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3/25/2019Conflict of Interest DisclosuresConsequences of PediatricObstructive Sleep Apnea(OSA)Matt Dennis, MDSleep Medicine Physician‐Children’s Hospital & Medical Center OmahaPediatric Pulmonology Fellow‐University of Nebraska Medical CenterConsultant/Speakers bureausNo DisclosuresResearch fundingUNMC Department of Pediatrics – Objectively measuring theadequacy of the nasal pressure signal during ards-employmentNo DisclosuresOff-label usesNo DisclosuresObjectives Describe basic sleep study terminology related toOSA Describe neurodevelopmental outcomes associatedwith pediatric OSA Describe cardiopulmonary outcomes associatedwith pediatric OSAPediatric Definitions per American Academy of SleepMedicine (AASM) Scoring Manual: Oxygen desaturation: SpO2 decrease of 3% frombaseline Oxygen desaturation index (ODI): number ofdesaturations averaged out over the total sleeptime, reported as average number of events perhourBerry 2018Basic Sleep Study TerminologyPediatric Definitions per AASM Scoring Manual (cont’d): Apnea: 90% reduction in airflow for 2 breaths Hypopnea: 30% reduction in airflow for 2 breaths thatis associated with an arousal or oxygen desaturation Obstructive Apnea: apnea associated with thepresence of respiratory effort (trying to breathe, butcan’t get the air in) Obstructive Hypopnea: hypopnea associated withevidence of obstructed airflow (snoring, thoraco‐abdominal paradox, or blunted inspiratory airflow) Apnea hypopnea index (AHI): number of apneas andhypopneas averaged out over the total sleep time,reported as average number of events per hourBerry 20181

3/25/2019OutcomesKaditis 2016Neurodevelopmental OutcomesBradley 2009 Tan 2017The Childhood AdenotonsillectomyTrial (CHAT)Inclusion criteria:o 5‐9 years oldo OSA confirmed by in‐lab PSG at study center (OSA defined as oAHI 2, or oAI 1)o Tonsil size 1 o Deemed suitable candidate for AT by ENT surgeonExclusion criteria:o AHI 30 or oAI 20o Hypoxemia (SpO2 90% for 2% of TST)o Craniofacial or airway abnormalities that would interfere with standard practice T&Ao Recurrent tonsillitiso Clinically significant cardiac arrhythmiao BMI z‐score 2.99o Severe medical problems that could be exacerbated by delayed treatment of OSAo Known chronic medical conditions likely to affect the airway, cognition, or behavioro Current use of: ADHD medications, psychotropic medication, hypoglycemic agents orinsulin, antihypertensives, growth hormone, anticonvulsants, anticoagulants, daily oralcorticosteroids.o Psychiatric or behavioral disorders likely to require initiation of new medication ortreatment during the 7‐month study periodRedline 20112

3/25/2019CHAT (cont’d) Subjects randomized to early AT (within 4wks ofrandomization) or watchful waiting Polysomnographic, cognitive, behavioral, sleepdysfunction, quality of life, and cardiometabolicparameters evaluated at baseline and at 7 monthsRedline 2011Marcus 2013Cardiovascular Outcomes Effect sizes calculated by Cohen’s d; relates the magnitude of group difference to thestandard deviation: 0.20 ‐ 0.49 small effect size; 0.50 ‐ 0.79 medium effect size; 0.80 large effect sizeMarcus 2013Pulmonary Artery PressuresTan 20173

3/25/2019Pulmonary artery pressuresbefore and after T&APulmonary artery pressuresbefore and after T&AYilmaz 2005Naiboglu 2008Impaired Cardiac FunctionFigured created from text provided by Kasai 2012DiastoleAmin 2005Amin 20054

3/25/2019SystoleObstructive AHI: 2 2, 5Amin 2005Obstructive AHI: 2 2, 5 5Kaditis 2010 5European Respiratory Society Task Force on the diagnosis and management of obstructivesleep disordered breathing (SDB) in childhood.Kaditis AG, et al. Obstructive sleep disordered breathing in 2‐ to 18‐year‐old children:diagnosis and management. Eur Respir J. 2016 Jan;47(1):69‐94.Kaditis 2010Questions that RemainKaditis 2016What to do Now? Statistical support for the clinical consequences of OSAremains equivocal in a number of areas Improvement of clinical outcomes with treatment ofunderlying OSAo Most recent studies focus on trying to answer this question (e.g.CHAT); suggest moderate improvement in a number of areas Risk stratification for clinical outcomes based on AHI level –just starting to get into this Risk stratification for clinical outcomes based on chronicduration of OSAo If OSA is only present for a few years during childhood should we beconcerned? Studies like CHAT suggest YESo Stay tuned for follow‐up studies on CHAT participants 5, 10, and 20years down the road Risk stratification for clinical outcome based onseverity/duration of underlying OSA insults (i.e. intermittenthypoxemia, negative intrathoracic pressure, arousals)Tan 20175

3/25/2019The Children’s Sleep Center TeamoGlennette White – Sleep CenterCoordinatoroMegan Black – Supervisor Sleep Center &NeurodiagnosticsoDiane Workman, Sleep Clinic NurseThe Children’s Sleep Center TeamoHeather Bohan, Respiratory TherapyoDanielle Brazzle, Respiratory TherapyAmin RS, Kimball TR, Kalra M, Jeffries JL, Carroll JL, Bean JA, Witt SA, Glascock BJ, DanielsSR. Left ventricular function in children with sleep‐disordered breathing. Am JCardiol. 2005 Mar 15;95(6):801‐4.Amin R, Somers VK, McConnell K, Willging P, Myer C, Sherman M, McPhail G, MorgenthalA, Fenchel M, Bean J, Kimball T, Daniels S. Activity‐adjusted 24‐hour ambulatoryblood pressure and cardiac remodeling in children with sleep disorderedbreathing. Hypertension. 2008 Jan;51(1):84‐91.Bass JL, Corwin M, Gozal D, Moore C, Nishida H, Parker S, Schonwald A, Wilker RE, StehleS, Kinane TB. The effect of chronic or intermittent hypoxia on cognition inchildhood: a review of the evidence. Pediatrics. 2004 Sep;114(3):805‐16.Berry RB, Budhiraja R, Gottlieb DJ, et al. Rules for scoring respiratory events in sleep:update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. JClin Sleep Med. 2012;8(5):597‐619.Berry RB, Brooks R, Gamaldo CE, Harding SM, Lloyd RM, Quan SF; for the AmericanAcademy of Sleep Medicine. The AASM Manual for the Scoring of Sleep andAssociated Events: Rules, Terminology and Technical Specifications. Version 2.4.Westchester, IL: American Academy of Sleep Medicine; 2018.Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences.Lancet. 2009 Jan 3;373(9657):82‐93.ReferencesChervin RD, Ruzicka DL, Giordani BJ, Weatherly RA, Dillon JE, Hodges EK, Marcus CL, GuireKE. Sleep‐disordered breathing, behavior, and cognition in children before andafter adenotonsillectomy. Pediatrics. 2006 Apr;117(4):e769‐78.Garetz SL, Mitchell RB, Parker PD, Moore RH, Rosen CL, Giordani B, Muzumdar H, ParuthiS, Elden L, Willging P, Beebe DW, Marcus CL, Chervin RD, Redline S. Quality of lifeand obstructive sleep apnea symptoms after pediatric adenotonsillectomy.Pediatrics. 2015 Feb;135(2):e477‐86.Hunter SJ, Gozal D, Smith DL, Philby MF, Kaylegian J, Kheirandish‐Gozal L. Effect of Sleep‐disordered Breathing Severity on Cognitive Performance Measures in a LargeCommunity Cohort of Young School‐aged Children. Am J Respir Crit Care Med.2016 Sep 15;194(6):739‐47.Kaditis AG, Alonso Alvarez ML, Boudewyns A, Alexopoulos EI, Ersu R, Joosten K, LarramonaH, Miano S, Narang I, Trang H, Tsaoussoglou M, Vandenbussche N, Villa MP, VanWaardenburg D, Weber S, Verhulst S. Obstructive sleep disordered breathing in 2‐to 18‐year‐old children: diagnosis and management. Eur Respir J. 2016Jan;47(1):69‐94.Kaditis AG, Alexopoulos EI, Dalapascha M, Papageorgiou K, Kostadima E, Kaditis DG,Gourgoulianis K, Zakynthinos E. Cardiac systolic function in Greek children withobstructive sleep‐disordered breathing. Sleep Med. 2010 Apr;11(4):406‐12.Kasai T. Sleep apnea and heart failure. J Cardiol. 2012 Aug;60(2):78‐85.6

3/25/2019Kohler M, Stradling JR. Mechanisms of vascular damage in obstructive sleep apnea. NatRev Cardiol. 2010 Dec;7(12):677‐85.Marcus CL, Greene MG, Carroll JL. Blood pressure in children with obstructive sleepapnea. Am J Respir Crit Care Med. 1998 Apr;157(4 Pt 1):1098‐103.Marcus CL, Moore RH, Rosen CL, Giordani B, Garetz SL, Taylor HG, Mitchell RB, Amin R,Katz ES, Arens R, Paruthi S, Muzumdar H, Gozal D, Thomas NH, Ware J, Beebe D,Snyder K, Elden L, Sprecher RC, Willging P, Jones D, Bent JP, Hoban T, Chervin RD,Ellenberg SS, Redline S; Childhood Adenotonsillectomy Trial (CHAT). A randomizedtrial of adenotonsillectomy for childhood sleep apnea. N Engl J Med. 2013 Jun20;368(25):2366‐76.Melendres MC, Lutz JM, Rubin ED, Marcus CL. Daytime sleepiness and hyperactivity inchildren with suspected sleep‐disordered breathing. Pediatrics. 2004Sep;114(3):768‐75.Mitchell RB, Archer SM, Ishman SL, Rosenfeld RM, Coles S, Finestone SA, Friedman NR,Giordano T, Hildrew DM, Kim TW, Lloyd RM, Parikh SR, Shulman ST, Walner DL,Walsh SA, Nnacheta LC. Clinical Practice Guideline: Tonsillectomy in Children(Update). Otolaryngol Head Neck Surg. 2019 Feb;160(1 suppl):S1‐S42.Naiboglu B, Deveci S, Duman D, Kaya KS, Toros S, Kinis V, Sürmeli M, Deveci I, Gokceer T.Effect of upper airway obstruction on pulmonary arterial pressure in children. Int JPediatr Otorhinolaryngol. 2008 Sep;72(9):1425‐9.Sedky K, Bennett DS, Carvalho KS. Attention deficit hyperactivity disorder and sleepdisordered breathing in pediatric populations: a meta‐analysis. Sleep Med Rev.2014 Aug;18(4):349‐56.Shamsuzzaman A, Amin R. Chapter 30, Cardiovascular consequences of obstructive sleepapnea. In: Sheldon SH, Ferber R, Kryger MH, Gozal D. Principles and Practice ofPediatric Sleep Medicine. 2nd ed. London: Elsevier Saunders, 2014.Tan HL, Alonso Alvarez ML, Tsaoussoglou M, Weber S, Kaditis AG. When and why to treatthe child who snores? Pediatr Pulmonol. 2017 Mar;52(3):399‐412.West JB, Luks AM. Chapter 6, Gas transport by the blood. In: West JB, Luks AM. West’sRespiratory Physiology. 10th ed. Philadelphia: Wolters Kluwer, 2016.Yilmaz MD, Onrat E, Altuntaş A, Kaya D, Kahveci OK, Ozel O, Dereköy S, Celik A. The effectsof tonsillectomy and adenoidectomy on pulmonary arterial pressure in children.Am J Otolaryngol. 2005 Jan‐Feb;26(1):18‐21.Ng DK, Wong JC, Chan CH, Leung LC, Leung SY. Ambulatory blood pressure before andafter adenotonsillectomy in children with obstructive sleep apnea. Sleep Med.2010 Aug;11(7):721‐5.Paruthi S, Buchanan P, Weng J, Chervin RD, Mitchell RB, Dore‐Stites D, Sadhwani A, KatzES, Bent J, Rosen CL, Redline S, Marcus CL. Effect of Adenotonsillectomy on Parent‐Reported Sleepiness in Children with Obstructive Sleep Apnea. Sleep. 2016 Nov1;39(11):2005‐2012.Quante M, Wang R, Weng J, Rosen CL, Amin R, Garetz SL, Katz E, Paruthi S, Arens R,Muzumdar H, Marcus CL, Ellenberg S, Redline S; Childhood AdenotonsillectomyTrial (CHAT). The Effect of Adenotonsillectomy for Childhood Sleep Apnea onCardiometabolic Measures. Sleep. 2015 Sep 1;38(9):1395‐403.Redline S, Budhiraja R, Kapur V, Marcus CL, Mateika JH, Mehra R, Parthasarthy S, SomersVK, Strohl KP, Sulit LG, Gozal D, Wise MS, Quan SF. The scoring of respiratory eventsin sleep: reliability and validity. J Clin Sleep Med. 2007 Mar 15;3(2):169‐200.Roland PS, Rosenfeld RM, Brooks LJ, Friedman NR, Jones J, Kim TW, Kuhar S, Mitchell RB,Seidman MD, Sheldon SH, Jones S, Robertson P; American Academy ofOtolaryngology—Head and Neck Surgery Foundation. Clinical practice guideline:Polysomnography for sleep‐disordered breathing prior to tonsillectomy in children.Otolaryngol Head Neck Surg. 2011 Jul;145(1 Suppl):S1‐15.Supplementary SlidesCurrent GuidelinesUpdated Recommendations fromAmerican Academy ofOtolaryngology‐Head and NeckSurgeryMitchell 20197

3/25/2019Current GuidelinesCurrent GuidelinesMitchell 2019Mitchell 2019Previous GuidelinesMitchell 2019Roland 2011Previous GuidelinesPathophysiologic Consequencesof OSARoland 20118

3/25/2019Bradley 2009Figured created from text provided by Kasai 2012Kohler 2010Kohler 2010Are oxygen desaturations ofpathologic consequence if their nadiris 90%?What is the desaturation durationthat is of pathologic consequence?Reasons to Consider these Questions: I’ve suggested that intermittent hypoxemia is adriving insult behind the pathology associated withOSA – So, what is the definition of intermittenthypoxemia? Allows us to briefly discuss the methodology thathas been used to generate the previous figures Helps us understand why clinical studies tend tofocus on the AHI rather than the ODI Frequent clinical question – On our sleep studieswe report desaturations that are often notrecorded, or deemed insignificant by homeoximetry and standard inpatient monitoring9

3/25/2019Are oxygen desaturations of pathologicconsequence if their nadir is 90%?Studies on isolated intermittent hypoxemia: Most of these studies exposed animals to low FiO2 ( 0.07)and did not monitor SpO2 or PaO2. Others used SpO2desaturations with a wide delta and nadir 90%.Studies on intermittent hypoxemia with obstructive events Several studies have demonstrated significant correlationbetween the AHI and OSA comorbidities regardless ofwhether a 3% or 4% oxygen desaturation was used to scorehypopneas. These conclusions were reached despite nothaving a required SpO2 nadir. Potential interpretations include: Oxygen desaturations with a small delta and SpO2 nadir 90%contribute significantly to the pathophysiology of OSA The unreported SpO2 nadirs in these studies were moresignificant than presumed, and are required to cause pathology Other obstructive phenomenon are driving thepathophysiology of OSA in these casesWest 2016What is the desaturation durationthat is of pathologic consequence? No uniform duration used in studies of isolatedintermittent hypoxemiao Duration of exposure to FiO2 0.21 standardized, butduration of time with SpO2 drop not standardized Risk stratification for duration of desaturation notperformed in studies of intermittent hypoxemia withobstructive events AASM Scoring Manual and guideline papers elude tothe significance of short desaturations: “use pulseoximetry with a maximum acceptable signal averagingtime of 3 seconds at a heart rate of 80 beats perminute.”o Equates to 4 beat averaging timeBass 2004; Berry 2012; Kohler 2010Moving Forward with OxygenDesaturations Direct consequences of oxygen desaturations with a nadir 90% remain unclear Duration of oxygen desaturation required to causepathology remains unclear The AASM has developed specific definitions for apneas andhypopneas, which have been consistently adopted byresearchers The cut‐points that have been set for the apnea/hypopneadefinitions may not be the natural line between normal andpathology, but they give us somewhere to start, particularlystandardization amongst researchers In theory the AHI value takes into account all insults that areassociated with obstructive apneas and hypopneas For these reasons the clinical outcomes of OSA have beenmore clearly associated with AHI values, than ODI valuesBass 2004; Berry 2018; Kohler 2010; Redline 2007Louisville & Chicago Cohort Study onNeurodevelopmental OutcomesNeurodevelopmental OutcomesHunter 201610

3/25/2019Meta‐Analysis:ADHD symptoms and OSAHunter 2016ADHD Symptoms Before & After T&ASedky 2014 The Conners’ Parent Rating Scales‐Revised and Child Symptom Inventory‐4: ParentChecklist were used to generate the behavioral hyperactivity index The Integrated Visual and Auditory Continuous Performance Test and Children’sMemory Scale were used to generate the cognitive attention indexTriangles T&A subjectsSquares control subjectsChervin 2006Chervin 2006Decreased Quality of LifeExcessive Daytime Sleepiness Effect sizes calculated by Cohen’s d; relates the magnitude of group difference to thestandard deviation 0.20 to 0.49 small effect size; 0.50 to 0.79 medium effect size; and 0.80 large effect sizeGaretz 201511

3/25/2019 Modified Epworth sleepiness scale (ESS) completedby parent/caregivero ESS 10 equates to excessive sleep propensity Mean ESS score was significantly higher in S‐SDBgroup vs. control group (8.1 4.9 vs 5.3 3.9; P 0.001)Paruthi 2016Melendres 2004Elevated Blood Pressure Mild OSAS: obstructive AI 1‐4 Moderate OSAS: obstructive AI 5‐9 Severe OSAS: obstructive AI 10Melendres 2004 Also, 6% of the healthy controls, 15% of the children with mildOSA, and 29% of the children with severe OSA had mean 24‐hour systolic blood pressures greater than the 95th percentile(P 0.01).Marcus 1998Amin 2008; Shamsuzzaman 201412

3/25/2019Does treating OSA improve bloodpressure?To allow comparison between different age groups, bloodpressure index (BPI) was calculated: BPI measured meanBP/95th percentile pressure for sex, age and height.Ng 2010Ng 201013

update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. J Clin Sleep Med. 2012;8(5):597‐619. Berry RB, Brooks R, Gamaldo CE, Harding SM, Lloyd RM, Quan SF; for the American Academy of Sleep Medicine. The AASM Manual for the Scoring of Sleep and

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