INTRODUCTION — The sleep of a healthy child can be viewed as the gold standard for sleep quality. Children normally have a brief latency to sleep onset and then breathe quietly and comfortably during sleep. Sleep efficiency (time asleep/time in bed) is high (greater than 90 percent). There are few behavioral arousals during the night, and the child awakens in the morning refreshed and ready to learn and play. During the day, children are normally very alert and do not display signs of sleepiness (which, in children, can include hyperactivity and poor impulse control). For younger children, a certain frequency of napping is normal and expected. Sleep-related breathing disorders in children occur along a spectrum of severity, ranging from primary snoring on the mild end to obstructive sleep apnea (OSA) on the serious end.
This topic review will discuss the normal physiology of sleep in children and the factors that disturb respiration during sleep and contribute to the development of a sleep-related breathing disorder, including OSA. The evaluation of the child with snoring or suspected OSA and the management of the child with OSA are discussed separately. (See "Evaluation of suspected obstructive sleep apnea in children" and "Management of obstructive sleep apnea in children" and "Adenotonsillectomy for obstructive sleep apnea in children".)
SLEEP STAGES — Starting at birth, a child's sleep can be divided into rapid eye movement (REM) and non-REM (NREM) sleep and scored polygraphically using the American Academy of Sleep Medicine (AASM) Manual for the Scoring of Sleep and Associated Events [1]. (See "Stages and architecture of normal sleep" and "Sleep physiology in children", section on 'Sleep states'.)
REM sleep is a physiologically activated sleep state characterized by:
●Generalized muscle atonia
●Increased cerebral blood flow
●Desynchronized electroencephalography (EEG)
●Variability of heart rate, respiratory rate, and blood pressure
●Increased upper airway resistance
During REM sleep, bursts of phasic events have both central and peripheral nervous system manifestations (for example, in the form of ponto-geniculo-occipital waves and muscle twitches despite the atonia, respectively). Most dreaming occurs during REM sleep.
By comparison, NREM sleep is a more quiescent state characterized by:
●Reduced, but not absent, muscle tone
●Decreased cerebral blood flow
●Synchronized EEG
●Regular heart rate, respiratory rate, and blood pressure
●Increased upper airway resistance [2,3]
After age two months, NREM sleep is subdivided into stages N1, N2, and N3 by EEG criteria, which roughly parallel increasing depth of sleep [1]. NREM sleep, REM sleep, and brief periods of wakefulness alternate in a regular and predictable pattern throughout the sleep period, defining the ultradian rhythm. (See "Stages and architecture of normal sleep".)
The NREM-REM cycle length increases from 60 minutes at infancy to 90 minutes in adolescents and adults. NREM sleep stage N3 is also labeled as "slow-wave sleep." Slow-wave sleep predominates in the early part of the sleep period, whereas REM sleep predominates in the latter part of the sleep period. A normal night's sleep for a child is comprised of 5 to 10 NREM-REM sleep cycles woven together seamlessly, so that the transitions from one cycle to the next are behaviorally inapparent.
CHANGES IN RESPIRATORY PHYSIOLOGY DURING SLEEP — During sleep in a normal child there is a modest increase in upper airway resistance and a small decrease in nocturnal ventilation. Overnight polysomnography (PSG) studies in normal children have quantified these changes, establishing norms for nocturnal ventilation in children (table 1) [4-6]. These normative studies have demonstrated that there is a small decrease in oxygen saturation (0 to 7 percent) and a rise in end-tidal PCO2 (0 to 13 mmHg). Brief central pauses are common in children, especially in association with movements, but obstructive apneas are never normal in children.
The decrease in ventilation is caused by both an increase in upper airway resistance and a decrease in central respiratory drive, as detailed below [2-4]:
Increased upper airway resistance — Although the nose is the site of greatest resistance in the upper airway, the pharynx is the site of the greatest increase in airway resistance during sleep [7]. This increase in resistance is due to the decreased size of the pharynx associated with relaxation of the pharyngeal dilators.
The pharynx provides a conduit for air, solids, and liquids, and is intimately involved in breathing, digestion, and speaking (image 1). In its role as an organ of respiration, the pharynx must remain patent. In its role as an organ of digestion, the pharynx moves to occlude and protect the nasopharynx and larynx, while directing solids and liquids into the esophagus during swallowing and out of the mouth during vomiting. In its role as an organ of speech, the pharynx provides a steady, highly regulated flow of air that is variably directed into the nose and mouth.
To fulfill these diverse functions, the pharynx is constructed as a rigid tube with a mobile, collapsible segment in the middle. The collapsible section of the pharynx is controlled by at least 20 sets of paired muscles, which can alter its size, shape, and dynamics, and behaves like a Starling resistor (figure 1). The collapsibility of the pharynx is a necessity for it to fulfill its roles in digestion, phonation, and to protect the airway from aspiration, but it is a liability in its role as an organ of respiration and is central to the understanding to the pathophysiology of sleep-related breathing disorders.
The pharyngeal dilators are a group of muscles that provide the postural tone to the pharynx during wakefulness and maintain pharyngeal patency in the face of the subatmospheric intraluminal pressure generated during inspiration. The pharyngeal dilators that have been studied during sleep in adults are [8,9]:
●Genioglossus [10-14]
●Posterior cricoarytenoids [15]
●Tensor veli palatini [16]
●The nasal inspiratory muscle (the alae nasi), which affects the airway patency by causing the nasal ala to flare and open during inspiration [17]
●Superior constrictor muscle, which also supports the tonsils and prevents them from collapsing when tonically contracted
●Levator veli palatine, which gives tone to the soft palate along with the tensor veli palatini
During wakefulness and sleep, the pharyngeal dilators help to maintain pharyngeal patency by tonic contraction (which is present throughout the respiratory cycle) and/or phasic contractions (which are synchronized with the contraction of the respiratory pump muscles, thereby helping to stiffen the upper airway prior to and during inspiration). During sleep in individuals without a sleep-related breathing disorder, there is a decrease in activity of the pharyngeal dilators that results in a decrease in pharyngeal size and a concomitant increase in upper airway resistance [8-10,15-19].
As a group, the pharyngeal dilators can be considered accessory muscles of respiration. Their activity during sleep is modulated by the respiratory control center of the medulla, which receives input from the pharyngeal mechanoreceptors. The mechanoreceptors are the afferent limb of a complex pharyngeal reflex that maintains pharyngeal patency during inspiration [20]. These reflexes have been demonstrated in both children and adults and they augment activation of the pharyngeal dilators in response to negative intraluminal pressure and hypercapnia [21-23]. Topical anesthesia of the pharynx and glottis in adults [24] and children [25] during wakefulness results in a substantial decrease in upper airway size and increase in upper airway resistance, suggesting that the pharyngeal mechanoreceptors play an important role in maintenance of pharyngeal patency during wakefulness. These reflexes likely play an even more important role during sleep in adults and children with sleep-disordered breathing.
In contrast with adults, normal children snore infrequently and rarely have obstructive apneas during sleep. This is consistent with the better preservation of upper airway patency in response to subatmospheric pressure. Adults with obstructive sleep apnea syndrome (OSAS) tend to have repetitive obstructive apneas, while children with OSAS frequently manifest a pattern of persistent, partial upper airway obstruction, rather than discrete apneas [4]. Thus, the pattern of upper airway muscle recruitment in children with OSAS [26] may be different from that in adults; children may have greater upper airway muscle activation, thereby preventing total airway occlusion [27].
Decreased central respiratory drive — If the increased upper airway resistance is reversed by nasal continuous positive airway pressure (CPAP) or is minimized by having patients breathe a low density gas, there is still a small decrease in ventilation, suggesting an independent decrease in central respiratory drive during sleep [18]. This decrease has been attributed to the loss of a "wakefulness respiratory drive," the nature of which is not completely understood. (See "Control of ventilation".)
Other factors — Other important changes in respiratory physiology during sleep include:
●A decrease in load compensation
●An increase in the contribution of the intercostal muscles to inspiratory effort during non-rapid eye movement (NREM) sleep
●A decrease in lung volumes during rapid eye movement (REM) sleep
●A decrease in synchronization of the pharyngeal dilators with diaphragmatic contractions during REM sleep
BALANCE OF FORCES MODEL OF UPPER AIRWAY OBSTRUCTION — The pharyngeal narrowing that occurs during sleep can be understood to result from a balance between forces that tend to collapse the airway and the pharyngeal dilators that attempt to maintain pharyngeal patency (figure 2) [28].
This balance is affected by:
●The skeletal and soft tissue anatomy of the upper airway
●The neuromuscular tone of the pharyngeal dilators
●Suction pressure generated by the inspiratory pump muscles
During wakefulness, obstructive apneas are rare even in individuals with markedly enlarged tonsils, obesity, craniofacial anomalies, and abnormal neuromuscular tone because the pharyngeal dilators are able to compensate for whatever factors are present that might lead to upper airway collapse. During sleep, the neuromuscular tone of the pharyngeal dilators, and possibly their coordination with the inspiratory pump muscles, is diminished so that they are less able to compensate. Pharyngeal dilator muscle activity decreases during NREM sleep in children and decreases further during REM sleep [13]. These changes in tone of the pharyngeal dilators result in one of three possible outcomes (figure 2):
●Normal sleep – During sleep in normal children and adults, there is a small decrease in the size of the pharyngeal airway, resulting in a small but clinically insignificant increase in upper airway resistance.
●Obstructive apneas and hypopneas – Obstructive sleep apnea (OSA) in most adults and many children is characterized by repeated transient collapse of the pharyngeal airway. These events are known as obstructive apneas if the airway closes completely or hypopneas if it closes partially.
●Obstructive hypoventilation – In obstructive hypoventilation (OHV) there is continuous partial collapse of the pharyngeal airway, resulting in increased upper airway resistance and continuous hypoventilation, associated with hypercapnia and hypoxemia but without cyclic discrete obstructive events. This finding is common in young children but less common in adults [29]. The International Classification of Sleep Disorders (ICSD) classifies obstructive hypoventilation as a form of pediatric OSA; obstructive hypoventilation is defined as at least 25 percent of total sleep time with hypercapnia (PaCO2>50 mmHg) associated with either snoring, flattening of the inspiratory nasal pressure waveform, or paradoxical thoracoabdominal motion [30]. There remains a lack of research to understand the risks and benefits of treating this isolated condition in children [31].
OBSTRUCTIVE SLEEP APNEA AND OBSTRUCTIVE HYPOVENTILATION — Sleep in children with sleep-related breathing disorders is different from sleep in normal children. For children with sleep-related breathing disorders, the increase in upper airway resistance during sleep is exaggerated and can lead to markedly increased work of breathing with snoring, obstructive sleep apnea (OSA), and/or obstructive hypoventilation (OHV), resulting in sleep disruption, hypoxia, and hypercarbia.
Sleep-related breathing disorders in children ranges on a spectrum from snoring to obstructive hypoventilation to complete obstructive apnea. The precise point along this spectrum that is defined as abnormal is subject to some controversy. There is a growing body of literature describing the physiologic consequences of sleep-related breathing disorders in a child, which include impaired growth, systemic or pulmonary hypertension, and myocardial remodeling. In addition, there appear to be associations between OSA and neurocognitive and behavioral problems, including attention deficit disorder and poor school performance [32]. (See "Evaluation of suspected obstructive sleep apnea in children", section on 'Screening'.)
OSA and OHV are present only in the sleeping state. Typically, normal children have no obstructive apneas or hypopneas during sleep. In adults, up to five apneas or hypopneas per hour may be normal (ie, an apnea/hypopnea index of less than five per hour). (See "Evaluation of suspected obstructive sleep apnea in children", section on 'Respiratory events'.)
Airway collapse — OSA or OHV is caused by complete or partial collapse of one or multiple segment(s) of the extrathoracic airway during sleep. This is the result of the cumulative effect of two factors, the relative contribution of which varies among individuals (see 'Increased upper airway resistance' above). It is important to be aware that the pathophysiology is multifactorial in pediatric OSA, where several contributing factors are normally present in the same patient [31]:
●Prenatal:
•An anatomically small upper airway
•Micrognathia, macroglossia, and midface hypoplasia
●Postnatal:
•Adenotonsillar hypertrophy
•Obesity
•Substrate deposition (eg, mucopolysaccharidoses)
•Local upper airway inflammation (eg, asthma, allergic rhinitis)
•Neurologic dysfunction of reflexes and/or muscle recruitment (eg, cerebral palsy, neuromuscular diseases)
The upper airway of children with OSA/OHV tends to be smaller than that of normal controls. This has been demonstrated by magnetic resonance imaging (MRI) [33-35], pharyngometry (image 2 and figure 3A-B) [36], and drug-induced sleep endoscopy (DISE). Dynamic MRI studies of the upper airway during tidal breathing under light sedation have demonstrated that the cross-sectional area of the upper airways of children with OSA are significantly smaller at all levels, from the epiglottis inferiorly to the nasopharynx superiorly, compared with normal controls; these differences are also seen dynamically when the inspiration of a normal control is compared with that of a child with OSA (image 3) [35]. Note that the airway of the normal control is:
●Larger at all pharyngeal levels
●The lateral dimension is consistently larger than the AP dimension
●There is very little change in the size and shape of the airway between inspiration and expiration
In contrast, in children with OSA the airway is:
●Smaller at all levels
●The AP dimension is consistently larger than the lateral dimension
●There is a substantial change in the size of the airway between inspiration and expiration, which is most apparent in the nasopharynx
Although children with OSA/OHV often have anatomically smaller upper airways compared with the general population, they do not usually exhibit any upper airway obstruction during wakefulness, because of neuromuscular compensation mediated by the pharyngeal dilators, particularly the genioglossus during wakefulness. However, upper airway obstruction occurs if this compensatory activation is eliminated, as occurs during sleep or during anesthesia with muscular paralysis [28].
Patterns of OSA/OHV in children — Sleep-related breathing disorders in children are most often characterized by prolonged obstructive hypoventilation during sleep, rather than by discrete obstructive apneas [13,37] (see 'Balance of forces model of upper airway obstruction' above). Sleep architecture often is preserved; there may be little sleep fragmentation and sleep stage distribution may appear normal. The polysomnogram often displays phasic augmentation of chin and intercostal electromyographic (EMG) activity during non-rapid eye movement (NREM) sleep. Paradoxical chest and abdominal movements suggest an obstructive breathing pattern in older children. They are seen during rapid eye movement (REM) sleep in normal children up until 31 months of age. By adolescence, paradoxical chest wall movement is not seen in normal subjects [29].
The hypoventilation typically worsens during REM sleep because lung volumes are lower, intercostal muscles do not substantially contribute to inspiratory effort, and the pharyngeal dilators are less effective as compared with NREM sleep. This often leads to an overnight oximetry tracing in which:
●REM periods are often associated with hypoventilation and significant oxygen desaturations
●NREM stage N3 (slow-wave sleep) is relatively protected without desaturations
●NREM stage N2 shows modest desaturations
These clinical findings can be understood in terms of how a child compensates for increased resistive loads. At sleep onset, there is decreased tone of the pharyngeal dilators, leading to a decrease in size of the airway. This in turn causes an increase in upper airway resistance, resulting in a decrease in intraluminal pressures in the pharynx. The decreased airflow, increased negative pressure, and increased CO2 stimulate the pharyngeal mechanoreceptors to augment pharyngeal dilator contractions [13]. In a child without sleep-related breathing disorders, this response maintains airway patency.
In children with sleep-related breathing disorders, this response does not completely relieve the upper airway obstruction. In the mildest form of sleep-disordered breathing, a modest decrease in the size of the pharyngeal airway leads to turbulent airflow causing vibration of the soft palate and snoring. As the upper airway obstruction worsens, hypoventilation ensues, with a rise in PCO2 and/or a decrease in arterial oxygen saturation. This further stimulates the pharyngeal dilators and the respiratory pump muscles. In many children with OSA, this response usually is sufficient to maintain a partially open pharyngeal airway for long periods of sleep without experiencing discrete obstructive apneic events. By contrast, adults with OSA are more likely to have acute obstructive apneic events, leading to arousal, perhaps because the pharyngeal dilators are less effective and/or the pharynx is more collapsible as compared with children.
Arousal — Arousal is the ultimate defense against obstructive apnea since it leads to a change from the sleeping to the waking state, which in turn results in the opening of the pharyngeal airway and relief of the obstruction. Children use this strategy much less often than adults. Several studies have demonstrated that the majority of obstructive apneas in children during both REM and NREM sleep are terminated without a cortical EEG arousal [37,38]. However, many of these events are associated with a subcortical arousal as manifest by a movement and a change in the pulse transit time [39]. The significance of these subcortical arousals is not known.
PREDISPOSING FACTORS — Sleep-disordered breathing in children has been associated with a variety of factors, including craniofacial anatomy, adenotonsillar hypertrophy, obesity, upper airway inflammatory processes, environmental exposures, asthma, prematurity, and genetic variation. Each of these factors likely contributes to sleep-disordered breathing because of effects on the anatomy of the upper airway, intrinsic compliance of its walls, and/or its neuromuscular control.
Anatomic factors anywhere along the upper airway can decrease airway size or stability, and may therefore contribute to the development of obstructive sleep apnea (OSA)/obstructive hypoventilation (OHV) (table 2).
Enlarged tonsils and adenoids — The most common and often the only obvious factor limiting airway size and leading to OSA/OHV in children is enlarged tonsils (palatine and lingual) and adenoids. The smallest cross-sectional area of the pharyngeal airway in children is the retropalatal area, where the tonsils and adenoids overlap (figure 3A) [33,38]. However, adenotonsillar size alone cannot explain the presence of OSA/OHV, since the majority of children with grossly enlarged tonsils and adenoids do not have OSA/OHV and the tonsils of children with OSA/OHV are not larger than those of children without OSA/OHV [40]. Most studies of children with sleep-disordered breathing have shown only a modest positive correlation between adenotonsillar size and severity of OSA [41,42], and some have shown no correlation [43]. There is an important interaction between obesity and adenotonsillar hypertrophy, which are the two most common predisposing factors for OSA/OHV. In nonobese, otherwise healthy children, the success rate of adenotonsillectomy for OSA is approximately 80 percent [44]. These and other factors relevant to decisions about whether to perform adenotonsillectomy are discussed in a separate topic review. (See "Adenotonsillectomy for obstructive sleep apnea in children".)
Most children with OSA/OHV and adenotonsillar hypertrophy and no other contributing factors are cured after a tonsillectomy and adenoidectomy, as indicated by a postoperative apnea index <1. Overall, tonsillectomy is effective for control of OSA/OHV in 60 to 80 percent of children with significant tonsillar hypertrophy [45]. In those children not cured of their OSA/OHV by adenotonsillectomy, it is presumed that a substantial part of the OSA/OHV was caused by subtle craniofacial or neuromuscular factors or pharyngeal instability, not simply enlarged tonsils and adenoids [46]. This is most apparent in children with obesity, in whom a minority have complete resolution of OSA/OHV after adenotonsillectomy, although most experience improvement in symptoms. In other children, the OSA/OHV initially improves after adenotonsillectomy but later recurs due to adenoidal tissue regrowth or other factors such as lingual tonsillar hypertrophy, and may resolve after a second surgery. Failure to resolve OSA/OHV following adenotonsillectomy in some patients highlights the complex nature of the airway; such patients may need further assessment to determine level of obstruction, as it may be multifactorial [47]. (See "Adenotonsillectomy for obstructive sleep apnea in children", section on 'Success rates'.)
Obesity — Obesity is a common factor contributing to the OSA in adults, probably because it decreases the size and/or increases the collapsibility of the pharyngeal airway. Although obesity is not as common a cause of OSA/OHV in children as it is in adults, the prevalence of OSA/OHV in obese children is higher than in nonobese children, and this is particularly true for adolescents [48-52]. Because the prevalence and severity of obesity in children is increasing, obesity is likely to become an increasingly important cause of pediatric sleep-related breathing disorders in the future. In a population-based study, the risk of sleep-disordered breathing was increased four- to fivefold in children with obesity, which was defined in this case by a body mass index (BMI) >28 [53]. The risk of OSA increased by 12 percent for every 1 kg/m2 increase in BMI above the mean.
Obesity contributes to airway narrowing in several ways, including fatty infiltration of areas surrounding the airway, tongue, or fat pads lateral to the airway. In many cases, obesity and adenotonsillar hypertrophy combine to cause OSA in an individual patient, and children with obesity are more likely than lean patients to have residual OSA after adenotonsillectomy; up to 75 percent of patients with obesity who undergo adenotonsillectomy for OSA have residual OSA postoperatively [54]. Essentially no improvement is seen with adenotonsillectomy alone in patients with severe obesity (body mass index [BMI] Z-score >3) [55]. (See "Adenotonsillectomy for obstructive sleep apnea in children", section on 'Risk factors for persistent disease'.)
Inflammation — Both obesity and OSA are inflammatory conditions with additive effects on comorbidities that are mediated by inflammatory processes [32]. These comorbidities include atherogenesis/cardiovascular disease and associated lipid abnormalities, insulin resistance, and fatty liver disease [56-59]. These comorbidities seem to be mediated at least in part by increased production of leptin, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha), which are independently induced by obesity and OSA [32]. Among children with asthma, those who are obese have a fourfold increase in their risk of OSA [53]. Moreover, children with poorly-controlled asthma are much more likely to have OSA than those with well-controlled asthma. Treatment of upper airway inflammation with montelukast and nasal corticosteroids improves OSA [60]. All of these lines of evidence suggest a causal relationship between upper airway inflammation and sleep-disordered breathing, although the precise mechanism has not been identified. (See "Management of obstructive sleep apnea in children", section on 'Adjunct therapies'.)
Environmental factors — Cigarette smoke exposure has been identified as a risk factor for children in the development of sleep-disordered breathing, after controlling for other relevant factors [43]. The mechanism for the association is not fully understood but may be related to irritation or inflammation of the mucosa in the upper airway. Exposure to secondhand smoke remains an important problem. In the United States in 2011 to 2012, 40 percent of 3- to 11-year-old children overall, and 70 percent of Black children, were regularly exposed to secondhand smoke [61]. Similarly, exposure to air pollutants have been associated with sleep-disordered breathing [62,63]. (See "Secondhand smoke exposure: Effects in children".)
Mucopolysaccharidoses — Children with any of the mucopolysaccharidoses and mucolipidoses who have significant infiltration and accumulation of macromolecules in the tissues of their upper airway are more likely to have OSA/OHV [64]. These children are also more likely to have respiratory complications in the perioperative period and to have persistent OSA after adenotonsillectomy. (See "Mucopolysaccharidoses: Clinical features and diagnosis" and "Adenotonsillectomy for obstructive sleep apnea in children", section on 'Risk factors for persistent disease'.)
Craniofacial anomalies — In children with craniofacial anomalies, the characteristics most commonly associated with OSA/OHV are:
●Midfacial hypoplasia
●Retro/micrognathia
●An acutely angled skull base
●Narrow maxillary arch
●Nasoseptal obstruction
●Macroglossia
●Other soft tissue abnormalities
These anomalies lead to a decrease in the size of the nasopharynx, oropharynx, or hypopharynx, and can predispose the pharynx to collapse during sleep [65]. In some syndromes associated with sleep-related breathing disorders, the obstruction can be attributed to specific anatomical sites (table 3). Management of these patients may include diagnostic procedures to determine the anatomic site(s) of obstruction, and adjunctive surgical procedures to relieve the obstruction. Drug-induced sleep endoscopy (DISE) is a diagnostic tool to identify the site or sites of upper airway collapse that leads to OSA; the technique utilizes an anesthetic induction to simulate the upper airway relaxation that occurs during natural sleep. The site of obstruction determined on DISE can then be appropriately addressed surgically [66,67]. (See "Adenotonsillectomy for obstructive sleep apnea in children", section on 'Management of patients with residual OSA after adenotonsillectomy'.)
The role of subtle craniofacial factors in the absence of obvious anomalies is less clear [68]. In one study, the mandibular dimensions of children with a sleep-related breathing disorder but without obvious craniofacial abnormalities were no different than in children without a sleep-related breathing disorder [69]. However, a narrow maxillary arch and dental malocclusion (crossbite) have been associated with OSA in children [70], and orthodontic correction with rapid maxillary expansion can result in improvement of the sleep-related breathing disorder. (See "Management of obstructive sleep apnea in children", section on 'Orthodontics'.)
Neuromuscular factors — Neuromuscular factors affect the size, shape, compliance, and coordination of the pharyngeal airway, which can have an important effect on the development of sleep-related breathing disorders. Neuromuscular control of the upper airway is mediated by local mechanoreceptor reflexes and by central drive, coordinated through the respiratory control center in the medulla.
The most common clinical neuromuscular problems contributing to OSA/OHV are alterations in muscle tone (either hypotonia or hypertonia). However, the precise mechanism by which changes in tone affect the pharyngeal airway has not yet been elucidated. Chronic changes in muscle tone may have prominent effects on growth and development of the facial skeleton, and thereby affect upper airway patency.
Impairment of the coordination and synchronization of the respiratory pump muscles with the pharyngeal dilator muscles may also be a cause of OSA/OHV in children. This occurs during hiccups [71] and when children with congenital alveolar hypoventilation are provided with diaphragmatic pacers during sleep [72]. In both cases, the inspiratory pump functions independently of the pharyngeal dilators, resulting in upper airway obstruction. This illustrates the importance of synchronization of the pharyngeal dilators with the muscles of inspiration.
Dysfunction of the central nervous system may cause central sleep apnea (CSA) when the respiratory control center of the medulla is affected or OSA/OHV if the central nervous system dysfunction leads to neuromuscular dysfunction. As examples, either CSA or OSA may result from compression of the brainstem as seen in children with Chiari malformation [73,74] or dysfunction of the brainstem as seen in children with bulbar palsy or brainstem tumors [75]. The airway obstruction may be caused by peripheral neuromuscular dysfunction or vocal cord paralysis. (See "Congenital central hypoventilation syndrome and other causes of sleep-related hypoventilation in children", section on 'Other causes of central sleep apnea'.)
Combined anatomic and neuromuscular factors — Anatomic and neuromuscular factors often combine to cause a sleep-related breathing disorder, but the relative contribution of each can be hard to predict. Both factors are often seen together in children with craniofacial syndromes, making them at especially high risk for the development of a sleep-related breathing disorder.
The most common example is found in children with trisomy 21 (Down syndrome), which is characterized by midfacial hypoplasia, a high-arched palate, macroglossia, cranial base anomalies, and hypotonia. In one report, 81 percent of children with trisomy 21 had OSA or OHV; this study used a daytime nap study, which may have underestimated the true incidence of OSA/OHV [76] (see "Down syndrome: Clinical features and diagnosis"). For this reason, the American Academy of Pediatrics (AAP) has recommended that all children with trisomy 21 have a polysomnogram before four years of age, to evaluate for sleep-disordered breathing [77].
Drugs — In human and/or animal studies, alcohol, chloral hydrate, benzodiazepines, and general anesthetics have all been shown to selectively decrease the activity of the pharyngeal dilators to a greater extent than they affect the diaphragm. This imbalance could lead to an increased tendency of the upper airway to collapse during inspiration. Case reports describe individuals who suffered acute and sometimes fatal worsening of their OSA after treatment with these agents.
Narcotic analgesics are powerful respiratory depressants, leading to a marked decrease in hypoxic and hypercarbic ventilatory drive and increased arousal threshold, making it harder for children to arouse after an obstructive apnea. Together, these factors can be a dangerous combination in a child with a sleep-related breathing disorder.
Genetics — The role of genetics in the development of OSA/OHV in children is intriguing but not well understood. Familial aggregation of OSA has been noted in studies of adults and children, in both obese and nonobese populations. In African American children, sleep-disordered breathing is 3.5 times more likely than in White children, after controlling for other factors such as obesity and asthma [43,53]. The mechanism for this association is not understood. Obesity, craniofacial morphology, and ventilatory control all are highly heritable traits and are important in the pathophysiology of sleep-related breathing disorders. However, the genetic determinants of sleep-related breathing disorders have not yet been delineated in either adults or children. This is an area of active research, and it is likely the genetic factors for OSA will be much better characterized in the next few years.
SUMMARY
●Definitions – An obstructive sleep-related breathing disorder (or sleep-disordered breathing) is characterized by discrete apneas, hypopneas, and respiratory effort-related arousals or by more continuous reductions in gas exchange (hypoventilation). These conditions are caused by upper airway obstruction that occurs exclusively during sleep. Sleep-related breathing disorders in children occur along a spectrum of severity. (See 'Introduction' above.)
●Impact of sleep stage – Sleep is categorized into rapid eye movement (REM) and non-REM sleep (NREM). REM sleep is associated with low muscle tone and in most pediatric patients, increased vulnerability to obstructive sleep apnea (OSA). (See 'Sleep stages' above.)
●Increased upper airway resistance – For children with a sleep-related breathing disorder, the increase in upper airway resistance during sleep is exaggerated. This can lead to markedly increased work of breathing, snoring, OSA, and/or obstructive hypoventilation (OHV). Immediate consequences can include sleep disruption, hypoxia, and hypercarbia. (See 'Balance of forces model of upper airway obstruction' above and 'Obstructive sleep apnea and obstructive hypoventilation' above.)
●Decreased upper airway size - The various factors that can limit the size of the upper airway are cumulative. In many children with sleep-related breathing disorders, multiple factors contribute to the problem and must be addressed for successful treatment. (See 'Predisposing factors' above.)
•Enlarged tonsils – The most common factor that restricts airway size and contributes to OSA/OHV in children is enlarged tonsils (palatine and lingual) and adenoids. However, the majority of children with grossly enlarged tonsils and adenoids do not have OSA/OHV, making it clear that adenotonsillar size alone cannot explain the presence of a sleep-related breathing disorder in children. (See 'Enlarged tonsils and adenoids' above.)
•Obesity – Obesity provides an increasingly common contribution to OSA/OHV in adults and children, probably because obesity decreases the size and/or increases the collapsibility of the pharyngeal airway. In many cases, both obesity and adenotonsillar hypertrophy together contribute to OSA in an individual patient. (See 'Obesity' above.)
●Other factors – Other factors contributing to OSA/OHV in some individuals include mucopolysaccharidoses, craniofacial anomalies, neuromuscular factors, drugs that relax pharyngeal dilators or decrease respiratory drive, inflammatory processes, environmental exposures, or genetic factors. Often, the causes of OSA/OHV are multifactorial. (See 'Predisposing factors' above and 'Genetics' above.)
