Obstructive sleep apnea in children: a critical update

Hui-Leng Tan, David Gozal, Leila Kheirandish-Gozal, Hui-Leng Tan, David Gozal, Leila Kheirandish-Gozal

Abstract

Obstructive sleep apnea (OSA) in children is a highly prevalent disorder caused by a conglomeration of complex pathophysiological processes, leading to recurrent upper airway dysfunction during sleep. The clinical relevance of OSA resides in its association with significant morbidities that affect the cardiovascular, neurocognitive, and metabolic systems. The American Academy of Pediatrics recently reiterated its recommendations that children with symptoms and signs suggestive of OSA should be investigated with polysomnography (PSG), and treated accordingly. However, treatment decisions should not only be guided by PSG results, but should also integrate the magnitude of symptoms and the presence or absence of risk factors and signs of OSA morbidity. The first-line therapy in children with adenotonsillar hypertrophy is adenotonsillectomy, although there is increasing evidence that medical therapy, in the form of intranasal steroids or montelukast, may be considered in mild OSA. In this review, we delineate the major concepts regarding the pathophysiology of OSA, its morbidity, diagnosis, and treatment.

Keywords: adenotonsillar hypertrophy; morbidity; pathophysiology; pediatric sleep disordered breathing; polysomnography; treatment.

Figures

Figure 1
Figure 1
Pathophysiological factors involved in pediatric OSA. Abbreviations: FRC, functional residual capacity; OSA, obstructive sleep apnea.
Figure 2
Figure 2
Morbidity of pediatric OSA. Abbreviations: BP, blood pressure; OSA, obstructive sleep apnea.

References

    1. Kheirandish-Gozal L, Gozal D, editors. Sleep Disordered Breathing in Children A Comprehensive Clinical Guide to Evaluation and Treatment. New York, NY: Springer Science; 2012.
    1. Bixler EO, Vgontzas AN, Lin HM, et al. Sleep disordered breathing in children in a general population sample: prevalence and risk factors. Sleep. 2009;32(6):731–736.
    1. Li AM, So HK, Au CT, et al. Epidemiology of obstructive sleep apnoea syndrome in Chinese children: a two-phase community study. Thorax. 2010;65(11):991–997.
    1. Marcus CL, Brooks LJ, Draper KA, et al. American Academy of Pediatrics Diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. 2012;130(3):e714–e755.
    1. Rosen CL, Larkin EK, Kirchner HL, et al. Prevalence and risk factors for sleep-disordered breathing in 8- to 11-year-old children: association with race and prematurity. J Pediatr. 2003;142(4):383–389.
    1. Tauman R, Gozal D. Obstructive sleep apnea syndrome in children. Expert Rev Respir Med. 2011;5(3):425–440.
    1. Arens R, McDonough JM, Costarino AT, et al. Magnetic resonance imaging of the upper airway structure of children with obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2001;164(4):698–703.
    1. Nandalike K, Shifteh K, Sin S, et al. Adenotonsillectomy in obese children with obstructive sleep apnea syndrome: magnetic resonance imaging findings and considerations. Sleep. 2013;36(6):841–847.
    1. Dayyat E, Kheirandish-Gozal L, Sans Capdevila O, Maarafeya MM, Gozal D. Obstructive sleep apnea in children: relative contributions of body mass index and adenotonsillar hypertrophy. Chest. 2009;136(1):137–144.
    1. Arens R, Sin S, Nandalike K, et al. Upper airway structure and body fat composition in obese children with obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2011;183(6):782–787.
    1. Parikh SR, Sadoughi B, Sin S, Willen S, Nandalike K, Arens R. Deep cervical lymph node hypertrophy: A new paradigm in the understanding of pediatric obstructive sleep apnea. Laryngoscope. 2013;123(8):2043–2049.
    1. Arens R, Sin S, Willen S, et al. Rhino-sinus involvement in children with obstructive sleep apnea syndrome. Pediatr Pulmonol. 2010;45(10):993–998.
    1. Gozal D. Pediatric OSA: a case for “United We Stand” in the way of a breath. Pediatr Pulmonol. 2010;45(12):1151–1152.
    1. Kim J, Bhattacharjee R, Dayyat E, et al. Increased cellular proliferation and inflammatory cytokines in tonsils derived from children with obstructive sleep apnea. Pediatr Res. 2009;66(4):423–428.
    1. Serpero LD, Kheirandish-Gozal L, Dayyat E, Goldman JL, Kim J, Gozal D. A mixed cell culture model for assessment of proliferation in tonsillar tissues from children with obstructive sleep apnea or recurrent tonsillitis. Laryngoscope. 2009;119(5):1005–1010.
    1. Goldbart AD, Krishna J, Li RC, Serpero LD, Gozal D. Inflammatory mediators in exhaled breath condensate of children with obstructive sleep apnea syndrome. Chest. 2006;130(1):143–148.
    1. Li AM, Hung E, Tsang T, et al. Induced sputum inflammatory measures correlate with disease severity in children with obstructive sleep apnoea. Thorax. 2007;62(1):75–79.
    1. Li AM, Wong E, Kew J, Hui S, Fok TF. Use of tonsil size in the evaluation of obstructive sleep apnoea. Arch Dis Child. 2002;87(2):156–159.
    1. Marcus CL, McColley SA, Carroll JL, Loughlin GM, Smith PL, Schwartz AR. Upper airway collapsibility in children with obstructive sleep apnea syndrome. J Appl Physiol. 1994;77(2):918–924.
    1. Schwartz AR, Smith PL. CrossTalk proposal: the human upper airway does behave like a Starling resistor during sleep. J Physiol. 2013;591:2229–2232.
    1. Gozal D, Burnside MM. Increased upper airway collapsibility in children with obstructive sleep apnea during wakefulness. Am J Respir Crit Care Med. 2004;169(2):163–167.
    1. Carrera HL, McDonough JM, Gallagher PR, et al. Upper airway collapsibility during wakefulness in children with sleep disordered breathing, as determined by the negative expiratory pressure technique. Sleep. 2011;34(6):717–724.
    1. Thong JF, Pang KP. Clinical parameters in obstructive sleep apnea: are there any correlations? J Otolaryngol Head Neck Surg. 2008;37(6):894–900.
    1. Strauss T, Sin S, Marcus CL, et al. Upper airway lymphoid tissue size in children with sickle cell disease. Chest. 2012;142(1):94–100.
    1. Huang J, Pinto SJ, Allen JL, et al. Upper airway genioglossal activity in children with sickle cell disease. Sleep. 2011;34(6):773–778.
    1. Gozal D, Kheirandish-Gozal L. Childhood obesity and sleep: relatives, partners, or both? – a critical perspective on the evidence. Ann NY Acad Sci. 2012;1264(1):135–141.
    1. Redline S, Tishler PV, Schluchter M, Aylor J, Clark K, Graham G. Risk factors for sleep-disordered breathing in children. Associations with obesity, race, and respiratory problems. Am J Respir Crit Care Med. 1999;159(5 Pt 1):1527–1532.
    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(5):676–683.
    1. Canapari CA, Hoppin AG, Kinane TB, Thomas BJ, Torriani M, Katz ES. Relationship between sleep apnea, fat distribution, and insulin resistance in obese children. J Clin Sleep Med. 2011;7(3):268–273.
    1. Tauman R, Gulliver TE, Krishna J, et al. Persistence of obstructive sleep apnea syndrome in children after adenotonsillectomy. J Pediatr. 2006;149(6):803–808.
    1. Mitchell RB, Boss EF. Pediatric obstructive sleep apnea in obese and normal-weight children: impact of adenotonsillectomy on quality-of-life and behaviour. Dev Neuropsychol. 2009;34(5):650–661.
    1. Marcus CL, Moore RH, Rosen CL, et al. Childhood Adenotonsillectomy Trial (CHAT) A randomized trial of adenotonsillectomy for childhood sleep apnea. N Engl J Med. 2013;368(25):2366–2376.
    1. Spruyt K, Sans Capdevila O, Serpero LD, Kheirandish-Gozal L, Gozal D. Dietary and physical activity patterns in children with obstructive sleep apnea. J Pediatr. 2010;156(5):724–730. 730. e1.
    1. Bhattacharjee R, Kim J, Kheirandish-Gozal L, Gozal D. Obesity and obstructive sleep apnea syndrome in children: a tale of inflammatory cascades. Pediatr Pulmonol. 2011;46(4):313–323.
    1. Gozal D. Sleep, sleep disorders and inflammation in children. Sleep Med. 2009;10(Suppl 1):S12–S16.
    1. Tauman R, O’Brien LM, Gozal D. Hypoxemia and obesity modulate plasma C-reactive protein and interleukin-6 levels in sleep-disordered breathing. Sleep Breath. 2007;11(2):77–84.
    1. Gozal D, Serpero LD, Kheirandish-Gozal L, Capdevila OS, Khalyfa A, Tauman R. Sleep measures and morning plasma TNF-alpha levels in children with sleep-disordered breathing. Sleep. 2010;33(3):319–325.
    1. Tam CS, Wong M, McBain R, Bailey S, Waters KA. Inflammatory measures in children with obstructive sleep apnoea. J Paediatr Child Health. 2006;42(5):277–282.
    1. Gozal D, Serpero LD, Sans Capdevila O, Kheirandish-Gozal L. Systemic inflammation in non-obese children with obstructive sleep apnea. Sleep Med. 2008;9(3):254–259.
    1. Khalyfa A, Capdevila OS, Buazza MO, Serpero LD, Kheirandish-Gozal L, Gozal D. Genome-wide gene expression profiling in children with non-obese obstructive sleep apnea. Sleep Med. 2009;10(1):75–86.
    1. Kim J, Bhattacharjee R, Khalyfa A, et al. DNA methylation in inflammatory genes among children with obstructive sleep apnea. Am J Respir Crit Care Med. 2012;185(3):330–338.
    1. Tan HL, Gozal D, Wang Y, et al. Alterations in circulating T-cell lymphocyte populations in children with obstructive sleep apnea. Sleep. 2013;36(6):913–922.
    1. Kheirandish-Gozal L, Gozal D. Genotype-phenotype interactions in pediatric obstructive sleep apnea. Respir Physiol Neurobiol. 2013 Apr 3; Epub.
    1. Guilleminault C, Eldridge FL, Simmons FB, Dement WC. Sleep apnea in eight children. Pediatrics. 1976;58(1):23–30.
    1. Serratto M, Harris VJ, Carr I. Upper airways obstruction. Presentation with systemic hypertension. Arch Dis Child. 1981;56(2):153–155.
    1. Ross RD, Daniels SR, Loggie JM, Meyer RA, Ballard ET. Sleep apnea-associated hypertension and reversible left ventricular hypertrophy. J Pediatr. 1987;111(2):253–255.
    1. Adegunsoye A, Ramachandran S. Etiopathogenetic mechanisms of pulmonary hypertension in sleep-related breathing disorders. Pulm Med. 2012;2012:273591.
    1. Nisbet RE, Graves AS, Kleinhenz DJ, et al. The role of NADPH oxidase in chronic intermittent hypoxia-induced pulmonary hypertension in mice. Am J Respir Cell Mol Biol. 2009;40(5):601–609.
    1. Abman SH, Ivy DD. Recent progress in understanding pediatric pulmonary hypertension. Curr Opin Pediatr. 2011;23(3):298–304.
    1. Marcus CL, Greene MG, Carroll JL. Blood pressure in children with obstructive sleep apnea. Am J Respir Crit Care Med. 1998;157(4 Pt 1):1098–1103.
    1. Kohyama J, Ohinata JS, Hasegawa T. Blood pressure in sleep disordered breathing. Arch Dis Child. 2003;88(2):139–142.
    1. Horne RS, Yang JS, Walter LM, et al. Elevated blood pressure during sleep and wake in children with sleep-disordered breathing. Pediatrics. 2011;128(1):e85–e92.
    1. Amin RS, Carroll JL, Jeffries JL, et al. Twenty-four-hour ambulatory blood pressure in children with sleep-disordered breathing. Am J Respir Crit Care Med. 2004;169(8):950–956.
    1. Verdecchia P, Schillaci G, Borgioni C, et al. Altered circadian blood pressure profile and prognosis. Blood Press Monit. 1997;2(6):347–352.
    1. Amin R, Somers VK, McConnell K, et al. Activity-adjusted 24-hour ambulatory blood pressure and cardiac remodeling in children with sleep disordered breathing. Hypertension. 2008;51(1):84–91.
    1. Nisbet LC, Yiallourou SR, Walter LM, Horne RS. Blood pressure regulation, autonomic control and sleep disordered breathing in children. Sleep Med Rev. July2013 Epub.
    1. Li AM, Au CT, Ho C, Fok TF, Wing YK. Blood pressure is elevated in children with primary snoring. J Pediatr. 2009;155(3):362–368. e1.
    1. Kwok KL, Ng DK, Cheung YF. BP and arterial distensibility in children with primary snoring. Chest. 2003;123(5):1561–1566.
    1. Goldbart AD, Levitas A, Greenberg-Dotan S, et al. B-type natriuretic peptide and cardiovascular function in young children with obstructive sleep apnea. Chest. 2010;138(3):528–535.
    1. Gozal D, Kheirandish-Gozal L, Serpero LD, Sans Capdevila O, Dayyat E. Obstructive sleep apnea and endothelial function in school-aged nonobese children: effect of adenotonsillectomy. Circulation. 2007;116(20):2307–2314.
    1. Kheirandish-Gozal L, Bhattacharjee R, Kim J, Clair HB, Gozal D. Endothelial progenitor cells and vascular dysfunction in children with obstructive sleep apnea. Am J Respir Crit Care Med. 2010;182(1):92–97.
    1. Kheirandish-Gozal L, Etzioni T, Bhattacharjee R, et al. Obstructive sleep apnea in children is associated with severity-dependent deterioration in overnight endothelial function. Sleep Med. 2013;14(6):526–531.
    1. Dubern B, Aggoun Y, Boulé M, Fauroux B, Bonnet D, Tounian P. Arterial alterations in severely obese children with obstructive sleep apnoea. Int J Pediatr Obes. 2010;5(3):230–236.
    1. Bhattacharjee R, Kim J, Alotaibi WH, Kheirandish-Gozal L, Capdevila OS, Gozal D. Endothelial dysfunction in children without hypertension: potential contributions of obesity and obstructive sleep apnea. Chest. 2012;141(3):682–691.
    1. Gozal D, Kheirandish-Gozal L. The obesity epidemic and disordered sleep during childhood and adolescence. Adolesc Med State Art Rev. 2010;21(3):480–490. viii.
    1. Pearson TA, Mensah GA, Alexander RW, et al. Centers for Disease Control and Prevention. American Heart Association Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003;107(3):499–511.
    1. Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation. 2000;102(18):2165–2168.
    1. Pasceri V, Cheng JS, Willerson JT, Yeh ET, Chang J. Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation. 2001;103(21):2531–2534.
    1. Kheirandish-Gozal L, Capdevila OS, Tauman R, Gozal D. Plasma C-reactive protein in nonobese children with obstructive sleep apnea before and after adenotonsillectomy. J Clin Sleep Med. 2006;2(3):301–304.
    1. Gozal D, Kheirandish-Gozal L, Bhattacharjee R, Kim J. C-reactive protein and obstructive sleep apnea syndrome in children. Front Biosci (Elite Ed) 2012;4:2410–2422.
    1. Ingram DG, Matthews CK. Effect of adenotonsillectomy on c-reactive protein levels in children with obstructive sleep apnea: a meta-analysis. Sleep Med. 2013;14(2):172–176.
    1. Gozal D, Kaditis AG, Khalyfa A, et al. Association between variants in CRP and IL-6 genes and susceptibility to OSA in children: A candidate-gene association study in European American and South-East European populations. 2013. In press.
    1. O’Brien LM, Serpero LD, Tauman R, Gozal D. Plasma adhesion molecules in children with sleep-disordered breathing. Chest. 2006;129(4):947–953.
    1. Kim J, Bhattacharjee R, Snow AB, Capdevila OS, Kheirandish-Gozal L, Gozal D. Myeloid-related protein 8/14 levels in children with obstructive sleep apnoea. Eur Respir J. 2010;35(4):843–850.
    1. Kim J, Bhattacharjee R, Kheirandish-Gozal L, Spruyt K, Gozal D. Circulating microparticles in children with sleep disordered breathing. Chest. 2011;140(2):408–417.
    1. Bhushan B, Khalyfa A, Spruyt K, et al. Fatty-acid binding protein 4 gene polymorphisms and plasma levels in children with obstructive sleep apnea. Sleep Med. 2011;12(7):666–671.
    1. Punjabi NM, Sorkin JD, Katzel LI, Goldberg AP, Schwartz AR, Smith PL. Sleep-disordered breathing and insulin resistance in middle-aged and overweight men. Am J Respir Crit Care Med. 2002;165(5):677–682.
    1. Lam JC, Mak JC, Ip MS. Obesity, obstructive sleep apnoea and metabolic syndrome. Respirology. 2012;17(2):223–236.
    1. Assoumou HG, Gaspoz JM, Sforza E, et al. Obstructive sleep apnea and the metabolic syndrome in an elderly healthy population: the SYNAPSE cohort. Sleep Breath. 2012;16(3):895–902.
    1. Basoglu OK, Sarac F, Sarac S, Uluer H, Yilmaz C. Metabolic syndrome, insulin resistance, fibrinogen, homocysteine, leptin, and C-reactive protein in obese patients with obstructive sleep apnea syndrome. Ann Thorac Med. 2011;6(3):120–125.
    1. Pillai A, Warren G, Gunathilake W, Idris I. Effects of sleep apnea severity on glycemic control in patients with type 2 diabetes prior to continuous positive airway pressure treatment. Diabetes Technol Ther. 2011;13(9):945–949.
    1. Bhushan B, Misra A, Guleria R. Obstructive sleep apnea is independently associated with the metabolic syndrome in obese Asian Indians in northern India. Metab Syndr Relat Disord. 2010;8(5):431–435.
    1. Ahmed QA. Metabolic complications of obstructive sleep apnea syndrome. Am J Med Sci. 2008;335(1):60–64.
    1. Redline S, Storfer-Isser A, Rosen CL, et al. Association between metabolic syndrome and sleep-disordered breathing in adolescents. Am J Respir Crit Care Med. 2007;176(4):401–408.
    1. Koren D, Levitt Katz LE, Brar PC, Gallagher PR, Berkowitz RI, Brooks LJ. Sleep architecture and glucose and insulin homeostasis in obese adolescents. Diabetes Care. 2011;34(11):2442–2447.
    1. Lesser DJ, Bhatia R, Tran WH, et al. Sleep fragmentation and intermittent hypoxemia are associated with decreased insulin sensitivity in obese adolescent Latino males. Pediatr Res. 2012;72(3):293–298.
    1. Tauman R, O’Brien LM, Ivanenko A, Gozal D. Obesity rather than severity of sleep-disordered breathing as the major determinant of insulin resistance and altered lipidemia in snoring children. Pediatrics. 2005;116(1):e66–e73.
    1. Kaditis AG, Alexopoulos EI, Damani E, et al. Obstructive sleep-disordered breathing and fasting insulin levels in nonobese children. Pediatr Pulmonol. 2005;40(6):515–523.
    1. Gozal D, Capdevila OS, Kheirandish-Gozal L. Metabolic alterations and systemic inflammation in obstructive sleep apnea among non-obese and obese prepubertal children. Am J Respir Crit Care Med. 2008;177(10):1142–1149.
    1. Khalyfa A, Gharib SA, Kim J, et al. Peripheral blood leukocyte gene expression patterns and metabolic parameters in habitually snoring and non-snoring children with normal polysomnographic findings. Sleep. 2011;34(2):153–160.
    1. Zong J, Liu Y, Huang Y, et al. Serum lipids alterations in adenoid hypertrophy or adenotonsillar hypertrophy children with sleep disordered breathing. Int J Pediatr Otorhinolaryngol. 2013;77(5):717–720.
    1. Kheirandish-Gozal L, Sans Capdevila O, Kheirandish E, Gozal D. Elevated serum aminotransferase levels in children at risk for obstructive sleep apnea. Chest. 2008;133(1):92–99.
    1. Verhulst SL, Jacobs S, Aerts L, et al. Sleep-disordered breathing: a new risk factor of suspected fatty liver disease in overweight children and adolescents? Sleep Breath. 2009;13(2):207–210.
    1. Verhulst SL, Rooman R, Van Gaal L, De Backer W, Desager K. Is sleep-disordered breathing an additional risk factor for the metabolic syndrome in obese children and adolescents? Int J Obes (Lond) 2009;33(1):8–13.
    1. Gozal D. Sleep-disordered breathing and school performance in children. Pediatrics. 1998;102(3 Pt 1):616–620.
    1. Chervin RD, Ruzicka DL, Hoban TF, et al. Esophageal pressures, polysomnography, and neurobehavioral outcomes of adenotonsillectomy in children. Chest. 2012;142(1):101–110.
    1. Giordani B, Hodges EK, Guire KE, et al. Changes in neuropsychological and behavioral functioning in children with and without obstructive sleep apnea following Tonsillectomy. J Int Neuropsychol Soc. 2012;18(2):212–222.
    1. Landau YE, Bar-Yishay O, Greenberg-Dotan S, Goldbart AD, Tarasiuk A, Tal A. Impaired behavioral and neurocognitive function in preschool children with obstructive sleep apnea. Pediatr Pulmonol. 2012;47(2):180–188.
    1. Bourke R, Anderson V, Yang JS, et al. Cognitive and academic functions are impaired in children with all severities of sleep-disordered breathing. Sleep Med. 2011;12(5):489–496.
    1. Garetz SL. Behavior, cognition, and quality of life after adenotonsillectomy for pediatric sleep-disordered breathing: summary of the literature. Otolaryngol Head Neck Surg. 2008;138(Suppl 1):S19–S26.
    1. Wei JL, Bond J, Mayo MS, Smith HJ, Reese M, Weatherly RA. Improved behavior and sleep after adenotonsillectomy in children with sleep-disordered breathing: long-term follow-up. Arch Otolaryngol Head Neck Surg. 2009;135(7):642–646.
    1. Wei JL, Mayo MS, Smith HJ, Reese M, Weatherly RA. Improved behaviour and sleep after adenotonsillectomy in children with sleep-disordered breathing. Arch Otolaryngol Head Neck Surg. 2007;133(10):974–979.
    1. Abman S, Jobe A, Chernick V, et al. NHLBI working group report Strategic plan for pediatric respiratory diseases research: an NHLBI working group report. Pediatr Pulmonol. 2009;44(1):2–13.
    1. Gozal D, Kheirandish-Gozal L. Neurocognitive and behavioral morbidity in children with sleep disorders. Curr Opin Pulm Med. 2007;13(6):505–509.
    1. Chervin RD, Ruzicka DL, Giordani BJ, et al. Sleep-disordered breathing, behaviour, and cognition in children before and after adenotonsillectomy. Pediatrics. 2006;117(4):e769–e778.
    1. Montgomery-Downs HE, Crabtree VM, Gozal D. Cognition, sleep and respiration in at-risk children treated for obstructive sleep apnoea. Eur Respir J. 2005;25(2):336–342.
    1. Friedman BC, Hendeles-Amitai A, Kozminsky E, et al. Adenotonsillectomy improves neurocognitive function in children with obstructive sleep apnea syndrome. Sleep. 2003;26(8):999–1005.
    1. Kaemingk KL, Pasvogel AE, Goodwin JL, et al. Learning in children and sleep disordered breathing: findings of the Tucson Children’s Assessment of Sleep Apnea (tuCASA) prospective cohort study. J Int Neuropsychol Soc. 2003;9(7):1016–1026.
    1. Kheirandish-Gozal L, De Jong MR, Spruyt K, Chamuleau SA, Gozal D. Obstructive sleep apnoea is associated with impaired pictorial memory task acquisition and retention in children. Eur Respir J. 2010;36(1):164–169.
    1. O’Brien LM, Mervis CB, Holbrook CR, et al. Neurobehavioral implications of habitual snoring in children. Pediatrics. 2004;114(1):44–49.
    1. Barnes ME, Gozal D, Molfese DL. Attention in children with obstructive sleep apnoea: an event-related potentials study. Sleep Med. 2012;13(4):368–377.
    1. Barnes ME, Huss EA, Garrod KN, et al. Impairments in attention in occasionally snoring children: an event-related potential study. Dev Neuropsychol. 2009;34(5):629–649.
    1. Perfect MM, Archbold K, Goodwin JL, Levine-Donnerstein D, Quan SF. Risk of behavioral and adaptive functioning difficulties in youth with previous and current sleep disordered breathing. Sleep. 2013;36(4):517B–525B.
    1. Gozal D, Crabtree VM, Sans Capdevila O, Witcher LA, Kheirandish-Gozal L. C-reactive protein, obstructive sleep apnea, and cognitive dysfunction in school-aged children. Am J Respir Crit Care Med. 2007;176(2):188–193.
    1. Gozal D, Khalyfa A, Capdevila OS, Kheirandish-Gozal L, Khalyfa AA, Kim J. Cognitive function in prepubertal children with obstructive sleep apnea: a modifying role for NADPH oxidase p22 subunit gene polymorphisms? Antioxid Redox Signal. 2012;16(2):171–177.
    1. Gozal D, Sans Capdevila O, McLaughlin Crabtree V, Serpero LD, Witcher LA, Kheirandish-Gozal L. Plasma IGF-1 levels and cognitive dysfunction in children with obstructive sleep apnea. Sleep Med. 2009;10(2):167–173.
    1. Gozal D, Capdevila OS, Kheirandish-Gozal L, Crabtree VM. APOE epsilon 4 allele, cognitive dysfunction, and obstructive sleep apnea in children. Neurology. 2007;69(3):243–249.
    1. Khadra MA, McConnell K, VanDyke R, et al. Determinants of regional cerebral oxygenation in children with sleep-disordered breathing. Am J Respir Crit Care Med. 2008;178(8):870–875.
    1. Hogan AM, Hill CM, Harrison D, Kirkham FJ. Cerebral blood flow velocity and cognition in children before and after adenotonsillectomy. Pediatrics. 2008;122(1):75–82.
    1. Gozal D, Kheirandish-Gozal L, Bhattacharjee R, Spruyt K. Neurocognitive and endothelial dysfunction in children with obstructive sleep apnea. Pediatrics. 2010;126(5):e1161–e1167.
    1. Gozal D, Pope DW. Snoring during early childhood and academic performance at ages thirteen to fourteen years. Pediatrics. 2001;107(6):1394–1399.
    1. Melendres MC, Lutz JM, Rubin ED, Marcus CL. Daytime sleepiness and hyperactivity in children with suspected sleep-disordered breathing. Pediatrics. 2004;114(3):768–775.
    1. Khalyfa A, Serpero LD, Kheirandish-Gozal L, Capdevila OS, Gozal D. TNF-α gene polymorphisms and excessive daytime sleepiness in pediatric obstructive sleep apnea. J Pediatr. 2011;158(1):77–82.
    1. Tarasiuk A, Greenberg-Dotan S, Simon-Tuval T, et al. Elevated morbidity and health care use in children with obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2007;175(1):55–61.
    1. Reuveni H, Simon T, Tal A, Elhayany A, Tarasiuk A. Health care services utilization in children with obstructive sleep apnea syndrome. Pediatrics. 2002;110(1 Pt 1):68–72.
    1. Tarasiuk A, Simon T, Tal A, Reuveni H. Adenotonsillectomy in children with obstructive sleep apnea syndrome reduces health care utilization. Pediatrics. 2004;113(2):351–356.
    1. Tsou YA, Lin CC, Lai CH, et al. Does Adenotonsillectomy really reduced clinic visits for pediatric upper respiratory tract infections? A national database study in Taiwan. Int J Pediatr Otorhinolaryngol. 2013;77(5):677–681.
    1. Weider DJ, Hauri PJ. Nocturnal enuresis in children with upper airway obstruction. Int J Pediatr Otorhinolaryngol. 1985;9(2):173–182.
    1. Jeyakumar A, Rahman SI, Armbrecht ES, Mitchell R. The association between sleep-disordered breathing and enuresis in children. Laryngoscope. 2012;122(8):1873–1877.
    1. Alexopoulos EI, Kostadima E, Pagonari I, Zintzaras E, Gourgoulianis K, Kaditis AG. Association between primary nocturnal enuresis and habitual snoring in children. Urology. 2006;68(2):406–409.
    1. Lehmann GC, Bell TR, Kirkham FJ, et al. Enuresis associated with sleep disordered breathing in children with sickle cell anemia. J Urol. 2012;188(Suppl 4):S1572–S1576.
    1. Sans Capdevila O, Crabtree VM, Kheirandish-Gozal L, Gozal D. Increased morning brain natriuretic peptide levels in children with nocturnal enuresis and sleep-disordered breathing: a community-based study. Pediatrics. 2008;121(5):e1208–e1214.
    1. Rechtschaffen A, Kales A, editors. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Los Angeles: Brain Information Service/Brain Research Institute, University of California; 1968.
    1. Berry RB, Brooks R, Gamaldo CE, Harding SM, Marcus CL, Vaughn BV, American Academy of Sleep Medicine . The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. 2nd ed. Darien, IL: American Academy of Sleep Medicine; 2012.
    1. Kaditis A, Kheirandish-Gozal L, Gozal D. Algorithm for the diagnosis and treatment of pediatric OSA: a proposal of two pediatric sleep centers. Sleep Med. 2012;13(3):217–227.
    1. Gozal D, Kheirandish-Gozal L. New approaches to the diagnosis of sleep-disordered breathing in children. Sleep Med. 2010;11(7):708–713.
    1. Marcus CL, Brooks LJ, Draper KA, et al. American Academy of Pediatrics Diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. 2012;130(3):576–584.
    1. Guilleminault C, Huang YS, Glamann C, Li K, Chan A. Adenotonsillectomy and obstructive sleep apnea in children: a prospective survey. Otolaryngol Head Neck Surg. 2007;136(2):169–175.
    1. Cantarella G, Viglione S, Forti S, Minetti A, Pignataro L. Comparing postoperative quality of life in children after microdebrider intracapsular tonsillotomy and tonsillectomy. Auris Nasus Larynx. 2012;39(4):407–410.
    1. Ericsson E, Lundeborg I, Hultcrantz E. Child behaviour and quality of life before and after tonsillotomy versus tonsillectomy. Int J Pediatr Otorhinolaryngol. 2009;73(9):1254–1262.
    1. Marcus CL, Ward SL, Mallory GB, et al. Use of nasal continuous positive airway pressure as treatment of childhood obstructive sleep apnea. J Pediatr. 1995;127(1):88–94.
    1. Marcus CL, Rosen G, Ward SL, et al. Adherence to and effectiveness of positive airway pressure therapy in children with obstructive sleep apnea. Pediatrics. 2006;117(3):e442–e451.
    1. Sawyer AM, Gooneratne NS, Marcus CL, Ofer D, Richards KC, Weaver TE. A systematic review of CPAP adherence across age groups: clinical and empiric insights for developing CPAP adherence interventions. Sleep Med Rev. 2011;15(6):343–356.
    1. DiFeo N, Meltzer LJ, Beck SE, et al. Predictors of positive airway pressure therapy adherence in children: a prospective study. J Clin Sleep Med. 2012;8(3):279–286.
    1. McGinley B, Halbower A, Schwartz AR, Smith PL, Patil SP, Schneider H. Effect of a high-flow open nasal cannula system on obstructive sleep apnea in children. Pediatrics. 2009;124(1):179–188.
    1. Kheirandish-Gozal L, Kim J, Goldbart AD, Gozal D. Novel pharmacological approaches for treatment of obstructive sleep apnea in children. Expert Opin Investig Drugs. 2013;22(1):71–85.
    1. Goldbart AD, Goldman JL, Li RC, Brittian KR, Tauman R, Gozal D. Differential expression of cysteinyl leukotriene receptors 1 and 2 in tonsils of children with obstructive sleep apnea syndrome or recurrent infection. Chest. 2004;126(1):13–18.
    1. Dayyat E, Serpero LD, Kheirandish-Gozal L, et al. Leukotriene pathways and in vitro adenotonsillar cell proliferation in children with obstructive sleep apnea. Chest. 2009;135(5):1142–1149.
    1. Goldbart AD, Goldman JL, Veling MC, Gozal D. Leukotriene modifier therapy for mild sleep-disordered breathing in children. Am J Respir Crit Care Med. 2005;172(3):364–370.
    1. Goldbart AD, Greenberg-Dotan S, Tal A. Montelukast for children with obstructive sleep apnea: a double-blind, placebo-controlled study. Pediatrics. 2012;130(3):e575–e580.
    1. Kheirandish-Gozal L, Serpero LD, Dayyat E, et al. Corticosteroids suppress in vitro tonsillar proliferation in children with obstructive sleep apnoea. Eur Respir J. 2009;33(5):1077–1084.
    1. Kheirandish-Gozal L, Gozal D. Intranasal budesonide treatment for children with mild obstructive sleep apnea syndrome. Pediatrics. 2008;122(1):e149–e155.
    1. Brouillette RT, Manoukian JJ, Ducharme FM, et al. Efficacy of fluticasone nasal spray for pediatric obstructive sleep apnea. J Pediatr. 2001;138(6):838–844.
    1. Kheirandish L, Goldbart AD, Gozal D. Intranasal steroids and oral leukotriene modifier therapy in residual sleep-disordered breathing after tonsillectomy and adenoidectomy in children. Pediatrics. 2006;117(1):e61–e66.
    1. Pirelli P, Saponara M, Guilleminault C. Rapid maxillary expansion in children with obstructive sleep apnea syndrome. Sleep. 2004;27(4):761–766.
    1. Villa MP, Malagola C, Pagani J, et al. Rapid maxillary expansion in children with obstructive sleep apnea syndrome: 12-month follow-up. Sleep Med. 2007;8(2):128–134.
    1. Villa MP, Miano S, Rizzoli A. Mandibular advancement devices are an alternative and valid treatment for pediatric obstructive sleep apnea syndrome. Sleep Breath. 2012;16(4):971–976.
    1. Hartzell LD, Guillory RM, Munson PD, Dunham AK, Bower CM, Richter GT. Tongue base suspension in children with cerebral palsy and obstructive sleep apnea. Int J Pediatr Otorhinolaryngol. 2013;77(4):534–537.
    1. Guilleminault C, Huang YS, Monteyrol PJ, Sato R, Quo S, Lin CH. Critical role of myofascial reeducation in pediatric sleep-disordered breathing. Sleep Med. 2013;14(6):518–525.
    1. Huang YS, Guilleminault C. Pediatric obstructive sleep apnea and the critical role of oral-facial growth: evidences. Front Neurol. 2012;3:184.
    1. Ruoff CM, Guilleminault C. Orthodontics and sleep-disordered breathing. Sleep Breath. 2012;16(2):271–273.
    1. Guilleminault C, Monteyrol PJ, Huynh NT, Pirelli P, Quo S, Li K. Adeno-tonsillectomy and rapid maxillary distraction in pre-pubertal children, a pilot study. Sleep Breath. 2011;15(2):173–177.
    1. Lin AC, Koltai PJ. Sleep endoscopy in the evaluation of pediatric obstructive sleep apnea. Int J Pediatr. 2012;2012:576719.
    1. Truong MT, Woo VG, Koltai PJ. Sleep endoscopy as a diagnostic tool in pediatric obstructive sleep apnea. Int J Pediatr Otorhinolaryngol. 2012;76(5):722–727.
    1. Maturo SC, Hartnick CJ. Pediatric lingual tonsillectomy. Adv Otorhinolaryngol. 2012;73:109–111.
    1. Sedaghat AR, Flax-Goldenberg RB, Gayler BW, Capone GT, Ishman SL. A case-control comparison of lingual tonsillar size in children with and without Down syndrome. Laryngoscope. 2012;122(5):1165–1169.
    1. Abdel-Aziz M, Ibrahim N, Ahmed A, El-Hamamsy M, Abdel-Khalik MI, El-Hoshy H. Lingual tonsils hypertrophy; a cause of obstructive sleep apnea in children after adenotonsillectomy: operative problems and management. Int J Pediatr Otorhinolaryngol. 2011;75(9):1127–1131.
    1. Fricke BL, Donnelly LF, Shott SR, et al. Comparison of lingual tonsil size as depicted on MR imaging between children with obstructive sleep apnea despite previous tonsillectomy and adenoidectomy and normal controls. Pediatr Radiol. 2006;36(6):518–523.
    1. Guimaraes CV, Kalra M, Donnelly LF, et al. The frequency of lingual tonsil enlargement in obese children. AJR Am J Roentgenol. 2008;190(4):973–975.
    1. Schaaf WE, Wootten CT, Donnelly LF, Ying J, Shott SR. Findings on MR sleep studies as biomarkers to predict outcome of genioglossus advancement in the treatment of obstructive sleep apnea in children and young adults. AJR Am J Roentgenol. 2010;194(5):1204–1209.
    1. Donnelly LF, Shott SR, LaRose CR, Chini BA, Amin RS. Causes of persistent obstructive sleep apnea despite previous tonsillectomy and adenoidectomy in children with down syndrome as depicted on static and dynamic cine MRI. AJR Am J Roentgenol. 2004;183(1):175–181.
    1. Gozal D. Serum, urine, and breath-related biomarkers in the diagnosis of obstructive sleep apnea in children: is it for real? Curr Opin Pulm Med. 2012;18(6):561–567.
    1. Kheirandish-Gozal L, Gozal D. The multiple challenges of obstructive sleep apnea in children: diagnosis. Curr Opin Pediatr. 2008;20(6):650–653.
    1. Kheirandish-Gozal L, McManus CJ, Kellermann GH, Samiei A, Gozal D. Urinary neurotransmitters are selectively altered in children with obstructive sleep apnea and predict cognitive morbidity. Chest. 2013;143(6):1576–1583.

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