Candidates for future OSA?

Obstructive sleep apnea (OSA) syndrome was described more than a century ago as being a result of increased upper airway resistance. First described in children in the 1970s, pediatric OSA is common but is often undiagnosed. Recent research on OSA has improved understanding of the pathophysiology of the syndrome, and an increasing awareness is now leading to improved diagnosis and management of OSA in children.

The primary cause of OSA in children is upper airway narrowing, and the majority of pediatric OSA is related to tonsillar and adenoidal hypertrophy. Although implicated in OSA, tonsillar and adenoidal hypertrophy, when present, is not thought to be the sole cause of OSA. Rather, underlying abnormalities in structure or function of the airway predispose to OSA, and tonsillar and adenoidal hypertrophy tips the scales toward obstruction.1 Relatively fixed resistance to airflow may be seen with some anatomic conditions such as choanal atresia, mid-face hypoplasia, or micrognathia. Variable or positional resistance to airflow is seen in conditions such as macroglossia, or laryngomalacia; simultaneous multiple conditions may form resistors in series. Coordinated efforts by the brain and the muscles of the upper airway are required to maintain patency during inspiration; any abnormality in this neuromechanical chain can lead to upper airway collapse and obstruction. Thus, for the upper airway musculature, any changes in positioning (as is seen in micrognathic infants), force generation (ie, myopathy), or coordinated CNS output (ie, brain damage) may lead to increased collapsibility of the upper airway and OSA.

In otherwise healthy children, abnormal respiratory control does not appear to play a significant role in upper airway obstruction. Hypoxic and hypercapnic response is generally normal, despite reports of blunted central chemosensitivity and diminished arousal to hypercapnia in some children with OSA.2 Similarly, children with OSA demonstrate impaired arousal to inspiratory loading compared with control children, but the neurologic responses to hypoxia and hypercapnia have not been well studied in this population. The mechanics of chest-wall function are not usually abnormal; but in older children, an increasing effect on sleep from obesity is seen. Increases in airflow resistance due to increased soft tissue mass and altered mechanics are similar to those seen in obese adults. The mechanics of breathing in children become more adult-like between the ages of 12 and 15 years, and the diagnostic and therapeutic options in older children generally start to mirror those in adults.

Underdiagnosed

It is axiomatic in medicine that one will not make a diagnosis if one does not think of it. OSA is not difficult to diagnose, but children with OSA often go undiagnosed because it is never considered. Any diagnosis requires an awareness of risk factors and a search for symptoms. Historical findings of snoring, gasps, snorts, respiratory pauses, unusual sleeping positions, morning headaches, daytime fatigue or sleepiness, behavioral problems, or changes in growth are all suggestive of OSA. Physical exam findings of tonsillar enlargement or obesity or diagnosis of the predisposing conditions listed in the Table should prompt further evaluation.

Even when a pediatric sleep specialist performs the history and physical examination, predicting OSA is difficult. The diagnostic “gold standard” remains the overnight polysomnogram (PSG), but scheduling a study can be difficult, due to a general lack of availability of pediatric-capable laboratories. As many as 2% of children have significant OSA, while 8% to 27% have snoring, so refining diagnostic screening criteria to avoid over- or under-testing in the sleep lab is an important field of research.

There is a relationship of OSA to obesity, and the current epidemic of obesity in children is leading to increased OSA in older, obese adolescents. In this age group, a slight predominance in males is similar to that found in adults. Otherwise, prepubertal pediatric OSA peaks between 2 and 8 years of age (coincident with growth of adenotonsillar tissue) and is equally distributed between boys and girls. With the current epidemic of obesity in the United States now extending into the pediatric population, an increase in the incidence of OSA due to obesity in younger children may occur, too. African American and Asian American children appear to be at a higher risk for OSA than white or Hispanic children.

Obstruction of the airway during sleep has the immediate effects of sleep fragmentation, increased work of breathing, hypercapnia (hypoventilation), and hypoxemia. These physiologic responses have been better studied in adults than children, but research shows children have unique pathologic consequences, because the OSA occurs in the context of development.

Consequences of Sleep Fragmentation

In adults, sleep fragmentation leads to daytime fatigue, diminished neuropsychological and cognitive performance, and significant deterioration in functions that require dexterity or concentration. These studies have not been replicated in children, but as early as 1889, Hill reported “backwardness and stupidity” in children with tonsillar and adenoidal hypertrophy. Learning difficulties have been reported repeatedly in children with OSA.3,4 Some studies have shown a connection between the OSA and hyperactivity, aggressive behavior, poor memory, and impaired learning performance. In another study, children with OSA had lower cognitive scores than did controls, and tonsillectomy and adenoidectomy (T&A) led to improved scores.5 Increasingly, school learning difficulties prompt evaluations for OSA.

Increased Work of Breathing

It is hypothesized that increased work of breathing leads to increased caloric expenditures, as failure to thrive (FTT) is more prevalent in children with OSA, and increased height and weight growth velocity has been documented in children after T&A. Similarly, reductions in resting energy expenditure and recovery in the insulin growth factor-1 axis after T&A suggest that increased energy expenditure and disrupted growth hormone production are consequences of OSA, and cause the FTT.6 The association of markers of inflammation with OSA suggests that FTT may be a chronic inflammatory state as well.7

Hypercapnia and Hypoxemia

In children with OSA, the ventilatory response to hypercapnia is normal, and daytime hypercapnia is less frequently seen than in adults with OSA.2 The pulmonary vasculature may be more responsive in some children (eg, those with Down syndrome), however, and pulmonary hypertension may develop as a consequence of nocturnal hypercapnia. As with hypercapnia, hypoxemia can lead to increases in pulmonary artery pressure and the development of pulmonary hypertension. Systemic arterial hypertension is now appreciated as a consequence of OSA in children.8 In the developing brain, intermittent hypoxia may affect cognitive and neuronal development. An animal model demonstrates deleterious changes in anatomy and function of the developing brain with intermittent hypoxia.9 As neurologic development is critical to adult cognitive and behavioral functioning, OSA at this age can have devastating long-term effects. However, the individual causes of cognitive delay in children with OSA remain to be determined.

Impaired learning, stunted growth, behavioral changes, and pulmonary hypertension are serious and major consequences of pediatric OSA. Early and accurate diagnosis, treatment, and prevention of these serious morbidities must be part of standard pediatric care.

PSG a Must

Diagnosis cannot be done by history and physical exam; it is difficult to predict who will have OSA, snoring, or another sleep disorder. A polysomnogram is required for accurate diagnosis; the PSG should be done at a pediatric facility, using pediatric norms. One cannot overstate the value of having a technician who is familiar with the needs of children set up the study. Gathering useful data requires a technician capable of working well with toddlers and their parents (who usually sleep in the room on a cot during the study).

Scoring of the study is done using adult scoring rules,10,11 although an apnea-hypopnea index (AHI) of 5 or greater is considered positive in a child. An AHI less than 2.5 is generally considered negative. A particular diagnostic dilemma may be found in the child with tonsillar and adenoidal hypertrophy, snoring, and evidence of increased upper airway resistance, but with a low AHI. In this child, who apparently can meet the increased demands of partial upper airway obstruction, benefit may yet be found with T&A; clinical judgment regarding consequences of increased upper airway resistance will come into play. Although data continue to be collected to define normal, standards now exist for scoring pediatric studies.

Treatment

Medical treatment of pediatric OSA with decongestants, topical steroids, or leukotriene modifier therapy may be attempted,12 but surgical therapy is more commonly used. Tonsillectomy and adenoidectomy is the treatment of choice and is often, though not always, completely curative.13 Surgical options continue to be refined in technique, and other surgical procedures such as uvulopalatopharyngoplasty are of unproven benefit in children. Potentially deleterious effects of other surgeries on swallowing and the ability to protect the airway mandate that more extensive surgical options be considered only at major pediatric centers.

When surgery is not an option or did not work, noninvasive mechanical ventilation may help. Using continuous (CPAP) or biphasic (BiPAP) modes of positive airway pressure support, most children can be treated. Getting such modes of noninvasive mechanical ventilation (NIMV) to work for children requires special consideration. A period of conditioning, sometimes quite lengthy, can give a child time to adapt to the mask. Using a reward system for wearing the mask for brief periods during the day, letting the patient sleep with the gear in bed, and having the device in the room before initiating use can all facilitate success in using NIMV support. Less often, a tracheotomy is used when facial anatomy or other problems prevent use of NIMV. Reconstructive surgeries such as jaw reconstruction should be done in large centers with experience in the procedures, and able to provide postoperative care in a pediatric intensive care unit. Patients with craniofacial syndromes and neuromuscular disease as a cause of their OSA require a team approach in such a pediatric center.

Summary

Children with OSA face potentially lifelong consequences with cognitive, behavioral, and learning impairments, as well as life-threatening problems with pulmonary hypertension. Suspected if there is a history of gasps or snorts during sleep, if there is tonsillar and/or adenoidal hypertrophy, or if there are developing learning or behavioral changes, the diagnosis is made by PSG. The treatment of choice is T&A, and noninvasive ventilatory support can be used if the mask is fitted well and introduced gradually. Further studies are needed to evaluate the long-term consequences of pediatric OSA and effective treatments for it.


Timothy D. Murphy, MD, is assistant professor of pediatrics for the Department of Pediatrics, and member of the pulmonary division, University of Pittsburgh School of Medicine. He is associate director of the pediatric sleep disorders clinic and director of the Home Ventilator Program of Western Pennsylvania. For further information, contact [email protected]

References

  1. Marcus CL. Pathophysiology of childhood obstructive sleep apnea: current concepts. Respir Physiol. 2000;119:143-54.
  2. Marcus CL, Lutz J, Carroll JL, Bamford O. Arousal and ventilatory responses during sleep in children with obstructive sleep apnea. J Appl Physiol. 1998;84:1926-36.
  3. Bonnet MH. Effect of sleep disruption on sleep, performance, and mood. Sleep. 1985;8:11-9.
  4. Gozal D. Sleep-disordered breathing and school performance in children. Pediatrics. 1998;102:616-20.
  5. Montgomery-Downs HE, Crabtree VM, Gozal D. Cognition, sleep and respiration in at-risk children treated for obstructive sleep apnoea. Eur Respir J. 2005;25:336-42.
  6. Bar A, Tarasiuk A, Segev Y, Phillip M, Tal A. The effect of adenotonsillectomy on serum insulin-like growth factor-I and growth in children with obstructive sleep apnea syndrome. J Pediatr. 1999;135:76-80.
  7. Li AM, Chan MHM, Yin J, et al. C-reactive protein in children with obstructive sleep apnea and the effects of treatment. Pediatr Pulmonol. 2008;43:34-40.
  8. Bixler EO, Vgontzas AN, Lin H-M, et al. Blood pressure associated with sleep-disordered breathing in a population sample of children. Hypertension. 2008;52:841-6. Epub 2008 Oct 6.
  9. Row BW, Kheirandish L, Neville JJ, Gozal D. Impaired spatial learning and hyperactivity in developing rats exposed to intermittent hypoxia. Pediatr Res. 2002;52:449-53.
  10. Standards and indications for cardiopulmonary sleep studies in children. American Thoracic Society. Am J Respir Crit Care Med. 1996;153:866-78.
  11. Cardiorespiratory sleep studies in children. Establishment of normative data and polysomnographic predictors of morbidity. American Thoracic Society. Am J Respir Crit Care Med. 1999;160:1381-7.
  12. Kheirandish L, Goldbart AD, Gozal D. Intranasal steroids and oral leukotriene modifier therapy in residual sleep-disordered breathing after tonsillectomy and adenoidectomy in children. Pediatrics. 2006;117:e61-6.
  13. Guilleminault C, Huang Y, Glamann C, Li K, Chan A. Adenotonsillectomy and obstructive sleep apnea in children: a prospective survey [see comment]. Otolaryngol Head Neck Surg. 2007;136:169-75.

Representative Medical Conditions Associated with OSA in Children

Fixed Upper Airway Obstruction

  • achondroplasia, Crouzon and Apert’s syndromes
  • choanal atresia, or stenosis
  • oropharyngeal papillomatosis
  • Pierre Robin/micrognathia sequence

Variable Upper Airway Obstruction

  • tonsillar and adenoidal hypertrophy
  • hypothyroidism
  • mucopolysaccharidosis
  • Beckwith-Wiedemann syndrome
  • sickle cell disease
  • retropharyngeal abscess

Abnormal Respiratory Mechanics, or CNS Control

  • obesity
  • neuromuscular disorders (eg, Duchenne muscular dystrophy, spinal muscular atrophy)
  • myelomeningocele/spina bifida
  • cerebral palsy
  • acquired/congenital brain injury or defect

Mixed Causes (multiple contributing factors to OSA)

  • Klippel-Feil and Hallermann-Streiff syndromes
  • Down syndrome
  • osteopetrosis
  • osteogenesis imperfecta