Use of Sleep Endoscopy to Predict Outcomes of Pediatric Adenotonsillectomy
Conditions: Obstructive Sleep Apnea
Sponsor: Oregon Health and Science University

Official Title:  Use of Sleep Endoscopy to Predict Outcomes of Pediatric Adenotonsillectomy 
 
Unique Protocol ID:  IRB00009825 
 
Identifiers: NCT02693977 
 
Document Date: 02/12/2018 
 
 

IRB Protocol for Study # 00009825 
 
I. Title 
 
Use of Sleep Endoscopy to Predict Outcomes of Pediatric Adenotonsillectomy  
 
II. Personnel 
 
Principal Investigator: Derek Lam MD, MPH 
Co-Investigators: Henry Milczuk MD, Carol Macarthur MD, Ericka King MD, Lourdes 
Quintanilla-Dieck, MD, and Steven Shea PhD 
Study Contact: Derek Lam MD, MPH 
 
III. Site of Study 
 
Doernbecher Children’s Hospital, Oregon Health and Science University 
 
IV. Purpose of Study 
 
The purpose of this study is to determine whether sleep endoscopy performed in high-risk 
pediatric patients with obstructive sleep apnea (OSA) at the time of adenotonsillectomy 
(AT) can predict whether the AT will be successful as an initial treatment for OSA. We 
hypothesize that patients with multiple sites of obstruction in addition to adenotonsillar 
hypertrophy (e.g. the nasal airway, velum, base of tongue, supraglottis) will be more likely 
to have residual sleep apnea on postoperative sleep testing.  
 
V. Background and Significance 
 
Pediatric Obstructive Sleep Apnea Syndrome, Health Care Utilization, and 
Adenotonsillectomy: Obstructive sleep apnea syndrome OSAS is defined as the 
symptomatic repetitive obstruction of the upper airway during sleep and has been 
estimated to affect 1-6% of the general pediatric population.1-3 Untreated OSAS in children 
has been associated with childhood hypertension,4,5 autonomic dysfunction,6,7 attention 
deficit/hyperactivity disorder,8,9 neurobehavioral impairment, 8, 10-13 and poor quality of 
life.14-16 These sequelae contribute to a 226% increase in health care utilization among 
children with OSAS compared to controls, primarily in the form of increased 
hospitalizations, emergency department visits, and medication use.17,18 Adenotonsillar 
hypertrophy is considered the most common risk factor for OSAS in children, therefore 
unlike in adult OSAS, adenotonsillectomy (AT) is the recommended first line treatment.19 In 
large part due to the increasing awareness and diagnosis of pediatric OSAS, the incidence of 
AT increased dramatically from 1980 to 2005.20 With more than 500,000 procedures 
performed per year, AT is now the second-most common procedure performed in children 
in the US, and 77% of these have OSAS as the primary indication.20, 21 
 
Persistent Obstructive Sleep Apnea Syndrome after Adenotonsillectomy: Current 
guidelines recommend AT as a first line treatment for pediatric OSAS even for those 

patients who may have significant risk of post-AT OSAS.19, 22 Estimates of the prevalence of 
persistent OSAS after AT vary widely due to use of different polysomnographic criteria for 
diagnosis. Studies that assessed the risk of post-AT OSAS using a conservative adult 
threshold for diagnosis demonstrated that even with this high threshold at least 13-29% of 
children undergoing AT for pediatric OSAS will have significant residual disease23-25 and 
approximately 75% of children will fail to achieve normalization on polysomnography.25, 26 
Specific populations of patients that have been recognized to be particularly at risk for 
post-AT OSAS include those with severe baseline OSAS,23, 25-27 Down syndrome,28 obesity,26, 
29-32 and age > 7 years.26 In obese patients, the prevalence of post-AT OSAS has been 
reported as high as 73-88%.30, 33 Since obesity has tripled over the last three decades and 
now affects approximately 8% of children aged 2-5 years, 18% of children aged 6-11 and 
21% of adolescents aged 12-19 years,34 the problem of persistent OSAS after AT is likely to 
continue to grow. 
 
No Reliable Method to Identify Patients Who Will Benefit Most from 
Adenotonsillectomy: Even within populations at risk for AT failure, there is a wide 
variation in treatment response. One study of morbidly obese children undergoing AT 
demonstrated only a 37% cure rate while 53% had sufficient residual OSAS to require 
further treatment with continuous positive airway pressure (CPAP). However, no 
significant baseline differences were identified between surgical responders and non-
responders.33 The mechanism for failure in this population is unclear, but it is presumed 
that increased generalized adiposity leads to multilevel obstruction similar to obese adults, 
thus decreasing the likelihood of success with AT.30 Similarly a poor but still 
variable response to AT was observed in children with Down syndrome with post-AT 
success varying between 18% and 55% depending on the specific criteria used.35, 36 There 
are no studies that have clearly identified predictors of AT outcome within the Down 
syndrome population, however, some studies of Down syndrome patients who failed AT 
have suggested that multilevel obstruction is common.37, 38 Thus, although specific 
populations of patients are known to have greater risk of post-AT OSAS on average, the 
individual characteristics causing persistent disease remain unclear. Accurate 
prognostication of the risk of residual OSA after AT for any individual patient remains a 
challenge. Studies of patients with persistent post-AT OSAS have suggested that multilevel 
obstruction at locations besides the tonsils or adenoids are likely contributors, but this has 
not been clearly demonstrated. In this study, we present a novel concept for building a 
composite model to predict the outcome of AT in children with OSAS. This model will 
include not just baseline features of history and physical exam but also the findings of 
dynamic sleep-related collapse at specific anatomic sites in the pharynx observed during 
sleep endoscopy. This model will give further insight into the mechanisms of airway 
obstruction as well as the possible reasons for persistent OSAS after AT.  
 
Standardized Approach to Drug Induced Sleep Endoscopy in Children: Kezarian et al 
have previously described a rating scale for DISE in an attempt to standardize the reporting 
of endoscopic findings in adults with OSAS.39 This rating scale evaluates the degree and 
pattern of obstruction at four levels of the pharynx: the Velum (soft palate), Oropharynx 
(including the tonsils), Tongue base, and Epiglottis (VOTE). The VOTE rating scale has been 
demonstrated to have moderate to substantial inter-rater reliability with kappa values 

ranging from 0.4-0.8 depending on the specific structures being compared.40 Other 
investigators have utilized modified versions of the VOTE rating scale in children, including 
other levels of the airway such as the nasal airway, nasopharynx, and supraglottis.41, 42 One 
recent study demonstrated that sleep endoscopy findings in children were more reliable 
than during awake endoscopy and noted a strong correlation between polysomnography 
results and the overall impression of OSA severity during endoscopy.43 
 
Dexmedetomidine, which will be used in this study, is a highly selective α2-adrenoceptor 
agonist that has been demonstrated to result in a sedated sleep similar to natural sleep 
without causing respiratory depression44. Though there have been some reports of 
transient bradycardia and blood pressure changes in response to dexmedetomidine 
infusion (usually transient hypotension of 10% with slow infusion) these cardiovascular 
effects are mitigated by co-administration of a bolus of ketamine as described in more 
detail in the Methods section.45 
 
Preliminary Data: In a preliminary retrospective review of our patient population and 
surgical volume, we examined the electronic medical record of all patients who underwent 
AT over a 12 month period. 498 patients were identified, operated on by the four pediatric 
otolaryngologists in the group at that time. Approximately 200 (40%) of these were 
performed for OSAS in patients that could be considered high risk for residual post-AT 
OSAS and would meet inclusion/exclusion criteria described below. Further retrospective 
review of patients who also underwent DISE at the time of AT with recorded videos 
available for review identified 20 patients, 10 of whom also had preoperative 
polysomnography data available. Among these patients, those who had at least one site of 
complete obstruction noted during sleep endoscopy had more severe OSAS than those with 
only partial obstruction (mean apnea-hypopnea index [AHI] 20.9 SD 26.9 vs 8.3 SD 9.8 (p = 
0.3, Mann-Whitney test). While this preliminary data does not indicate a statistically 
significant difference in mean baseline AHI, this is based on a very small sample size, thus it 
is possible that with a larger sample size, this large difference would become statistically 
significant. 
 
Further Research Needed: Untreated OSA in children has been associated with childhood 
hypertension, autonomic dysfunction, attention-deficit/hyperactivity disorder, poor school 
performance, and poor quality of life. These sequelae contribute to a 226% increase in 
health care utilization among children with OSA compared to controls. Residual OSA after 
AT in the pediatric population remains a serious concern; as the patient grows and 
changes, their airway physiology also changes. Although there is a growing body of 
research suggesting demographic and comorbidity risk factors for post-AT residual OSA, 
the ability to accurately predict the likelihood or severity of residual OSA for any given 
individual remains elusive. Possible tools for the evaluation of post-AT OSA in pediatric 
populations include radiologic examinations, cine MRI scanning, and endoscopic 
evaluation, along with polysomnography, validated questionnaires, and physical 
examinations. Determining what instruments best predict residual OSA after surgical 
intervention is an important step towards more effective OSA management.  
 
 
 

 
VI. Methods  
 
Study Design: This will be a prospective cohort study of pediatric OSAS patients who are 
considered high risk for having residual OSAS after AT. This study does not involve any 
experimental procedures or medication.   
 
Specific Aim 1: Propose a sleep endoscopy rating scale and evaluate its reliability and correlation 
with baseline OSA. 
Hypothesis 1: In pediatric OSA patients undergoing AT, compared to patients with only partial 
obstruction, patients with complete obstruction at one or more anatomic sites will be more 
strongly correlated with worse 1) polysomnography parameters, 2) quality of life, and 3) 
executive functioning. 
 
Specific Aim 2: Determine associations between a proposed sleep endoscopy rating scale and the 
outcomes of AT. 
Hypothesis 2: In pediatric OSA patients undergoing AT, compared to patients with obstruction only 
at the tonsils or adenoids, patients with complete obstruction at other sites will show a greater 
risk of post AT OSA and decreased improvement from baseline with respect to 1) 
polysomnography parameters, 2) quality of life, and 3) executive functioning. 
 
Specific Aim 3: Develop and validate a composite predictive model of the outcomes of AT 
including the proposed sleep endoscopy rating scale, demographic variables, 
comorbidities, and physical exam. 
Hypothesis 3: A composite model including a sleep endoscopy rating scale and other 
preoperative risk factors will be predictive of the risk of residual OSA after AT.  
 
Subjects:  
Inclusion criteria: Patients with OSA demonstrated by polysomnography (AHI ≥ 2 or 
obstructive apnea index ≥ 1) aged 2-18 years who are candidates for AT and also satisfy 
one or more of the following criteria considered high risk for residual OSA after AT: 
 Obesity (BMI > 95th percentile or z-score > 1.96 for age) 
 Down syndrome 
 African American race 
 Pre-operative AHI > 10 
 Age > 7 years 
 Tonsils rated 1+ but persistent symptoms of OSA 
 
Exclusion criteria: Patients with one or more of the following criteria will be excluded from 
the study: 
 Craniofacial anomalies (including cleft lip and palate, Pierre Robin sequence) 
 Genetic abnormalities 
 Neuromuscular disorders (including cerebral palsy, hypotonia) 
 Subglottic or tracheal stenosis 
 Tracheostomy dependence 

 Severe cardiopulmonary disease requiring supplemental oxygen at night 
 Primary caregiver(s) are unable to complete questionnaires in English or Spanish, 
cannot be reached by telephone, or are planning to move during the study period 
 
Recruitment: Daily clinic schedules will be reviewed by the PI or the research 
assistant to determine in advance which patients of participating providers might be 
eligible for the study based on the above inclusion and exclusion criteria. Two 
recruitment scenarios are anticipated: 1) Patients who have previously been diagnosed 
with OSAS by polysomnography and are referred to Pediatric Otolaryngology for 
consideration of AT: In this scenario the patients will proceed with surgery scheduling 
according to routine clinical care, with postoperative follow-up to be coordinated with the 
assistance of the RC to ensure timely follow-up and administration of follow-up 
questionnaires. 2) Patients referred to Pediatric Otolaryngology for consideration of AT for 
symptoms of sleep disordered breathing without a polysomnographic diagnosis of OSAS: 
These patients will be requested to undergo polysomnography prior to scheduling surgery 
in order to confirm the diagnosis of OSAS. Should any enrolled study subjects turn out to 
not have OSAS according to polysomnography, they will subsequently be excluded from the 
study and will be notified of such in writing.  
 
Once the clinical decision is made by the pediatric otolaryngologist and family to proceed 
with AT, patients who meet the inclusion and exclusion criteria as noted above will be 
identified to the RC by the PI or collaborating pediatric otolaryngologist staffing the clinic. 
They will be informed of the study’s purpose, risks, and benefits, and invited to participate. 
Parental written informed consent and child assent (if applicable) will be obtained by the 
research coordinator. The importance of the follow-up evaluation (questionnaires and 
postoperative sleep study) will be emphasized at enrollment. Also at that time, they will be 
provided with several questionnaires above and beyond the traditional clinical sleep 
questionnaires, including Infant/Toddler Quality of Life Questionnaire [ITQOL], which is a 
general quality of life instrument for patients 2 months through 5 years of age; Child Health 
Questionnaire [CHQ], a general quality of life instrument for patients 5 years through 18 
years of age; a modified Epworth Sleepiness Scale [ESS], which measures daytime 
sleepiness in patients over the age of 5; and a neuro-cognitive instrument, called the 
Behavior Rating Inventory of Executive Function, or BRIEF. Each of these instruments has 
been in use for a number of years and has been well-validated through clinical and non-
clinical studies, showing reliability and validity in a variety of settings and populations. 
Patients will have the option to complete these forms on paper or online. If they choose to 
complete the forms online, they will be allowed access to complete the questionnaires 
through OHSU’s RedCap online database system; access will be restricted using a 
personalized password for each subject.  
 
Consent and Assent: Written informed consent and authorization will be obtained from all 
parents or legal guardians of the patient participating in this study, as stated in the 
Informed Consent section of the case of Federal Regulations, Title 21, Part 50.  The consent 
and authorization form includes information on the data repository as well as the primary 
study. If a parent’s signature cannot be obtained, the investigator or RC will ensure that the 

informed consent is signed by the patient’s legal guardian. Only one parent’s signature will 
be required (the study involves greater than minimal risk but includes the prospect of 
direct benefit to individual subjects). If the patient is a child between the ages of 7 and 18 
and is cognitively able, assent from the patient will also be obtained. If the patient and/or 
the patient’s legal guardian does not speak fluent English but does speak Spanish, they will 
be provided with a translated consent/assent form. Patients who do not speak English or 
Spanish will not be included in this study. Documentation of the consent process and a copy 
of the signed consent shall be maintained in the research record and patient’s medical 
record.  
 
Compensation and Costs: Patients’ parents/guardians will be compensated for their 
study participation. They will receive $30.00 after completing the second set of 
questionnaires OR, if applicable, $75.00 after completing the second set of questionnaires 
and their child’s post-surgery sleep study. They will not incur costs for the sleep endoscopy 
procedure (provided it takes place at the same time as their T&A). They may incur costs if 
their insurance applies cost-sharing to their polysomnography, but this procedure is 
medically important to managing patients at high risk for residual OSA and is considered 
part of routine clinical care.  
 
Third party payers will incur costs related to the procedures in this study (sleep 
endoscopies and polysomnography), but, given the high risk nature of the patients who will 
be enrolled in this study, these procedures are reasonable, clinically indicated, and 
necessary in the proactive management of OSA and residual OSA.   
 
Grant funding is available under NHLBI grant number 1K23HL127132 - 01A1,  PPQ of 
1009531.  
 
Termination and Withdrawal: Subjects have the right to withdraw from (i.e., discontinue 
participation in) this research at any time without any repercussions by notifying the 
principal investigator or the study coordinator either in writing or via email. If a subject 
decides to withdraw from this research study, the following research activities involving 
that subject’s participation will be discontinued: 
 
Interacting or intervening with the subject in order to obtain data about him or her for 
the study (e.g., obtaining polysomnography or questionnaire data, initiating follow-up 
contacts with the subject) and 
 
Obtaining additional identifiable private information about the subject for the study by 
collecting or receiving additional information from any source (e.g., obtaining 
additional information from the patient’s medical records) 
Each patient may also withdraw from one component of the study (for example, the follow-
up polysomnography), but may choose to allow the investigator to continue other research 
activities described in the IRB-approved protocol and informed consent document that 
involve participation of the subject, such as obtaining data about the patient through 
interaction with the patient (e.g., through follow-up interviews or physical exams).  Also, 

already-collected data about the patients will be retained and analyzed even if the patients 
choose to withdraw from the research.  
The primary investigator may choose to terminate a patient’s participation in the study for 
the following reasons: if polysomnography shows that the patient does not have OSA; if the 
investigator stops the study; and if the patient does not follow study instructions within a 
reasonable period of time (for example, if the patient is asked to complete post-surgery 
questionnaires, not having completed them twelve weeks later). 
Sedation Protocol: Patients will be sedated with a combination of sevoflurane and 
dexmedetomidine similar to the protocols described in previous studies46, 47. In brief, 
patients will be premedicated with oral midazolam (0.5mg/kg) 20 minutes before 
induction of general anesthesia. General anesthesia will be induced using inhaled 
sevoflurane via face mask to allow insertion of an IV catheter. The sevoflurane will then be 
discontinued and sedation will be maintained with an infusion of dexmedetomidine (1 
mcg/kg) with no loading dose and a bolus of ketamine (1 mg/kg) with the patient 
spontaneously breathing 100% O2.  This combination has been demonstrated to maintain 
general anesthesia while preserving respiratory drive and spontaneous breathing 44, 49. 
Once sleep endoscopy has been completed, the dexmedetomidine infusion will be 
discontinued and anesthesia will be maintained using the standard sevoflurane-opiate-
propofol combination that is typically administered for general anesthesia. The level of 
sedation will be continuously assessed using bispectral index monitoring to ensure an 
adequate sedation without causing oversedation.48 
 
Sleep Endoscopy: Sleep endoscopy will be performed just prior to the adenotonsillectomy, 
under the same general anesthetic, thereby avoiding the need for a separate sedation. The 
endoscopy will be performed using either a 3.4mm or a 2.7mm flexible fiber optic 
endoscope (depending on age and size of the nasal passageway) which will be advanced 
trans nasally into the pharynx down to the level of the hypopharynx. We will take note of 
any obvious septal deviation or nasal obstruction as well as adenoid hypertrophy, and 
dynamic collapse at the level of the velum, oropharynx/lateral walls, tongue base, 
epiglottis, and supraglottis. The entire procedure should require no more than 10 minutes 
to complete. Relatively fixed structures such as the nasal airway and adenoids should 
require no more than approximately 1 minute to fully assess. The endoscope will then be 
held for approximately 2 minutes of observation above each subsequent site of potential 
dynamic airway collapse (the velum, oropharynx/lateral walls, tongue base, 
epiglottis/supraglottis). Should the airway obstruct in such a manner that the SpO2 begins 
to decrease to a level below 85% for a continuous duration of at least 15 seconds, the 
endoscope will be removed and positive pressure ventilation via face mask will be used to 
restore the airway and re-oxygenate the patient. Once the SpO2 has been returned to a 
normal level (>95%), endoscopy will resume, beginning from the previous point of 
cessation. Should the oxygen level decrease in a similar manner two more times, the 
endoscopy will be aborted entirely, and the patient will be intubated using an age-
appropriate endotracheal tube in order to proceed with the adenotonsillectomy.  
 

A total of 5 ENT surgeons in the group (including the Principal Investigator) will participate 
in patient recruitment and performance of DISE. Each endoscopic evaluation will be 
digitally recorded and a smaller subset will be later reviewed anonymously by two of the 
other four ENT surgeons who will not be familiar with the patient’s history. These patients 
will have a total of 3 ratings at each anatomic site which will be averaged, and the average 
rating will be used in subsequent analysis. A subset of 30 patients will be rated a second 
time by the same raters one week later to determine intra-rater reliability. The validity of 
the findings on DISE is predicated on the idea that the proposed sedation protocol can 
achieve a level of sedation that reasonably mimics natural sleep. In order to ensure the 
proper level of sedation, we will plan to use a bispectral (BIS) index monitor which uses 
processed electroencephalographic signals to measure sedation on a unitless scale from 0 
to 100 with 0 indicating coma and 100 indicating fully awake and conscious. Several 
studies have validated the use of the BIS monitor in children to reliably indicate the level of 
consciousness using a variety of anesthetic protocols.68-70  
 
Airway Assessment: The subjective rating of the airway will be accomplished using a 
modified VOTE rating scale as originally described by Kezirian et al49. This rating scale 
allows assessment of the dynamic collapse of the airway characterized by location (Velum, 
Oropharynx/lateral walls, Tongue base, Epiglottis), pattern of collapse (anterior-posterior, 
concentric, lateral), and degree of obstruction (0-none, 1-partial, 2-complete). This rating 
scale has been demonstrated to have moderate to substantial interrater reliability with 
kappa values ranging from 0.4-0.8 depending on the specific structures being compared50.  
The kappa statistic is a quantitative measure of the magnitude of agreement between 
observers that is standardized to lie on a -1 to 1 scale where 1 is perfect agreement, 0 is 
what would be expected by chance, and -1 represents a perfect inverse relationship51. The 
typical interpretation of this statistic is presented in Table 1. 
 
Table 1. Interpretation of Kappa Statistic 
Kappa 
Agreement 
<0 
Less than chance agreement 
0.01-0.20 
Slight agreement 
0.21-0.40 
Fair agreement 
0.41-0.60 
Moderate agreement 
0.61-0.80 
Substantial agreement 
0.81-0.99 
Almost perfect agreement 
 
Only four areas of the upper airway are included in the original VOTE classification as 
applied to adult airway assessments; we will break the rating down into the following 
areas: nasal airway (inferior turbinates, septum), nasopharynx/adenoids, velopharynx, 
oropharynx/tonsils, base of tongue/lingual tonsil hypertrophy/epiglottic retroflexion, and 
supraglottis. This is similar to the method described by Durr et al52.  
 
Surgery: Sleep endoscopy and adenotonsillectomy will be performed by one of five 
fellowship-trained pediatric otolaryngologists using standard techniques of tonsillectomy. 
Three commonly used methods will be employed which have all been well-described in the 

literature as safe and effective techniques: 1) stainless steel (cold) instruments for both 
tonsillectomy and adenoidectomy and monopolar cautery for hemostasis, or 2) Monopolar 
cautery for both dissection of the tonsils during tonsillectomy and suction cautery for 
adenoidectomy, 3) microdebrider tonsillectomy and either of the previously described 
techniques for adenoidectomy.  
 
Postoperative care: Although there is no broad consensus regarding the optimal protocol 
for post tonsillectomy monitoring, all patients <3 yrs of age or with severe OSA 
documented on a preoperative sleep study (AHI ≥ 10 or lowest oxygen saturation < 80%) 
will be admitted for overnight observation according to the Clinical Practice Guideline 
published by the American Academy of Otolaryngology-Head and Neck Surgery regarding 
the use of polysomnography prior to tonsillectomy in children46. Other patients will be 
monitored for at least an hour in the recovery room before being discharged, according to 
the usual postoperative protocol. 
 
Follow-Up: Patients will either be seen in the otolaryngology clinic for a follow-up 
appointment or receive a post-surgery telephone or email contact by the study coordinator 
1 to 2 months after their T&A. This clinic appointment or email or phone contact and the 
subsequent questionnaires the patients will be asked to complete (on paper or online) will 
allow assessment of relevant postoperative outcomes including standardized 
questionnaire responses and postoperative adverse events such as postoperative bleeding 
and/or dehydration. Patients will also be requested to return for a postoperative sleep 
study approximately 3 months after surgery (scheduled during the pre-operative period). 
Patients who are found to have residual sleep apnea during polysomnography will be asked 
to follow-up with a sleep medicine physician and the otolaryngologist who performed the 
adenotonsillectomy to consider further treatment options. These would include CPAP 
versus a repeat sleep endoscopy procedure to determine the pattern and location of 
residual obstruction. Adjunct surgery for residual OSA would be offered if indicated.  
 
Assessment of Interrater Reliability: Although DISE and the VOTE classification have 
been demonstrated to have moderate to substantial inter-rater reliability in adults, we will 
confirm these findings in children; each endoscopic evaluation will be digitally recorded 
and later reviewed anonymously by two of the other four ENT surgeons who will not be 
familiar with the patient’s history. Each patient will have a total of 3 ratings at each 
anatomic site which will be averaged and the average rating will be used in subsequent 
analysis. A subset of 30 patients will be rated a second time by the same raters one week 
later to determine intra-rater reliability. Inter-rater and intra-rater reliability for three 
independent raters will be calculated at each anatomic site using a kappa statistic with 
linear weighting. 
 
Data Collection Procedures: Baseline and follow-up measures will be collected at initial 
clinic enrollment and 1 - 2 months postoperatively as summarized in Table 2. DISE will be 
performed at the time of AT. This 2 month interval should allow sufficient time to establish 
a new baseline with respect to OSAS and parental judgment of QOL while optimizing 
patient follow-up. At the time of subject enrollment, parents will be asked to schedule a 
follow-up sleep study 3 months after AT is scheduled. They will be reminded on the day of 

surgery to schedule this post-operative sleep study and will be sent follow-up 
questionnaires with a self-addressed stamped envelope so that they can be returned by 
mail. 
 
 
 
 
 
 
 
  Table 2: Data Collection Variables/Schedule 
Variable Type 
Description 
Baseline 
1-3 Months 
Polysomnography 
Components 
Apnea-Hypopnea Index (AHI) 
X 
X 
Minimum Oxygen Saturation (Min SpO2) 
X 
X 
Desaturation > 3% Index 
X 
X 
Mean/Max End Tidal CO2 (ETCO2) 
X 
X 
% Total Sleep Time with ETCO2 > 45/50 mmHg 
X 
X 
Generic Quality of 
Life (QOL) 
 
Child Health Questionnaire (5-18 
yrs)  
Infant/Toddler QOL Questionnaire 
(2mo-5 yrs)  
X 
X 
Sleep-related QOL 
OSA-18 Questionnaire 
Epworth Sleepiness Scale 
Pediatric Sleep Questionnaire (PSQ) 
X 
X 
Executive 
Functioning 
BRIEF Questionnaire 
X 
X 
Physical Exam 
Tonsil size 
Modified Mallampati/Friedman  Tongue Position 
Body Mass Index (BMI) 
X 
Sleep Endoscopy 
Rating Scale 
Subjective ratings of degree of obstruction at 6 
levels of the upper airway (described below) 
X 
Potential 
confounders 
Demographic Variables 
• Age, gender, race 
• Family composition 
• Family income, education 
• Smoke exposure 
Medical History 
Variables 
• Down syndrome 
• Asthma 
• Environmental 
allergies 
• Nasal obstruction 
X 
X 
 
Polysomnography: The gold standard for diagnosis of sleep apnea in children is overnight 
attended polysomnography which consists of cardiorespiratory recording including 

oronasal airflow, oxyhemoglobin saturation, end-tidal carbon dioxide, electrocardiogram, 
pulse rate, pulse wave form, and calibrated respiratory inductive plethysmography (to 
assess respiratory effort) along with assessment of sleep staging by electroencephalogram, 
electrooculogram, and submental electromyogram.53 Although a polysomnogram includes 
many output parameters, the primary parameter that is commonly used to diagnose and 
characterize the severity of OSA is the apnea-hypopnea index (AHI). The definition of AHI 
often includes central (nonobstructive) events, but for the purposes of this proposal, AHI 
will be defined as the number of obstructive apneas and hypopneas per hour of sleep. An 
obstructive apneic episode is defined as cessation of oronasal airflow for two consecutive 
breathing cycles with continued respiratory effort while a hypopneic episode is a reduction 
of oronasal airflow of ≥30% for two consecutive breathing cycles with continued  
espiratory effort and associated cortical arousal or ≥3% oxyhemoglobin desaturation. 
Other commonly reported parameters are listed in Table 2. 
 
Quality of Life Measures: Both generic and disease-specific quality of life (QOL) outcomes 
will be assessed as secondary outcomes in this study. Several studies have demonstrated 
poor QOL in children with OSAS especially in domains related to physical health  
outcomes,54-56 and significant changes in QOL after treatment that have not always 
correlated with changes in polysomnographic parameters.57 Lack of correlation between 
objective and subjective measures of disease has been demonstrated in many different 
disease processes including nasal obstruction and adult and pediatric OSAS.58, 59 
 
Generic: The Child Health Questionnaire (CHQ)60 and the Infant Toddler Quality of 
Life Questionnaire (ITQOL)61 are validated generic quality of life instruments that are 
based on caregiver responses. The CHQPF28 is a 28-item short form questionnaire that 
assesses 14 physical and psychosocial concepts for patients ages 5-18 yrs. The ITQOL-47 is 
a 47 item questionnaire validated for infants and children aged 2 months to 5 years of age 
that assesses both child-specific concepts of overall health as well as parent-focused 
concepts related to caring for the child. 
 
Sleep-related: The OSA-18 is an 18 item validated questionnaire assessing five different 
domains of sleep-related quality of life, specifically sleep disturbance, physical symptoms, 
emotional distress, daytime function, and caregiver concerns.62 This instrument has been 
used in many studies to demonstrate response to treatment after AT and has been shown 
to be valid and responsive to change.63 The Epworth Sleepiness Scale (ESS) is a self-
administered questionnaire with 8 questions. It provides a measure of a person’s general 
level of daytime sleepiness, or their average sleep propensity in daily life, and is considered 
a standard worldwide.77, 78 The Pediatric Sleep Questionnaire (PSQ) contains two 
validated scales: sleep-related breathing disorders like obstructive sleep apnea, and 
restless legs/periodic leg movements. The SRBD scale contains validated subscales for 
snoring, sleepiness, and daytime disruptive behavior.79 
 
Executive Functioning: Executive functioning refers to skills that control and regulate 
other cognitive processes such as impulse control, mental flexibility, and working memory. 
The Behavior Rating Inventory of Executive Function (BRIEF) is a caregiver and 

teacher-rated instrument assessing executive behaviors with three composite indices 
(Behavioral Regulation, Metacognition, and Global Executive Composite).64 It was 
developed to assess the executive functions in children ages 5 to 18 years as observed by 
parents and teachers on a day-to-day basis and has commonly been used in studies 
assessing symptoms of attention deficit/hyperactivity disorder (ADHD). The original 86-
item Parent Form was shortened to a 24-item abbreviated version with similar 
psychometric properties as the original scale.65 The BRIEF-P is a version that 
was adapted for use in pre-school age children aged 25-74 months with similar 
psychometric properties.69  
 
 
VII. Analysis 
 
Statistical Power and Sample Size: Based on the preliminary data described in section 
3.C.2, we estimate that approximately 200 patients per year will be eligible for study 
inclusion. If we assume a 50% enrollment, this equates to 450 patients over the first 
4.5 years of the award period. We will aim for 80% patient retention; however we 
recognize the possibility of a lower rate of follow up. If we assume 50% attrition, this 
results in 225 patients who will complete the study protocol. To simplify the power 
calculation, we chose to treat the SERS findings as a simple sum of the scores of the six 
anatomic sites (SERS Total Score). In the final analysis, depending on the results of Aims 1 
and 2, we may choose to use a subset or a weighted linear combination of the scores at the 
individual anatomic sites. 
 
Aim 1: Preliminary data is available from the retrospective review of patients who 
previously underwent DISE at the time of AT and have preoperative sleep study data 
available (n = 20). Using this data, we estimate that the mean correlation between the SERS 
Total Score and OAHI is rho = 0.4 (Pearson correlation coefficient). If we assume a null 
hypothesis of rho = 0.2 (weak correlation), using a Fisher’s Z-r transformation with a 
sample size of 225, we should have >90% power to detect this difference. This sample size 
assumes 50% attrition, but because these calculations are all based on baseline measures, 
the true sample size for Aim1 should be 450, thus we should have excess statistical power 
for further adjusted and subgroup analysis. 
Aim 2: We modeled the SERS Total Score as a predictor in a logistic regression model with 
presence of post-AT OSA as a binary outcome variable, using OAHI > 5 as a cut-off for 
diagnosis (a conservative threshold). From this calculation we obtained a beta0 constant = 
-3.58 and beta1 coefficient = 0.764, with a mean and standard deviation for the SERS Total 
Score for three surgeons = 5.59 (SD 2.07). Assuming a normal distribution of the data, we 
would need only 32 patients to have at least 90% power to detect a significant association 
between the SERS Total Score and the outcome of interest. Since we anticipate a sample 
size of 225, this should be more than sufficient to accomplish Aim 2 and provide sufficient 
power for subgroup analyses and further adjusted analysis. 
Aim 3: We plan to divide the cohort evenly between a training set and a validation set so 
that each set would include 112 patients. A similar regression model was constructed as in 
Aim 2 except we also included several additional covariates including BMI z-score, tonsil 
size, and lowest oxygen saturation. With this limited model, with a sample size of 112, we 

calculate >90% power to detect a significant association with the primary outcome of 
presence of post-AT OSAS. 
 
Data Analysis: 
 
Analyses 
Aim 1: The objective of this aim is to evaluate the reliability of the proposed SERS and 
to test its correlation with several baseline measures of OSAS disease burden: 1) OSAS 
severity on polysomnography, 2) QOL measures, both generic and OSAS-specific, and 
3) executive functioning. Our hypothesis is that complete obstruction at any level 
observed during DISE will be associated with greater severity of OSAS with respect to 
objective and subjective outcomes compared to patients with partial obstruction 
(Hypothesis 1). 
Reliability: Inter-rater and intra-rater reliability for three independent raters will be 
calculated at each anatomic site using a kappa statistic with linear weighting. Previous 
studies investigating the reliability of similar rating scales have reported kappa scores 
of DISE ratings in the range of 0.4-0.8.
40, 71  Our preliminary data suggest comparable 
reliability of the proposed SERS, but in order to confirm the reliability in this cohort, 
we will plan on performing a preliminary analysis based on the first 30 patients 
enrolled. If the minimum kappa range does not exceed 0.5, we will conduct an 
additional group training session to arrive at more precise definitions of the different 
anatomic levels and the degree of obstruction at each level. These refined ratings will 
then be applied to the videos for the subsequent 30 subjects enrolled to confirm 
adequate reliability. 
 
Correlation of DISE with Baseline Sleep Apnea Severity: Spearman correlation 
coefficients will be calculated for the mean obstruction at each anatomic site against 
the baseline AHI and the secondary outcomes listed in Table 3. Subgroup analysis will 
be conducted for each of the high-risk subgroups. Compared to patients with only 
partial obstruction, we expect to demonstrate strong correlation between complete 
obstruction at any level and 1) increased severity of OSAS, 2) worse quality of life, and 
3) worse executive functioning. Moreover we expect that greater sites of complete 
obstruction will correlate with worse disease burden. Exploratory analysis of 
independent correlations between each anatomic site and OSAS outcomes may suggest 
that certain anatomic sites have stronger correlations with disease severity than 
others. 
Dependent (Outcome) 
Variable 
Independent 
(Explanatory & 
Adjustment) 
Variables 
Statistical Method 
Test For: 
PRELIMINARY  BIVARIATE ANALYSES 
AHI (continuous) 
Complete obstruction at 
any site (dichotomous) 
T-test, 
Mann- 
Whitney* 
Unadjusted 
correlation 

AHI (continuous) 
Sleep Endoscopy Rating 
at each anatomic site 
(ordinal) 
Spearman 
correlation 
coefficient 
Correlation 
AHI (continuous) 
Each Potential 
confounder 
T-test, 
Mann- 
Whitney* 
Spearman 
correlation 
Find sig 
confounders to 
adjust 
PRIMARY ANALYSIS (PRIMARY HYPOTHESIS) 
AHI (continuous) 
• Complete obstruction at 
any site (dichotomous) 
• Sig confounders 
MV linear 
regression 
Independent 
association 
SECONDARY  ANALYSES (SECONDARY  HYPOTHESES) 
• AHI (continuous) 
• Other 
polysomnography 
measures 
(continuous) 
• CHQ/ITQOL (continuous) 
• OSA-18 (continuous) 
• BRIEF score (continuous) 
• Complete obstruction at 
any site (dichotomous) 
• # sites with complete 
obstruction (ordinal) 
• Sleep Endoscopy Rating 
at each anatomic site 
(ordinal) 
• Sig confounders 
MV linear 
regression 
Independent 
association 
RELIABILITY ANALYSIS 
•Sleep Endoscopy Rating 
(ordinal) 
•Sleep Endoscopy Rating 
(ordinal) 
Kappa statistic 
Inter-rater reliability 
Intra-rater reliability 
Table 3: Aim 1 Analyses 
 
MV = Multivariable. * Non-parametric  testing if outcome variables not normally distributed 
 
Aim 2: The objective here is to determine the relationships between the degree 
and pattern of obstruction observed on baseline DISE and the outcomes after AT, 
using the same measures as those in Aim 1. 
 
DISE Associations with Outcomes of AT: Analyses for Aim 2 will be similar to those 
performed in Aim 1, except the primary outcome of interest will be presence of 
residual OSAS by polysomnography after AT. We will use a dichotomous outcome with 
a conservative threshold for diagnosis of AHI > 5. Though higher than the typical 
threshold of AHI > 1 for diagnosis of OSAS in children, this is a more clinically 
meaningful threshold suggesting at least a moderate degree of residual OSAS.  
Secondary outcomes will include the severity of post-AT OSAS and the magnitude of 
change from baseline. To account for the different contributions of each anatomic site 
to the overall level of obstruction, factor analysis will be performed to determine the 
optimal weighting of each anatomic site. The association between this composite 
rating scale variable and the outcomes of interest will then be tested using 
multivariable regression analysis (Table 4). Our hypothesis is that patients with 
obstruction at sites other than the tonsils or adenoids will have greater risk of residual 
OSAS and decreased improvement from baseline in all outcome measures. In addition, 

we expect to identify specific sites where obstruction is most strongly associated with 
AT failure. We will perform subgroup analyses to assess for these relationships within 
high-risk subgroups. 
 
Table 4. Aim 2 Analyses 
Dependent (Outcome) 
Variable 
Independent 
(Explanatory & 
Adjustment) 
Variables 
Statistical 
Method 
Test For: 
PRELIMINARY  BIVARIATE ANALYSES 
Postop AHI (continuous) 
Total obstruction at non-
T&A site (dichotomous) 
T-test, Mann-
Whitney* 
Unadjusted association 
Postop AHI (continuous) 
DISE Rating at each 
anatomic site (ordinal) 
Linear 
regression, 
Spearman 
correlation 
Unadjusted association 
Postop AHI (continuous) 
Each Potential 
confounder 
T-test, Mann-
Whitney* 
Find sig confounders to 
adjust 
PRIMARY ANALYSIS (PRIMARY HYPOTHESIS) 
• Residual OSA 
(dichotomous) 
• Total obstruction at non-
T&A site (dichotomous) 
• Sig confounders 
• MV logistic 
regression 
Independent 
association 
SECONDARY  ANALYSES (SECONDARY  HYPOTHESES) 
• Δ AHI (continuous) 
• Δ CHQ/ITQOL (continuous) 
• Δ OSA-18 (continuous) 
• Δ BRIEF score (continuous) 
• Total at non-T&A site 
(dichotomous) 
• # sites with complete 
obstruction (ordinal) 
• DISE Rating at each 
anatomic site (ordinal) 
• Sig confounders 
• MV logistic 
regression 
• Factor analysis 
• Independent 
association 
• Optimize weighting of 
site ratings 
MV = Multivariable. * Non-parametric  testing if outcome variables not normally distributed 
 
Aim 3: Our goal here is to develop a comprehensive model that includes pre-AT DISE 
ratings, demographic variables, physical exam findings, baseline OSAS severity, and 
relevant comorbidities to predict the outcomes of AT. We will then validate this 
model in an independent sample of patients. During model development, the 
statistical analysis used to identify relevant component variables and associated 
weighting factors will involve two strategies: 1) multivariate regression analysis, and 
2) conjunctive consolidation.
72-74  Baseline variables will be tested for unadjusted 
associations with AT outcomes (Table 5). Significant independent variables (p<0.20) 
will be included in the final regression model, and weights will be proportional to the 
strength of association with post-AT AHI. The final multivariate models will be 
constructed in a stepwise manner with a significance level for entry of 0.05 and for 
removal 0.10. 
 
A second sleep endoscopy staging system will be developed using conjunctive 
consolidation. Significant (p<0.20) variables from simple bivariate associations with 

AT outcomes will be used to build the final model. The relevant variables will be 
merged in a series of steps using the principles of conjunctive consolidation.
72-74 
 
Table 5. Variables for Predictive Model of AT Outcomes 
 
Variables 
Variable 
Type 
Instrument 
development 
Instrument 
Validation 
Sample (N) 
 
 
112 
112 
Predictor (Independent) 
Variables 
DISE Rating 
Scale * 
Ordinal 
X 
 
Baseline AHI, 
QOL 
Continuous 
X 
 
BMI Z-score 
Continuous 
X 
 
Age at Surgery 
Continuous 
X 
 
Comorbidity 
Categorical 
X 
 
Demographics 
Categorical 
X 
 
Primary Outcome 
(Dependent) Variable 
Post AT OSA 
Binary 
X 
X 
Secondary (Dependent) 
Outcome Variables 
Δ AHI 
Continuous 
 
X 
Δ OSA-18 
Continuous 
 
X 
Δ BRIEF score 
Continuous 
 
X 
Δ CHQ/ITQOL 
Continuous 
 
X 
*Total score, specific anatomic site ratings, or combination of linear weights per analysis in Aim 2 
 
VIII. Study Duration 
 
Timeline: As noted in the preliminary studies section above, we anticipate at least 200 
patients per year will meet inclusion/exclusion criteria. This is likely a conservative 
estimate, as it is based on aggregate surgical volume when two of the participating 
surgeons were new to the department and not yet fully active. If we estimate that only 50% 
of eligible subjects agree to participate, then we can anticipate approximately 100 patients 
enrolled per year for a total of 450 patients after 54 months. With a minimum follow-up of 
3 months, data collection should be completed after 57 months (Table 6). 
 
  Table 6: Anticipated Timeline 
Year 1
Year 2
Year 3
Year 4
Year 5
Coursework
Data Collection
Analysis Aims 1 & 2
Analysis Aim 3
Manuscript
Prepare R01
 
IX. Changes to Protocol 
 
Any modification of this protocol will be documented in the form of a protocol revision or 
amendment signed by the principal investigator and approved by the OHSU IRB, before the 
revision or amendment is implemented.   
 
X. Data Protection 
 

Baseline data will be collected at the time of study enrollment by a research coordinator 
(RC) who will also obtain informed consent for study participation. Follow-up 
questionnaire data will be collected at the one to two month follow-up visit, by mail, or 
online through a secure REDCap website if parents have internet access. Only the PI and 
members of the study team will have direct access to identifiable private information. All 
data extracted from the Electronic Medical Record (EMR) or paper questionnaires will be 
input by either the PI or RC into a password-protected REDCap database stored on firewall-
protected institutional servers maintained by the Oregon Clinical and Translational 
Research Institute (OCTRI). Subjects will be assigned a unique randomly generated study 
identification number and extracted datasets will be coded for use in subsequent analysis. 
Paper copies of questionnaires will be stored in a locked file cabinet in the PI’s office and 
only the PI or RC will have direct access to these files. Videos of sleep endoscopy 
examinations will be uploaded to an institutional firewalled password-protected server at 
the time of video capture by the PI or his clinical collaborators. These videos will then be 
copied, edited, and coded for subsequent rating and analysis. Edited videos will be stored 
in a separate research file on the institutional server. No published materials will reveal the 
identities of any patient participating in the study. The database will be maintained until all 
pertinent research is concluded or one year after collection of follow-up data for the last 
subject enrolled, whichever occurs first. At that time, all paper records will be shredded 
and all computer database files will be deleted, other than the IRB-approved repository.  
 
Data Management and Quality Control: To ensure consistency and reliability of DISE 
assessments, all participating ENT surgeons will undergo a detailed training session to 
review both the sedation protocol and the SERS. In addition, the PI will observe patient 
enrollment, data collection, and DISE assessments for each collaborating surgeon every 3 
months to ensure consistency in research procedures.  
 
XI. Data Safety Monitoring  
 
Data and safety monitoring will be the responsibility of the principal investigator. The 
following is an outline of the roles and responsibilities of the study PI and the research 
coordinator. All study staff will be trained on the protocol and the data and safety 
monitoring plan. The following activities and responsibilities for data and safety 
monitoring for the proposed study are the following: 
 
1) Principal Investigator: The PI will be responsible for all aspects of data and safety 
monitoring including but not limited to: assuring written informed consent is obtained 
from a parent and assent from the child (when appropriate); verifying inclusion/exclusion 
criteria for all subjects prior to surgery. PI will review dropouts, adverse events and 
protocol deviations in real time, to determine if the events require medical follow-up 
and/or IRB reporting. Comprehensive adverse event (AE) and protocol deviation (PD) 
reports will be reviewed for trends quarterly. If AE or PD trends are identified the PI will 
determine appropriate course of action (e.g. protocol revision, staff retraining, IRB 
notifications, etc.). The PI will review enrollment monthly until the study recruitment is 
met. 

2) Research Coordinator: A research coordinator will record AEs from the medical 
records, and solicit self-reporting of adverse events from the subjects after surgery, and 
again at the one to two month follow up. The research coordinator will report AEs and PDs 
to the PI within one working day of becoming aware of an event, and compile a list of all 
AEs for the PI in preparation for IRB continuing review. The research coordinator will 
provide the PI an enrollment report on a monthly basis until enrollment is met. 
3) OHSU Institutional Review Board: Fatal and life-threatening UPs will be reported to 
OHSU IRB and the NHLBI within 7 days of notification of the event. All other UP reports will 
be submitted to OHSU IRB and the NHLBI no later than 15 days after occurrence or 
notification of the event. 
4) Data integrity and security: Computers at the site connected to the internet will be 
used to collect data that is directly entered into the REDCap database. REDCap employs a 
variety of data verification features including limiting entries by data type, using drop-
down menu items, and setting range limits. Further data confirmation by the RC will occur 
by visual verification at time of data entry. The REDCap electronic database is stored 
behind the OHSU firewall. It will be password-protected and only PI and IRB approved 
study staff will have access to any study data. Each patient will have a unique patient ID 
number; patient names will not be included in REDCap database reports or subsequent 
data analysis. 
 
XII. Potential Benefits of the Proposed Research to Human Subjects and Others 
 
Potential direct benefits: Patients may potentially benefit directly from this study by 
three mechanisms: 
 
1) Confirmation of OSAS diagnosis and severity by polysomnography: It is possible 
that patients who have not previously been tested and are referred for pre-AT 
polysomnography may be found to have a normal study. This would rule out clinically 
significant OSAS in which case AT would be unnecessary, so the patient would be saved the 
risks and discomfort of undergoing a surgical procedure. In this scenario, the patient would 
then be excluded from further study. Conversely, if the patient is found to have severe 
OSAS, this could alter the perioperative management so that a patient who might otherwise 
be treated as an outpatient would be admitted for overnight observation. If the OSAS is 
severe enough, admission to the intensive care unit postoperatively might be indicated for 
more vigilant monitoring and prevention of perioperative complications. 
2) Characterization of nature of obstruction by sleep endoscopy: If the sleep 
endoscopy reveals an unexpected finding with respect to location or pattern of airway 
obstruction such as collapse at the base of tongue or supraglottis, this finding might suggest 
strategies for further intervention in the event that the patient is diagnosed with residual 
OSAS after AT. 
3) Confirmation of cure or presence of residual OSAS based on postoperative 
polysomnography: Most patients undergoing AT for OSAS are inconsistently followed 
postoperatively despite the high rate of residual disease in this population of patients. Thus 
patients with significant residual OSAS may be left untreated with the potential for long 
term sequelae of incompletely treated OSAS. Because all patients in this study will be asked 

to follow-up for postoperative polysomnography, patients with residual OSAS will be 
identified and the need for further follow-up or intervention will be clearly indicated. 
 
Potential benefit to future patients: Development of a predictive model of AT outcomes 
can potentially benefit future patients by allowing accurate and reliable prognostication of 
AT outcome based on anatomic predictors of surgical success. This could help to identify 
patients who are likely to fail AT alone and possibly suggest the need for alternative 
treatments including non-surgical treatment (e.g. oral appliances) or adjunct procedures 
that could be implemented at the time of the initial surgery which could decrease the 
prevalence or severity of residual OSAS as well as save the patient the risk of a second 
surgical procedure and general anesthetic. 
 
Importance of the knowledge to be gained: The knowledge gained from this project will 
allow more accurate prognostication of the outcome of AT and thus facilitate more 
individualized treatment plans based on individual patient risk factors. In addition, the 
findings of this study may give greater insight into the mechanism of failure of AT and 
suggest more effective therapeutic interventions for those patients who are likely to fail AT. 
This study has the potential to allow improvement in individual surgical outcomes and 
could lead to more cost-effective delivery of health care through more efficient targeting of 
patients who are most likely to benefit from AT, thus decreasing the need for secondary 
interventions whether surgical or non-surgical and thereby decreasing health care 
utilization among children with OSAS. 
 
XIII. Potential Risks 
  
The subjects in this study are scheduled to have a tonsillectomy or adenotonsillectomy. 
That procedure is not experimental and is not part of this study. 
 
One risk to taking part in this study is that the sleep endoscopy subjects receive may not be 
effective in treating OSA. The study may not provide subjects with any actual health-related 
benefits. The risks of sleep endoscopy itself are minor. Previous studies have demonstrated 
that drug-induced sleep endoscopy can be done safely in adults and children with no 
adverse events reported either during or immediately after sleep endoscopy. Subject vital 
signs will be carefully monitored as is the standard protocol during any operative 
procedure. These include heart rate, blood pressure, oxygen saturation, and end tidal CO2 
levels. The primary risk is an apneic event due to either airway obstruction or over 
sedation. Because the goal of the endoscopy involves visualizing the dynamic collapse of 
the airway during respiration in as natural a state as possible, this requires that the subject 
is kept breathing spontaneously without an endotracheal tube or other airway intervention 
in place to maintain a stable airway. If an obstructive event resulting in oxygen 
desaturation or cardiopulmonary instability were to occur, the appropriate 
personnel and equipment required to secure a stable airway (i.e. the Anesthesiology 
team and the Otolaryngology team) will already be present. Repeated airway 
obstruction resulting in prolonged oxygen desaturation below 90% will result in aborting 
of the endoscopy procedure and intubation of the patient for the remainder of the 
procedure. The duration of the endoscopy would also necessarily extend the operative 

time, but typically the duration of endoscopy lasts no longer than 5-10 minutes. Since this 
represents a relatively small proportion of the overall operating time (typically 25-30 
minutes), this poses little additional risk to the subject with respect to duration of general 
anesthesia.  
 
The endoscopy may give subjects a sore throat. However, the T&A will make a subject’s 
throat sorer than the endoscopy by itself. Appropriate pain medication will be prescribed. 
There is a small chance a subject’s esophagus may bleed or the subject may get an infection. 
Rarely, an endoscopy makes a hole in someone’s esophagus. This happens about 1 time in 
every 5,000 endoscopies. If this happens to a subject, they may need additional surgery to 
repair the hole.     
 
Sleep studies are very low risk events. Obtaining sleep studies may be inconvenient for 
subjects and families. The sleep study location may not be near their home, and they may 
need to find alternate care for other family members overnight. The wires and monitors 
worn during the sleep study may be uncomfortable or frightening. Subjects may not get a 
full night of quality sleep while undergoing a sleep study.  
 
Subjects in the study will complete several questionnaires (instruments). All of these 
questionnaires have been in use for many years and have been tested and proven to 
provide valuable information and assessment. Although the majority of questions on these 
forms concern general health and sleep habits, some of these questions may seem personal 
or embarrassing and may upset the subject. Subjects may refuse to answer any of the 
questions that they do not wish to answer.  If the questions make them very upset, we will 
help them to find a counselor.   
 
Certain risks may result from storage of information in a repository and/or use of 
information in future research studies. Despite our best efforts to protect patients’ 
identities, breaches of confidentiality could occur. Such a breach could cause mild 
psychological trauma or a loss of confidence in OHSU.  Breach of confidentiality could 
impact insurability, employability, family plans, and family relationships, although the risks 
of this are low as we will not be recording mental health or family status information for 
this study. There could also be a risk of stigmatization for the subject if details of certain 
medical disorders are made known publically. 
 
Other Potential Problems and Alternative Approaches:  
 
 Similarity between DISE and Natural Sleep: Several studies investigating adult DISE 
have concluded that propofol-induced sedation is a reasonable mimic of natural 
sleep because it does not induce symptoms of OSAS in control subjects without a 
diagnosis of OSAS or are non-snorers, whereas snoring and obstruction were 
observed among patients with a history of OSAS.75, 76 Among children, both propofol 
and dexmedetodomine have been utilized as sedating agents, and both have been 
observed to induce sedation that produces snoring and obstruction while 
preserving spontaneous breathing. Regardless of the agent used, drug-induced 
sedation is likely to be a closer mimic of natural sleep than awake examination, and 

we will use the BIS monitor as previously described to help ensure an adequate and 
consistent level of sedation. Should the findings in Aims 1 and 2 suggest inadequate 
reliability of the sedation protocol, we will consider the use of propofol as a primary 
sedating agent as in reports of adult DISE. 
 Lack of Association Between SERS and baseline OSAS severity (Aim 1) or outcomes of 
AT (Aim 2): Though previous studies and our preliminary data suggest an 
association between significant obstruction observed on DISE and both the severity 
of disease at baseline and the response to AT, it is possible that no significant 
associations will be observed (null hypothesis in Aims 1 and 2). However, as part of 
Aim 2, we will plan on an exploratory analysis including factor analysis to determine 
if the different components of the SERS can be weighted or combined to optimize 
the strength of association with the outcomes of interest. This optimized variable 
will be applied only in the training set for development of the predictive model in 
Aim 3. Testing of the model in an independent sample of patients will ensure its 
validity. In this setting, it is still possible that individual items or some combination 
of the SERS could be included with other potential risk factors (demographics, 
comorbidities, physical exam findings) to generate a model that is predictive of AT 
outcome. However, it is possible that the most predictive model may not ultimately 
include any DISE findings. Such a model would still be a useful clinical tool and is in 
fact similar to predictive models that have previously been proposed. Thus, even a 
negative result in Aims 1 and 2 would not preclude a useful result of Aim 3. 
 Low Enrollment and Patient Retention: To anticipate possible low enrollment, we 
have planned for only 50% enrollment among eligible subjects. Because the primary 
procedures in this study are clinically indicated, it is likely that enrollment will be 
higher than this. We will review enrollment data every 6 months and if it is slower 
than expected we will consider loosening inclusion criteria such as including 
overweight in addition to obese children. With respect to patient retention, because 
there is typically significant symptomatic improvement with AT, parents are less 
inclined to follow-up routinely unless their child remains significantly symptomatic. 
For these reasons, we are prepared for a 50% attrition rate among enrolled subjects. 
The importance of postoperative follow-up will be emphasized to parents at study 
enrollment. Parents will also receive voice and email reminders (if available) to 
return questionnaires and follow-up for postoperative sleep studies. Finally, a $50 
remuneration at the completion of data collection will provide additional incentive 
to complete the study protocol. Analysis will be performed to determine if patients 
lost to follow-up differ significantly in baseline characteristics from subjects who 
complete the study protocol.  
 
Future Directions: With a model that can accurately predict the outcome of AT, we can 
then propose a trial, possibly randomized, of standard treatment for pediatric OSAS (AT) 
compared to DISE directed surgery to determine if improved outcomes can be achieved 
with an alternative surgical intervention. In addition, we are planning a follow-up study 
that includes repeating DISE in patients with sufficient post-AT OSAS to warrant further 
surgical intervention. Findings of the post AT DISE could then be compared to the initial 
endoscopy findings to see if the dynamics of airway obstruction changed significantly after 

AT. Further studies would include refining the predictive model and applying it in all AT 
patients to determine if it could be generalized beyond the high-risk groups specified in 
this proposal. 
 
 

 
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