h - h sherri katz, md, cm, frcpc pediatric respirologist assistant professor children’s hospital...
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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