Pavilion Publishing and Media Ltd
Blue Sky Offices Shoreham, 25 Cecil Pashley Way, Shoreham-by-Sea, West Sussex, BN43 5FF, UNITED KINGDOM
Tel: +44 (0)1273 434 943
Email: [email protected]
Here, the author looks at diagnosing sleep disordered breathing, including obstructive sleep apnoea, how to treat and when to refer
Dr Michael Yanney
Consultant Paediatrician, Sherwood Forest Hospitals NHS Foundation Trust
Sleep disordered breathing (SDB) is a spectrum of disease characterised by abnormal breathing patterns and adverse consequences of sleep disturbance. It encompasses obstructive sleep apnoea (OSA) at one end of the spectrum, upper airway resistance syndrome (UARS) and habitual snoring at the other end. OSA is defined as repeated episodes of partial or complete upper airway obstruction during sleep resulting in disruption of normal gas exchange and sleep patterns.1
UARS is a less severe form of upper airway obstruction characterised by increased work of breathing and sleep fragmentation resulting from frequent arousals, but without significant desaturation episodes or gas exchange abnormalities.2 Habitual or primary snoring is a description of mild upper airway resistance resulting in noisy breathing but no associated sleep fragmentation or gas exchange abnormalities. Problems of central breathing control make up another group of sleep related breathing disorders and includes the rare but life threatening disorder congenital central hypoventilation syndrome.
Obstructive sleep apnoea affects about 2% of children with a peak presentation between 2-8 years.3 There is an increasing body of evidence that demonstrates that neurocognitive, metabolic and cardiovascular impairment results from OSA in childhood, some of which may be only partly reversible following treatment.3,4 Along with other sleep problems in children, sleep disordered breathing is under-recognised by clinicians in both primary and secondary care.2,5
Comorbidities associated with SDB
The frequent apnoeas that occur with OSA lead to oxygen desaturation episodes that are associated with arousals (i.e. waking into a lighter phase of sleep). Frequent arousals are associated with sleep fragmentation and it appears the disruption of sleep architecture underlies the neurocognitive effects that have been shown to be associated with OSA.
Behaviour problems are the commonest encountered comorbidity of OSA with studies consistently reporting an association between OSA and attention deficit hyperactivity disorder (ADHD) like symptoms in children.4
Unlike adults, daytime sleepiness is a less prominent feature of OSA in children, but lower Epworth sleepiness scores have been demonstrated in children with OSA compared to controls.6 OSA is associated with impaired school performance and lower IQ scores, which appear to be only partially reversed following treatment.7,8 The oxygen desaturation changes, carbon dioxide retention and intrathoracic pressure swings associated with OSA cause rapid changes in heart rate and surges in blood pressure due to increased release of catecholamines. These changes result in dysfunction of the autonomic nervous system and underlie the cardiovascular abnormalities associated with OSA, such as systemic hypertension. Recurrent hypoxic episodes also result in elevated pulmonary vascular resistance leading to pulmonary hypertension and, at its most severe, right heart faliure.4 OSA has been associated with faltering growth in children although this is now seen much less commonly, possibly due to earlier treatment.9 Obesity is also linked with OSA as a risk factor for developing the condition in both adults and children. However, there is emerging evidence of OSA contributing to the development of obesity by its effect on metabolic pathways.3
History
The commonest symptom of SDB is snoring, which may occur intermittently in association with upper respiratory tract infections or seasonal rhinitis, or regularly on most nights. There is often an associated history of witnessed apnoeas or restless sleep due to frequent arousals. Unusual sleeping positions may be reported, particularly postures with a hyperextended neck.
Other symptoms may include behaviour problems, such as hyperactivity, inattention and impulsivity, i.e. symptoms of ADHD. Daytime tiredness may also be reported although this occurs much less frequently in children than it does in adults.9 Other presentations include apparent life threatening events in infants, which may include apnoea with an associated colour change, floppiness, choking or gagging. Drooling or morning headaches may be reported in preschool or school age children. Symptoms associated with SDB are listed in Table 2.
The limitation of the clinical history to discriminate children with habitual snoring from those with OSA has long been recognised. This has led to an acceptance that OSA cannot be reliably diagnosed based on history alone. However, a study by Spruyt and Gozal evaluating a 37 item sleep questionnaire in a group of 5-9 year old children found the six questions in Table 3 to be the most discriminatory for detecting OSA.10
The authors used a scoring system incorporating the responses to these six most discriminatory questions and found a score >2.72 on the severity scale was predictive of OSA.
Examination
Examination should assess factors likely to predispose to SDB as well as looking for evidence of comorbidities.
An assessment of growth and blood pressure should be done. The presence of any craniofacial or palatal abnormalities should be noted including conditions such as Pierre Robin sequence, an association of micrognathia with a cleft palate. Examination of the upper airway should include assessment for evidence of rhinitis or prominent inferior turbinates; the presence of adenoidal facies – ‘a long face and open-mouthed look’ associated with adenoid hypertrophy; mouth breathing and evidence of tonsillar hypertrophy. The presence of Harrison’s sulci; a fixed concave deformity of the lower chest wall, would suggest chronic upper airway obstruction. Conditions associated with a high risk of SDB are listed in Table 4.
Investigation of sleep disordered breathing
Despite its importance, a thorough history and clinical examination is not usually sufficient to make an accurate diagnosis of SDB. A positive predictive value of 65% for history and 46% for clinical examination has been reported, which is not much better than tossing a coin2,11 A sleep study is usually needed to confirm a suspected diagnosis of OSA in children.
Parents are increasingly using mobile devices to record video clips of sleep related breathing problems in children. This can provide useful corroborative evidence of the concerns about a child’s breathing pattern and in some cases can even be diagnostic. Yet video evidence on its own provides no information about the physiological effects of any observed obstructive events, particularly whether or not they are associated with desaturation episodes and how significant these might be.
Types of sleep study
Polysomnography (PSG) is a multi-modality sleep study which can monitor a wide range of physiological parameters including EEG (Table 5). It is considered the gold standard investigation for SDB but is only available in a limited number of tertiary paediatric centres.12 Table 5 lists the different types of sleep studies and the modalities they include.
Screening sleep studies, which mainly measure pulse oximetry, are used in high risk groups or as a preliminary assessment of children with symptoms of OSA. Oximetry has good specificity but poor sensitivity.14 A positive result is often helpful but a negative result does not exclude OSA. An advantage of oximetry studies is the ability to assess children in their home environment where sleep is likely to be of much better quality than in the unfamiliar surroundings of a sleep unit. Many sleep related breathing disorders occur during REM sleep and may be missed if the period of sleep being monitored only includes non-REM sleep.
Studies that incorporate additional modalities, such as video, sound and arousal detection, including pulse transit time, can further improve the sensitivity and specificity of screening for sleep disordered breathing.15 Pulse transit time (PTT) is a non-invasive marker of blood pressure computed from the interval between the QRS complex on the ECG and the peak of the plethysmographic waveform on the pulse oximetry signal outputs. PTT provides a quantitative measurement of arousals and inspiratory effort in patients with sleep disordered breathing and is a helpful, non-invasive marker of arousals.16,17 The disadvantage of multi-modality screening studies is the need for admission to a sleep unit, which makes them more costly and may result in sleep of poorer quality than is achieved at home. Sleep systems that make it possible to assess multiple modalities in the home environment have recently become available and appear to be a promising development.
Second-line studies, often referred to as cardiorespiratory studies, are used to assess children where the diagnosis is in doubt or treatment decisions cannot be made following a screening study. As well as ECG, video, sound and arousal detection, these studies will often have a measurement of airflow, effort and end tidal or transcutaneous CO2 for a better assessment of breathing problems.
The main additional benefit of polysomnography over a cardiorespiratory study is the ability to assess sleep architecture and an accurate evaluation of arousals and the presence or absence of REM sleep.
PSG is most useful for identifying children in whom the disruption to sleep architecture is important to decision-making or diagnosis. It is an expensive resource and is not necessary for the majority of children with SDB. Its use tends to be reserved for children with atypical symptoms, where there is uncertainty after less invasive testing or when there are ongoing symptoms following surgery for OSA.
Obstructive sleep apnoea and upper airway resistance syndrome
Adenotonsillar hypertrophy is the leading cause of OSA in children, yet a combination of anatomical structure, neuromotor tone and inflammation are all likely to contribute to the upper airway obstruction.9
Craniofacial factors including a small receding mandible or a relatively large tongue make OSA more likely in conditions such as Pierre Robin sequence, Down’s syndrome or Prader-Willi syndrome. Increased pharyngeal fat pads due to obesity or upper airway inflammation in children with allergic rhinitis, are additional factors that contribute to obstruction.
Episodes of obstruction are more likely to occur during REM sleep due to the reduced airway muscle tone and increased airway collapsibility that occurs during this stage of sleep.
UARS is characterised by increased upper airway resistance, increased work of breathing and frequent arousals during sleep but without significant desaturation episodes or gas exchange abnormalities.5
The sleep fragmentation associated with UARS causes neurocognitive impairment or excessive daytime sleepiness. The lack of desaturation episodes or gas exchange abnormalities differentiates UARS from OSA.
Habitual or primary snoring is at the opposite end of the spectrum from OSA and is due to a degree of upper airway resistance but no gas exchange abnormality or disruption of sleep architecture. It is a common disorder and occurs in about 10-12% of children.12 It has been presumed to be benign but there is limited evidence to suggest it may be associated with mild neurocognitive impairment.2,18
Central breathing control disorders
Disorders of central breathing control make up a less common but important group of problems identified by sleep studies. They may be due to a rare primary disorder such as congenital central hypoventilation syndrome (CCHS) or secondary to diseases affecting the spinal cord or brain stem. Infants may present with cyanosis, apnoeas or apparent life threatening events from birth or during the first few months of life. PSG is often needed to measure gas exchange during wakefulness, REM, and non-REM sleep states. CCHS requires treatment with long-term respiratory support.5
Other conditions requiring sleep studies
Children with a range of lung disorders that require continuous oxygen therapy, including chronic lung disease of prematurity, interstitial lung disease or cystic fibrosis need regular monitoring with sleep studies.
These children typically require oximetry studies for a minimum of about four hours to assess for any evidence of disease progression or spontaneous improvement that might require a change in the oxygen flow rate. Sleep studies are also needed to monitor children with progressive neuromuscular disorders such as Duchenne muscular dystrophy to determine if non-invasive respiratory support is needed or for titrating ventilator requirements. CO2 monitoring is generally needed in addition to oximetry in this group of children.5
Treatment
Adenotonsillectomy is the first line treatment for children with OSA due to adenotonsillar hypertrophy being the commonest cause. It is curative in the majority of children but those with residual symptoms post-operatively may require alternative therapies.
Surgery may also be indicated for some children where obesity is the underlying cause of OSA but in whom there is also mild-moderate adenotonsillar hypertrophy. In children with no adenotonsillar enlargement, surgery is unlikely to be of any benefit and alternative therapies, such as nasal CPAP, may need to be considered.
A multi-centre randomised controlled study comparing the use of early adenotonsillectomy with watchful waiting in school-aged children with mild-moderate OSA found no significant difference in the primary outcome measure of the attention and executive-function score on the Developmental Neuropsychological Assessment (NEPSY). However, there was an improvement in secondary outcome measures such as parent reported behaviour, quality of life scores and in PSG findings.19 A watchful waiting approach may therefore be appropriate in some children with mild-moderate OSA.
Other successful treatment strategies include the use of anti-inflammatory agents such as leukotriene antagonists or nasal corticosteroids in children with mild OSA.20-22 There appears to be increased expression of leukotriene receptors in the tonsils of children with OSA compared with the tonsils of children with recurrent tonsillitis.23 A prospective double-blind randomised trial comparing montelukast with placebo in 46 children with mild-moderate OSA showed that montelukast effectively reduced adenoid size, improved symptoms and polysomnographic findings in those studied.22 A randomised crossover trial of six weeks treatment with intranasal budesonide for mild OSA similarly showed a reduction in the severity of OSA and in the size of adenoidal tissues with no worsening of symptoms up to eight weeks after the treatment had been discontinued.21The effect of intranasal steroids and leukotriene receptor antagonists appeared to be independent of the presence of atopy in the subjects studied.
Weight reduction has also been effective in reducing the severity of symptoms in some children where obesity is a significant contributory factor to upper airway obstruction.24,25 Respiratory support with nasal CPAP is reserved for children with severe OSA who remain symptomatic despite adenotonsillectomy or if surgery is not feasible.
Conclusion
Sleep disordered breathing is relatively common in children and is probably under-recognised. Surgical intervention or respiratory support may be needed to avoid neurocognitive or cardiovascular effects, while in some children other conservative therapies or watchful waiting may be an option. It is important that clinicians seeing children who may have SDB are aware of the presenting symptoms and clinical findings to ensure that they are investigated and treated appropriately.
References
1. American Thoracic Society. Standards and indications for cardiopulmonary sleep studies in children. Am J Respir Crit Care Med 1996;153:866–78.
2. Whiteford L, Fleming P, Henderson AJ. Arch Dis Child 2004;89:851–855
3. Tan HL, Gozal D, Kheirandish-Gozal L. Nature and Science of Sleep 2013:5 109–123
4. Tauman R, Gozal D. Expert Review of Respiratory Medicine. 2011 5(3): 425-440
5. Blunden S, Lushington K, Lorenzen B. et al. Arch Dis Child 2004 89: 708-712
6. Melendres MC, Lutz JM, Rubin ED, Marcus CL. Pediatrics. 2004;114(3):768–775.
7. Gozal D. Pediatrics 1998;102:616–20.
8. Kohler MJ, Lushington K, van den Heuvel CJ et al. PLoS ONE 2009 4(10): e7343.
9. Sinha D, Guilleminault G. Indian J Med 2010, 131:311-320
10. Spruyt K, Gozal D. Chest 2012; 142(6):1508–1515
11. Marcus CL, Brooks LJ, Draper KA, et al. Pediatrics. 2012;130(3):e714–e755.
12. Primhak R, O’Brien C. Arch Dis Child Educ Pract Ed 2005;90:ep87–ep91.
13. RCPCH Working Party on Respiratory Physiology and Sleep Control Disorders in Children, Sept 2009
14. Brouillette RT, Morielli A, Leimanis A, et al. Pediatrics 2000;105:405–412
15. Rowbotham NJ, Dove H, Yanney, MP. Arch Dis Child 2015;100:A162-A163
16. Rowbotham NJ, Yanney MP. Arch Dis Child 2015;100:A163-A164
17. Katz ES, Lutz J, Black C, Marcus CL. Pediatr Res. 2003;53:580–588
18. Goodwin JL, Kaemingk KL, Mulvaney SA, et al. Journal of clinical sleep medicine 2005, 1 (3): 247-254.
19. Marcus CL, Moore RH, Rosen CL, et al, N Engl J Med. 2013;368(25):2366–2376.
20. Kheirandish L, Goldbart A, Gozal D. Pediatrics 2006;117;e61-e66
21. Kheirandish-Gozal L, Gozal D. Pediatrics 2008;122:e149–e155
22. Goldbart AD, Greenberg-Dotan S, Tal A. Pediatrics.2012;130(3):e575–e580.
23. Goldbart AD, Goldman JL, Li RC, Brittian KR, Tauman R, Gozal D. Chest. 2004;126(1):13–18.
24. Ng DK, Lam YY, Chan CH. Circulation, 2004,110 e314
25. Willi SM, Oexmann MJ, Wright NM, Collop NA, Key LL Jr.Pediatrics 101, 61–67