h - h Obesity & OSA in Kids Sherri Katz, MD, CM, FRCPC Pediatric Respirologist Assistant Professor Children’s Hospital of Eastern Ontario University of Ottawa
Objectives • Understand the pathophysiologic mechanisms of obstructive sleep apnea in obese children • Recognize associated co-morbidities of obesity and concurrent OSA in childhood • Review alternative treatment strategies for children with obesity and obstructive sleep apnea
A growing problem… • OSA has a prevalence of 1-3% in children • Prevalence of sleep disordered breathing in obese children is 13-66% - 10-20 x • 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;
A growing problem… As OSA is strongly linked to obesity, this means more kids with OSA!
What is OSA? • 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 • Apnea-Hypopnea Index: # of events/hour • Used to categorize severity of condition
Why does OSA occur? • We don’t breathe as deeply while sleeping as when awake • blunting of hypoxic / hypercapnic drive • 25% ¯ tidal volume • arterial pCO2 3-4 mmHg • arterial pO2¯ 5-10 mmHg
Why does OSA occur? • Upper airway tone is decreased during sleep, especially in REM • Collapse/obstruction of the upper airway during sleep causes obstruction & apnea
Why does OSA occur? • 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
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
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
What are the consequences? • Health Care Utilization • Inflammation • Metabolic • Cardiovascular • Neurobehavioural • Quality of life
Health Care Burden • Economic burden of untreated OSA alone is comparable to that of diabetes • Children with OSA have 226% health care utilization • 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 AlGhanim, 2008; Reuveni, 2002; Tarasiuk, 2004&2007
Common Pathophysiology Obesity OSA Changes in renin-angiotensin-aldosterone system & renal sympathetic activity Hypoxia and micro-arousals Oxidative stress Sympathetic Nervous System Activation Systemic inflammation
Inflammation • C-reactive protein is released during systemic inflammatory processes • Can assess risk of heart disease using hs-CRP assay • Hs-CRP levels in OSA and correlate with severity • Hs-CRP following OSA treatment with T&A Goldbart, 2008; Bassuk, 2004;Li, 2008; Kheirandish-Gozal, 2006;
Insulin Resistance • 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
Insulin Resistance • Precursor of type 2 diabetes and cardiovascular disease • Elevated insulin levels in childhood persist into adulthood & are predictive of cardiovascular disease risk • Severity of insulin resistance is α OSA (independent of BMI) Combo of OSA & Obesity = Greater risk of endocrine dysfunction
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 • 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
Insulin Resistance • 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: • 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
Cardiovascular Disease • Hypertension is a well-described consequence of both OSA and obesity • Common mechanism: sympathetic nervous system activation & endothelial dysfunction • Children with OSA lose normal nocturnal dip in BP, eventually get daytime hypertension • Best assessed with 24 hour ambulatory BP monitoring Bhattacharjee, 2009; Gozal. 2008; Kheirandish-Gozal, 2010
Neurobehavioral • 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 Ali, Eur J Peds, 1996, Suratt, Pediatrics, 2006, Kaemingk (tuCASA), J Int Neuropsychol Soc., 2003 ; Gozal, Peds, 1998
Neurobehavioral • 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
Quality of Life • Improves with OSA treatment
Treatment Options for OSA with Obesity
Treatments • 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: • Improves obesity-related OSA • Difficult to achieve & sustain • Positive Airway Pressure (PAP) Shine, 2006; Amin, 2008
PAP Treatment • 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% Marcus, J Pediatr, 1995; Padman, Clin Pediatr, 2002
PAP Treatment • CPAP used initially • If needing CPAP > 10 cmH2O, or evidence of hypoventilation, use Bi-level
Future Directions • 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
Future Directions • 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 INSULIN RESISTANCE INSULIN RESISTANCE PAP
Thank you
