Pediatric sleep-disordered breathing (SDB) includes an increasingly recognized, highly prevalent, yet still underdiagnosed spectrum of respiratory disorders, the most common and clinically significant of which is obstructive sleep apnea. SDB is linked with significant end-organ dysfunction across various systems, particularly with cardiovascular, neurocognitive, and metabolic consequences. This review summarizes recent advances in understanding of pediatric SDB and discusses the challenges inherent in diagnosing and treating children with SDB.
The woods are lovely, dark and deep. But [we] have promises to keep, And miles to go before [we] sleep, And miles to go before [we] sleep. Robert Frost
Despite the many advances in the field of pediatric sleep medicine over the past decade, the science and knowledge of this area (our woods) are largely unexplored and remain unknown, dark and deep. That an understanding of pediatric sleep has only begun to be formed is reflected in the common clinical view of pediatric sleep-disordered breathing (SDB) as a picture of enlarged tonsils and adenoids requiring surgical intervention. Such a limited perspective veils the complexity of SDB in children and requires a significant re-evaluation to improve the outcomes of children and adolescents affected by this burdensome health problem and its wide-ranging consequences. This article provides readers with the most current knowledge and understanding of pediatric SDB, discusses diagnostic issues and management challenges of SDB in children and adolescents, and builds on a previous Pediatric Clinics of North America review of this topic.
When dealing with a patient presenting with possible SDB, the primary care provider is confronted with the daunting task of effectively diagnosing and treating the child or adolescent. To facilitate understanding of SDB in the pediatric population, this discussion is limited to otherwise healthy children with suspected SDB who are habitual snorers. Those with high risk of SDB related to genetic or craniofacial syndromes or neuromuscular weakness are beyond the scope of this review. In otherwise healthy children, the spectrum of SDB is best conceptualized as a range of conditions. The spectrum ranges from primary snoring (ie, without associated ventilatory abnormalities) to increased upper airway resistance to the most severe form, obstructive sleep apnea (OSA), characterized by repetitive prolonged partial or complete upper airway obstruction leading to fragmented sleep and gas exchange abnormalities. To appropriately identify children suspected of having SDB, the American Academy of Pediatrics published practice guidelines almost a decade ago recommending an overnight sleep study or nocturnal polysomnogram (PSG) as the gold standard for diagnosing SDB in otherwise healthy children without comorbidity. This recommendation was put forth by the American Academy of Pediatrics based on studies that failed to find any combination of history and physical findings that reliably identify those children with SDB. Despite the practice guidelines, PSG still are not routinely used in clinical practice. Approximately 10% of children with chronic snoring referred for adenotonsillectomy actually have the PSG to confirm the diagnosis. The huge disparity between the recommendations and what is current practice must be addressed. What are the reasons for the gap between the practice guidelines and the reality of clinical practice? Why does it matter and what should be done to bridge the gaps and advance the field? This review attempts to address these important clinical questions by summarizing what is currently known about SDB in children, including discussions of causes, consequences, and treatment options.
Pathophysiology of SDB
Several elegant discussions regarding alterations in the upper airway and subsequent increased airway resistance resulting in SDB are available in the literature. In brief, the cause of SDB is likely related to a combination of several factors that results in upper airway dysfunction during sleep. These factors can include any of the following: structural abnormalities anywhere along the entire airway from the nose to the trachea, soft tissue hypertrophy (typically adenotonsillar hypertrophy), craniofacial dysmorphology (posteriorly placed mandible or micrognathia or midfacial hypoplasia), neuromuscular or neuromotor dysfunction, and alterations in sensation of the upper airway. Other important factors that help determine the airway’s ability to compensate appropriately in the face of obstruction include neuromotor activation, arousal thresholds, and central nervous system ventilatory control. Inflammation also likely plays a role in the pathophysiology of SDB; the resulting disruption of the homeostasis from sleep fragmentation and hypoxemia may lead to inflammation at the cellular level and the ability of the airway to respond appropriately may be limited in the context of inflammation. There are also be genetic and environmental factors that further influence the imbalance causing upper airway dysfunction and subsequent SDB because the presence of one of these factors alone does not always guarantee the presence of the disorder. Although the exact mechanism involving SDB in children needs to be elucidated further, an increasingly important risk factor in the pediatric population is obesity because parapharyngeal fat deposition associated with obesity may add further load to an already compromised airway by increasing critical airway closing pressure and altering chest wall mechanics. Identifying the underlying factors contributing to SDB in individual children is important because it affects not only the choice of treatment (likelihood that an adenotonsillectomy is warranted) but also the likely efficacy of treatment and outcomes. For example, in children with swallowing dysfunction or altered sensation at the level of the upper airway, in the context of inadequate neuromuscular compensation, addressing only the structural elements of the obstruction by removing the tonsils and adenoids may not cure the SDB but may worsen it. This is challenging in the clinical setting because there are no readily available, specific measures to assess and weigh the significance of these factors and their interaction for each individual patient.
Risk factors that contribute to SDB
Epidemiologic studies, mostly based on parent-report questionnaires, have identified various risk factors for SDB. SDB seems more common in boys and African American children. Another putative risk factor is recurrent otitis media, which is most likely related to chronic adenotonsillar hypertrophy. Disorders of the upper and lower respiratory system, including asthma and persistent wheezing and recurrent sinus infections, are also risk factors. Environmental tobacco smoke exposure and maternal smoking during pregnancy not only exacerbate these other respiratory disorders but also have been shown to result in higher rates of snoring and likely SDB. Epidemiologic studies have also suggested that children with a past history of prematurity are at increased risk of SDB. One recent study showed that in children with delayed motor milestones, prenatal and perinatal stressors play a role in predisposing children to moderate or severe SDB. All these wide-ranging risk factors together suggest that the mechanisms involved in SDB likely involve gene and environment interactions resulting in morbidity.
Furthermore, many studies, using different methodologies, have identified obesity as a major risk factor for the development, persistence, and recurrence of SDB, conferring up to a 4-fold increase in the risk for SDB. Not all obese children have SDB ; therefore, further studies are required to determine which obese children are more vulnerable to developing SDB and how to identify and stratify their risk factors in a clinical setting for optimizing treatment. Preliminary studies of SDB phenotypes in children have suggested that older children with SDB are more likely to be obese and to present with a more adult-like clinical picture, including excessive daytime sleepiness; they may also have a higher risk of end-organ dysfunction. The mechanism related to excessive daytime sleepiness and SDB is complex because not all individuals with SDB have excessive daytime sleepiness. Nevertheless, clinicians should maintain a high index of suspicion for SDB in obese children and adolescents, and these individuals should be systematically screened and evaluated for symptoms of SDB.
Consequences of SDB in children
It is difficult to know whether the negative outcomes related to SDB result primarily from the sleep disruption and fragmentation related to frequent arousals, from end-organ effects of related hypoxemia, or from both. Most of the relationships between end-organ dysfunction and SDB are documented using pretreatment and post-treatment studies for SDB in small numbers of patients. Overall, the evidence to date suggests that the end-organ effects of SDB are widespread and that untreated disease may have significant measurable consequences. Although it is not clearly established, there may even be a period of increased vulnerability during specific developmental periods, such that the delay in diagnosis and treatment may have long-term, potentially irreversible sequalae. What is known is that children who have SDB have significantly higher health care use costs and that treatment reduces these expenditures by lowering hospitalization rates, emergency room visits, and medication use. What is not known is how individual susceptibility and environmental interactions merge together for individual children, such that there is end-organ dysfunction and morbidity because the severity of the SDB alone may not be enough to determine the type and timing of intervention. Thus, treating children for SDB can result in improvements in various domains but it is not possible to predict which children will benefit and to what extent.
Consequences of SDB in children
It is difficult to know whether the negative outcomes related to SDB result primarily from the sleep disruption and fragmentation related to frequent arousals, from end-organ effects of related hypoxemia, or from both. Most of the relationships between end-organ dysfunction and SDB are documented using pretreatment and post-treatment studies for SDB in small numbers of patients. Overall, the evidence to date suggests that the end-organ effects of SDB are widespread and that untreated disease may have significant measurable consequences. Although it is not clearly established, there may even be a period of increased vulnerability during specific developmental periods, such that the delay in diagnosis and treatment may have long-term, potentially irreversible sequalae. What is known is that children who have SDB have significantly higher health care use costs and that treatment reduces these expenditures by lowering hospitalization rates, emergency room visits, and medication use. What is not known is how individual susceptibility and environmental interactions merge together for individual children, such that there is end-organ dysfunction and morbidity because the severity of the SDB alone may not be enough to determine the type and timing of intervention. Thus, treating children for SDB can result in improvements in various domains but it is not possible to predict which children will benefit and to what extent.
Neurocognitive dysfunction
The challenge in trying to distinguish neurocognitive dysfunction resulting from SDB from other factors, such as genetics, environment, and social factors, is a complex one. There are several excellent reviews for interested readers. Briefly, investigators have attempted to identify whether any specific neurocognitive or psychological tests can identify those at risk for PSG confirmed SDB. Because various studies have used different parameters and criteria to characterize neurocognitive functioning and have also used a variety of PSG-related cutoff values to define SDB, making comparisons across studies is challenging. Several studies in children with primary snoring (defined as apnea-hypopnea index >1/h and <5 events/h) have been shown to have performance deficits compared with controls (apnea-hypopnea index <1 event/h) on measures related to attention, overall cognitive functioning, language, and visuospatial abilities and to score higher on measures of anxiety and depression. Even mild SDB may be associated with impairments in behavior and neuropsychological functioning as a result of the perturbations in sleep or gas exchange parameters but only one study did not find such an association. The explanation for this discrepancy may be that the children in the latter group are younger and there is more scatter in the findings or that group of patients reflects a different genetic vulnerability to end-organ effects of SDB. Although SDB does contribute to neurocognitive dysfunction, the overall morbidity in a patient with neurocognitive dysfunction reflects the combined influence of genetic, environmental, and sociocultural factors in addition to the independent impact of SDB. Furthermore, translating the epidemiologic evidence to the clinical setting does not reflect potential differences in duration of disease, timing of exposure, and other similarly complex relationships because not all children show impairments in functioning that are linked to the severity of the SDB. Furthermore, there may be mediating neuroprotective factors (cytokines, cerebral oxygenation, and other factors) to explain the variance in neurocognitive deficits among children with SDB. Given the evidence, it is reasonable to conclude that all children with learning or attention problems or poor academic functioning should be evaluated for SDB in the clinical setting.
Cardiovascular dysfunction
In adults, the relationship between SDB and related cardiovascular morbidity and mortality is well established. Although the data in children are limited predominantly to studies of small samples of school-aged and older children, the evidence to date is compelling. These studies have established an increased risk of cardiovascular dysfunction in children with SDB, ranging from increases in blood pressure and abnormal echocardiographic findings to more subtle perturbations in autonomic functions and alterations, in inflammatory markers, such as C-reactive protein. For example, there is evidence to suggest that children with SDB have alterations in blood pressure and heart rate during obstructive events similar in magnitude to those described in adults and that there is a strong, dose-dependent relationship between elevated systolic and diastolic blood pressures and severity of SDB. This relationship could have tremendous implications for long-term cardiovascular morbidity. In addition, obesity substantially increases the likelihood of having hypertension in the presence of SDB. Echocardiographic evidence of cardiovascular dysfunction, including left ventricular dysfunction, increased pulmonary pressures, and end-diastolic dysfunction, has been reported in children with SDB. Most studies, with one exception, have shown that markers of inflammation, such as C-reactive protein and N-terminal pro–B-type natriuretic peptide, are elevated in children with SDB and decline after therapy. Elevated cardiovascular sympathetic activity, in addition to other various inflammatory mediators, which may or may not be directly related to intermittent hypoxemia, could be an important mediator of cardiovascular morbidity. Although children with SDB seem to be at increased risk for cardiovascular dysfunction, the explanation may not be as straightforward because other factors, including disease exposure and genetic permutations, which confer increased vulnerability, may also play a role. In support of that view is recent evidence that shows effects related to cardiovascular dysfunction improve with treatment but may not resolve entirely, particularly if there is a family history of cardiovascular disease. These children may continue to be vulnerable after treatment and likely warrant extended follow-up.
Metabolic dysfunction
Emerging evidence suggests that metabolic dysfunction is also associated with SDB. The nature of the relationship in the context of obesity and other potential confounding factors needs further study. Metabolic syndrome, defined as a constellation of features, including hypertension, insulin resistance, dyslipidemia, and abdominal obesity, has been increasingly recognized in children. Obesity and SDB are important risk factors for metabolic syndrome. For example, one study found that adolescents with SDB have a 6.5-fold higher risk of metabolic syndrome compared with those without SDB. Other associated features of metabolic dysfunction include fatty liver disease, which has been reported in children with SDB. Obese children with SDB seem to have higher levels of insulin resistance but whether this is related to SDB or obesity (or both) requires further study. Some studies have reported post-treatment improvements after adenotonsillectomy in the metabolic profile but the results are not consistent across studies.
Diagnosis of SDB
The first step in determining the likelihood of SDB in pediatric patients is to screen for possible symptoms, especially in high-risk groups. In addition to the high-risk groups discussed previously (patients with adenotonsillar hypertrophy, obesity, prematurity, and so forth), children with attention-deficit/hyperactivity disorder are considered high risk because symptoms of SDB are more commonly found in this group. Despite the diagnostic limitations of the history and physical examination (discussed previously), a history of nightly snoring and sleep disruption is an important clue to the possible presence of SDB. An accurate history, however, is largely dependent on the accuracy and quality of a caregiver’s observations. It is not clear whether the frequency, severity, and duration of the snoring change the diagnostic yield of SDB. Children with SDB may also primarily exhibit daytime manifestations of poor sleep, such as sleepiness, inattention, or irritability; thus, it is incumbent on primary care clinicians to identify these as potential symptoms of SDB. Although there certainly are challenges to obtaining a valid pediatric patient history, specific and routine questions regarding cardinal symptoms, such as apneic pauses and snoring, should be a part of the assessment. The prevalence of witnessed apneas in children, however, is exceedingly uncommon (<1%); thus, requiring the presence of apneic events as part of the diagnostic criteria may result in underdiagnosis of SDB. Clinicians should ask about other possible symptoms of SDB, such as poor quality or disrupted sleep, evidence of increased work of breathing (nocturnal diaphoresis, paradoxic chest, and abdominal wall movements), or even end-organ dysfunction secondary to SDB, such as hypertension.
In addition to nocturnal symptoms, including restless sleep and secondary enuresis, other aspects of a child’s daily functioning that are potentially related to sleep disruption, such as mood, behavior, and daytime sleepiness, should be assessed. Although SDB has been associated with poor academic performance, other causes of sleep disruption (insufficient sleep, restless legs syndrome, and insomnia) may also contribute to neurobehavioral morbidity. In addition, there is a great deal of overlap between the symptoms that may be attributable to SDB and those associated with other common diagnoses, such as attention-deficit/hyperactivity disorder, which further limits the ability of the clinical history alone to distinguish children who have SDB from those with another disorder. It is imperative for the clinician to maintain a high index of suspicion in such children and regularly evaluate for symptoms of sleep disruption or sleep disorders when children are reported to have a change in level of functioning at school or in the home.
Questionnaires
Various questionnaires have been developed to aid in the identification of children who have SDB. In general, they ultimately rely on parent reports when used diagnostically in the clinical setting. For example, the 22-item sleep-related breathing disorder subscale in the Pediatric Sleep Questionnaire, used in screening children ages 2 through 18 for SDB, has reasonable sensitivity (0.85) and specificity (0.87). This questionnaire has been validated in several clinical settings and a score of greater than 0.33 has been shown to predict a 3-fold increased risk of SDB on PSG. Other pediatric SDB questionnaires are limited by the fact that they have undergone limited testing in clinical settings outside the areas of research centers for which they were developed or because they have poor psychometric properties. Although questionnaires can help standardize history-taking inquiry, they may not adequately reflect the entire spectrum of disease presentation and ultimately may not be useful in conclusively determining which individual children require immediate evaluation and treatment in the clinical setting.
Physical examination
Similar to history and questionnaires, physical examination also has limited ability to specifically identify children who will have SDB. There are several reasons for this. First, most physicians and primary care providers are not trained to evaluate aspects of craniofacial morphology, other than adenotonsillar hypertrophy, that may predispose children to SDB, such as malocclusion; position of the palate, maxilla, and mandible; and crowding of the posterior pharynx. Furthermore, end-organ effects from SDB, such as hypertension or altered metabolic parameters, may not be immediately obvious or may occur late in the disease process. The addition of diagnostic radiologic tests may increase the sensitivity of the physical examination. For example, one study reported a sensitivity of 90% using a lateral neck radiograph when combined with findings of upper airway narrowing and enuresis. The constellation of features failed, however, to identify all children with SDB. The bottom line is that children with clinical symptoms, physical findings, and/or risk factors for SDB warrant further evaluation to confirm the diagnosis and help determine both the timing and type of treatment.
Imaging
Further characterization of the upper airway using sophisticated imaging modalities not only has been shown to distinguish between children with and without SDB but also may help to identify specific airway findings that contribute to the etiology of SDB. Investigators have found differences in the airways of children with SDB using MRI or imaging CT, namely, a smaller cross-sectional area and smaller airway volume. Although these methods may eventually help to predict, triage, and evaluate outcomes of treatment, these testing modalities are not universally available and require sedation, thus are primarily used for research purposes only. Endoscopy of the airway has also been widely used by pediatric otolaryngologists to evaluate the upper airway and identify potential contributory factors (ie, region of collapse, such as laryngomalacia, or obstruction). Visualization under anesthesia may not accurately reflect the appearance of the upper airway during normal sleep, which has been the most significant criticism. Sleep endoscopy, using a standardized technique of evaluating the airway, has been shown to have a positive predictive value of 0.94 and a negative predictive value of 0.8 in children presenting with SDB compared with PSG (Hamdy El-Hakim, MD, unpublished data, University of Alberta, Edmonton, Alberta, 2010). Finally, acoustic pharyngometry accurately predicts associated SDB diagnosed by PSG with high sensitivity (90.9%) and specificity (88.4%) but is also not widely available. In summary, although novel diagnostic methods to evaluate the airway show promise, routine use of imaging tools is not routinely used in primary care practice settings.
PSG and other techniques for diagnosing OSA
One important advancement in diagnosing SDB in children is the development of standardized, yet unvalidated, clinical diagnostic criteria for OSA that include symptoms and criteria for PSG. Despite this development, arriving at a diagnosis of SDB does not help clinicians to determine who should be referred for treatment and how urgently treatment is warranted. PSG is considered the diagnostic gold standard for evaluating children and adolescents for SDB. A PSG is a composite of simultaneously recorded physiologic variables, including respiratory variables, heart rate, and sleep stages. Each of the signals has inherent strengths and limitations. Advances in pediatric PSG over the past decade include advances in digital recording techniques, improvements in signal acquisition and processing, improved ability to measure various physiologic parameters, and recognition that a child-friendly atmosphere is necessary when dealing with children. Another significant landmark advancement was the 2007 publication by the Academy of Sleep Medicine of an updated scoring manual for sleep and associated events, which provides explicit rules for scoring various parameters of the PSG in both adults and children and standardizes the process of PSG review, interpretation, and reporting across centers. Although normative reference values have been determined for PSG in some children, standardized values are not available for all age groups for PSG. Furthermore, the data generated by PSG does not speak to the various sociocultural or genetic aspects affecting sleep parameters. When diagnostic tests, such as PSG, are used to diagnose OSA in epidemiologic studies, the prevalence rates vary from 1% to 4%. This likely under-represents the actual prevalence of SDB, because the usual basis for initiating PSG testing in clinical settings is the inherent assumption that the presence of habitual snoring (3 or more nights a week) is required.
There are inherent limitations in using the PSG as the sole diagnostic test for SDB. First, PSG is a de facto gold standard, because other methods of making a diagnosis of SDB, including history and physical examination, are inaccurate. PSG is a cumbersome, expensive, resource-intensive, and at times inconvenient, diagnostic procedure. Currently, the lack of sleep laboratories with expertise in studying children limits the accessibility of PSG in many regions, making it a relatively inaccessible test. Furthermore, PSG-derived respiratory parameters, including the apnea-hypopnea index and the number of desaturations and arousals, have not been found to reliably predict the degree of physical or psychological impairment in children with SDB. More recent research has attempted to examine other specific aspects of sleep (staging, cycle length, and microarchitecture) in an effort to predict outcomes as well as neurocognitive dysfunction associated with SDB.
The PSG does provide both objective qualitative and quantitative information regarding the key aspects of OSA, including hypoxia indices, hypercapnea, and degree of altered intrathoracic pressures as a measure of upper airway obstruction. It is important for clinicians to keep in mind that children symptomatic for SDB may have normal PSG parameters or, alternatively, that PSG parameters may be abnormal in relatively asymptomatic children. As a result, the American Academy of Sleep Medicine suggests that diagnosis of SDB in children should be based on the integration of the clinical data with the interpretation of the PSG by individuals qualified in the field of pediatric sleep medicine.
Alternatives to in-laboratory PSG are actively being sought, although currently their use is largely limited to research settings. It should be emphasized that each abbreviated testing modality, which uses a fraction or a single aspect of PSG (for example, limited channel monitoring, video, and so forth) or oximetry alone, results in a limited acquisition of information regarding respiratory parameters or sleep disruption or fragmentation, potentially leading to underdiagnosis or detection of only a subset of patients with severe disease. The development of more sophisticated techniques evaluating autonomic nervous system tone that enable measurement of arousal and more subtle forms of sleep fragmentation in association with oximetry is worthy of further consideration. To date, however, there is insufficient evidence supporting the use in clinical settings of unattended portable monitoring or abbreviated PSG testing in children over the traditional observed in-laboratory monitoring (PSG).
Finally, advances in proteonomics, genomics, and metabolomics have led to attempts to identify biomarkers in the blood or urine that could be used in a primary care setting to either diagnose children at risk for SDB or to identify the end-organ effect consequences of SDB, such as urine protein metabolites. Preliminary findings suggest a high sensitivity and specificity with a combination of biomarkers and clinical diagnostic criteria. This is still a research tool at present but may be a viable option for diagnosing children in the near future.
Treatment options
Surgical Treatments
Enlarged tonsils and adenoids constitute just one aspect of the pathophysiologic mechanism of SDB in children, treatment considerations should take into account all possible underlying etiologic factors involved that may contribute to airway dysfunction in the individual child. In contrast to older studies in which adenotonsillectomy was reported as “curative” for OSA, more recent literature using PSG confirmation of outcomes as well as improvement in clinical parameters suggests that treatment failures are increasingly common. For example, a recent multicenter longitudinal retrospective study of 578 children (mean age 6.9 ± 3.8 y) showed that adenotonsillectomy was curative, as defined by an apnea-hypopnea index less than 1 event per hour of total sleep time, in only 27.2% of children. Treatment failures may be especially prevalent in children with obesity. For example, studies have suggested that predictive factors for failure of adenotonsillectomy include age and body mass index z-score. Not only are obese children at much higher risk of persistent SDB but also data show that the risk of perioperative complications is up to 40-fold higher in obese children with SDB undergoing surgery. Unfortunately, the link between obesity and SDB has not been fully elucidated because some children, even though obese, respond to adenotonsillectomy. This implies a limited role for adenotonsillectomy in obese children much like in adult sleep apnea.
Other predictors of residual SDB across various studies have included a preoperative apnea-hypopnea index as a marker of severity as well as asthma. Asthma and obesity have also both been described as inflammatory states, so that those who are obese may have more asthma-like symptoms and, in turn, children with asthma tend to be more obese. In the same retrospective cohort study, it was found that among non-obese children, asthma also was a predictor of failure. The explanation could be that the underlying inflammation is the putative mechanism that results in an elevated apnea-hypopnea index, or SDB, or asthma. Allergic rhinitis was insignificant as a factor in that study but has previously been reported as a risk factor independent of asthma. The role of asthma and wheezing in association with tonsillar hypertrophy and SDB has been reported by several groups.
These findings on cure rates in healthy and obese children are based on the assumption that every surgical technique for adenotonsillectomy is equivalent and that for every child, adenotonsillar hypertrophy is the underlying pathophysiologic mechanism for SDB. Current investigations, such as the Randomized Controlled Study of Adenotonsillectomy (CHAT), a multicenter study currently under way with recruitment of more than 200 children, ages 5 to 9, are evaluating the current standard of OSA treatment in affected children. In the CHAT study, an early treatment group will receive adenotonsillectomy within 1 month of enrollment whereas the watchful waiting group will receive treatment within 7 months. Desired outcomes include the determination of which children should be treated and how urgently they should be managed.
There may still be a role for adenotonsillectomy in as the correct first line intervention for a specific phenotype of obstructive sleep apnea in the spectrum of SDB.
Although adenotonsillectomy is beneficial for some children, what is unknown is the magnitude and duration of the benefit of this procedure. The change in growth velocity postsurgery (ie, an increase in height and weight), which used to be a marker for success, has instead been shown consistently across studies to be a predictor of recurrence. One meta-analysis, encompassing 10 studies, evaluated growth and biomarker changes after adenotonsillectomy and found that height, weight, and biomarkers (insulinlike growth factor 1 and insulinlike growth factor binding protein) increased substantially post-treatment, indicating that some evidence of growth failure preoperatively may be related to SDB. Long-term follow-up studies in children up to 3 years postsurgical intervention found improvements in SDB symptoms using validated SDB symptom questionnaires in the short term. Unfortunately, the initial improvements were found to have a tendency to decline. In view of limited resolution or cure after treatment of SDB, it is often recommended that children have PSG preintervention and postintervention. This may not always be practical, however, especially when many children may not even have access to baseline testing. The significance of these shortfalls in diagnostic resources continues to be a challenge for many geographic regions in spite of the substantially increased number of accredited sleep facilities.
Nonpharmacologic Treatments
Positive airway pressure therapy
Those children and adolescents who do not have adenotonsillar hypertrophy, those who are not surgical candidates, or those who have different or additional risk factors for SDB require other treatment considerations. The common endpoint for these patients, irrespective of the underlying cause, is upper airway dysfunction and resulting airway collapse. Continuous positive airway pressure (CPAP) is used widely for treating adult SDB. In some instances, CPAP, even in children and adolescents, may be considered the first line of treatment in children for those who’s surgery is considered high risk or contraindicated. The key to establishing successful CPAP use in children involves an approach that engages the child and family that includes an experienced multidisciplinary health care team that is knowledgeable in the management of children or adolescents with SDB. Even with the involvement and support of professionals, the data suggest that compliance with treatment is found only in approximately 65% to 70%. Although few empirical data exist about the efficacy of positive airway pressure therapy in children, the treatment is becomingly more widely used. In contrast to adults, there are few data about the role of positive airway pressure therapy in treating end-organ dysfunction for children, and further research is needed.
Oral appliances
Limited ability to tolerate CPAP has resulted in patients and families seeking out alternative options for treatment of SDB. Oral appliances for treatment of patients with moderate sleep apnea or for those who do not tolerate CPAP have become more widely available for adults. The hesitation for widespread use in children has been the inability to anchor the devices to the primary teeth and potential long-term consequences on myofascial functioning and orthodontia. Oral appliances for treating SDB in children have only been studied in small samples to date, and although improved functional outcomes have been reported in one small study, this was not confirmed by PSG. Rapid maxillary expansion has also been evaluated in a few patients and was reported to result in a significant decrease in the apnea-hypopnea index even up to a year after treatment. Although initial results are promising, further research is warranted to determine the utility of such devices in the management of pediatric SDB outside of the research setting.
Pharmacologic Treatments
Previously, nonsurgical treatment, including the use of either intranasal or oral steroids, was used largely as a bridge to surgery. Medications are now are being considered as a viable, routinely used treatment option for those with mild SDB or snoring. The mechanism for the efficacy of steroids has been studied in cell culture from the harvested tonsils of children with PSG-confirmed SDB. A variety of steroids (decreasing in potency from fluticasone to budesonide to dexamethasone) have been shown to reduce proliferation rates of lymphoid tissue in a dose-dependent fashion and to enhance cellular apoptosis. The efficacy of intranasal steroids (budesonide) has also been demonstrated in a rigorous level I trial for mild SDB; the effect persisted after the end of the 8-week medication trial. Although the long-term benefit or the duration of treatment with this method is not known, it is likely beneficial for those children with mild SDB and/or with intermittent, seasonal symptoms, and for those for whom surgery is not indicated.
Tonsillar and adenoidal tissues have also been shown to express an abundance of leukotrienes and their receptors. The leukotriene pathway plays a role in both the inflammatory signaling pathway and the proliferation of adenotonsillar tissue in children with OSA. As a result, leukotriene receptor antagonists may be a useful adjunct in the array of treatments available for children with SDB. A 16-week open-label trial of a leukotriene receptor antagonist in a few children with mild SDB showed an improvement in breathing parameters. One small randomized controlled trial using a combination of intranasal steroids and leukotriene receptor antagonist for 12 weeks showed normalization of sleep parameters in 54% for those with residual SDB post-adenotonsillectomy. What is yet to be determined is which children are most likely to benefit from these pharmacologic treatments either before, in combination with, or in lieu of surgery.
With a better understanding of the mechanisms that cause SDB at the cellular level, development of other novel treatments may be considered. More recently, tonsil proliferating genes are being evaluated. A protein called phosphoserine phosphatase seems to be elevated in those with adenotonsillar hypertrophy. Pharmacologic inhibition of the protein results in reductions in B-cell and T-cell proliferation and apoptosis. Therefore, the development of pharmacologic treatments targeted toward these phosphatases may open up novel forms of nonsurgical treatments for SDB. With novel research such as this, the breadth of interventions for SDB is being expanded beyond the airway to a broader and global focus on prevention and treatment in vulnerable populations of children.
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