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Sherri Katz, MD, CM, FRCPCSherri Katz, MD, CM, FRCPCPediatric RespirologistPediatric Respirologist

Assistant ProfessorAssistant ProfessorChildren’s Hospital of Eastern OntarioChildren’s Hospital of Eastern Ontario

University of OttawaUniversity of Ottawa

Obesity & OSA in Obesity & OSA in KidsKids

ObjectivesObjectives

Understand the pathophysiologic Understand the pathophysiologic mechanisms of obstructive sleep apnea mechanisms of obstructive sleep apnea in obese children in obese children

Recognize associated co-morbidities of Recognize associated co-morbidities of obesity and concurrent OSA in childhoodobesity and concurrent OSA in childhood

Review alternative treatment strategies Review alternative treatment strategies for children with obesity and obstructive for children with obesity and obstructive sleep apnea sleep apnea

A growing problem…A growing problem…

OSA has a prevalence of 1-3% in childrenOSA has a prevalence of 1-3% in children

Prevalence of sleep disordered breathing Prevalence of sleep disordered breathing in in obeseobese children is 13-66% children is 13-66% - 10-20 x - 10-20 x

Obesity is a rising epidemic in pediatrics Obesity is a rising epidemic in pediatrics – 5-fold increase in the past 15 years5-fold increase in the past 15 years– Prevalence of 10%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…A growing problem…

As OSA is strongly linked to obesity, As OSA is strongly linked to obesity, this means more kids with OSA!this means more kids with OSA!

What is OSA?What is OSA?

Partial (Partial (hypopneahypopnea) or complete () or complete (apneaapnea) ) upper airway obstruction during sleep upper airway obstruction during sleep associated with: associated with: – Sleep disruptionSleep disruption– HypoxemiaHypoxemia– HypercapniaHypercapnia– Daytime symptomsDaytime symptoms

Continued chest and abdominal motion in the Continued chest and abdominal motion in the absence of airflow during sleepabsence of airflow during sleep

Apnea-Hypopnea Index:Apnea-Hypopnea Index: # of events/hour # of events/hour • Used to categorize severity of conditionUsed to categorize severity of condition

Why does OSA occur?Why does OSA occur?

We don’t breathe as deeply We don’t breathe as deeply while sleeping as when awakewhile sleeping as when awake

– blunting of hypoxic / hypercapnic blunting of hypoxic / hypercapnic drivedrive

– 25% 25% tidal volume tidal volume

– arterial pCOarterial pCO22 3-4 mmHg 3-4 mmHg

– arterial pOarterial pO22 5-10 mmHg 5-10 mmHg

Why does OSA occur?Why does OSA occur? Upper airway tone is decreased Upper airway tone is decreased

during sleep, especially in REMduring sleep, especially in REM

Collapse/obstruction of the upper Collapse/obstruction of the upper airway during sleep causes airway during sleep causes obstruction & apneaobstruction & apnea

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Nares /hard palate

Pharynx

Larynx / trachea

Why does OSA occur?Why does OSA occur?

Adenotonsillar hypertrophyAdenotonsillar hypertrophy

– Most common cause of OSA in Most common cause of OSA in childrenchildren

– Between 3-6 yrs, tonsils & adenoids Between 3-6 yrs, tonsils & adenoids are largest relative to size of airway are largest relative to size of airway peak incidence of OSA peak incidence of OSA

Why does OSA occur?Why does OSA occur?Large tonsils and adenoids Large tonsils and adenoids

BUT BUT

No direct correlation between airway or No direct correlation between airway or adenotonsillar size & OSAadenotonsillar size & OSA

Upper airway is narrower and more collapsible in children with OSA Upper airway is narrower and more collapsible in children with OSA Airway patency is maintained by increased neuromuscular activityAirway patency is maintained by increased neuromuscular activity

THEREFORETHEREFORE

Combination of structural abnormalities & Combination of structural abnormalities & neuromotor tone abnormalities must be neuromotor tone abnormalities must be

present for OSA to occurpresent for OSA to occur

Isono, AJRCCM, 1998, Marcus, Respiration Physiology, Isono, AJRCCM, 1998, Marcus, Respiration Physiology, 19991999

Why do Obese Kids get Why do Obese Kids get OSA?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 What are the consequences?consequences?

Health Care UtilizationHealth Care Utilization InflammationInflammation Metabolic Metabolic CardiovascularCardiovascular NeurobehaviouralNeurobehavioural Quality of lifeQuality of life

Health Care BurdenHealth Care Burden Economic burden of untreated OSA Economic burden of untreated OSA alonealone

is comparable to that of diabetesis comparable to that of diabetes

Children with OSA have Children with OSA have 226% 226% health health care utilizationcare utilization

Treating OSA in children Treating OSA in children health care health care costs by 1/3 costs by 1/3

In adults, PAP therapy is as effective as In adults, PAP therapy is as effective as cholesterol-lowering agents in preventing cholesterol-lowering agents in preventing cardiovascular diseasecardiovascular disease

AlGhanim, 2008; Reuveni, 2002; Tarasiuk, 2004&2007

Common Common PathophysiologyPathophysiology

Obesity OSA

Sympathetic Nervous System Activation

Oxidative stress

Changes in renin-angiotensin-aldosterone system & renal sympathetic activity

Hypoxia and micro-arousals

Systemic inflammation

InflammationInflammation

C-reactive protein is released C-reactive protein is released during systemic inflammatory during systemic inflammatory processesprocesses

Can assess risk of heart disease Can assess risk of heart disease using hs-CRP assayusing hs-CRP assay

Hs-CRP levels Hs-CRP levels in OSA and in OSA and correlate with severitycorrelate with severity

Hs-CRP Hs-CRP following OSA treatment following OSA treatment with T&Awith T&A

Goldbart, 2008; Bassuk, 2004;Li, 2008; Kheirandish-Gozal, 2006;

Insulin ResistanceInsulin Resistance

Consequence of both childhood obesity Consequence of both childhood obesity + OSA+ OSA

Hypoxia and micro-arousals activate sympathetic nervous system

Pro-inflammatory state

Insulin Insulin resistanceresistance 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 ResistanceInsulin Resistance

Precursor of type 2 diabetes and Precursor of type 2 diabetes and cardiovascular diseasecardiovascular disease

Elevated insulin levels in childhood Elevated insulin levels in childhood persist into adulthood & are predictive persist into adulthood & are predictive of cardiovascular disease riskof cardiovascular disease risk

Severity of insulin resistance is Severity of insulin resistance is αα OSA OSA (independent of BMI)(independent of BMI)

Combo of OSA & Obesity = Greater risk Combo of OSA & Obesity = Greater risk of endocrine dysfunctionof endocrine dysfunction

Insulin ResistanceInsulin Resistance

In obese and non-obese adults, PAP In obese and non-obese adults, PAP treatment for severe OSA improved treatment for severe OSA improved insulin sensitivity within 2 days and insulin sensitivity within 2 days and sustained effect over 3 months sustained effect over 3 months – Improvements more rapid in non-obese Improvements more rapid in non-obese

subjectssubjects– Suggests obesity is contributing to insulin Suggests obesity is contributing to insulin

resistanceresistance– Treating OSA alone, independent of body Treating OSA alone, independent of body

composition, improves insulin resistancecomposition, improves insulin resistanceHarsch, AJRCCM. 2004

Insulin ResistanceInsulin Resistance

4 Pediatric studies of effect of T&A for 4 Pediatric studies of effect of T&A for OSA on insulin resistance showed OSA on insulin resistance showed improvementimprovement– Small sample size, young children, mostly Small sample size, young children, mostly

non-obesenon-obese

PAP therapy for OSA in obese kids with PAP therapy for OSA in obese kids with pre-existing insulin resistance: pre-existing insulin resistance: – Improved fasting glucose & insulin levels Improved fasting glucose & insulin levels

without change in BMIwithout change in BMI– Not statistically significant, small sample sizeNot 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 DiseaseCardiovascular Disease

Hypertension is a well-described Hypertension is a well-described consequence of both OSA and obesityconsequence of both OSA and obesity

Common mechanismCommon mechanism: : sympathetic nervous sympathetic nervous system activation & endothelial dysfunctionsystem activation & endothelial dysfunction

Children with OSA lose normal nocturnal dip Children with OSA lose normal nocturnal dip in BP, eventually get daytime hypertensionin BP, eventually get daytime hypertension

Best assessed with 24 hour ambulatory BP Best assessed with 24 hour ambulatory BP monitoringmonitoring

Bhattacharjee, 2009; Gozal. 2008; Kheirandish-Gozal, 2010

NeurobehavioralNeurobehavioral

Neurobehavioral & learning deficits Neurobehavioral & learning deficits common and reversiblecommon and reversible

Young children who snore frequently & Young children who snore frequently & loudly are at risk of lower grades in loudly are at risk of lower grades in school several years after OSA is school several years after OSA is resolved resolved

Ali, Eur J Peds, 1996, Suratt, Pediatrics, 2006, Ali, Eur J Peds, 1996, Suratt, Pediatrics, 2006, Kaemingk (tuCASA), J Int Neuropsychol Soc., 2003 ; Kaemingk (tuCASA), J Int Neuropsychol Soc., 2003 ; Gozal, Peds, 1998Gozal, Peds, 1998

NeurobehavioralNeurobehavioral

Magnitude of impairment in Magnitude of impairment in cognitive function cognitive function attributable to sleep-attributable to sleep-disordered breathing, is disordered breathing, is profoundprofound

– Similar in magnitude to the effects Similar in magnitude to the effects of lead exposure in childrenof lead exposure in children

Suratt, Pediatrics, 2006Suratt, Pediatrics, 2006

Quality of LifeQuality of Life Improves with OSA treatmentImproves with OSA treatment

Treatment Options Treatment Options for OSA with Obesityfor OSA with Obesity

TreatmentsTreatments

Adenotonsillectomy (T&A):Adenotonsillectomy (T&A): – First-line therapy for younger children with First-line therapy for younger children with

OSAOSA– In obese children, cure rates are much In obese children, cure rates are much

lower: ineffective in 70-80%lower: ineffective in 70-80%

Weight loss:Weight loss: – Improves obesity-related OSAImproves obesity-related OSA– Difficult to achieve & sustainDifficult to achieve & sustain

Positive Airway Pressure (PAP)Positive Airway Pressure (PAP)

Shine, 2006; Amin, 2008

PAP TreatmentPAP Treatment

86% success rate in kids to 86% success rate in kids to improve OSA with CPAP improve OSA with CPAP

In 10 children using CPAP/BIPAP In 10 children using CPAP/BIPAP AHI decreased from 20 to 1 and AHI decreased from 20 to 1 and lowest oxygen saturation lowest oxygen saturation increased from 76% to 90%increased from 76% to 90%

Marcus, J Pediatr, 1995; Padman, Clin Pediatr, 2002Marcus, J Pediatr, 1995; Padman, Clin Pediatr, 2002

PAP Treatment PAP Treatment

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CPAP used initiallyCPAP used initially If needing CPAP > 10 cmHIf needing CPAP > 10 cmH22O, or O, or

evidence of hypoventilation, use Bi-evidence of hypoventilation, use Bi-levellevel

Future DirectionsFuture Directions

Emerging evidence that PAP for OSA Emerging evidence that PAP for OSA improves obesity-related conditions:improves obesity-related conditions:

– Insulin resistanceInsulin resistance– HypertensionHypertension– Quality of lifeQuality of life

** Unfortunately does not assist weight ** Unfortunately does not assist weight loss in adults!loss in adults!

Redenius, 2008

INSULIN RESISTANCE

Future DirectionsFuture Directions

Long-term outcomes of PAP therapy for Long-term outcomes of PAP therapy for OSA in obese children not yet studied in OSA in obese children not yet studied in long-term prospective manner long-term prospective manner – CIHR funded study now ongoing in CanadaCIHR funded study now ongoing in Canada

PAP INSULIN RESISTANCE

Thank you