Key Points
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Sleep-disordered breathing is an important cause of morbidity in children and may lead to growth failure, neurocognitive and behavioral abnormalities, cardiovascular dysfunction, and rarely death.
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Workup includes a comprehensive history and physical examination. Polysomnography is recommended prior to adenotonsillectomy for selected children with premorbid conditions and for otherwise healthy children for whom the need for surgery is uncertain or for whom there is a discordance between tonsil size and reported severity of symptoms.
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Adenotonsillectomy is the first-line therapy for obstructive sleep apnea (OSA) in otherwise healthy children and often for complex patients if the tonsils and adenoids are enlarged.
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Children with OSA are at risk for postoperative respiratory complications, and children with risk factors should be admitted overnight after surgery.
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The cure rate of OSA after adenotonsillectomy varies among studies, but in general, it is about 60%.
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Additional therapies include topical nasal steroids for milder cases, nasal continuous positive airway pressure or bilevel positive airway pressure, orthodontic appliances, weight loss, and tracheotomy. Emerging surgical therapies include lingual tonsillectomy, supraglottoplasty, uvulopalatopharyngoplasty, genioglossus advancement, mandibular distraction, and bariatric surgery. Data regarding the outcomes of many of these procedures in children are limited.
Pediatric sleep-disordered breathing (SDB) is viewed as a continuum of severity from partial obstruction of the upper airway that produces snoring to increased upper airway resistance to continuous episodes of complete upper airway obstruction or obstructive sleep apnea (OSA). Although the prevalence of primary snoring in children is 8%, the prevalence of OSA is 1% to 4%. SDB is an important cause of morbidity in children and may lead to growth failure, neurocognitive and behavioral abnormalities, cardiovascular dysfunction, and rarely death. Early recognition and treatment are important to prevent or treat these complications.
Historic Perspective
The earliest description of pediatric OSA was an obese, red-faced, hypersomnolent boy named Joe, found in an 1837 novel by Charles Dickens, The Posthumous Papers of the Pickwick Club . In the medical literature, William Osler gave an extremely accurate description of pediatric OSA in his textbook in 1892: “At night the child’s sleep is greatly disturbed; the respirations are loud and snorting, and there are sometimes prolonged pauses, followed by deep, noisy inspirations.” Osler also coined the term pickwickian to describe morbidly obese, hypersomnolent patients. In 1956, Spector and Bautista associated pediatric respiratory distress with tonsillitis and adenoiditis. In 1965, both Noonan and Menashe described reversible cor pulmonale in children with adenotonsillar hypertrophy. Guilleminault and colleagues first described the clinical features of pediatric OSA in 1976. In the last quarter of the twentieth century, the published literature dramatically increased and expanded our knowledge regarding the potential morbidities and treatment of SDB. Studies from the 1990s also demonstrated that primary snoring in the absence of classic sleep apnea could also be associated with neurocognitive abnormalities.
Definitions
Classically, childhood OSA has been defined as partial or complete upper airway obstruction during sleep, usually associated with sleep disruption, hypoxemia, hypercapnia, or daytime symptoms ( Fig. 5-1, D and E ). The diagnosis of OSA has been based on threshold criteria on the overnight polysomnogram (PSG) such as apnea index (AI) or degree of oxygen desaturation. Children who snored but did not meet the threshold criteria for OSA were considered to be primary snorers (see Fig. 5-1, B ), a condition believed to be clinically insignificant. In recent years, upper airway resistance syndrome (UARS) has identified children with elevated upper airway resistance characterized by snoring, labored breathing, and paradoxic breathing without classic apnea or hypopnea (see Fig. 5-1, C ). These children exhibit clinical features similar to children with classic OSA and improve after treatment.
Etiology and Pathogenesis
Pediatric OSA is caused by fixed and/or dynamic narrowing of the airway that may occur at several sites. Most commonly, enlarged tonsils and adenoids are the source of nasopharyngeal and oropharyngeal narrowing. The tissues of the Waldeyer ring—the tonsils, adenoids, and lingual tonsils—progressively enlarge between the age of 2 and 8 years and are largest in relation to the airway between 3 and 6 years of age. Craniofacial abnormalities such as micrognathia or maxillary hypoplasia can also narrow the upper airway, and lower airway abnormalities such as laryngomalacia can impact airway patency. Rapid air movement through a narrowed airway from any of these conditions induces further airway collapse and obstruction. The pharyngeal muscular hypotonia and incoordination found in children with neuromuscular conditions and cerebral palsy produce dynamic airway narrowing.
Given the multiple predisposing factors for pediatric SDB, no single factor accounts for all cases ( Fig. 5-2 ). Large tonsils and adenoids alone do not cause SDB. Numerous studies have been unable to find a relationship between tonsil and adenoid size and the development of OSA. Children with OSA may not exhibit obstruction when awake, which underscores the need to evaluate sleep-related dynamic airway collapse. Upper airway muscle electromyography (EMG) activity is increased in awake children with SDB compared with normal children, and there is an increase in EMG activity during sleep in children with SDB. The obstructive phenotype depends on the ability of the upper airway muscles to compensate for airway narrowing. The current view is that children with OSA have an underlying abnormality of upper airway motor control or tone that when combined with enlarged tonsils and adenoids results in dynamic airway obstruction during sleep.
The mechanisms that underlie the development of the neurocognitive and behavioral deficits found in pediatric SDB are unknown. Proposed mechanisms include sleep disruption, sleep fragmentation, intermittent hypoxia, episodic hypercapnia, alterations in brain neurochemistry, brain inflammation, hormonal changes, changes in cerebral blood flow, or altered cerebral perfusion pressure. Rodent models of OSA have shown that oxidative stress and inflammatory processes lead to neuronal cell loss in the regions of the brain that underlies learning, behavior, executive function, and memory. Other consequences of pediatric SDB include cardiac dysfunction, blood pressure dysregulation, and growth impairment and are likely caused by similar mechanisms. Hypoxemia or sleep fragmentation may affect brain neurochemistry and growth hormone secretion; increased work of breathing with fewer calories available for growth may lead to failure to thrive; large swings in intrathoracic pressure may affect cardiac afterload directly; and increased circulating inflammatory mediators, endothelial dysfunction, and increased insulin resistance—particularly in obese children—are thought to contribute to cardiovascular morbidity. The etiology of enuresis is unclear but may be secondary to increased urine production as a result of OSA or abnormal secretion of antidiuretic hormone (ADH), or it may merely reflect increased awakenings and arousals.
Mounting evidence suggests a familial predisposition to the development of OSA, because genetic-epidemiologic surveys of families of index patients with OSA have demonstrated a higher prevalence of SDB in family members as compared with the general population. Genes associated with obesity, craniofacial structure, and muscle development of the upper airway soft tissues are likely involved in the development of OSA, but further work is needed to identify specific loci. Gene-specific polymorphisms may explain the variability in morbidities associated with SDB. The apolipoprotein E epsilon 4 allele is more common in nonobese children with OSA compared with controls, particularly in children with neurocognitive dysfunction.
Epidemiology
The prevalence of snoring has been estimated from community-based cross-sectional surveys of parental reports of snoring and difficulty breathing during sleep. A meta-analysis of published studies found the prevalence of snoring to be 7.45% (95% confidence interval, 5.75-9.61). The prevalence of SDB estimated from parental reports with additional diagnostic testing ranges from 0.1% to 13.0%, but most studies suggest a prevalence of 1% to 4%. The peak incidence of pediatric OSA is between 2 and 6 years of age, when the tonsils and adenoids are largest in relation to the size of the underlying airway. A second peak occurs during adolescence with the development of the adult body habitus and craniofacial structure. Boys are affected at rates that are 50% to 100% higher than girls. Black children have been reported to be at increased risk (3.5 times) for developing OSA and to be at increased risk for the morbidity associated with OSA. Most studies report that overweight/obesity is an independent risk factor for SDB. Some data suggest that weight status may have more of an influence in older children, and adenotonsillar hypertrophy is considered the major risk factor in younger children. Prematurity and asthma are also risk factors for SDB, but studies have reported conflicting results regarding the effects of allergic rhinitis, exposure to passive cigarette smoking, and low socioeconomic status.
Clinical Features
Nighttime Symptoms
Snoring is the most common symptom of SDB, and OSA is extremely unusual in children who do not snore ( Box 5-1 ). Other nighttime symptoms include apneic pauses, snorting, gasping, restless sleep, frequent arousals, frequent awakenings, sleeping with the neck hyperextended, unusual sleeping positions (sitting, propped up on pillows, fetal position), diaphoresis, enuresis, and other parasomnias. A resuscitative snort often follows the apneic episodes, and occasionally, stridor is found. Children may exhibit paradoxic inward rib cage motion, but cyanosis is rarely observed. In children, OSA occurs mainly in rapid eye movement sleep; therefore symptoms may be absent for a significant portion of the night.
Nighttime Symptoms
Snoring
Apneic pauses
Gasping
Restless sleep
Frequent arousals and awakenings
Neck extension
Unusual sleeping positions
Diaphoresis
Paradoxic chest wall motion
Enuresis
Parasomnias
Daytime Symptoms
Mouth breathing
Hyponasality
Chronic rhinorrhea
Nasal obstruction
Dysphagia
Behavior and neurocognitive difficulties
Poor school performance
Daytime sleepiness
General
Poor growth or failure to thrive
Pulmonary hypertension/cor pulmonale/ventricular dysfunction
Systemic hypertension
Daytime Symptoms
Hypertrophy of the tissues of the Waldeyer ring may lead to daytime obstructive symptoms that include mouth breathing, hyponasality, chronic rhinorrhea, nasal obstruction, and dysphagia (see Box 5-1 ). A history of any of these symptoms should lead to an investigation of nighttime symptoms that include snoring and possible apnea. During an acute upper respiratory infection, enlargement of the lymphoid tissues of the Waldeyer ring can result in snoring and nighttime breathing difficulties; these symptoms may be temporary and resolve once the infection resolves, but they may signal the onset of chronic upper airway obstruction.
Failure to thrive has been reported to occur in approximately 10% of children and 42% to 56% of infants with OSA. Several reports have documented improvement in growth for children with failure to thrive and OSA after adenotonsillectomy.
Early reports found systemic hypertension in 10% to 25% of children with OSA, although these children were severely affected. Marcus and colleagues found that 41 children with OSA had significantly higher diastolic blood pressure than 26 children with primary snoring, although no significant difference was found in systolic blood pressure between the two groups. Body mass index was a significant predictor of elevated blood pressure. Amin and associates found significant increases in blood pressure surge, blood pressure load, and 24-hour ambulatory blood pressure in children with SDB (AHI >5) compared with controls, and this was independent of body mass index. Although the data are heterogeneous, several meta-analyses have shown a higher risk of hypertension in children with more severe SDB. Ventricular hypertrophy, reduced ejection fraction, wall motion abnormalities, ventricular dysfunction, cor pulmonale ( Fig. 5-3 ), and increased mean arterial pulmonary pressures have been demonstrated in children with SDB. Studies have also demonstrated a correlation between cardiac dysfunction and OSA severity. Most of the cardiovascular morbidities improve after adenotonsillectomy. Whereas daytime sleepiness is extremely common in adults with OSA, it is a relatively infrequent finding in children and occurs in about 13% to 20%. Behavioral and neurocognitive difficulties have been found in 8.5% to 63% of children with SDB. Behavioral problems include attention problems, hyperactivity, aggression, emotional distress, irritability, somatic complaints, and difficulties with peers. The neurocognitive skills affected include memory, recall, vigilance and attention, mental flexibility, and visual-spatial tasks. Children with primary snoring but otherwise normal sleep study indices have also been shown to have lower scores on measures of behavior and cognition using a battery of neurobehavioral tests compared with control children, although the mean scores for both groups were still in the normal range. Studies that used standardized behavioral and neurocognitive assessments have documented significant improvements in test scores after adenotonsillectomy in children with SDB, which suggests that neurocognitive deficits are potentially reversible.
Poor academic performance has also been found in several studies of children with SDB. Gozal evaluated 297 first grade children in the lowest 10 th percentile of their class by overnight pulse oximetry and transcutaneous CO 2 measurement. Fifty-four children demonstrated sleep-associated gas exchange abnormalities, and 24 of these children underwent adenotonsillectomy. The mean grades of the children who underwent surgery increased significantly during the following academic year compared with the children whose parents refused surgery. No academic improvement was reported in the children with primary snoring and the children without SDB. These finding also suggest that the neurocognitive difficulties found in children with SDB are reversible with treatment. To further evaluate the long-term impact of SDB in early childhood, Gozal and Pope mailed questionnaires to the parents of seventh and eighth graders whose school performance was in the top 25% of the class or the bottom 25% of the class and who were matched for age, gender, race, school, and street of residence. Snoring in early childhood was significantly more common in the low-performance group than in the high-performance group, but no significant difference was reported in current snoring. Significantly more low-performance children had a history of adenotonsillectomy than did high-performance children. These findings suggest that the neurocognitive impairments of pediatric SDB may not be fully reversible, especially if they occur during a critical period of brain development.
Predisposing Conditions
Obesity
Although obesity is a risk factor for pediatric SDB, most children with SDB are not obese ( Box 5-2 ). However, the prevalence of SDB in obese children is 25% to 40%. Obesity predisposes children to SDB by decreasing the cross-sectional area of the upper airway by the deposition of adipose tissue adjacent to the pharynx and also because of compression from subcutaneous fat deposits in the neck. Individual symptoms and PSG abnormalities do not correlate with the degree of obesity. Soultan and colleagues found that 10 of 17 children who were obese or morbidly obese with OSA had substantial weight gain after adenotonsillectomy. Therefore treatment of the SDB will not help with weight reduction in obese children and might exacerbate the obesity. Diet, exercise, and behavior therapy are needed in addition to surgical therapy. OSA adversely affects several of the components associated with metabolic syndrome, the clustering of insulin resistance, dyslipidemia, hypertension, and obesity, that is a known risk factor for cardiovascular disease in adults.
Obesity
Down syndrome
Craniofacial syndromes
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Craniosynostoses (Apert, Crouzon, Pfeiffer, and Saethre-Chotzen syndromes)
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Pierre Robin sequence
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Stickler syndrome
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CHARGE syndrome
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Mandibulofacial dysostosis (Treacher Collins syndrome)
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Craniofacial microsomia (hemifacial microsomia, Goldenhar syndrome, first and and second branchial arch syndrome)
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Hallerman-Streiff syndrome
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Mucopolysaccaridoses
Achondroplasia
Neuromuscular disease
Cerebral palsy
Beckwith-Weideman syndrome
Klippel-Feil syndrome
Prader-Willi syndrome
Arnold-Chiari malformation
Sickle cell disease
Post pharyngoplasty patients
Down Syndrome
The anatomic and physiologic factors that predispose children with Down syndrome to OSA include midfacial and maxillary hypoplasia, macroglossia, a narrow nasopharynx, a shortened palate, generalized hypotonia, and a tendency to obesity. Shott and colleagues found the incidence of OSA to be 57% in a 5-year longitudinal study of 56 children with Down syndrome. Of the children with abnormal sleep studies, 77% of the parents reported no sleep problems in their children. Because many of the manifestations of SDB—including daytime sleepiness, behavioral problems, developmental delay, and pulmonary hypertension—are also common in children with Down syndrome, there is often a delay in diagnosis.
Although adenotonsillectomy is usually the first-line treatment for SDB in Down syndrome children, persistent significant PSG abnormalities have been reported in up to 80% of children. Additional therapies may include nasal continuous positive airway pressure (CPAP), uvulopalatopharyngoplasty (UPPP), tongue reduction, genioglossus advancement, lingual tonsillectomy, radiofrequency ablation (RFA) of the tongue base, supraglottoplasty, or tracheotomy. Few outcome studies available, although Wooten and Shott reported a success rate of 58% after genioglossus advancement and RFA of the tongue base.
Craniofacial Syndromes
The prevalence of SDB in children with craniofacial syndromes is estimated to be 40% to 50%. Abnormalities that predispose these children to OSA include midfacial and mandibular hypoplasia, increased nasal resistance, macroglossia, soft palate abnormalities, hypotonia, abnormal neural control of the airway, and structural defects. OSA has been found in children with Pierre Robin sequence, Treacher Collins syndrome, Apert syndrome, Pfeiffer syndrome, Larsen syndrome, Crouzon syndrome, Stickler syndrome, Goldenhar syndrome, velocardiofacial syndrome, and fragile X syndrome. Infants with Pierre Robin sequence (micrognathia, glossoptosis, and cleft palate) may present with severe upper airway obstruction. PSG is important for the diagnosis of SDB in children with craniofacial abnormalities and to evaluate response to therapy, which includes adenotonsillectomy, UPPP, midface advancement, mandibular distraction osteogenesis, nasal CPAP, and tracheotomy.
Achondroplasia
Achondroplasia is an autosomal-dominant syndrome and is the most common form of dwarfism, which results from mutations in the fibroblast growth factor receptor 3 gene ( FGFR3 ). Midfacial hypoplasia, dysplasia of the basiocciput, foramen magnum stenosis with compression of the cervical spinal cord, and thoracic cage restriction predispose these children to OSA. Surgical management may involve adenotonsillectomy, ventriculoperitoneal shunt, and foramen magnum decompression. PSG and neurologic and respiratory assessments are important in the workup of these patients.
Mucopolysaccharide Storage Diseases
The mucopolysaccharidoses are genetic disorders in which enzyme deficiencies lead to defective degradation of lysosomal glycosaminoglycans with accumulation of mucopolysaccharides in the soft tissues of the body, which includes the respiratory tract. The type of mucopolysaccaridosis is determined by the particular enzyme deficiency. Examples are Hurler and Scheie syndrome (α-L-iduronidase deficiency), Hunter syndrome (iduronate sulfatase deficiency), and Sly syndrome (β-glucuronidase deficiency). In addition to hypertrophy of the tonsils, adenoids, tongue, and oropharyngeal mucosa, deposits in the tracheobronchial tree often lead to chronic pulmonary disease. These children often develop scoliosis, spinal problems, and hepatosplenomegaly. OSA may be severe and may cause death. Treatment options include adenotonsillectomy, nasal CPAP, and tracheotomy. These patients require very complex airway management, and even tracheotomy may not ensure control of the airway.
Neuromuscular Disease and Cerebral Palsy
Children with neuromuscular disease are a heterogeneous group and include children with neuropathies, congenital myopathies, muscular dystrophies, myotonias, and myasthenia gravis. These children have a loss of respiratory muscle function and a drop in central respiratory drive that lead to both obstructive and central apnea. The symptoms of SDB may be underestimated, because they may be difficult to distinguish from the underlying disease. Treatment options include adenotonsillectomy, UPPP, tracheotomy, or CPAP. Children with cerebral palsy have poor neuromuscular control, increased oropharyngeal secretions, seizures, and gastroesophageal reflux disease (GERD) that may predispose them to SDB. Adenotonsillar hypertrophy and decreased pharyngeal tone contribute to upper airway collapse. Treatment options include adenotonsillectomy, UPPP, tongue hyoid advancement, tongue-base suspension, mandibular advancement, tongue reduction, CPAP, and tracheotomy.
Miscellaneous
Children with Arnold-Chiari malformations present with central and obstructive apnea as a result of brainstem compression. Treatment involves decompression of the malformation. Children with sickle cell disease are at risk for the development of SDB, and SDB may be a predisposing factor for the occurrence of cerebrovascular accidents. Adenotonsillectomy has been shown to be successful in the resolution of symptoms and improvement in alveolar hyperventilation. Children with Prader-Willi syndrome, the absence of expression of the paternally derived Prader-Willi syndrome/Angelman syndrome (region q11-q13 of chromosome 15), have severe infantile hypotonia, feeding difficulties, developmental delay, craniofacial abnormalities, and obesity, all of which contribute to the development of SDB. These children exhibit both central and obstructive apnea, likely as a result of hypothalamic dysfunction. Children treated with growth hormone have been shown to have a higher risk of SDB, and thus screening with PSG at initiation of therapy and with worsening of snoring is recommended. Adenotonsillectomy is effective in children with mild or moderate SDB, but less than half of children with severe OSA are cured. Iatrogenic causes of SDB are possible, most commonly from flap surgery to treat velopharyngeal dysfunction.
Physical Examination
The child’s general appearance should be assessed with measurement of height, weight, and blood pressure. The craniofacial structure should be assessed for midfacial hypoplasia, retrognathia, micrognathia, and adenoid facies (open mouth, long face, mandibular hypoplasia). The presence of mouthbreathing, stertor, and hyponasality should also be assessed. The nose should be examined for the presence of structural abnormalities, and the oropharyngeal examination should evaluate tonsil size, tongue size, position of the palate, dentition, and the presence of any structural abnormalities. The neck should be examined for any neck masses, and adenoids can be evaluated by flexible fiberoptic nasopharyngoscopy or by the use of a small rigid telescope. If laryngeal abnormalities are suspected, flexible fiberoptic laryngoscopy may also be performed. The chest should be examined for the presence of pectus excavatum, and neurologic function and development should also be assessed.
Ancillary Studies
A lateral neck film may be obtained to assess adenoid size. Cephalometric studies and upper airway fluoroscopy may be useful in children with craniofacial abnormalities but are not routinely used for otherwise healthy children. Magnetic resonance imaging (MRI) may be used for three-dimensional reconstruction of the soft tissues and skeletal structures of the upper airway, as well as for evaluation of dynamic collapse, but it is mostly used for patients who fail adenotonsillectomy (see Other Surgical Modalities below). An electrocardiogram, echocardiogram, and chest radiograph may be obtained in children with severe OSA or in children with signs of congestive heart failure to evaluate for pulmonary hypertension and ventricular hypertrophy or dysfunction.
A home audiotape recording of the child’s breathing during sleep has a reported sensitivity of 71% to 88% and a specificity of 52% to 72% in predicting a positive result on PSG in otherwise healthy children. A home videotape recording has been shown to have a sensitivity of 94% and a specificity of 68% in predicting a positive PSG. Although not specific enough to distinguish children with positive and negative sleep studies, such tapes are useful in the clinical setting as convenient, inexpensive methods to confirm the parents’ description of the child’s nighttime breathing difficulties.
Pulse oximetry is not useful as a screening tool because of its low sensitivity, but it may prove useful if positive in a snoring child in whom a high index of suspicion for OSA exists. Nap PSGs also exhibit poor sensitivity and are only useful if they are positive. The difficulty with nap studies is that children over 4 years of age rarely nap, and rapid eye movement sleep may be missed on a nap study. Ambulatory, unattended PSG is performed in the child’s home, but measurement of end-tidal CO 2 , electroencephalography, and upper airway resistance are not performed. Few data are available to evaluate at-home unattended PSG in children, and currently home PSG is not recommended unless laboratory PSG is not available. Newer, less invasive techniques include acoustic pharyngometry, which measures upper airway cross-sectional area, and the pulse transit time, the interval between the R wave of the electrocardiogram and the arrival of the photoplethysmographic pulse at the finger. Pulse transit time is reduced in patients with OSA because of the transient increase in blood pressure associated with respiratory arousal from sleep. These techniques show promise in children with SDB, but their usefulness awaits further study. Biomarkers that include serum and urine proteins may prove useful for identifying children at risk for SDB and its neurobehavioral and cardiovascular complications, but at this point in time, they lack the sensitivity and specificity needed for diagnosis.
Polysomnography
Polysomnography (PSG) consists of electroencephalography, electrooculography, and electromyography (EMG) for sleep staging, chest/abdominal motion by strain gauges, chest wall impedance or respiratory inductive plethysmography, electrocardiography (ECG), pulse oximetry, nasal/oral airflow, and end-tidal or transcutaneous CO 2 . UARS is best detected by esophageal pressure monitoring, but this is not routine in most centers. Ideally, pediatric sleep studies should be performed in a pediatric sleep laboratory with a technical staff trained to work with children.
Obstructive apnea, or the cessation of airflow with continued respiratory effort, is defined as lasting at least 10 seconds in adults ( Fig. 5-4, A ). Because children have faster respiratory rates than adults, the duration of an obstructive apnea in a child is two times the typical breath interval. An obstructive hypopnea (see Fig, 5-4, B ) is the partial cessation of airflow with continued respiratory effort, although there is no uniform definition of hypopnea in children among sleep laboratories. Central apnea is the cessation of airflow as a result of lack of respiratory effort. Sleep study findings are commonly reported as the apnea-hypopnea index (AHI), defined as the number of apneas plus hypopneas per hour of sleep, or the respiratory disturbance index (RDI), defined as the number of all respiratory events, including respiratory arousals per hour of sleep.
