Review Article

Update on paediatric obstructive sleep apnoea

Eleonora Dehlink1, Hui-Leng Tan1,2
1
Department of Pediatric Respiratory Medicine, Royal Brompton Hospital, London, UK; 2National Heart and Lung Institute, Imperial College,
London, UK
Contributions: (I) Conception and design: All authors; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV)
Collection and assembly of data: None; (V) Data analysis and interpretation: None; (VI) Manuscript writing: All authors; (VII) Final approval of
manuscript: All authors.
Correspondence to: Dr. Hui-Leng Tan. Department of Pediatric Respiratory Medicine, Royal Brompton Hospital, London, SW3 6NP, UK.
Email: [email protected].

Abstract: Obstructive sleep apnoea (OSA) is one of the most common causes of sleep-disordered breathing
(SDB) in children. It is associated with significant morbidity, potentially impacting on long-term neurocognitive
and behavioural development, as well as cardiovascular outcomes and metabolic homeostasis. The low grade
systemic inflammation and increased oxidative stress seen in this condition are believed to underpin the
development of these OSA-related morbidities. The significant variance in degree of end organ morbidity in
patients with the same severity of OSA highlights the importance of the interplay of genetic and environmental
factors in determining the overall OSA phenotype. This review seeks to summarize the current understanding
of the aetiology and mechanisms underlying OSA, its risk factors, diagnosis and treatment.

Keywords: Paediatric obstructive sleep apnoea (paediatric OSA); sleep-disordered breathing in childhood (SDB
in childhood)

Submitted Nov 02, 2015. Accepted for publication Nov 05, 2015.
doi: 10.3978/j.issn.2072-1439.2015.12.04
View this article at: http://dx.doi.org/10.3978/j.issn.2072-1439.2015.12.04

Introduction diagnosis and management of obstructive SDB in childhood

has defined obstructive SDB as “a syndrome of upper
Obstructive sleep apnoea (OSA) is a common paediatric
airway dysfunction during sleep, characterized by snoring
health problem and children at risk need to be identified,
and/or increased respiratory effort secondary to increased
investigated and treated in a timely manner because the
upper airway resistance and pharyngeal collapsibility” (1).
resultant activation of inflammatory cascades can impose wide
ranging effects, impacting on neurocognitive, cardiovascular This can potentially result in hypoxia, hypercarbia, increase
and metabolic systems. The adverse consequences of in respiratory effort, pronounced intrathoracic pressure
paediatric OSA may not simply be confined to the child’s changes and sleep fragmentation.
immediate well-being and development, but may continue The spectrum of paediatric obstructive SDB in increasing
to be detrimental to the patient’s long-term health in order of severity encompasses (Figures 1-3):
adulthood. The emphasis of this article is to summarize the (I) Primary snoring, the mildest and most prevalent
latest research and developments in paediatric OSA and to manifestation, which is defined as habitual snoring
provide a practical approach to the recognition, diagnosis and for more than 3 nights per week without apnoeas,
treatment of this condition. hypopnoeas, frequent arousals or gas exchange
abnormalities. Its estimated population prevalence is
7.45% (95% confidence interval: 5.75−9.61%) (2-4);
Definition of obstructive sleep-disordered
(II) Upper airway resistance syndrome (UARS)
breathing (SDB) and clinical entities
comprises snoring, increased work of breathing and
The European Respiratory Society (ERS) taskforce on the frequent arousals, without recognizable obstructive

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Journal of Thoracic Disease, Vol 8, No 2 February 2016 225

Pressure snore
NPT

Thermistor

RIP thorax

RIP abdomen
Sum RIP
SpO2

Obstruction
Pulse
pCO2
Position

Figure 1 Cardiorespiratory polygraphy: snoring with flow limitation seen on the nasal pressure airflow transducer suggestive of increased
upper airway resistance. Normal work of breathing (RIP thorax and RIP abdomen), normal breathing pattern (RIP thorax and RIP abdomen
are in phase), stable saturations (SpO2).

Pressure snore

NPT

Thermistor

RIP thorax

RIP abdomen

Sum RIP
SpO2

Obstruction
Pulse

ECG

Position

Figure 2 Cardiorespiratory polygraphy: obstructive hypopnoeas. Snoring followed by reduced flow in the presence of continued breathing
effort. Notice paradoxical breathing (RIP thorax and RIP abdomen), desaturation (SpO2), breakthrough breath with breakthrough snoring
and recovery of SpO2 at the end of hypopnoea.

Pressure snore

NPT

Thermistor

RIP thorax

RIP abdomen
SpO2

Pulse

pCO2

ECG
Position

Figure 3 Cardiorespiratory polygraphy: run of obstructive apnoeas. Snoring and increase work of breathing (pressure flow, RIP thorax and
RIP abdomen) followed by complete stop of airflow despite breathing effort. Notice paradoxical breathing (RIP thorax and RIP abdomen
out of phase) and desaturations (SpO2), breakthrough breath with breakthrough snoring and recovery of SpO2 at the end of each apnoea.

© Journal of Thoracic Disease. All rights reserved. www.jthoracdis.com J Thorac Dis 2016;8(2):224-235
226 Dehlink and Tan. Aetiology, diagnosis and treatment

events or gas exchange abnormalities; collapsibility can be caused either by conditions leading to a
(III) Obstructive hypoventilation is characterized by decrease in muscle tone in the upper airway, such as cerebral
snoring plus elevated end-expiratory carbon dioxide palsy, neuromuscular disorders, or inflammatory conditions
partial pressure in the absence of recognizable affecting the upper airways, such as allergic rhinitis and
obstructive events; asthma.
(IV) OSA syndrome manifests with recurrent events Whilst previously, the typical paediatric OSA patient was
of partial or complete upper airway obstruction one with adenotonsillar hypertrophy and failure to thrive,
(hypopnoeas, obstructive or mixed apnoeas) with with the current obesity epidemic, there are an increasing
disruption of normal oxygenation, ventilation and number of children diagnosed with OSA who are obese.
sleep pattern. The prevalence of OSA has been These patients often suffer from more prominent daytime
reported to be between 1% and 5% (4,5). sleepiness symptoms, similar to adult OSA patients. A
recent cross-sectional, prospective multicenter study, the
NANOS study, assessed the contribution of obesity and
Aetiology and mechanisms of OSA
adenotonsillar hypertrophy to paediatric OSA and found
Although the aetiologies of paediatric OSA are multiple, that 46.6% of obese children in the community had an
they can be broadly classified into conditions which result obstructive apnoea hypopnoea index (OAHI) >1/hr total
in intrinsic upper airway narrowing and those that result sleep time (TST) (9). The degree of tonsillar and adenoidal
in increased upper airway collapsibility. Adenotonsillar hypertrophy emerged as the most important risk factors for
hypertrophy is currently the most common example of the paediatric OSA in this nonreferral cohort of obese children.
former. Magnetic resonance imaging (MRI) studies have Whilst the degree of obesity appeared to contribute to the
shown that the size of the adenoids and tonsils in children risk of OSA in the single factorial analysis, it did not retain
with OSA is significantly increased compared to healthy its statistical significance as a major determinant of OSA in
controls (6). The causes of this lymphoid tissue hypertrophy the multivariate analysis model.
are not completely understood. The concurrent presence of adenotonsillar hypertrophy
Other anatomical features resulting in upper airway and obesity appears to facilitate the emergence of OSA.
narrowing such as micrognathia, macroglossia, and midface Obesity can contribute to OSA in mechanical ways: fatty
hypoplasia, are often found in children with craniofacial infiltrates within the upper airway structure and neck
syndromes (e.g., Treacher Collins syndrome, Crouzon contribute to upper airway narrowing as well as pharyngeal
syndrome, Apert syndrome, Pierre Robin sequence), collapsibility. Accumulation of abdominal visceral fat
achondroplasia, trisomy 21, Beckwith Wiedemann impinging on the chest cavity limits diaphragmatic descent,
syndrome, and mucopolysaccharidoses. particularly when supine, and adipose tissue in the chest
To understand upper airway collapsibility, researchers wall can impair lung compliance, leading to hypoventilation,
have modeled the upper airway as a Starling resistor, atelectasis and ventilation perfusion mismatch. The
essentially a rigid tube with a collapsible segment, the consequent excessive daytime sleepiness from OSA is likely
collapsible segment being the pharynx bordered by rigid to impact on physical activity, which in turn favours more
upstream (nasal passages) and downstream (trachea) weight gain (10). Furthermore, OSA and obesity might
segments. Under conditions of flow limitation, the also be linked via an imbalance between leptin and ghrelin,
maximum inspiratory airflow is determined by the pressure two hormones crucial in regulating satiety and hunger.
changes upstream to the collapsible segment (nasal passages) While leptin is secreted by adipocytes and promotes satiety,
rather than downstream changes (pressures generated in ghrelin is secreted in the gut and creates a feeling of hunger.
the trachea by the diaphragm). Collapse occurs when the OSA has been shown to be associated with leptin resistance
pressure outside the collapsible segment is greater than that and increased ghrelin levels, which could favour obesity (11).
within the segment, and is referred to as the critical closing
pressure (Pcrit). Disturbances in Pcrit are believed to play a
Consequences of OSA
key role in OSA pathogenesis (7). Children with OSA have
been found to have significantly more collapsible upper OSA is associated with significant morbidity: impairment
airways with elevated (i.e., less negative) Pcrit during sleep of neurocognitive development, school performance, and
than children without OSA (8). Increased upper airway behaviour are the most commonly reported consequences

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Journal of Thoracic Disease, Vol 8, No 2 February 2016 227

of paediatric OSA, but it has also been linked with Neurocognitive and behavioural comorbidities
cardiovascular morbidity, metabolic consequences, and
It is important to consider OSA as a differential diagnosis
nocturnal enuresis. Children with OSA have also been shown
when investigating children with behavioural problems
to have increased healthcare utilization compared with
or attention deficit hyperactivity disorder (ADHD) since
their peers, with more hospital visits and more medication
there can be considerable overlap of symptoms. Even mild
prescriptions, mainly for respiratory infections (12).
OSA and habitual snoring have been associated with hyper
Healthcare utilization and annual health care costs
activity, difficulties concentrating, attention problems and
decreased following adenotonsillectomy (13).
impulsivity. The Tucson Children’s Assessment of Sleep
Apnoea (TuCASA) study revealed that young people with
OSA and inflammation untreated OSA had attention problems and hyperactivity,
aggressive behaviours, lower social competencies, poor
There is emerging evidence that OSA is a disease with
chronic low grade systemic inflammation and increased communication and/or diminished adaptive skills (21).
oxidative stress which likely lead to the end organ This study also showed a negative correlation between
morbidities described above. At the local level, nasal nitric apnoea-hypopnoea index (AHI) and immediate recall,
oxide (NO), a marker of airway inflammation, is elevated full-scale intelligence quotient (IQ), performance IQ and
in children with OSA and primary snoring compared with mathematics achievements, while nocturnal hypoxaemia
healthy controls (14). Levels of H2O2 in morning exhaled adversely affected nonverbal skills (22). In a prospective
breath condensate of children with OSA have been shown study in first-grade school children, OSA has been shown
to be elevated, suggesting increased oxidative stress (15). to be disproportionally high in children whose school
Systemically, the pro-inflammatory cytokines, TNF-α, IL-6, performance was in the lowest 10% of their class. Strikingly,
and IL-8 have been found to be elevated in the serum of while children who were treated for OSA showed significant
OSA patients. Levels of regulatory cytokines such as IL-10 academic improvement, children who did not receive
are decreased and correlate with the severity of OSA (16). treatment did not improve (23). However, the Childhood
The peripheral Th17/Treg ratio is skewed towards Th17 Adenotonsillectomy Trial (CHAT), a randomized controlled
predominance, further suggesting a systemic pro-inflammatory trial that compared the effects of adenotonsillectomy versus
milieu in OSA. The Th17/Treg ratio correlates with severity watchful waiting in children with mild OSA, did not find
of OSA, and adenotonsillectomy reverses this Th17/Treg any significant improvements in cognitive function after
imbalance and reduces serum inflammatory cytokine levels (17). treatment, although there were improvements in behaviour,
The mechanisms underlying these imbalances are not symptoms and quality of life. This may be because, due to
fully understood, but some interesting findings have ethical considerations, only children with mild OSA with
been made recently. For example, a single nucleotide no significant oxygen desaturations were included in the
polymorphism in the TNF alpha coding region—TNF-α study and the follow-up period was only 7 months (24). A
(308A) SNP—appears to be significantly associated with recent meta-analysis including 16 studies confirmed clear
OSA (18). There is also evidence of epigenetic alterations links between OSA and poor academic performance for
in OSA, for instance the promoter region of the FOXP3 core academic domains related to language, arts, maths and
gene, which is crucially involved in the development of science in school-aged children (25). There is however,
regulatory T cells, shows severity dependent increased considerable phenotypic variability whereby some children
methylation in paediatric OSA (19). OSA and obesity seem with severe OSA do not appear to experience neurocognitive
to mutually amplify the systemic inflammatory pathways, or behavioural morbidity, whereas some children with
for instance monocyte chemoattractant protein 1 and relatively mild OSA do. Part of this may be explained by
plasminogen activator-inhibitor 1 levels have been found the differential compensatory mechanisms adopted and
to be significantly raised in obese OSA children compared individual variability in neuroplasticity which are influenced
with body mass index (BMI)-matched obese children by genetic and environmental factors. Recent functional
without OSA (20). It is postulated that this induction of MRI-imaging data have demonstrated changes in cognitive
inflammatory cascades along with increased oxidative stress and empathetic processing in children with OSA, with
gives rise to the morbidities associated with OSA. greater neural recruitment of regions of the brain involved

© Journal of Thoracic Disease. All rights reserved. www.jthoracdis.com J Thorac Dis 2016;8(2):224-235
228 Dehlink and Tan. Aetiology, diagnosis and treatment

in cognitive control, conflict monitoring, and attentional robust than in adults, and interpretation is complicated
allocation observed in children with OSA compared with by pubertal status and the presence of obesity. Elevations
children without OSA, even when no differences were in low density lipoprotein (LDL) cholesterol along
discernable on standardized neuropsychological testing by with reduced levels in high density lipoprotein (HDL)
experienced child psychologists (26). cholesterol were observed in both obese and non-obese
children with OSA, with significant improvements after
OSA treatment (34,35). Associations between OSA and
Cardiovascular comorbidities
the metabolic syndrome have been shown in postpubertal
The most severe cardiovascular consequence of OSA is adolescents (36). In young children, OSA has been shown
pulmonary hypertension, and the resultant cor pulmonale if to be associated with reduced insulin sensitivity in obese
the OSA is left untreated. Fortunately, this is not commonly children, with improvements in homeostatic model
seen in children, who tend to have more subtle evidence assessment (HOMA) when OSA was treated (37). Elevated
of cardiovascular dysfunction, such as dysregulation of liver enzymes have also been reported which improved after
blood pressure (BP), cardiac remodeling and endothelial treatment of OSA in the majority of these patients (38). Two
dysfunction. Amin et al. observed reduced nocturnal other groups have recently demonstrated that the presence
dipping, greater mean BP variability during wakefulness and severity of OSA was associated with the presence of
and sleep, and higher night/day systolic BP ratios, which are non-alcoholic fatty liver disease, liver fibrosis independent
known risk factors for cardiovascular events in adults (27,28). of BMI, abdominal adiposity, metabolic syndrome and
Children with OSA have also been shown to have insulin resistance, while the percentage of time with oxygen
diminished cardiac output and oxygen consumption at peak saturation below 90% correlated with increased intrahepatic
exercise capacity (29). Cardiac remodeling may be due leukocytes, activated Kupffer cells, and circulating markers
to greater overnight changes in brain natriuretic peptide of hepatocyte apoptosis and fibrogenesis (39,40).
(BNP) observed in children with moderate to severe OSA
compared with mild OSA and controls (30). Assessment
Excessive daytime sleepiness
of post-occlusive hyperaemic responses in children with
OSA has revealed evidence of endothelial dysfunction. With the exception of obese children who more closely
Interestingly, in a study by Gozal et al., while endothelial resemble the adult OSA phenotype, excessive daytime
dysfunction improved after treatment of the OSA with sleepiness is not a frequently reported symptom in children
adenotonsillectomy in the majority of children, in those with with OSA. In children, sleep fragmentation often manifests
a strong family history of cardiovascular disease it remained as hyperactivity, difficulties concentrating, and irritability
abnormal, once again suggesting the influence of genetic instead. However, they do have severity-dependent
and environmental factors on phenotypic expression (31). shortening of their sleep latencies (41), and there seems to
Furthermore, a recent study suggests that even children be an association between the magnitude of sleep latency
with primary snoring already display evidence of reduction and TNF-alpha gene polymorphisms (42).
endothelial dysfunction and have significantly higher serum
isoprostanes and soluble NOX2-dp levels compared with
Nocturnal enuresis
healthy controls (32).
In the CHAT study, overnight heart rate emerged as A higher prevalence of nocturnal enuresis has been
the most sensitive parameter for determining the severity reported in children with OSA (43). This may be due to the
of paediatric OSA. Adenotonsillectomy did not have inhibitory effects of OSA on arousal responses to changes
significant effects on cardiometabolic measures compared in bladder pressure, or effects of elevated BNP levels which
with watchful waiting. Again, it should be noted that affect the renin-angiotensin pathway, vasopressin, and
children in this study only had mild OSA without significant excretion of sodium and water (44).
oxygen desaturations (33).

When to suspect obstructive SDB?—symptoms

Metabolic comorbidities of OSA in children

Data on metabolic consequences of paediatric OSA are less OSA should be suspected when nocturnal symptoms of

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Journal of Thoracic Disease, Vol 8, No 2 February 2016 229

snoring, gasping, increased work of breathing or paradoxical ICSD-3 PSG criteria for diagnosis are either (I) one or
breathing, restless sleep, witnessed apnoeas or mouth more obstructive events (obstructive or mixed apnoea or
breathing are reported. Some children with OSA will obstructive hypopnoea) per hour of sleep or (II) obstructive
also sleep with their neck in a hyperextended position to hypoventilation, as manifest by PaCO 2 >50 mmHg for
maintain their airway. Daytime symptoms of OSA are very >25% of sleep time, together with snoring, paradoxical
non-specific, but together with nighttime symptoms may thoracoabdominal movement, or flattening of the nasal
help alert clinicians to clinically significant obstructive SDB: airway pressure waveform implying flow limitation (46).
hyperactivity, difficulty concentrating/learning difficulties, Most sleep centers consider an obstructive AHI ≤1/hrTST
behavioural difficulties, excessive daytime sleepiness, and to be normal, 1< AHI ≤5 to be mild OSA, 5< AHI ≤10 to be
moodiness. A history of prematurity is associated with an moderate OSA, and an AHI >10/hrTST as severe OSA.
increased risk of OSA, and there is some evidence that a Full PSGs are labour and resource intensive, requiring in
family history of OSA may also be a risk factor (1). hospital monitoring of the patient by skilled staff overnight,
On physical examination, findings of tonsillar hypertrophy, and subsequent scoring and analysis. They may also not
obesity, midface deficiency, macroglossia or mandibular be widely available in all countries. When PSGs are not
hypoplasia may strengthen the suspicion of OSA (1). available, possible alternatives include:
Other groups at risk for obstructive SBD are children with (I) Nocturnal oximetry studies: oximetry studies have
uncontrolled epilepsy, neuromuscular disorders, Prader- a high specificity but low sensitivity in the diagnosis
Willi syndrome, and complex medical conditions, such of paediatric OSA (47). Three or more clusters
as achondroplasia, Chiari malformation, Ehlers-Danlos of desaturation events ≥4% and at least three
syndrome, mucopolysaccharidoses, and trisomy 21. In most desaturations to <90% are considered abnormal
complex conditions there is a mix of obstructive and central (McGill criteria). However, the rate of false negative
SBD and often a component of alveolar hypoventilation. or inconclusive results is high. Nocturnal oximetry
While adenotonsillar hypertrophy identified on MRI studies could help in the prioritization of treatment in
has been shown to be associated with OSA, there is little resource poor countries where PSGs are not available;
evidence from the literature for an association of tonsillar (II) Respiratory polygraphy (RP) studies: respiratory
size evaluated subjectively during physical examination and polygraphies are essentially PSGs without
OSA severity determined by polysomnography (PSG) (1,45). the EEG, EMG, and EOG sensors. They are
The ERS taskforce proposed that in clinical practice, performed commonly in Europe and are quicker
techniques for objective evaluation of abnormalities to set up and score than PSGs. Some centers have
predisposing for obstructive SDB, such as lateral neck reported good agreement with in-lab PSGs (48),
X-ray, flexible nasopharyngoscopy, cephalometry, MRI or but there is the possibility that the AHI may be
computed tomography (CT) of the upper airway, should be underestimated due to missed hypopnoeas resulting
reserved for more complex cases (1). in arousals but not desaturation (49);
(III) Ambulatory RP or PSG: there has been a recent
drive towards performing ambulatory PSG or
Diagnosis of OSA in children
RP studies, not only because they are seen as a
The gold standard test for the diagnosis of obstructive SDB less expensive alternative to in-lab PSGs, but also
and assessment of its severity is an overnight, attended, in- because the results may be more representative of
laboratory PSG study. PSGs allow for objective diagnosis the child’s typical night’s sleep at home. Data on
and assessment of disturbances in respiratory parameters direct comparison with in-lab PSG are still limited
and sleep patterns, allowing for classification of patients but a recent study by Alonso-Álvarez et al. compared
into differential disease severities, thus enabling clinicians home RP with in-lab PSG in 50 children clinically
to tailor clinical management accordingly. The AHI is the suspected to have OSA and showed that all the home
most commonly used PSG parameter for the quantification RP studies were successful and the area under the
of SDB severity. It comprises the number of mixed, curve was consistently >90% when various PSG cut-
obstructive and central apnoeas and hypopnoeas per hour off values OAHI ≥1, 3 and 5/hrTST were used (50).
of total sleep time. It is often helpful to report the central This would suggest the validity of home RP for
apnoea index and obstructive apnoea index separately. The the diagnosis of OSA in children with a high

© Journal of Thoracic Disease. All rights reserved. www.jthoracdis.com J Thorac Dis 2016;8(2):224-235
230 Dehlink and Tan. Aetiology, diagnosis and treatment

pre-test probability of having OSA. However, OSA, the presence of OSA-related co-morbidities, and
more research is required to further optimize the the kind and severity of symptoms should determine the
sensitivity and specificity of home RP testing for priority for treatment and the therapeutic strategy (53).
the diagnosis of children with mild OSA; The ERS taskforce advises a stepwise treatment approach,
(IV) Paediatric sleep questionnaire: this parent-filled until complete resolution of the OSA. This may include a
questionnaire assesses symptoms of SDB, such as combination of different treatment modalities depending
snoring, excessive daytime sleepiness, attention on severity and cause for the upper airway obstruction.
problems, and hyperactive behaviour in children The taskforce acknowledges that data on the appropriate
aged 2−18 years. Its sensitivity and specificity for sequence of interventions is scarce, but they propose the
diagnosing OSA in otherwise healthy children are following steps:
78% and 72%, respectively, but it may be useful in (I) Weight loss if the child is overweight or obese:
predicting OSA-related neurobehavioural morbidity there is data supporting the efficacy of weight loss
and its improvement after adenotonsillectomy (51); as a treatment intervention in obese adolescents
(V) Sleep clinical record: this is a diagnostic tool (54,55). However, there are currently no studies on
composed of physical examination, subjective obese younger children;
symptoms and clinical history of behavioural (II) Nasal corticosteroids and/or oral montelukast:
and cognitive problems. These items are used to children with OSA have increased expression of
determine the sleep clinical score (SCS). A SCS leukotriene C4 synthase as well as leukotriene
of ≥6.5 is considered positive for OSA, with a receptors 1 and 2 in tonsillar lymphocytes compared
sensitivity of 96.05% and specificity of 67.00%. with controls (56). Addition of leukotriene receptor
This may potentially be a useful tool to screen antagonists to tonsillar cells from children with
patients for suspected OSA (52). OSA in vitro resulted in dose-dependent reductions
Whilst these investigations may be less sensitive and in cell proliferation and secretion of TNF-α, IL-6,
specific than PSGs, they can still be valuable in assessing and IL-12. A 6 to 12 weeks course of nasal steroids
SDB as long as clinicians are aware of their limitations. and/or montelukast may reduce adenoidal size and
The ERS taskforce, in line with the American Academy has shown favourable results in children with mild
of Otolaryngology-Head and Neck Surgery, recommends to moderate OSA (57,58);
that children with co-existing obesity, Down syndrome, (III) Adenotonsillectomy: there is good evidence that
craniofacial abnormalities, neuromuscular disorders, sickle adenotonsillectomy is efficacious in children with
cell disease, mucopolysaccharidoses or children in whom OSA and adenotonsillar hypertrophy (59,60), and the
the need for treatment is unclear should have priority American Academy of Pediatrics (AAP) recommends
in accessing PSG or RP prior to adenotonsillectomy. adenotonsillectomy as the first line treatment
These children should also have a PSG or RP post for children with adenotonsillar hypertrophy (5).
adenotonsillectomy due to their increased risk of persistent Subtotal tonsillectomies, also known as tonsillotomies,
OSA. PSGs/RPs should also be performed in patients with have been gaining popularity recently as they have
persistent symptoms of OSA despite surgery and those who lower postoperative complication rates. However
had moderate-to-severe OSA pre-surgery also to assess for there are no well-designed studies directly comparing
residual OSA. PSG is also indicated before and after rapid the two surgical approaches and their OSA
maxillary expansion, application of orthodontic appliances, treatment outcomes. Subtotal resection also carries
continuous positive airway pressure (CPAP) and bi-level an increased risk of tonsillar regrowth (61). Whilst
positive pressure ventilation (BiPAP) (1). adenotonsillectomy is an effective treatment, recent
studies have demonstrated that although the majority
of children show marked improvement in their PSG
Treatment of OSA
parameters post-surgery, a significant number do not
Most physicians would consider treatment in children achieve complete normalization (62). In otherwise
with an AHI ≥5/hrTST. In children with 1< AHI ≤5, healthy, non-obese children, the success rate of
treatment may be beneficial especially in the presence adenotonsillectomy is approximately 75%. Risk
of comorbidities. Individual risk factors predisposing for factors for residual OSA include obesity, severe

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Journal of Thoracic Disease, Vol 8, No 2 February 2016 231

OSA pre-surgery with an AHI of >20/hrTST, the more challenging cases, clinical psychologists,
children aged >7 years, high Mallampati score, can make the process fun and reduce anxiety. For
African-American ethnicity, children with asthma, most children with OSA, CPAP will be effective.
craniofacial abnormalities (e.g., Pierre Robin However, if the nocturnal CO2 is significantly raised,
syndrome), chromosomal abnormalities (e.g., which is more often seen in children with other
trisomy 21), and neuromuscular disease. Families co-existing conditions such as neuromuscular disease,
should be counselled that OSA may recur after craniofacial syndromes or obesity hypoventilation,
initial postoperative improvement; BiPAP may be needed. In BiPAP the machine delivers
(IV) R a p id m a x i l l a ry ex p a ns i o n o r o rtho don tic a higher inspiratory pressure when the child breathes
appliances: a number of small studies have shown in, and a lower pressure when the child breaths out.
that rapid maxillary expansion can be efficacious in BiPAP may also be better tolerated in children who
the treatment of OSA in carefully selected patients do not tolerate CPAP due to high positive end-
(63,64). A previous Cochrane review concluded expiratory pressure requirements. Complications
that oral appliances are beneficial as an auxiliary of CPAP and BiPAP include nasal congestion,
treatment in children with OSA and non-syndromic rhinorrhoea, epistaxis, facial skin erythema related
craniofacial abnormalities. However, this review to the mask, discomfort from air leak, abdominal
was only based on one study (65). A more recent distension, and midface retrusion. It is important
meta-analysis including six studies concluded to monitor adherence to CPAP or BiPAP and to
that orthodontic treatments may be effective in manage complications to optimize patient adherence.
managing snoring and OSA. The authors noted Regular long-term follow-up is necessary as pressure
however, that the efficacy of orthodontic treatments requirements will change and the interface will need
with regards to improving consequences of OSA to be upsized and adjusted with the growth and
e.g., neurocognitive and cardiovascular functions development of the child;
have not yet been systematically addressed (66); (VI) Tracheostomy, craniofacial surgery: craniofacial
(V) CPAP or non-invasive positive pressure ventilation surgery has been shown to be successful in children
(NIPPV) for nocturnal hypoventilation: in children with syndromic craniofacial abnormalities. Success
who have residual OSA after adenotonsillectomy, rates of 95.6% have been reported in patients with
OSA related to obesity, craniofacial abnormalities, micrognathia (68), but success rates tend to be lower
neuromuscular disorders, those who do not have in the presence of other abnormalities. Tracheostomy
significant adenotonsillar hypertrophy, or those has the highest efficacy in the treatment of
who choose not to undergo surgery, positive airway obstructive SDB when compared to other surgical
pressure therapy is recommended. The goal is to interventions but is associated with worse quality
maintain patency of the upper airway throughout of life and psychosocial development (69,70). Early
the respiratory cycle, improve functional residual onset complications include pneumomediastinum,
lung capacity and decrease work of breathing. pneumothorax, wound infection and bleeding, whilst
Starting CPAP in children can be challenging, a late-onset complications include granulation tissue
multidisciplinary team approach works best and formation, tracheocutaneous fistulae, laryngo-tracheal
parental involvement and education is crucial (67). stenosis, delayed language skills acquisition and
In our center, once the child has been fitted with the increased rates of respiratory infections. In clinical
correct size mask, the family is given the mask to go practice, craniofacial surgery and tracheostomy are
home with so the child can play with it and practice mostly reserved for the most severe cases when all
wearing it. Once the child is happy to wear the mask other treatment options have failed.
for brief periods of time when awake, an inpatient
admission is arranged, nocturnal CPAP is started and
Prognosis of OSA and recognition and
pressures titrated. The admission sometimes needs
management of persistent SDB
to be for several nights, depending on how the child
tolerates CPAP. Play therapists working together The goal of OSA treatment is complete resolution of
with specialist nurses/respiratory therapists, and in the SDB. This may require combining treatments in

© Journal of Thoracic Disease. All rights reserved. www.jthoracdis.com J Thorac Dis 2016;8(2):224-235
232 Dehlink and Tan. Aetiology, diagnosis and treatment

a stepwise manner as proposed by the ERS taskforce. approaches will hopefully help in determining a patient’s
Treatment outcomes should be monitored after each risks for comorbidities and their likelihood of responding
intervention and include assessment of symptoms and to treatment interventions. An example of the former was a
the presence of any cardiovascular and central nervous study by Khalyfa et al. which showed preliminary evidence
co-morbidities and growth, as well as objective measures to that exosomal miRNAs may be a potential biomarker of
detect residual OSA, such as PSG, or polygraphy, oximetry cardiovascular risk in children with OSA (74). As an example
and capnography when PSG is not available. Generally, of the latter, Kheirandish-Gozal et al. discovered that a
PSG is recommended 6 weeks after adenotonsillectomy, combination of serum biomarkers including MCP-1, PAI-1,
after 12 weeks of montelukast/nasal steroid treatment, MMP-9, IL-19, IL-6, adropin and osteocrin provided
12 months after rapid maxillary expansion and after excellent sensitivity and moderate specificity in predicting
6 months with orthodontic appliances. Children on residual OSA in obese children after adenotonsillectomy (75).
CPAP or BiPAP should be re-evaluated at least every
12 months after initial titration (1). In children with
Conclusions
persistent SDB after intervention it may also be worth
looking for additional upper airway abnormalities, such as In summary, considerable progress has been made in
laryngomalacia or adenoid regrowth. the field of paediatric sleep medicine in the past few
It is worth mentioning that weight gain can sometimes years. However, there still remain gaps in our knowledge
be seen post treatment of OSA. Katz et al. found that the particularly concerning the mechanistic pathways in the
BMI score increased more in children who underwent pathogenesis of paediatric OSA and factors influencing the
adenotonsillectomy compared with those in the watchful phenotypic variability of the disease. A better understanding
waiting group (71). Children who have a rapid increase of these will help in the development of novel therapies.
in BMI postoperatively are at increased risk of having Further research is also needed to identify biomarkers
recurrent OSA (72). These findings highlight the for patients at risk for consequences of OSA as well as
importance of weight monitoring, nutritional counselling, predictors for treatment success to enable the development
and encouragement of physical activity and follow-up of individual therapeutic approaches for the implementation
assessment for residual OSA. of personalized medicine.
Obstructive SDB can resolve spontaneously, particularly
in children with mild OSA and adenotonsillar hypertrophy.
Acknowledgements
In the CHAT study, 42% of the children in the watchful-
waiting group showed normalization of their AHI score None.
after 5 months, no longer fulfilling the PSG criteria for
OSA (73). Improvements may be due to growth of the
Footnote
airway or regression of lymphoid tissue, routine medical
care, or regression to the mean (24). Risk factors for the Conflicts of Interest: The authors have no conflicts of interest
persistence of untreated OSA include obesity and increasing to declare.
body mass index percentile, male gender, more severe
OSA with an obstructive AHI >5 episodes/hour, African-
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Cite this article as: Dehlink E, Tan HL. Update on paediatric

obstructive sleep apnoea. J Thorac Dis 2016;8(2):224-235. doi:
10.3978/j.issn.2072-1439.2015.12.04

© Journal of Thoracic Disease. All rights reserved. www.jthoracdis.com J Thorac Dis 2016;8(2):224-235