Chapter 7

OSA syndrome in children

S.L. Verhulst* and W. De Backer#

Summary
Obstructive sleep apnoea (OSA) is frequently encountered in children, with an estimated prevalence of 14%. Childhood OSA is a different entity compared to OSA in adults. Adenotonsillar hypertrophy is the most common anatomical risk factor. Obesity is increasingly becoming an important risk factor for childhood OSA, although the exact risk mechanisms by which obesity results in an increased prevalence of OSA syndrome remain to be defined. Polysomnography remains the golden standard in the diagnosis of OSA syndrome. Complications include neurobehavioural effects, metabolic and cardiovascular complications and impaired growth. Adenotonsillectomy is the first-line treatment but is associated, especially in obese children, with a high failure rate and thus, there is a clear need for alternative treatment options. Keywords: Child, obstructive sleep apnoea, sleep-disordered breathing
Depts of *Paediatrics, and # Respiratory Medicine, University of Antwerp, Antwerp, Belgium. Correspondence: S.L. Verhulst, Dept of Paediatrics, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium, Email stijn.verhulst@ua.ac.be

CHILDHOOD OSAS

Eur Respir Mon 2010. 50, 104120. Printed in UK all rights reserved. Copyright ERS 2010. European Respiratory Monograph; ISSN: 1025-448x. DOI: 10.1183/1025448x.00024309

he various forms of obstructive sleep-disordered breathing (SDB) in children encompass an entire continuum ranging from primary snoring to full blown obstructive sleep apnoea syndrome (OSAS). OSAS is characterised by recurrent events of partial and/or complete upper airway obstruction resulting in a disruption of normal ventilation and sleep [1]. A second obstructive breathing disorder to be considered is upper airway resistance syndrome (UARS), in which the increased resistance at the upper airway is sufficiently large, which causes sleep fragmentation in the absence of blunt apnoeas and abnormalities in gas exchange. Finally, primary snoring is considered to be a relatively more benign expression of abnormal upper airway resistance [2]. OSAS, at least in young children, is a clearly different entity compared to OSAS in adults. Adenotonsillar hypertrophy remains the most important risk factor, excessive daytime sleepiness is not the primary symptom and children can present more predominantly with hypopnoeas and obstructive hypoventilation. Scoring criteria and diagnostic thresholds clearly differ between children and adults. Sleep stage distribution is more preserved in children while subcortical arousals rather than EEG arousals are seen more often, finally, first-line treatment is often upper airway surgery rather than noninvasive ventilation. In this chapter, we will review the current understanding on epidemiology, pathophysiology, diagnosis, complications and treatment of OSAS in children.

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Epidemiology
An important remark to make at the beginning of this section is that studies which have assessed the prevalence of OSAS in children have used a wide variety in diagnostic criteria. There are no population-based studies which have assessed the prevalence of both UARS and obstructive hypoventilation. Therefore, the true prevalence of all obstructive types of SDB might be underestimated. Furthermore, most epidemiological studies have only performed diagnostic testing, including polysomnography, on snoring children. Since not all children with OSAS snore, this can also result in an underestimation of the prevalence of OSAS.

Prevalence in the general population, and effects of age, sex and race
In a recent meta-analysis, the prevalence of snoring, as assessed by a questionnaire, was found to be 7.5% (95% CI 5.89.6%) [3]. Most studies using a combination of a screening questionnaire and additional diagnostic testing in an entire or part of a study population reported a prevalence of OSAS ranging from 1% to 4% [3]. Epidemiological studies have also shown that African American race is a risk factor for OSAS in the US population [47]. Young males seem to be at a higher risk for OSAS than young females, especially during puberty [3]. Finally, age does not seem to be a mediator of OSAS severity [3].

Childhood obesity
An important emerging risk factor for OSAS in children is obesity. Indeed, various studies have shown that obese children and adolescents have a higher prevalence of OSAS compared to their normal-weight peers. For example, an Italian review of questionnaires from .2,000 teenagers found that the frequency of snoring was significantly higher in children with a body mass index (BMI) in the 90th percentile or greater. Furthermore, subjects with a BMI greater than the 95th percentile were 2.6 times more likely to snore than children with a BMI below the 75th percentile [8]. Similar findings were noted in a German study which demonstrated that obese children had more than four times the risk of snoring when compared to their peers with a BMI in the 75th percentile or less [9]. A number of population-based studies have used nocturnal cardiorespiratory monitoring or polygraphy to delineate factors that predispose to OSAS in children. In the Cleveland Family Study, both AfricanAmerican race and obesity in children age 218 yrs were NCHEZ-ARMENGOL et al. [10] associated with a three to five-fold higher likelihood of OSAS [6]. SA found that snoring adolescents, as assessed by questionnaire, expressed higher weight and higher waist-to-hip ratios and were more frequently obese as a group than their non-snoring peers. Various studies have used nocturnal polysomnography in hospital settings to determine the prevalence of OSAS [11]. Three general conclusions are warranted. First, obese children are at greater risk of OSAS. However, there are large variations in observed prevalence rates among studies, ranging from 13% to 59%. The observed differences in prevalence probably reflect a number of factors, including differences in the ethnicity, age, pubertal status of the studied subjects and, more importantly, the use of different diagnostic criteria for childhood obesity and for childhood OSAS. These factors make the calculation of a pooled estimate for the prevalence of OSAS in childhood obesity very difficult, if not impossible. Secondly, in the majority of cases the OSAS is generally mild. Finally, not all studies found the expected association between BMI and the apnoea/hypopnoea index (AHI): the classical marker of the severity of OSAS. However, the AHI may correlate more strongly with the distribution of body fat than with BMI per se. For instance, we reported a significant association between waist-to-hip ratio and the AHI in one of our studies but failed to find a significant association with BMI [12]. Moreover, the AHI is not the only marker of the severity of sleep apnoea: various studies have demonstrated that the degree of obesity is associated with other consequences of OSAS, such as oxygen desaturation. Our study, for instance, reported a correlation between BMI and the minimal oxygen saturation during sleep [13]; this finding had been described previously by MARCUS et al. [14].

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Genetic disorders
There are a number of genetic disorders which show an increased prevalence of OSAS. These syndromes all affect upper airway anatomy and include, for example, Crouzon, Apert, Treacher Collins, BeckwithWioedemann, KlippelFeil, and Marfan Syndromes, PierreRobin sequence, choanal stenosis and mucopolysaccharidosis. Some craniofacial syndromes, such as Down syndrome, are also associated with hypotonia, which can contribute to upper airway obstruction. For instance, the prevalence of OSAS in Down syndrome ranges from 30% to 60% [15, 16]. Finally, children with neuromuscular disease also show an increased prevalence of OSAS and OSAS often precedes the development of nocturnal hypoventilation [17].

Pathophysiology
It is important to note that obstructive events (obstructive apnoeas, hypopnoeas, inspiratory flow limitation and respiratory-related arousals) rarely occur and that oxygen saturation rarely drops below 90% in normal children without SDB [1823]. As in adults, an anatomical narrowing of the airway is an important factor in the pathogenesis of childhood OSAS. However, other factors also play a role including neuromuscular compensation, ventilator control and arousal threshold.

Developmental issues concerning upper airway anatomy

From birth to adulthood the human face undergoes a 2.5-fold increase in size. This facial growth is influenced principally by genetic factors, but also environmental factors, such as the route of breathing. For instance, there is considerable evidence that mouth breathing and OSAS induce morphological maxillomandibular changes, such as the long face syndrome [24, 25]. Consequently, these changes do increase future risk of OSAS. However, treatment may, at least partially, reverse this adverse craniofacial development [2628]. Also, adenoids and tonsils grow more rapidly than the facial skeleton between 35 yrs of age [29]. This excessive tissue causes a pharyngeal airway narrowing that is consistent with the reported peak prevalence of obstructive sleep apnoea (OSA) in children. Very recently, LI et al. [30] reported that mild OSAS caused by adenotonsillar hypertrophy did not resolve spontaneously in children when growing up. In a recent study, RONEN et al. [31] studied the effects of age and sex on upper airway length in children and adolescents. This is of interest since airway length has a major impact on airway mechanics because longer airways are more susceptible to OSAS. This study gave us insight in possible explanations for the observed male predominance for OSA, which is present in adults but less so in children. Indeed, the authors showed that upper airway length of pre-pubertal males and females is similar [31]. However, during puberty the pharyngeal airway becomes significantly longer in males. Furthermore, upper airway length normalised for body height of pre-pubertal males is shorter than that of females, but post-pubertal males have a larger upper airway length to height ratio than females [31]. Another recent study by ABRAMSON et al. [32] aimed to assess the relationship between several airway characteristics and age and sex in children and adults with OSA. Paediatric airways were smaller, more narrow and shorter, and its shape, in general, was less elliptical in cross section and more uniform and compact than in adults. Adolescents demonstrated greater volume, surface area and mean cross-sectional area than the youngest age group studied. The authors hypothesised that a disturbance in this normal pattern of airway growth and development could have implications for future occurrence of OSA [32].

CHILDHOOD OSAS

Anatomical correlates: bone and lymphoid tissue

Various studies reported a more narrow pharyngeal airway in children with OSAS compared to control children [33] during wakefulness [34], sedation [35] and paralysis [36] using different observation methods, such as cephalometry [24], acoustic reflection [34], endoscopy [36] and magnetic resonance imaging (MRI) [35, 37, 38].

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Several studies have reported that skeletal dimensions influence the size of the pharyngeal airway. LOFSTRAND-TIDESTROM et al. [39] reported a smaller cranial base angle, a lower ratio of posterior/anterior total face height and a narrower dental arch in Swedish children with SDB [39, 40]. Mandibular retrognathia [24, 25, 41] and a longer lower facial height [2426] were identified as risk factors for OSA by several groups. PIRILA-PARKKINEN et al. [41] described several other dental arch deformations that play a role in OSAS. Besides cephalometric dimensions of the skull itself, a more caudal placement of the hyoid bone [42] was also shown to correlate with the severity of OSA. Concerning soft tissue, the classical risk factor for OSA in normal-weight children is an enlargement of the adenoids and tonsils. ARENS et al. [35] showed a correlation between increased tonsil and adenoid volume and the AHI in sedated children. FREGOSI et al. [38] obtained similar results in slightly older, unsedated children, with a correlation between increasing tonsil crosssectional area (CSA), soft palate CSA and the obstructive AHI. Their results indicated that 74.3% of the variance in obstructive AHI could be explained by the tonsil and soft palate CSAs, implicating that in this population OSAS is mainly an anatomical disorder. Besides the influence of increased soft tissue volumes on the static dimensions of the pharyngeal airway, a dynamic inspiratory airway narrowing during tidal breathing has also been observed in children with OSAS [29, 37]. Therefore, patients with OSAS must either have increased airway compliance or higher pressure gradients due to increased resistance due to local narrowing of the airway. This is confirmed by literature where an increased adenotonsillar size did correlate, even in asymptomatic children, with increased nasopharyngeal airway narrowing during inspiration [43]. Nasal resistance was also reported to be increased in children with OSAS compared with control subjects [44]. During tidal breathing, the narrowest airway segment in OSAS children occurs at the site of overlap between the tonsils and adenoids [35, 38]. ISONO et al. [36] looked at the different sites of collapse during paralysis in both OSAS children and controls and showed: 1) that a negative pressure is needed to collapse the airway in normal children while this is not necessary for children with OSAS; and 2) that OSAS children had a generalised increased collapsibility of the pharynx compared with normal control subjects. DONNELLY et al. [37] used cine-MRI during sedation and found similar results showing that: 1) hypopharyngeal airway collapse was observed in the vast majority of children with OSAS, but in none of the normal control subjects; and 2) patients with OSAS were more likely to have intermittent airway collapse at the level of the nasopharynx.

Anatomical correlates: obesity

In obese children, one can expect that both lymphoid hypertrophy and obesity could compromise the upper airway. Recent reviews have indicated that there is not a straightforward relationship between the degree of obesity as indicated by BMI and the AHI [11, 45]. Although a number of hypotheses have been proposed to explain these contradicting results [46], age seems to be an important factor. Indeed, there seems to be a correlation between the degree of adiposity and AHI in obese adolescents, while in younger children adenotonsillar hypertrophy seems to be responsible for OSAS. However, a recent study by DAYYAT et al. [47] showed that there was no correlation between adenotonsillar hypertrophy and AHI both in young and older obese children. However, Mallampati scores were significantly higher in young and older obese children compared to their age-matched peers, suggesting that the more crowded the airway is the lesser the size of adenotonsillar tissues is required to elicit OSA [47]. This relationship was present independent of age, sex and ethnicity, and therefore strongly supports a major role for obesity in the pathophysiology of OSAS. This also suggests that fatty infiltration of the soft tissues of the upper airway due to obesity is already a major contributing factor in the pathophysiology of OSA in obese children. However, it is important to note that, to date, there is only one imaging study which included overweight children. This study failed to find any correlation between BMI and OSA severity, pharyngeal airway dimensions and soft tissue anatomy [38]. Thus, further studies are warranted to determine the extent of fatty infiltration around the upper airway in obese

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children with and without OSAS. This finding could also partly explain the high rates of residual OSAS in obese children after adenotonsillectomy [48]. Analogously, it can also explain the better success rates of weight loss as a treatment for OSA in adolescents [49, 50]. These findings clearly indicated that the main challenge in coupling obesity with AHI is the determination of the exact location(s) of upper airway collapse and its relationship with surrounding tissue, resulting in an optimal treatment plan.

Neuromuscular compensation, ventilator control and arousal threshold

Studies in children have also assessed the critical closing pressure or critical value of positive endexpiratory pressure (Pcrit) which combines both the viscoelastic and the neuromuscular properties of the upper airway and is measured in the same way as in studies in adults. Studies have shown that children with OSAS have a higher Pcrit than children with simple snoring and those in a normal sleep study [51, 52]. Although there is a decrease in Pcrit after adenotonsillectomy, it does not reach control levels suggesting that subtle deficits in anatomy or neuromuscular compensation persist after treatment. Importantly, the upper airway in controls is not collapsible when allowing for neuromuscular compensation. In a more passive state, the average Pcrit was approximately -25 cmH20. In contrast, Pcrit in children with OSAS was relatively similar in both an active and passive state indicating a deficit in neuromuscular compensation (fig. 1). Furthermore, children with OSAS also have an impaired airflow response to hypercapnia [52], although the hypercapnic ventilator response both during wakefulness and sleep is similar to controls [53, 54]. It is not clear whether these impaired responses to negative pressures in children with OSAS are related to an impaired neural processing [55] or to an impaired sensoring effect secondary to increased inflammation in the upper airway. Finally, it is also important to note that the upper airway becomes somewhat more collapsible with increasing age probably due to the depressant effect of age on ventilatory drive, leading to a decrease in upper airway neuromotor tone [56]. Children with OSAS also express increased activation of the genioglossus EMG during wakefulness and topical anaesthesia during wakefulness results in a greater decline in airway size [57, 58]. At sleep onset, EMG activity of the genioglossus muscle shows a more pronounced decrease [57]. Children with OSAS also have an increase in EMG activity during stage 2 sleep, which is not seen in Control OSAS 400 normal children. The application 350 of continuous positive airway pres 300 sure diminishes this activity [59].
250 200 150 100 50 0 -30 -25 -20 -15 -10 -5 0

CHILDHOOD OSAS

V'max mLs-1

5 -25 -20 -15 -10 -5 0 PN cmH2O

5 10

Figure 1. Typical examples of pressureflow relationships using

the gradual ($) versus intermittent (#) techniques are shown for a control child and a child with obstructive sleep apnoea syndrome (OSAS). In the control child, the intermittent technique resulted in a more collapsible upper airway, with a steeper slope and a more negative critical value of positive end-expiratory pressure. There was no change in upper airway properties between the two techniques in the child with OSAS [52]. V 9max: maximal flow; PN: nasal pressure. Reproduced from [52] with permission from the publisher.

Studies investigating arousals in children have shown that children with OSAS have decreased arousal responsiveness to respiratory loading and hypercapnia [53, 60]. In contrary, the arousal response to acoustic stimuli was not different, implying that children with OSAS do not have global arousal impairment [61].

Diagnosis
History
Among nocturnal symptoms, snoring and difficult breathing during

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sleep are most commonly reported. However, it is important to note that a minority of children with OSAS do not snore and that parents are not always aware of their child snoring. BROUILETTE et al. [62] developed a clinical scoring system using the combination of three symptoms (snoring, witnessed apnoeas and difficulty breathing during sleep) to diagnose OSAS in children. However, studies have demonstrated that a positive history is insufficient to differentiate between primary snoring and OSAS in children [63]. Other commonly reported nocturnal symptoms include chest retractions, restless sleep, nocturnal sweating, nocturnal enuresis and a higher frequency of various parasomnias (nightmares, sleep walking, night terrors, etc.). Daytime breathing in children with OSAS is typically unaffected, except in children with severe forms of OSAS. These symptoms are then frequently related to the presence of adenotonsillar hypertrophy and include frequent upper respiratory tract infections, chronic mouth breathing, hearing and eating problems. The classical daytime symptom of OSAS in adults, excessive daytime sleepiness, is less commonly reported in children. In contrary, most children present with behavioural and neurocognitive symptoms including hyperactivity, aggressive behaviour and poor school performance. In general, it is important to note that daytime symptoms related to degraded sleep are highly variable and age dependent (table 1).

Physical examination
It is important to note that there is no straightforward correlation between the magnitude of adenotonsillar hypertrophy and the severity of OSAS. Therefore, a normal physical examination does not exclude OSAS in children. Standard scales to assess the amount of lymphoid hyperplasia and upper airway patency include the Brodsky and Mallampati scales. The Brodsky scale [65] assesses tonsillar hypertrophy on a five-point scale as follows: 1) tonsils are entirely within the tonsillar fossa; 2) tonsils occupy ,25% of the lateral dimension of the oropharynx; 3) tonsils occupy ,50% of the lateral dimension of the oropharynx; 4) tonsils occupy ,75% of the lateral dimension of the oropharynx; and 5) tonsils occupy o75% of the lateral dimension of the oropharynx. Other upper airway related factors that need to be documented are adenoidal facies, mouth breathing, nasal voice tone, retrognathia, micrognatia, midfacial hypoplasia. Furthermore, the nose and palate also need to be assessed. A neurological examination is also necessary to document any neurological impairment. A blood pressure measurement should also be performed. Finally, since paediatric OSAS can be a cause of growth delay or can be related to obesity, it is important to document the growth pattern in any child with suspected OSAS.

Technical investigations
Although frequently used in adults, there is limited experience in children with techniques such as sleep endoscopy and acoustic pharyngometry. Several radiological techniques have been used in children including lateral neck radiographs, cephalometrics, computerised tomography and MRI. Although these techniques have certainly proven their role in a research setting investigating the pathophysiology of OSAS in children, their routine use in a clinical setting remains to be established. In general, these techniques are reserved for the more complicated patients including patients with neurological and craniofacial syndromes. Whether or not these techniques will be useful in the obese child with OSAS to document the individual contribution of adenotonsillar hypertrophy and obesity needs to be demonstrated in future studies [66].

Polysomnography
Polysomnography remains the golden standard in the diagnosis of paediatric OSAS. Although it is an expensive and time consuming investigation, no formal screening study has been shown to be sensitive and specific enough to diagnose OSAS in children. Questionnaires are not able to differentiate OSAS from primary snoring in children [63]. Although there are some promising studies on the usefulness of several screening instruments, such as audio and video recording,

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CHILDHOOD OSAS

Table 1 Symptoms related to obstructive sleep apnoea in children

Age group and age Toddlers 13 yrs Noisy breathing or snoring Agitated sleep or disrupted nocturnal sleep Crying spells or sleep terrors Grouchy and/or aggressive daytime behaviour Daytime fatigue Nocturnal sweating Mouth breathing Poor eating or failure to thrive Repetitive URI Witnessed apnoeic episodes Sleep walking Sleep terrors Nocturnal sweating Abnormal sleeping positions Persistence of bed wetting Abnormal daytime behaviour Aggressiveness Hyperactivity Inattention Daytime fatigue Hard to wake up in the morning Morning headache Increased need for napping compared with peers Poor eating Growth problems Frequent URTI Regular heavy snoring Mouth breathing Drooling during sleep Agitated sleep Nocturnal awakenings Confusion arousals Preschool-aged children School-aged children Regular heavy breathing Agitated sleep Abnormal sleeping position Insomnia Delayed sleep phase syndrome Confusional arousal Sleep walking Sleep talking Persistence of bed wetting Nocturnal sweating Hard to wake up in the morning Mouth breathing Drooling Morning headache Daytime fatigue Daytime sleepiness with regular napping Abnormal daytime behaviours Patterns of attention-deficit/hyperactivity disorder Aggressiveness Abnormal shyness, withdrawn and depressive presentation Learning difficulties Abnormal growth patterns Delayed puberty Repetitive URTI Dental problems appreciated by dentist Crossbite Malocclusion (class II or III) Small jaw with overcrowding of teeth

Infants 312 months

Disturbed nocturnal sleep with repetitive crying Poorly established day/night cycle Noisy breathing or snoring Nocturnal sweating Poor suck

Absence of normal growth pattern or failure to thrive Observation of apnoeic events Report of apparent life-threatening event Presence of repetitive ear ache or URTI

URTI: upper respiratory tract infection. Reproduced from [64] with permission from the publisher.

oximetry and home recording, polysomnography still remains the gold standard in the diagnosis of OSAS in children [67].

Definitions of respiratory events during sleep

The scoring of respiratory events during sleep in children differs from the definitions used in adults. For a detailed overview of technical prerequisites refer to the guidelines of the American Academy of Sleep Medicine [68]. It is important to note that these guidelines can be used to score respiratory events for adolescents up to 18 yrs of age. However, an individual sleep specialist can choose to score children of at least 13 yrs of age by using the adult criteria. In brief, the recommended sensor for apnoea detection is an oronasal thermal sensor. Alternatives include nasal air pressure transducer, end-tidal CO2 and summed calibrated inductance plethysmography. Hypopnoeas should be scored by a nasal pressure transducer without square root transformation of the signal. An oronasal thermal sensor may be used when the nasal pressure transducer is not reliable. Respiratory effort is detected by oesophageal manometry, calibrated inductance plethysmography or uncalibrated inductance plethysmography. Oxygen saturation should be monitored by pulse oximetry with a signal averaging time of f3 s and alveolar ventilation by either end-tidal or transcutaneous CO2. The definitions of respiratory events during sleep in children are as follows.

Obstructive apnoea
A .90% drop in the signal amplitude of airflow for .90% of the entire event, compared with the baseline amplitude, and the event lasts for at least two breaths (or the duration of two baseline breaths) with continued inspiratory effort throughout the entire period of decreased airflow.

Mixed apnoea
The airflow signal meets duration and amplitude criteria for obstructive apnoea, and the event is associated with an absent inspiratory effort in the initial portion of the effort, followed by respiratory effort before the end of the event.

Central apnoea
The respiratory event is associated with absent inspiratory effort throughout the duration of the event and one of the following is present: 1) the event lasts for o20 s; or 2) the event lasts for at least two missed breaths (or the duration of two baseline breaths) and is associated with an arousal, an awakening or a .3% desaturation.

Hypopnoea
A .50% drop in airflow signal amplitude compared with the baseline amplitude for o90% of the duration of the event. In addition, the event must last for at least two missed breaths (or a duration of two baseline breaths) and should be associated with an arousal, awakening or a .3% desaturation.

Respiratory-effort-related arousal
An event is accompanied by snoring, noisy breathing, an increase in end-tidal CO2 tension (PET,CO2)/transcutaneous CO2 tension (Ptc,CO2) or visual evidence of increased work of breathing, and the event lasts for at least two breath cycles (or the duration of two baseline breaths) if one of the following is present: 1) a discernable reduction in amplitude of the nasal air pressure sensor

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that is ,50% in comparison to the baseline level with a flattening of the nasal pressure waveform; or 2) there is a progressive increase in inspiratory effort during the event on an oesophageal pressure sensor tracing.

Hypoventilation
Sleep-related hypoventilation may be scored when o25% of the total sleep time is spent with CO2 o50 mmHg, measured by Ptc,CO2 and/or PET,CO2 sensors.

Diagnostic thresholds
Diagnostic thresholds for OSAS in children are based on normative polysomnographic values in children [1823]. It is important to note that these studies differ in patient selection criteria and sometimes use different definitions for the various respiratory events. A comparison of the major findings of these studies is presented in table 2. In spite of differences in study designs, it is clear from these studies that obstructive events in normal children are rare (fig. 2). Also, the distribution of respiratory events is not influenced by Tanner stage [69]. Therefore, obstructive sleep apnoea in children is commonly diagnosed with an obstructive apnoea index o1 and/or an obstructive AHI o2. Studies have also shown that a single night polysomnography is sufficient to diagnose sleep apnoea in children [7072]. A proposed diagram to diagnose OSAS in children is presented in figure 3 [67].

Table 2 Comparison of published normative data in children

CHILDHOOD OSAS

Variable V ERHULST [22] Subjects Age group yrs OAI OAHI RDI TAI 60 11.72.6 7.116.6 0.060.16 0.000.87 0.080.17 0.000.87 1.981.39 0.147.18 6.11.8 2.710.9 97.00.6 96.098.0 91.82.7 82.096.0 98.72.1 90.8100.0 0.80.9 0.04.9

First author [Ref.] M ARCUS [18] W ITMANS [19] 50 9.74.6 1.117.4 0.100.50 0.003.10 0.200.60 NP NP NP 96.02.0 89.098.0 NP U LIEL [21] 70 7.94.4 1.015.0 0.02 NP NP 5.293.49 97.20.9 94.62.2 89.0NP NP T RAEGER [20] 66 6.61.9 2.59.4 0.010.03 0.000.10 0.230.31 0.40.6 0.04.0 11.24.3 5.421.5 97.01.0 95.098.0 92.03.0 81.095.0 NP M ONTGOMERYD OWNS [23] 388 6.8 6.08.6 0.050.11 0.000.90 NP 0.680.75 0.006.60 9.55.3 NP 92.63.6 99.61.0 92.3100.0 0.51.0

Sa,O2 % Sa,O2 nadir %

% of TST with Sa,O2 o95% ODI

0.30.7 0.04.4

NP

NP

Data are presented as n, mean SD or range. OAI: obstructive apnoea index; OAHI: obstructive apnoea/ hypopnoea index; RDI: respiratory disturbance index; TAI: total arousal index; Sa,O2: arterial oxygen saturation; TST: total sleep time; ODI: oxygen desaturation index; NP: not provided. Comparison with the study by M ONTGOMERY-D OWNS [23] was limited to the group of children aged o6 yrs. Reproduced from [22] with permission from the publisher.

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Complications
The main consequence of repetitive apnoeas and hypopnoeas during sleep is intermittent hypoxia, which is a potent trigger of oxidative stress and inflammation [74]. Indeed, several studies have documented increased markers of oxidative stress and inflammation in children who exhibit sleep apnoea [7577]. Other mechanisms by which OSAS may cause complications include increased sympathetic activity [78], higher serum cortisol [79] and other hormonal changes resulting from secondary sleep debt [8082].

0.55 0.50 0.45 0.40 0.35 0.30 0.25 0.20 0.15 0.10 0.05 0

OAHI

Figure 2. Scatter plot of individual data of the obstructive apnoea/

hypopnoea index (OAHI) showing that obstructive events in normal data are rare. - - - - -: 95th percentile; ???????: 90th percentile. Reproduced from [22] with permission from the publisher.

Neurocognitive and behavioural complications

One of the most extensive studied consequences of OSAS in children is neurobehavioural complications. Despite of major differences in study design, definitions of OSAS and outcome measures, and study sample, most studies have described an increase in subjective sleepiness, mood disturbance, behaviour problems and deficits in attention, memory and executive functions [83]. Other studies have also found an association between OSAS and lower academic achievement, an effect which might persist in adolescence [84, 85]. HALBOWER et al. [86] found signs of neuronal damage in children with OSAS using proton magnetic resonance spectroscopic imaging. Since this is a cross-sectional study, it is not clear whether this damage would be fully reversible after appropriate treatment. Another interesting fact is that the prevalence of snoring and OSAS is significantly increased in children with attention deficit/hyperactivity disorder, and that a clear improvement is seen after adenotonsillectomy [83]. Not all studies report a dose response relationship between the severity of OSAS and neurobehavioural morbidity. Other factors including genetic susceptibility, passive smoking exposure, obesity and short sleep duration, and other sleep disorders may also cause neurocognitive outcomes [83].

Metabolic and cardiovascular complications

Cross-sectional studies indicate that increasing severity of OSAS in obese children and adolescents is associated with an increased risk of the metabolic syndrome [12, 87]. Moreover, several studies show a positive correlation between sleep apnoea and insulin resistance and dyslipidemia in children [12, 87, 88]. However, it must be noted that other studies failed to find a similar relationship [8991]. These conflicting results could be explained by variations in the magnitude of obesity and the ages of study subjects, reflecting varying severity and/or duration of disease. In addition, pubertal status probably plays an important role. It should be emphasised that no randomised controlled trials of the effects of OSAS treatment on metabolic function have been conducted to date; cross-sectional studies of patients prior to and following treatment have yielded conflicting results [9294]. In general, OSAS appears to have modest effects on metabolic function in children, and the long-term consequences of childhood sleep apnoea on metabolic morbidity in early adulthood remain to be demonstrated in longitudinal investigations. Nevertheless, it is important to note that OSAS in obese children is also associated with cardiovascular complications, including increases in diastolic blood pressure, blunting of the nocturnal fall in blood pressure [95, 96] and increases in left ventricular mass and decreases in function [97, 98].

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Children screened for snoring during health supervision visit

Findings associated with OSAS include: History Habitual snoring with laboured breathing Observed apnoea Restless sleep Daytime neurobehavioural abnormalities or sleepiness Physical examination Growth abnormalities Signs of nasal obstruction, enlarged tonsils, adenoidal facies Increased pulmonic component of second heart sound Patients may have no abnormalities on physical examination No Continue screening during health supervision visits

Are symptoms or examination suggestive of OSAS being present? High-risk patients: Infants Patients with: Craniofacial disorders Trisomy 21 Cerebral palsy Neuromuscular diseases Sickle cell disease
CHILDHOOD OSAS

Yes Is this a high-risk patient? Yes Refer to a specialist Other studies to consider: Audiovisual recording Overnight pulse oximetry Unattended home study Polysomnography is considered "gold standard" No Evaluate for OSAS

Refer for polysomnography

No

Were any of the studies positive? Yes Treat for OSAS Yes

Was polysomnography positive? No Continue evaluation

Figure 3. Flow diagram for the diagnosis of paediatric obstructive sleep apnoea syndrome (OSAS) [67].
Reproduced from [73] with permission from the publisher.

Effects on growth
Although obesity is more and more becoming an important risk factor of childhood OSAS, early studies reported growth failure in children with sleep apnoea [99101]. Although a complete failure to thrive caused by OSA alone is rarely seen nowadays, it is well known that most children gain weight after adenotonsillectomy [102, 103]. Possible mechanisms for growth impairment include increased energy expenditure during sleep, altered production of growth hormone and increased peripheral resistance to growth factors [104106].

Treatment
Since the most common risk factor for OSAS in children is adenotonsillar hypertrophy, the recommended initial treatment is surgical removal of adenoids and tonsils. However, not all children with OSAS are completely cured after adenotonsillectomy. Recent meta-analyses have

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shown that the success rate of adenotonsillectomy is ,8085% [107, 108]. FRIEDMAN et al. [109] found a cure rate of 74% in uncomplicated patients, which was significantly higher than that of 39% in complicated patients (obesity and severe OSAS). Obesity, severe pre-operative AHI, high Mallampati scores, retro position of the mandible, enlargement of nasal inferior turbinates and deviated septum have all been found with a suboptimal response to adenotonsillectomy [11, 110 112]. A recent large, multi-centre, retrospective study showed that only 27.2% had complete resolution of OSAS (defined as AHI ,1). Age and BMI emerged as the two principal factors contributing to post-surgery AHI, with modest contributions by the presence of asthma and magnitude of pre-surgery AHI among non-obese children [113]. These findings stress the importance of a control polysomnography several months after treatment. In view of the increasing importance of obesity in the context of childhood OSAS, the specific treatment of sleep apnoea in obese children will be discussed in a separate chapter. Additional issues which require more study involve the specific surgical technique (cold surgery, a) coblation and harmonic laser) and Narrowed airway the need for both adenoidectomy and tonsillectomy, either one of these two procedures, or only tonsillectomy [114]. Alternative treatment options for children with mild sleep apnoea include pharmacological treatments, such as leukotriene receptor antagonists and intranasal steroids [115 118]. KHEIRANDISH-GOZAL et al. [118] also reported that these therapies could be beneficial for children with residual SDB after surgery. Although the exact selection criteria and longterm success rate have not yet been established, oral appliances or functional orthopedica appliances have also been used with some degree of success [119122]. Children with severe OSAS either before or after surgery are candidates for noninvasive ventilation. Although there are often difficulties in finding the correct interface, especially for young children, the adherence rates are satisfactory.
Normal airway

Fat

b)

Streamline through the upper airway (exhalation)

3D-model of the upper airway

Treatment options for obese children with OSAS

A multidisciplinary approach to treatment is essential: an obese child with OSAS should be evaluated by a paediatric sleep physician, an ear nose and throat specialist and a paediatric endocrinologist, and should be enrolled in a weight-management

Total pressure contours (exhalation)

Total pressure drop over 35 streamline (exhalation) 30 25 20 15 10 5 Nasopharyngeal region 0 Streamline length

Figure 4. a) Computed tomography scan and b) a threedimensional (3D) reconstruction with velocity and pressure profile of an overweight child with obstructive sleep apnoea syndrome. PA: alveolar pressure.

PA

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programme staffed by physicians and nutritionists, exercise physiologists and counsellors providing psychological support. Treatment should also be individualised. Although adenotonsillectomy is the first-line treatment for sleep apnoea in a child with significant adenotonsillar hypertrophy, a recent meta-analysis showed that adenotonsillectomy reverses OSAS in less than half of obese children with the condition [48]. Moreover, several studies indicate that obese children may gain weight after adenotonsillectomy [11]. This post-operative weight gain can result in treatment failure and an increase in insulin resistance after surgery [94, 123]. This does not imply that adenotonsillectomy should be completely abandoned. However, additional studies are required to identify those children most likely to benefit from adenotonsillectomy. In our centre (Antwerp University Hospital, Edegem, Belgium), we have begun to use ultra-low dose computed tomography (CT) scans and functional imaging to identify the subset of obese children who are most likely to benefit from surgery. Figure 4 presents a CT scan from an overweight child with mild OSAS; it clearly shows that airway narrowing is most severe at the level of the adenoids. Using sophisticated mathematical techniques we can simulate flows through a three dimensional computer model generated from the CT scan and calculate velocities, pressures and resistances across the airway [124]. Figure 4 also shows that the pressure drop indeed coincides with narrowing in the region of the adenoids. It is our intention to implement this technique in future clinical practice in order to create an individualised treatment plan for each obese child with OSAS. Should the child undergo adenotonsillectomy, it is mandatory to assess the efficacy of the procedure with a follow-up sleep study. Systematic studies of the effect of weight loss on the severity of SDB in children are scarce. However, KALRA et al. [49] studied 34 morbidly obese adolescents who underwent bariatric surgery. Prior to surgery, 55% of the subjects were diagnosed with OSAS. After surgical weight loss only one subject continued to experience sleep apnoea. VERHULST et al. [50] studied the effect of weight loss on SDB in 61 obese teenagers enrolled in an inpatient weight loss programme. 37 subjects were diagnosed with sleep apnoea; SDB resolved in 23 out of the 37 subjects, but 14 had residual SDB despite a median weight loss of 24 kg. Interestingly, the AHI of the baseline screening study correlated significantly with the amount of weight loss that was achieved during the treatment programme, suggesting that children with sleep apnoea lost more weight than their peers without sleep apnoea. Although our weight loss data seem promising, it needs to be emphasised that we have no data from obese children aged ,10 yrs and no long-term results thus far. Nevertheless, weight loss is an essential component of any treatment regimen for obese children with sleep apnoea and represents the first-line approach in those without adenotonsillar obstruction. Whether adenotonsillectomy is indicated in subjects resistant to weight loss remains to be determined. Finally, the use of noninvasive ventilation (continuous positive airway pressure) should be considered in children with severe OSAS. Continuous positive airway pressure can be poorly tolerated in children. Therefore, these children should undergo close follow-up to ensure maximal compliance. The additional value of upper airway surgery and/or weight loss in these subjects requires further study.

CHILDHOOD OSAS

Statement of Interest
None declared.

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