1. h - h Sherri Katz, MD, CM, FRCPC Pediatric Respirologist Assistant Professor Children’s Hospital of Eastern Ontario University of Ottawa Obesity & OSA in Kids

2. Objectives Understand the pathophysiologic mechanisms of obstructive sleep apnea in obese children Understand the pathophysiologic mechanisms of obstructive sleep apnea in obese children Recognize associated co-morbidities of obesity and concurrent OSA in childhood Recognize associated co-morbidities of obesity and concurrent OSA in childhood Review alternative treatment strategies for children with obesity and obstructive sleep apnea Review alternative treatment strategies for children with obesity and obstructive sleep apnea

3. A growing problem… OSA has a prevalence of 1-3% in children OSA has a prevalence of 1-3% in children Prevalence of sleep disordered breathing in obese children is 13-66% - 10-20 x  Prevalence of sleep disordered breathing in obese children is 13-66% - 10-20 x  Obesity is a rising epidemic in pediatrics Obesity is a rising epidemic in pediatrics –5-fold increase in the past 15 years –Prevalence of 10% Ali, 1994, Gislason, 1995, Brunetti, 2001; Mallory, 1989; Silvestri, 1993;Chay, 2000; Marcus, 1996, Wing, 2003; Shields, 2009; Willms, 2003;

4. A growing problem… As OSA is strongly linked to obesity, this means more kids with OSA!

5. What is OSA? Partial (hypopnea) or complete (apnea) upper airway obstruction during sleep associated with: Partial (hypopnea) or complete (apnea) upper airway obstruction during sleep associated with: –Sleep disruption –Hypoxemia –Hypercapnia –Daytime symptoms Continued chest and abdominal motion in the absence of airflow during sleep Continued chest and abdominal motion in the absence of airflow during sleep Apnea-Hypopnea Index: # of events/hour Apnea-Hypopnea Index: # of events/hour Used to categorize severity of condition Used to categorize severity of condition

6. Why does OSA occur? We don’t breathe as deeply while sleeping as when awake We don’t breathe as deeply while sleeping as when awake –blunting of hypoxic / hypercapnic drive –25%  tidal volume –arterial pCO 2  3-4 mmHg –arterial pO 2  5-10 mmHg

7. Why does OSA occur? Upper airway tone is decreased during sleep, especially in REM Upper airway tone is decreased during sleep, especially in REM Collapse/obstruction of the upper airway during sleep causes obstruction & apnea Collapse/obstruction of the upper airway during sleep causes obstruction & apnea

8. Why does OSA occur? Adenotonsillar hypertrophy Adenotonsillar hypertrophy –Most common cause of OSA in children –Between 3-6 yrs, tonsils & adenoids are largest relative to size of airway  peak incidence of OSA

9. Why does OSA occur? Large tonsils and adenoids BUT No direct correlation between airway or adenotonsillar size & OSA Upper airway is narrower and more collapsible in children with OSA Airway patency is maintained by increased neuromuscular activity THEREFORE Combination of structural abnormalities & neuromotor tone abnormalities must be present for OSA to occur Isono, AJRCCM, 1998, Marcus, Respiration Physiology, 1999

10. Why do Obese Kids get OSA? Older kids & teens Increased fat mass around the neck & trunk, resulting in: – –Reduction in thoracic cage compliance – –Mass loading of the respiratory muscles – –Increased pharyngeal resistance May be obstructive initially, but resetting of chemoreceptor sensitivity  hypoventilation Mallory, J Peds, 1989

11. What are the consequences? Health Care Utilization Health Care Utilization Inflammation Inflammation Metabolic Metabolic Cardiovascular Cardiovascular Neurobehavioural Neurobehavioural Quality of life Quality of life

12. Health Care Burden Economic burden of untreated OSA alone is comparable to that of diabetes Economic burden of untreated OSA alone is comparable to that of diabetes Children with OSA have 226%  health care utilization Children with OSA have 226%  health care utilization Treating OSA in children  health care costs by 1/3 Treating OSA in children  health care costs by 1/3 In adults, PAP therapy is as effective as cholesterol-lowering agents in preventing cardiovascular disease In adults, PAP therapy is as effective as cholesterol-lowering agents in preventing cardiovascular disease AlGhanim, 2008; Reuveni, 2002; Tarasiuk, 2004&2007

13. Common Pathophysiology ObesityOSA Sympathetic Nervous System Activation Oxidative stress Changes in renin- angiotensin-aldosterone system &  renal sympathetic activity Hypoxia and micro-arousals Systemic inflammation

14. Inflammation C-reactive protein is released during systemic inflammatory processes C-reactive protein is released during systemic inflammatory processes Can assess risk of heart disease using hs-CRP assay Can assess risk of heart disease using hs-CRP assay Hs-CRP levels  in OSA and correlate with severity Hs-CRP levels  in OSA and correlate with severity Hs-CRP  following OSA treatment with T&A Hs-CRP  following OSA treatment with T&A Goldbart, 2008; Bassuk, 2004;Li, 2008; Kheirandish-Gozal, 2006;

15. Insulin Resistance Consequence of both childhood obesity + OSA Consequence of both childhood obesity + OSA Hypoxia and micro-arousals activate sympathetic nervous system Pro-inflammatory state Insulin resistance Kheirandish-Gozal, Sleep Med, 2010; Gozal, AJRCCM, 2008; Waters, J Sleep Res, 2007; Li, Ped Pulm, 2008; Esler, J Appl Physiol, 2006; Sinha, NEJM, 2002; Vgontzas, J Intern Med, 2003; Somers, J Clin Invest 1995

16. Insulin Resistance Precursor of type 2 diabetes and cardiovascular disease Precursor of type 2 diabetes and cardiovascular disease Elevated insulin levels in childhood persist into adulthood & are predictive of cardiovascular disease risk Elevated insulin levels in childhood persist into adulthood & are predictive of cardiovascular disease risk Severity of insulin resistance is α OSA (independent of BMI) Severity of insulin resistance is α OSA (independent of BMI) Combo of OSA & Obesity = Greater risk of endocrine dysfunction

17. Insulin Resistance In obese and non-obese adults, PAP treatment for severe OSA improved insulin sensitivity within 2 days and sustained effect over 3 months In obese and non-obese adults, PAP treatment for severe OSA improved insulin sensitivity within 2 days and sustained effect over 3 months –Improvements more rapid in non-obese subjects –Suggests obesity is contributing to insulin resistance –Treating OSA alone, independent of body composition, improves insulin resistance Harsch, AJRCCM. 2004

18. Insulin Resistance 4 Pediatric studies of effect of T&A for OSA on insulin resistance showed improvement 4 Pediatric studies of effect of T&A for OSA on insulin resistance showed improvement –Small sample size, young children, mostly non- obese PAP therapy for OSA in obese kids with pre- existing insulin resistance: PAP therapy for OSA in obese kids with pre- existing insulin resistance: –Improved fasting glucose & insulin levels without change in BMI –Not statistically significant, small sample size Nakra, Pediatrics, 2008; Gozal, AJRCCM, 2008; Apostolidou, Ped Pulm, 2008; Waters, AJRCCM, 2006; Kaditis, Ped Pulm 2005; Reinehr, Pediatrics 2004

19. Cardiovascular Disease Hypertension is a well-described consequence of both OSA and obesity Hypertension is a well-described consequence of both OSA and obesity Common mechanism: sympathetic nervous system activation & endothelial dysfunction Common mechanism: sympathetic nervous system activation & endothelial dysfunction Children with OSA lose normal nocturnal dip in BP, eventually get daytime hypertension Children with OSA lose normal nocturnal dip in BP, eventually get daytime hypertension Best assessed with 24 hour ambulatory BP monitoring Best assessed with 24 hour ambulatory BP monitoring Bhattacharjee, 2009; Gozal. 2008; Kheirandish-Gozal, 2010

20. Neurobehavioral Neurobehavioral & learning deficits common and reversible Neurobehavioral & learning deficits common and reversible Young children who snore frequently & loudly are at risk of lower grades in school several years after OSA is resolved Young children who snore frequently & loudly are at risk of lower grades in school several years after OSA is resolved Ali, Eur J Peds, 1996, Suratt, Pediatrics, 2006, Kaemingk (tuCASA), J Int Neuropsychol Soc., 2003 ; Gozal, Peds, 1998

21. Neurobehavioral Magnitude of impairment in cognitive function attributable to sleep-disordered breathing, is profound Magnitude of impairment in cognitive function attributable to sleep-disordered breathing, is profound –Similar in magnitude to the effects of lead exposure in children Suratt, Pediatrics, 2006

22. Quality of Life Improves with OSA treatment Improves with OSA treatment

23. Treatment Options for OSA with Obesity

24. Treatments Adenotonsillectomy (T&A): Adenotonsillectomy (T&A): –First-line therapy for younger children with OSA –In obese children, cure rates are much lower: ineffective in 70-80% Weight loss: Weight loss: –Improves obesity-related OSA –Difficult to achieve & sustain Positive Airway Pressure (PAP) Positive Airway Pressure (PAP) Shine, 2006; Amin, 2008

25. PAP Treatment 86% success rate in kids to improve OSA with CPAP 86% success rate in kids to improve OSA with CPAP In 10 children using CPAP/BIPAP AHI decreased from 20 to 1 and lowest oxygen saturation increased from 76% to 90% In 10 children using CPAP/BIPAP AHI decreased from 20 to 1 and lowest oxygen saturation increased from 76% to 90% Marcus, J Pediatr, 1995; Padman, Clin Pediatr, 2002

26. PAP Treatment CPAP used initially CPAP used initially If needing CPAP > 10 cmH 2 O, or evidence of hypoventilation, use Bi-level If needing CPAP > 10 cmH 2 O, or evidence of hypoventilation, use Bi-level

27. Future Directions Emerging evidence that PAP for OSA improves obesity-related conditions: Emerging evidence that PAP for OSA improves obesity-related conditions: –Insulin resistance –Hypertension –Quality of life ** Unfortunately does not assist weight loss in adults! Redenius, 2008

28. INSULIN RESISTANCE Future Directions Long-term outcomes of PAP therapy for OSA in obese children not yet studied in long-term prospective manner Long-term outcomes of PAP therapy for OSA in obese children not yet studied in long-term prospective manner – CIHR funded study now ongoing in Canada PAP INSULIN RESISTANCE

29. Thank you