A Research Study for Children About Heart Changes and Obstructive Sleep Apnea (OSA)

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.

Inclusion Criteria:

- Normal controls will be enrolled from children who have a signed informed consent and
who have completed the initial polysomnography; whose history does not reveal any
symptoms of obstructive breathing during sleep; and who have a polysomnogram that is
considered normal.

- SDB groups will be enrolled from children who have a signed informed consent and who
have completed the initial polysomnography with OI>1; whose history includes snoring,
hypertrophied tonsils or hypertrophied adenoids. Subjects will be assigned to a study
group based on results of the overnight polysomnogram.

Exclusion Criteria:

Exclusion criteria:

- Children with positive history of snoring without evidence of AHI> 1 and who do not
follow through with tonsillectomy or adenoidectomy surgery.

- Children with chronic pulmonary conditions including asthma (children with mild,
intermittent asthma will be included and are defined as use of rescue inhaler < 1/wk
unless treatment for exercise induced asthma).

- Children with cardiac disease

- Children with neuromuscular disorders

- Children with developmental delay such as Down syndrome

- Children with chronic renal disease such as chronic pyelonephritis or
glomerulonephritis

- Children with endocrinological disorders or who are on chronic steroid therapy
including inhaled steroids.

- Children using medications which influence the autonomic nervous system such as
adrenergic and cholinergic drugs, alpha and beta blockers, and drugs with
parasympatholytic action.

- Children with any acute or chronic inflammatory condition.

- Children with BMI Z score that exceeds 2.9 for age and gender.

- Children who do not complete the first 36 hour AMBP study with a 70% success rate of
BP readings.

- Children with a history of chronic or recurrent tonsillitis (by parent or physician
report) defined as 6 episodes of tonsillitis / year for a period of one year; 5
episodes of tonsillitis / year for 2 years; 4 episodes of tonsillitis / year for 3
years.