REVIEW URRENT C OPINION
Sleep medicine Aviv D. Goldbart a,b,c
Purpose of review To reflect the recent advances in the field of pediatric sleep medicine. The pediatrician will be able to define which children to refer for a sleep study and what to expect from the sleep specialist in 2015. Recent findings In the first study that compared adeno tonsillectomy (TA) to watchful waiting, TA reduced symptoms and improved children’s behavior, quality of life, and polysomnographic results. Anti-inflammatory therapy for mild obstructive sleep apnea was effective and well tolerated according to a double-blind study. A retrospective study showed that it is beneficial for 80% of the patients. TA is associated with a decrease in asthma symptoms and medication utilization. Summary Pediatricians need to be aware of the clear benefits of tonsillectomy (including better asthma control), although anti-inflammatory therapy may improve symptoms and polysomnographic findings in children with nonsevere obstructive sleep apnea. Keywords anti-inflammatory, obstructive sleep apnea, tonsillectomy
INTRODUCTION Although sleep has always been considered a crucial component of our lives, medicine did not see it as a distinct field until the second half of the 20th Century. The first studies on children’s sleep were performed in the late 70s. More recently, in the past decade, sleep medicine has gained recognition as an accredited pediatric subspecialty. The knowledge gained over the past 40 years is enormous, but there is still a need for more research in order to improve our understanding of the basic mechanisms (such as in insomnia) and to investigate new environmental changes that affect sleep and daytime functioning (such as daily use of smartphones). Today, pediatricians understand that the sleep specialist can provide assistance in areas in which previously they stood alone with their patient. Sleep medicine specialists can be especially helpful in cases of sleep apnea in which case parents refuse to go for surgery, and in adolescents with poor school performance as a result of a shifted night/day schedule. The present review will educate the pediatrician with regard to the most current findings in the field of sleep medicine.
OBSTRUCTIVE SLEEP APNEA Until a year ago, the best data on the polysomnographic outcome of adenotonsillectomy (TA) came
from a multicenter study that assessed the results of a polysomnography (PSG) performed before and 1 year after surgery in 578 children [1]. The authors reported normalization of the PSG results only in 27.2% of the patients! The risk factors for failure were the patient’s age (>7 years) and BMI (z-score >1.65). A recent and comprehensive study, published in the New England Journal of Medicine [2 ], randomized 464 children (5–9 years old) with PSG confirmed diagnosis of obstructive sleep apnea (OSA), to receive either TA or watchful waiting for 6 months. The researchers found that TA reduced the symptoms and improved the children’s behavior, quality of life, and PSG results. TA did not improve attention or executive function. The authors concluded that the study provides evidence of beneficial effects of early adenotonsillectomy. &&
a Department of Pediatrics, bPediatric Pulmonary and Sleep Research Laboratory and cSleep-Wake Disorders Center, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
Correspondence to Aviv D. Goldbart, MD, MSc, Department of Pediatrics, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.B. 151, Beer Sheva 84101, Israel. Tel: +972 8 6244465; fax: +972 8 6244465; e-mail: avivgold@ bgu.ac.il Curr Opin Pediatr 2015, 27:329–333 DOI:10.1097/MOP.0000000000000218
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Pulmonology
KEY POINTS
62%. Older (> 7 years) and obese children (BMI z-score >1.65) were less likely to benefit from the therapy [7 ]. Anti-inflammatory treatment for nonsevere OSA appears be effective and stands as an alternative to TA, especially in young and nonobese children. There is a need in more randomized trials to validate this therapeutic avenue. &
TA for OSA reduces symptoms, and improves children’s behavior, quality of life, and polysomnographic findings. Anti-inflammatory therapy for mild OSA is effective, safe, and beneficial for up to 80% of patients. TA is associated with a major decrease in asthma symptoms and medication consumption.
However, close review of the study results demonstrates that 46% of the nonobese, 46% of the nonblack, and 65% of the lower median apnea– hypopnea index (AHI) normalized their PSG findings in the watchful waiting arm, without TA. The discussion in the New England Journal of Medicine ends with this sentence: ‘Normalization of polysomnographic findings in a large number of children in the watchful waiting group and an absence of significant cognitive decline in this group indicate that medical management and reassessment after a period of observation may be a valid therapeutic option’. Since TA can be painful and complications may occur, pediatricians can justifiably employ medical treatments in patients with surgical contraindications or those with residual OSA after surgery. Current American Academy of Pediatrics (AAP) practice guidelines recommend intranasal corticosteroids as an option for children with mild OSA in whom adenotonsillectomy is contraindicated, or used for mild postoperative OSA [3 ]. Leukotriene receptor antagonists represent another therapeutic option in nonsevere OSA. The rationale for a trial of leukotriene receptor antagonists in children with mild OSA includes the anti-inflammatory properties of the medication and evidence that leukotriene receptors are abundantly expressed in tonsils of children with OSA [4]. Montelukast treatment was assessed in an open fashion [5] in a double-blind, placebo-controlled approach [6 ], and proved to be safe, well tolerated, and efficient. It reduced the size of the adenoids (based on radiograph) and the AHI significantly, and a validated questionnaire reflected major improvement compared to placebo. Recently, a retrospective study evaluated the efficacy of a combination of intranasal corticosteroid and oral montelukast for 12 weeks in 2–14-yearold children with OSA. In 752 children who received the therapy, beneficial effects were noted in more than 80%, and tonsillectomy was performed in 12.3%. Follow-up PSG showed normalization in &
&
330
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SLEEP DEPRIVATION: OLD AND NEW CAUSES Shorter self-reported sleep times in adolescents are associated with poor school performance, and emotional and behavioral problems [8]. The effects of sleep impairment have been most intensively studied in children with OSA. A recent comprehensive review [9] concludes that inadequate sleep quality, quantity, or a combination of both these factors, can cause sleepiness, inattention, and, very likely, other cognitive and behavioral deficits in children and adolescents. Electronic media have a negative impact on children’s sleep. The most recent review in this field identified 36 studies that examined the relationship between sleep and electronic media in children and adolescents. The mechanisms whereby sleep quality or quantity might be compromised by electronic media include the following: directly displace sleep or other activities related to good sleep hygiene; and evening use might lead to physiologic arousal and reluctance to relax prior to bedtime [10]. Following this meta-analysis and other studies, the AAP decided to limit electronic media use because of the effects it has on children’s development, socialization, general health, and sleep. The current recommendations call for limiting total screen time to less than 1–2 h per day, discourage screen media exposure for children aged below 2 years of age, and keep the television set and internet-connected electronic devices out of the child’s bedroom [11].
THE INTERACTIONS BETWEEN SLEEP AND GENERAL PEDIATRIC DISORDERS Sleep plays an important role in virtually every area of clinical medicine. The most striking recent findings are summarized in the next paragraphs.
Sleep and asthma Obstructive sleep-disordered breathing is highly prevalent in children with poorly controlled asthma. Data from an observational study suggest that TA markedly improves asthma outcomes in Volume 27 Number 3 June 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Sleep medicine Goldbart
children with poorly controlled asthma and comorbid OSA [12]. Using the 2003–2010 Market Scan database, researchers from Chicago identified 13 506 children with asthma in the United States who underwent TA, and found that the procedure was associated with significant reductions in most asthma prescription refills 1 year after tonsillectomy, supporting tonsillectomy as an important strategy for improving asthma control [13 ]. &
Sleep and obesity Short sleep duration is considered a potential risk for overweight/obesity in childhood and adolescence. A recent meta-analysis of longitudinal studies included 24 821 children and revealed that short sleepers had twice the risk of being overweight/ obese [odds ratio (OR) 2.15] [14]. The Avon Longitudinal Study collects data from birth through 6.75 years (n ¼ 1899). Using several models, and adjusting for several confounders, the investigators report that SDB and short sleep duration significantly and independently increase children’s odds of becoming overweight [15]. A recent case-control study in the United States demonstrated that obese adolescents with OSA had significantly worse executive function and attention, and more depression and externalizing symptoms compared to lean controls [16].
Sleep and epilepsy Sleep deprivation has long been recognized to lower seizure thresholds in persons with epilepsy. Acute sleep deprivation causes a rebound increase in the stage of sleep known as N3 or slow-wave sleep. Slow-wave sleep is the most highly synchronized sleep stage; its slow oscillations are closely associated with epileptogenesis [17]. Children with refractory epilepsy have a greater frequency of OSA symptoms relative to children with mild epilepsy (44 vs. 31%) [18]. Treatment of OSA can improve seizure control, sometimes to a striking degree [19].
WHO NEEDS A REFERRAL TO THE SLEEP LAB? Although there are many reasons to refer a child to the sleep lab, the leading cause for referrals to perform PSG is to rule out OSA. There is no current consensus on when children, who are candidates for tonsillectomy due to suspected OSA, should undergo overnight PSG. Separate guidelines have been developed by ear nose and throat (ENT) specialists and pediatricians. ENT pediatric society guidelines are evidencebased [20]. The authors recommend performing PSG prior to tonsillectomy if the child has a complex medical condition such as obesity, Down’s syndrome, craniofacial abnormalities, neuromuscular
Table 1. Summary of action statements for polysomnography Statement
Action
Evidence
I: Indications for PSG
Before performing tonsillectomy, the clinician should refer children with SDB for PSG if they exhibit any of the following: obesity, Down’s syndrome, craniofacial abnormalities, neuromuscular disorders, sickle cell disease, or mucopolysaccharidoses.
Recommendation based on observational studies with a preponderance of benefit over harm.
II: Advocating for PSG
The clinician should advocate for PSG prior to tonsillectomy for SDB in children ‘without’ any of the comorbidities listed in statement I for whom the need for surgery is uncertain or when there is discordance between tonsillar size on physical examination and the reported severity of SDB.
Recommendation based on observational and case-control studies with a preponderance of benefit over harm.
III: Communication with anesthesiologist
Clinicians should communicate PSG results to the anesthesiologist prior to the induction of anesthesia for tonsillectomy in a child with SDB.
Recommendation based on observational studies with a preponderance of benefit over harm.
IV: Inpatient admission for children with OSA documented in results of PSG
Clinicians should admit children with OSA documented in results of PSG for inpatient, overnight monitoring after tonsillectomy if they are younger than age 3 or have severe OSA (apnea– hypopnea index of 10 or more obstructive events/hour, oxygen saturation nadir less than 80%, or both).
Recommendation based on observational studies with a preponderance of benefit over harm.
V: Unattended PSG with portable monitoring device
In children for whom PSG is indicated to assess SDB prior to tonsillectomy, clinicians should obtain laboratory-based PSG, when available.
Recommendation based on diagnostic studies with limitations and a preponderance of benefit over harm.
OSA, obstructive sleep apnea; PSG, polysomnography; SDB, sleep-disordered breathing [20].
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Pulmonology
disorders, sickle cell disease, or mucopolysaccharidoses. PSG is also recommended when the need for surgery is uncertain or when there is discordance between tonsillar size on physical examination, and the reported severity of sleep-disordered breathing. The recommendations are summarized in Table 1. The 2012 AAP guidelines recommend that children who snore regularly (>3/week), and have signs or symptoms of OSA should be evaluated either by PSG, alternative tests, or referral to a sleep specialist or an ENT specialist. In the absence of ready availability to PSG, alternative tests such as nocturnal video recording, nocturnal oximetry, daytime nap PSG, or ambulatory PSG can be obtained to lend support to a particular therapeutic course recommendation [3 ]. &
WHAT CAN THE SLEEP LAB OFFER IN 2015 APART FROM POLYSOMNOGRAPHY Several standard and newer methods are available in most pediatric sleep labs. Relatively widely available diagnostic tools are described in the following paragraphs. The multiple sleep latency test (MSLT) determines sleepiness according to standard published values. The test is performed following an overnight PSG and is composed of 4–5 tests. Contingent upon the results of the MSLT, a sleep specialist can make a diagnosis (e.g. narcolepsy narcolepsy) and offer a therapeutic option (e.g. medications). Actigraphy is a small device that the patient wears on the nondominant arm (or foot in babies) and which depicts the wake–sleep cycle [21]. The device is an accelerometer that differentiates (with high sensitivity and specificity) between wake and sleep. Actigraphy provides a more objective measure than parent report, and is capable of measuring sleep–wake configurations over an extended period, in the ambulatory setting. Classically, this technology is used to demonstrate delayed sleep phase syndrome, insomnia, or the response to drug therapy (e.g. melatonin). Peripheral arterial tonometry (PAT) is a relatively new technology in use for patients older than 18 years and may soon be applied to children. This device is a home testing device for OSA, currently recommended by the American Academy of Sleep Medicine for the diagnosis of OSA in adults [22]. Although several companies are developing mobile apps for the diagnosis of sleep disorders in children, currently none is available [23]. The sleep specialist is trained to identify the chief complaint and pick the best tools in order to provide an accurate diagnosis and precise therapy. The pediatrician must discern which children will most benefit from referral to a sleep medicine specialist. 332
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CONCLUSION Current data support a role for tonsillectomy (and perhaps to optimize asthma control) in OSA, although anti-inflammatory medications improve objective physical and PSG findings in most of the children with OSA (nonsevere OSA). Acknowledgements None. Financial support and sponsorship This work was supported by the Israel Science Foundation (ISF 753/11). Conflicts of interest There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Bhattacharjee R, Kheirandish-Gozal L, Spruyt K, et al. Adenotonsillectomy outcomes in treatment of obstructive sleep apnea in children: a multicenter retrospective study. Am J Respir Crit Care Med 2010; 182:676–683. 2. Marcus CL, Moore RH, Rosen CL, et al. A randomized trial of adenotonsil&& lectomy for childhood sleep apnea. N Engl J Med 2013; 368:2366–2376. The first ever randomized double blind study that assessed the effects of tonsillectomy in children, a landmark in the fields of Pediatrics and Sleep Medicine. 3. Marcus CL, Brooks LJ, Draper KA, et al. Diagnosis and management of child& hood obstructive sleep apnea syndrome. Pediatrics 2012; 130:576–584. The current up-to-date guidelines of the AAP regarding children with OSA. 4. Goldbart AD, Goldman JL, Li RC, et al. Differential expression of cysteinyl leukotriene receptors 1 and 2 in tonsils of children with obstructive sleep apnea syndrome or recurrent infection. Chest 2004; 126:13–18. 5. Goldbart AD, Goldman JL, Veling MC, et al. Leukotriene modifier therapy for mild sleep-disordered breathing in children. Am J Respir Crit Care Med 2005; 172:364–370. 6. Goldbart AD, Greenberg-Dotan S, Tal A. Montelukast for children with & obstructive sleep apnea: a double-blind, placebo-controlled study. Pediatrics 2012; 130:e575–e580. The first double blind study that examined the effects of montelukast in children with OSA. It reinforced the findings of the previous open study (Ref. 5) 7. Kheirandish-Gozal L, Bhattacharjee R, Bandla HP, et al. Antiinflammatory & therapy outcomes for mild OSA in children. Chest 2014; 146:88–95. The largest group of OSA patients treated in a nonsurgical approach. 8. Dewald JF, Meijer AM, Oort FJ, et al. The influence of sleep quality, sleep duration and sleepiness on school performance in children and adolescents: a meta-analytic review. Sleep Med Rev 2010; 14:179–189. 9. Beebe DW. Cognitive, behavioral, and functional consequences of inadequate sleep in children and adolescents. Pediatr Clin North Am 2011; 58:649–665. 10. Cain N, Gradisar M. Electronic media use and sleep in school-aged children and adolescents: a review. Sleep Med 2010; 11:735–742. 11. American Academy of Pediatrics. Policy Statement: Children, Adolescents, and the Media. Council on communications and media. Pediatrics 2013; 132:958–961. 12. Ross K. Sleep-disordered breathing and childhood asthma: clinical implications. Curr Opin Pulm Med 2013; 19:79–83. 13. Bhattacharjee R, Choi BH, Gozal D. Association of adenotonsillectomy with & asthma outcomes in children: a longitudinal database analysis. PLoS Med 2014; 11:e1001753. The first large-scale study that supports the hypothesis that TA can improve asthma control. 14. Fatima Y1, Doi SA, Mamun AA. Longitudinal impact of sleep on overweight and obesity in children and adolescents: a systematic review and biasadjusted meta-analysis. Obes Rev 2015; 16:137–149; doi: 10.1111/ obr.12245. [Epub ahead of print] 15. Bonuck K, Chervin RD, Howe LD. Sleep-disordered breathing, sleep duration, and childhood overweight: a longitudinal cohort study. J Pediatr 2015; 166:632–639; doi: 10.1016/j.jpeds.2014.11.001. [Epub ahead of print]
Volume 27 Number 3 June 2015
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Sleep medicine Goldbart 16. Xanthopoulos MS1, Gallagher PR, Berkowitz RI. Neurobehavioral functioning in adolescents with and without obesity and obstructive sleep apnea. Sleep 2015; 38:401–410. doi: 10.5665/sleep.4498. 17. Gogou M, Gogou M, Haidopoulou K, et al. Sleep apneas and epilepsy comorbidity in childhood: a systematic review of the sleep breath. 2014. doi: 10.1007/s11325-014-1076-8. [Epub ahead of print] 18. Jain SV, Simakajornboon S, Shapiro SM, et al. Obstructive sleep apnea in children with epilepsy: prospective pilot trial. Acta Neurol Scand 2012; 125:e3–e6. 19. Accardo JA1, Malow BA2. Sleep, epilepsy, and autism. Epilepsy Behav 2014; doi: 10.1016/j.yebeh.2014.09.081. [Epub ahead of print]
20. Roland PS, Rosenfeld RM, Brooks L J, et al. Clinical practice guideline: polysomnography for sleep-disordered breathing prior to tonsillectomy in children. Otolaryngol Head Neck Surg 2011; 145 (1 Suppl):S1–S15. 21. Galland B, Meredith-Jones K, Terrill P, et al. Challenges and emerging technologies within the field of pediatric actigraphy. Front Psychiatry 2014; 5:99. 22. Collop NA, Anderson WM, Boehlecke B, et al. Clinical guidelines for the use of unattended portable monitors in the diagnosis of obstructive sleep apnea in adult patients. Portable Monitoring Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med 2007; 3:737–747. 23. Behar J, Roebuck A, Domingos JS, et al. A review of current sleep screening applications for smartphones. Physiol Meas 2013; 34:R29–R46.
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333
Sleep medicine Aviv D. Goldbart a,b,c
Purpose of review To reflect the recent advances in the field of pediatric sleep medicine. The pediatrician will be able to define which children to refer for a sleep study and what to expect from the sleep specialist in 2015. Recent findings In the first study that compared adeno tonsillectomy (TA) to watchful waiting, TA reduced symptoms and improved children’s behavior, quality of life, and polysomnographic results. Anti-inflammatory therapy for mild obstructive sleep apnea was effective and well tolerated according to a double-blind study. A retrospective study showed that it is beneficial for 80% of the patients. TA is associated with a decrease in asthma symptoms and medication utilization. Summary Pediatricians need to be aware of the clear benefits of tonsillectomy (including better asthma control), although anti-inflammatory therapy may improve symptoms and polysomnographic findings in children with nonsevere obstructive sleep apnea. Keywords anti-inflammatory, obstructive sleep apnea, tonsillectomy
INTRODUCTION Although sleep has always been considered a crucial component of our lives, medicine did not see it as a distinct field until the second half of the 20th Century. The first studies on children’s sleep were performed in the late 70s. More recently, in the past decade, sleep medicine has gained recognition as an accredited pediatric subspecialty. The knowledge gained over the past 40 years is enormous, but there is still a need for more research in order to improve our understanding of the basic mechanisms (such as in insomnia) and to investigate new environmental changes that affect sleep and daytime functioning (such as daily use of smartphones). Today, pediatricians understand that the sleep specialist can provide assistance in areas in which previously they stood alone with their patient. Sleep medicine specialists can be especially helpful in cases of sleep apnea in which case parents refuse to go for surgery, and in adolescents with poor school performance as a result of a shifted night/day schedule. The present review will educate the pediatrician with regard to the most current findings in the field of sleep medicine.
OBSTRUCTIVE SLEEP APNEA Until a year ago, the best data on the polysomnographic outcome of adenotonsillectomy (TA) came
from a multicenter study that assessed the results of a polysomnography (PSG) performed before and 1 year after surgery in 578 children [1]. The authors reported normalization of the PSG results only in 27.2% of the patients! The risk factors for failure were the patient’s age (>7 years) and BMI (z-score >1.65). A recent and comprehensive study, published in the New England Journal of Medicine [2 ], randomized 464 children (5–9 years old) with PSG confirmed diagnosis of obstructive sleep apnea (OSA), to receive either TA or watchful waiting for 6 months. The researchers found that TA reduced the symptoms and improved the children’s behavior, quality of life, and PSG results. TA did not improve attention or executive function. The authors concluded that the study provides evidence of beneficial effects of early adenotonsillectomy. &&
a Department of Pediatrics, bPediatric Pulmonary and Sleep Research Laboratory and cSleep-Wake Disorders Center, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
Correspondence to Aviv D. Goldbart, MD, MSc, Department of Pediatrics, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.B. 151, Beer Sheva 84101, Israel. Tel: +972 8 6244465; fax: +972 8 6244465; e-mail: avivgold@ bgu.ac.il Curr Opin Pediatr 2015, 27:329–333 DOI:10.1097/MOP.0000000000000218
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Pulmonology
KEY POINTS
62%. Older (> 7 years) and obese children (BMI z-score >1.65) were less likely to benefit from the therapy [7 ]. Anti-inflammatory treatment for nonsevere OSA appears be effective and stands as an alternative to TA, especially in young and nonobese children. There is a need in more randomized trials to validate this therapeutic avenue. &
TA for OSA reduces symptoms, and improves children’s behavior, quality of life, and polysomnographic findings. Anti-inflammatory therapy for mild OSA is effective, safe, and beneficial for up to 80% of patients. TA is associated with a major decrease in asthma symptoms and medication consumption.
However, close review of the study results demonstrates that 46% of the nonobese, 46% of the nonblack, and 65% of the lower median apnea– hypopnea index (AHI) normalized their PSG findings in the watchful waiting arm, without TA. The discussion in the New England Journal of Medicine ends with this sentence: ‘Normalization of polysomnographic findings in a large number of children in the watchful waiting group and an absence of significant cognitive decline in this group indicate that medical management and reassessment after a period of observation may be a valid therapeutic option’. Since TA can be painful and complications may occur, pediatricians can justifiably employ medical treatments in patients with surgical contraindications or those with residual OSA after surgery. Current American Academy of Pediatrics (AAP) practice guidelines recommend intranasal corticosteroids as an option for children with mild OSA in whom adenotonsillectomy is contraindicated, or used for mild postoperative OSA [3 ]. Leukotriene receptor antagonists represent another therapeutic option in nonsevere OSA. The rationale for a trial of leukotriene receptor antagonists in children with mild OSA includes the anti-inflammatory properties of the medication and evidence that leukotriene receptors are abundantly expressed in tonsils of children with OSA [4]. Montelukast treatment was assessed in an open fashion [5] in a double-blind, placebo-controlled approach [6 ], and proved to be safe, well tolerated, and efficient. It reduced the size of the adenoids (based on radiograph) and the AHI significantly, and a validated questionnaire reflected major improvement compared to placebo. Recently, a retrospective study evaluated the efficacy of a combination of intranasal corticosteroid and oral montelukast for 12 weeks in 2–14-yearold children with OSA. In 752 children who received the therapy, beneficial effects were noted in more than 80%, and tonsillectomy was performed in 12.3%. Follow-up PSG showed normalization in &
&
330
www.co-pediatrics.com
SLEEP DEPRIVATION: OLD AND NEW CAUSES Shorter self-reported sleep times in adolescents are associated with poor school performance, and emotional and behavioral problems [8]. The effects of sleep impairment have been most intensively studied in children with OSA. A recent comprehensive review [9] concludes that inadequate sleep quality, quantity, or a combination of both these factors, can cause sleepiness, inattention, and, very likely, other cognitive and behavioral deficits in children and adolescents. Electronic media have a negative impact on children’s sleep. The most recent review in this field identified 36 studies that examined the relationship between sleep and electronic media in children and adolescents. The mechanisms whereby sleep quality or quantity might be compromised by electronic media include the following: directly displace sleep or other activities related to good sleep hygiene; and evening use might lead to physiologic arousal and reluctance to relax prior to bedtime [10]. Following this meta-analysis and other studies, the AAP decided to limit electronic media use because of the effects it has on children’s development, socialization, general health, and sleep. The current recommendations call for limiting total screen time to less than 1–2 h per day, discourage screen media exposure for children aged below 2 years of age, and keep the television set and internet-connected electronic devices out of the child’s bedroom [11].
THE INTERACTIONS BETWEEN SLEEP AND GENERAL PEDIATRIC DISORDERS Sleep plays an important role in virtually every area of clinical medicine. The most striking recent findings are summarized in the next paragraphs.
Sleep and asthma Obstructive sleep-disordered breathing is highly prevalent in children with poorly controlled asthma. Data from an observational study suggest that TA markedly improves asthma outcomes in Volume 27 Number 3 June 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Sleep medicine Goldbart
children with poorly controlled asthma and comorbid OSA [12]. Using the 2003–2010 Market Scan database, researchers from Chicago identified 13 506 children with asthma in the United States who underwent TA, and found that the procedure was associated with significant reductions in most asthma prescription refills 1 year after tonsillectomy, supporting tonsillectomy as an important strategy for improving asthma control [13 ]. &
Sleep and obesity Short sleep duration is considered a potential risk for overweight/obesity in childhood and adolescence. A recent meta-analysis of longitudinal studies included 24 821 children and revealed that short sleepers had twice the risk of being overweight/ obese [odds ratio (OR) 2.15] [14]. The Avon Longitudinal Study collects data from birth through 6.75 years (n ¼ 1899). Using several models, and adjusting for several confounders, the investigators report that SDB and short sleep duration significantly and independently increase children’s odds of becoming overweight [15]. A recent case-control study in the United States demonstrated that obese adolescents with OSA had significantly worse executive function and attention, and more depression and externalizing symptoms compared to lean controls [16].
Sleep and epilepsy Sleep deprivation has long been recognized to lower seizure thresholds in persons with epilepsy. Acute sleep deprivation causes a rebound increase in the stage of sleep known as N3 or slow-wave sleep. Slow-wave sleep is the most highly synchronized sleep stage; its slow oscillations are closely associated with epileptogenesis [17]. Children with refractory epilepsy have a greater frequency of OSA symptoms relative to children with mild epilepsy (44 vs. 31%) [18]. Treatment of OSA can improve seizure control, sometimes to a striking degree [19].
WHO NEEDS A REFERRAL TO THE SLEEP LAB? Although there are many reasons to refer a child to the sleep lab, the leading cause for referrals to perform PSG is to rule out OSA. There is no current consensus on when children, who are candidates for tonsillectomy due to suspected OSA, should undergo overnight PSG. Separate guidelines have been developed by ear nose and throat (ENT) specialists and pediatricians. ENT pediatric society guidelines are evidencebased [20]. The authors recommend performing PSG prior to tonsillectomy if the child has a complex medical condition such as obesity, Down’s syndrome, craniofacial abnormalities, neuromuscular
Table 1. Summary of action statements for polysomnography Statement
Action
Evidence
I: Indications for PSG
Before performing tonsillectomy, the clinician should refer children with SDB for PSG if they exhibit any of the following: obesity, Down’s syndrome, craniofacial abnormalities, neuromuscular disorders, sickle cell disease, or mucopolysaccharidoses.
Recommendation based on observational studies with a preponderance of benefit over harm.
II: Advocating for PSG
The clinician should advocate for PSG prior to tonsillectomy for SDB in children ‘without’ any of the comorbidities listed in statement I for whom the need for surgery is uncertain or when there is discordance between tonsillar size on physical examination and the reported severity of SDB.
Recommendation based on observational and case-control studies with a preponderance of benefit over harm.
III: Communication with anesthesiologist
Clinicians should communicate PSG results to the anesthesiologist prior to the induction of anesthesia for tonsillectomy in a child with SDB.
Recommendation based on observational studies with a preponderance of benefit over harm.
IV: Inpatient admission for children with OSA documented in results of PSG
Clinicians should admit children with OSA documented in results of PSG for inpatient, overnight monitoring after tonsillectomy if they are younger than age 3 or have severe OSA (apnea– hypopnea index of 10 or more obstructive events/hour, oxygen saturation nadir less than 80%, or both).
Recommendation based on observational studies with a preponderance of benefit over harm.
V: Unattended PSG with portable monitoring device
In children for whom PSG is indicated to assess SDB prior to tonsillectomy, clinicians should obtain laboratory-based PSG, when available.
Recommendation based on diagnostic studies with limitations and a preponderance of benefit over harm.
OSA, obstructive sleep apnea; PSG, polysomnography; SDB, sleep-disordered breathing [20].
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Pulmonology
disorders, sickle cell disease, or mucopolysaccharidoses. PSG is also recommended when the need for surgery is uncertain or when there is discordance between tonsillar size on physical examination, and the reported severity of sleep-disordered breathing. The recommendations are summarized in Table 1. The 2012 AAP guidelines recommend that children who snore regularly (>3/week), and have signs or symptoms of OSA should be evaluated either by PSG, alternative tests, or referral to a sleep specialist or an ENT specialist. In the absence of ready availability to PSG, alternative tests such as nocturnal video recording, nocturnal oximetry, daytime nap PSG, or ambulatory PSG can be obtained to lend support to a particular therapeutic course recommendation [3 ]. &
WHAT CAN THE SLEEP LAB OFFER IN 2015 APART FROM POLYSOMNOGRAPHY Several standard and newer methods are available in most pediatric sleep labs. Relatively widely available diagnostic tools are described in the following paragraphs. The multiple sleep latency test (MSLT) determines sleepiness according to standard published values. The test is performed following an overnight PSG and is composed of 4–5 tests. Contingent upon the results of the MSLT, a sleep specialist can make a diagnosis (e.g. narcolepsy narcolepsy) and offer a therapeutic option (e.g. medications). Actigraphy is a small device that the patient wears on the nondominant arm (or foot in babies) and which depicts the wake–sleep cycle [21]. The device is an accelerometer that differentiates (with high sensitivity and specificity) between wake and sleep. Actigraphy provides a more objective measure than parent report, and is capable of measuring sleep–wake configurations over an extended period, in the ambulatory setting. Classically, this technology is used to demonstrate delayed sleep phase syndrome, insomnia, or the response to drug therapy (e.g. melatonin). Peripheral arterial tonometry (PAT) is a relatively new technology in use for patients older than 18 years and may soon be applied to children. This device is a home testing device for OSA, currently recommended by the American Academy of Sleep Medicine for the diagnosis of OSA in adults [22]. Although several companies are developing mobile apps for the diagnosis of sleep disorders in children, currently none is available [23]. The sleep specialist is trained to identify the chief complaint and pick the best tools in order to provide an accurate diagnosis and precise therapy. The pediatrician must discern which children will most benefit from referral to a sleep medicine specialist. 332
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CONCLUSION Current data support a role for tonsillectomy (and perhaps to optimize asthma control) in OSA, although anti-inflammatory medications improve objective physical and PSG findings in most of the children with OSA (nonsevere OSA). Acknowledgements None. Financial support and sponsorship This work was supported by the Israel Science Foundation (ISF 753/11). Conflicts of interest There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Bhattacharjee R, Kheirandish-Gozal L, Spruyt K, et al. Adenotonsillectomy outcomes in treatment of obstructive sleep apnea in children: a multicenter retrospective study. Am J Respir Crit Care Med 2010; 182:676–683. 2. Marcus CL, Moore RH, Rosen CL, et al. A randomized trial of adenotonsil&& lectomy for childhood sleep apnea. N Engl J Med 2013; 368:2366–2376. The first ever randomized double blind study that assessed the effects of tonsillectomy in children, a landmark in the fields of Pediatrics and Sleep Medicine. 3. Marcus CL, Brooks LJ, Draper KA, et al. Diagnosis and management of child& hood obstructive sleep apnea syndrome. Pediatrics 2012; 130:576–584. The current up-to-date guidelines of the AAP regarding children with OSA. 4. Goldbart AD, Goldman JL, Li RC, et al. Differential expression of cysteinyl leukotriene receptors 1 and 2 in tonsils of children with obstructive sleep apnea syndrome or recurrent infection. Chest 2004; 126:13–18. 5. Goldbart AD, Goldman JL, Veling MC, et al. Leukotriene modifier therapy for mild sleep-disordered breathing in children. Am J Respir Crit Care Med 2005; 172:364–370. 6. Goldbart AD, Greenberg-Dotan S, Tal A. Montelukast for children with & obstructive sleep apnea: a double-blind, placebo-controlled study. Pediatrics 2012; 130:e575–e580. The first double blind study that examined the effects of montelukast in children with OSA. It reinforced the findings of the previous open study (Ref. 5) 7. Kheirandish-Gozal L, Bhattacharjee R, Bandla HP, et al. Antiinflammatory & therapy outcomes for mild OSA in children. Chest 2014; 146:88–95. The largest group of OSA patients treated in a nonsurgical approach. 8. Dewald JF, Meijer AM, Oort FJ, et al. The influence of sleep quality, sleep duration and sleepiness on school performance in children and adolescents: a meta-analytic review. Sleep Med Rev 2010; 14:179–189. 9. Beebe DW. Cognitive, behavioral, and functional consequences of inadequate sleep in children and adolescents. Pediatr Clin North Am 2011; 58:649–665. 10. Cain N, Gradisar M. Electronic media use and sleep in school-aged children and adolescents: a review. Sleep Med 2010; 11:735–742. 11. American Academy of Pediatrics. Policy Statement: Children, Adolescents, and the Media. Council on communications and media. Pediatrics 2013; 132:958–961. 12. Ross K. Sleep-disordered breathing and childhood asthma: clinical implications. Curr Opin Pulm Med 2013; 19:79–83. 13. Bhattacharjee R, Choi BH, Gozal D. Association of adenotonsillectomy with & asthma outcomes in children: a longitudinal database analysis. PLoS Med 2014; 11:e1001753. The first large-scale study that supports the hypothesis that TA can improve asthma control. 14. Fatima Y1, Doi SA, Mamun AA. Longitudinal impact of sleep on overweight and obesity in children and adolescents: a systematic review and biasadjusted meta-analysis. Obes Rev 2015; 16:137–149; doi: 10.1111/ obr.12245. [Epub ahead of print] 15. Bonuck K, Chervin RD, Howe LD. Sleep-disordered breathing, sleep duration, and childhood overweight: a longitudinal cohort study. J Pediatr 2015; 166:632–639; doi: 10.1016/j.jpeds.2014.11.001. [Epub ahead of print]
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Sleep medicine Goldbart 16. Xanthopoulos MS1, Gallagher PR, Berkowitz RI. Neurobehavioral functioning in adolescents with and without obesity and obstructive sleep apnea. Sleep 2015; 38:401–410. doi: 10.5665/sleep.4498. 17. Gogou M, Gogou M, Haidopoulou K, et al. Sleep apneas and epilepsy comorbidity in childhood: a systematic review of the sleep breath. 2014. doi: 10.1007/s11325-014-1076-8. [Epub ahead of print] 18. Jain SV, Simakajornboon S, Shapiro SM, et al. Obstructive sleep apnea in children with epilepsy: prospective pilot trial. Acta Neurol Scand 2012; 125:e3–e6. 19. Accardo JA1, Malow BA2. Sleep, epilepsy, and autism. Epilepsy Behav 2014; doi: 10.1016/j.yebeh.2014.09.081. [Epub ahead of print]
20. Roland PS, Rosenfeld RM, Brooks L J, et al. Clinical practice guideline: polysomnography for sleep-disordered breathing prior to tonsillectomy in children. Otolaryngol Head Neck Surg 2011; 145 (1 Suppl):S1–S15. 21. Galland B, Meredith-Jones K, Terrill P, et al. Challenges and emerging technologies within the field of pediatric actigraphy. Front Psychiatry 2014; 5:99. 22. Collop NA, Anderson WM, Boehlecke B, et al. Clinical guidelines for the use of unattended portable monitors in the diagnosis of obstructive sleep apnea in adult patients. Portable Monitoring Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med 2007; 3:737–747. 23. Behar J, Roebuck A, Domingos JS, et al. A review of current sleep screening applications for smartphones. Physiol Meas 2013; 34:R29–R46.
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