The overall objective of this randomized clinical trial is to test the effectiveness of a
novel personalized approach to the surgical treatment of OSA in children with Down
syndrome (DS). DS is a common disorder, affecting 1 in 691 births. The estimated
prevalence of obstructive sleep apnea (OSA) in children with DS ranges from 45-83%,
compared to 1-6% in the general pediatric population. Untreated OSA in children has been
associated with daytime sleepiness, cognitive and behavioral problems, and cardiovascular
complications, all of which are common in children with DS. Adenotonsillectomy (AT) is
the first line treatment for OSA in children, however, most large studies of AT outcomes
have excluded children with DS. Available evidence demonstrates that AT is far less
effective in children with DS than in the general pediatric population, with 48 to 95% of
children with DS having persistent OSA after AT. Medical treatments such as positive
airway pressure (PAP) therapy are frequently inadequate or poorly tolerated in this
population, so many children with DS and OSA remain untreated.
Pharyngeal hypotonia, unfavorable craniofacial anatomy, and adiposity are commonly cited
risk factors for OSA and failure of AT in children with DS, however, there have been few
attempts to characterize the pharyngeal anatomy or mechanisms of obstruction in this
population. Drug-induced sleep endoscopy (DISE) enables direct observation of the sites
and patterns of pharyngeal obstruction during sedated sleep using a flexible endoscope
passed through the nose into the pharynx. DISE was developed to guide surgical decisions
in adult OSA, and in recent years has also been used to design personalized surgical
interventions in children. To help standardize DISE assessments, the investigators
previously developed and validated the DISE Rating Scale in children based on ordinal
ratings of maximal airway obstruction (none, partial, complete) at six anatomic sites
from the nose to the larynx. Using this DISE Rating Scale, the investigators have
demonstrated that children with DS are more prone to tongue base and supraglottic
obstruction than non-DS children, suggesting the need for more personalized surgical
treatments that are tailored to the common sources of obstruction in this population.
Several small case series demonstrate that DISE-directed surgery can be effective in
treating OSA in children with DS. However, because there have been few prospective
studies and no randomized trials comparing different treatment options in this
population, there remains uncertainty about whether such a personalized approach leads to
superior outcomes compared to the first line AT.
It is the investigators' central hypothesis that a personalized DISE-directed surgical
approach that uses existing procedures to address the specific fixed and dynamic anatomic
features causing obstruction in each child with DS will be superior to the currently
recommended first line approach of AT. This novel approach may improve OSA outcomes and
reduce the burden of unnecessary AT or secondary surgery for persistent OSA after an
ineffective AT.
To test this hypothesis, the investigators propose to study children with DS and OSA ages
2-17 years with the following specific aims:
Aim 1: Compare the physiological outcomes of DISE-directed surgery vs AT in children with
DS and OSA.
Hypothesis 1: DISE-directed surgery will result in a greater improvement in the
obstructive apnea-hypopnea index compared to the standard AT intervention (effect size ≥
0.36) after 6 months.
Aim 2: Compare the clinical outcomes of DISE-directed surgery vs AT in children with DS
and OSA.
Hypothesis 2: DISE-directed surgery will result in a clinically significantly greater
improvement (≥ 9 point improvement) in OSA-specific quality of life (OSA-18) compared to
the standard AT intervention after 6 months. Secondarily, the investigators will test
other clinical outcomes such as executive function (BRIEF2).
The investigators propose a randomized single-blind comparative effectiveness trial of AT
vs DISE-directed sleep surgery for the treatment of OSA in children with DS (Figure 4).
The investigators' primary hypothesis is that a personalized surgical intervention based
on DISE findings will be more effective in treating OSA in children with DS than the
standard AT. The first aim will compare the change in the obstructive apnea-hypopnea
index (oAHI) between these treatment arms, and the second aim will compare the change in
subjective measures of sleep apnea related quality of life (OSA-18) and executive
function (BRIEF2). Outcomes will be assessed 6 months after surgery. The trial will be
conducted at seven sites: Oregon Health and Science University, Cincinnati Children's
Hospital and Medical Center, University of Michigan, University of Texas-Southwestern,
Eastern Virginia Medical School, Texas Children's, and Children's Hospital Colorado.