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UBC Theses and Dissertations

Effect of orthodontic treatment on the upper airway volume Tam, Isaac Timothy 2014

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!!EFFECT!OF!ORTHODONTIC!TREATMENT!ON!THE!UPPER!AIRWAY!VOLUME!by#Isaac#Timothy#Tam#D.M.D.,#University#of#Pennsylvania,#2005#B.S.,#Hope#College#2001##A#THESIS#SUBMITTED#IN#PARTIAL#FULFILLMENT#OF#THE#REQUIREMENTS#FOR#THE#DEGREE#OF#MASTER#OF#SCIENCE#in#THE#FACULTY#OF#GRADUATE#AND#POSTDOCTORAL#STUDIES#(Craniofacial#Science)##THE#UNIVERSITY#OF#BRITISH#COLUMBIA#(Vancouver)##August#2014#©#Isaac#Timothy#Tam,#2014# ii Abstract! Introduction:#Currently,#the#influence#of#orthodontic#treatment#on#the#volume#of#the#upper#airway#is#not#well#understood.#The#aim#of#this#study#is#to#examine#the#effects#of#orthodontic#treatment#both#with#and#without#extractions#on#the#anatomical#characteristics#of#the#upper#airway#in#adults.##Methods:#For#this#retrospective#study,#the#pre#and#post#orthodontic#treatment#CBCT#scans#of#adult#patients#treated#at#the#UMN#Division#of#Orthodontics#between#2008#and#2012#were#reviewed.#From#a#pool#of#1680#patient#records,#74#patients#met#the#eligibility#criteria#of#the#study#and#were#included#for#further#analysis.##3D#imaging#analysis#software#was#used#to#segment#and#measure#upper#airway#regions#including#the#nasopharynx#(NP),#the#retropalatal#(RP)#and#retroglossal#(RG)#areas#of#the#oropharynx,#as#well#as#total#airway#(TA).#Coefficient#of#variation#and#the#intraclass#correlation#coefficient#were#calculated.#The#Wilcoxon#signed\rank#test#was#used#to#compare#volumetric#and#minimal#cross\sectional#area#changes#from#pre#(T0)#to#post#(T1)#treatment.#Results:#The#reliability#was#high#for#all#measurements#with#an#ICC#≥0.82.#Cephalometric#analysis#revealed#no#significant#skeletal#changes#from#T0#to#T1.##The#T0#to#T1#treatment#changes#for#the#upper#airway#for#the#extraction#and#non\extraction#groups#were#as#follows:#TA:#1039.6#±#3674.3mm3##vs.#1719.2.2#mm3##±##4979.2,#NP:#136.1#mm3#±##1379.3#vs#\36.5#mm3#±##1139.8,#RP:#412.7#mm3##±##3042.5#vs.#399.3#mm3#±##3294.6#,#and#RG#412.5mm3#±##1503.2#vs.#1109.3mm3#±##2328.6,#respectively.#The#treatment#changes#for#all#airway#regions#examined#were#not#significantly#(p>0.05)#different#between#the#extraction#and#non\extraction#groups.##Similarly,#changes#in#the#minimum#cross\sectional#area#were#also#not#significantly#different#between#the#two#types#of#treatment.##Conclusions:#Orthodontic#treatment#in#adults#does#not#cause#clinically#significant#changes#to#the#volume#or#minimally#constricted#area#of#the#upper#airway.## iii Preface! The#project#and#associated#methods#were#approved#by#the#University#of#British#Columbia’s#Research#Ethics#Board#certificate#H12\00951.## iv Table!of!Contents!#Abstract!...................................................................................................................................................!ii#Preface!....................................................................................................................................................!iii#Table!of!Contents!................................................................................................................................!iv#List!of!Tables!........................................................................................................................................!vii#List!of!Figures!.......................................................................................................................................!ix#List!of!Abbreviations!............................................................................................................................!x#Acknowledgements!............................................................................................................................!xi#Dedication!............................................................................................................................................!xii#Chapter!!1:!Introduction!....................................................................................................................!1#1.1# Extraction!vs.!NonMextraction!...........................................................................................................!1#1.1.1# Dental#Arch#Length#Deficiency#...................................................................................................................#2#1.1.2# Stability#.................................................................................................................................................................#3#1.1.3# Temporomandibular#Joint#Disorder#........................................................................................................#3#1.1.4# Smile#and#Soft#Tissue#Esthetics#..................................................................................................................#4#1.2# Sleep!Apnea!in!Adults!..........................................................................................................................!6#1.2.1# Epidemiology#of#OSAS#....................................................................................................................................#6#1.2.2# Pathophysiology#...............................................................................................................................................#7#1.3# CBCT!and!ThreeMDimensional!Airway!Analysis!.........................................................................!9#1.4# Orthodontic!Effects!On!Airway!.....................................................................................................!14#1.5# Objectives!.............................................................................................................................................!18#1.5.1# Null#Hypothesis#..............................................................................................................................................#18# v 1.5.2# Study#Hypothesis#...........................................................................................................................................#18#Chapter!!2:!Methodology!..................................................................................................................!20#2.1# Demographic!.......................................................................................................................................!20#2.2# Confounding!Factors!........................................................................................................................!24#2.2.1# Influence#of#CBCT#Scan#Settings#..............................................................................................................#24#2.3# Data!Collection!and!Measurements!.............................................................................................!26#2.3.1# Orientation#.......................................................................................................................................................#26#2.3.2# Cephalometric#Measurements#.................................................................................................................#30#2.3.2.1# Linear#Measurements#...........................................................................................................................................#30#2.3.2.2# Angular#Measurements#........................................................................................................................................#32#2.3.2.3# Volumetric#Measurements#.................................................................................................................................#33#2.4# Statistical!Analysis!............................................................................................................................!42#2.4.1# Reliability#Testing#.........................................................................................................................................#43#Chapter!!3:!Results!.............................................................................................................................!44#3.1# Error!Analysis!.....................................................................................................................................!44#3.2# Demographics!.....................................................................................................................................!45#3.3# Confounding!Factors!........................................................................................................................!47#3.4# Treatment!Effects!on!Upper!Airway!............................................................................................!54#3.5# Impact!of!Dental!Crowding!on!Treatment!Associated!Airway!Changes!..........................!57#3.6# PostMhoc!Power!Calculation!...........................................................................................................!60#Chapter!!4:!Discussion!......................................................................................................................!61#4.1# Previous!Investigations!...................................................................................................................!61#4.2# Demographics!.....................................................................................................................................!62#4.3# Confounding!Factors!........................................................................................................................!63# vi 4.4# Airway!Assessment!...........................................................................................................................!65#4.5# Treatment!Effects!on!the!Upper!Airway!....................................................................................!66#4.6# Impact!of!Dental!Crowding!on!Treatment!Associated!Airway!Changes!..........................!67#4.7# Measurement!Error!..........................................................................................................................!68#4.8# Limitations!...........................................................................................................................................!69#Conclusion!............................................................................................................................................!71#Bibliography!........................................................................................................................................!72#Appendix!A!...........................................................................................................................................!86## vii List!of!Tables! Table 1.1 Scan protocols and settings used for CBCT scans with next generation i-CAT machine....................................................................................................................................................... 11#Table 1.2 Threshold value ............................................................................................................. 13#Table 1.3 Previous investigations on orthodontic treatment effects on airway ............................ 14#Table 2.1 Screening Form for Eligibility Criteria ......................................................................... 21#Table 2.2 Inclusion and Exclusion Criteria ................................................................................... 22#Table 2.3 Orientation hard tissue landmarks ................................................................................ 27#Table 2.4 Cephalometric landmarks and linear measurements. ................................................... 32#Table 2.5 Angular Measurements ................................................................................................. 32#Table 2.6 Definitions of anatomic areas ....................................................................................... 35#Table 2.7 Protocol for volumetric and minimum axial area airway measurement ....................... 36#Table 3.1 Cephalogram variance of error ..................................................................................... 44#Table 3.2 Airway variance of error ............................................................................................... 45#Table 3.3 Descriptive statistics of the sample population ............................................................. 47#Table 3.4 Airway measurements divided into low, normal and high mandibular plane angles. .. 48#Table 3.5 Airway measurements divided by Class I and Class II craniofacial classifications. .... 50#Table 3.6 Airway measurements divided by gender. .................................................................... 52#Table 3.7 Initial, final, and change in airway measurements between extraction and nonextraction groups ..................................................................................................................... 56#Table 3.8 Crowding sample characteristics .................................................................................. 57#Table 3.9 Spearman’s rank correlation coefficient between crowding and volumetric changes in airway and minimum axial areas .................................................................................................. 58# viii Table 3.10 Method error means and standard deviations for each airway region ........................ 60#Table 4.1 Measurement error compared with other studies .......................................................... 68##Table A.1 Airway morphometric changes from pre- to post-treatment. ....................................... 85#Table A.2 Airway measurements of patients with identical pre and post treatment .................... 86#Table A.3 Power calculation for each airway section ................................................................... 87#Table A.4 Initial measurements of airways of patients with identical pre and post treatment scan settings divided based on  mandibular plane angle. ...................................................................... 88#Table A.5 Initial measurements of airways of patients with identical pre and ............................. 89#Table A.6 Initial measurements of airways of patients with identical pre and post treatment scan settings divided by gender. ........................................................................................................... 90#Table A.7 Analysis of variance of airway changes between crowding severity in the extraction group. ............................................................................................................................................ 91#Table A.8 Analysis of variance of airway changes between crowding severity in the non-extraction group. ........................................................................................................................... 94#Table A.9 Patient characteristics with identical pre and post treatment scan settings .................. 98#Table A.10 Treatment time, gender distribution, and age between dynamic and fixed threshold airway analysis .............................................................................................................................. 99#  ix List!of!Figures!#Figure 1.1 Anatomy of the airway divided into the nasopharynx, oropharynx, and hypopharynx........................................................................................................................................................ 19#Figure 2.1 Flow Diagram of Sample Selection ............................................................................. 23#Figure 2.2 Orientation of the coronal plane using the Frankfort Horizontal Plane (porion to orbitale). ........................................................................................................................................ 27#Figure 2.3 Orientation of the axial plane using the lower border of the orbit landmarks. ............ 28#Figure 2.4 Orientation of the midsagital plane using the upper incisive foramen to opisthion. ... 29#Figure 2.5 Cephalometric landmarks and planes .......................................................................... 31#Figure 2.6 Defined total airway, consisting of the nasopharyngeal (NP), as well as the retropalatal (RP) and retroglossal (RG) regions of the oropharynx. Palatal plane set as horizontal, with measurements taken in mid-sagittal plane. ........................................................................... 37#Figure 2.7 Nasopharyngeal airway volume .................................................................................. 38#Figure 2.8 Retropalatal airway region of the oropharynx ............................................................. 39#Figure 2.9 Retroglossal airway region of the oropharynx ............................................................ 40#Figure 2.10 Total airway ............................................................................................................... 41#Figure 3.1 Crowding and difference in the retroglossal airway in the extraction group .............. 59# x !List!of!Abbreviations! CBCT:#cone#beam#computed#tomography#DICOM:#Digital#Imaging#and#Communications#in#Medicine#FOV:#field#of#view#NP:#nasopharynx#OSA:#obstructive#sleep#apnea#RG:#retroglossal#RP:#retropalatal#SD:#standard#deviation#TA:#total#airway#T0:#time#pre]orthodontic#treatment#T1:#time#post]orthodontic#treatment#TSALD:#tooth#size]arch#length#discrepancy  xi Acknowledgements!# I#would#like#to#thank#Dr.#Benjamin#Pliska#for#his#mentorship#and#camaraderie.#Under#his#guidance#I#developed#an#appreciation#for#the#research#process#and#valuable#experience#that#has#shaped#the#orthodontist#in#me.#I#would#also#like#to#show#my#deep#appreciation#for#Dr.#Fernanda#Almeida,#Dr.#Alan#Lowe,#and#Dr.#Virginia#Diewert#for#serving#on#my#thesis#committee.#Their#encouragement#and#support#were#integral#to#my#educational#and#research#experience.# xii Dedication!# I#dedicate#this#thesis#to#my#family,#Drs.#Timothy#Tam,#Remedios#Tam,#Esther#Tam#and#Samuel#Tam,#for#their#faith,#support,#and#encouragement#in#our#commitment#to#life#long#learning.#   1 Chapter!!1: Introduction!#1.1 Extraction!vs.!NonMextraction!The#supposed#benefits#and#negative#sequelae#associated#with#the#extraction#of#teeth#have#long#been#debated#in#the#profession#of#orthodontics.#In#the#early#1900s,#Edward#H.#Angle#was#one#of#the#earliest#pioneers#in#orthodontics#who#first#classified#different#types#of#malocclusion,#defined#normal#occlusion,#and#advocated#for#non]extraction#orthodontic#therapy#to#obtain#ideal#facial#esthetics#and#function.{Proffit:2007tz}.##One#of#his#apprentices,#Charles#H.#Tweed,#was#dissatisfied#with#the#relapsing#of#Class#II#crowded#cases#in#his#patients#while#treating#a#full#complement#of#teeth.#Consequently,#with#the#hopes#of#improving#treatment#stability#he#directed#the#profession#to#extraction#therapy#involving#4#first#premolars#and#uprighting#lower#incisors{Tweed:1946vb}.##Another#student#of#Angle,#Percy#R.#Begg#of#Adelaide#Australia,#adhered#to#the#nonextraction#philosophy#until#he#found#more#favorable#facial#balance#and#stability#through#the#routine#removal#of#teeth#making#waves#in#the#orthodontic#community{Begg:1977wb}.#The#shift#towards#extraction#of#premolar#teeth#within#the#profession#to#aid#in#orthodontic#treatment#reached#its#peak#in#the#1960’s#when#it#is#estimated#that#greater#than#60%#of#all#treatment#involved#the#removal#of#permanent#teeth.#{Proffit:2007tz}###The#popularity#of#non]extraction#treatments#returned#to#orthodontics#in#the#last#2#decades#with#an#improved#understanding#of#the#biological#underpinnings#of#treatment#effects#in#regards#to#both#soft#tissue#esthetics#and#stability.{OConnor:1993wi,#Weintraub:1989wu}.##Numerous#studies,#most#notably#by#Little#and#his#collaborators#at#the#University#of#Washington#looked#at#long]term#alignment#and#concluded#that#extraction#treatment#does#not#prevent#long]term#post]retention#crowding.{Little:1988ti}#Also#a#paradigm#shift#in#treatment#planning#towards#a#greater#focus#on#the#soft#tissue#profile#and#smile#esthetics#as#opposed#to#the#static#articulation#of#the#dentition#led#many#clinicians#to#limit#extractions#to#all#but#severely#crowded#cases.###   2 Thorough#diagnosis#after#careful#examination#of#complete#patient#records#must#be#completed#before#a#decision#of#whether#extractions#are#warranted#in#orthodontics.#Evaluation#of#several#factors#are#taken#into#consideration#including:#the#prominence#of#the#nose#and#chin,#the#position#of#the#mandible,#the#growth#potential#available#in#a#patient,#compliance#for#extraoral#and#intraoral#appliances,#the#degree#of#tooth#size]arch#length#discrepancy,#and#the#status#of#the#lower#anterior#teeth#periodontium#{Bishara:2006fs}.##Evaluation#of#these#variables#enables#the#orthodontist#to#treat#the#case#to#optimum#stability,#attain#patient#satisfaction,#and#ideal#soft#tissue#and#smile#esthetics.#A#review#of#the#current#understanding#on#these#various#aspects#of#the#orthodontic#patient#to#be#considered#when#deciding#on#extractions#with#orthodontic#treatment#will#follow. #1.1.1 Dental!Arch!Length!Deficiency!# Underlying#the#majority#of#extraction#and#nonextraction#treatments#recommended#by#orthodontists{McDougall:1982uh}#is#the#issue#of#tooth#size#arch]length#deficiency.##Also#known#as#dental#crowding,#an#overly#simple#explanation#of#the#cause#of#this#orthodontic#problem#is#genetics#{Normando:2012cu},#where#big#teeth#are#inherited#from#one#parent#and#a#small#jaw#from#the#other,#hence#causing#a#space#discrepancy.#However,#there#are#instances#where#a#normal#sized#dental#arch#is#crowded#in#a#developmentally#deficient#jaw.####Another#explanation#for#dental#crowding#involves#environmental#factors#such#as#those#best#demonstrated#in#Begg’s#study{Begg:1954tp}#on#primitive#man.##Begg#believed#that#a#reduced#amount#of#grit#in#modern#diets#caused#less#interproximal#wear#and#thus#larger#tooth#sizes,#leading#to#increases#in#crowding.##In#1990,#Corruccini{Corruccini:1990kt}#refuted#Begg’s#research#because#both#crowding#and#attrition#increased#with#age.#Although#Begg’s#theory#was#discredited,#it#is#not#uncommon#for#academic#institutions#to#reference#Begg’s#rationale#for#orthodontists#to#undergo#extractions#for#space#management.##   3 Space#required#to#align#crowding#is#achieved#by#either#arch#expansion#or#dental#extractions,#although#there#is#not#much#agreement#among#orthodontists#with#regards#to#when#these#two#differing#approaches#should#be#applied.{Han:1991uv}#Although#extraction#rates#reported#by#orthodontists#did#not#correlate#with#the#age#of#the#orthodontist,#experience#or#training#program,#a#survey#of#238#Michigan#orthodontists#revealed#that#there#exists#a#wide#range#of#extraction#frequency#and#that#a#large#discrepancy#is#evident#between#perceived#and#actual#extraction#rates{Weintraub:1989wu}.###1.1.2 Stability!# Stability#in#treatment#has#been#a#main#concern#for#orthodontists#where#long#term#alignment#is#variable#and#unpredictable.{Little:1981tt}.#Studies#examining#orthodontic#treatment#stability#has#noted#similar#relapse#tendencies#for#both#extraction#and#non]extraction#approaches,#with#expansion#at#the#mandibular#canine#region#being#least#stable#regardless#of#type#of#malocclusion#or#extraction#therapy.{Uhde:1983dt,#Shapiro:1974wv}#However#these#retrospective#studies{Uhde:1983dt,#Shapiro:1974wv,#Little:1981tt}#were#subject#to#sampling#bias.#More#recently#in#2006,#Erdinc#et#al{Erdinc:2006bk}#confirmed#the#similar#relapse#patterns#for#the#extraction#and#nonextraction#treatment#modalities.##In#principle,#extractions#in#orthodontics#were#used#to#avoid#proclining#incisors#out#of#the#osseous#envelope#from#the#alveolar#process#to#avoid#the#higher#tendency#for#developing#gingival#recessions.{JossVassalli:2010ee}#However,#thickness#of#the#free#gingival]margin#has#been#shown#to#be#more#relevant#than#the#final#inclination#of#the#incisors.{Yared:2006ea}##1.1.3 Temporomandibular!Joint!Disorder!# The#prevalence#of#temporomandibular#joint#disorder#(TMD)#and#extraction#orthodontic#therapy#has#been#another#subject#of#debate#in#both#the#clinic#and#courtroom.#In#1987,#a#lawsuit#was#filed#that#claimed#that#extraction#orthodontic#treatment#had#caused#TMD#in#a#patient#during#the#case#of#Brimm#vs.#Malloy#which#revealed#to#the#orthodontic#   4 community#the#lack#of#good#evidenced#based#literature#available.#Consequently,#the#American#Association#of#Orthodontists#focused#their#resources#on#researching#the#possibility#of#an#association#between#TMD#and#orthodontic#treatment.#On#one#hand,#the#controversy#revolves#around#the#belief#that#premolar#extractions#lead#to#joint#dysfunction{Just:1991wa}#while#on#the#other#hand,#there#is#no#such#evidence#available#as#seen#in#the#14#year#average#postreatment#study{Beattie:1994vg}#consisting#of#30#extraction#and#30#nonextraction#borderline#patients#as#sorted#by#discriminant#analysis.#With#time,#the#preponderance#of#evidence#has#led#to#the#conclusion#that#orthodontic#treatment#with#extractions#did#not#increase#the#risk#for#development#of#TMD.20]28##1.1.4 Smile!and!Soft!Tissue!Esthetics!# Dental#extractions#have#been#linked#to#smile#and#soft#tissue#esthetics.#Features#of#an#attractive#smile#include#a#smile#arc#that#parallels#the#lower#lip#and#the#minimization#of#the#buccal#corridor,#which#is#the#space#between#the#buccal#surface#of#the#dentition#and#the#corresponding#soft#tissue#of#the#corners#of#the#mouth.29#The#misdiagnosis#of#indications#for#extraction#treatment#in#orthodontics#has#been#linked#to#excessive#buccal#corridors.#30#However,#when#applied#appropriately,#there#was#no#relationship#between#extraction#aesthetics#and#width#of#the#dentition#or#buccal#corridor#variables.29,31#A#study32#on#attractiveness#using#computerized#variations#of#smile#arcs#and#buccal#corridors#revealed#that#for#laypersons#and#orthodontists,#flat#smile#arcs#were#more#of#a#factor#in#decreasing#attractiveness#regardless#of#buccal#corridors.#Furthermore,#Johnson#et#al.29found#that#there#were#no#differences#judged#by#laypersons#and#practitioners#in#the#mean#aesthetic#score#of#extraction#and#non#extraction#patients#after#reviewing#frontal#photographs#of#30#patients#with#4#bicuspid#extraction#and#30#patients#without#extractions.#More#recently,#Schabel#et#al33#looked#at#48#subjects#and#found#that#the#attractiveness#of#smiles#were#not#related#to#whether#patients#had#extraction#or#nonextraction#orthodontic#therapy.##Related#to#soft#tissue#is#the#characteristic#of#the#profile#and#the#contention#that#extractions#can#possibly#lead#to#a#“dished#in”#appearance#by#retraction#of#the#upper#incisors#   5 when#closing#the#remaining#extraction#spaces,#thus#compromising#facial#esthetics.#Paquette#et#al34#sampled#33#extraction#and#30#nonextraction#patients#with#borderline#Class#II#Division#I#malocclusions,#and#using#lateral#cephalograms,#study#models,#and#self]evaluation#questionnaires,#evaluated#the#esthetic#impact#of#extraction#orthodontic#treatment.##The#extraction#group,#where#4#first#premolars#were#removed,#retracted#the#lower#incisors#on#average#2#mm#with#the#lower#lip#following#1.2#mm#when#compared#to#the#nonextraction#group.#Not#only#did#premolar#extraction#not#flatten#the#profile#enough#to#negatively#effect#esthetics,#but#both#groups#were#happy#with#their#appearance.##As#for#the#upper#incisors,#when#retracted#by#5mm,#there#is#on#average#a#negligible#1.4#mm#posterior#movement#of#the#upper#lip.27,34#At#the#end#of#treatment#those#patients#treated#with#extractions#had#slightly#more#prominent#lips#compared#to#those#treated#nonextraction#due#to#maintenance#of#pre]treatment#differences#between#groups.35.#Further#studies36#using#the#same#population#supported#that#extraction#treatment#does#not#flatten#the#profile#excessively.#A#more#recent#article37#by#Bowman#and#Johnson#looked#at#the#profiles#of#70#extraction#and#50#nonextraction#patients#evaluated#by#58#laypersons#and#42#dentists,#and#found#that#extraction#treatment#improved#facial#esthetics#for#those#presenting#with#crowding#and#protrusion.#Moreover,#the#risks#of#nonextraction#treatment#possibly#resulting#in#instability,#procumbency,#and#inefficiency#should#warrant#extraction#therapy#to#be#a#consideration#after#careful#diagnosis#and#evidence#based#treatment#plans.37#The#focus#should#not#be#whether#extraction#treatment#“dish#in”#the#profile#or#not,#but#rather#identifying#which#patients#are#vulnerable#to#worsening#an#already#flat#profile#in#the#initial#treatment#planning#stage#for#they#may#need#surgical#treatment#options#in#addition#to#orthodontics#to#obtain#an#esthetic#profile.##Thankfully#continued#research#has#shown#that#when#applied#appropriately#extractions#have#a#positive#treatment#effect#and#continue#to#be#an#important#treatment#option#in#the#management#of#malocclusion.##More#recently#the#supposed#restrictive#effects#of#dental#extractions#in#orthodontics#has#shifted#to#focus#on#the#airway#and#the#health#implications#of#obstructive#sleep#apnea.#This#alleged#association#stands#on#two#assumptions;#the#first#being#that#when#permanent#teeth#are#removed#and#the#remaining#teeth#are#retracted,#there#is#a#reduced#volume#for#the#   6 tongue#and#airway.##And#two,#that#this#decrease#in#airway#volume#increases#a#patient’s#risk#of#obstructive#sleep#apnea.#The#primary#intention#of#this#thesis#is#to#examine#the#former#assumption,#with#the#later#beyond#the#scope#of#the#current#study.#However#as#will#be#discussed,#further#research#is#needed#to#examine#the#relationship#between#orthodontic#treatment#and#health#of#the#airway.##1.2 Sleep!Apnea!in!Adults!# Sleep#Apnea#is#a#life#threatening#disorder#that#is#categorized#into#Central#Sleep#Apnea#(CSA)#and#Obstructive#Sleep#Apnea#(OSA).#CSA#occurs#when#the#brain#temporarily#stops#sending#signals#to#the#muscles#that#control#breathing,#leading#to#repeated#cessation#episodes#of#breathing#during#sleep38,39.#OSA#is#a#condition#characterized#by#repetitive#partial#or#complete#airway#collapse#resulting#in#abnormal#sleep#and#changes#in#ventilatory#parameters39.##An#apnea#in#adults#is#characterized#by#complete#cessation#of#airflow#for#at#least#10#seconds,#and#a#hypopnea#is#defined#as#a#decrease#in#airflow#by#50#percent#for#10#seconds#or#a#decrease#by#30#percent#if#there#is#an#associated#decrease#in#the#oxygen#saturation#or#an#arousal#from#sleep.40#The#apnea]hypopnea#index#(AHI)#is#the#combined#total#number#of#apneas#and#hypopneas#per#hour#of#sleep.#39,41#Obstructive#Sleep#Apnea#syndrome#(OSAS)#in#adults#is#diagnosed#when#the#AHI#is#5#or#higher#plus#symptoms#such#as#fatigue,#excessive#daytime#sleepiness,#non]refreshing#sleep,#awaking#with#gasping#or#choking,#and#bed#partner#reports#of#loud#snoring#or#breathing#pauses#during#a#patients#sleep#are#present42,43.#An#index#of#5#to#15#is#considered#mild#OSA,#between#15]30#defines#moderate#OSA,#whereas#30#events#per#hour#or#more#is#defined#as#severe#OSA.44###1.2.1 Epidemiology!of!OSAS!# Individuals#with#OSAS#are#most#commonly#middle]aged#overweight#men,#though#overall#OSAS#is#observed#in#4%#of#men#and#2%#of#women#ages#30]60#years#old45,46,#but#   7 many#cases#may#be#undiagnosed38,39.#However,#OSA#is#often#asymptomatic#and#the#prevalence#of#patients#with#OSA,#who#do#not#present#with#a#clinical#syndrome,#might#be#as#high#as#30%#in#the#middle]aged#population39,41.### Apneas#result#in#trigger#signals#from#the#brain#to#disrupt#and#awaken#sleep#patterns#to#restart#the#breathing#process41,45,46.#An#underlying#abnormality#of#neurological#control#of#the#upper#airway#musculature#or#ventilation#during#sleep#may#be#present38,39,42,47.#During#sleep,#this#repetitive#cycle#occurs#frequently#and#results#in#sleep#deprivation#and#health#problems#such#as#hypertension42,43,45,48,#cardiovascular#disease38,47,49,50,#coronary#artery#disease45,46,51,52,#stroke38,39,48,53,#sudden#death39,41,50,54,#daytime#sleepiness42,43,46,51,#deep#vein#thrombosis38,49,53,55,#motor#vehicle#accidents41,45,46,54,56,#and#a#decrease#in#quality#of#life41,46.#In#advanced#cases,#OSAS#are#associated#with#pulmonary#hypertension55,57,#corpulmonale48,56,#chronic#carbon#dioxide#retention,#polycythemia41,58,59#and#is#associated#with#metabolic#syndromes57,60.#Consequently,#OSAS#is#a#debilitating#and#life]threatening#condition.## #1.2.2 Pathophysiology!# Anatomic#abnormalities#can#contribute#to#pharyngeal#airway#collapse#in#normal#body#weight#individuals.#The#pharynx#is#a#fibromuscular,#funnel]shaped#tube#that#is#approximately#15cm#long#and#acts#as#a#conduit#for#air#and#food61,62.#Moreover,#the#pharynx#lays#dorsal#to#the#oral#and#nasal#cavities,#and#superior#to#the#larynx,#esophagus#and#trachea.#62]66.#The#nasopharynx,#oropharynx,#and#hypopharynx#make#up#the#pharynx#as#seen#in#(Figure#1.1).#Posterior#to#the#nasal#cavity#and#superior#to#the#hard#palate#lies#the#nasopharynx,#and#the#oropharynx#is#posterior#to#the#oral#cavity.#62,67,68#The#hypopharynx#is#posterior#to#the#larynx,#from#the#hyoid#bone#and#narrowest#at#its#inferior#end,#where#it#is#continuous#with#the#esophagus#posteriorly.61,62,69###The#constriction#of#the#airway#associated#with#OSA#occurs#mostly#in#the#retropalatal#and#retroglossal#regions#of#the#oropharynx#as#seen#on#lateral#cephalograms,#magnetic#resonance#imaging#(MRI),#and#cone#beam#computed#tomography#(CBCT)63]66,70,71.##This#   8 region#is#specifically#vulnerable#in#patients#with#OSA#compared#to#normal#control#subjects#due#to#the#lower#collapsing#pressures#and#smaller#airway#size#as#seen#in#patients#under#general#anesthesia#with#complete#muscle#paralysis.69,72]74.###Craniofacial#characteristics#associated#with#OSA#revealed#by#radiography#include#a#retruded#maxilla46,70,71,73#and#mandible71,75]79#relative#to#the#cranial#base,#short#anterior#cranial#bases72]74,#steep#mandibular#planes46,71,73,#large#gonial#angle#71,78,80,81,#small#upper#to#lower#facial#height#ratios73,80,#high#upper#and#lower#facial#heights#71,74,82,#and#inferior#counterclockwise#displacement#of#the#hyoid#bone#78,80,81,83#can#lead#to#the#development#of#a#compromised#airway#space.###The#soft#tissue#also#plays#a#significant#role#in#upper#airway#risk#factors#for#OSA.#Using#lateral#and#frontal#cephalometry,#investigations#80,84,85#looked#at#the#narrowed#posterior#airway#space#and#found#that#airway#compromise#was#due#to#the#thickening#of#the#velum#and#velopharyngeal#lumen.##Adding#to#the#airway#insult#in#OSA#patients#were#the#longer#soft#palate,#the#increased#tongue#size,#and#the#lateral#pharyngeal#wall#size.67,68,71,74]79,82,84#Other#risk#factors#for#adults#include#excess#weight#or#high#Body#Mass#Index#(BMI),#large#neck#circumference,#narrow#airway,#males,#age,#family#history,#race,#use#of#alcohol,#sedatives,#smoking,#and#nasal#congestion#48,86.##However,#women#tend#to#have#a#lower#prevalence#of#OSA,#suggesting#that#other#factors#such#as#neuromuscular#pathways#may#play#a#role#in#protecting#the#airway83,85.#### Neurologic#control#of#the#upper#airway#plays#an#interrelated#role#in#OSA.#The#normal#physiological#process#includes#signals#from#the#medulla#to#the#respiratory#centers,#which#through#the#inspiratory#phase#activates#the#genioglossus,#preparing#the#upper#airway#for#the#development#of#negative#intrapharyngeal#pressure,#and#thus#patency#is#maintained#by#the#pharyngeal#abductor#and#dilator#muscles.84,85#After#the#central#nervous#system#(CNS)#signals#the#upper#airway#and#diaphragm,#the#muscles#become#hypotonic,#and#the#pharyngeal#size#and#tissue#determine#the#airway#stability#during#sleep.71,84,87#If#the#negative#intraluminal#pressure#created#during#inspiration#overcomes#the#soft#tissues#   9 support#in#the#airway,#airway#obstruction#occurs85,88.#Hence#the#central#nervous#system#responds#with#hypertonicity#of#the#muscles#to#allow#patency#of#the#airway#to#resume#breathing#activity#leading#to#a#lighter#level#of#sleep85,89.###1.3 CBCT!and!ThreeMDimensional!Airway!Analysis!# ##Two]dimensional#radiographic#imaging#techniques#have#been#utilized#in#orthodontics#for#decades#as#a#diagnostic#adjunct#to#the#clinical#assessment,#however,#with#the#introduction#of#three]dimensional#(3D)#radiology,#the#benefits#to#diagnosis#and#treatment#planning#have#the#potential#to#be#greatly#enhanced.##Previous#techniques#looking#at#the#upper#airway#volume#have#been#applied#with#acoustic#reflection,#fluoroscopy,#nasopharyngoscopy#68,#computed#tomography#scans#(CT),#magnetic#resonance#imaging#(MRI)90,91,#and#now#with#cone#beam#computed#tomography#(CBCT)92.### Since#1998,#Cone#beam#computed#tomography#(CBCT)#has#provided#image#volumes#of#the#maxillofacial#region#and#can#be#applied#as#a#valuable#tool#in#clinical#dentistry.93#Advantages#of#CBCT#versus#other#imaging#modalities#include#three]dimensional#images,#ability#to#generate#2]dimensional#images#from#3D#data,#isotropic#voxel#size,#lower#radiation#dose#than#a#medical#computed#tomography#(MCT),#less#disturbance#from#metal#artifacts,#reduced#cost#relative#to#MCT,#easy#accessibility,#in]office#imaging,#easy#handling,#smaller#footprint,#digital#imaging#and#communications#in#medicine#(DICOM)#compatible,#user]friendly,#and#energy#saving#versus#MCT.94#On#the#other#hand,#limitations#include#low#contrast#range,#limited#detector#size,#limited#field#of#view,#limited#inner#soft#tissue#information,#increased#noise#and#scatter#radiation#and#loss#of#contrast#resolution,#shortened#images#due#to#region#of#interest,#and#inability#to#be#used#for#estimation#of#Hounsfield#units#(HU).94#Relative#to#standard#2D#radiographic#imaging#in#orthodontics,#CBCT#also#exposes#the#patient#to#increased#levels#of#radiation.##Dosimetry#of#a#cone]beam#computed#tomography#machine#compared#with#a#digital#x]ray#machine#in#orthodontic#imaging#was#evaluated#and#used#the#same#scan#protocols#as#this#study#(Table#1.1)95#To#   10 date,#imaging#techniques#except#with#the#MRI,#do#not#account#for#imaging#in#the#supine#position#which#could#have#confounding#effects#on#airway#analysis.## !   11 Table!1.1!Scan!protocols!and!settings!used!for!CBCT!scans!with!next!generation!iMCAT!machine!Scan#protocol FOV#(cm) Voxel#size#(mm) Scan#time#(s) Tube#Voltage#(kV) Tube#current#(mAs) 0.3#voxel#portrait#CBCT 17 0.3 8.9 120 18.54 0.3#voxel#HR#portrait#CBCT 17 0.3#enhanced 17.8 120 37.1 0.4#voxel#portrait#CBCT 17 0.4 8.9 120 18.54 0.4#voxel#HR#portrait#CBCT 17 0.4#enhanced 17.8 120 37.1 FOV,#Field#of#view;#HR,#high#resolution### The#generation#of#CBCT#images#involves#a#rotating#gantry#with#a#fixed#x]ray#source#and#detector#that#produces#a#cylindrical#fan]shaped#or#cone]shaped#source#of#ionizing#radiation#that#is#directed#through#the#center#of#the#target#onto#an#area#x]ray#detector#on#the#opposite#side.96##The#source#and#detector#are#meanwhile#rotating#around#the#center#of#the#target#creating#multiple#sequential#planar#projection#images#of#the#field#of#view#(FOV).96##As#the#CBCT#exposure#incorporates#the#entire#FOV,#only#one#rotational#sequence#of#the#gantry#is#necessary#to#acquire#adequate#data#for#image#reconstruction.96##In#contrast,#a#traditional#medical#CT,#which#uses#a#fan]shaped#x]ray#beam#in#a#helical#progression#to#produce#image#slices#of#the#FOV#and#then#sandwiches#the#slices#to#produce#a#3D#image.96#The#scanning#software#collects#the#multiple#raw#images#and#reconstructs#them#into#digital#volumes#units#called#voxels.#The#three]dimensional#voxels#of#anatomical#data#are#then#analyzed#and#displayed#by#the#software.93#Better#spatial#resolution#is#obtained#when#scanning#uses#high#settings#(small#voxel#size,#longer#scan#time).97## # #Radiation#dosimetry#is#a#concern#when#considering#a#new#x]ray#technology.#According#to#the#International#Commission#on#Radiological#Protection#2007#estimates,#a#   12 panoramic#with#24.3#μSv#and#cephalometric#radiograph#with#5.6#μSv#are#the#effective#doses#for#common#radiographs#taken#in#orthodontics.98#CBCT#has#an#effective#dose#for#a#small#field#of#view#(FOV)#of#48]652#μSv#and#a#large#FOV#of#68]1073#μSv,#relative#to#a#CT#scan#which#has#a#dosage#of#534#μSv99#to#2100#μSv.100#The#dosages#vary#substantially#across#different#CBCT#devices#and#is#much#higher#than#panoramic#imaging,#but#significantly#less#than#conventional#CT.101###However,#efforts#to#reduce#radiation#dosage#with#CBCT#technology#are#evident#such#as#changing#the#rotational#angle#to#180°#instead#of#360°#102,#maximizing#the#dose#reduction#while#minimizing#the#image#quality#loss103,#and#narrow#collimation104.#Scarfe#et#al.96#suggests#that#future#enhancements#in#CBCT#technology#may#include#reducing#scan#time,#improving#image#quality,#minimizing#patient#dose#with#high#resolution,#and#variability#for#field#of#view.### The#accuracy#and#reliability#of#CBCT#for#orthodontic#diagnosis#has#been#previously#validated.#There#are#no#significant#differences#between#craniometric#measurements#made#on#CBCT#scans#and#those#made#on#skulls105,106,#or#between#similar#measurements#made#on#lateral#cephalometric##radiographs#and#CBCT.#107,108#Also,#measurements#were#found#to#be#reliable#and#accurate#when#the#skull#was#measured#using#different#orientations109,#and#when#measuring#the#airway#volume.110#Recently#CBCT#technology#has#been#applied#to#evaluation#of#the#upper#airway,#and#has#been#validated#in#previous#studies.#66,111]114#CBCT#has#been#used#reliably#to#aid#in#maxillomandibular#surgeries115,116,#and#comparing#the#shape#of#the#airway#among#subjects#with#the#use#of#landmarks#and#3D#superimposition.117###More#recently,#Mattos#et#al.118#looked#at#the#intraexaminer#and#interexaminer#reliabilities#of#the#upper#airway#linear,#area,#and#volumetric#measurements#in#CBCT#scans.#Using#an#undergraduate#student,#an#orthodontist,#and#a#dental#radiologist,#they#found#that#airway#assessments#have#reliable#anterior#posterior#linear#measurements;#cross#sectional#areas#at#the#levels#of#the#palatal#plane,#soft#palate,#and#tongue;#and#sagittal#area#and#   13 volume.#However,#unreliable#measurements#found#were#linear#width,#cross#sectional#area#at#the#level#of#the#vallecula,#and#minimum#axial#area.#### The#upper#airway#volume#assessment#depends#on#segmentation#accuracy,#image#quality#and#threshold#interval#selection.##Segmentation#of#the#airway#within#a#CBCT#scan#depends#on#setting#the#threshold#value#before#imaging.##Using#Dolphin#Imaging#software,#the#program#used#in#this#thesis#project,#a#number#of#studies110,119]123#have#looked#at#different#threshold#values#that#range#from#25#to#75#units#using#a#variety#of#CBCT#scanners#and#settings#(table#1.2).##Table!1.2!Threshold!value!Value Author Year  CBCT Seconds KVP (V) Current (mA) 73 Alves 2012 Icat 40 120 5 25 Alves 2011 Icat 20 120 5 51  El 2010 Hitachi N/A 120 2 52 Iannetti 2011 N/A N/A N/A N/A N/A Smith 2010 Hitachi N/A 120 2 N/A Valiathan 2012 Toshiba N/A 120 20 60/50 (2)* Chang 2013 Scanora 20 125 N/A 65 Tam 2014 Icat 8.9-17.8 120 5 *Only#2#cases#had#a#threshold#segmentation#value#of#50#### !   14 1.4 Orthodontic!Effects!On!Airway!# Initial#investigations#on#the#effects#of#orthodontic#treatment#on#the#pharyngeal#airway#space#have#used#lateral#cephalometry.#Wang#et#al63#examined#44#adults#with#Class#I#bimaxillary#protrusion#treated#with#4#bicuspid#extractions#and#found#that#the#pharyngeal#airway#size#narrowed#after#orthodontic#treatment.#Although#the#study#had#an#adequate#sample#size#and#low#systematic#error,#the#measurements#were#based#on#2]dimensional#lateral#cephalometric#x]rays.##Similarly#Germec]cakan#et#al65#looked#at#39#adults#with#lateral#cephalograms#and#found#that#extraction#of#the#4#first#bicuspids#had#a#reducing#effect#on#the#middle#and#inferior#airway#space.#In#contrast,#Maaitah#et#al124#looked#at#40#bimaxillary#adults#with#lateral#cephalometry#and#concluded#that#extraction#of#the#first#premolars#for#the#treatment#of#bimaxillary#proclination#does#not#affect#the#upper#airway#dimensions#despite#the#significant#reduction#in#tongue#length#and#arch#dimensions.###Table!1.3!Previous!investigations!on!orthodontic!treatment!effects!on!airway!Author# Year# Sample# Type# Findings#Wang# 2012# 44 lateral cephs# 4 bicuspid extraction# Airway size narrowed#Germec-cakan# 2011# 39 lateral cephs# 4 bicuspid extraction# Airway decrease in non-extraction group, and increase in extraction group Maaitah# 2012# 40 lateral cephs# 4 bicuspid extraction# No effect on upper airway size#Chen# 2012# 30 CT scans# 4 bicuspid extraction# Narrowing of upper airway#Stefanovic# 2012# 31 CBCT# 4 bicuspid extraction# No effects on airway### With#CBCT,#our#understanding#of#airway#and#craniofacial#morphology#are#expanded#to#allow#a#three]dimensional#assessment#of#anatomical#relationships.##Ogawa#et#al92#evaluated#10#patients#with#CBCT#and#found#that#patients#with#OSA#had#a#concave#or#elliptic#shaped#airway,#and#the#non]OSA#group#had#a#concave,#round#or#square#shaped#airway.#A#later#study#that#used#a#larger#sample#size#and#CBCT#confirmed#that#an#elliptical#shaped#airway#had#a#increased#tendency#toward#obstruction#and#that#the#presence#of#OSA#was#   15 associated#with#an#increase#in#airway#length.125#In#another#study111#looking#at#the#nasopharyngeal#airway,#it#was#found#that#the#inferior#turbinates#may#cause#severe#airway#restrictions.##Others#have#commented#on#the#contributing#effect#of#a#retrognathic#mandibular#position#to#narrowing#of#the#oropharyngeal#airway#volume#compared#with#class#I#and#class#III#subjects.77##Applications#for#CBCT#in#research#were#used#to#assess#the#upper#airway#and#its#relationship#to#surgery#and#orthodontic#treatment.##CBCT#has#been#used#as#an#effective#tool#to#evaluate#outcomes#after#surgery#such#as#the#affects#of#irreversible#narrowing#of#the#pharyngeal#airway#after#mandibular#setback#surgery.116#Valiathan#et#al.61#used#CBCT#to#analyze#20#patients#with#4#bicuspid#orthodontic#extraction#and#20#nonextraction#cases#matched#for#age,#gender,#ethnicity,#height#weight,#body#mass#index,#to#assess#the#oropharyngeal#volume.# The#mean#extraction#group#ages#were#13.8#±#1.3#years#for#boys#and#13.5#±#1.6#years#for#girls.#The#mean#ages#for#the#non]extraction#group#were#13.8#±#1.2#years#for#boys#and#13.5#±#1.6#years#for#girls.##The#length#of#treatment#for#extraction#and#non]extraction#orthodontic#treatment#was#30.9#±#3.9#months#and#25.4#±#4.4#months#respectively.##What#they#found#was#no#difference#in#the#oropharyngeal#airway#volume#changes#between#the#two#groups#despite#changes#in#incisor#angulations#and#positions.61#However,#the#results#of#this#study#may#have#been#influenced#by#an#increase#in#airway#volume#because#of#the#growth#of#the#patient#pool#and#limited#sample#size.# # A#study#by#Shannon#et#al.126#also#looked#at#adolescents#to#investigate#the#relationship#between#orthodontic#extraction#treatment#and#the#oropharyngeal#airway#volume#using#CBCT#images.##With#a#sample#size#of#27#four#premolar#extraction#and#61#nonextraction#patients,#they#found#that#there#were#net#increases#in#the#oropharyngeal#widths,#cross]sectional#areas,#and#oropharyngeal#volumes#for#both#treatment#groups.#Hence,#no#findings#of#airway#constriction#between#extraction#and#none]extraction#treatment#were#present,#and#it#was#concluded#that#reducing#dental#arch#perimeter#has#no#effect#on#oropharyngeal#size.#   16 #A#similar#study#by#Stefanovic#et#al.127#also#used#CBCT#to#analyze#the#pharyngeal#airway#between#extraction#of#four#first#premolars#and#non]extraction#orthodontic#treatment.##With#31#subjects#(15#males#and#16#females)#in#the#adolescent#age,#they#found#no#statistically#significant#differences#in#the#pharyngeal#airway#between#extraction#and#non]extraction#groups#either#at#the#beginning#or#end#of#treatment.#Consequently,#they#found#no#affects#on#the#pharyngeal#airway#between#extraction#and#non]extraction#treatment.###Conversely,#a#study#by#Chen#et#al128#investigated#the#effect#of#large#incisor#retraction#on#the#upper#airway#in#adult#patients#using#multi]slice#computed#tomography.#With#a#sample#size#of#30#bimaxillary#protrusive#patients#with#4#first#premolars#extracted#followed#by#space#closure#with#maximum#anchorage,#they#found#a#decrease#in#mean#cross]sectional#areas#of#the#palatopharynx#(21%),#glossopharynx#(25%),#and#hypopharynx#(38%),#but#no#difference#in#the#nasopharynx.#Although#there#were#no#investigations#with#volumetric#measurements,#they#concluded#that#the#narrowing#of#the#upper#airway#was#present#with#extraction#orthodontics.#!! !   17 Statement!of!the!Problem!! 1. OSA#is#a#common#and#serious#medical#condition.#2. A#narrow#airway#is#a#general#risk#factor#for#OSA#3. The#extent#to#which#orthodontic#treatment#with#dental#extractions#may#reduce#the#volume#of#the#upper#airway#remains#unclear.### #   18 1.5 Objectives!# The#aims#of#this#present#study#were#to#describe#the#linear#and#volumetric#changes#of#the#upper#airway#using#three]dimensional#data#in#adults#who#have#undergone#extraction#therapy#as#compared#to#those#who#have#had#non]extraction#orthodontic#therapy.#A#second#aim#is#to#investigate#how#the#airway#and#airway#change#is#affected#by#different#baseline#craniofacial#morphologies.####1.5.1 Null!Hypothesis!# There#will#be#no#difference#in#effects#on#the#upper#airway#volume#between#orthodontic#treatment#with#and#without#the#extraction#of#teeth.##1.5.2 Study!Hypothesis!# Our#hypothesis#states#that#there#is#a#reduction#in#upper#airway#volume#in#adults#as#a#result#of#orthodontic#treatment#with#dental#extractions#as#compared#to#non]extraction#orthodontic#treatment.!!   19 Figure!1.1!Anatomy!of!the!airway!divided!into!the!nasopharynx,!oropharynx,!and!hypopharynx.! !The oropharynx is divided into the retropalatal and retroglossal regions: OP-RP is the retropalatal region of the oropharynx. OP-RG is the retroglossal region of the oropharynx. HP is the hypopharynx, and NP is the nasopharynx.    20 Chapter!!2: Methodology!#2.1 Demographic!## This#retrospective#study#complied#with#the#Health#Information#Protection#Act#(HIPA),#and#was#approved#by#the#Research#Ethics#Board#at#the#University#of#British#Columbia#(H12]00951)#on#June#4th#2012.##All#patient#DICOM#and#demographic#data#was#obtained#in#de]identified#form#from#the#University#of#Minnesota#School#of#Dentistry,#Division#of#Orthodontics#(UMN)#in#Minneapolis,#Minnesota.### Initial#compilation#of#the#study#data#consisted#of#application#of#screening#criteria#(Table#2.1)#to#all#patients#treated#between#September#2008#to#June#2012#at#the#UMN#Division#of#Orthodontics.#All#patient#identifiers#were#removed,#and#data#collected#included#gender,#amount#of#crowding#in#the#maxillary#and#mandibular#dentition,#amount#of#overbite#and#overjet,#start#and#end#of#orthodontic#treatment,#age,#number#of#teeth#removed,#orthodontic#appliances#used#(such#as#fixed#egdewise#appliances,#aligners,#inter]arch#elastics,#fixed#class#2#correctors,#transpalatal#arch#appliance,#headgear#or#temporary#anchorage#devices),#presence#or#absence#of#orthognathic#treatment#or#craniofacial#syndrome,#history#of#cleft#lip#and#palate,#extraction#or#non]extractions,#complete#CBCT#pre#and#post#records,#previous#orthodontic#treatment,#previous#airway#surgery.##### #   21 Table!2.1!Screening!Form!for!Eligibility!Criteria!ID#Code:### Age#at#start#of#treatment:###Sex:#M/F# Complete#pre#and#post#treatment#CBCT#scans:#Y/N#Orthognathic#Treatment:#Y/#N*# Previous#Orthodntic#Treatment#Y/N#Craniofacial#Syndrome:#Y#/N# Previous#Airway#Surgery#Y/N#History#of#Cleft#lip/palate:#Y/N# Other/Details:#Extractions#Y/N# Teeth#removed:###Upper#crowding:### Lower#crowding:###Overbite:### Overjet:###Date#of#treatment#start:#MM/DD/YYYY# #Orthodontic#Appliances#Used:# Fixed#edgewise#Appliances## Invisalign## Inter]arch#Elastics#–#Class#I/II/III## Forsus## Transpalatal#Arch## Headgear## TAD#(mini]implant)#Date#braces#removed:#MM/DD/YYYY# #*#Y/N#=#Yes/No### !   22 Table!2.2!Inclusion!and!Exclusion!Criteria!Inclusion#Criteria#########Ages#18]65#years#old#########Pre#and#post]treatment#CBCT#scans#########ANB#>0º#Exclusion#Criteria#########History#or#airway#surgery#########Previous#orthodontic#treatment#prior#to#initial#records#########Craniofacial#abnormalities#########History#of#Cleft#lip#and#Palate#########Compromised#Periodontal#Status#########Missing#Teeth#(excluding#3rd#molars)#########Developmental#defects.#     23 Within#this#time#period#202#patients#were#adults#and#99#patients#met#the#initial#eligibility#criteria.#(Table#2.2)#The#inclusion#criteria#included#adults#ages#18]65#years#old,#the#presence#of#both#pre#and#post]treatment#CBCT#scans,#and#patients#with#an#ANB#≥0°.##The#following#factors#were#part#of#the#exclusion#criteria:#history#of#airway#surgery,#previous#orthodontic#treatment#prior#to#initial#records,#craniofacial#abnormalities,#history#of#cleft#lip#and#palate,#compromised#periodontal#status,#missing#teeth#(excluding#3rd#molars)#and#developmental#defects.##After#further#initial#cephalometric#and#volumetric#analysis,#an#additional#25#cases#were#excluded#from#final#study#including#9#cases#with#an#ANB#<#0°,#3#cases#with#soft#tissue#occlusion#of#the#airway#and#13#cases#had#missing#teeth.#This#resulted#in#74#patients#meeting#the#eligibility#criteria.#(Figure#2.1)####!Figure!2.1!Flow!Diagram!of!Sample!Selection!###!# !Final#sample:#74#with#no#missing#teeth#87#with#patent#airways#90#ANB#>#0°#99#met#initial#eligibility#criteria#202#adults#and#1478#adolescents#1680#patients#   24 Airway#structures#were#studied#in#74#healthy#patients#treated#orthodontically#at#the#UMN#Division#of#Orthodontics.#The#non]extraction#group#was#composed#of#17#males#and#31#females#who#were#treated#orthodontically#without#the#removal#of#any#teeth,#excluding#third#molars.##The#extraction#group#consisted#of#8#males#and#18#females#who#each#had#teeth#extracted#as#part#of#their#orthodontic#treatment.###2.2 Confounding Factors To#investigate#possible#confounding#factors,#the#sample#was#analyzed#for#airway#volume#differences#based#on#gender,#skeletal#classification#(Class#I#with#an#ANB#≤#4°#and#Class#II#patients#with#an#ANB#≥#4°),#mandibular#plane#angle#(SN]MP#of#low#≤27°,#normal#>27°#and#<38°,#and#high#angle#patients#≥38°),#and#CBCT#scan#settings.###Possible#influences#from#gender#that#could#contribute#to#airway#change#differences#stems#from#the#fact#that#males#are#larger#than#females,#and#hence#could#result#in#a#larger#airway#change.129##With#mandibular#plane#angle,#high#angle#patients#tend#to#have#smaller#airways#due#to#the#mandible#being#rotated#down#and#back,#and#hence#could#influence#the#change#in#airways.130#Similarly,#Class#II#patients#(ANB#>#4°)#also#have#smaller#airways#compared#to#Class#I#skeletal#pattern#(ANB#≤4°).#77#Different#scan#setting#may#affect#the#grey#levels#that#the#software#reads#as#air,#hard#and#soft#tissue.##2.2.1 Influence!of!CBCT!Scan!Settings! Due#to#changes#in#the#imaging#protocol#at#the#UMN#Division#of#Orthodontics#that#occurred#from#2008]2012,#the#majority#of#the#sample#had#their#initial#and#final#CBCT#scans#taken#with#different#scan#settings#(Table#1.1).#The#segmentation#of#airway#volume#with#Dolphin#Imaging#software#is#performed#qualitatively#based#on#a#user]defined#segmentation#value.#As#the#scan#settings#may#influence#the#segmentation#value#selected#due#to#qualitative#differences#in#the#image,#the#CBCT#scan#settings#were#considered#to#be#a#possible#confounding#factor#in#our#analysis#of#the#airway.#   25 # To#determine#the#effect#of#the#threshold#value#on#the#upper#airway#volume,#the#airways#of#the#20#patients#that#had#pre#and#post#treatment#scans#taken#with#identical#settings#(0.3mm#voxel#size,#120#kV,#18.54#mA#tube#current,#and#a#scan#time#of#8.9#seconds)#were#analyzed#in#two#differing#ways.#For#the#first#method,#the#airway#was#measured#with#a#dynamic#segmentation#threshold#value#derived#from#a#free#hand#determination#of#the#airway#based#on#its#qualitative#appearance#for#each#DICOM#file.#In#the#second#method,#all#scans#were#analyzed#using#a#segmentation#value#of#65#after#taken#into#consideration#previous#studies61,110,119]121,123,131.#This#value#routinely#demarcated#the#airway#clearly#without#any#artifacts,#for#the#largest#number#of#patients.#Differences#between#the#two#methods#for#both#absolute#airway#volumes#in#the#initial#scans,#as#well#as#for#volumetric#changes#due#to#treatment#were#then#determined.#! !   26 2.3 Data!Collection!and!Measurements! The#research#protocol#for#this#study#was#developed#to#measure#the#structural#responses#of#the#hard#and#soft#tissues#surrounding#the#airway#during#orthodontic#treatment.##Scans#were#taken#using#an#i]CAT#Next#Generation#cone]beam#computed#tomography#unit#(Imaging#Sciences#International,#Hatfield,#PA).#The#unit#was#used#at#various#scan#settings#for#orthodontic#imaging#(Table#1.1).##CBCT#and#lateral#cephalometric#digital#radiographic#imaging#with#i]CAT#3D#scans#were#viewed#on#the#same#monitor#(21]inch#monitor;#Dell,#Round#Rock,#Tx;#1680#x#1050#pixels).##All#linear,#angular,#cross]sectional#areas,#and#volume#measurements#were#determined#using#the#Dolphin#Imaging#®#11.5#(Dolphin#Imaging#&#Management#Solutions,#Chatsworth,#CA)#for#this#study.# 2.3.1 Orientation! The#3D#images#were#oriented#with#the#Dolphin#Imaging#®#11.5#(Dolphin#Imaging#&#Management#Solutions,#Chatsworth,#CA)#software#prior#to#generation#of#lateral#cephalometric#and#airway#images.##The#midsagittal#plane#was#determined#by#skeletal#midline#of#the#face#using#a#line#connecting#the#Incisive#foramen#to#Opisthion#(Figure#2.4).##The#axial#plane#was#adjusted#with#a#line#connecting#the#inferior#border#of#the#left#and#right#orbits#parallel#to#the#horizontal#grid#(Figure#2.3).##The#coronal#plane#was#adjusted#from#the#Frankfort#horizontal#plane#(right#porion#to#right#orbitale)#perpendicular#to#a#line#passing#through#the#level#of#the#furcation#point#of#the#right#maxillary#first#molar#(Figure#2.2).#### !   27 Table!2.3!Orientation!hard!tissue!landmarks!Opisthion# On#the#occipital#bone,#the#midpoint#on#the#posterior#margin#of#the#foramen#magnum!Incisive#Foramen# Opening#in#the#hard#palate#immediately#behind#the#maxillary#incisor#teeth!Porion# Point#on#the#cranium#located#at#the#upper#margin#of#each#ear#canal#(external#auditory#meatus)!Orbitale# A#point#midway#between#the#lowest#point#on#the#inferior#margin#of#the#two#orbits.!!!Figure!2.2!Orientation!of!the!coronal!plane!using!the!Frankfort!Horizontal!Plane!(porion!to!orbitale).!!! !   28 Figure!2.3!Orientation!of!the!axial!plane!using!the!lower!border!of!the!orbit!landmarks.!! !   29 Figure!2.4!Orientation!of!the!midsagital!plane!using!the!upper!incisive!foramen!to!opisthion.! !# !   30 2.3.2 Cephalometric!Measurements! 2.3.2.1 Linear Measurements  # Cephalometric#analysis#according#to#the#American#Board#of#Orthodontics#was#used#to#measure#the#angular#and#linear#skeletal#measurements#(Figure#2.5,#Table#2.4]2.5).##Cephalometric#landmarks#and#planes#used#in#the#study#are#the#following:#S,#Sella;#N,#nasion;#ANS,#anterior#nasal#spine;#PNS,#posterior#nasal#spine;#Me,#menton;#Go,#gonion;#palatal-plane,#the#horizontal#line#through#ANS#and#PNS;#and#mandibular-plane,#the#horizontal#line#through#Me#and#Go.##A#total#of#13#landmarks#and#planes#were#identified#on#each#cephalometric#image.##! !   31 Figure!2.5!Cephalometric!landmarks!and!planes!     32 Table!2.4!Cephalometric!landmarks!and!linear!measurements.!!A# Point#A#(Subspinale):#The#most#posterior#point#on#the#exterior#ventral#curve#of#the#maxilla#between#the#anterior#nasal#spine#and#the#supradentale!B# Point#B#(Supramentale):#the#most#posterior#point#on#the#bony#curvature#of#the#mandible#between#Infradentale#and#Pogonion!FH# Frankfort#Horizontal:#a#horizontal#plane#drawn#from#porion#to#orbitale,#with#patient#in#natural#head#position!Gn# Gnathion#(anatomic):#the#most#anterior#inferior#point#of#the#mandibular#symphysis!L6# L6#mesial:#the#most#mesial#point#on#the#height#of#contour#of#lower#first#molar!Me# Menton:#the#most#inferior#point#on#the#symphysis#of#the#mandible#!N# Nasion:#the#anterior#point#of#the#intersection#between#the#nasal#and#frontal#bones!Or# Orbitale:#the#most#inferior#point#on#the#lower#margin#of#the#bony#orbit!Pg# Pogonion:#the#most#anterior#point#on#the#anterior#contour#of#the#bony#chin#below#B#point#and#above#Gnathion.!PNS# Posterior#Nasal#Spine:#the#most#posterior#point#at#the#midsagittal#plane#on#the#bony#hard#palate.!Po# Porion:#the#midpoint#on#the#superior#aspect#of#the#rim#of#the#external#auditory#meatus!S# Sella#turcica:#the#center#of#the#hypophyseal#fossa,#determined#by#inspection!U6# U6#mesial:#the#most#mesial#point#on#the#upper#first#molar! 2.3.2.2 Angular Measurements  A#total#of#4#angular#measurements#(Table#2.5)#were#obtained#from#each#cephalometric#image,#generated#by#Dolphin#Imaging#®#11.5#(Dolphin#Imaging#&#Management#Solutions,#Chatsworth,#CA).##Table!2.5!Angular!Measurements!ANB# The#difference#between#the#SNA#and#SNB#angles!SNA# Sella–Nasion–A#Point:#the#posterior]inferior#angle#formed#by#the#intersection#of#the#two#lines#formed#by#Sella–Nasion#and#Nasion–A#Point.!SNB# Sella–Nasion–B#Point:#the#posterior]inferior#angle#formed#by#the#intersection#of#the#two#lines#formed#by#Sella–Nasion#and#Nasion–B#Point.!SN]MP# Angle#formed#at#the#intersection#of#a#line#from#Sella#to#Nasion#and#a#line#from#Gonion#to#Gnathion.#!   33 #2.3.2.3 Volumetric Measurements ! Airway#volumetric#renderings#of#the#subjects’#CBCT#scans#were#generated#with#Dolphin#Imaging#®#11.5#(Dolphin#Imaging#&#Management#Solutions,#Chatsworth,#CA).#This#3]dimensional#imaging#software#functioned#by#detecting#large#differences#in#x]ray#attenuation#between#air#in#the#pharynx#and#the#high#water#content#of#the#surrounding#tissues,#resulting#in#a#visualization#of#the#airway#in#3#dimensions.##The#protocol#(table#2.7)#was#developed#to#measure#the#volume#and#minimum#axial#areas.##Airway#segmentation#threshold#values#were#adjusted#to#eliminate#imaging#artifacts#and#ranged#from#50]75.##The#airway#volume#was#then#calculated#in#cubic#millimeters#and#the#most#constricted#axial#area#of#the#airway#was#calculated#in#square#millimeters.### Volumetric#measurement#of#the#upper#airway#starts#with#segmentation,#which#is#the#isolation#of#a#region#for#visualization#and#analysis.##The#3D#imaging#software#differentiates#the#air#and#surrounding#soft#tissues#by#differences#in#density#values#or#grey#levels#of#these#structures.132##The#volumetric#calculation#involves#setting#up#the#borders#of#the#regions#in#the#sagittal,#coronal,#and#axial#slices,#and#selection#of#an#initial#threshold.#The#user#defines#the#threshold#filter#for#surface#rendering,#which#designates#a#color#and#opacity#to#the#grey#value#of#the#volume#image132.###The#anatomic#landmarks#(Table#2.6)#were#identified#and#airways#were#measured#in#the#Nasopharygeal#(NP),#Retropalatal#(RP),#Retroglossal#(RG),#and#Total#Airway#(TA)#regions#(Figures#2.6]2.10)#as#defined#in#a#previous#study#by#Arens#et#al.133.#The#posterior#superior#pharyngeal#wall#point#(SP)#is#defined#as#a#line#extending#posteriorly#from#the#palatal#plane#to#the#posterior#pharyngeal#wall.#The#palatal#plane#is#defined#as#a#line#connecting#the#anterior#nasal#spine#(ANS)#to#the#posterior#nasal#spine#(PNS).#The#posterior#middle#pharyngeal#wall#point#(MP)#is#defined#as#a#line#extending#from#the#posterior#inferior#tip#of#the#soft#palate#to#the#posterior#pharyngeal#wall#and#parallel#to#the#palatal#plane.#The#   34 posterior#inferior#pharyngeal#wall#point#(IP)#is#defined#as#a#line#extending#posteriorly#from#the#tip#of#the#epiglottis#to#the#posterior#pharyngeal#wall#and#parallel#to#the#palatal#plane.#The#tip#of#the#epiglottis#was#used#rather#than#the#base#because#visualization#of#the#base#was#not#available#for#several#of#the#scans.#! !   35 Table!2.6!Definitions!of!anatomic!areas!! Anterior!boundary! Posterior!boundary! Superior!boundary! Inferior!boundary!Nasopharynx! Line#extending#from#sella#(S)#to#the#posterior#nasal#spine#(PNS)#Line#extending#from#S#to#the#posterior#pharyngeal#wall#Sella#(S)#point# Line#extending#from#the#PNS#to#the#posterior#superior#pharyngeal#wall#(SP)#Retropalatal! Line#extending#from#the#posterior#nasal#spine#(PNS)#to#the#most#posterior#inferior#point#of#the#soft#palate#Line#extending#from#the#posterior#superior#pharyngeal#wall#(SP)#to#the#posterior#middle##pharyngeal#wall#(MP)#Line#extending#from#the#PNS#the#posterior#pharyngeal#wall#(SP)#Line#extending#from#the#posterior#inferior#point#of#the#soft#palate#to#the#posterior#middle#pharyngeal#wall#(MP)#Retroglossal! Line#extending#from#the#posterior#inferior#point#of#the#soft#palate#to#the#tip#of#the#epiglottis.#Line#extending#from#the#posterior#middle#pharyngeal#wall#(MP)#to#the#posterior#inferior#pharyngeal#wall#(IP)#Line#extending#from#the#posterior#inferior#point#of#the#soft#palate#to#the#posterior#middle#pharyngeal#wall#(MP)#Line#extending#from#the#tip#of#the#epiglottis#to#the#posterior#inferior#pharyngeal#wall#(IP)#Total!Airway! Line#extending#from#sella#to#the#PNS#to#the#tip#of#the#epiglottis#Line#extending#from#sella#to#the#superior#pharyngeal#wall#to#the#inferior#pharyngeal#wall#Sella#(S)#point# Line#extending#from#the#tip#of#the#epiglottis#to#the#posterior#inferior#pharyngeal#wall#(IP)# ! !   36 Table!2.7!Protocol!for!volumetric!and!minimum!axial!area!airway!measurement!!Open#Dolphin#Imaging#11.5#Program#Click#on#3D#Icon#Import#new#DICOM#Open#the#Orientation#icon#for#Mid]Sagittal,#Axial#and#Coronal#Plane#Configuration#Open#the#Sinus/Airway#icon#Orient#the#Sagittal#image#with#the#incisive#foramen#viewable#to#the#largest#diameter,#and#the#palatal#plane#parallel#to#the#horizontal#edge#of#the#viewer.#Select#border#points#of#desired#airway#to#be#measured.#Add#seed#points#(yellow#dot)#at#the#center#of#the#airway#to#be#measured#Adjust#slice#airway#sensitivity#to#remove#image#artifacts.#Click#on#update#volume#for#measurement#of#airway#volume#Click#on#‘Surface’#under#‘show#airway#as’#for#volume#rendering#options#Under#Volume#Rendering#Options:#select#soft#and#hard#tissue#if#desired.#Click#on#‘Enable#Minimum#Axial#Area’#to#include#measurement#Record#Readings#into#Excel#spreadsheet#!!!!     37 Figure!2.6!Defined!total!airway,!consisting!of!the!nasopharyngeal!(NP),!as!well!as!the!retropalatal!(RP)!and!retroglossal!(RG)!regions!of!the!oropharynx.!Palatal!plane!set!as!horizontal,!with!measurements!taken!in!midMsagittal!plane.!##!!!!!   38 Figure!2.7!Nasopharyngeal!airway!volume!!!! !   39 Figure!2.8!Retropalatal!airway!region!of!the!oropharynx! ! !!   40 Figure!2.9!Retroglossal!airway!region!of!the!oropharynx!#! !   41 Figure!2.10!Total!airway!    42 2.4 Statistical Analysis  # The#records#were#transferred#onto#an#Excel®#spreadsheet#(Microsoft#Corporation,#Redmond#WA)#for#data#analysis#with#SPSS®#statistics#version#21#software#(International#Business#Machine,#Aramonk#NY).###Descriptive#statistics#134,135#were#computed,#including#sample#size#(N),#mean#( ),#and#standard#deviation#(SD).### The#normally#distributed#sample#of#the#initial#volume#measurements#were#compared#with#the#unpaired#Student’s#t]test#to#evaluate#the#influence#of#confounding#variables#such#skeletal#classification#Class#I#(ANB#≤4°)#vs.#Class#II#(ANB#>#4°),#and#gender#classification#(Male#vs.#Female).##Mann]Whitney#U#test#was#used#for#non]normally#distributed#variables#to#compare#the#change#in#volume#between#extraction#and#non]extraction#groups.#Analysis#of#Variance#(ANOVA)#was#used#to#compare#the#groups#between#the#low,#normal,#and#high#mandibular#plane#angle#groups.# # ## A#paired#Student’s#t]test#was#used#to#compare#the#volumetric#changes#between#the#pre#(T0)#and#post#(T1)#treatment#for#normally#distributed#variables.#The#Wilcoxon#Signed#Rank#Test#was#used#for#comparing#the#non]normally#distributed#volumetric#changes#variable.#The#Bonferroni#adjustment#was#applied#to#p]values#for#multiple#comparisons#to#reduce#the#chances#of#obtaining#false]positive#results#(type#1#errors).###In#the#analysis#of#the#effects#of#CBCT#scan#settings,#a#paired#Student’s#t]test#was#used#to#compare#the#means#of#using#a#dynamic#threshold#with#different#scan#settings#and#a#fixed#threshold#with#same#scan#settings.## ## #A#Spearman’s#Rank#correlation#coefficient#test#was#used#to#evaluate#the#effects#of#crowding#on#the#change#in#volumetric#airway#and#minimum#axial#areas#of#the#different#airway#regions.###   43 2.4.1 Reliability!Testing! Forty#CBCT#scans#were#randomly#selected#and#their#cephalometric#variables,#as#well#as#airway#dimensions#were#re]measured#2#weeks#after#the#initial#measurements#by#the#same#investigator.##Method#errors#were#calculated#using#the#intraclass#correlation#coefficient#(ICC)136#and#Dahlberg’s137#statistic.#For#Dahlberg’s#formula,#d#is#the#difference#between#the#first#and#second#measurements,#and#n#is#the#number#of#cephalograms#or#airways#studied.##The#coefficient#of#variation#provides#a#measure#of#the#variation#due#to#repeatability#for#a#single#parameter#dimension138.#Intraclass#correlation#coefficient#describes#how#similar#units#in#the#same#group#resemble#each#other#where#a#value#of#1#would#represent#a#complete#agreement#between#examiners#and#a#value#approaching#0#would#represent#no#agreement#between#examiners.136#Ranges#for#ICC#from#0.81#to#100#indicate#almost#perfect#agreement139,#and#between#0.7#and#0.9#are#acceptable.140##   44 Chapter!!3: Results! 3.1 Error Analysis # Analysis#included#13#cephalometric#measurements,#4#pharyngeal#airway#volumes#(Table#2.6)#and#3#minimum#axial#airway#areas.##The#reliability#was#high#after#retracing#40#measurements#with#an#ICC#≥0.82.#The#range#of#error#between#the#two#registrations#was#0.51°]1.24°#for#angular#measurements.##Reliability#of#head#film#measurements#was#comparable#with#a#previous#study141#using#Dahlberg’s137#formula#and#our#results#for#cephalometric#measurement#error#was#found#to#have#a#lower#level#of#random#errors#(Table#3.8).## #Table!3.1!Cephalogram!variance!of!error!# Baumrind#1971# Current#Results#ANB# 0.62# 0.28#SNA# 1.18# 0.54#SNB# 0.96# 0.51#Mandibular#Plane#Angle# 1.81# 0.62#Sample# 100# 40#! After#40#records#of#repeated#airway#and#linear#measurements,#reliability#was#found#to#be#higher#with#linear#and#angular#measurements#than#volumetric#measurements#using#Dahlberg’s#formula.##The#minimum#axial#areas#had#the#most#variation#when#analyzed#with#the#coefficient#of#variation#(Table#3.9).   !   45 Table!3.2!Airway!variance!of!error!# Dahlberg# Mean#volume#(mm3)#and#area#(mm)## Coefficient#of#Variation#(%)#NP#airway# 221.39# 6702.98# 3.3#Total#airway# 294.32# 22011.92# 1.34#Total#minimum#area# 17.65# 220.01# 8.02#RP#airway# 281.34# 10111.44# 2.78#RP#minimum#area# 23.96# 235.02# 10.19#RG#airway# 201.36# 5202.96# 3.87#RG#minimum#area# 46.7# 238.18# 19.61#ANB# 0.28# 3.87# 7.13#SNA# 0.54# 83.83# 0.65# #SNB# 0.51# 79.96# 0.64#SNMP# 0.62# 30.88# 2#Definitions: NP: nasopharyngeal, RP: retropalatal, RG: retroglossal   3.2 Demographics The#sample#consisted#of#pre]and#post]treatment#pairs#of#CBCT#DICOM#files#of#seventy]four#adult#patients#who#had#been#treated#orthodontically.#The#DICOM#files#were#collected#from#the#orthodontic#residency#program#at#the#University#of#Minnesota.#The#cases#were#divided#into#two#groups:#48#patients#were#treated#without#extractions,#and#26#patients#had#teeth#extracted#as#part#of#the#orthodontic#treatment.##At#the#start#of#orthodontic#treatment,#the#mean#age#of#the#non]extraction#group#was#31.9#years#(SD±12.0)#and#the#extraction#group#was#27.4#years#(SD±9.7).##The#mean#age#of#the#total#sample#was#30.4#years#(SD±11.4).#The#mean#treatment#times#for#the#non]extraction#and#extraction#groups#were#18.7#months#(SD±5.4)#and#23.5#months#(SD±4.5)#respectively.##The#mean#treatment#time#for#the#total#sample#was#20.4#months#(SD±5.6).##The#sample#characteristics#   46 for#this#study#are#presented#(Table#3.1).#Patient#descriptive#statistics#for#the#sub]sample#of#patients#with#the#same#pre#and#post#treatment#scan#settings#can#be#found#in#Table#A.8. !   47 Table!3.3!Descriptive!statistics!of!the!sample!population!!# Total# Non]extraction# Extraction#No.# 74# 48# 26#No.#female# 49# 31# 18#No.#male# 25# 17# 8#Age#(years)# 30.4#±#11.4# 31.9#±#12.0# 27.4#±#9.7#Treatment#length#(months)# 20.4#±#5.6# 18.7#±5.4# 23.5#±#4.5#Class%I%skeletal%relationship# 38# 29# 9#Class#II#skeletal#relationship# 36# 19# 17#Md#planeº##(low)# 15# 13# 2#Md#planeº##(normal)# 45# 29# 16#Md#planeº#!(high)# 14# 6# 8##3.3 Confounding Factors  No#significant#differences#were#found#in#the#mean#initial#and#final#airway#volumes#between#mandibular#plane#angles#(normal#vs.#high#vs.#low)#(Table#3.3),#anterior]posterior#skeletal#relationships#(Class#I#vs.#Class#II)#(Table#3.4),#and#genders#(Table#3.5).##Consequently,#the#females#and#males,#all#three#mandibular#plane#angle#groups,#and#the#Class#I#and#Class#II#groups#were#combined#as#one#sample#to#examine#the#effects#of#extraction#and#non]extraction#treatment#on#the#airway#volumetric#change.# !! When#using#the#same#scan#settings#or#fixed#threshold#analysis#for#pre#and#post]treatment#CBCT#records,#similar#findings#were#found.#The#changes#in#airway#volume#and#the#changes#in#the#minimum#axial#area#for#all#regions#were#not#significantly#(p>0.05)#different#between#extraction#and#non]extraction#groups#(Table#A.2).##Furthermore,#when#comparing#the#dynamic#and#fixed#threshold#techniques,#the#treatment#time,#age,#and#gender#distributions#were#not#significantly#(p>0.05)#different#(Table.#A.10).#   48 Table&3.4&Airway&measurements&divided&into&low,&normal&and&high&mandibular&plane&angles.&! ≤26°!(N=15)! ≥38°!(N=14)! >26°!or!<38°!(N=45)! p5value!! Mean! SD! Mean! SD! Mean! SD! !Nasopharyngeal-airway-volume- ! ! ! ! ! ! !measurement!T0!(mm³)! 7295.86! 2997.58! 5630.47! 2855.89! 6846.37! 2585.25! NS!measurement!T1!(mm³)! 6982.72! 2979.80! 6894.24! 2292.12! 5684.54! 2523.55! NS!measurement!T1!–!T0!(mm³)! 5313.14! 1551.82! 1263.77! 1016.78! 51161.83! 1171.6! NS!Retropalatal-airway-volume- ! ! ! ! ! ! !measurement!T0!(mm³)! 10865.86! 4074.70! 8303.95! 3740.59! 10279.62! 4070.92! NS!measurement!T1!(mm³)! 10109.02! 3679.26! 10020.80! 4093.54! 7811.49! 4462.36! NS!measurement!T1!–!T0!(mm³)! 5756.84! 4293.75! 1716.85! 2059.19! 52468.13! 3109.41! NS!Retropalatal-minimum-axial-area- ! ! ! ! ! ! !measurement!T0!(mm2)! 211.00! 112.29! 201.88! 111.61! 225.12! 110.64! NS!measurement!T1!(mm2)! 203.01! 104.80! 199.56! 112.71! 176.54! 92.21! NS!measurement!T1!–!T0!(mm2)! 57.99! 124.15! 52.32! 58.9! 548.58! 72.2! NS!Retroglossal-airway-volume! ! ! ! ! ! ! !measurement!T0!(mm³)! 5456.86! 3502.93! 4111.64! 1906.36! 5386.54! 3193.01! NS!measurement!T1!(mm³)! 4776.10! 2897.62! 4407.45! 2918.89! 3418.84! 1547.81! NS!measurement!T1–!T0!(mm³)! 5680.76! 1849.81! 295.81! 955.33! 51967.70! 2422.67! NS!!!!! ! ! ! ! ! !   49 ! ≤26°!(N=15)! ≥38°!(N=14)! >26°!or!<38°!(N=45)! p5value!! Mean! SD! Mean! SD! Mean! SD! !Retroglossal-minimum-axial-area-- ! ! ! ! ! ! !measurement!T0!(mm2)! 212.73! 106.59! 215.73! 82.37! 223.33! 114.41! NS!measurement!T1!(mm2)! 182.89! 89.99! 188.43! 114.94! 170.18! 74.25! NS!measurement!T1!–!T0!(mm2)! 529.84! 96.38! 527.30! 67.60! 553.15! 93.39! NS!Total-airway-volume- ! ! ! ! ! ! !measurement!T0!(mm³)! 23918.48! 8086.60! 18164.91! 6872.89! 22632.5! 7716.9! NS!measurement!T1!(mm³)! 22026.38! 7865.06! 21219.92! 7389.32! 16907.72! 7610.27! NS!measurement!T1!–!T0!(mm³)! 51892.10! 5763.53! 53055.01! 1547.07! 55724.78! 4793.52! NS!Total-minimum-axial-area! ! ! ! ! ! ! !measurement!T0!(mm2)- 240.13! 116.30! 190.76! 91.31! 222.53! 104.91! NS!measurement!T1!(mm2)! 196.20! 107.08! 195.24! 97.70! 153.44! 74.35! NS!measurement!T1–!T0!(mm2)! 543.93! 99.38! 4.48! 49.43! 569.09! 67.13! NS!& &   50 Table&3.5&Airway&measurements&divided&by&Class&I&and&Class&II&craniofacial&classifications.&! Class!I!(ANB!>0°!and!<!4°)! Class!II!(ANB!>!4°)! !! N=38! n=36! !Nasopharyngeal-airway-volume- Mean! SD! Mean! SD! p5!value!measurement!T0!(mm³)! 6699.92! 2538.73! 6715.40! 2974.78! NS!measurement!T1!(mm³)! 6502.62! 2395.51! 6874.04! 2622.45! NS!measurement!T1!–!T0!(mm³)! 5197.3! 1237.73! 158.64! 1196.39! NS!Retropalatal-airway-volume- ! ! ! ! !measurement!T0!(mm³)! 10212.8! 4311.81! 9826.10! 3809.23! NS!measurement!T1!(mm³)! 9766.15! 4173.52! 9467.19! 4127.17! NS!measurement!T15T0!(mm³)! 5446.65! 3473.01! 5358.91! 2903.89! NS!Retropalatal-minimum-axial-area- ! ! ! ! !measurement!T0!(mm2)! 238.18! 104.3! 196.42! 113.26! NS!measurement!T1!(mm2)! 201.01! 111.86! 190.53! 102.10! NS!measurement!T15T0!(mm2)! 537.17! 85.87! 55.89! 76.15! NS!Retroglossal-airway-volume- ! ! ! ! !measurement!T0!(mm³)! 5376.18! 3512.93! 4930.98! 2543.21! NS!measurement!T1!(mm³)! 4467.71! 2745.90! 4112.98! 2710.04! NS!measurement!T15T0!(mm³)! 5908.47! 2377.44! 5818.00! 1774.8! NS!Retroglossal-minimum-axial-area-- ! ! ! ! !measurement!T0!(mm2)! 213.95! 104.59! 225.86! 109.20! NS!measurement!T1!(mm2)! 181.68! 89.01! 186.14! 16.67! NS!   51 ! Class!I!(ANB!>0°!and!<!4°)! Class!II!(ANB!>!4°)! !! N=38! n=36! !measurement!T15T0!(mm2)! 532.27! 104.88! 539.72! 69.09! NS!Total-airway-volume- ! ! ! ! !measurement!T0!(mm³)! 22411.19! 7981.14! 21664.54! 7667.66! NS!measurement!T1!(mm³)! 20600.68! 7592.43! 20532.62! 7795.74! NS!measurement!T15T0!(mm³)! 51810.51! 5577.02! 51131.92! 3168.21! NS!Total-minimum-axial-area- ! ! ! ! !measurement!T0!(mm2)! 229.56! 106.71! 210.08! 103.09! NS!measurement!T1!(mm2)! 191.33! 92.75! 183.51! 100.43! NS!measurement!T15T0!(mm2)! 538.23! 80.77! 526.57! 60.45! NS!! &   52 Table&3.6&Airway&measurements&divided&by&gender.&! Female!(N=49)! Male!(N=25)! p5value!! Mean! SD! Mean! SD! !Nasopharyngeal-airway-volume- ! ! ! ! !measurement!T0!(mm³)! 6431.35! 2898.63! 7248.59! 2361.53! NS!measurement!T1!(mm³)! 6518.68! 2548.29! 7006.00! 2414.76! NS!measurement!T15T0!(mm³)! 87.33! 1006.27! 5242.59! 1564.14! NS!Retropalatal-airway-volume- ! ! ! ! !measurement!T0!(mm³)! 9046.40! 3257.29! 11942.10! 4789.02! NS!measurement!T1!(mm³)! 8880.02! 4072.82! 11072.45! 3907.86! NS!measurement!T15T0!(mm³)! 5166.38! 3014.05! 5869.65! 3519.75! NS!Retropalatal-minimum-axial-area- ! ! ! ! !measurement!T0!(mm2)! 203.59! 104.96! 245.83! 116.44! NS!measurement!T1!(mm2)! 181.01! 109.33! 225.11! 96.58! NS!measurement!T15T0!(mm2)! 522.58! 78.39! 520.72! 91.02! NS!Retroglossal-airway-volume- ! ! ! ! !measurement!T0!(mm³)! 4424.49! 2710.89! 6600.41! 3262.92! NS!measurement!T1!(mm³)! 3416.10! 2073.42! 6018.06! 3027.15! NS!measurement!T15T0!(mm³)! 51008.39! 1424.28! 5582.35! 3021.83! NS!Retroglossal-minimum-axial-area-! ! ! ! ! !measurement!T0!(mm2)- 206.15! 102.18! 246.38! 111.21! NS!measurement!T1!(mm2)! 160.46! 86.24! 229.69! 117.89! NS!   53 ! Female!(N=49)! Male!(N=25)! p5value!! Mean! SD! Mean! SD! !measurement!T15T0!(mm2)! 545.69! 82.67! 516.69! 98.56! NS!Total-airway-volume! ! ! ! ! !measurement!T0!(mm³)- 20056.44! 6848.80! 25951.33! 8160.29! NS!measurement!T1!(mm³)! 18690.18! 7284.96! 24247.26! 7075.26! NS!measurement!T15T0!(mm³)! 51366.26! 4061.18! 51704.07! 5466.11! NS!Total-minimum-axial-area! ! ! ! ! !measurement!T0!(mm2)- 206.56! 98.40! 246.60! 113.47! NS!measurement!T1!(mm2)! 174.98! 99.38! 212.11! 85.54! NS!measurement!T15T0!(mm2)! 531.58! 66.18! 534.49! 82.01! NS!NS=!nonsignificant   54  3.4 Treatment Effects on Upper Airway !The!initial!and!final!volumetric!measurements!and!areas!were!not!significantly!(p>0.05)!different!for!the!nasopharyngeal,!retropalatal,!retroglossal,!and!total!airway!regions!between!the!extraction!and!non@extraction!groups.!(Table!3.5)!Similarly,!the!initial!and!final!minimum!axial!area!measurements!were!not!significantly!(p>0.05)!different!for!the!retropalatal,!retroglossal,!and!total!airway!regions!between!the!extraction!and!non@extraction!groups.!(Table!3.5).!!!The!mean!volume!changes!were!compared!between!extraction!and!non@extraction!groups!for!the!nasopharyngeal,!retropalalatal,!retroglossal,!and!total!airway!regions.!In!the!nasopharyngeal!region,!the!mean!volume!change!in!the!extraction!group!decreased!(!136.1&±&1379.3)&while!the!nonextraction!group!mean!volume!increased!slightly!(36.5&±&1139.8).&In&the&retropalatal&region,&the&mean&volume&change&in&the&extraction&(!412.7&±&3042.5)&and&non!extraction&(!399.3&±&3294.6)&group&decreased.!Likewise,!the!mean!volume!change!in!the!retroglossal!region!between!extraction!(!412.5&±&1503.2)&and!non@extraction!(!1109.3&±&2328.6)&group!decreased.!In!the!total!airway!region,!the!mean!volume!change!in!the!extraction!(!1366.3&±&4061.2)&and!non@extraction!(!1704.1&±&5466.1)&group!decreased.!!For!each!airway!region,!the!treatment!changes!for!the!nasopharyngeal,!retropalatal,!retroglossal,!and!total!airway!regions!examined!were!not!significantly!(p>0.05)!different!between!the!extraction!and!non@extraction!groups.!(Table!3.6).!!!!The!change!in!minimum!axial!area!for!the!retropalatal,!retroglossal!and!total!airway!regions!were!examined.!!In!the!retropalatal!minimum!axial!area!region,!there!was!an!decrease!in!both!the!extraction!(!20.8&±&84.7)&and&non!extraction&(!22.9&±&81.8)&groups.&In&the&retroglossal&minimum&axial&area&region,&there&was&also&an&decrease&in&the&extraction&(!33.1±&53.4)&and&non!extraction&(!32.3&±&80.0)&groups.&Likewise,&in&the&total&minimum&axial&area&region,&there&was&an&decrease&in&the&extraction&(!412.5&±&1503.2)&and&non!extraction&groups&(!412.5&±&   55 1503.2).!!The!changes!in!the!minimum!cross@sectional!area!were!also!not!significantly!(p>0.05)!different!between!the!two!treatment!modalities.!!!       56 Table&3.7&Initial,&final,&and&change&in&airway&measurements&between&extraction&and&nonextraction&groups& !NS=!Non!significant! &&& Extraction&(N=26)& Nonextraction&(N=48)& p!value&&& Mean& SD& Mean& SD&Nasopharyngeal-airway- && && && && &&&&&&&measurement&T0&(mm³)& 5937.6& 2117.1& 7124.5& 2962.1& NS&&&&&&measurement&T1&(mm³)&volume&changes&between&T1!T0& 5801.4&!136.2& 2009.8&1379.3& 7161.0&36.5& 2623.2&1139.8& NS&NS&Retropalatal-airway-- & & & & &&&&&&measurement&T0&(mm³)& 9866.1& 3965.1& 10110.6& 4137.2& NS&&&&&&measurement&T1&(mm³)&volume&changes&between&T1!T0& 9453.5&!412.6& 4760.3&3042.5& 9711.3&!399.3& 3788.7&3294.6& NS&NS&Retropalatal-minimum-axial-area- & & & & &&&&&&measurement&T0&(mm2)& 202.46& 95.19& 226.2& 117.39& NS&&&&&&measurement&T1&(mm2)&area&changes&between&T1!T0& 182.28&!20.2& 102.17&84.7& 203.29&!22.9& 109.29&81.8& NS&NS&Retroglossal-airway- & & & & &&&&&&measurement&T0&(mm³)& 4356.13& 2334.81& 5594.8& 3340.55& NS&&&&&&measurement&T1&(mm³)&volume&changes&between&T1!T0& 3943.61&!412.5& 2582.79&1503.2& 4485.55&!1109.3& 2792.97&2328.6& NS&NS&Retroglossal-minimum-axial-area-- & & & & &&&&&&measurement&T0&(mm2)& 206.22& 93.37& 227.07& 112.94& NS&&&&&&measurement&T1&(mm2)&area&changes&between&T1!T0& 173.93&!32.3& 98.91&72.6& 189.23&!37.8& 105.32&97.1& NS&NS&Total-airway-volume- & & & & &&&&&&measurement&T0&(mm³)& 20056.44& 6848.80& 25951.33& 8160.29& &NS&&&measurement&T1&(mm³)&&volume&change&T1!T0&(mm³)& 18690.18&!1366.3& 7284.96&4061.2& 24247.26&!1704.1& 7075.26&5466.1& NS&NS&Total-minimum-axial-area& & & & & &measurement&T0&(mm2)& 206.56& 98.40& 246.60& 113.47& NS&&&&&&measurement&T1&(mm2)&area&changes&between&T1!T0& 160.6&!46& 92.4&53.4& 202.1&!44.5& 95.6&80.0& NS&NS&   57 3.5 Impact&of&Dental&Crowding&on&Treatment&Associated&Airway&Changes&!! To!assess!the!possible!impact!of!the!amount!of!initial!dental!crowding!on!the!magnitude!and!direction!of!dimensional!changes!of!the!upper!airway,!differences!between!the!initial!amount!of!dental!crowding!and!airway!change!for!both!extraction!and!non@extraction!groups!were!tested.!Crowding!was!divided!into!4!groups:!dentition!with!spacing,!minimal!(≥!0mm!and!≤!3!mm),!moderate!(>3!and!≤7!mm),!and!severe!crowding(>7!mm)!(Table!3.6).!!Table&3.8&Crowding&sample&characteristics&Crowding! Spacing!! ≥!0mm!and!≤!3!mm!(minimal)! >3!and!≤7!mm!(moderate)! >7!mm!(severe)!Non@Extraction! 4! 25! 16! 3!Extraction! 0! 5! 16! 5!! The!effects!of!crowding!on!the!non@extraction!and!extraction!samples!were!tested!using!the!Spearman’s!rank!correlation!coefficient.!There!was!no!correlation!found!between!crowding!and!the!nonextraction!group!for!all!regions!of!the!airway.!However,!for!the!extraction!group,!only!the!change!in!airway!volume!in!the!retroglossal!region!had!a!higher!correlation!(r=0.34)!than!the!other!regions!and!was!significant!(p<0.05)!((Table!3.7).!For!all!other!sections!of!the!airway!tested!with!respect!to!volume!and!minimum!axial!areas,!there!was!a!weak!correlation!between!crowding!and!changes!in!airway!volume!or!minimum!axial!areas.!! &   58 Table&3.9&Spearman’s&rank&correlation&coefficient&between&crowding&and&volumetric&changes&in&airway&and&minimum&axial&areas&Change in Volume or Area Crowding P-value Nasopharyngeal airway volume 0.09 NS Total airway volume 0.11 NS Total minimum axial area 0.09 NS Retropalatal airway volume 0.06 NS Retropalatal minimum axial area 0.09 NS Retroglossal airway volume 0.35 0.003** Retroglossal minimum axial area 0.13 NS NS=!non@signficant.!**.!Correlation!is!significant!at!the!0.01!level!(2@tailed)!! In!the!retroglossal!region,!there!was!a!decrease!in!mean!volume!change!with!minimal!crowding!(@1880.3mm3!±!586)!and!an!increase!with!severe!crowding!(875.2mm3!±!2165.7)!when!extractions!were!involved!as!part!of!orthodontic!treatment!(Figure!3.1).!When!comparing!the!minimal!and!severe!crowding!groups!in!the!retroglossal!region,!there!was!a!significant!difference!(p<0.05)!found!(2755.5!mm3).!All!other!airway!regions!showed!no!significant!difference!between!the!amount!of!crowding!and!change!in!airway!volume!and!minimum!axial!areas!with!extraction!orthodontic!treatment!(Table!A.7).!!For!the!non@extraction!orthodontic!group,!no!significant!differences!between!the!amount!of!crowding!and!the!change!in!airway!and!minimum!axial!areas!were!found.!(Table!A.8)!&& &   59 Figure&3.1&Crowding&and&difference&in&the&retroglossal&airway&in&the&extraction&group&   60    3.6 Post-hoc Power Calculation   The!power!analysis!for!each!airway!region!was!calculated!to!test!the!validity!of!the!sample!(Table!A.3).!The!parameters!used!were!effect!size!based!on!the!method!error!mean!and!standard!deviations!for!each!airway!region!(Table!3.8),!two@sided!test,!an!alpha!value!of!0.05,!and!a!power!value!of!0.8!to!calculate!the!required!sample.!The!Nasopharynx!airway!volume!group!required!a!sample!of!705,!the!Total!airway!volume!group!required!a!sample!of!1111125,!the!Total!minimum!axial!area!group!required!a!sample!of!491,!the!Retropalatal!airway!volume!group!required!a!sample!of!236,!the!Retropalatal!minimum!axial!area!group!required!a!sample!of!269,!the!Retroglossal!airway!volume!group!required!a!sample!of!23,!and!the!Retroglossal!minimum!axial!area!group!required!a!sample!of!82.! Table&3.10&Method&error&means&and&standard&deviations&for&each&airway&region&Difference Mean  Standard Deviation Nasopharyngeal Airway Volume -33.8 319.4 Retropalatal Airway Volume 73.5 401.2 Retropalatal Minimum Axial Area 5.9 34.2 Retroglossal Airway Volume -153.8 245.9 Retroglossal Minimum Axial Area -20.3 64.5 Total Airway Volume -1.1 427.0 Total Minimum Axial Area 3.2 25.4     61 Chapter  4: Discussion  Orthodontic!treatment!has!many!known!beneficial!effects!to!the!function!and!esthetics!of!the!masticatory!system,!and!often,!dental!extractions!are!employed!to!reach!these!treatment!goals.!Extraction!or!non@extraction!orthodontic!treatment!affects!on!the!dental,!skeletal!and!soft!tissue!continue!to!be!discussed!in!the!orthodontic!literature.!!Considerations!of!extraction!treatment!in!orthodontics!include!arch!length!deficiency,!stability,!smile!esthetics,!and!profile.!! There!is!a!growing!interest!in!in!the!dental!community!about!orthodontic!treatment!in!adults!with!extractions!and!it’s!relation!to!OSA.!!Anecdotally,!there!is!a!notion!that!the!extraction!of!teeth!leads!to!a!smaller!arch!length,!and!the!subsequent!retraction!of!teeth!displace!the!tongue!posteriorly!into!the!airway.!Consequently,!the!airway!is!narrowed!which!could!possibly!lead!to!an!increased!risk!of!obstructive!sleep!apnea.!As!OSA!is!a!common!and!serious!medical!condition,!and!the!narrow!airway!a!general!risk!factor!of!OSA,!a!clear!understanding!of!the!effects!of!orthodontic!treatment!on!the!upper!airway!volume!is!warranted.!!!4.1 Previous Investigations  This!study!set!out!to!answer!the!clinical!question!of!how!orthodontic!treatment!with!the!extraction!of!teeth!affects!the!upper!airway!volume,!and!analysis!shows!that!the!extraction!of!teeth!has!similar!affects!as!the!non@extraction!modality!on!the!upper!airway!volume.!!Previous!investigations63,65,124!have!looked!at!the!airway!with!2D!cephalometric!imaging,!showing!either!a!narrowing,!no!effect,!or!an!increase!in!volume!with!extractions.!Using!2@dimensional!radiography,!no!reliable!conclusions!can!be!made!about!the!effects!of!orthodontic!treatment!on!airway!volume!because!the!transverse!dimensions!are!unknown.!!   62 More!recently!other!studies61,126,127!have!analyzed!the!effect!of!orthodontics!on!the!airway!with!3D!CBCT!data!in!growing!patients.!!Although!the!conclusion!of!these!investigations!revealed!no!differences!in!the!change!in!airway!volume!between!extraction!and!non@extraction!orthodontic!treatment,!the!adolescent!patients!had!structural!dimensions!that!increased!over!the!approximate!2@year!treatment!period,!as!the!face!grew!downward!and!forward.!In!other!words,!a!decrease!in!the!airway!due!to!extractions!could!be!compensated!by!an!increase!in!growth!of!the!hard!and!soft!tissues!of!the!airway.!!Therefore,!the!confounding!effects!of!growth!may!be!a!factor!when!comparing!the!airways!of!extraction!and!non@extraction.!!A!study128!by!Chen!et!al.!looked!at!30!CT!scans!of!adult!patients!with!bimaxillary!protrusion!treated!with!four!bicuspid!extraction.!This!is!the!only!3D!study!with!an!adult!patient!cohort!looking!at!extraction!treatment!and!airway!volume.!The!authors!reported!narrowing!of!the!airway!with!extraction!orthodontics!and!maximum!retraction!of!the!maxillary!anterior!teeth!with!temporary!anchorage!devices.!However,!the!method!for!analyzing!airway!constriction!involved!taking!cross!sectional!areas!of!the!airway!to!represent!change!in!airway!anatomy.!Their!stated!rationale!for!using!cross!sectional!areas!to!assess!the!change!in!airway!is!based!on!the!irregular!airway!lumen!and!that!thus!the!volume!cannot!reflect!the!narrowest!position!of!the!airway.!In!contrast,!a!reliability!study118!found!that!minimum!cross@sectional!areas!were!the!least!reliable!measurement!in!airway!analysis.!Our!study!looked!at!volumetric!change!to!represent!change!in!airway!volume!as!a!representation!of!the!irregular!lumen!size,!and!also!agreed!with!Mattos!et!al118!that!the!minimum!cross@sectional!area!measurements!were!the!least!reliable.!!!4.2 Demographics !The!present!study!analyzed!74!patients!with!pretreatment!and!posttreatment!CBCT!records!from!the!orthodontic!residency!at!the!University!of!Minnesota.!An!iCAT!CBCT!machine!was!used!to!collect!all!samples!and!each!scan!recorded!patient!in!an!upright!   63 position,!with!a!17!cm!field!of!view!to!include!the!full!craniofacial!anatomy.!!Of!the!74!patients,!48!were!treated!without!extraction!and!26!patients!had!teeth!extracted!as!part!of!orthodontic!treatment.!!!!The!average!age!of!the!sample!was!30.4!years!and!therefore!this!sample!was!of!a!non@growing!population.!No!further!delineation!of!the!sample!into!age!categories!was!considered!as!it!is!assumed!that!changes!in!airway!would!not!be!different!between!a!young!and!an!older!adult.!!Although!increased!age!is!a!risk!factor!for!OSA,!it!would!be!inappropriate!to!extend!the!anatomical!findings!in!this!study!to!children!and!the!complex!functional!deficits!characteristic!of!OSA.!  4.3 Confounding Factors !The!eligibility!criteria!included!ages!18@65!years,!pre@treatment!ANB!>!0º,!no!history!of!airway!surgery,!no!previous!orthodontic!treatment,!no!craniofacial!abnormalities!or!developmental!defects,!no!missing!teeth!(ignoring!3rd!molars),!no!compromised!periodontal!status!and!no!cases!involving!orthognathic!surgery.!In!this!study,!we!aimed!to!focus!on!Class!II!(ANB!>!4º)!craniofacial!morphologies!because!previous!studies46,71,74,78,142!have!suggested!that!retrognathia!may!be!one!anatomic!risk!in!acquiring!OSA.!Skeletal!class!III!patients!were!excluded!from!analysis!due!to!their!minimal!representation!in!the!sample.!We!also!wanted!to!limit!our!sample!to!non@growing!individuals!to!address!the!confounders!of!growth!from!previous!studies.!This!is!a!challenging!task!as!most!of!the!patients!who!seek!orthodontic!care!are!children!and!adolescents,!thus!limiting!our!sample!size.!!Other!exclusion!criteria!that!could!be!confounders!in!airway!change!with!extraction!and!non@extraction!orthodontic!treatment!included!history!of!airway!surgery,!previous!orthodontic!treatment,!craniofacial!and!developmental!defects,!missing!teeth,!compromised!periodontal!status,!and!orthognathic!surgery.!    64 The!Class!I!(ANB!>!0°!and!<4°)!and!Class!II!(ANB!≥4°)!skeletal!relationships!were!divided!into!two!groups!to!evaluate!the!affects!on!the!upper!airway!volume.!!A!study!143!by!Hochban!in!1994!identified!retrognathism!!as!a!possible!risk!factor!for!OSAS.!!From!this!study,!it!was!observed!that!in!Class!II!skeletal!patients,!the!jaw!rotates!down!and!back!in!a!clockwise!direction!toward!the!airway,!causing!possible!compression!of!the!soft!tissue!surrounding!the!upper!airway.!We!did!not!find!any!significant!(p!<!0.05)!differences!in!the!initial!airway!volumes!between!the!Class!II!and!Class!I!patients,!nor!did!we!find!any!significant!differences!between!the!changes!due!to!treatment!in!the!upper!airway!volume.!Furthermore,!we!did!not!find!any!significant!differences!between!the!pre!and!post!treatment!cephalometric!values!of!SNA,!SNB,!and!ANB.!!A!larger!sample!size!may!have!been!able!to!detect!differences!in!airway!size!and!shape!between!Class!I!and!Class!II!patients!that!were!not!found!in!our!analysis.!! We!investigated!the!initial!volumes!and!change!in!volume!between!High!(SN@MP!≥38°),!Normal!(SN@MP!<38°!and!>27°),!and!Low!Mandibular!Plane!Angle!(SN@MP!≤26°)!patients.!Vertical!growth!patterns!and!high!angle!patients!have!been!established!as!risk!factors!for!OSAS.71,143!A!study!by!Celikoglu!et!al.!130!found!significant!differences!in!the!pharyngeal!airway!volume!among!different!skeletal!vertical!patterns.!They!concluded!that!in!high!angle!patients,!the!airway!volume!was!the!lowest!compared!to!normal!and!low!angle!patients.!This!study!did!not!find!any!significant!difference!between!the!initial!volumes!of!high,!normal,!and!low!angle!patients.!Similarly,!no!significant!differences!were!found!between!the!changes!in!volume!between!the!3!mandibular!plane!groups.!!Moreover,!there!were!no!craniofacial!changes!pre!and!post!orthodontic!treatment!as!measured!by!cephalometric!variables!SN@MP.!!Similarly!to!anterior@posterior!skeletal!relationships,!the!large!variations!in!airway!measurement!and!relatively!small!sample!sizes!may!have!prevented!detection!of!differences!previously!reported!in!the!literature.!! ! Another!possible!confounding!factor!is!the!role!of!gender!in!affecting!the!airway!volume.!Tanner!et!al.129!in!1962!reported!that!males!have!larger!airways!and!greater!growth!changes!relative!to!females.!Our!results!showed!that!there!were!no!significant!   65 differences!between!the!initial!airway!volumes,!nor!were!there!significant!differences!in!the!changes!of!airway!volumes!between!genders.!Hence!gender!was!not!a!confounding!factor!on!the!airway!volume.!Since!gender!did!not!influence!the!initial!airway!volumes,!we!were!able!to!combine!the!groups!for!further!analysis.!!! In!our!study,!treatment!time!was!not!a!factor!between!extraction!and!non@extraction!groups.!If!the!sample!included!growing!individuals,!treatment!time!may!have!been!a!confounder!as!seen!in!the!Valiathan!et!al.!study61,!where!mainly!due!to!differences!in!treatment!time!the!extraction!group!had!a!greater!increase!in!airway!than!the!non@extraction!group.!With!five!more!months!of!growth!over!the!course!of!treatment!and!observation!period!in!the!extraction!group,!an!increase!in!airway!size!would!be!expected.!!!4.4 Airway Assessment !! ! Three@dimensional!imaging!modalities!have!increasingly!been!at!the!forefront!of!dental!technology!for!visualizing!and!analyzing!upper!airways.!!Although!validation!studies111,113,114,144!on!the!accuracy!of!CBCT!for!upper!airway!evaluation!have!been!confirmed,!airway!segmentation!reliability!is!not!without!its!challenges.!!! ! Assessment!of!the!upper!airway!depends!on!DICOM!segmentation,!image!quality,!and!threshold!selection.!!Before!quantification,!segmentation!of!the!airway!depends!on!setting!the!threshold!value!at!which!the!software!will!distinguish!air!from!soft!tissue.!!A!number!of!studies110,119@123!using!Dolphin!Imaging!have!looked!at!different!threshold!values!!ranging!from!25!to!75!units!using!a!variety!of!CBCT!scanners!and!settings!(Table!1.2)!.!!Our!study!used!a!dynamic!threshold!value,!which!involves!selecting!the!value!based!on!the!operator’s!visual!discernment!of!the!outline!of!the!airway.!The!volumetric!measurements!of!the!present!study!were!similar!with!Smith!et!al131!who!segmented!the!airway!with!means!into!nasopharynx!(3221mm3 ±!1660),!the!oropharynx!(10688mm3 ±!6019),!and!the!   66 hypopharynx!(3319mm3 ±!1216),!yielding!a!total!mean!airway!of!17228!mm3.!!! The!CBCT!scan!settings!could!have!presented!a!possible!confounding!factor!in!our!analysis.!Overall!four!different!CBCT!settings!were!used!with!the!patient!sample!as!the!imaging!protocol!changed!at!the!University!of!Minnesota!from!2008!to!2012!with!the!aim!of!reducing!patient!radiation!exposure.!The!variable!scan!settings!for!each!sample!could!influence!the!sensitivity!of!the!Dolphin!software!when!segmenting!the!airway.!Specifically,!the!different!voxel!sizes!of!0.3mm!and!0.4mm!could!possible!give!a!different!output!on!airway!volumes.!Uniform!scan!settings!would!allow!us!to!ideally!use!a!fixed!threshold!setting!to!segment!the!airway!for!all!patients,!thus!eliminating!the!qualitative!and!subjective!aspect!of!airway!assessment!inherent!to!CBCT!scans!and!Dolphin!Imaging!software.!!To!investigate!the!potential!influences!of!scan!settings,!the!sub@sample!of!20!patients!with!the!same!scan!settings!for!both!the!pre!and!post!treatment!scans!was!analyzed.!The!first!assessment!found!that!changes!in!airway!volume!for!these!patients!were!no!different!than!for!the!rest!of!the!sample.!Second,!comparing!the!measured!airway!volumes!for!this!group!when!using!a!fixed!threshold!value!for!airway!segmentation,!or!a!variable!threshold!value!did!not!result!in!statistically!significant!differences.!!!4.5 Treatment Effects on the Upper Airway ! The!premise!that!orthodontic!treatment!can!have!an!affect!on!airway!size!is!evident!in!oral!surgery!literature!where!the!jaws!and!teeth!are!repositioned.!With!maxillomandibular!advancement,!3D!analysis!has!shown!that!the!airway!increases.115,145.!!With!the!opposite!movement,!such!as!in!a!mandibular!setback!surgery,!airway!structures!have!adjusted!to!preserve!the!airway!volume.!146.!!Our!findings!agree!with!the!studies61,126,127!that!have!concluded!that!there!were!no!significant!differences!between!the!change!in!airway!volume!between!extraction!and!non@extraction!orthodontic!treatment.!!   67 Although!there!were!no!significant!changes!in!the!airway!between!extraction!and!non@extraction!orthodontic!groups,!volumetric!assessment!of!the!airway!is!complicated!by!several!factors.!Any!increases!or!decreases!in!the!airway!volume!could!be!attributed!to!mode!of!breathing!or!variation!in!the!position!of!the!tongue!position!during!image!acquisition,!measurement!error,!or!to!changes!in!the!soft!tissue!due!to!adiposity!and!general!inflammation!over!the!approximately!two!years!of!treatment.!To!further!put!the!reported!values!in!perspective,!5000!mm3!is!about!the!size!of!a!sugar!cube,!thus!the!differences!measured!in!airway!volumes!may!be!insignificant!clinically.!!!!4.6 Impact&of&Dental&Crowding&on&Treatment&Associated&Airway&Changes&! A!potential!explanation!why!no!significant!decrease!in!airway!volume!in!the!extraction!group!was!found!could!be!the!mechanics!of!closing!extraction!spaces.!When!extraction!spaces!are!closed!after!removal!of!a!1st!permanent!premolar,!reciprocal!anchorage!mechanics!are!in!play!as!seen!when!the!posterior!teeth!move!mesially!as!the!anterior!teeth!retract!distally.!Hence!anchorage!loss!of!the!posterior!segment!is!seen!as!the!anterior!segment!is!retracted.!Most!of!the!time,!the!extraction!space!is!required!to!resolve!crowding!of!the!anterior!segment,!thus!the!posterior!segment!needs!to!move!mesially!in!order!to!close!the!extraction!space.!The!mesial!movement!of!the!posterior!segment,!and!the!effects!of!anchorage!loss!lessens!impact!of!the!anterior!segment!displacing!the!tongue!posteriorly!into!the!oropharynx.!In!comparison!to!the!previously!discussed!study!by!Chen!et!al128,!which!found!a!reduction!in!airway!volume!when!extraction!spaces!were!closed!using!maximum!anchorage,!the!anchorage!used!with!our!sample!was!not!uniform!and!thus!likely!had!an!influence!on!our!results.!!Directly!related!to!the!mechanics!used!in!closing!extraction!spaces!is!the!diagnosis!leading!to!extraction!therapy.!The!reasons!for!extraction!of!teeth!in!orthodontics!are!either!for!correction!of!anterior@posterior!occlusal!discrepancies,!crowding!or!both.!!We!looked!at!   68 the!correlation!between!crowding!and!change!in!airway,!and!found!significant!differences!in!volume!change!between!patients!with!minimal!or!severe!crowding!when!extractions!were!employed!during!orthodontic!treatment.!The!severe!crowding!patients!tended!to!see!an!increase!in!airway!between!pre!and!post@orthodontic!treatment.!Conversely,!patients!with!minimal!crowding!tended!to!see!decreases!in!airway!volume.!This!can!be!explained!by!space!closure!mechanics,!that!when!extractions!are!performed!in!minimally!crowded!cases,!a!greater!amount!of!the!extraction!space!will!be!present!following!dental!alignment,!resulting!in!greater!retraction!of!the!anterior!teeth!and!constriction!of!the!arches.!If!extractions!are!treatment!planned!for!crowding!reasons,!there!may!not!be!any!anticipated!decrease!in!airway,!as!the!extractions!would!have!alleviated!the!space!for!the!adjacent!teeth!to!align!and!maintain!the!original!airway!dimensions.!! 4.7 Measurement Error  With!respect!to!measurement!error,!the!area!and!volume!measurement!error!of!coefficient!of!variation!fell!within!the!similar!ranges!with!previous!studies!(Table!4.1)76,147@149.!!However,!there!was!almost!a!20%!variation!in!the!retroglossal!minimum!axial!area,!highlighting!the!variability!of!this!particular!region!of!the!upper!airway.&Table&4.1&Measurement&error&compared&with&other&studies&Author Journal Year Dahlberg Area mm2 oropharynx Dahlberg Volume mm3 oropharynx % volume % area Hong AJODO 2011 78.67 171.4 - - Ghoneima Eur JO 2011 0.15 0.98 - - Kim AJODO 2010 36.12 97.37 - - Guijarro-Martinez Int J Oral Mx Surg 2013 18.95 304.5 1.45-3.26 12.36-18.48 Present study - - 46.7 294 1.34-3.87 8-19.6    69   4.8 Limitations As!with!any!retrospective!study,!the!present!findings!are!met!with!several!limitations.!Factors!that!influenced!the!records!include,!mode!of!breathing,!BMI!of!the!patient,!adiposity!of!the!patient,!soft!tissue!changes!of!the!2!years!of!treatment,!and!minor!effects!of!the!tongue!position.!!All!these!factors!could!influence!and!increases!and!decreases!in!airway!changes.!!In!future!studies,!height!and!weight!data!would!help!us!correlate!BMI!and!change!in!airway!between!extraction!and!non@extraction!groups.!The!need!for!accurate!records!also!limited!our!sample!size.! CBCT!image!quality!is!limited!by!the!CBCT!device’s!settings,!patient!positioning!and!management,!volume!reconstruction,!and!DICOM!export.114!Movement!of!the!patient!during!the!scan!(8.9@17.8!seconds!scan!time)!and!noise!artifacts!may!affect!segmentation!accuracy!and!the!contrast!images.!This!could!affect!the!discrimination!between!densities!during!the!threshold!filtering!process!and,!consequently,!the!segmentation!accuracy.150!As!the!threshold!is!being!set!by!the!operator,!other!factors!such!as!lighting!conditions,!fatigue!during!long!hours!of!data!analysis,!gray@scale!ability,!and!visual!acuity!can!contribute!to!measurement!error.151!Measurement!of!the!upper!airway!is!not!without!its!challenges.!!The!airway!sections!measured!at!the!levels!of!the!hard!palate,!posterior!inferior!soft!palate,!and!tip!of!the!epiglottis,!provided!a!consistent!method!of!measurement!of!the!upper!airway!volume.!!The!hard!palate!enabled!a!consistent!horizontal!reference!plane!when!orienting!the!subject.!The!tip!of!the!epiglottis!enabled!us!to!visualize!a!consistent!landmark,!as!some!records!did!not!have!the!base!of!the!epiglottis!visible!due!to!anatomic!variation!and!limitation!of!the!field!of!view.! !   70 The!CBCT!images!were!taken!with!the!patients!in!an!upright!position!while!awake.!How!the!shape!and!function!of!the!airway!during!this!scenario!relates!to!those!of!a!patient!who!is!supine!and!sleeping!is!not!known,!and!in!fact!very!little!correlation!may!exist!at!all.!Therefore!caution!is!warranted!when!extending!the!findings!of!this!or!any!other!examination!of!the!airway!anatomy!while!the!patient!is!upright!and!awake.!The!non@significant!findings!between!extraction!and!nonextraction!orthodontic!treatment!on!airway!changes!are!applicable!to!anatomical!findings!alone,!and!not!necessarily!to!airway!function,!particularly!to!the!complex!neuromuscular!functional!deficits!associated!with!OSA.!!!!To!truly!assess!the!implications!of!orthodontic!treatment!with!extractions!on!airway!function,!future!studies!that!incorporate!large!sample!sizes!are!required.!Furthermore!these!studies!should!assess!not!only!anatomical!changes!but!also!changes!in!respiratory!function!during!sleep.!!!    71 Conclusion&! 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  84 151.!Mah!P,!Reeves!TE,!McDavid!WD.!Deriving!Hounsfield!units!using!grey!levels!in!cone!beam!computed!tomography.!Dentomaxillofacial+Radiology!2010;39(6):323–35.!!!   85  Appendix A    Table&A.1&Airway&morphometric&changes&from&preN&to&postNtreatment.&&! Extraction!(N=26)! Nonextraction!(N=48)! p@value!! Mean! SD! Mean! SD! !NP!airway! ! ! ! ! !!!!!!Volume!changes! @136.1! 1379.3! 36.5! 1139.8! NS!RP!airway! ! ! ! ! !!!!!!Volume!changes! @412.7! 3042.46! @399.3! 3294.6! NS!!!!!!Minimum!axial!changes!! @20.8! 84.7! @22.9! 81.8! NS!RG!airway! ! ! ! ! !!!!!!Volume!changes!! @412.5! 1503.2! @1109.3! 2328.6! NS!!!!!!Minimum!axial!changes! @32.3! 72.6! @37.8! 97.1! NS!Total!airway! ! ! ! ! !!!!!!Volume!changes! @1039.6! 3674.3! @1719.2! 4979.4! !NS!!!!!!Minimum!axial!changes! @33.1! 53.4! @32.3! 80! NS!*!min.=!minimum,!NS=!non@significant!&   86 *!min.=!minimum,!NS=!non@significant!& &Table&A.2&Airway&measurements&of&patients&with&identical&pre&and&post&treatment&&scan&settings.&&& & & & &&& Extraction&(N=4&)& Nonextraction&(N=16)& p!value&&& Mean& SD& Mean& SD&Nasopharyngeal&airway&volume& && && && && &&&&&&&measurement&T0&(mm³)& 7198.2& 1011.8& 7593.2& 3895.0& NS&&&&&&measurement&T1&(mm³)& 6681.3& 1399.0& 8490.6& 4170.2& NS&&&&&&Volume&changes&between&T0&!&T1& 516.9& 1412.6& !897.4& 1761.9& NS&Retropalatal&airway&volume& && && && && &&&&&&&measurement&T0&(mm³)& 12396.3& 1226.5& 10868.7& 3542.8& NS&&&&&&measurement&T1&(mm³)& 11040.9& 3458& 9510.3& 3130.5& NS&&&&&&Volume&changes&between&T0&!&T1& 1355.4& 4158.3& 1358.5& 2587.0& NS&Retropalatal&minimum&axial&area& && && && && &&&&&&&measurement&T0&(&mm2)& 312.5& 115.9& 256.8& 80.7& NS&&&&&&measurement&T1&(&mm2)& 253.6& 87.1& 182.3& 76.1& NS&&&&&&Area&changes&between&T0&!&T1& 58.9& 85.6& 74.5& 107.3& NS&Retroglossal&airway&volume& && && && && &&&&&&&measurement&T0&(mm³)& 7834.3& 2398.7& 4478.3& 2531.1& NS&&&&&&measurement&T1&(mm³)& 7339.1& 3419.2& 4032.8& 2439.6& NS&&&&&&Volume&changes&between&T0&!&T1& 495.2& 1509.8& 445.5& 1675.0& NS&Retroglossal&minimum&axial&area&& && && && && &&&&&&&measurement&T0&(mm2)& 312.5& 115.9& 256.8& 80.7& NS&&&&&&measurement&T1&(mm2)& 267.5& 75.0& 199.3& 87.9& NS&&&&&&Area&changes&between&T0&!&T1& 45.0& 100.4& 57.5& 78.0& NS&Total&airway&volume& && && && && &&&&&&&measurement&T0&(mm³)& 27423.1& 1736.0& 23142.2& 7922.1& NS&&&&&&measurement&T1&(mm³)& 24615.7& 4771.8& 22215.0& 7627.2& NS&&&&&&Volume&changes&between&T0&!&T1& 2807.4& 3505.7& 927.2& 3606.2& NS&Total&minimum&axial&area& && && && && &&&&&&&measurement&T0&(mm2)& 303.4& 100.4& 239.6& 82.2& NS&&&&&&measurement&T1&(&mm2)& 236.8& 87.9& 198.7& 60.2& NS&&&&&&Area&changes&between&T0&!&T1& 66.6& 67.1& 40.9& 65.8& NS&   87 Table&A.3&Power&calculation&for&each&airway&section&Section! Sample!Nasopharynx!Airway!Volume! 705!Total!Airway!Volume! 1111125!Total!Minimum!Axial!Area! 491!Retropalatal!Airway!Volume! 236!Retropalatal!Minimum!Axial!Area! 269!Retroglossal!Airway!Volume! 23!Retroglossal!Minimum!Axial!Area! 82!&&&   88 Table&A.4&Initial&measurements&of&airways&of&patients&with&identical&pre&and&post&treatment&scan&settings&divided&based&on&&mandibular&plane&angle.&! ≤26°!(N=4)! ≥38°!(N=5)! >26°!or!<38°!(N=11)! p5value!! Mean! SD! Mean! SD! Mean! SD! !Nasopharyngeal!airway! ! ! ! ! ! ! !!!!!!measurement!T0!(mm³)! 9079.2! 4538.0! 6593.6! 1507.1! 7363.5! 3820.8! NS!Retropalatal!airway! ! ! ! ! ! ! !!!!!!measurement!T0!(mm³)! 11548.5! 4950.9! 13726.3! 1501.1! 9878.1! 2571.0! NS!Retropalatal!min.!area! ! ! ! ! ! ! !!!!!!measurement!T0!(mm2)! 218.3! 103.4! 280.8! 65.6! 261.3! 96.2! NS!Retroglossal!airway! ! ! ! ! ! ! !!!!!!measurement!T0!(mm³)! 4658.6! 1282.8! 5686.7! 2577.3! 5083.8! 3397.6! NS!Retroglossal!min.!area!! ! ! ! ! ! ! !!!!!!measurement!T0!(mm2)! 238.0! 95.0! 292.6! 91.4! 268.0! 90.0! NS!Total!airway!! ! ! ! ! ! ! !!!!!!measurement!T0!(mm³)! 25571.9! 9794.3! 25882.1! 3806.5! 22569.9! 7831.0! NS!Total!min.!area! ! ! ! ! ! ! !!!!!!measurement!T0!(mm2)! 232.4! 95.0! 271.6! 78.7! 250.9! 94.5! NS!& *"min.="minimum,"NS="non-significant"   89 Table&A.5&Initial&measurements&of&airways&of&patients&with&identical&pre&and&&post&treatment&scan&settings&divided&by&craniofacial&classifications.&! Class!I!(ANB!>0°!and!<!4°)! Class!II!(ANB!>!4°)! !! N=12! n=8! !Nasopharyngeal!airway! Mean! SD! Mean! SD! p5!value!!!!!!measurement!T0!(mm³)! 7905.8! 2937! 6926.8! 4336.7! NS!Retropalatal!airway!!! ! ! ! ! !!!!!!measurement!T0!(mm³)! 10622.7! 3151.8! 12001.6! 3419.6! NS!Retropalatal!min.!axial!area! ! ! ! ! !!!!!!measurement!T0!(mm2)! 257! 80.8! 259.1! 106.2! NS!Retroglossal!airway! ! ! ! ! !!!!!!measurement!T0!(mm³)! 5297.4! 2973! 4927.6! 2713! NS!Retroglossal!min.!axial!area! ! ! ! ! !!!!!!measurement!T0!(mm2)! 262! 87.3! 276.9! 94.8! NS!Total!airway!! ! ! ! ! !!!!!!measurement!T0!(mm³)! 23995.1! 6524.9! 24003.3! 8789.2! NS!Total!min.!axial!area! ! ! ! ! !!!!!!measurement!T0!(mm2)! 255.7! 77.1! 247.5! 106.1! NS!*"min.="minimum,"NS="non-significant"" &   90 Table&A.6&Initial&measurements&of&airways&of&patients&with&identical&&pre&and&post&treatment&scan&settings&divided&by&gender.&! Female!(N=14)! Male!(N=6)! p5value!! Mean! SD! Mean! SD! !Nasopharyngeal!airway! ! ! ! ! !!!!!!measurement!T0!(mm³)! 7310.8! 3428.5! 7988.8! 3908.9! NS!Retropalatal!airway!! ! ! ! ! !!!!!!measurement!T0!(mm³)! 10799.5! 2818.9! 12048.6! 4252.1! NS!Retropalatal!min.!area! ! ! ! ! !!!!!!measurement!T0!(mm2)! 263.2! 87.9! 244.5! 98.9! NS!Retroglossal!airway! ! ! ! ! !!!!!!measurement!T0!(mm³)! 4431.8! 2319.6! 6824! 3329.2! NS!Retroglossal!min.!area! ! ! ! ! !!!!!!measurement!T0!(mm2)! 267.2! 86.4! 269.6! 100.7! NS!Total!airway!! ! ! ! ! !!!!!!measurement!T0!(mm³)! 22756.2! 6813.3! 26896.8! 8168.2! NS!Total!min.!area! ! ! ! ! !!!!!!measurement!T0!(mm2)! 257.8! 88.3! 239.9! 91.4! NS!*"min.="minimum,"NS="non-significant"&& &   91 Table&A.7&Analysis&of&variance&of&airway&changes&between&crowding&severity&in&the&extraction&group.&Region Crowding vs. Crowding Mean difference Mean Standard Deviation P-Value DNPAIR Minimal (N=5) Minimal 0 74.8 984.4 NS Minimal Moderate 269   NS Minimal Severe 236.3   NS Moderate N=(16) Moderate 0 -194.2 1498.8 NS Moderate Severe 32.7   NS Severe (N=5) Severe 0 -136.2 1379.3 NS DRPAIR Minimal Minimal 0 -812.2 3160.6 NS Minimal Moderate 769   NS Minimal Severe 383   NS Moderate Moderate 0 -43.3 2866 NS Moderate Severe 1152   NS Severe Severe 0 -1195.2 3943.5 NS DRPMIN Minimal Minimal 0 -46.8 162.3 NS Minimal Moderate 26.7   NS Minimal Severe 53.2   NS Moderate Moderate 0 -20.1 54.5 NS Moderate Severe 26.5   NS Severe Severe 0 6.3 74.7 NS DRGAIR Minimal Minimal  - 586 NS    92 Region Crowding vs. Crowding Mean difference Mean Standard Deviation P-Value 1880.3 Minimal Moderate 1524   NS Minimal Severe 2755.5   0.006 Moderate Moderate 0 -356.3 1072.2 NS Moderate Severe 1231.5   NS Severe Severe 0 875.2 2165.7 NS DRGMIN Minimal Minimal 0 -86.9 79.1 NS Minimal Moderate 65.2   NS Minimal Severe 75.4   NS Moderate Moderate 0 -21.7 67.8 NS Moderate Severe 10.2   NS Severe Severe 0 -11.5 68.8 NS DTOT Minimal Minimal 0 -2627.6 3818.1 NS Minimal Moderate 1932.1   NS Minimal Severe 2075   NS Moderate Moderate 0 -695.5 3650.4 NS Moderate Severe 142.9   NS Severe Severe 0 -552.6 3988.6 NS DTOTMIN Minimal Minimal 0 -50 60.25 NS Minimal Moderate 19.7   NS Minimal Severe 24.7   NS    93 Region Crowding vs. Crowding Mean difference Mean Standard Deviation P-Value Moderate Moderate 0 -30.3 46.6 NS Moderate Severe 5.1   NS Severe Severe 0 -25.2 74.8 NS *NS&=&nonsignificant,&DNPAIR&=&difference&in&nasopharyngeal&airway&volume,&&DTOT&=&difference&in&the&total&airway&volume,&&DTOTMIN&=&difference&in&the&total&minimum&axial&area,&&DRPAIR&=&difference&in&the&retropalatal&airway&volume,&&DRPMIN&=&difference&in&the&retropalatal&minimum&axial&area,&&DRGAIR&=&difference&in&the&retroglossal&airway&volume,&&DRGMIN&=&difference&in&the&retroglossal&minimum&axial&area.&  "   94 Table&A.8&Analysis&of&variance&of&airway&changes&between&crowding&severity&in&the&nonLextraction&group.&Region Crowding vs. Crowding Mean Difference Mean Standard Deviation P-Value (ANOVA) DNPAIR Spacing (N=4) Spacing  465.5 1084.1  Spacing Minimal  680.2   NS Spacing Moderate  230.9   NS Spacing Severe  -36.8   NS Minimal (N=25) Minimal  -214.7 1033.1 NS Minimal Moderate  -449.3   NS Minimal Severe  -717.0   NS Moderate N= (16) Moderate  234.6 1332 NS Moderate Severe  -267.8   NS Severe N= (3) Severe  502.3 924.7 NS DRPAIR Spacing Spacing  1131.1 2667.4 NS Spacing Minimal 1839.9   NS Spacing Moderate 1422.8   NS Spacing Severe 1564.4   NS Minimal Minimal  -708.8 4004.7 NS Minimal Moderate -417.1   NS Minimal Severe -275.5   NS Moderate Moderate  -291.7 2436.1 NS Moderate Severe 141.6   NS Severe Severe  -433.3 1211.9 NS DRPMIN Spacing Spacing  5 76.5 NS    95 Region Crowding vs. Crowding Mean Difference Mean Standard Deviation P-Value (ANOVA) Spacing. Minimal 35.8   NS Spacing. Moderate 22.6   NS Spacing. Severe 28.0   NS Minimal Minimal  -30.8 95.3 NS Minimal Moderate -13.2   NS Minimal Severe -7.8   NS Moderate Moderate  -17.6 59.7 NS Moderate Severe 5.5   NS Severe Severe  -23 101 NS DRGAIR Spacing Spacing  -1834.6 346.1 NS Spacing Minimal -474.7   NS Spacing Moderate -980.4   NS Spacing Severe -2420.9   NS Minimal Minimal  -1360 2469.3 NS Minimal Moderate -505.7   NS Minimal Severe -1946.3   NS Moderate Moderate  -854.2 2464.4 NS  Moderate Severe -1440.5   NS Severe Severe  586.3 1363.1 NS DRGMIN Spacing Spacing  -117.3 66.7 NS Spacing Minimal -94.9   NS Spacing Moderate -69.6   NS    96 Region Crowding vs. Crowding Mean Difference Mean Standard Deviation P-Value (ANOVA) Spacing Severe -108.7   NS Minimal Minimal  -22.3 100.4 NS Minimal Moderate 25.3   NS Minimal Severe -13.8   NS Moderate Moderate  -47.7 94.7 NS Moderate Severe 39.1   NS Severe  Severe   -8.6 94 NS DTOT Spacing Spacing  -220.1 3916.2 NS Spacing Minimal 2162.2   NS Spacing Moderate 1284.1   NS Spacing Severe -880.8   NS Minimal Minimal  -2382.2 5572.2 NS Minimal Moderate -878.1   NS Minimal Severe -3043.0   NS Moderate Moderate  -1504.1 4547.5 NS Moderate Severe -2164.9   NS Severe Severe  660.8 3622.2 NS DTOTMIN Spacing Spacing  15.6 90.5 NS Spacing Minimal 65.2   NS Spacing Moderate 49.0   NS Spacing Severe -38.1   NS Minimal Minimal  -49.6 87.6 NS    97 Region Crowding vs. Crowding Mean Difference Mean Standard Deviation P-Value (ANOVA) Minimal Moderate -16.2   NS Minimal Severe -103.4   NS Moderate Moderate  -33.3 56.8 NS Moderate Severe -87.1   NS Severe Severe  53.8 46 NS *NS&=&nonsignificant,&DNPAIR&=&difference&in&nasopharyngeal&airway&volume,&&DTOT&=&difference&in&the&total&airway&volume,&&DTOTMIN&=&difference&in&the&total&minimum&axial&area,&&DRPAIR&=&difference&in&the&retropalatal&airway&volume,&&DRPMIN&=&difference&in&the&retropalatal&minimum&axial&area,&&DRGAIR&=&difference&in&the&retroglossal&airway&volume,&&DRGMIN&=&difference&in&the&retroglossal&minimum&axial&area.&&& &   98 Table&A.9&Patient&characteristics&with&identical&pre&and&post&treatment&scan&settings&" Total" Non-extraction" Extraction"Sample" 20" 16" 4"Females" 14" 11" 3"Males" 6" 5" 1"Age"(years)" 33.7±13.8" 34.4"±14.2" 31.0±14.1"Treatment"length"(months)" 17.6±5.8" 17.6"±5.8" 17.8"±5.5"Class%I%skeletal%relationship" 12" 9" 3"Class"II"skeletal"relationship" 8" 7" 1"Md#planeº##(low)" 4" 4" 0"Md#planeº##(normal)" 11" 9" 2"Md#planeº##(high)" 5" 3" 2"*Md&=&mandibular& &&&&&&&&&   99 Table&A.10&Treatment&time,&gender&distribution,&and&age&between&&dynamic&and&fixed&threshold&airway&analysis&&Variables& &Fixed&Threshold&Mean& &Fixed&Threshold&&SD& Dynamic&Threshold&Mean& Dynamic&Threshold&SD& pLvalue&Sample& 20& 20& 54& 54& &&Treatment&(months)& 21.3& 4.4& 20.1& 6.0& NS&Age&(years)& 34.0& 14.5& 29.0& 9.9& NS&Male*& 8& L& 17& L& NS&Female*& 12& L& 37& L& NS&• Pearson&chiLsquared&tests.&NS&=&nonsignificant&   

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