with OSA exhibits neutrophilia
as compared with controls.
Sequelae of OSA
OSA causes intermittent hypoxemia and subsequent
sleep fragmentation which induces local and systemic
infl ammation. The combination of these infl ammatory
cascades and oxidative stress mechanisms lead to cell
injury, dysfunction and cell death affecting various
targeted organs.
Cardiovascular system
OSA can promote cardiovascular disturbances in
blood pressure regulation, ventricular remodelling
and endothelial dysfunction. Children can have a
vast variety of cardiovascular symptoms including
systemic and pulmonary hypertension, and cor
pulmonale with heart failure. 2 Majority of children,
show signifi cant improvement in endothelial function
after treatment of OSA with adenotonsillectomy.9,11,13
Children with OSA have a higher diastolic BP during
sleep as compared with primary snorers though
elevations in systemic BP were noted even in children
with primary snoring.
Amin et al demonstrated overnight greater changes
in brain natriuretic peptide (BNP) in children with
moderate to severe OSA as a result of frequent
negative intrathoracic pressure swings. This accounts
for the ventricular dysfunction in these children.9
Endothelial dysfunction is known to be a precursor of
atherosclerosis. Children with concomitant obesity and
OSA have a greater degree of endothelial dysfunction
as compared to children with only OSA.OSA
severity is associated with a decrease in T regulatory
lymphocytes (Tregs) in peripheral blood of children
with OSA. Tregs have shown to inhibit development
and progression of atherosclerosis. Gozal et al stated
that OSA in children is strongly related to changes in
Tregs and their function. This in turn contributes to
cardiovascular morbidity in children.13
C- reactive protein (CRP), an acute phase reaction protein has recently emerged as one of the
powerful independent predictors of risk for future
cardiovascular morbidity and is now widely used
to stratify risk for ischemic heart disease. Increased
CRP levels have been demonstrated in children
with OSA and the level of rise in CRP levels is
proportionate to the severity of OSA. However, there
is signifi cant reduction in these levels following
effective treatment. 6,9
Polverino and associates studied 101 children and
found that AHI (Apnea- Hypopnea index) was
signifi cantly associated with Hs-CRP (high sensitivity
CRP). Hs-CRP was signifi cantly higher in children
with OSA. Children with OSA and raised CRP levels
are found to be at a greater risk for the development
of long term cardiovascular complications.14
Behavioural and neurocognitive impairment
SDB is associated with poor learning, poor school
performance, attention defi cits, concentration
diffi culties, hyperactivity and impulsivity. This
is secondary to fragmented, non-restorative sleep
with intermittent hypoxia and its effect on the
development of prefrontal cortex. Prefrontal cortex
is responsible for behavioural control, working
memory, organisation, analysis and self-regulation of
motivation. 2,15 ‘Memory consolidation’ occurs during
REM sleep whilst growth hormone is produced in
slow wave sleep. Thus sleep fragmentation occurring
in OSA affects both cognition and interferes with
growth. Even children with ‘primary snoring’
(without gas exchange abnormalities) or mild OSA
can present with neurobehavioral changes.12Maria et
al concluded in their study that executive dysfunction
is related to nocturnal hypoxemia rather than daytime
sleepiness.15
Gozal in 1998 performed a study in children whose
school performance was in the lowest 10th percentile
of their class. There was a marked prevalence of
OSA in these children. Moreover, children who were
treated (adenotonsillectomy) showed signifi cant
improvement in school grades.2,9,12Khadra et al
hypothesized that neurocognitive impairment occurs
as a result of changes in cerebral blood fl ow during
sleep.9
It is further emphasized that not all children with
OSA exhibitbehavioural and cognitive defi cits. Both
genetic and environmental factors play a major role
in phenotypic expression of these defi cits. Following
treatment of OSA improvement occurs in behaviour
and cognition. However, early diagnosis and prompt
treatment is advised as some neurocognitive changes
are only partially reversed if left too long.
Metabolic sequelae
OSA has been associated with failure to thrive.
Children with OSA and primary snorers have
disruption of slow wave sleep, during which growth
hormone (GH) and insulin-like growth factor (IGF-1)
are secreted. Failure to thrive results from reduction of
IGF-1 or insulin-like growth factor binding proteins
(IGFBPs) which signifi cantly reverses following
adenotonsillectomy(AT).5Furthermore, there may be
dysphagia and increased energy expenditure leading
to lesser intake.4
In contrast to the earlier presentation of failure to
thrive, more and more children presenting with OSA
are now obese. Sleep fragmentation and intermittent
hypoxia is associated with reduced insulin sensitivity
and dyslipidemia in obese children.Fatty liver disease
has been demonstrated in children with OSA and
obesity. Treatment with AT followed by continuous
positive airway pressure led to improvement in liver
serum aminotransferases. 9
Rise in low-density lipoprotein (LDL) cholesterol
along with lowering of high-density lipoprotein
(HDL) cholesterol is seen in OSA children
irrespective of the presence or absence of obesity.9
Diagnosis
Clinical manifestations
Early diagnosis and prompt management of OSAS,
results in decreased morbidity and reversal of most of
the sequelae of OSA. Primary snoring and OSA cannot
be differentiated by history and examination alone.
Symptoms in pediatric age group are dependent on
the age of the child. Nocturnal symptoms noticed by
parents are seen in all age groups. They include loud,
frequent snoring,choking, breathing pauses, restless
sleep, arousals and nocturnal enuresis. These children usually have unusual sleeping postures. They keep
their necks hyperextended to maintain patency of
upper airway. They are also known to present with
paradoxical breathing, mouth breathing, nocturnal
sialorrhea, nocturnal sweating, parasomnia, and
bruxism.2, 6,7 (see box 2)
Most of the time daytime symptoms are more
pronounced and apparent in older children. Excessive
daytime sleepiness (EDS) is seen only in 7-10% of
the cases. EDS is seen in children with severe OSA
and obesity and is associated with higher incidence of
complications (40-50%). More commonly pediatric
OSA presents as hyperactivity and inattention during
the day, moodiness, poor learning in school as
explained earlier.2,9
Examination
First step to examining a child suspected to have
OSA is to note the height and the weight of the
child, because growth can be impaired in the child.
A full otorhinolaryngologic examination must be
conducted to establish the site of static or dynamic
airway obstruction.4,6,7,12,16 Child suspected to be suffering from OSA will have a
typical ‘long face syndrome’. These mouth breathers
have altered dento-alveolar morphology. The
characteristic features include high arched palate,
increased lower facial height, narrow maxilla and
retrognathia.5(see box 3)
Polysomnography
Overnight polysomnography in a sleep laboratory is
the gold standard for diagnosis of pediatric OSAS
and is the best technique to differentiate between
primary snoring and OSA.7 Accurate diagnosis of the
severity of OSA will ensure the proper treatment in
children and will defer unnecessary surgeries where
ever not required.
American Academy of Thoracic Society, Standards
and Indications of Cardiopulmonary Studies in
children recommends measurement of the following
parameters: 7
1. Sleep State: Electroencephalogram,
electromyogram, electro-oculogram.
2. Respiratory parameters: abdominal and chest
wall movements, oronasal airfl ow, end tidal CO2, oxygen saturation with pulse oximetry
3. Non respiratory parameters: electrocardiogram,
electromyogram.
4. Audio video recording
Sleep related upper airway obstruction is diagnosed
in children who have evidence of signifi cant
obstructive hypoventilation or more than one
obstructive apneic episode per hour. Obstructive
apneic episodes in children often are shorter than
10 seconds as compared with adults where they last
for more than 10 seconds. Two or more consecutive
breaths with obstructive apneas or hypopneas are
considered abnormal in children.7
Obstructive apnea is defi ned as near complete
cessation of airfl ow despite on-going respiratory
effort.Obstructive hypopnea is defi ned as partial
upper airway obstruction resulting in greater than
50% reduction in airfl ow associated with either
an arousal or desaturation of 3% or greater from
baseline.Apnea-hypopnea index (AHI) refl ects the
number of discrete obstructive events per hour.
There is no international consensus for AHI cut off
values to initiate treatment in children. The current
accepted arbitrary cut off for AHI is > 3 standard
deviations beyond mean of normative AHI in healthy
children. Children with an AHI <1/ hour total sleep
time (TST) do not have signifi cant OSA. On the
other hand a child with AHI>5/ hour TST requires
treatment.9 However, as there is no evidence based cutoff
some children with AHI<5 may be symptomatic
and require intervention.2 The American Society of
Anesthesiologistsguidelines defi nes severe OSA as
AHI of 10 or more.2
It is seen that only 10% of children with habitual snoring
referred for adenotonsillectomy actually undergo
overnight sleep study. AAOHNS published clinical
practice guidelines for use of PSG before tonsillectomy
in children(see box 4).17 Many factors like the cost,
inconvenience to the child and parents, expertise in
pediatric sleep study and interpretation make most of the
physicians consider PSG not necessary for diagnosis.8
Conventional numerical measures (eg. obstructive
apnea-hypopnea index, arousal index, oxyhemoglobin
desaturation index etc.) are poorindicators of morbidity
in children.17 Additionally, many morbidities in
children present after a long period of time. Children
who are symptomatic, may show ‘normal PSG’ in the
presence of habitual snoring and conversely, relatively asymptomatic snoring children, may have severe
respiratory disturbances in their NPSG.
To overcome the drawbacks of using as a only NPSG
as a diagnosing tool for the severity of OSA an
Other studies 4,7,11
In view of the expertise and resources required to
perform a PSG several alternative studies under
evaluation are:
1. Nap PSG can be helpful if positive but it has a
high false-negative rate attributed to shorter total
sleep time and lesser proportion of REM sleep in
daytime nap.
2. Unsupervised overnight pulse oxymetry gives
information about desaturation but cannot rule
out OSA if negative. Associated recording of
end-tidal CO2 provides additional information of
cessation of airfl ow.
3. Video and audio recordings
4. Multichannel devices for home recordings offer
cost effective details on sleep information in an
unsupervised setting.
5. Flexible nasendoscopy can be used to evaluate
the level of airway obstruction, lymphoid tissues
and post nasal space.Sleep endoscopy- fi bre optic
endoscopy is performed under artifi cially induced
sleep to determine the site of obstruction and plan
the treatment subsequently.
Treatment
Surgical
Adenotonsillectomy (AT) is the fi rst line of treatment
in children with OSA and adenotonsillar hypertrophy.
Combination of adenoid and tonsil surgery is
considered superior and more effective in treating
OSA than both alone.8,12
As compared to watchful waiting, surgical treatment
of OSA improved symptoms, behavioural changes
and quality of life according to a recently published
Childhood adenotonsillectomy trial (CHAT).9AT
reduces AHI to < 1 event/hour in 25% to 71% children
with OSA. Signifi cant improvements are seen in
quality of life, attention span,growth, behaviour,
school performance and cognition.16
Surgery is associated with complications which
are more common in high risk group.5,9,16 The risk
factors include children younger than 3 years, severe
OSAS(apnea- hypopnea index more than or equal to
10 and/or oxygen saturation nadir less than or equal to
80%), failure to thrive, obesity, cardiac complications
of OSAS, craniofacial and neuromuscular disorders
and current respiratory infections. 1,2 Careful pediatric
intensive care monitoring is recommended for all
high risk children in the post-operative period.
According to a retrospective study, although majority
of the children showed marked improvements
following AT, residual OSA was prevalent in a large
subset of cases. Residual OSA was seen in severe
OSA cases ( AHI> 20/ hour TST), children older
than 7 years, asthmatics, positive family history of
OSA, African American race, high Mallampati score,
craniofacial abnormalities, chromosomal defects and
neuromuscular disordersand other obstructive causes
like enlarged turbinates, deviated septum. 5Residual
OSA is seen in >40% of children. A repeat sleep study
is recommended 6-8 weeks post-surgery in these high
risk children for recurrence or persistence of OSA
Coblation assisted tonsillectomy is a new
technique used at present, demonstrating decreased
intraoperative blood loss and markedly reduced
postoperative oedema and pain. Conventional adenoid
curettage is now being replaced increasingly with
endoscopic microdebridor assisted adenoidectomy.
Since the adenoid removal is done under direct
vision, it allows complete removal of both choanal
and tubal lymphoid tissue causing obstruction.
Other surgical options
Palatal surgery(Uvulopalatopharyngoplasty,UPPP)
is indicated in complicated OSAS in obese children,
cerebral palsy, Down syndrome and children with
craniofacial anomalies and neurologic impairments.
Kershner and colleagues demonstrated a modest
improvement in oxygen saturation nadir on PSG
following UPPP.2
Tongue base procedures : Genioglossal advancement,
radiofrequency ablation or coblation assisted tongue
base reduction, partial midline glossectomy and
lingual tonsillectomy are a list of a few procedures
recommended in children with tongue base
obstruction. Tongue base obstruction leading to OSA
is typically seen in children with Down syndrome
and Beckwith-Wiedmann syndrome.2,12
Other craniofacial procedures include distraction
osteogenesis and mandibular distraction in children
with mandibular hypoplasia and retrognathia. 2,18
Tracheostomy is reserved for severe OSAS in children
who have failed other medical and surgical therapy,
children with anatomic and neuromotor issues.
Nasal surgeries like septum correction and
turbinectomy are very rarely conducted in children.
Positive Airway Pressure(PAP)
This is often considered as second line therapy
in children with OSAS in the following clinical
situations2
• Persistence of symptoms (in children with other
risk factors like obesity)
• Recurrence of symptoms after AT
• AT not performed or contraindicated
• Before surgery in severe OSAS
PAP involves delivery of pressurized air by an
electronic device via a nasal or face mask acting
as a pneumatic stent of the airway. PAP can be
delivered as continuous(CPAP) or as bilevel pressure
(BIPAP)12,16Home nasal CPAP has been used in
infants, prepubertal and pubertal children.2 Even
though this therapy is highly effi cacious adherence is
particularly challenging in children. Complications
of CPAP or BIPAP use in children, are global nasal
fl attening, midfacial hypoplasia, local discomfort
like eye irritation, skin ulceration, rhinorrhea.2,5,8
Pharmacologic Therapies
Medical therapy is considered as the fi rst line option
for children with mild OSA or as an adjunct to
treatment of severe OSA.
Nasal steroids
Intranasal steroids have been known to be effective in
residual lymphoid tissue or adenoidal regrowth after
adenotonsillar hypertrophy or in situations where
surgery is not performed.Nasal corticosteroids exert
lympholytic action; reduce infl ammation and upper
airway edema.8 A small study with children younger
than 10 years found that use of nasal fl uticasone
proprionate decreased AHI from 10.7±2.6 to
6.8±2.2.16
Leukotriene receptor antagonists
Leukotrienes regulate infl ammation in respiratory
system. Both leukotrienes and their receptors are
increased in adenotonsillar tissue and exhaled
condensate of children with OSAS. 5 Leukotriene
receptor antagonists like montelukast treat OSA
through anti-infl ammatory action on this pathway.
Concomitant use of both montelukast and and nasal
budesonide for 12 weeks in children who had residual
mild OSA after AT lead to signifi cant improvement
in AHI, respiratory arousal index and nadir oxygen
saturation.9
Other Non-Surgical Therapies
Rapid maxillary expansion devices are used to
widen hard palate by opening mid palatal suture and
enlarging nasal cavities in prepubertal children. After
4 months of therapy, nasal resistance decreases and
there is signifi cant improvement in OSA symptoms in
children with maxillary constriction.2,5 Oral appliances
are also used which can be worn during sleep. They
advance the mandible or the tongue increasing the size
of the upper airway. Mandibular advancement and
nasopharyngeal airways are other options in children
with dysgnathia and hypotonia respectively.
Future Developments
Even though sleep studies provide an objective
measure of sleep disturbances, the parameters used
are not predictive of OSA associated morbidities.
Home based studies and limited multichannel
studies may provide a more economical option.
Moreover, identifi cation and use of biomarker
approaches requires further exploration. Some data has shown a strong association between paediatric
OSA and nocturnal rise in urinary neurotransmitters.
Episodic hypoxemia and arousals result in increase
in sympathetic activity causing rise in urinary
epinephrine and norepinephrine. Overnight changes
in 3 neurotransmitters: gamma - aminobutyric
acid (GABA), decrease in taurine and decrease in
beta-phenyl ethylamine (PEA) are postulated to
differentiate children with OSA with neurocognitive
defects from those without.9
Summary
OSA is common in children and early recognition and
referral is helpful in preventing longterm morbidity
related to neuro development and pulmonary
hypertension. Risk factors such as craniofacial
abnormalities, Downs Syndrome, neuromuscular
abnormalities should be identifi ed early and
addressed appropriately. A thorough evaluation
of growth and development and otolarynologic
evaluation, Investigations such as Sleep study
(polysomnography), nasendoscopy are required
before considering surgical options. Night CPAP ot
BIPAP therapy is also becoming more available in
Indian setups for resistant cases of OSA not amenable
to surgical correction.A clinical approach to any
child with persistent snoring or episodes of apnea or
hypopnea is shown in the fl ow diagram.
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