eMedicine Specialties > Pediatrics: General Medicine > Pulmonology

Obstructive Sleep Apnea Syndrome

Author: Timothy D Murphy, MD, Assistant Professor, Department of Pediatrics, Division of Pulmonology, University of Pittsburgh; Consulting Staff, Division of Pulmonology, Children's Hospital of Pittsburgh
Coauthor(s): Andrew J Lipton, MD, MPH and TM, Staff Pediatric Pulmonologist, Assistant Professor of Pediatrics, Department of Pediatrics, Walter Reed Army Medical Center; David Gozal, MD, Vice-Chairman of Research and Director, Kosair Children's Hospital Comprehensive Sleep Medicine Center, Professor, Department of Pediatrics, University of Louisville
Contributor Information and Disclosures

Updated: Feb 27, 2009

Introduction

Background

Obstructive sleep apnea (OSA) syndrome was described more than a century ago; however, obstructive sleep apnea in children was first described in the 1970s. Obstructive sleep apnea is a common but underdiagnosed condition in children that may lead to substantial morbidity if left untreated. The mechanisms of obstruction, adverse effects of obstructive sleep apnea, diagnostic criteria, and recommended treatment options are different in children than in adults. Important recent advances in the understanding of the underlying pathophysiological mechanisms of obstructive sleep apnea in children have been coupled with improved approaches to the diagnosis and management of obstructive sleep apnea.

Pathophysiology

Snoring and obstructive apnea are symptoms of increased upper airway resistance. The ability to maintain upper airway patency during the normal respiratory cycle is the result of a delicate equilibrium between the forces that promote airway closure and dilation. This "balance of forces" concept was initially proposed by 2 independent groups and reflects the current line of thought regarding the underlying pathophysiological mechanisms that result in the clinical spectrum of obstructive apnea. The 4 major predisposing factors for upper airway obstruction include anatomic narrowing, abnormal mechanical linkage between airway dilating muscles and airway walls, muscle weakness, and abnormal neural regulation.

Anatomic narrowing

At any point in life, a smaller cross-sectional area of the upper airway is associated with decreased ability to maintain upper airway patency. In adults, the upper airway behaves as predicted by the Starling resistor model. According to this model, under conditions of flow limitation, maximal inspiratory flow is determined by the pressure changes upstream (nasal) to a collapsible site of the upper airway, and flow is independent of downstream (tracheal) pressure generated by the diaphragm. Pressures at which the airway collapses have been termed critical closing pressures, or P_crit. In other words, in the presence of a collapsible segment of the upper airway, such as the pharyngeal introitus, the overall resistance to airflow proximal to that segment is the major factor responsible for occlusion of the collapsible segment. This model explains why, for example, snoring and obstructive apnea worsen during a common cold (increased nasal-upstream resistance).

The validity of this model was also confirmed in children, and, interestingly, the collapsibility of the upper airway in children was reduced when compared with that of adults. As predicted by the Starling resistor model, the collapsible segment of the upper airway in children displayed less negative (higher and, therefore, more collapsible) pressures in children with obstructive sleep apnea. Components that affect the upstream segment pressures or increase P_crit are of major consequence to the ability to maintain airway patency. For example, a viral cold or allergic rhinitis that induces increased secretion in the nasal passages and mucosal swelling is associated with increased nasal resistance to airflow. Not surprisingly, the magnitude of snoring and the severity of obstructive apnea are increased during periods in which the upstream segment pressure has been adversely affected.

The contribution of the various anatomical nasopharyngeal structures to P_crit and the interactions between these structures that lead to upper airway patency or obstruction during sleep are of obvious importance in increasing the understanding of the pathophysiology of obstructive sleep apnea in children. For most children, enlargement of the tonsils and/or adenoid is the proximate cause for the development of obstructive sleep apnea.

The static pressure and/or area relationships of the passive pharynx were endoscopically measured in 14 children with obstructive sleep apnea and in 13 healthy children under general anesthesia with complete paralysis.¹ Children with obstructive sleep apnea closed their airways at the level of enlarged adenoids and tonsils at low positive pressures, whereas healthy children required subatmospheric pressures to induce upper airway closure. The cross-sectional area of the narrowest segment was significantly smaller in children with obstructive sleep apnea and particularly involved the retropalatal and retroglossal segments. Thus, both congenital and acquired anatomic factors clearly play a significant role in the pathogenesis of pediatric obstructive sleep apnea.

Abnormal mechanical linkage between airway dilating muscles and airway walls

Malposition or malinsertion of specific dilating muscles is likely to have major consequences on the mechanical dilating efficiency. Therefore, even if a major weakness is not present, the mechanical disadvantage imposed by muscle shortening or by displacement of the muscle insertion on the pharyngeal wall undoubtedly results in diminished ability to stiffen the airway, thus leading to increased collapsibility or elevation of P_crit.

Control of the upper airway size and stiffness depends on the relative and rhythmic contraction of a host of paired muscles, which include the palatal, pterygoid, tensor palatini, genioglossus, geniohyoid, and sternohyoid muscles. These muscles tend to promote a patent pharyngeal lumen and receive phasic activation in synchrony with phrenic nerve activation. Upon contraction, these muscles promote motion of soft palate, mandible, tongue, and hyoid bone. Although the coordinated action of these muscles during the respiratory cycle has yet to be deciphered, a reasonable generalization is that inspiratory muscle output stiffens the pharynx and related structures and enlarges the lumen.

The optimal activity of these muscles depends on their anatomic arrangement; for example, airway patency is compromised during increased neck flexion by changing the points of attachment of muscles acting on the hyoid bone, such that the resulting vector of their forces may be nullified. The activity of pharyngeal muscles greatly depends on various factors within the CNS and, more particularly, on the brainstem respiratory network. Wakefulness conveys a supervisory function that ensures airway patency, and sedative agents, which compromise genioglossal muscle activity, may result in significant upper airway compromise.

Mechanoreceptor-mediated and chemoreceptor-mediated genioglossal activity is critical for maintenance of upper airway patency in healthy and micrognathic infants. Changes in genioglossal activity during transitions, from oral to nasal breathing and relative to P_crit, suggest that genioglossus activation is critical for airway patency in micrognathic infants.

Muscle weakness

Little evidence suggests that intrinsic muscle weakness is a major contributor to upper airway dysfunction in conditions other than those associated with neuromuscular disorders. However, in neuromuscular disorders, upper airway obstruction is frequently observed during sleep, further reinforcing the validity of the balance-of-pressures concept.

Abnormal neural regulation

Abnormal respiratory control does not appear to play a significant role in upper airway obstruction during sleep in children with obstructive sleep apnea. The ventilatory response to hyperoxic hypercapnic challenge in children and adolescents with obstructive sleep apnea was similar to that measured in age-matched and sex-matched control children.² Similarly, no differences were found in the ventilatory response to isocapnic hypoxia. Blunting in central chemosensitivity was reported in some children with obstructive sleep apnea undergoing surgery; however, despite such reports, central chemosensitivity during sleep was similar in children with obstructive sleep apnea and matched controls. However, arousal to hypercapnia was blunted, suggesting that subtle alterations in the central chemosensitive arousal network may have occurred in these children.

These subtle changes have been further substantiated by examining the ventilatory response to repeated hypercapnia, whereby reciprocal changes in respiratory frequency and tidal volume occur. In addition, children with obstructive sleep apnea demonstrate impaired arousal responses to inspiratory loads during rapid eye movement (REM) and non-REM sleep compared with control children. Neural responses to hypoxia and hypercarbia have not been well studied in children with obstructive sleep apnea and underlying syndromes.

In addition to the aforementioned considerations, diminished laryngeal reflexes to mechanoreceptor and chemoreceptor stimulation, with reduced afferent inputs into central neural regions underlying inspiratory inputs, can be present. For example, chemoreceptor stimuli, such as increased PaCO₂ or decreased PaO₂, stimulate the airway, dilating muscles in a preferential mode (ie, upper airway musculature is more stimulated than the diaphragm).

This preferential recruitment tends to correct an imbalance of forces acting on the airway and, therefore, maintains airway patency. Similarly, stimuli that result from suction pressures in the nose, pharynx, or larynx rapidly stimulate the activity of upper airway dilators. This effect is also preferential to the upper airway, causing some degree of diaphragmatic inhibition and, thus, compensating for increases in upstream resistance. The function of these upper airway receptors in children with adenotonsillar hypertrophy with and without obstructive sleep apnea is not known.

Summary

Several potential mechanisms in the maintenance of upper airway patency during sleep and wakefulness have been identified. Each of these mechanisms, or a combination thereof, plays a role in the causation of respiratory compromise in the healthy child or in children with clinical problems that predispose to obstructive sleep apnea. A systematic approach to identification and modification of these mechanisms may lead to improvement in therapeutic approaches and avoidance of unnecessary morbidity in these patients. For many pediatric patients, the cause of the obstructive sleep apnea is enlargement of the tonsils and/or adenoid; and when other resistors to airflow are present, removal of the tonsils and adenoid may still prove adequate to relieve the obstruction.

Frequency

United States

Precise prevalence figures for obstructive sleep apnea in children are currently unavailable. Estimates from limited field studies suggest that as many as 2% of all children may be affected; however, the prevalence of snoring in the general pediatric population is much higher and has been estimated at 8-27%.

Mortality/Morbidity

Despite the misleadingly benign clinical presentation, the pathological consequences of obstructive sleep apnea in children may be severe, and some pathological consequences are still being uncovered. These morbidities can be divided as the corollary of the 4 immediate consequences of upper airway obstruction during sleep, which include sleep fragmentation, increased work of breathing, alveolar hypoventilation, and intermittent hypoxemia. Other consequences are related to more than one factor.

• Sleep fragmentation
  • Experimental fragmentation of the sleep of healthy adults may be achieved with auditory stimuli–inducing arousals. Subjects who were awakened at various intervals during the night demonstrated performance decrements and increased sleepiness on the following day.³ This was also true when EEG arousals, rather than behavioral arousals, were induced.
  • The physiological and behavioral effects of partial and total sleep loss due to obstructive sleep apnea in adults have been extensively investigated. Daytime tiredness or fatigue is a common symptom, although sleepiness, which is a subjective notion, may not be directly reported. Significant deterioration in functions that require concentration or dexterity, as well as automatic behavior with retrograde amnesia, disorientation, and morning confusion, have all been reported in patients with sleep fragmentation and has led to the term sleep drunkenness. In addition, personality changes and abnormal behavioral outbursts follow sleep fragmentation. Aggressiveness, irritability, anxiety attacks, and depression may occur.
  • Sleep fragmentation in adults affects neuropsychological and cognitive performance. No evidence suggests such impairments are absent in children, and such deleterious effects may be worse, given that the child's brain is undergoing active developmental changes. Reports of decreased intellectual function in children with tonsillar and adenoidal hypertrophy date from 1889 when Hill reported on "some causes of backwardness and stupidity in children." Schooling problems have been repeatedly reported in case studies of children with obstructive sleep apnea and, in fact, may underlie more extensive behavioral disturbances, such as restlessness, aggressive behavior, excessive daytime sleepiness, and poor test performances.
  • The neurocognitive and behavioral consequences of disrupted sleep architecture and hypoxemia caused by sleep-disordered breathing in children with obstructive sleep apnea have only recently been defined by appropriate scientific methodology in the pediatric population. However, some studies have documented that children with sleep disorders tend to have behavioral problems similar to those observed in children with attention deficit hyperactivity disorder (ADHD). A survey study of 782 children recently documented daytime sleepiness, hyperactivity, and aggressive behavior in children who snore.⁴ Inverse correlations between memory and learning performance and the severity of obstructive sleep apnea were also found, and other studies have clearly demonstrated significant improvements in school performance after treatment of obstructive sleep apnea.
  • In a study of 19 preschool-aged children with obstructive sleep apnea, prior to tonsillectomy and adenoidectomy (T&A), cognitive scores were significantly lower in children with obstructive sleep apnea versus control subjects.⁵ Following T&A, the scores of the children with obstructive sleep apnea improved compared with preoperative scores and did not differ from those of the matched controls. This underscores the importance of diagnosis and treatment, insofar as the cognitive impairments of children, unlike adults, take place in the developing brain.
  • Sleep deprivation, sleep disruption, and intermittent hypoxia independently may be sufficient to cause daytime effects in vulnerable children. Preliminary evidence suggests that, if left untreated, sleep-disordered breathing may impose long-term decrements in academic performance and the combination of 2 or more of these factors can result in particularly impaired daytime functioning.
  • Although empirical awareness of the deleterious consequences of obstructive sleep apnea on neurocognitive function and behavior is well established, the scientific foundation for the causal mechanisms underlying such detrimental effect on intellectual function has yet to be determined. This endeavor is currently a major focus of research programs.
• Increased work of breathing
  • A major cardiovascular consequence of obstructive sleep apnea in adults is arterial hypertension. Although the pathophysiological mechanisms of elevation in arterial tension are still under debate, intermittent arousal, hypoxemia, and increases in cardiac afterload during the obstructive apneic event apparently lead to enhanced sympathoadrenal discharge and heightened sympathetic tone, even during waking hours. Significant alterations in autonomic nervous system tone have been documented in children with obstructive sleep apnea, and modest diurnal elevations in arterial blood pressure have also been reported.
  • Sleep-disordered breathing is associated with higher systolic blood pressures in children aged 5-12 years and supports the use of an apnea hypopnea index (AHI) threshold of 5 for initiating treatment.⁶ The long-term effects of this process in childhood and the effect on adult health are unknown.
  • A prominent clinical manifestation of increased work of breathing in children with obstructive sleep apnea is failure to thrive (FTT). Indeed, reports from the early 1980s found more than a 50% prevalence of FTT in patients with pediatric obstructive sleep apnea, and significant catch-up growth patterns have recently been reported after T&A, even in children with obesity and obstructive sleep apnea. The causes of poor growth include anorexia and dysphagia due to tonsillar and adenoid hypertrophy, diminished or altered patterns of nocturnal growth hormone secretion, hypoxemia, acidosis, and increased work of breathing during sleep.
  • In one study, a substantial reduction in resting energy expenditure was reported after adenotonsillectomy in children with obstructive sleep apnea and FTT with concomitant gains in body weight.⁷ Another study demonstrated significant recovery in the insulin growth factor 1 axis.⁸ These findings suggest that an important factor that mediates FTT in pediatric obstructive sleep apnea involves the combination of increased energy expenditure caused by increased respiratory effort and disruption of the pathways of the growth hormone somatomedin.
• Alveolar hypoventilation
  • Intermittent hypercapnia frequently occurs among patients with various respiratory disorders, becomes more prominent or sustained during sleep, and is minimal or absent during wakefulness.
  • Children with obstructive sleep apnea who snore exhibit classic intermittent alveolar hypoventilation, which is elicited by increased upper airway resistance, concurrent with diminished or insufficient compensatory mechanisms developing during sleep.
  • In adults with obstructive sleep apnea, blunted ventilatory drive to hypercapnia during wakefulness develops and may potentially contribute to the pathophysiology of upper airway obstruction.
  • In contrast, waking and sleeping ventilatory responses to hypercapnia in children with obstructive sleep apnea are similar to those measured in healthy children. However, arousal responses are attenuated during sleep, suggesting that long-standing interactions between sleep and upper airway resistance in these children primarily affect arousal mechanisms during sleep. Another potential contribution of alveolar hypoventilation and hypercapnia during sleep may relate to exacerbation of the effect of intermittent hypoxia on the vasomotor tone of the pulmonary circulation.
• Intermittent hypoxemia
  • A serious consequence of intermittent hypoxia is elevation of pulmonary artery pressure due to pulmonary vasoconstriction, such that chronic intermittent nocturnal hypoxemia leads to development of pulmonary hypertension and cor pulmonale. In 27 pediatric patients with moderate-to-severe obstructive sleep apnea, radionuclide assessment of right ventricular function revealed reduced ejection fraction in 37% of these children and wall motion abnormality in 45%.⁹ Another potentially serious consequence of intermittent hypoxia may involve its long-term deleterious effects on neuronal and intellectual function. Indeed, in a study on an animal model developed in the coauthor's laboratory, intermittent hypoxia was associated with significant increases in neuronal apoptosis and reduced functionality within brain regions that mediate learning and memory.
  • Because the peak age for obstructive sleep apnea coincides with that of a critical period for brain development, delayed diagnosis and treatment of obstructive sleep apnea possibly imposes a greater burden on vulnerable brain structures and ultimately hampers the overall neurocognitive potential of children with obstructive sleep apnea.
  • Neurobehavioral disturbances and diminished learning capabilities, stunted growth, altered respiratory load response patterns, and pulmonary hypertension are major consequences of obstructive sleep apnea in childhood. Early diagnosis and prevention of such morbidities are fundamental aspects of adequate pediatric care in the community.
• Inflammation
  • The association of inflammation with obstructive sleep apnea in relation to this schema is uncertain.
  • Markers of systemic inflammation such as interleukin (IL)-6¹⁰ and C-reactive protein¹¹ are elevated in obstructive sleep apnea and decrease following T&A, suggesting that the elevation was due to the obstructive sleep apnea.
  • An increased inflammatory response may be associated with infectious diseases associated with tonsillar and adenoidal hypertrophy; thus, the issue of cause and effect can be difficult to ascertain.

Race

The current evidence assigns a particularly higher risk for obstructive sleep apnea among black children compared with white children. However, the high frequency of obstructive sleep apnea among adult Asian populations indicates that the anthropometric characteristics of the craniofacial structures in this racial group also predispose for higher obstructive sleep apnea rates in children. The frequency of obstructive sleep apnea in Hispanic children is equal to that of white children.

Sex

The prevalence of snoring and obstructive sleep apnea among prepubertal children does not differ based on sex. In older adolescents, a male preponderance emerges that essentially reflects the typical male predominance observed in the adult population.

Age

The peak prevalence is in children aged 2-8 years (coinciding with adenotonsillar lymphatic tissue growth). Preterm babies are at risk for more obstructive events while supine but are still at a lower risk of death from sudden infant death syndrome.

Clinical

History

The clinical presentation of a child with obstructive sleep apnea (OSA) syndrome is nonspecific and requires increased awareness by the primary care physician. Indeed, the medical history is usually normal, unless the pathophysiology of sleep-associated airway obstruction is related to one of the various conditions delineated in Causes.

Clinical findings of tonsillar enlargement or obesity should prompt questioning regarding snoring. Family history of snoring, allergies, and exposure to environmental tobacco smoke are all strongly related to snoring. In the otherwise healthy child, parents principally report snoring during sleep. History of loud snoring 3 or more nights per week should increase suspicion of obstructive sleep apnea.

Parents occasionally comment on breathing difficulties during sleep (eg, gasps or heroic snorts), unusual sleeping positions, morning headaches, daytime fatigue, irritability, poor growth and weight gain, and behavioral problems. Nevertheless, even in cases in which a sleep specialist conducts the diagnostic interview, the accuracy of obstructive sleep apnea prediction is poor and does not exceed a sensitivity and specificity of 50-60%, particularly in distinguishing obstructive sleep apnea from benign snoring.

Physical

Physical examination findings are generally normal while awake, with the exception of findings related to the predisposing conditions noted (see Causes). Plot a growth chart, including a height-adjusted, weight-adjusted, and age-adjusted body mass index in order to identify obesity or failure to thrive (FTT). Carefully examine the nasal passages for mucosal swelling, cobblestone pattern of the mucosa, polyps, and reduced nasal airflow. Carefully evaluate the size and position of tonsils and uvula, particularly noting hypertrophy or malformation. Unfortunately, although tonsillar hypertrophy may contribute to the severity of obstructive sleep apnea, the data available to date have not established a clear relationship between tonsillar size and frequency or severity of apneic events. Furthermore, although more prevalent in patients with obstructive sleep apnea, tonsillar hypertrophy is also common in healthy children without obstructive sleep apnea, with a prevalence as high as57%.

Document the width and height of the hard palate, as well as the overall appearance of the soft palate, looking for evidence of cleft or pharyngeal narrowing or compression.

Although not extensively evaluated in children, the Mallampati classification may help quantify the degree of oropharyngeal anatomical obstruction. This classification is based on the structures visualized with maximal mouth opening and the tongue extended. The classes are determined by the visible structures. In class I, the soft palate, fauces, uvula, and pillars are visible. In class II, the soft palate, fauces, and a portion of uvula are visible. In class III, the soft palate and base of uvula are visible. In class IV, only the hard palate is visible. The higher the Mallampati classification, the greater the likelihood of oropharyngeal obstruction, and the greater the risk of persistent obstruction following tonsillectomy and adenoidectomy (T&A).¹²

The relative position of the chin with respect to the maxilla is helpful in the identification of mild micrognathia or retrognathia.

Cardiac examination may reveal the presence of a prominent pulmonic second heart sound suggestive of pulmonary hypertension.

No other distinctive findings are usually present unless one of the medical conditions is present.

Causes

Medical conditions associated with obstructive sleep apnea in children include the following:

• Tonsillar and adenoid hypertrophy
• Achondroplasia, Crouzon syndrome, and Apert syndrome
• Neuromuscular disorders (eg, Duchenne muscular dystrophy, spinal muscular atrophy)
• Myelomeningocele
• Obesity
• Pierre Robin sequence
• Cerebral palsy
• Down syndrome
• Sickle cell diseases
• Choanal stenosis
• Hypothyroidism
• Klippel-Feil syndrome and Hallermann-Streiff syndrome
• Mucopolysaccharidosis
• Osteopetrosis
• Oropharyngeal papillomatosis
• Beckwith-Wiedemann syndrome
• Pfeiffer syndrome, Prader-Willi syndrome, and Treacher-Collins syndrome

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