Treatment of Obstructive Sleep Apnea in Children: An Opportunity for Cardiovascular Risk Modification
Condition: Obesity; Obstructive Sleep Apnea; Sleep Disorders; Cardiovascular Disease
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Sleep Wake Disorders; Cardiovascular Diseases
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): cPAP; cPAP, Continuation; cPAP, Discontinuation
Intervention type(s): Device; Device; Device
Intervention description(s): All participants diagnosed with obstructive sleep apnea will be required to use cPAP for 6 months prior to the RCT component of this trial; Participants will be randomized to continue cPAP for a 2 week period; Participants will be randomized to discontinue cPAP for a 2 week period
Other intervention name(s): continuous Positive Airway Pressure
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: Children; Obesity; Cardiovascular; Sleep; Apnea; Obstructive