Pediatric OSA in Obesity: Challenges in Treatment Baha Al-Shawwa, MD, FCCP Associate Professor of Pediatrics Director of Sleep Medicine Pediatric Sleep Fellowship Program Director Children’s Mercy Hospital © The Children's Mercy Hospital, 2017

Disclosure None

Aim Obesity pandemic in children Relationship of Obesity and SDB Pathogenesis Treatment options

Childre KANSAS CIT

Prevalence* of Self-Reported Obesity Among U.S. Adults BRFSS, 2012 *Prevalence reflects BRFSS methodological changes in 2011, and these estimates should not be compared to those before 2011. 15%–<20% 20%–<25% 25%–<30% 30%–<35% ≥35%

by State and Territory, BRFSS, 2016 Prevalence¶ of Self-Reported Obesity Among U.S. Adults by State and Territory, BRFSS, 2016 ¶ Prevalence estimates reflect BRFSS methodological changes started in 2011. These estimates should not be compared to prevalence estimates before 2011. No state had a prevalence of obesity less than 20% *Sample size <50 or the relative standard error (dividing the standard error by the prevalence) ≥ 30%.

17% of children are Obese 2011-2014:The prevalence of obesity has remained fairly stable at about 17% and affects about 12.7 million children and adolescents.

Prevalence of obesity* among children and adolescents, ages 5– 19, 1975–2016 (crude estimate): Both sexes, 2016-WHO 8

Association between OSA & Obesity

Prevalence of OSA in children Graff et al, Sleep 2009;32(6):731-736.

Prevalence of OSA in children (Preschoolers) N= 60 participants included Mean age was 4.4 years (± 1.7), Mean BMI z-score was 3.0 (SD ± 1.2). 22/60 (36.6%) had OSA (AHI > 2/hr) 11

More OSA in Morbidly Obese Children OSA increases as BMI increase Karla et al, OBESITY RESEARCH Vol. 13 No. 7 July 2005

More obesity in OSA patients Redline et al, AM J RESPIR CRIT CARE MED 1999;159:1527–1532.

More obesity in OSA patients Redline et al, AM J RESPIR CRIT CARE MED 1999;159:1527–1532.

Pathophysiology of OSA in Obese Children Mechanical Factors Adeno-tonsillar hypertrophy Adipose tissue Restrictive Pulmonary impairment and Decrease FRC leading to more hypoxia, hypoventilation Functional Factors Altered neuromuscular tone leading to increase collapsibility Increased tissue inflammation leading to more collapsibility

OSA Obesity ?

Insulin Resistance/ MS OSA Obesity Insulin Resistance/ MS Inflammation Sleep disruption duration EDS/ Energy Level Leptin/ Ghrelin/ Cortisol Eating pattern Cardiovascular/HTN

Meta-analysis Sleep Duration and Obesity in Children

Insulin Resistance/ MS OSA Obesity Insulin Resistance/ MS Inflammation Sleep disruption duration EDS/ Energy Level Leptin/ Ghrelin/ Cortisol Eating pattern Cardiovascular/HTN 19

EDS and Obesity/OSA 50 obese and 50 non-obese children (6-9 yrs) underwent PSG and MSLT Obese children had MSL 12.9 min vs. 17.9 min in non-obese Obese children had lower MSL (more sleepy) in any level of OSA More EDS lead to decrease level of activity and less energy expenditure and Obesity Gozal et al, Pediatrics 2009;123:13–18

Insulin Resistance/ MS OSA Obesity Insulin Resistance/ MS Inflammation Sleep disruption duration EDS/ Energy Level Leptin/ Ghrelin/ Cortisol Eating pattern Cardiovascular/HTN

Sleep Fragmentation and inflammation Kim and Gozal et al, Respir Physiol Neurobiol. 2011 September 30; 178(3): 465–474.

Insulin Resistance/ MS OSA Obesity Insulin Resistance/ MS Inflammation Sleep disruption duration EDS/ Energy Level Leptin/ Ghrelin/ Cortisol Eating pattern Cardiovascular/HTN

Gozal 2012, Ann. N.Y. Acad. Sci. ISSN 0077-8923

Treatment Effect © The Children's Mercy Hospital, 2017

A Randomized Trial of T&A Childhood Adenotonsillectomy Trial (CHAT) 464 children (5 to 9 years) with OSA Comparison between Early adenotonsillectomy or a strategy of watchful waiting. Polysomnographic, cognitive, behavioral, and health outcomes were assessed at baseline and at 7 months Improvement in behavioral, QOL, PSG finding (79% compared to 46%) with early intervention But did not significantly improve attention or executive function as measure by neuropsychological testing Marcus et al, N Engl J Med. 2013 June 20; 368(25): 2366–2376

A Randomized Trial of T&A Childhood Adenotonsillectomy Trial (CHAT) Normalization of Polysomnographic Findings Marcus et al, N Engl J Med. 2013 June 20; 368(25): 2366–2376

Effect of T&A in obese children 578 children (mean age, 6.9 ± 3.8 yr) 50% were obese. Adeno-Tonsilectomy resulted in a significant AHI reduction from 18.2 to 4.1 /hour (P < 0.001). Only 157 (27.2%) had complete resolution of OSAS (AHI < 1/hr) Gozal et al, Am J Respir Crit Care Med Vol 182. pp 676–683, 2010

Effect of T&A in obese children Gozal et al, Am J Respir Crit Care Med Vol 182. pp 676–683, 2010 29

Effect of T&A in obese children Gozal et al, Am J Respir Crit Care Med Vol 182. pp 676–683, 2010 30

Effect of T&A in obese children Gozal et al, Am J Respir Crit Care Med Vol 182. pp 676–683, 2010 31

Effect of T&A in obese children Gozal et al, Am J Respir Crit Care Med Vol 182. pp 676–683, 2010

Effect of T&A in obese children Meta-analysis of 110 obese children underwent T&A Results 49% had AHI < 5/hr 25% had AHI < 2/hr 12% had AHI < 1/hr Otolaryngology -- Head and Neck Surgery April 2009 140: 455-460

Effect of T&A in obese children 100 90 80 70 87% 81% Meta-analysis 51 studies 3413 subjects were enrolled 61% 60 50 40 30 20 10 56% 51% 34% AHI < 1/hr Total AHI < 5/hr Non-Obese Obese 34 Clin Otolaryngol.2016 Oct;41(5):498-510.

Long term effect of A &T Amin et al, Am J Respir Crit Care Med Vol 177. pp 654–659, 2008

Effect of OSA after Bariatric Surgery Amin et al, OBESITY RESEARCH Vol. 13 No. 7 July 2005

Children'sMercy KANSAS CITY

Obesity Hypoventilation (Pickwikian Syndrome) Significant Hypoventilation with or without OSA High morbidity and mortality Needs aggressive therapy and NIV Think about ROHHAD

ROHHAD Rapid-onset obesity, hypothalamic dysfunction, hypoventilation and autonomic dysfunction Used to be named LO-CHS (late onset central hypoventilation syndrome) Starts usually with very rapid weight gain but the hypothalamic dysfunction may comes years later Think about it and continue to follow the patient closely

Children'sMercy KANSAS CITY

Gozal et all, Proc Am Thorac Soc Vol 5. pp 274–282, 2008

Conclusions Obesity is a pandemic SDB is very common in Obese patients The interaction between OSA and obesity goes both way T & A is less helpful in obese children with OSA compared to non- obese children Close follow up and repeating of PSG is important in obese children since a very high chance of residual disease (may be more important than having the baseline study)

Thank you

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