A Research Study for Children About Heart Changes and Obstructive Sleep Apnea (OSA)
Condition: Obstructive Sleep Apnea
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Study type: Observational

Summary: 
      In this research study the investigators want to learn more about the risk of developing
      blood vessel and heart disease from night-time sleep apnea. Sleep apnea is a condition that
      results from blocking of the throat during sleep. This study examines changes in blood
      pressure, blood vessel stiffness, heart size and levels of specific substances in the blood
      which may cause heart disease.

      This study is for children ages 5 to 13 years. The study involves 3 visits over 18 months.
      The first and last visits include an overnight sleep study (polysomnography or PSG). All the
      visits will include:

        -  body measurements to measure growth and how weight is distributed,

        -  resting blood pressure measurements,

        -  heart measurements (electrocardiogram and ultrasounds of the heart and blood vessels),

        -  36 hour home ambulatory blood pressure measurements,

        -  blood tests to look at things like fats, cholesterol, inflammatory factors,

        -  questionnaires

      Optional parts of the study include DNA and for children 8 years and older, testing and
      questionnaires to learn more about how sleep relates to learning, memory and behavior issues.
    

Detailed description: 
      This study is designed primarily to investigate the changes in blood vessels compliance and
      stiffness in children ages 5 to 13 years with the syndrome of obstructive breathing during
      sleep. It is designed to examine the relationship of the severity of the syndrome to vascular
      functions and to specific inflammatory mediators related to early stages of arterial
      stiffness and their effect on cardiovascular end-points, namely twenty-hour ambulatory blood
      pressure and left ventricular mass. The study will also examine the relationship between
      plasma and tonsillar tissue levels of inflammatory cytokines, and as well as the
      relationships between obstructive breathing during sleep and children's attention and
      problem-solving skills. Our aim is to identify vascular risk factors in childhood and to
      determine whether sleep disordered breathing in children represents an independent risk
      factor for cardiovascular disease and neurodevelopmental deficits which if left inadequately
      identified could track into adult years

        -  Hypothesis that increased levels of inflammatory cytokines will correlate with severity
           of the OSA disorder.

        -  Hypothesis that severity of the OSA disorder will correlate with measures of increased
           arterial wall stiffness, which in turn will lead to an increase in pulse pressure and
           left ventricular mass.

      This study will examine the vascular function in children, both lean and obese, with the
      syndrome of obstructive breathing during sleep which encompasses children with varying
      degrees of sleep disordered breathing (SDB). Children included in the SDB groups will have
      OSA above 1 obstructive episode per hour of sleep. The standard of care for a child with
      symptoms of obstructive breathing during sleep in otolaryngology practices is to undergo a
      tonsillectomy and or adenoidectomy (T&A). Children with SDB and who are scheduled to have T&A
      will be followed for 18 months and compared to children without SDB. To discern the effect of
      obesity on vascular function from the effects of sleep disordered breathing (SDB), the study
      will consist of four groups. Two groups, one lean and one obese, will have SDB and two
      groups, one lean and one obese, will be normal controls. Efforts will be made to match
      subjects across all groups. There is the potential that all groups will not contain the same
      number due to differences in incidence of OSA in relation to weight.

      There are 3 visits over approximately 18 months. The first visit will function as a
      qualifying visit based on the Obstructive Index from the polysomnography (OI>1 for SDB group
      and OI<1 with no snoring for the control group). Visits are approximately 9 months apart with
      the first and last visit including overnight polysomnography (PSG). Tonsillar tissue
      specimens will be obtained from a subset of SDB subjects who are scheduled for T&A.

      Data captured will include:

        -  Blood will be measured for high-sensitivity C reactive protein (hsCRP), serum amyloid A,
           cytokine panel, fasting lipoprotein analysis, complete blood count (CBC), glucose,
           insulin direct renin and DNA (optional).

        -  Tonsillar tissue will be measured for hsCRP, serum amyloid A, cytokine panel.

        -  Anthropometrics including height, weight, arm and finger circumferences, neck
           circumference, waist to hip ratio, and arm lengths.

        -  Left ventricular structure and vascular stiffness measurements include echocardiogram,
           carotid ultrasound, and radial tonometry.

        -  Resting blood pressure measurements include a continuous beat to beat BP recording
           obtained by a Portapres monitor with ECG and respiration monitoring done throughout
           sleep during the PSG and 30 minutes while awake in the morning.

        -  Activity and home ambulatory blood pressure (AMBP)measurements will be continuously
           monitored (every 30 minutes) using an automated oscillometric BP monitor over a 36 hour
           period simultaneously with actigraphy.

        -  Questionnaires about sleep and QOL.

        -  A subset of subjects aged 8 and older can participate in a neurobehavioral component
           that includes a formal assessment of attention and problem-solving.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Children 5-13 years recruited from the community, otolaryngology and sleep disorder clinics
      
Biospecimen description: 
      Serum, plasma, tissue
    
Keywords: Obstructive Sleep Apnea; Sleep Disordered Breathing; Vascular function; Arterial stiffness; Polysomnography; Cytokines