More Medical Issues in Down's Syndrome. A conference held under the auspices of the Royal Society of Medicine RESPIRATORY Forum on Learning Disability and The Down's Syndrome Medical Interest Group. Royal Society of Medicine, London, Thursday 26th April 2001 DISORDERS (srUAO) Chaired by Dr Patricia Jackson, Edinburgh and Dr Liz Marder, Nottingham Sleep-related upper airway obstruction in Down's syndrome Summary of a presentation by Dr Martin Samuels Senior Lecturer in Paediatrics, Keele University and Consultant Paediatrician, North Staffordshire Hospital Sleep-related upper airway obstruction (srUAO), some- Sleep-related UAO may be difficult to diagnose due to its times called obstructive sleep apnoea, is only one of a insidious onset. A child may appear completely normal in a broader range of respiratory control disorders associated clinic setting and although parents may be aware that snoring with sleep, known collectively as sleep disordered breathing and restlessness have increased over a period of time, they (SDB). These disorders are not related only to the upper may not realise that this is abnormal. Restless sleep is airway; there are complex relationships between the upper experienced by many children both with and without Down's and lower airway and it is important to be aware that lower syndrome and with and without sleep-related UAO. airway problems may also cause problems that are aggravated by sleep. Panel 1: Clinical features which may be associated with sleep-related UAO General features of sleep-related UAO Frequent: Clinical Presentation · Snoring. A UK study (Ali et al 1993) suggests Panel 1 lists clinical features which suggest the possibility around 12% of all children in the UK below the of sleep-related UAO, but which may also occur naturally age of 6 are habitual snorers whereas only 1­2% or be associated with other disorders have sleep-related UAO. Snoring may also be related to atopy (asthma, rhinitis) Snoring is one feature which manifests during the early · Sleep disturbance. Very common in childhood. stages of sleep disordered breathing and is therefore an Underlying UAO must be distinguished from important symptom to consider. However, many children nocturnal cough, pruritus, polyuria, parasomnias or psychological and drug-related factors without Down's syndrome snore and the relationship · Mouth breathing and halitosis between snoring and sleep-related UAO in Down's · Restless sleep syndrome requires further research. · Chronic rhinorrhea · Subcostal and sternal recession Upper airway resistance syndrome. There are children who · Odd sleep positions, such as hanging over the snore and have other symptoms suggestive of UAO but bed or sleeping upright with the head extended to who, on standard sleep studies, do not demonstrate optimise the upper airway noteable hypoxaemic episodes or increased upper airway Less frequent: resistance. On oesophageal manometry these children may · Swallowing difficulties show large negative pleural pressures, reflecting the · Recurrent upper respiratory tract infections increased work of breathing. This condition is called upper · Nausea and vomiting airway resistance syndrome. Opinion is divided as to the · Daytime sleepiness clinical relevance of this syndrome. · Persistent or secondary enuresis · Nocturnal sweating It is important to recognise that the spectrum of sleep · Cyanosis · disordered breathing is not static ­ for instance children can Apnoea develop into snorers abruptly, perhaps as a result of upper Associated only with severe problems: airway resistance syndrome due to a respiratory infection, · Pulmonary hypertension and then spontaneously revert to a normal breathing pattern · Heart failure during sleep. © Down's Syndrome Medical Interest Group · Children's Centre · City Hospital Campus · Nottingham NG5 1PB · www.dsmig.org.uk T: 0115 962 7658 ext 45667 · F: 0115 962 7915 · info@dsmig.org.uk Therefore, historical accounts and observations of symptoms Clinical effects of sleep-related UAO and their progression over time are important. · Neurocognitive (learning difficulties, behavioural Pathophysiology disturbances, personality changes) The pathophysiology of sleep-related UAO is not · Cardiovascular effects, pulmonary hypertension straightforward. Factors that lead to the development of · Poor growth upper airway problems include anatomical factors, such as · Lower airway effects: cyanotic-apnoeic episodes, changes in cranio-facial structure, obesity and lymphoid bronchoreactivity labelled as asthma hyperplasia (particularly between 2 and 6 years of age), and central effects such as abnormalities in pharyngeal (30­60 years). Adults are generally obese whereas children tone. In addition, there are undoubtedly genetic factors; frequently exhibit growth failure. Children desaturate more sleep-related UAO often runs within families. easily than adults but arouse less and tend to preserve better sleep architecture. Adults are more likely than Prevalence children to have episodes of complete obstruction. In the absence of widely accepted diagnostic criteria for Children are more likely to show daytime behavioural this disorder, prevalence estimates vary from study to problems whereas adults may have daytime hyper- study. A UK study by Ali et al (1993) used as diagnostic somnolence. Adults are at risk of pulmonary hypertension criteria a combination of clinical features, need for and cardiac arrhythmias. adenotonsillectomy, and certain desaturation criteria and found that around 2% of all children under 5 years of age Sleep-related UAO in Down's syndrome may have significant sleep-related UAO. Where There is a much higher prevalence of sleep-related desaturation figures alone are taken into account, the UAO in children with Down's syndrome than in other prevalence appears much higher (Owen et al. 1995). children. Estimates vary from 30­60% according to the diagnostic criteria used. Therefore, all children Adverse effects with Down's syndrome would benefit from regular Most adverse effects are mediated through hypoxaemia. respiratory review and general clinical assessments Dips in oxygen saturation due to episodic obstruction are should always include specific enquiries for symptoms observed rather than an overall drop in baseline oxygen of sleep-related breathing disorders. saturation. In children with Down's syndrome, baseline Some factors which predispose to sleep-related lowering is also seen and this may reflect lower airway UAO in Down's syndrome are shown in Panel 2. problems or an inter-relationship of the two. A further primary physiological consequence is hypercapnia. Panel 2: Factors predisposing to sleep-related UAO Disruption of sleep architecture and nocturnal arousals in Down's syndrome from sleep are secondary physiological effects which · themselves have clinical consequences. Maxillary/mandibular hypoplasia · Macroglossia · Small upper airway Physiological effects of sleep-related UAO · Increased secretions · Increased lower respiratory tract anomalies · Hypoxaemia · Sleep disruption · Obesity · Hypercapnia · Nocturnal arousal from sleep · Hypotonia · Lymphoid hyperplasia There are significant clinical effects of sleep-related UAO and it can be difficult in individual children to Features of sleep-related UAO in Down's syndrome determine the extent to which symptoms of UAO relate to Not only do children with Down's syndrome have a daytime problems in individual children. Cohort studies different pathophysiology from adults, they also differ in have identified that learning difficulties, behavioural some respects from other children with sleep-related UAO. problems and personality changes can be related to sleep- The recognised childhood tendency to desaturate more related UAO. There are also cardiovascular effects and than adults (see previously) is further exacerbated in those poor growth. Furthermore, the effects of hypoxaemia on with Down's syndrome for reasons such as airway(s) and the lower airways may produce a rise in airway resistance lung hypoplasia, and abnormalities in alveolar structure. which may have been labelled as asthma. In other children, desaturations and arousals occur mainly Children with UAO differ in many ways from adults. In in REM sleep but in Down's syndrome they may occur children it is the younger age group which is most affected through the whole of sleep and therefore children with (2­3 years) reflecting relatively large lymphoid tissue at Down's syndrome have more disturbance of their sleep this age. In adults it is the older group who are affected architecture. A UK study by Stebbens et al (1991) of 32 preschool within the oximeter, dips in oxygenation are damped children with Down's syndrome used a questionnaire for out, and falsely low baselines in oxygenation may six signs and symptoms, overnight tape recordings and an be measured. Therefore, short averaging times are overall clinical assessment. The questionnaire findings preferred in sleep studies. It is also important that age- suggested that in a population group of children with appropriate normative data are used when comparing Down's syndrome, one third would have at least three measures of baseline and dips in oxygenation. symptoms suggesting sleep-related problems. The most · Inspiratory resistance. This can be recognised by frequent clinically significant problems were snoring and examination of the breathing pattern: a shouldering of chest wall recession. Other sleep-related problems the inspiratory waveform on respiratory inductance included restlessness, mouth breathing and excessive plethysmography (Respitrace) is found with upper sweating, although these were not significantly increased. airway obstruction. · Carbon dioxide measurements. These can be The overnight recordings showed that 41% of the children performed using both end-tidal and transcutaneous with Down's syndrome had a pattern of an increased sensors in hospital-based studies. inspiratory resistance on the respiratory waveform · Home video-oximetry. This is a screening tool that compared to 3% of controls. Two-thirds of the children has been found to be very helpful. A video camera and with Down's syndrome had oxygen saturation levels below oximeter are set up in a child's home next to their bed. that of the lowest found in controls, possibly reflecting A low level light or infra red light and camera are used exacerbation of UAO by lung hypoplasia. Unsurprisingly, and preferably the child is exposed down to the waist. they also had an increased number of dips in oxygen The tapes are reviewed for falls in baseline oxygen saturation during sleep. These occurred particularly during saturation, chest wall recession, snoring, sleep position non-regular breathing. and nocturnal movement. Other assessments could include: Investigation of sleep-related UAO · Hypopnoea. A greater than a 50% reduction in The key investigation of sleep-related UAO is the sleep amplitude of either airflow or breathing movements. observation or sleep study, but additional investigations · Paradoxical inward rib cage movement (PIRCM). may be helpful. This is appropriate for children older than 3­4 years of age; recorded by a band around the chest which Sleep studies. The methodology used in sleep studies is measures the increased work of breathing. It may very variable and includes studies of daytime naps, night prove to be as useful as oesophageal manometry. studies and the traditional full polysomnogram. This · Arousals detected on EEG. Criteria for arousal method has been adapted from investigations in adults and thresholds and their relevance to daytime symptoms is it has been questioned whether all the measures used being investigated in adults but little is known about (shown in Panel 3) are relevant for children. Additional this in children. measurements could include oesophageal manometry, but · Oesophageal pressure measurements (manometry). this procedure may be too invasive in children. In addition to sleep studies, there are a number of other investigations that may be required. Panel 3: Measures used in full polysomnogram · Respiratory movements · Oxygenation Fibreoptic endoscopy is very useful to help identify the site · Airflow · Carbon dioxide of obstruction. This is best performed under a light general · ECG · Movement anaesthetic to give a much better picture of the dynamics of · EEG, EOG, EMG · Video recordings the airway rather than under a deep anaesthetic with a rigid scope. There may be multiple sites or there may be one main In the UK, paediatric sleep study facilities and site which, when dealt with, predominantly overcomes the procedures are fragmented and variable around the obstruction. In Down's syndrome, obstruction is often country. There is little consistency in the measurements tongue-based, where the tongue approximates to the pharynx that are undertaken and it is therefore difficult to compare during sleep. This appears to be the most predominant studies. The simple straightforward measurements used at problem and the most difficult to treat. North Staffordshire Hospital include: · Video recordings. Particularly useful if the child is Barium/cine swallow. Noisy breathing may be due to exposed from neck to waist so that chest wall upper airway problems or there may be an additional lower recession and increased work of breathing can be seen. airway component. A barium/cine swallow looking for a · Pulse oximetry. Most clinical oximeters provide vascular ring as a cause of large airway obstruction can be average measurements. With longer averaging times useful in establishing the source of the noise. DSMIG is indebted to the Down's Syndrome Association who have met all the production costs for this summary. MRI or CT imaging can be useful if the anatomy is For this reason, after investigation and diagnosis, complicated or endoscopy proves difficult. consideration should be given to a period of observation (3­6 months) and reassessment before pursuing treatment ECG and echocardiogram are useful in assessing possible options (Panel 4). cardiac effects of a sleep-related breathing disorder. There are also particular surgical issues for children with Down's syndrome as shown in Panel 5. Haemoglobin measurement should be carried out if any procedure is to be performed or if severe hypoxaemia is Panel 5: Particular surgical issues for children with suspected. Down's syndrome · Hospital admission recommended for all Investigations used in the investigation of surgery, including tonsillo-adenoidectomy and sleep-related UAO endoscopy. Frequent Additional · Pre-med sedation for tonsillo-adenoidectomy or · Sleep observation/ · Barium/cine swallow endoscopy should be avoided as it may sleep study · CT/MRI aggravate UAO. · Fibre-optic endoscopy · ECG/Echocardiogram · Admittance to PICU or high dependency unit · Hb measurement recommended as there is a high incidence of post-surgery airway problems. Management There is no one ideal treatment for sleep-related UAO in Conclusion children with Down's syndrome. Treatments are not always The high prevalence of sleep-related UAO in people with effective and have associated morbidity and mortality risks. Down's syndrome, and its associated significant morbidity, Spontaneous resolution may occur over time but less suggests that those with the syndrome would benefit from frequently than for other children. regular respiratory review. Any clinical assessment should always include specific enquiry for symptoms of sleep- related breathing disorders. Panel 4: Management options for sleep-related UAO in Down's syndrome · Wait and reassess if necessary. Further reading · Topical decongestants/steroids may be useful Ali NJ, Pitson DJ, Stradling JR. Snoring, sleep disturbance, and for intermittent problems. behaviour in 4­5 year olds. Arch Dis Child 1993;68(3):360­6 · Tonsillo-adenoidectomy. Gislason T, Bendiktsdottir B. Snoring, apneic episodes, and · Nasal CPAP. Effective and non-invasive. Compli- nocturnal hypoxaemia among children 6 months to 6 years: ance issues and side effects (pressure sores, nosebleeds, excessive drooling and abdominal an epidemiological study of lower limit of prevalence. Chest distension due to swallowed air) may be problematic. 1995;107:963­6. · Nasopharyngeal tubes. Particularly useful in Kohyama J, Shiiki T, Shimohira M, Hasegawa T. young children and infants. Avoids tracheostomy. Asynchronous breathing during sleep. Arch Dis Child Needs to be placed under endoscopy to ensure 2001;84:174­7 that the tip is in an appropriate position to over- come tongue base obstruction. Requires periodic Levanon A, Tarasiuk A, Tal A. Sleep characteristics in review and replacement to account for growth. children with Down's syndrome. J Pediatr · ENT procedures. These include: 1999;134(6):755­60 ­ Tonsillectomy Marcus CL, Keens TG, Bautista DB, von Pechmann WS, ­ Adeniodectomy Ward SL. Obstructive sleep apnea in children with Down's ­ Uvulopalatopharyngoplasty (mainly adults) syndrome. Pediatrics 1991;88(1):132­9 ­ Tonsillar pillar plication ­ Midface advancement Owen G, Canter R, Robinson A. Overnight oximetry in ­ Tongue hyoid suspension snoring and nonsnoring children. Clin Otolaryngol ­ Anterior tongue reduction 1995;20:402­6. ­ Laryngotracheostomy Stebbens VA, Dennis J, Samuels MP, Croft CB, Southall DP. ­ Mandibular splint ­ Tracheostomy (usually an emergency or last Sleep related upper airway obstruction in a cohort with resort procedure). Down's syndrome. Arch Dis Child. 1991;66(11):1333­8 The most suitable treatment option depends upon the particular patient. Advice from an expert in A complete transcript of this presentation, together with paediatric ENT surgery should be sought for all ENT references, is available at www.dsmig.org.uk. procedures. © 2002 Down's Syndrome Medical Interest Group. Produced by Oxford PharmaGenesisTM Ltd, UK