Original Research—Sleep Medicine and Surgery
Otolaryngology–
Transverse Maxillary Deficiency Predicts
Increased Upper Airway Collapsibility
during Drug-Induced Sleep Endoscopy
Eric Thuler, MD, PhD1 , Everett G. Seay, RPSGT1, John Woo,
MD2,3, Jane Lee, MD2, Niusha Jafari, MS4, Brendan T. Keenan,
MS4, Raj C. Dedhia, MD, MSCR1,4, and Alan R. Schwartz,
MD1,3,5
Abstract
Objective. To examine the relationship between craniofacial
skeletal anatomy and objective measures of pharyngeal
collapse obtained during drug-induced sleep endoscopy. We
hypothesized that transverse maxillary deficiency and an
increased pharyngeal length will be associated with higher
levels of pharyngeal collapsibility.
Study Design. Cross-sectional analysis in a prospective cohort.
Setting. University Hospital.
Methods. A cross-sectional analysis was conducted in a
cohort of consecutive patients from the positive airway
pressure (PAP) alternatives clinic who underwent com-
puted tomography (CT) analysis and drug-induced sleep
endoscopy for characterization of upper airway collapsi-
bility. PAP titration was used to determine pharyngeal
critical pressure (PCRIT ) and pharyngeal opening pressure
(PhOP). CT metrics included: Transverse maxillary
dimensions (interpremolar and intermolar distances) and
pharyngeal length (posterior nasal spine to hyoid dis-
tance).
Results. The cohort (n = 103) of severe obstructive sleep
apnea (Apnea and Hipopnea Index 32.1 ± 21.3 events/h) was
predominantly male (71.8%), Caucasian (81.6%), middle-
aged (54.4 ± 14.3 years), and obese (body mass
index [BMI] = 30.0 ± 4.9 kg/m2). Reduced transverse maxil-
lary dimensions were associated with higher PCRIT (inter-
molar distance: β [95% confidence interval, CI] =
−.25 [−0.14, −0.36] cmH2O/mm; p = .03) and PhOP
(Interpremolar distance: β = −.25 [−0.14, −0.36] cmH2O/
mm; p = .02). Longer pharyngeal length was also associated
with higher PCRIT (β = .11 [0.08, 0.14] cmH2O/mm, p = .04)
and PhOP (β [95% CI] = .06 [0.03, 0.09] cmH2O/mm,
p = .04). These associations persisted after adjustments for
sex, age, height, and BMI.
Conclusion. Our results further the concept that skeletal
restriction in the transverse dimension and hyoid descent
are associated with elevations in pharyngeal collapsibility
during sleep, suggesting a role of transverse deficiency in the
pathogenesis of airway obstruction.
Head and Neck Surgery
2023, Vol. 00(00) 1–10
© 2023 American Academy of
Otolaryngology–Head and Neck
Surgery Foundation.
DOI: 10.1002/ohn.258
http://otojournal.org
Keywords
craniofacial analysis, CT scan, maxillary transverse deficiency,
sleep apnea, upper airway collapse
Received September 26, 2022; accepted December 17, 2022.
O
bstructive sleep apnea (OSA) is characterized by
recurrent episodes of upper airway obstruction
during sleep resulting in increased respiratory
effort, intermittent hypoxemia, and sleep fragmentation.1
Obstruction is due to increases in pharyngeal collapsibility
that result from anatomic alterations and disturbances in
neuromuscular control.2 Positive airway pressure (PAP)
remains the first‐line therapy for OSA. PAP prevents
pharyngeal collapse, and specific levels that open the airway
provide metrics of airway collapsibility.3 Nevertheless, some
50% of patients do not adhere to PAP therapy,4 suggesting
that therapeutic alternatives are needed. Nevertheless, the
criteria for selecting these patients for specific therapies have
not yet been well established.5 Insight into the mechanism of
upper airway obstruction is needed to develop a rational basis
1
Division of Sleep Surgery, Department of Otorhinolaryngology, University of
Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania,
USA
2
Department of Radiology, University of Pennsylvania Perelman School of
Medicine, Philadelphia, Pennsylvania, USA
3
Department of Otolaryngology, Vanderbilt University School of Medicine,
Nashville, Tennessee, USA
4
Division of Sleep Medicine, Department of Medicine, University of
Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
5
Department of Otorhinolaryngology, Universidad Peruana Cayetano
Heredia School of Medicine, Lima, Peru
This manuscript was presented at the AAO-HNSF 2022 Annual Meeting &
OTO Experience; October 11-14, 2022; Philadelphia, Pennsylvania.
Corresponding Author:
Eric Thuler, MD, PhD, Department of Otorhinolaryngology, University of
Pennsylvania Perelman School of Medicine, 3400 Spruce Street, Ravdin 5
Philadelphia, PA, USA.
Email: erthuler@gmail.com

2 Otolaryngology–Head and Neck Surgery 00(00)
for selecting the appropriate therapeutic strategy for each
patient.6
Upper airway obstruction has been attributed to
abnormal skeletal dimensions, soft tissue volumes, and
pharyngeal neuromuscular tone.7‐9 Skeletal restrictions
can compromise pharyngeal patency, particularly in
patients with maxillomandibular deficiency.10,11 The
surgical treatment of those skeletal deficiencies can relieve
upper airway obstruction and reduce OSA severity.12,13
An increase in soft tissue volume (e.g., obesity, tonsillar
hypertrophy) within the bony enclosure can further
compress the pharynx and contribute to OSA pathogen-
esis.14‐16 Even so, cephalometric evaluations of craniofa-
cial structures with lateral x‐rays,17,18 computed tomo-
graphy (CT),19‐21 and magnetic resonance imaging
(MRI)22‐24 have not succeeded in predicting upper airway
obstruction during sleep.25,26 Investigators have suggested
that sagittal views overlook transverse maxillary defi-
ciency (TMD), which may still play a critical role in the
pathogenesis of obstruction during sleep.27,28 Recent CT
work has suggested that craniofacial transverse measure-
ments can predict velopharyngeal circumferential col-
lapse, tongue base collapse, and multilevel collapse during
DISE,29 yet the impact of this anatomic defect on
pharyngeal collapsibility remains unclear.
Pharyngeal collapsibility can be assessed during sleep
and sedation by establishing the PAP level at which the
airway obstructs.30,31 Early studies demonstrated that
pharyngeal collapsibility is represented by the nasal
pressure level at which airflow ceases (critical pressure,
PCRIT), and that the severity of upper airway obstruction
during sleep was associated with quantitative differences
in PCRIT.32 Moreover, therapeutic success with weight loss
and upper airway reconstructive surgery have been
characterized by decreases in PCRIT, reflecting improve-
ment in pharyngeal collapsibility.33,34 Recently, we and
others have enhanced drug‐induced sleep endoscopy
(DISE) by assessing metrics of upper airway collapsi-
bility. This approach has allowed us to determine both the
PCRIT at which the airway starts to open and also the
pressure at which inspiratory flow limitation was abol-
ished, viz., pharyngeal opening pressures (PhOPs).35,36 In
fact, differences in PhOP can predict responses to
hypoglossal nerve stimulation with greater response rates
in patients with lower PhOP levels.37,38 The relationship
between skeletal TMD and these measures of pharyngeal
collapsibility, however, has not yet been explored before.
The present study was designed to examine the relation-
ship between skeletal transverse maxillary anatomy and
pharyngeal collapsibility quantified by the PCRIT and
PhOP obtained while titrating PAP during DISE.32,35 We
expected that transverse maxillary dimensions would be
associated with PCRIT and PhOP. Our primary hypothesis
was that more positive PCRIT and PhOP would be associated
with TMD, represented by reduced interpremolar (IPMD)
and/or intermolar distances (IMD). Our secondary hypoth-
esis sought to confirm prior studies demonstrating an
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association between collapsibility and pharyngeal length.39
An exploratory analysis was included to examine additional
craniofacial skeletal predictors of upper airway collapsibility
during DISE. Our plan was to develop a set of standardized
anatomic predictors grouped by X‐Y‐Z dimensions (width,
length, depth) to capture the potential association of skeletal
alterations within each plane with upper airway collapsibility.
Methods
Participants
A prospective study of consecutively enrolled patients
presenting to the PAP Alternatives Clinic at the University
of Pennsylvania was conducted from July 1, 2019, until
December 31, 2021. Patients were included if they were
consenting, English‐speaking adults (>18 years) with a
diagnosis of OSA (Apnea and Hipopnea Index
(AHI) > 5 events/h) who were seeking alternatives to
PAP treatment. All patients underwent a standard clinical
assessment including a noncontrast facial CT and a DISE
exam. The study was approved by Institutional Review
Board at the University of Pennsylvania (IRB# 833511).
A total of 199 subjects were initially screened for
inclusion. Thirty‐nine patients were excluded for missing
CT scan Digital Imaging an Communication in Medicine
(DICOM) files. In addition, 16 subjects were excluded for
inadequate CT scan DICOM file (ie, mouth open, missing
dental landmarks), which would jeopardize craniofacial
measurement accuracy. From the remaining 144 subjects,
high‐fidelity pressure‐flow data from physiologic recordings
were obtained in 118. Finally, due to technical issues, patient
safety, and protocol deviations, an additional 15 patients
were excluded, yielding 103 included subjects (Figure 1).
Study Protocols and Data Collection Procedures
Clinical Data
Demographic information including sex, age, body mass
index (BMI), and race was obtained from the electronic
medical record.
DISE for Characterizing Airway Dynamics (DISE-CAD)
Set-Up. The DISE‐CAD study was performed on an
integrated recording platform designed to acquire clinically
relevant anatomic and physiologic upper airway character-
istics, as previously described.35 During the endoscopic exam,
PAP was titrated through a nasal mask attached to a
pneumotachometer. Pulse oximetry was monitored, and a
dual lumen oral cannula provided supplemental oxygen
(2‐4 L/min), and end‐tidal CO2 was monitored to detect
mouth breathing. Propofol anesthesia was administered to
achieve sedation with a probability ramp infusion40 to
achieve a target bispectral index (BIS) of 50‐70.
Physiologic Acquisition Protocol. PAP was progressively
increased step‐wise after: (1) at least 1‐2 obstructive

Thuler et al.
Figure 1. CONSORT diagram. The figure presents the reasons for patient exclusion through each stage of the study.
apneas or hypopneas, or (2) every 5‐6 breaths during
periods of stable flow limitation.35 Titration was termi-
nated when the inspiratory airflow limitation was
abolished. Pressure‐flow relationships were generated
from the resulting data and were used to derive airway
collapsibility measures (see section Definition of
Variables).
Image Acquisition. CT scans were performed at kV 120, with
slice thickness <1 mm, a pitch of 1.0, Fild of view of
25 cm, and no gantry tilt. Thin‐section reconstructions
were generated in axial, sagittal, and coronal planes, with
bone and soft tissue algorithms. Patients were oriented to
lie down on their backs on a flat table, with a thin support
under the head to keep the neck in a neutral position. The
body was oriented midline, symmetrically in the gantry,
maintaining the occlusal plane aligned with the gantry. To
avoid mouth opening, subjects were asked to smile with
their teeth touching, breathe in through their nose,
breathe out, and then pause during CT acquisition. The
raw files (DICOM format) were anonymized for analysis.
Craniofacial Measurements. Invivo 6 software (Anatomage)
was used to take the measures from DICOM files,
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3
applying tools for 3‐dimensional reconstruction
of the anatomic structures.41 After uploading the
DICOM files, image correction was performed in three
spatial planes: yaw in axial orientation, referencing
the anterior nasal spine to the midline of the
odontoid process; pitch in sagittal orientation, referencing
the superior aspect of the porion to the inferior‐lateral
aspect of the orbital rim; roll in coronal orientation,
referencing the plane of the bilateral infra‐orbital
rim. A comprehensive craniofacial analysis protocol was
developed following a thorough literature review of the
anatomical structures previously associated with
OSA.11,25,42‐47 Multiple metrics were obtained by a
trained physician (E.T.) blinded to clinical data
(Supplemental Figure S1 and Table S1, available online).
Definition of Variables
Outcome Variables
• PCRIT is defined by the pressure at which
inspiratory airflow first commenced as nasal
pressure was increased progressively.

4 Otolaryngology–Head and Neck Surgery 00(00)
• PhOP is the pressure at which inspiratory flow
limitation was abolished with progressive in-
creases in nasal pressure.
Predictor Variables
• Primary variables: Transverse dimension (width)
was represented in the coronal view by the
distance between premolars (IPMD), first teeth
after the canines, and molars (IMD). IPMD and
IMD were both measured in millimeters on the
lingual side of the alveolar bone at the level of
tooth furcation (root) in the upper jaw.
• Secondary variables: The craniocaudal dimension
(pharyngeal length) was measured in millimeters
in the sagittal view as the distance between the
posterior nasal spine (PNS) to the hyoid bone
(PNS‐hyoid distance).
• Exploratory variables (see description in S1): 32
additional skeletal craniofacial measurements of
the transverse dimension (width), craniocaudal
dimension (length), anteroposterior dimension
(depth), and neck extension were obtained in
coronal, sagittal, and axial views. These included
sella‐nasion A point angle (SNA), sella‐nasion B
point angle (SNB), intramaxillary axial area, and
neck extension (which was inversely related to the
angle from the posterior rim of the foramen
magnum to the plane created through the most
anterior and most posterior aspect of atlas).
Statistical Methods
Continuous data are summarized as means and
standard deviations (SDs), and categorical data are
as frequencies and percentages. Associations between
CT‐based anatomy measures and measures of upper
airway collapsibility (P CRIT and PhOP) were evaluated
with linear regression models. Analyses were per-
formed as unadjusted, adjusted for age, sex, and race
(adjusted model 1), and adjusted for age, sex, race,
height, and BMI (adjusted model 2) in order to
understand the association independent of obesity
and body size. Results are reported using beta
coefficients (β) and standard errors (SE) representing
the expected change in outcome for a 1‐unit increase in
predictor and associated p values. In addition,
standardized β equal to the expected SD difference in
outcome for an SD increase in the predictor is
presented. These estimates can be interpreted as
representing small (0.2), medium (0.5), or large (0.8)
thresholds for effect sizes and provide estimates that
are directly comparable across predictors. Statistical
significance in exploratory analyses that included
multiple CT measurements were determined with a
Hochberg step‐up procedure to maintain the overall
type I error at 5% 48 ; significance in secondary
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comparisons of PNS‐hyoid distance was based on a
p < .05 given a single secondary measure. A p < .05 was
considered nominally significant across all analyses.
All analyses were performed using SAS software,
version 9.4 (SAS Institute Inc) or Stata/SE 14.2
(StataCorp).
Results
Patient Characteristics
The clinical characteristics of the analysis sample are
presented in Table 1. On average, the cohort was
predominately male (71.8%) and Caucasian (81.6%),
middle‐aged (54.4 ± 14.3 years), obese (BMI of
30.0 ± 4.9 kg/m2), and had severe OSA (AHI of
32.1 ± 21.3 events/h).
Associations Between CT Measurements and Upper
Airway Collapsibility
Physiologic metrics of upper airway collapsibility (PCRIT
and PhOP) were both associated with (1) reductions in the
maxillary transverse dimension (width) and (2) increases
in craniocaudal dimension (pharyngeal length), as illu-
strated in Figure 2. In 2 patients with severe OSA of
similar age, BMI, and sex, the IPMD and IMD were
lower, and PNS‐hyoid distance was increased in the
patient with high versus low PhOP. These collapsibility
metrics were positively associated with greater degrees of
neck extension and reductions in maxillary axial area, but
not with reductions in anteroposterior facial dimensions,
as detailed below.
Primary Analysis
• Reduced maxillary transverse dimension (width)
predicted higher PCRIT and PhOP (Tables 2 and
3, respectively).
Primary analyses examined associations between max-
illary transverse dimensions (including IMPD and IMD)
and either PCRIT or PhOP. In unadjusted analysis, larger
IMD was associated with more negative PCRIT (Std.
β = −.250; p = .0317), and larger IPMD was associated
with more negative PhOP (Std. β = −.259; p = .0278). The
strength of both associations persisted after controlling
for relevant covariates including age, sex, race, height,
and BMI (see Tables 2 and 3). Lower jaw transverse
dimensions were not significantly associated with either
measure of collapsibility.
Secondary Analysis
• Increased craniocaudal dimension (pharyngeal
length) predicted higher PCRIT and PhOP
(Tables 2 and 3, respectively).
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Thuler et al. 5

Table 1. Baseline Characteristics of the Study Population unadjusted analyses, there was evidence of a relationship
Characteristic Estimate
between larger intramaxillary axial area and more
negative PCRIT (Std. β = −.005; p = .013) and PhOP (Std.
Total N 103 β = −.003; p = .073). In covariate‐adjusted analyses, asso-
Age, years 54.4 ± 14.3 ciations with PCRIT and PhOP remained significant. Hard
<40 16 (15.5%) palate length was only associated with PCRIT in both
40-49 18 (17.5%) unadjusted (Std. β = −.110; p = .004) and adjusted (Std.
50-59 30 (29.1%) β = −.1; p = .009) analyses. Thus, overall, measures of
60-69 24 (23.3%) collapsibility were higher in those presenting with an
≥70 15 (14.6%) increased pharyngeal length, greater neck extension, and
Sex, n (%) a deficient maxilla.
Female 29 (28.2%) Associations between PCRIT and PhOP were evaluated
Male 74 (71.8%) for a number of other landmarks quantified from the CT
Race/ethnicity, n (%) imaging (see Supplemental Tables S1 and S2, available
White 84 (81.6%) online). No additional statistically significant associations
Black 8 (7.8%) were observed.
Asian 6 (5.8%)
Unknown 5 (4.9%) Discussion
BMI, kg/m2 30.0 ± 4.9 This study examined the associations between skeletal
<30 53 (51.5%) craniofacial transverse (width) and craniocaudal (length)
≥30 50 (48.5%) dimensions with measures of upper airway collapsibility
Weight, kg 89.9 ± 16.8 (PCRIT and PhOP) derived during DISE. The following
Height, cm 172.6 ± 10.0 were the main findings of our study. First, pharyngeal
AHI, events/h 32.1 ± 21.3 collapsibility was associated with maxillary transverse
<5 2 (1.9%) deficiency, represented by the IPMD and IMD of the
5-15 19 (18.5%) upper jaw. Specifically, PhOP was inversely associated
15-30 38 (36.9%) with IPMD, and PCRIT was inversely associated with
≥30 44 (42.7%) IMD. Second, analysis of associations between pharyn-
Abbreviation: AHI, Apnea and Hipopnea Index. geal collapsibility confirmed that an increased pharyngeal
length, as represented by PNS‐hyoid distance, was
positively associated with both PhOP and PCRIT. Third,
hard palate length was associated with PCRIT. Forth, neck
Secondary analyses examined associations between
extension and intramaxillary axial area were associated
collapsibility and pharyngeal length. Longer pharyngeal
with both PCRIT and PhOP. The strength of all associa-
length (increased distance from PNS to hyoid bone) was
tions persisted after adjustments for demographic and
associated with higher PCRIT (Std. β = .110; p = .004) and
anthropometric factors. Nevertheless, the effect sizes were
PhOP (Std. β = .066; p = .0453); both associations were
modest, suggesting that other factors as soft tissue volume
considered statistically significant and persisted, with
play a role in modulating pharyngeal collapsibility, our
stronger effect sizes, in covariate‐adjusted analyses.
study reinforces the concept that, in addition to airway
length, the transverse skeletal restriction can contribute to
Exploratory Analysis (Salient Skeletal Dimensions)
increases in pharyngeal collapsibility.
Prior studies have elucidated associations between cepha-
• Neck extension, hard palate length, and intramax- lometric anatomy, particularly in the craniocaudal dimension,
illary axial area predicted collapsibility (Tables 2 and upper airway collapsibility (PCRIT).39,49,50 A previous
and 3). study from our group, however, indicated that TMD can also
predict both the site and pattern of airway collapse during
Neither collapsibility measure was associated with DISE.29 The present study extends these findings with new
SNA or SNB angles. On the other hand, neck extension, evidence that IPMD, IMD, hard palate length, and
hard palate length, and intramaxillary axial area pre- intramaxillary axial area can predict indices of airway
dicted collapsibility. In unadjusted analyses, larger neck collapsibility (PCRIT and PhOP) obtained during DISE.
extension (reduced Foramen Magnum—Atlas plane These findings suggest that TMD increases pharyngeal
angle) was associated with a higher PCRIT (Std. collapsibility by compressing soft tissues that surround the
β = −.313; p = .0001) and PhOP (Std. β = −.200; pharyngeal airway within the oral cavity.51‐53
p = .004); both associations were significant after Two additional findings in our study offer further
Hochberg correction and remained similarly strong after insight into the relationship between pharyngeal bony
adjustment for clinical covariates. Similarly, in structures and upper airway collapsibility. First, both
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6 Otolaryngology–Head and Neck Surgery 00(00)

Figure 2. Representative CT scans of 2 men matched for age and BMI (low vs high PhOP). The figure demonstrates that interpremolar
distance (top) and intermolar distance (middle) were higher, and PNS-hyoid distance (bottom) was reduced. BMI, body mass index;
CT, computed tomography; PhOP, pharyngeal opening pressure; PNS, posterior nasal spine.

PCRIT and PhOP were moderately associated with an
increased distance from the PNS to the hyoid bone. A
caudally positioned hyoid bone has been consistently
associated with elevations in collapsibility.54,55 Second,
the degree of neck extension was associated with both
measures of collapsibility, despite having standardized
the head and neck posture during image acquisition.
These findings suggest that patients with pharyngeal
restriction can compensate during wakefulness by
extending their neck unwittingly. Prior work, however,
indicates that increased neck extension and downward
hyoid movement both decrease collapsibility by
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Thuler et al. 7

Table 2. Associations of CT Variables With Critical Closing Pressure (PCRIT)

Unadjusted Adjusted model 1a Adjusted model 2b

Predictors β ± SEc Std. βd p β ± SE Std. β p β ± SE Std. β p

Primary
IPMD (mm) −.215 ± 0.138 −.152 .1244 −.217 ± 0.146 −.154 .1399 −.218 ± 0.152 −.151 .1543
IMD upper jaw (mm) −.250 ± 0.115 −.212 .0317 −.274 ± 0.120 −.232 .0247 −.272 ± 0.123 −.229 .0295
Secondary
PNS to hyoid distance (mm) .110 ± 0.037 .279 .0043 .155 ± 0.045 .396 .0009 .192 ± 0.051 .458 .0003
Exploratory
Hard palate length (mm) .11 ± 0.037 .279 .0041 .155 ± 0.045 .396 .0009 .192 ± 0.051 .458 .0003
Neck extension (mm) −.313 ± 0.078 −.372 .0001 −.333 ± 0.079 −.396 .0001 −.344 ± 0.083 −.404 .0001
Intramaxillary axial area (mm) −.005 ± 0.002 −.244 .0131 −.006 ± 0.002 −.299 .005 −.006 ± 0.002 −.322 .0035
Nominally significant association (p < .05) shown in bold.
Abbreviations: BMI, body mass index; CT, computed tomography; IMD, intermolar distance; IPMD, interpremolar distance; PCRIT, critical pressure.
a
Model adjusted for age, sex, and race.
b
Model adjusted for age, sex, race, height, and BMI.
c
Beta coefficient from linear regression represents the expected change in PCRIT for a 1 unit increase in CT measurement.
dStandardized beta represents the expected standard deviation change in PCRIT for a standard deviation change in predictor, with estimates of 0.2, 0.5, and 0.8
representing small, medium and large effects.

Table 3. Associations of CT Variables With PHOP

Unadjusted Adjusted model 1a Adjusted model 2b

Predictors β ± SEc Std. βd p β ± SE Std. β p β ± SE Std. β p

Primary
IPMD upper jaw (mm) −.259 ± 0.116 −.217 .0278 −.245 ± 0.120 −.205 .0434 −.268 ± 0.117 −.219 .0248
IMD upper jaw (mm) −.093 ± 0.099 −.093 .3503 −.078 ± 0.102 −.078 .4453 −.075 ± 0.099 −.075 .4487
Secondary
PNS to hyoid distance (mm) .066 ± 0.032 .198 .0453 .113 ± 0.038 .338 .0039 .101 ± 0.042 .283 .0186
Exploratory
Neck extension (degrees) −.200 ± 0.068 −.28 .0041 −.214 ± 0.068 −.299 .0022 −.200 ± 0.068 −.276 .0041
Intramaxillary axial area (mm) −.003 ± 0.002 −.177 .073 −.003 ± 0.002 −.198 .0602 −.004 ± 0.002 −.227 .0278
Nominally significant association (p < .05) shown in bold.
Abbreviations: BMI, body mass index; CT, computed tomography; IMD, intermolar distance; IPMD, interpremolar distance; PhOP, pharyngeal opening pressure;
PNS, posterior nasal spine.
a
Model adjusted for age, sex, and race.
b
Model adjusted for age, sex, race, height, and BMI.
c
Beta coefficient from linear regression represents the expected change in PhOP for a 1 unit increase in CT measurement.
d
Standardized beta represents the expected standard deviation change in PhOP for a standard deviation change in predictor, with estimates of 0.2, 0.5, and 0.8
representing small, medium, and large effects.

increasing caudal traction on airway structures.56,57
Our findings when considered in the context of previous
work imply that subjects compensate for TMD and a
loss of pharyngeal patency by adjusting their neck
posture and, as a result, hyoid position.58 Moreover,
both anatomic characteristics are often accompanied by
oral breathing,59 vertical growth pattern of the face,60
and high palate arch,59 which have all been shown to
increase OSA susceptibility.11,27,28
Several limitations should be considered when
interpreting our findings. First, we recognize that we
derived inferences from a clinical cohort rather than a
systematic cross‐section of the OSA population.
Studying a convenience sample such as ours could
have biased our results toward specific characteristics of
a relatively large group of PAP‐intolerant patients
seeking therapeutic alternatives to PAP. Second, PAP
application could have confounded our measures of
upper airway collapsibility by differences in lung
volume and pharyngeal muscle tone between low and
high‐pressure levels61 at which PCRIT and PhOP were
measured, respectively. Nevertheless, significant asso-
ciations were detected between both metrics and key
skeletal markers, to which biological plausibility can be

8 Otolaryngology–Head and Neck Surgery 00(00)
attributed, as discussed above. Third, despite imple-
menting a standardized protocol for CT image acquisi-
tion, unanticipated variations in head posture (neck
extension) predicted alterations in PCRIT and PhOP,
highlighting the possibility that the ‘sniff position’
could predict elevations in airway collapsibility during
sleep. Fourth, we acknowledge that our analysis was
not designed to integrate soft tissue volumes as
predictors of pharyngeal collapsibility, which still
represents a promising area of future research.
Our findings have implications for understanding the
potential impact of craniofacial dimensions on airway
collapsibility and related therapeutic strategies in OSA.
Our approach greatly simplifies the analysis of skeletal
dimensions by identifying specific transverse, cranio-
caudal, and anteroposterior markers of pharyngeal
collapsibility. It furthers the concept that skeletal
restriction in the transverse, rather than anteropos-
terior, dimension can play a prominent role in the
pathogenesis of upper airway obstruction during sleep,
while neck extension and hyoid descent may compen-
sate for transverse skeletal restriction by decompressing
the bony enclosure and stiffening pharyngeal structures
longitudinally. These skeletal dimensions may also
serve as anatomic markers for elevations in pharyngeal
collapsibility during sleep. Further research is required
to demonstrate whether these markers can guide patient
selection for specific procedures that reverse defects in
skeletal anatomy and upper airway function during
sleep.
Acknowledgments
This study was supported by NIH HL144859. We acknowledge
Kendra Troske for assistance with data collection and physio-
logic analysis.
Author Contributions
Eric Thuler, study design, data collection, data analysis,
writing the manuscript; Everett G. Seay, study design,
data collection, data analysis; John Woo, data
collection; Jane Lee, data collection; Brendan T.
Keenan, data analysis, reviewing the manuscript; Raj C.
Dedhia, study design, data analysis, reviewing the
manuscript; Alan R. Schwartz, study design, data
analysis, writing and reviewing the manuscript.
Disclosures
Competing interests: There is no conflict of interest.
Sponsorships: Research project sponsored by the National
Institute of Health (NIH).
Funding source: None.
Supplemental Material
Additional supporting information is available in the online
version of the article.
10976817, 0, Downloaded from https://aao-hnsfjournals.onlinelibrary.wiley.com/doi/10.1002/ohn.258 by Universidad Mayor, Wiley Online Library on [24/05/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
ORCID iD
Eric Thuler http://orcid.org/0000-0003-4670-4399
References
1. Tietjens JR, Claman D, Kezirian EJ, et al. Obstructive sleep
apnea in cardiovascular disease: a review of the literature and
proposed multidisciplinary clinical management strategy. J Am
Heart Assoc. 2019;8(1):e010440. doi:10.1161/JAHA.118.010440
2. Dempsey JA, Veasey SC, Morgan BJ, O'Donnell CP.
Pathophysiology of sleep apnea. Physiol Rev. 2010;90(1):
47‐112. doi:10.1152/physrev.00043.2008
3. Landry SA, Joosten SA, Eckert DJ, et al. Therapeutic
CPAP level predicts upper airway collapsibility in patients
with obstructive sleep apnea. Sleep. 2017;40(6):zsx056.
doi:10.1093/sleep/zsx056
4. Bakker JP, Weaver TE, Parthasarathy S, Aloia MS.
Adherence to CPAP. Chest. 2019;155(6):1272‐1287. doi:10.
1016/j.chest.2019.01.012
5. Lorenzi‐Filho G, Almeida FR, Strollo PJ. Treating OSA:
Current and emerging therapies beyond CPAP. Respirology.
2017;22(8):1500‐1507. doi:10.1111/resp.13144
6. Eckert DJ. Phenotypic approaches to obstructive sleep
apnoea—new pathways for targeted therapy. Sleep Med
Rev. 2018;37:45‐59. doi:10.1016/j.smrv.2016.12.003
7. Agha B, Johal A. Facial phenotype in obstructive sleep apnea‐
hypopnea syndrome: a systematic review and meta‐analysis. J
Sleep Res. 2017;26(2):122‐131. doi:10.1111/jsr.12485
8. Eckert DJ, Malhotra A. Pathophysiology of adult obstruc-
tive sleep apnea. Proc Am Thorac Soc. 2008;5(2):144‐153.
doi:10.1513/pats.200707-114MG
9. Eckert DJ, Malhotra A, Jordan AS. Mechanisms of apnea.
Prog Cardiovasc Dis. 2009;51(4):313‐323. doi:10.1016/j.
pcad.2008.02.003
10. Sutherland K, Phillips CL, Yee BJ, Grunstein RR, Cistulli
PA. Maxillomandibular volume influences the relationship
between weight loss and improvement in obstructive sleep
apnea. Sleep. 2016;39(1):43‐49. doi:10.5665/sleep.5314
11. Johal A, Conaghan C. Maxillary morphology in obstructive
sleep apnea: a cephalometric and model study. Angle
Orthod. 2004;74(5):648‐656. doi:10.1043/0003-3219(2004)
074%3C0648:MMIOSA%3E2.0.CO;2
12. Abdullatif J, Certal V, Zaghi S, et al. Maxillary expansion
and maxillomandibular expansion for adult OSA: a
systematic review and meta‐analysis. J Craniomaxillofac
Surg. 2016;44(5):574‐578. doi:10.1016/j.jcms.2016.02.001
13. Vale F, Albergaria M, Carrilho E, et al. Efficacy of rapid
maxillary expansion in the treatment of obstructive sleep
apnea syndrome: a systematic review with meta‐analysis. J
Evid Based Dent Pract. 2017;17(3):159‐168. doi:10.1016/J.
JEBDP.2017.02.001
14. Camacho M, Li D, Kawai M, et al. Tonsillectomy for adult
obstructive sleep apnea: a systematic review and meta‐analysis.
Laryngoscope. 2016;126(9):2176‐2186. doi:10.1002/lary.25931
15. Friedman M, Yalamanchali S, Gorelick G, Joseph NJ,
Hwang MS. A standardized lingual tonsil grading system:

Thuler et al.
interexaminer agreement. Otolaryngol Head Neck Surg.
2015;152(4):667‐672. doi:10.1177/0194599815568970
16. Isono S. Obesity and obstructive sleep apnoea: mechanisms
for increased collapsibility of the passive pharyngeal airway.
Respirology. 2012;17(1):32‐42. doi:10.1111/j.1440-1843.2011.
02093.x
17. Denolf PL, Vanderveken OM, Marklund ME, Braem MJ.
The status of cephalometry in the prediction of non‐CPAP
treatment outcome in obstructive sleep apnea patients. Sleep
Med Rev. 2016;27:56‐73. doi:10.1016/j.smrv.2015.05.009
18. Poirrier AL, Pire S, Raskin S, Limme M, Poirrier R.
Contribution of postero‐anterior cephalometry in obstruc-
tive sleep apnea. Laryngoscope. 2012;122(10):2350‐2354.
doi:10.1002/lary.23458
19. Chen H, Aarab G, de Ruiter MH, de Lange J, Lobbezoo F,
van der Stelt PF. Three‐dimensional imaging of the upper
airway anatomy in obstructive sleep apnea: a systematic review.
Sleep Med. 2016;21:19‐27. doi:10.1016/j.sleep.2016.01.022
20. Shigeta Y, Enciso R, Ogawa T, Shintaku WH, Clark GT.
Correlation between retroglossal airway size and body mass
index in OSA and non‐OSA patients using cone beam CT
imaging. Sleep Breath. 2008;12(4):347‐352. doi:10.1007/
s11325-008-0186-6
21. Passos UL, Genta PR, Marcondes BF, Lorenzi‐Filho G,
Gebrim EMMS. State‐dependent changes in the upper airway
assessed by multidetector CT in healthy individuals and
during obstructive events in patients with sleep apnea. J Bras
Pneumol. 2019;45(4):1‐9. doi:10.1590/1806-3713/e20180264
22. Gamaleldin O, Bahgat A, Anwar O, et al. Role of dynamic
sleep MRI in obstructive sleep apnea syndrome. Oral Radiology.
2021;37(3):376‐384. doi:10.1007/s11282-020-00455-w
23. Schwab RJ, Pasirstein M, Pierson R, et al. Identification of
upper airway anatomic risk factors for obstructive sleep
apnea with volumetric magnetic resonance imaging. Am J
Respir Crit Care Med. 2003;168(5):522‐530. doi:10.1164/
rccm.200208-866OC
24. Kavcic P, Koren A, Koritnik B, Fajdiga I, Groselj LD.
Sleep magnetic resonance imaging with electroencephalo-
gram in obstructive sleep apnea syndrome. Laryngoscope.
2015;125(6):1485‐1490. doi:10.1002/lary.25085
25. Neelapu BC, Kharbanda OP, Sardana HK, et al.
Craniofacial and upper airway morphology in adult
obstructive sleep apnea patients: a systematic review and
meta‐analysis of cephalometric studies. Sleep Med Rev.
2017;31:79‐90. doi:10.1016/j.smrv.2016.01.007
26. Isono S, Tanaka A, Nishino T. Dynamic interaction
between the tongue and soft palate during obstructive
apnea in anesthetized patients with sleep‐disordered
breathing. J Appl Physiol. 2003;95(6):2257‐2264. doi:10.
1152/japplphysiol.00402.2003
27. Seto BH. Maxillary morphology in obstructive sleep apnoea
syndrome. Eur J Orthod. 2001;23:703‐714. doi:10.1093/ejo/
23.6.703
28. Kushida CA. A predictive morphometric model for the
obstructive sleep apnea syndrome. Ann Intern Med.
1997;127(8_part_1):581. doi:10.7326/0003-4819-127-8_Part_
1-199710150-00001
10976817, 0, Downloaded from https://aao-hnsfjournals.onlinelibrary.wiley.com/doi/10.1002/ohn.258 by Universidad Mayor, Wiley Online Library on [24/05/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
9
29. Thuler E, Rabelo FAW, Yui M, Tominaga Q, Dos Santos V
Jr., Arap SS. Correlation between the transverse dimension
of the maxilla, upper airway obstructive site, and OSA
severity. J Clin Sleep Med. 2021;17(7):1465‐1473. doi:10.
5664/jcsm.9226
30. Carberry JC, Jordan AS, White DP, Wellman A, Eckert DJ.
Upper airway collapsibility (Pcrit) and pharyngeal dilator
muscle activity are sleep stage dependent. Sleep.
2016;39(3):511‐521. doi:10.5665/sleep.5516
31. Ordones AB, Grad GF, Cahali MB, Lorenzi‐Filho G,
Sennes LU, Genta PR. Comparison of upper airway
obstruction during zolpidem‐induced sleep and propofol‐
induced sleep in patients with obstructive sleep apnea: a
pilot study. J Clin Sleep Med. 2020;16(5):725‐732. doi:10.
5664/jcsm.8334
32. Gold AR, Schwartz AR. The pharyngeal critical pressure.
Chest. 1996;110(4):1077‐1088. doi:10.1378/chest.110.4.1077
33. Schwartz AR, Gold AR, Schubert N, et al. Effect of weight
loss on upper airway collapsibility in obstructive sleep
apnea. Am Rev Respir Dis. 1991;144(3_pt_1):494‐498.
doi:10.1164/ajrccm/144.3_Pt_1.494
34. Schwartz AR, Schubert N, Rothman W, et al. Effect of
uvulopalatopharyngoplasty on upper airway collapsibility
in obstructive sleep apnea. Am Rev Respir Dis.
1992;145(3):527‐532. doi:10.1164/ajrccm/145.3.527
35. Dedhia RC, Seay EG, Schwartz AR. Beyond VOTE: the
new frontier of drug‐induced sleep endoscopy. ORL J
Otorhinolaryngol Relat Spec. 2022;84(4):296‐301. doi:10.
1159/000518660
36. Lan MC, Hsu YB, Lan MY, et al. The predictive value of
drug‐induced sleep endoscopy for CPAP titration in OSA
patients. Sleep Breath. 2018;22(4):949‐954. doi:10.1007/
s11325-017-1600-8
37. Lee CH, Seay EG, Walters BK, Scalzitti NJ, Dedhia RC.
Therapeutic positive airway pressure level predicts response to
hypoglossal nerve stimulation for obstructive sleep apnea. J Clin
Sleep Med. 2019;15(08):1165‐1172. doi:10.5664/jcsm.7814
38. Seay EG, Keenan BT, Schwartz AR, Dedhia RC.
Evaluation of therapeutic positive airway pressure as a
hypoglossal nerve stimulation predictor in patients with
obstructive sleep apnea. JAMA Otolaryngol Head Neck
Surg. 2020;146(8):691‐698. doi:10.1001/jamaoto.2020.1018
39. Genta PR, Schorr F, Eckert DJ, et al. Upper airway
collapsibility is associated with obesity and hyoid position.
Sleep. 2014;37(10):1673‐1678. doi:10.5665/sleep.4078
40. Atkins JH, Mandel JE, Rosanova G. Safety and efficacy of
drug‐induced sleep endoscopy using a probability ramp
propofol infusion system in patients with severe obstructive
sleep apnea. Anesth Analg. 2014;119(4):805‐810. doi:10.
1213/ANE.0000000000000229
41. Weissheimer A, Menezes LM, Sameshima GT, Enciso R,
Pham J, Grauer D. Imaging software accuracy for 3‐
dimensional analysis of the upper airway. Am J Orthod
Dentofacial Orthop. 2012;142(6):801‐813. doi:10.1016/j.
ajodo.2012.07.015
42. Cakirer B, Hans MG, Graham G, Aylor J, Tishler PV,
Redline S. The relationship between craniofacial

10
morphology and obstructive sleep apnea in whites and in
African‐Americans. Am J Respir Crit Care Med.
2001;163(4):947‐950. doi:10.1164/ajrccm.163.4.2005136
43. Al Ali A, Richmond S, Popat H, et al. The influence of
snoring, mouth breathing and apnoea on facial morphology
in late childhood: a three‐dimensional study. BMJ Open.
2015;5(9):e009027. doi:10.1136/bmjopen-2015-009027
44. Gupta J, Makhija P, Gupta K. Does a correlation exist
between nasal airway volume and craniofacial morphology:
a cone beam computed tomography study. Indian J Dent
Res. 2016;27(4):359‐363. doi:10.4103/0970-9290.191882
45. Chi L, Comyn FL, Mitra N, et al. Identification of
craniofacial risk factors for obstructive sleep apnoea using
three‐dimensional MRI. Eur Respir J. 2011;38(2):348‐358.
doi:10.1183/09031936.00119210
46. Cistulli PA. Craniofacial abnormalities in obstructive sleep
apnoea: implications for treatment. Respirology.
1996;1(3):167‐174.
47. Gong A, Li J, Wang Z, et al. Cranial base characteristics in
anteroposterior malocclusions: a meta‐analysis. Angle
Orthod. 2016;86(4):668‐680. doi:10.2319/032315-186.1
48. Hochberg Y. A sharper Bonferroni procedure for multiple
tests of significance. Biometrika. 1988;75(4):800‐802. doi:10.
1093/biomet/75.4.800
49. Schorr F, Kayamori F, Hirata RP, et al. Different
craniofacial characteristics predict upper airway collapsi-
bility in Japanese‐Brazilian and white men. Chest.
2016;149(3):737‐746. doi:10.1378/chest.15-0638
50. Sforza E, Bacon W, Weiss T, Thibault A, Petiau C, Krieger J.
Upper airway collapsibility and cephalometric variables in
patients with obstructive sleep apnea. Am J Respir Crit Care
Med. 2000;161(2 pt 1):347‐352. doi:10.1164/ajrccm.161.2.
9810091
51. Iwasaki T, Saitoh I, Takemoto Y, et al. Tongue posture
improvement and pharyngeal airway enlargement as secondary
effects of rapid maxillary expansion: a cone‐beam computed
tomography study. Am J Orthod Dentofacial Orthop.
2013;143(2):235‐245. doi:10.1016/j.ajodo.2012.09.014
52. Vinha PP, Faria AC, Xavier SP, Christino M, de Mello‐Filho
FV. Enlargement of the pharynx resulting from surgically
assisted rapid maxillary expansion. J Oral Maxillofac Surg.
2016;74(2):369‐379. doi:10.1016/j.joms.2015.06.157
10976817, 0, Downloaded from https://aao-hnsfjournals.onlinelibrary.wiley.com/doi/10.1002/ohn.258 by Universidad Mayor, Wiley Online Library on [24/05/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Otolaryngology–Head and Neck Surgery 00(00)
53. Vinha PP, Thuler ER, de Mello‐Filho FV. Effects of surgically
assisted rapid maxillary expansion on the modification of the
pharynx and hard palate and on obstructive sleep apnea, and
their correlations. J Craniomaxillofac Surg. 2020;48(4):339‐348.
doi:10.1016/j.jcms.2020.02.007
54. Ayuse T, Inazawa T, Kurata S, et al. Mouth‐opening
increases upper‐airway collapsibility without changing
resistance during midazolam sedation. J Dent Res.
2004;83(9):718‐722. doi:10.1177/154405910408300912
55. Jose N, Shetty S, Mogra S, Shetty VS, Rangarajan S, Mary
L. Evaluation of hyoid bone position and its correlation
with pharyngeal airway space in different types of skeletal
malocclusion. Contemp Clin Dent. 2014;5(2):187. doi:10.
4103/0976-237X.132313
56. Thut DC, Schwartz AR, Roach D, Wise RA, Permutt S,
Smith PL. Tracheal and neck position influence upper
airway airflow dynamics by altering airway length. J Appl
Physiol. 1993;75(5):2084‐2090. doi:10.1152/jappl.1993.75.
5.2084
57. Isono S, Tanaka A, Ishikawa T, Tagaito Y, Nishino T.
Sniffing position improves pharyngeal airway patency in
anesthetized patients with obstructive sleep apnea.
Anesthesiology. 2005;103(3):489‐494. doi:10.1097/00000542-
200509000-00010
58. Adamidis IP, Spyropoulos MN. Hyoid bone position and
orientation in class i and class iii malocclusions. Am J
Orthod Dentofacial Orthop. 1992;101(4):308‐312. doi:10.
1016/S0889-5406(05)80323-3
59. Pereira Coelho Ferraz MJ, Flávio Nouer D, Ricardo
Teixeira J, Bérzin F. Cephalometric assessment of the hyoid
bone position in oral breathing children. Braz J
Otorhinolaryngol. 2007;73(1):45‐50. doi:10.1016/S1808-
8694(15)31121-6
60. Vieira BB, Itikawa CE, de Almeida LA, et al. Cephalometric
evaluation of facial pattern and hyoid bone position in
children with obstructive sleep apnea syndrome. Int J
Pediatr Otorhinolaryngol. 2011;75(3):383‐386. doi:10.1016/j.
ijporl.2010.12.010
61. Jordan AS, White DP, Lo YL, et al. Airway dilator muscle
activity and lung volume during stable breathing in
obstructive sleep apnea. Sleep. 2009;32(3):361‐368. doi:10.
1093/sleep/32.3.361