Treatment of Obstructive Sleep Apnea in Children: An Opportunity for Cardiovascular Risk Modification
Treatment of Obstructive Sleep Apnea in Children: An Opportunity for Cardiovascular Risk Modification
Heart disease is a major cause of ill-health and death in adults. The risk factors for heart
 disease, if present in children, carry over into adult life. Childhood obesity has reached
 epidemic proportions in Canada and is associated with many heart disease risk factors such as
 high blood pressure. Another complication of obesity is obstructive sleep apnea. Sleep apnea
 is marked by snoring at night, pauses in breathing and low oxygen levels and occurs in up to
 60% of obese children, but it is diagnosed in less than 20% of obese children. Importantly,
 sleep apnea in children, like obesity, is linked with high blood pressure and heart disease.
 Thus, children with sleep apnea who are obese are likely to have an increased risk for high
 blood pressure and heart disease. Currently, there is little knowledge of the extent of heart
 disease in obese children with sleep apnea.

 The best treatment for both obesity and sleep apnea is weight loss. Weight loss strategies
 are generally not very successful and since 75% of obese children will become obese adults,
 urgent treatments are needed to reduce heart disease in the long-term. Treating sleep apnea
 in obese children may be one of the ways to reduce heart disease. Sleep apnea can be treated
 with continuous positive airway pressure (CPAP), which involves wearing a mask attached to a
 breathing machine while asleep. It is unknown how effective CPAP is in reducing heart disease
 in obese children.

 The investigators will recruit children with sleep apnea who are obese and test for heart
 disease risk. The investigators will then treat these children with CPAP. After 6 months of
 CPAP, the investigators will repeat the tests to determine if CPAP lowers the risk for heart
 disease. At the end of the 6 months, those receiving CPAP will be randomized to either
 continue CPAP or discontinue CPAP for a 2 week period. At the end of the 2 week period the
 participants will repeat the tests again to determine the magnitude of the effect of CPAP.

 The investigators expect that CPAP treatment for sleep apnea in obese children will reduce
 blood pressure and lower heart disease. These results will increase awareness of the dangers
 of sleep apnea in obese children, which will facilitate early diagnosis and treatment,
 ultimately reducing heart disease long-term.
Statement of the Problem: In Canada, child and adolescent obesity, defined as a body mass
 index (BMI) of >95th percentile for age and gender1 represents one of the most common
 conditions effecting children in Canada with an obesity rate of 10% in 12-17 year old
 children, which currently equates to approximately half a million obese children in Canada.
 Obesity is not only complicated by cardiovascular and metabolic dysfunction, such as left
 ventricular modeling, hypertension, glucose intolerance and dyslipidaemia, it is also
 associated with obstructive sleep apnea syndrome (OSAS), occurring in up to 60% of obese
 children.

 OSAS is characterized by snoring, recurrent partial (hypopneas) or complete obstruction
 (apneas) of the upper airway, frequently associated with intermittent oxyhaemoglobin
 desaturations, sleep disruption and fragmentation. The gold standard test for diagnosing
 obstructive sleep apnea is a polysomnogram (PSG). Specifically, OSAS affects 1-4% of healthy
 children who are typically 2-8 years of age6, coinciding with adenotonsillar hypertrophy, the
 commonest cause of OSAS in children. Usual treatment for OSAS in children with adenotonsillar
 hypertrophy is an adenotonsillectomy (AT). However, there is clear evidence that not only is
 there a high prevalence of obstructive sleep apnea in obese children, but further, the AT is
 not successful for resolution of OSAS. This is, in part due to the fact that adenotonsillar
 hypertrophy is not the single most significant risk factor for OSAS in the obese population.

 The factors implicated in the pathophysiology of OSAS in obese children include soft tissues
 restricting the upper airway size such as fat pads in the soft palate, lateral pharyngeal
 wall and at the base of the tongue. However, despite the anatomic evidence predisposing obese
 children to OSAS there are also alterations in functional mechanisms that lead to increased
 airway collapsibility predisposing these children to OSAS. Specifically, obesity is
 associated with significant alterations in body composition that could affect chest wall
 mechanics by weighting the chest wall and reducing lung compliance. Functional residual
 capacity is diminished to abdominal visceral fat impinging on the chest cavity. Such a
 reduction in functional residual capacity and compliance increases the risk for sleep
 disordered breathing by mechanisms of hypoventilation, atelectasis and ventilation perfusion
 mismatch all increasing the work of breathing and fatigue. Moreover, hypoventilation in
 itself may reduce upper airway motor tone. Further, ventilator responses may be altered as
 studies focusing on obese adults have shown that morbidly obese subjects are more susceptible
 to decreased ventilatory responses to both hypoxia and hypercapnia.

 Given this understanding that adenotonsillectomy is not curative in obese children with
 obstructive sleep apnea, weight loss would be considered the treatment of choice. However,
 obesity intervention programs have not been wholly successful in BMI reduction in children
 although in overweight adults, magnitude of weight loss was related to an improvement in
 OSAS. Thus, the delivery of positive airway pressure (PAP) either continuous positive airway
 pressure (CPAP) or bilevel positive airway pressure (BiPAP) is increasingly used as the first
 line of treatment for OSAS in obese children, although usually in conjunction with weight
 loss strategies.

 Although the benefits of PAP are well established in adults, there is a paucity of available
 paediatric data.

 As previously mentioned, obesity is a risk factor for cardiovascular and metabolic
 dysfunction; however, OSAS independent of obesity is further associated with cardiac
 remodeling and cardiovascular metabolic dysfunction. Specifically, if untreated, obstructive
 sleep apnea in children may lead to excessive daytime sleepiness, poor school performance,
 hypertension, changes in left ventricular mass and geometry, endothelial cell dysfunction,
 arterial stiffness, autonomic dysfunction inflammation, and the Metabolic Syndrome (MetS).
 Thus, OSAS in the context of obesity may independently or synergistically magnify the risk of
 an already compromised cardiometabolic regulation.

 Several metrics will be utilized. Physical activity levels will be measured utilizing
 Habitual Activity Questionnaires. Insulin resistance will be measured using Fasting Glucose
 and Fasting Insulin Levels. Cardiovascular markers will include 24 hour blood pressure and
 cardiograms - left ventricular mass index. C Reactive Protein (CRP) will be utilized as the
 marker of inflammation.

 The mechanisms linking both OSAS and obesity to cardiometabolic dysfunction is believed to be
 due to activity of the sympathetic nervous system (SNS) and effects of oxidative stress,
 exacerbating proinflammatory states. Chronic, awake sympathoactivation may promote vascular
 remodeling and can induce significant cardiovascular morbidity.
Inclusion Criteria:

 -  Obesity, BMI > 95th centile for age and gender

 -  10-18 years of age

 -  Informed consent and the ability to perform the tests

 -  Moderate to sever OSAS (will be eligible for inclusion in the treatment group for this
 study)

 Exclusion Criteria:

 -  Use of anti-hypertensive medication

 -  Medications known to alter glucose and insulin regulation

 -  Significant central sleep apnea

 -  Currently unwell or recent viral/bacterial infection in the previous 4 weeks

 -  Currently hospitalized

 -  Known underlying neuromuscular disorder, congenital heart disease, diagnosed
 ventricular disorder

 -  Syndrome's e.g. Down (high prevalence of OSAS independent of obesity)

 -  Pregnancy

 -  Gastric bypass surgery

 -  Unable to have a PSG perfumed for whatever reason