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The role of drug-induced sleep endoscopy and position-dependency in the diagnostic work-upof obstructive sleep apnea

Vonk, P.E.

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Download date: 21 Aug 2020

The role of drug-induced sleep endoscopy and

position-dependency in the diagnostic work-up of

obstructive sleep apnea

Patty E. Vonk

The role of drug-induced sleep endoscopy and position-dependency in the diagnostic w

ork-up of obstructive sleep apneaPatt

y E. Vonk

Uitnodigingvoor het bijwonen van de openbare

verdediging van het proefschrift

THE ROLE OF DRUG-INDUCED SLEEP ENDOSCOPY AND

POSITION-DEPENDENCY IN THE DIAGNOSTIC WORK-

UP OF OBSTRUCTIVE SLEEP APNEA

door

Patty Vonk

op vrijdag 24 januari 2020 om 13.00 uur

in de Aula der Universiteit, Singel 411 (hoek Spui), 1012 WN

Amsterdam

Na afloop bent u van harte uitgenodigd voor de receptie in

de Tetterode Bibliotheek

Patty VonkWichersstraat 72

1051 ML Amsterdam06-42853615

p.e.vonk@outlook.com

PARANIMFENMarleen van Tetering

06-30107053mvantetering@outlook.com

Fenna Peper06-23102428

fennapeper@hotmail.com

THEROLEOFDRUG-INDUCEDSLEEPENDOSCOPYAND

POSITION-DEPENDENCYINTHEDIAGNOSTICWORK-UPOF

OBSTRUCTIVESLEEPAPNEA

PattyE.Vonk

@2020PattyVonk

ISBN:978-94-6332-590-5

Coverdesign:PattyVonk

Layout:PattyVonkenGVOdrukkers&vormgeversB.V.

Printing:GVOdrukkers&vormgeversB.V.

Allrightsarereserved.Nopartofthisthesismaybereproduced,stored,ortransmittedinanyform

orbyanymeans,withoutpriorwrittenpermissionoftheauthor.

THEROLEOFDRUG-INDUCEDSLEEPENDOSCOPYAND

POSITION-DEPENDENCYINTHEDIAGNOSTICWORK-UPOFOBSTRUCTIVE

SLEEPAPNEA

ACADEMISCHPROEFSCHRIFT

terverkrijgingvandegraadvandoctor

aandeUniversiteitvanAmsterdam

opgezagvandeRectorMagnificus

prof.dr.ir.K.I.J.Maex

tenoverstaanvaneendoorhetCollegevoorPromotiesingesteldecommissie,

inhetopenbaarteverdedigenindeAuladerUniversiteit

opvrijdag24januari2020te13.00uur

doorPattyElisabethVonk

geborenteGeldrop

@2020PattyVonk

ISBN:978-94-6332-590-5

Coverdesign:PattyVonk

Layout:PattyVonkenGVOdrukkers&vormgeversB.V.

Printing:GVOdrukkers&vormgeversB.V.

Allrightsarereserved.Nopartofthisthesismaybereproduced,stored,ortransmittedinanyform

orbyanymeans,withoutpriorwrittenpermissionoftheauthor.

THEROLEOFDRUG-INDUCEDSLEEPENDOSCOPYAND

POSITION-DEPENDENCYINTHEDIAGNOSTICWORK-UPOFOBSTRUCTIVE

SLEEPAPNEA

ACADEMISCHPROEFSCHRIFT

terverkrijgingvandegraadvandoctor

aandeUniversiteitvanAmsterdam

opgezagvandeRectorMagnificus

prof.dr.ir.K.I.J.Maex

tenoverstaanvaneendoorhetCollegevoorPromotiesingesteldecommissie,

inhetopenbaarteverdedigenindeAuladerUniversiteit

opvrijdag24januari2020te13.00uur

doorPattyElisabethVonk

geborenteGeldrop

PROMOTIECOMMISSIE

Promotor

Prof.dr.N.deVries UniversiteitvanAmsterdam

Copromotores

Dr.M.J.L.Ravesloot OLVG

Dr.J.P.vanMaanen OLVG

Overigeleden

Prof.dr.J.deLange UniversiteitvanAmsterdam

Prof.dr.F.G.Dikkers UniversiteitvanAmsterdam

Prof.dr.F.Lobbezoo UniversiteitvanAmsterdam

Prof.dr.B.G.Loos UniversiteitvanAmsterdam

Prof.dr.F.R.Rozema UniversiteitvanAmsterdam

Prof.dr.O.M.Vanderveken UniversitairZiekenhuisAntwerpen

Prof.dr.J.Verbraecken UniversitairZiekenhuisAntwerpen

FaculteitderTandheelkunde

TABLEOFCONTENTS

CHAPTER1 Generalintroductionandoutlineofthesis

CHAPTER2 Towardsapredictionmodel fordrug-inducedsleependoscopyasselectiontool for

oral appliance treatment and positional therapy in obstructive sleep apnea

SleepBreath2018Dec;22(4):901-907

CHAPTER3 Drug-induced sleep endoscopy (DISE): New insights in lateral head rotation

compared to lateral head and trunk rotation in (non) positional obstructive sleep

apneapatients

Laryngoscope2019Oct;129(10):2430-2435

CHAPTER4 Jaw thrust versus the use of a boil and bitemandibular advancement device as a

screeningtoolduringdrug-inducedsleependoscopy

Submitted

CHAPTER5 Floppy epiglottis during drug-induced sleep endoscopy: an almost complete

resolutionbyadoptingthelateralposture

SleepBreath.2019Apr24.doi:10.1007/s11325-019-01847-x.

CHAPTER6 Short-term resultsofupperairway stimulation inobstructive sleepapneapatients:

theAmsterdamexperience

Submitted

CHAPTER7 Polysomnography and sleep position, an Heisenberg phenomenon? - a large scale

series

HNO.2019Sep;67(9):679-684.

CHAPTER8 Theinfluenceofposition-dependencyonsurgicalsuccessinobstructivesleepapnea

patientsundergoingupperairwaysurgery:asystematicreview

SleepBreath.2019Oct17.doi:10.1007/s11325-019-01935-y.

CHAPTER9 Theinfluenceofposition-dependencyonsurgicalsuccessinobstructivesleepapnea

patientsundergoingmaxillomandibularadvancement

JClinSleepMed.2019Nov27.pii:jc-19-00306.

CHAPTER10 Discussionandfutureperspectives

CHAPTER11 Summary/Samenvatting

Appendices Listofpublicationsandpresentations

PhDportfolio

CurriculumVitae

Dankwoord

TABLEOFCONTENTS

CHAPTER1 Generalintroductionandoutlineofthesis

CHAPTER2 Towardsapredictionmodel fordrug-inducedsleependoscopyasselectiontool for

oral appliance treatment and positional therapy in obstructive sleep apnea

SleepBreath2018Dec;22(4):901-907

CHAPTER3 Drug-induced sleep endoscopy (DISE): New insights in lateral head rotation

compared to lateral head and trunk rotation in (non) positional obstructive sleep

apneapatients

Laryngoscope2019Oct;129(10):2430-2435

CHAPTER4 Jaw thrust versus the use of a boil and bitemandibular advancement device as a

screeningtoolduringdrug-inducedsleependoscopy

Submitted

CHAPTER5 Floppy epiglottis during drug-induced sleep endoscopy: an almost complete

resolutionbyadoptingthelateralposture

SleepBreath.2019Apr24.doi:10.1007/s11325-019-01847-x

CHAPTER6 Short-term resultsofupperairway stimulation inobstructive sleepapneapatients:

theAmsterdamexperience

Submitted

CHAPTER7 Polysomnography and sleep position, an Heisenberg phenomenon? - a large scale

series

HNO.2019Sep;67(9):679-684

CHAPTER8 Theinfluenceofposition-dependencyonsurgicalsuccessinobstructivesleepapnea

patientsundergoingupperairwaysurgery:asystematicreview

SleepBreath.2019Oct17.doi:10.1007/s11325-019-01935-y

CHAPTER9 Theinfluenceofposition-dependencyonsurgicalsuccessinobstructivesleepapnea

patientsundergoingmaxillomandibularadvancement

JClinSleepMed.2019Nov27.pii:jc-19-00306

CHAPTER10 Discussionandfutureperspectives

CHAPTER11 Summary/Samenvatting

Appendices Listofpublicationsandpresentations

PhDportfolio

CurriculumVitae

Dankwoord

7

35

53

69

89

105

123

138

165

185

191

202

203

207

210

PROMOTIECOMMISSIE

Promotor

Prof.dr.N.deVries UniversiteitvanAmsterdam

Copromotores

Dr.M.J.L.Ravesloot OLVG

Dr.J.P.vanMaanen OLVG

Overigeleden

Prof.dr.J.deLange UniversiteitvanAmsterdam

Prof.dr.F.G.Dikkers UniversiteitvanAmsterdam

Prof.dr.F.Lobbezoo UniversiteitvanAmsterdam

Prof.dr.B.G.Loos UniversiteitvanAmsterdam

Prof.dr.F.R.Rozema UniversiteitvanAmsterdam

Prof.dr.O.M.Vanderveken UniversitairZiekenhuisAntwerpen

Prof.dr.J.Verbraecken UniversitairZiekenhuisAntwerpen

FaculteitderTandheelkunde

1Generalintroductionandoutlineofthesis

1Generalintroductionandoutlineofthesis

1Generalintroductionandoutlineofthesis

1Generalintroductionandoutlineofthesis

8

Chapter 1

GENERALINTRODUCTION

Sleepisoneofthemostimportantaspectsofourlives.Eventhoughhumansspendnearlyonethirdof

theirlivesasleep,thepurposeofsleephaslongremainedelusive.Inrecentyears,however,scientific

findings have shed new light on the vital importance of sufficient sleep. Among its many other

functions, sleepenhancesmemoryconsolidationandbrainplasticity, restockingour immunesystem

andabilitytolearn.1-3

Sleepdisorders

Research in a Dutch population has estimated the prevalence of too little sleep to be 30.4% and

insufficientsleeptobe43.2%.Generalsleepdisturbance(GSD)wasreportedin34.8%offemalesand

in29.1%inmales.FemaleadolescentsseemtohavethehighestprevalenceratesofGSDanddaytime

fatigue.4

Due to the gradual increase in public interest in sleep, and also due to increased knowledgeof the

impact of disturbed sleep on public heath, it is important to rely on an international, standardized

system for diagnosing patients with sleep-related problems. The most widely used classification

system for sleepdisorders is the InternationalClassificationof SleepDisorders (ICSD). The thirdand

latestedition,ICSD-3,comprisessevenmajorcategoriesofsleepdisorders:

• Insomnia

• Sleep-relatedbreathingdisorders

• Centraldisorderofhypersomnolence

• Circadianrhythmsleep-wakedisorders

• Parasomnias

• Sleep-relatedmovementdisorders

• Othersleepdisorders5

The ICSD-3 refers to and complements theManual for the Scoring of Sleep and Associated Events

publishedbytheAmericanAcademyofSleepMedicine(AASM).6

Inthisthesiswefocusonsleep-relatedbreathingdisorders,inparticularobstructivesleepapnea(OSA)

inadults.

Sleep-relatedbreathingdisorders

Sleep-disorderedbreathingisachronicdisordercharacterizedbyrecurrentepisodesofupperairway

(UA) collapse resulting in fragmented sleep, periodic oxygen desaturations and increases in blood

pressureduetoapneicevents.Ingeneral,sleep-relatedbreathingdisorders(SBD)canbedividedinto

fourcategories:

• Centralsleepapnea(CSA)

• Sleep-relatedhypoventilation

• Sleep-relatedhypoxemiadisorder

• Obstructivesleepapnea(OSA)6

Despite thedifferent ICSD-3classifications,patientsoftenmeet thecriteria formore thanonesleep

disorder. Forexample,manypatientshave featuresofbothOSAandCSA,which can changeduring

overnightrecording.Insomecases,CSAcanalsooccuraftereffectivetreatmentofobstructiveevents.

Inthesepatientsthetermtreatment-emergentCSAorcomplexsleepapneaisappropriate.5,7Table1

providesanoverviewofthedifferentformsofSBD.

9

General introduction and outline of thesis

1

GENERALINTRODUCTION

Sleepisoneofthemostimportantaspectsofourlives.Eventhoughhumansspendnearlyonethirdof

theirlivesasleep,thepurposeofsleephaslongremainedelusive.Inrecentyears,however,scientific

findings have shed new light on the vital importance of sufficient sleep. Among its many other

functions, sleepenhancesmemoryconsolidationandbrainplasticity, restockingour immunesystem

andabilitytolearn.1-3

Sleepdisorders

Research in a Dutch population has estimated the prevalence of too little sleep to be 30.4% and

insufficientsleeptobe43.2%.Generalsleepdisturbance(GSD)wasreportedin34.8%offemalesand

in29.1%inmales.FemaleadolescentsseemtohavethehighestprevalenceratesofGSDanddaytime

fatigue.4

Due to the gradual increase in public interest in sleep, and also due to increased knowledgeof the

impact of disturbed sleep on public heath, it is important to rely on an international, standardized

system for diagnosing patients with sleep-related problems. The most widely used classification

system for sleepdisorders is the InternationalClassificationof SleepDisorders (ICSD). The thirdand

latestedition,ICSD-3,comprisessevenmajorcategoriesofsleepdisorders:

• Insomnia

• Sleep-relatedbreathingdisorders

• Centraldisorderofhypersomnolence

• Circadianrhythmsleep-wakedisorders

• Parasomnias

• Sleep-relatedmovementdisorders

• Othersleepdisorders5

The ICSD-3 refers to and complements theManual for the Scoring of Sleep and Associated Events

publishedbytheAmericanAcademyofSleepMedicine(AASM).6

Inthisthesiswefocusonsleep-relatedbreathingdisorders,inparticularobstructivesleepapnea(OSA)

inadults.

Sleep-relatedbreathingdisorders

Sleep-disorderedbreathingisachronicdisordercharacterizedbyrecurrentepisodesofupperairway

(UA) collapse resulting in fragmented sleep, periodic oxygen desaturations and increases in blood

pressureduetoapneicevents.Ingeneral,sleep-relatedbreathingdisorders(SBD)canbedividedinto

fourcategories:

• Centralsleepapnea(CSA)

• Sleep-relatedhypoventilation

• Sleep-relatedhypoxemiadisorder

• Obstructivesleepapnea(OSA)6

Despite thedifferent ICSD-3classifications,patientsoftenmeet thecriteria formore thanonesleep

disorder. Forexample,manypatientshave featuresofbothOSAandCSA,which can changeduring

overnightrecording.Insomecases,CSAcanalsooccuraftereffectivetreatmentofobstructiveevents.

Inthesepatientsthetermtreatment-emergentCSAorcomplexsleepapneaisappropriate.5,7Table1

providesanoverviewofthedifferentformsofSBD.

10

Chapter 1

Table1.Sleep-RelatedBreathingDisorders5

Disorder

OSAdisorders

OSA,adult

OSA,pediatric

Centralsleepapneasyndromes

CentralsleepapneawithCheyne-Stokesbreathing

CentralsleepapneaduetoamedicaldisorderwithoutCheyne-Stokesbreathing

Centralsleepapneaduetohighaltitudeperiodicbreathing

Centralsleepapneaduetoamedicationorsubstance

Primarycentralsleepapnea

Primarycentralsleepapneaofinfancy

Primarycentralsleepapneaofprematurity

Treatment-emergentcentralsleepapnea

Sleep-relatedhypoventilationdisorders

Obesityhypoventilationsyndrome

Congenitalcentralalveolarhypoventilationsyndrome

Late-onsetcentralhypoventilationwithhypothalamicdysfunction

Idiopathiccentralalveolarhypoventilation

Sleep-relatedhypoventilationduetoamedicationorsubstance

Sleep-relatedhypoventilationduetoamedicaldisorder

Sleep-relatedhypoxemiadisorder

Obstructivesleepapnea

DefinitionandprevalenceOSA is defined according to the criteria of the ICSD and scoring rules of the AASM. Its diagnosis is

based on an apnea-hypopnea index (AHI) of ≥ 5 predominantly obstructive events or respiratory

effort-related arousals (RERAs) per hour in combination with OSA-associated symptoms, such as

fatigue, insomnia,snoringandexcessivedaytimesleepiness. ThecriteriaforOSAarealsometwhen

theAHI is ≥ 15withprimarily obstructive respiratory events per hour, even in the absenceofOSA-

relatedsymptomsorcomorbidities.5,8,9 IntheDutchguidelinepublished in2018thedistinctionhas

beenmadebetweenasymptomaticandsymptomaticOSA.InpatientswithelevatedAHIlevelswithout

anyclinicalsymptomsorcomorbiditiesrelatedtoOSA, ithasbeenquestionedwhethertreatment is

indicated,evenwhentheAHIis≥15events/h.10

OSA is themost prevalent SBD. In a recent large study in Switzerland, 49.7% ofmen and 23.4% of

womenaged40yearsorolder,werefoundtohaveanAHIof≥15events/h.12.5%ofmenand5.9%of

women had an AHI ≥ 15 events/h and excessive daytime sleepiness. 11 Other symptoms associated

withOSAincludesnoring,diminishedintellectualabilitiesandchangesinpersonality.12,13

Currently, the idea is reinforcedthatnotonlyan increasedAHI,butalsoOSA-relatedsymptomsand

comorbiditiesmustbe considered inpatient-specific treatmentplanning. 14 The clinical relevanceof

elevatedAHIlevelswithoutanyclinicalsymptoms,orcomorbiditiesrelatedtoOSA,hasnotyetbeen

determined.

RiskfactorsandconsequencesofuntreatedOSA

ThemostcommonriskfactorsfordevelopingOSAareobesity,increasedage,malegenderandasmall

or posteriorly positioned lower jaw, also called retrognathia. In obese patients, fatty tissue is often

depositedintheneckortongue,compressingtheUAduringsleepwhenthemuscletoneisreduced.15

Inwomen,ithasalsobeenshownthatpregnancyandmenopausecanbeariskfactorfordeveloping

OSA.16-18Otherpredisposingfactorsarealcoholuse,smokingandtheuseofsedatives.19WhenOSA

remainsuntreated,patientsareatahigherriskofdevelopingcardiovasculardiseasesorbeinginvolved

inatrafficaccident.20StudiesalsosuggestthatOSAisariskfactorforstroke,andisanindependent

predictorforfunctionalrecoveryandmortalityinstrokepatients.21-24

11

General introduction and outline of thesis

1

Table1.Sleep-RelatedBreathingDisorders5

Disorder

OSAdisorders

OSA,adult

OSA,pediatric

Centralsleepapneasyndromes

CentralsleepapneawithCheyne-Stokesbreathing

CentralsleepapneaduetoamedicaldisorderwithoutCheyne-Stokesbreathing

Centralsleepapneaduetohighaltitudeperiodicbreathing

Centralsleepapneaduetoamedicationorsubstance

Primarycentralsleepapnea

Primarycentralsleepapneaofinfancy

Primarycentralsleepapneaofprematurity

Treatment-emergentcentralsleepapnea

Sleep-relatedhypoventilationdisorders

Obesityhypoventilationsyndrome

Congenitalcentralalveolarhypoventilationsyndrome

Late-onsetcentralhypoventilationwithhypothalamicdysfunction

Idiopathiccentralalveolarhypoventilation

Sleep-relatedhypoventilationduetoamedicationorsubstance

Sleep-relatedhypoventilationduetoamedicaldisorder

Sleep-relatedhypoxemiadisorder

Obstructivesleepapnea

DefinitionandprevalenceOSA is defined according to the criteria of the ICSD and scoring rules of the AASM. Its diagnosis is

based on an apnea-hypopnea index (AHI) of ≥ 5 predominantly obstructive events or respiratory

effort-related arousals (RERAs) per hour in combination with OSA-associated symptoms, such as

fatigue, insomnia,snoringandexcessivedaytimesleepiness. ThecriteriaforOSAarealsometwhen

theAHI is ≥ 15withprimarily obstructive respiratory events per hour, even in the absenceofOSA-

relatedsymptomsorcomorbidities.5,8,9 IntheDutchguidelinepublished in2018thedistinctionhas

beenmadebetweenasymptomaticandsymptomaticOSA.InpatientswithelevatedAHIlevelswithout

anyclinicalsymptomsorcomorbiditiesrelatedtoOSA, ithasbeenquestionedwhethertreatment is

indicated,evenwhentheAHIis≥15events/h.10

OSA is themost prevalent SBD. In a recent large study in Switzerland, 49.7% ofmen and 23.4% of

womenaged40yearsorolder,werefoundtohaveanAHIof≥15events/h.12.5%ofmenand5.9%of

women had an AHI ≥ 15 events/h and excessive daytime sleepiness. 11 Other symptoms associated

withOSAincludesnoring,diminishedintellectualabilitiesandchangesinpersonality.12,13

Currently, the idea is reinforcedthatnotonlyan increasedAHI,butalsoOSA-relatedsymptomsand

comorbiditiesmustbe considered inpatient-specific treatmentplanning. 14 The clinical relevanceof

elevatedAHIlevelswithoutanyclinicalsymptoms,orcomorbiditiesrelatedtoOSA,hasnotyetbeen

determined.

RiskfactorsandconsequencesofuntreatedOSA

ThemostcommonriskfactorsfordevelopingOSAareobesity,increasedage,malegenderandasmall

or posteriorly positioned lower jaw, also called retrognathia. In obese patients, fatty tissue is often

depositedintheneckortongue,compressingtheUAduringsleepwhenthemuscletoneisreduced.15

Inwomen,ithasalsobeenshownthatpregnancyandmenopausecanbeariskfactorfordeveloping

OSA.16-18Otherpredisposingfactorsarealcoholuse,smokingandtheuseofsedatives.19WhenOSA

remainsuntreated,patientsareatahigherriskofdevelopingcardiovasculardiseasesorbeinginvolved

inatrafficaccident.20StudiesalsosuggestthatOSAisariskfactorforstroke,andisanindependent

predictorforfunctionalrecoveryandmortalityinstrokepatients.21-24

12

Chapter 1

PathogenesisofOSA

OSAischaracterizedbyrecurrentepisodesduringwhichairflowdecreasesduringsleepduetoapartial

or complete obstruction in the collapsible segment of the UA. The pathophysiological mechanism

behind this—whichalsodefines itsdifferentphenotypes—hasattractedgreatattention in recent

years. This is not surprising, since understanding of thesemechanisms is of paramount importance

when developing effective individual therapies for OSA patients. Historically, treatment modalities

such as continuous positive airway pressure (CPAP), mandibular advancement devices (MADs) and

different forms of UA surgery were introduced, aiming to reverse anatomical UA obstruction.

Nevertheless,thesetherapiesarenotalwayssuccessfulandrecentstudieshaveshownthatnotonly

anatomical,butalsonon-anatomicaltraitscontributetothepathophysiologyofOSA.25,26

In recent decades, four key contributors to the pathogenesis of OSA have been identified. These

include a narrow and/or collapsible airway — anatomical contributors — and non-anatomical

contributors, such as a low arousal threshold to narrowing of the upper airway during sleep, an

unstablecontrolofbreathing(highloopgain)andineffectiveUAdilatormuscleresponsiveness.25,26

AnatomicalcontributorstoOSA

ImpairedUAanatomyTheprimarycauseofOSAisimpairedUAanatomy.Itisself-evidentthatanarrowUAismoreproneto

collapse.Inthemajorityofpatients,themaincauseofanarrowUAisobesity.Thisismainlyduetothe

deposition of adipose tissue in the regions that surround the UA. The most common anatomical

structures can be involved inUA collapse: the soft palate (i.e., velum), the oropharynx (e.g., lateral

walls or tonsils), the tonguebase and the epiglottis. ComparisonofOSApatientswith healthy non-

apneiccontrolsshowsthatOSApatientstendtohavelargerpharyngealwalls,asmallerairwayatthe

retropalatal levelandnarrowingof theairway,predominantly in the lateraldimension. 27Thecross-

sectionalareaoftheUAmeasuredbycomputerizedtomography(CT) isalsosmaller inpatientswith

SDBthaninnon-apneiccontrols.28

UAcollapsibility

TheUAcontainsacollapsiblesegmentthatisinfluencedbythepressureofthesurroundingtissueof

the airway. If the pressure of the airway exceeds the intraluminal pressure, a negative intraluminal

pressurewillbecreated,causingUAcollapseandadecreaseinairflow.Theairwaypressurerequired

tocollapsetheUAisbestdesignatedbythepharyngealcriticalclosingpressure(Pcrit).Pcritisdependent

onmanyvariablesandisnotactuallyaproductofhypopharyngealpressure,butofthepressureinthe

UAmovingupstreamtowards thecollapsingsegment.Thus, thenegativepressuregeneratedby the

respiratorypumpmusclescanreduceairwaysize,butwillgenerallynotcollapsetheairway.Inother

words, as long as the intraluminal pressure remains higher than the Pcrit, inspiratory flow will be

maintained. As previous studies have shown, a high Pcrit is related to increasedUA pressure and to

OSA.29-32

Non-anatomicalcontributorstoOSA

Arousalthreshold

Formanydecades,corticalarousalshavebeenassumedtobeanimportantdefensivemechanismfor

re-establishingUApatencyinOSApatients.However,asubstantialproportionofrespiratoryeventsdo

not terminate inacorticalarousal; in someOSApatients, thesearousalsevenprecedea respiratory

event.Whereasarousalsmayreducethedurationofindividualrespiratoryevents,theyalsointerfere

withventilator stabilityandprogression todeeper sleepstages, thereby increasing the frequencyof

respiratoryevents.IthasalsobeensuggestedthatalowarousalthresholdisassociatedwithOSA.33,34

Loopgain

AnothermechanismthatcontributestothepathogenesisofOSAisthestabilityofloopgain(i.e.,the

respiratorycontrolsystem).Astherespiratorysystemisinfluencedbyloopgain,ithasthepotentialto

becomeunstable.Ahigh-gainsystemrespondseffectiveandquicklytoanevent,whereasalow-gain

systemrespondsmoreslowlyandweakly.Loopgaincanbebestdescribedbythefollowingformula:

Responsetoadisturbance/disturbanceitself(apneaorhypopnea)

If loop gain is less than 1, a respiratory disturbance such as an apnea or hypopnea will lead to a

response, but the responsewill be small and sufficient, enabling relatively quick stabilizationof the

ventilation.Iftheloopgainisgreaterthan1,theoppositewillhappen,causingawaxingandwaning

pattern of the ventilation. In summary, high gain destabilizes ventilation, and is generally more

prevalentduringsleep.32,35

Dilatormuscleresponsiveness

Thekeyprocess that counteracts thecollapsibilityof theUA ispharyngealdilatormuscleactivation.

Activation of the pharyngeal dilator muscles protects UA patency and counteracts the collapsing

forces. Although many dilator muscles maintain UA patency, the genioglossus muscle is the best

studied.Thismuscleisaninspiratoryphasicmuscle,whichiscontrolledbythreeprimaryneuralinputs.

First of all, negative pressure in the UA activatesmechanoreceptors that are locatedmainly in the

larynx.Activationof these receptors increaseshypoglossaloutput to thegenioglossusmuscle. Thus,

13

General introduction and outline of thesis

1

PathogenesisofOSA

OSAischaracterizedbyrecurrentepisodesduringwhichairflowdecreasesduringsleepduetoapartial

or complete obstruction in the collapsible segment of the UA. The pathophysiological mechanism

behind this—whichalsodefines itsdifferentphenotypes—hasattractedgreatattention in recent

years. This is not surprising, since understanding of thesemechanisms is of paramount importance

when developing effective individual therapies for OSA patients. Historically, treatment modalities

such as continuous positive airway pressure (CPAP), mandibular advancement devices (MADs) and

different forms of UA surgery were introduced, aiming to reverse anatomical UA obstruction.

Nevertheless,thesetherapiesarenotalwayssuccessfulandrecentstudieshaveshownthatnotonly

anatomical,butalsonon-anatomicaltraitscontributetothepathophysiologyofOSA.25,26

In recent decades, four key contributors to the pathogenesis of OSA have been identified. These

include a narrow and/or collapsible airway — anatomical contributors — and non-anatomical

contributors, such as a low arousal threshold to narrowing of the upper airway during sleep, an

unstablecontrolofbreathing(highloopgain)andineffectiveUAdilatormuscleresponsiveness.25,26

AnatomicalcontributorstoOSA

ImpairedUAanatomyTheprimarycauseofOSAisimpairedUAanatomy.Itisself-evidentthatanarrowUAismoreproneto

collapse.Inthemajorityofpatients,themaincauseofanarrowUAisobesity.Thisismainlyduetothe

deposition of adipose tissue in the regions that surround the UA. The most common anatomical

structures can be involved inUA collapse: the soft palate (i.e., velum), the oropharynx (e.g., lateral

walls or tonsils), the tonguebase and the epiglottis. ComparisonofOSApatientswith healthy non-

apneiccontrolsshowsthatOSApatientstendtohavelargerpharyngealwalls,asmallerairwayatthe

retropalatal levelandnarrowingof theairway,predominantly in the lateraldimension. 27Thecross-

sectionalareaoftheUAmeasuredbycomputerizedtomography(CT) isalsosmaller inpatientswith

SDBthaninnon-apneiccontrols.28

UAcollapsibility

TheUAcontainsacollapsiblesegmentthatisinfluencedbythepressureofthesurroundingtissueof

the airway. If the pressure of the airway exceeds the intraluminal pressure, a negative intraluminal

pressurewillbecreated,causingUAcollapseandadecreaseinairflow.Theairwaypressurerequired

tocollapsetheUAisbestdesignatedbythepharyngealcriticalclosingpressure(Pcrit).Pcritisdependent

onmanyvariablesandisnotactuallyaproductofhypopharyngealpressure,butofthepressureinthe

UAmovingupstreamtowards thecollapsingsegment.Thus, thenegativepressuregeneratedby the

respiratorypumpmusclescanreduceairwaysize,butwillgenerallynotcollapsetheairway.Inother

words, as long as the intraluminal pressure remains higher than the Pcrit, inspiratory flow will be

maintained. As previous studies have shown, a high Pcrit is related to increasedUA pressure and to

OSA.29-32

Non-anatomicalcontributorstoOSA

Arousalthreshold

Formanydecades,corticalarousalshavebeenassumedtobeanimportantdefensivemechanismfor

re-establishingUApatencyinOSApatients.However,asubstantialproportionofrespiratoryeventsdo

not terminate inacorticalarousal; in someOSApatients, thesearousalsevenprecedea respiratory

event.Whereasarousalsmayreducethedurationofindividualrespiratoryevents,theyalsointerfere

withventilator stabilityandprogression todeeper sleepstages, thereby increasing the frequencyof

respiratoryevents.IthasalsobeensuggestedthatalowarousalthresholdisassociatedwithOSA.33,34

Loopgain

AnothermechanismthatcontributestothepathogenesisofOSAisthestabilityofloopgain(i.e.,the

respiratorycontrolsystem).Astherespiratorysystemisinfluencedbyloopgain,ithasthepotentialto

becomeunstable.Ahigh-gainsystemrespondseffectiveandquicklytoanevent,whereasalow-gain

systemrespondsmoreslowlyandweakly.Loopgaincanbebestdescribedbythefollowingformula:

Responsetoadisturbance/disturbanceitself(apneaorhypopnea)

If loop gain is less than 1, a respiratory disturbance such as an apnea or hypopnea will lead to a

response, but the responsewill be small and sufficient, enabling relatively quick stabilizationof the

ventilation.Iftheloopgainisgreaterthan1,theoppositewillhappen,causingawaxingandwaning

pattern of the ventilation. In summary, high gain destabilizes ventilation, and is generally more

prevalentduringsleep.32,35

Dilatormuscleresponsiveness

Thekeyprocess that counteracts thecollapsibilityof theUA ispharyngealdilatormuscleactivation.

Activation of the pharyngeal dilator muscles protects UA patency and counteracts the collapsing

forces. Although many dilator muscles maintain UA patency, the genioglossus muscle is the best

studied.Thismuscleisaninspiratoryphasicmuscle,whichiscontrolledbythreeprimaryneuralinputs.

First of all, negative pressure in the UA activatesmechanoreceptors that are locatedmainly in the

larynx.Activationof these receptors increaseshypoglossaloutput to thegenioglossusmuscle. Thus,

14

Chapter 1

when a respiratory event causes negative pressure in the UA, genioglossal activity will increase,

therebycounteringtheevent.Secondly,genioglossalactivationisinfluencedbyrespiratoryneuronsin

themedulla.Thirdly,neuronsthatmodulatearousal–whichareactiveinthewakingstateandinactive

duringsleep–haveatonicinfluenceontheactivityofthehypoglossalmotorneurons,whichgenerally

increasemuscle activity. Naturally, it is important that, upon the onset of sleep, the control of the

musclesintheUAisretained.Unfortunately,duetolossofwakefulneuronalinputandadecreasein

responsetonegativepressureintheUA,thereisageneralfallinmuscleactivity.32

Non-positionalOSAandpositionalOSA

Definitionandprevalence

AnotherphenotypicapproachistocategorizeOSApatients innon-positionalOSApatients(NPP)and

positionalOSApatients(PP).36Inapproximately56-75%ofpatientsdiagnosedwithOSA,theseverity

ofUAcollapse is influencedbybodyposition. Inthesepatientsobstructiveeventsalmostexclusively

occurinthesupineposture.12,36-40Theprevalenceofposition-dependentOSA(POSA)decreasesasthe

severityofsleepapneaincreasesandthemajorityofPP(70-80%)havemildormoderateOSA.12,36,38,

41 PP also have a lowerbodymass index (BMI), and are younger in comparisonwithNPP. 12,36,38,42

Furthermore,theprevalenceofPOSAisthoughttobehigherinAsianpopulations.43-45

The literatureprovidesmanydefinitionsofPOSA. In1984,Cartwrightwasthefirst todescribePOSA

with the arbitrary cut-off point of a differenceof 50%ormore in apnea index between supine and

non-supine positions. 39 Since then, additions to these criteria have been introduced such as a

minimumsleepingtimespentinsupineandnon-supinepositionsandcut-offvaluesforthenon-supine

AHI. 41,46-48 In addition,POSAcanbedivided into supine isolatedOSA (non-supine<5events/h) and

supinepredominantOSA(non-supineAHI≥5events/h).49,50

Upperairwaycollapsepatterns

The underlying pathophysiological mechanism explaining different collapse patterns in supine and

non-supine sleeping position remains poorly understood. Over the past years, several studies have

beenpublishedaimingatunravelingtheunderlyingcauseofthesetwodifferentphenotypes.

Asdescribedbefore, thereareseveral levels intheUAthatcanbe involved inUAcollapse.Previous

studieshaveshownthatespeciallyobstructionatthelevelofthetonguebaseandepiglottis,andtoa

lesser extent the soft palate, are under influence of body position. The prevalence of lateral wall

obstruction is in general not affected by change in posture. However, persistent obstruction at the

level of the lateral walls of the pharynx in the non-supine position in NPP is more frequent in

comparisontoPP.51,52

Another interesting phenomenon is the presence of a primary epiglottic collapse, not secondary to

tonguebasecollapse(i.e.,floppyepiglottis[FE]). IthasbeensuggestedthataFEismainlypresentin

the supine position and to a lesser extent when the head is rotated to lateral position. 53 This

phenomenonisdescribedinmoredetailinchapter5.

Tocomplicatematters,evidence isalsogrowing thatPOSA isnotonlydependentonbodyposition,

butalsoonheadposition. Ithaspreviouslybeensuggested,thatOSAseveritysignificantlydecreases

whentheheadisrotatedfromsupinetoalateralposition,inparticularinnon-obesepatients.54,55

Diagnosis

ClinicalassessmentTheclinicalpresentationofpatientssuspectedtohaveOSAcanvaryamongpatients.Inallpatientsa

comprehensivesleepandmedicalhistoryshouldbetakenaswellasphysicalexamination.Information

concerningintoxications(i.e.,smoking,alcoholanddruguse),medicationuse,inparticulartheuseof

sedatives, and changes in weight should also be obtained. Symptoms related to OSA are snoring,

chokingorgaspingepisodesduringsleep,unrefreshingsleep,excessivedaytimesleepiness,observed

apneas,nocturia,drymouth,morningheadache,memoryloss,erectiledysfunction,andadecreasein

libidoandconcentration.

OnemethodtoassessdaytimesleepinessistheEpworthSleepinessscale(ESS).Thisself-administered

questionnaireprovideseight itemswherepatientsanswerquestionsbasedonhowlikelytheyareto

dozeoffor fall asleepduringseveralactivities (i.e.,0=wouldneverdoze;1=slightchanceofdozing;

2=moderate chance of dozing; 3=high chance of dozing). A total ESS score of more than 10 is

consideredtocorrelatewithexcessivedaytimesleepiness.56,57Whenusingself-reportingscalessuch

astheESS,itisimportanttokeepinmindthattheoutcomeofthesescalescanbeinfluencedbyother

externalfactorsaswell—andnotonlyOASseverity—Severalstudieshavequestionedthestrengthof

the correlation between the ESS and objective measures of sleep. 58-60 In addition, improving the

assessment of sleepiness in patients with OSA was recently identified as a key area that future

researchshouldprioritize.61

Physical examination should include BMI, neck circumference, the size of both palatine and tongue

tonsils,positionofthesoftpalate,lengthoftheuvula,mandiblepositionandsize,anddentalstatus.

15

General introduction and outline of thesis

1

when a respiratory event causes negative pressure in the UA, genioglossal activity will increase,

therebycounteringtheevent.Secondly,genioglossalactivationisinfluencedbyrespiratoryneuronsin

themedulla.Thirdly,neuronsthatmodulatearousal–whichareactiveinthewakingstateandinactive

duringsleep–haveatonicinfluenceontheactivityofthehypoglossalmotorneurons,whichgenerally

increasemuscle activity. Naturally, it is important that, upon the onset of sleep, the control of the

musclesintheUAisretained.Unfortunately,duetolossofwakefulneuronalinputandadecreasein

responsetonegativepressureintheUA,thereisageneralfallinmuscleactivity.32

Non-positionalOSAandpositionalOSA

Definitionandprevalence

AnotherphenotypicapproachistocategorizeOSApatients innon-positionalOSApatients(NPP)and

positionalOSApatients(PP).36Inapproximately56-75%ofpatientsdiagnosedwithOSA,theseverity

ofUAcollapse is influencedbybodyposition. Inthesepatientsobstructiveeventsalmostexclusively

occurinthesupineposture.12,36-40Theprevalenceofposition-dependentOSA(POSA)decreasesasthe

severityofsleepapneaincreasesandthemajorityofPP(70-80%)havemildormoderateOSA.12,36,38,

41 PP also have a lowerbodymass index (BMI), and are younger in comparisonwithNPP. 12,36,38,42

Furthermore,theprevalenceofPOSAisthoughttobehigherinAsianpopulations.43-45

The literatureprovidesmanydefinitionsofPOSA. In1984,Cartwrightwasthefirst todescribePOSA

with the arbitrary cut-off point of a differenceof 50%ormore in apnea index between supine and

non-supine positions. 39 Since then, additions to these criteria have been introduced such as a

minimumsleepingtimespentinsupineandnon-supinepositionsandcut-offvaluesforthenon-supine

AHI. 41,46-48 In addition,POSAcanbedivided into supine isolatedOSA (non-supine<5events/h) and

supinepredominantOSA(non-supineAHI≥5events/h).49,50

Upperairwaycollapsepatterns

The underlying pathophysiological mechanism explaining different collapse patterns in supine and

non-supine sleeping position remains poorly understood. Over the past years, several studies have

beenpublishedaimingatunravelingtheunderlyingcauseofthesetwodifferentphenotypes.

Asdescribedbefore, thereareseveral levels intheUAthatcanbe involved inUAcollapse.Previous

studieshaveshownthatespeciallyobstructionatthelevelofthetonguebaseandepiglottis,andtoa

lesser extent the soft palate, are under influence of body position. The prevalence of lateral wall

obstruction is in general not affected by change in posture. However, persistent obstruction at the

level of the lateral walls of the pharynx in the non-supine position in NPP is more frequent in

comparisontoPP.51,52

Another interesting phenomenon is the presence of a primary epiglottic collapse, not secondary to

tonguebasecollapse(i.e.,floppyepiglottis[FE]). IthasbeensuggestedthataFEismainlypresentin

the supine position and to a lesser extent when the head is rotated to lateral position. 53 This

phenomenonisdescribedinmoredetailinchapter5.

Tocomplicatematters,evidence isalsogrowing thatPOSA isnotonlydependentonbodyposition,

butalsoonheadposition. Ithaspreviouslybeensuggested,thatOSAseveritysignificantlydecreases

whentheheadisrotatedfromsupinetoalateralposition,inparticularinnon-obesepatients.54,55

Diagnosis

ClinicalassessmentTheclinicalpresentationofpatientssuspectedtohaveOSAcanvaryamongpatients.Inallpatientsa

comprehensivesleepandmedicalhistoryshouldbetakenaswellasphysicalexamination.Information

concerningintoxications(i.e.,smoking,alcoholanddruguse),medicationuse,inparticulartheuseof

sedatives, and changes in weight should also be obtained. Symptoms related to OSA are snoring,

chokingorgaspingepisodesduringsleep,unrefreshingsleep,excessivedaytimesleepiness,observed

apneas,nocturia,drymouth,morningheadache,memoryloss,erectiledysfunction,andadecreasein

libidoandconcentration.

OnemethodtoassessdaytimesleepinessistheEpworthSleepinessscale(ESS).Thisself-administered

questionnaireprovideseight itemswherepatientsanswerquestionsbasedonhowlikelytheyareto

dozeoffor fall asleepduringseveralactivities (i.e.,0=wouldneverdoze;1=slightchanceofdozing;

2=moderate chance of dozing; 3=high chance of dozing). A total ESS score of more than 10 is

consideredtocorrelatewithexcessivedaytimesleepiness.56,57Whenusingself-reportingscalessuch

astheESS,itisimportanttokeepinmindthattheoutcomeofthesescalescanbeinfluencedbyother

externalfactorsaswell—andnotonlyOASseverity—Severalstudieshavequestionedthestrengthof

the correlation between the ESS and objective measures of sleep. 58-60 In addition, improving the

assessment of sleepiness in patients with OSA was recently identified as a key area that future

researchshouldprioritize.61

Physical examination should include BMI, neck circumference, the size of both palatine and tongue

tonsils,positionofthesoftpalate,lengthoftheuvula,mandiblepositionandsize,anddentalstatus.

16

Chapter 1

PSG

Thegold standard todiagnoseOSA is a full-nightpolysomnography (PSG),duringwhich information

regardingthestagesofsleepcanbedeterminedusinganelectroencephalogram(Fp1,Fp2,C3,C4,O1,

O2), electro-oculogramand electromyogram (EMG)of the submentalmuscle. Tomeasure the nasal

airflow,anasalcannulawithapressuretransduceris insertedintheopeningofthenostrils.Afinger

pulseoximeter isalsoplacedtorecordarterialbloodoxyhemoglobin.Tomeasurethoracoabdominal

excursions, respiratory effort belts are placed over the abdomen and rib cage. Furthermore, limb

movementsaredetectedbyusingananteriortibialEMGwithsurfaceelectrodes.Apositionsensoris

used todeterminebodypositionof thepatient,whichdifferentiatesbetweenupright, rightand left

side,proneandsupinesleepposition.

DatacollectedshouldbescoredaccordingtotheAASMscoringmanual8,preferablybyanexperienced

sleepinvestigator.Anobstructiverespiratoryeventinadultsisscoredasanapneaifthereisadropin

thepeaksignalexcursionby≥90%withadurationofatleast≥10seconds.Ahypopneaisdefinedasa

decreaseofairflowby≥30%duringaperiodof≥10secondscombinedwithanoxygendesaturationof

≥3%.

Upperairwayassessment

Drug-inducedsleependoscopy(DISE)isadynamicanduniquediagnostictoolthatprovidesadditional

informationregardingthedegree,level(s)andconfigurationofobstructionofthecollapsiblesegment

oftheUA.DISEshouldbeperformedinselectedpatientsinwhomadditionalinformationconcerning

thedynamicsoftheUAisconsideredtobeofaddedvalue.Therefore,DISE isespecially indicated in

OSApatientswhenUAsurgeryorUAstimulationisconsidered,orincaseofCPAPorMADfailure.Less

wellexplored,andperhapsmorecontroversial, is the indication forDISEwhenMADorcombination

treatment(e.g.,MAD+positionaltherapy[PT],UAsurgery+PT)isconsidered.

DISEshouldonlybeperformedinpatientswithanacceptableoverallanestheticriskprofile.Absolute

contraindications areAmerican Society ofAnesthesiologists (ASA) classification 4, pregnancy and an

allergy to DISE sedative agents. Relative contraindications may include morbid obesity, since UA

surgeryisingeneralnotindicatedinmorbidlyobesepatients.62

DISEcanbeperformedinanysafeclinicalsetting,suchasanoperatingtheatre,endoscopysuite,ora

similarclinicalroomsetupwithstandardanestheticequipment.Aquietroomwithdimmed lights is

desirable,sinceonewants tomimic thesituationduringnaturalsleepascloseaspossible.Although

severaldrugsusedforDISEarereportedintheliterature,midazolamandpropofolarethetwodrugs

most widely used. 63 In 2018, an update of the European Position Paper on DISE was published,

recommending the use of propofolwith target-controlled infusion (TCI), since this provides amore

stableandreliablesedationincomparisontomanualinfusionorbolustechnique.62

Historically,DISEisperformedinthesupineposition.Althoughitmaybetechnicallyeasiertoperform

theprocedureonly in the supineposition, various studieshave found significantdifferences inDISE

findingsinthesupinepositionincomparisontonon-supinebodyposition.51-53Theroleofpostureand

differencesbetween lateralheadrotationand lateralheadandtrunkpositionaredescribed inmore

detailinchapter3.

OneoftheadvantagesofDISE isthat itallowsthephysiciantoperformdifferentpassivemaneuvers

withreassessmentofUApatencyaftereachoneofthem.Besidesbodyposture,twoothermaneuvers

havebeendescribedintheliterature:chin-liftandjawthrust,alsoknownastheEsmarchmaneuver.A

chin-liftisamanualclosureofthemouth,whilstajawthrustisagentleadvancementofthemandible

up to approximately 5mm. 64 By performing either one of thesemaneuvers, the physician aims to

mimic the effect of a MAD. As previously mentioned, the use of DISE before initiation of MAD

treatmentiscontroversialandthepredictivevalueofDISEforMADtreatmentsuccessvariesamongst

studies.65-67

Themaincauseforconcernisthatthepassivemaneuversperformedmimic,butarenotanexactand

accuratereproductionoftheeffectofaMAD.First,thethicknessofaMADisnottakenintoaccount,

which isrelevantsincetheverticalopening(VO)ofthemouthaffectsUApatency.Second,aMADis

usuallysetat60-75%ofmaximumprotrusion.Whenapplyingjawthrustitisdifficulttoestimatethe

desireddegreeofmandibleadvancement.Subsequently,theuseofasimulationbiteinareproducible

maximalcomfortableprotrusion(MCP)duringDISEhasbeensuggested.Studiessuggestthatthelatter

isabetterpredictorofMADresponse.68,69ThevalueofDISEasapredictiontoolforMADtreatmentis

discussedinmoredetailinchapter4.

ClassificationsystemforDISE

There are several classification systems described in the literature, but the most widely used and

acceptedoneistheVOTEclassificationsystem.TheVOTEclassificationsystemdistinguishesbetween

the four different levels and structures that may be involved in UA collapse, namely velum (V),

oropharynx(O),tonguebase(T)andepiglottis(E).Todefinethedegreeofobstruction,threedifferent

categories are used: 0) no obstruction (collapse less than 50%); 1) a partial obstruction (a collapse

between50-75%and typicallywith vibrationor 2) a complete obstruction (a collapse ofmore than

75%).AnXisusedwhennoobservationcanbemadeduetoforexamplehypersecretion.Depending

onthedifferentsite(s) involvedinUAobstruction,theconfigurationmaybeanterior-posterior(A-P),

17

General introduction and outline of thesis

1

PSG

Thegold standard todiagnoseOSA is a full-nightpolysomnography (PSG),duringwhich information

regardingthestagesofsleepcanbedeterminedusinganelectroencephalogram(Fp1,Fp2,C3,C4,O1,

O2), electro-oculogramand electromyogram (EMG)of the submentalmuscle. Tomeasure the nasal

airflow,anasalcannulawithapressuretransduceris insertedintheopeningofthenostrils.Afinger

pulseoximeter isalsoplacedtorecordarterialbloodoxyhemoglobin.Tomeasurethoracoabdominal

excursions, respiratory effort belts are placed over the abdomen and rib cage. Furthermore, limb

movementsaredetectedbyusingananteriortibialEMGwithsurfaceelectrodes.Apositionsensoris

used todeterminebodypositionof thepatient,whichdifferentiatesbetweenupright, rightand left

side,proneandsupinesleepposition.

DatacollectedshouldbescoredaccordingtotheAASMscoringmanual8,preferablybyanexperienced

sleepinvestigator.Anobstructiverespiratoryeventinadultsisscoredasanapneaifthereisadropin

thepeaksignalexcursionby≥90%withadurationofatleast≥10seconds.Ahypopneaisdefinedasa

decreaseofairflowby≥30%duringaperiodof≥10secondscombinedwithanoxygendesaturationof

≥3%.

Upperairwayassessment

Drug-inducedsleependoscopy(DISE)isadynamicanduniquediagnostictoolthatprovidesadditional

informationregardingthedegree,level(s)andconfigurationofobstructionofthecollapsiblesegment

oftheUA.DISEshouldbeperformedinselectedpatientsinwhomadditionalinformationconcerning

thedynamicsoftheUAisconsideredtobeofaddedvalue.Therefore,DISE isespecially indicated in

OSApatientswhenUAsurgeryorUAstimulationisconsidered,orincaseofCPAPorMADfailure.Less

wellexplored,andperhapsmorecontroversial, is the indication forDISEwhenMADorcombination

treatment(e.g.,MAD+positionaltherapy[PT],UAsurgery+PT)isconsidered.

DISEshouldonlybeperformedinpatientswithanacceptableoverallanestheticriskprofile.Absolute

contraindications areAmerican Society ofAnesthesiologists (ASA) classification 4, pregnancy and an

allergy to DISE sedative agents. Relative contraindications may include morbid obesity, since UA

surgeryisingeneralnotindicatedinmorbidlyobesepatients.62

DISEcanbeperformedinanysafeclinicalsetting,suchasanoperatingtheatre,endoscopysuite,ora

similarclinicalroomsetupwithstandardanestheticequipment.Aquietroomwithdimmed lights is

desirable,sinceonewants tomimic thesituationduringnaturalsleepascloseaspossible.Although

severaldrugsusedforDISEarereportedintheliterature,midazolamandpropofolarethetwodrugs

most widely used. 63 In 2018, an update of the European Position Paper on DISE was published,

recommending the use of propofolwith target-controlled infusion (TCI), since this provides amore

stableandreliablesedationincomparisontomanualinfusionorbolustechnique.62

Historically,DISEisperformedinthesupineposition.Althoughitmaybetechnicallyeasiertoperform

theprocedureonly in the supineposition, various studieshave found significantdifferences inDISE

findingsinthesupinepositionincomparisontonon-supinebodyposition.51-53Theroleofpostureand

differencesbetween lateralheadrotationand lateralheadandtrunkpositionaredescribed inmore

detailinchapter3.

OneoftheadvantagesofDISE isthat itallowsthephysiciantoperformdifferentpassivemaneuvers

withreassessmentofUApatencyaftereachoneofthem.Besidesbodyposture,twoothermaneuvers

havebeendescribedintheliterature:chin-liftandjawthrust,alsoknownastheEsmarchmaneuver.A

chin-liftisamanualclosureofthemouth,whilstajawthrustisagentleadvancementofthemandible

up to approximately 5mm. 64 By performing either one of thesemaneuvers, the physician aims to

mimic the effect of a MAD. As previously mentioned, the use of DISE before initiation of MAD

treatmentiscontroversialandthepredictivevalueofDISEforMADtreatmentsuccessvariesamongst

studies.65-67

Themaincauseforconcernisthatthepassivemaneuversperformedmimic,butarenotanexactand

accuratereproductionoftheeffectofaMAD.First,thethicknessofaMADisnottakenintoaccount,

which isrelevantsincetheverticalopening(VO)ofthemouthaffectsUApatency.Second,aMADis

usuallysetat60-75%ofmaximumprotrusion.Whenapplyingjawthrustitisdifficulttoestimatethe

desireddegreeofmandibleadvancement.Subsequently,theuseofasimulationbiteinareproducible

maximalcomfortableprotrusion(MCP)duringDISEhasbeensuggested.Studiessuggestthatthelatter

isabetterpredictorofMADresponse.68,69ThevalueofDISEasapredictiontoolforMADtreatmentis

discussedinmoredetailinchapter4.

ClassificationsystemforDISE

There are several classification systems described in the literature, but the most widely used and

acceptedoneistheVOTEclassificationsystem.TheVOTEclassificationsystemdistinguishesbetween

the four different levels and structures that may be involved in UA collapse, namely velum (V),

oropharynx(O),tonguebase(T)andepiglottis(E).Todefinethedegreeofobstruction,threedifferent

categories are used: 0) no obstruction (collapse less than 50%); 1) a partial obstruction (a collapse

between50-75%and typicallywith vibrationor 2) a complete obstruction (a collapse ofmore than

75%).AnXisusedwhennoobservationcanbemadeduetoforexamplehypersecretion.Depending

onthedifferentsite(s) involvedinUAobstruction,theconfigurationmaybeanterior-posterior(A-P),

18

Chapter 1

lateral or concentric. 70 Table 2 provides an overview of the degree and possible configurations of

obstruction at each level according to the VOTE classification system. In figure 1-6 examples of

collapsepatternscanbefound.

Table1.TheVOTEclassificationsystem70

Structure Degreeof

obstructionaConfigurationc

A-P Lateral Concentric

Velum

Oropharynxb

TongueBase

Epiglottis

A-PAntero-posterior

a. Degreeofobstruction:0noobstruction;1partialobstruction;2completeobstruction

b. Oropharynxobstruction canbedistinguishedas related solely to the tonsilsor including the

lateralwalls

c. Configurationnotedforstructureswithdegreeofobstruction>0

Figure1.Completeantero-posteriorcollapseatthelevelofthevelum(B)

Figure2.Partial(B)andcomplete(C)concentriccollapseatthelevelofthevelum

Figure 3. Partial (B) and complete (C) lateral wall collapse at the level of the velum and lateral

pharyngealwalls

(A) (B) (C)

(A) (B)

(B) (C)(A)

19

General introduction and outline of thesis

1

lateral or concentric. 70 Table 2 provides an overview of the degree and possible configurations of

obstruction at each level according to the VOTE classification system. In figure 1-6 examples of

collapsepatternscanbefound.

Table1.TheVOTEclassificationsystem70

Structure Degreeof

obstructionaConfigurationc

A-P Lateral Concentric

Velum

Oropharynxb

TongueBase

Epiglottis

A-PAntero-posterior

a. Degreeofobstruction:0noobstruction;1partialobstruction;2completeobstruction

b. Oropharynxobstruction canbedistinguishedas related solely to the tonsilsor including the

lateralwalls

c. Configurationnotedforstructureswithdegreeofobstruction>0

Figure1.Completeantero-posteriorcollapseatthelevelofthevelum(B)

Figure2.Partial(B)andcomplete(C)concentriccollapseatthelevelofthevelum

Figure 3. Partial (B) and complete (C) lateral wall collapse at the level of the velum and lateral

pharyngealwalls

(A) (B) (C)

(A) (B)

(B) (C)(A)

20

Chapter 1

Figure 4. A complete antero-posterior collapse (B) at the level of the epiglottis (i.e., FE, trapdoor

phenomenon)

Figure5.Atonguebasecollapseduetolingualtonsilhypertrophy(A,BandC)

Figure6.Acompleteantero-posteriorcollapse(B)ofthelevelofthetonguebasecollapseduetomuscle

relaxation

(A) (B)

(A) (B) (C)

(A) (B)

Conservativetreatment

Lifestylealterations

Standard recommendations in OSA patients include weight loss in overweight patients (BMI >

25kg/m2),avoidanceofsedativesandalcohol,propersleephygieneandcessationofsmoking.InOSA

patientswith a BMI ofmore than 35 kg/m2, bariatric surgery has proven to be effective aswell in

reducingOSAseveritywhenother—moreconservative—attemptstoloseweighthavefailed.71

CPAP

In1981,CPAPwasintroducedforthetreatmentofpatientswithOSA.72Sincethen,CPAPisconsidered

thegoldstandardtreatmentinpatientswithmoderatetosevereOSA.CPAPactsasapneumaticsplint,

preventing the UA from collapsing. CPAP has proven to be highly effective in reducing AHI and

improvementofqualityoflife,cognitivefunctionandsubjectivedaytimesleepiness.73

Despite its effectiveness in reversingOSA, patients are non-adherent in 29-83%when adherence is

defined as at least 4 hours of CPAPusageper night. 74Oneout of threepatients does not tolerate

CPAP. 75Possible sideeffectscontributing toCPAP intoleranceor failureare related to the interface

(e.g., skin abrasion from contactwith themask, claustrophobia,mask leak, irritated eyes), pressure

(e.g., nasal congestion and rhinorrhea with dryness or irritation of the nasal and pharyngeal

membranes,sneezing,gastricandboweldistension,recurrentearandsinus infections)andnegative

socialimpact.

PT

InPP,OSAseveritydependsonthetotalsleepingtime(TST)inthesupineposition.Avoidanceofthe

supine position is therefore a valuable therapeutic option. PT is aimed at preventing patients from

sleepinginthesupineposition.Varioustechniqueshavebeendescribed,butthemajorityofstudieson

PTusetheso-calledtennisballtechnique(TBT)whereabulkymassisstrappedtothepatient’sback.37

Even though TBT has proven to be effective in reducing the AHI and the percentage of TST in the

supine position, long-term compliance is poor. This is mainly due to backache, discomfort and no

improvement,orevendeteriorationofsleepqualityand/ordaytimealertness.37,76Compliancerates

ofTBTreportedintheliteraturerangefrom40-70%short-termtoonly10%atlong-termfollow-up.37,

77-79

Recentdevelopmentshaveseenthe introductionofanewgenerationofsmall, lightweight,battery-

powered vibro-tactile devices, which are either attached to the neck or chest. 13, 37, 48, 80When the

supinepositionisidentified,thesedevicesprovideavibratingstimulusaimingtoturnthepatienttoa

non-supine sleeping position. In a recentmeta-analysis, data for studies reporting on the effect of

21

General introduction and outline of thesis

1

Figure 4. A complete antero-posterior collapse (B) at the level of the epiglottis (i.e., FE, trapdoor

phenomenon)

Figure5.Atonguebasecollapseduetolingualtonsilhypertrophy(A,BandC)

Figure6.Acompleteantero-posteriorcollapse(B)ofthelevelofthetonguebasecollapseduetomuscle

relaxation

(A) (B)

(A) (B) (C)

(A) (B)

Conservativetreatment

Lifestylealterations

Standard recommendations in OSA patients include weight loss in overweight patients (BMI >

25kg/m2),avoidanceofsedativesandalcohol,propersleephygieneandcessationofsmoking.InOSA

patientswith a BMI ofmore than 35 kg/m2, bariatric surgery has proven to be effective aswell in

reducingOSAseveritywhenother—moreconservative—attemptstoloseweighthavefailed.71

CPAP

In1981,CPAPwasintroducedforthetreatmentofpatientswithOSA.72Sincethen,CPAPisconsidered

thegoldstandardtreatmentinpatientswithmoderatetosevereOSA.CPAPactsasapneumaticsplint,

preventing the UA from collapsing. CPAP has proven to be highly effective in reducing AHI and

improvementofqualityoflife,cognitivefunctionandsubjectivedaytimesleepiness.73

Despite its effectiveness in reversingOSA, patients are non-adherent in 29-83%when adherence is

defined as at least 4 hours of CPAPusageper night. 74Oneout of threepatients does not tolerate

CPAP. 75Possible sideeffectscontributing toCPAP intoleranceor failureare related to the interface

(e.g., skin abrasion from contactwith themask, claustrophobia,mask leak, irritated eyes), pressure

(e.g., nasal congestion and rhinorrhea with dryness or irritation of the nasal and pharyngeal

membranes,sneezing,gastricandboweldistension,recurrentearandsinus infections)andnegative

socialimpact.

PT

InPP,OSAseveritydependsonthetotalsleepingtime(TST)inthesupineposition.Avoidanceofthe

supine position is therefore a valuable therapeutic option. PT is aimed at preventing patients from

sleepinginthesupineposition.Varioustechniqueshavebeendescribed,butthemajorityofstudieson

PTusetheso-calledtennisballtechnique(TBT)whereabulkymassisstrappedtothepatient’sback.37

Even though TBT has proven to be effective in reducing the AHI and the percentage of TST in the

supine position, long-term compliance is poor. This is mainly due to backache, discomfort and no

improvement,orevendeteriorationofsleepqualityand/ordaytimealertness.37,76Compliancerates

ofTBTreportedintheliteraturerangefrom40-70%short-termtoonly10%atlong-termfollow-up.37,

77-79

Recentdevelopmentshaveseenthe introductionofanewgenerationofsmall, lightweight,battery-

powered vibro-tactile devices, which are either attached to the neck or chest. 13, 37, 48, 80When the

supinepositionisidentified,thesedevicesprovideavibratingstimulusaimingtoturnthepatienttoa

non-supine sleeping position. In a recentmeta-analysis, data for studies reporting on the effect of

22

Chapter 1

new-generationdevicesforPTwerecombined.ThepooledmeanreductioninAHIwas11.3events/h

(54%) and the pooledmean reduction in percentage of TST in supine position was 33.6%; amean

differenceof84%.81Short-termcomplianceishigh,varyingfrom76%to96%,whendefinedasatleast

4hoursofusepernightduring7daysaweek.80,82,83Long-termcomplianceisvaryingamongstudies

between64.4and75.5%.84,85Inanotherstudytheproportionofpatientsusingtheirdevicemorethan

4hoursduring5daysaweekafter12monthsoffollow-upwas100%.86

MAD

MADs are commonly used in patients with mild to moderate OSA or in case of CPAP failure in

moderate and severe disease. In order to preventUAobstruction,MADs are designed tomove the

mandible in a forward position. The tongue base, epiglottis and soft palate are protruded and as a

consequence, cross-sectional UA dimensions are increased reducing snoring and UA collapse. 87 In

addition,MADsmay also stimulate themusculature of the palate, tongue and pharynx, resulting in

decreasedUAresistance.88PreviousstudieshaveshownthatMADsaresuccessfulin84%ofpatients

withmild tomoderate OSA and in 69.2% of severe OSA patients. 89 Variety in reported treatment

successofMADismostlikelycausedbyapplicationofdifferentdefinitionsoftreatmentsuccess.

Combinationtreatment

During the past few years, combination treatment of non-surgical and surgical interventions has

gainedmoreground.Oneparticularstudysuggestedthat inpatientswithresidualsupine-dependent

OSAunderMADtreatment,combinationtreatmentwithPT leads toahigher therapeuticefficacyof

50%. 90 Another study also reported effective application of additional PT in patients with residual

POSAafterUAsurgery.91PTcanalsobecombinedwithlessinvasiveformsofUAsurgeryorcan,for

example, be applied in patients using CPAP to decrease the pressure needed, potentially improving

treatmentadherence.

Upperairwaysurgery

SleepapneasurgeryaimstoincreasethesurfaceareaoftheUA,tobypassthepharyngealairway(e.g.,

tracheotomy)ortoremovespecificpathologyandcanbeclassifiedintofourtypes:softtissuesurgery,

skeletal surgery, neurostimulatory or airway bypass. After identification of the structures or levels

involved inUAobstruction, surgical interventions canaddressone levelormultiple levels in theUA

(i.e.,multilevelUAsurgery).Inmorbidlyobesepatients,bariatricsurgeryisahighlyeffectivetreatment

forOSA.

Palatalandoropharyngealprocedures

The most commonly performed surgical procedure in OSA patients is still the

uvulopalatopharyngoplasty (UPPP) with or without tonsillectomy. UPPP aims to increase the

retropalatallumenandreducethecollapsibilityofthepharynxbyresectionofthefreeedgeofthesoft

palateanduvula,incombinationwithatonsillectomy.ThesurgicalsuccessoftheUPPPvariesamongst

studiesand isbetween35and95.2%. 92 In recentyears,newpalatal surgicalprocedureshavebeen

described, addressing the lateral pharyngeal wall to enlarge the oropharyngeal lumen, such as the

expansionsphincterpharyngoplasty(ESP)andbarbedrepositionpharyngoplasty(BRP).Thelatterisa

modificationofESPusingmultiple lateral sustaining loopsofbarbedsutureaiming tocreateamore

stableUAincomparisontotheESPtechnique,althoughstudiesreportthatBRPisnotmoreeffective

than ESP. 93-95 Previous studies have shown that both ESP and BRP have better postoperative AHI

valuesandhighersurgicalsuccessratesthanUPPP.

In patients with OSA based on hypertrophic tonsils, a classical tonsillectomy can suffice without

additionalpalatalsurgery.

Tonguebasesurgery

Many surgical procedures to address the area of the tongue base have been described in the

literature. These procedures include midline glossectomy 96, radiofrequency thermotherapy of the

tonguebase97,genioglossusadvancement98,hyoidthyroidpexia99,transoralroboticsurgery(TORS)100

andhypoglossalnervestimulation.101

Hypoglossalnervestimulation

Hypoglossalnervestimulation,alsoreferredtoasselectiveUAstimulation(UAS), isthemostrecent,

andinnovative,developmentfortreatmentofmoderatetosevereOSApatientswithCPAPintolerance

orfailure.Byusingaunilateralstimulation,selectivefibers,whicharemainly innervatingthetongue

protrusors, are stimulated during every breathing cycle. When the cervical spinal nerve (C1) is

included,thehyoidboneisalsomobilizeddisplacedinananterosuperiordirection.UASdoesnotonly

improve UA patency at the level of the tongue base, but also at retropalatal level. It has been

suggestedthatthismultileveleffectiscausedbypalatoglossalcoupling.102Inaddition,UASseemsto

be successful not only in patients with a primary tongue base collapse, but also in patients with

isolatedpalatalobstruction.103

23

General introduction and outline of thesis

1

new-generationdevicesforPTwerecombined.ThepooledmeanreductioninAHIwas11.3events/h

(54%) and the pooledmean reduction in percentage of TST in supine position was 33.6%; amean

differenceof84%.81Short-termcomplianceishigh,varyingfrom76%to96%,whendefinedasatleast

4hoursofusepernightduring7daysaweek.80,82,83Long-termcomplianceisvaryingamongstudies

between64.4and75.5%.84,85Inanotherstudytheproportionofpatientsusingtheirdevicemorethan

4hoursduring5daysaweekafter12monthsoffollow-upwas100%.86

MAD

MADs are commonly used in patients with mild to moderate OSA or in case of CPAP failure in

moderate and severe disease. In order to preventUAobstruction,MADs are designed tomove the

mandible in a forward position. The tongue base, epiglottis and soft palate are protruded and as a

consequence, cross-sectional UA dimensions are increased reducing snoring and UA collapse. 87 In

addition,MADsmay also stimulate themusculature of the palate, tongue and pharynx, resulting in

decreasedUAresistance.88PreviousstudieshaveshownthatMADsaresuccessfulin84%ofpatients

withmild tomoderate OSA and in 69.2% of severe OSA patients. 89 Variety in reported treatment

successofMADismostlikelycausedbyapplicationofdifferentdefinitionsoftreatmentsuccess.

Combinationtreatment

During the past few years, combination treatment of non-surgical and surgical interventions has

gainedmoreground.Oneparticularstudysuggestedthat inpatientswithresidualsupine-dependent

OSAunderMADtreatment,combinationtreatmentwithPT leads toahigher therapeuticefficacyof

50%. 90 Another study also reported effective application of additional PT in patients with residual

POSAafterUAsurgery.91PTcanalsobecombinedwithlessinvasiveformsofUAsurgeryorcan,for

example, be applied in patients using CPAP to decrease the pressure needed, potentially improving

treatmentadherence.

Upperairwaysurgery

SleepapneasurgeryaimstoincreasethesurfaceareaoftheUA,tobypassthepharyngealairway(e.g.,

tracheotomy)ortoremovespecificpathologyandcanbeclassifiedintofourtypes:softtissuesurgery,

skeletal surgery, neurostimulatory or airway bypass. After identification of the structures or levels

involved inUAobstruction, surgical interventions canaddressone levelormultiple levels in theUA

(i.e.,multilevelUAsurgery).Inmorbidlyobesepatients,bariatricsurgeryisahighlyeffectivetreatment

forOSA.

Palatalandoropharyngealprocedures

The most commonly performed surgical procedure in OSA patients is still the

uvulopalatopharyngoplasty (UPPP) with or without tonsillectomy. UPPP aims to increase the

retropalatallumenandreducethecollapsibilityofthepharynxbyresectionofthefreeedgeofthesoft

palateanduvula,incombinationwithatonsillectomy.ThesurgicalsuccessoftheUPPPvariesamongst

studiesand isbetween35and95.2%. 92 In recentyears,newpalatal surgicalprocedureshavebeen

described, addressing the lateral pharyngeal wall to enlarge the oropharyngeal lumen, such as the

expansionsphincterpharyngoplasty(ESP)andbarbedrepositionpharyngoplasty(BRP).Thelatterisa

modificationofESPusingmultiple lateral sustaining loopsofbarbedsutureaiming tocreateamore

stableUAincomparisontotheESPtechnique,althoughstudiesreportthatBRPisnotmoreeffective

than ESP. 93-95 Previous studies have shown that both ESP and BRP have better postoperative AHI

valuesandhighersurgicalsuccessratesthanUPPP.

In patients with OSA based on hypertrophic tonsils, a classical tonsillectomy can suffice without

additionalpalatalsurgery.

Tonguebasesurgery

Many surgical procedures to address the area of the tongue base have been described in the

literature. These procedures include midline glossectomy 96, radiofrequency thermotherapy of the

tonguebase97,genioglossusadvancement98,hyoidthyroidpexia99,transoralroboticsurgery(TORS)100

andhypoglossalnervestimulation.101

Hypoglossalnervestimulation

Hypoglossalnervestimulation,alsoreferredtoasselectiveUAstimulation(UAS), isthemostrecent,

andinnovative,developmentfortreatmentofmoderatetosevereOSApatientswithCPAPintolerance

orfailure.Byusingaunilateralstimulation,selectivefibers,whicharemainly innervatingthetongue

protrusors, are stimulated during every breathing cycle. When the cervical spinal nerve (C1) is

included,thehyoidboneisalsomobilizeddisplacedinananterosuperiordirection.UASdoesnotonly

improve UA patency at the level of the tongue base, but also at retropalatal level. It has been

suggestedthatthismultileveleffectiscausedbypalatoglossalcoupling.102Inaddition,UASseemsto

be successful not only in patients with a primary tongue base collapse, but also in patients with

isolatedpalatalobstruction.103

24

Chapter 1

Epiglottissurgery

Severalsurgicaltechniqueshavebeendevelopedtoresolveepiglotticcollapse,includingacompleteor

partialepiglottectomywitha(CO2)laser.104-106ManystudiesreportobjectiveimprovementoftheAHI,

but also several (major) complications—aspiration,bleedingwithandwithoutairway compromise,

dysphagiaandodynophagia—relatedtoepiglottissurgery,whichcanhaveseriousimplications.

Maxillomandibularadvancement

Maxillomandibular advancement (MMA) consists of a combination of a Le Fort I osteotomy and

bilateralsagittalsplitosteotomytoenlargethepharyngealairwayspace.Advancementofthemaxilla

andmandibleleadstoenlargementofthemedial-lateralandanteroposteriordimensionsoftheUA.107

Thistechniqueishighlyeffective intreatingsevereOSApatientswithsurgicalsuccessratesbetween

80and90%.108-112ComparedtoothersurgicaltechniquesMMAisconsideredtobemoreinvasiveand

inadditionassociatedwithconsiderablemorbidity.

OUTLINEOFTHISTHESIS

The general aim of this thesis is to assess the role of during DISE and position-dependency in the

diagnostic work-up of OSA patients to enable patient-specific treatment planning. In the end, the

ultimategoalistoimprovetreatmentoutcomeofbothsurgicalandnon-surgicaltreatmentmodalities

forOSA.

As previously mentioned, DISE has become an accepted tool in the diagnostic work-up for the

evaluationof surgical interventions inOSApatients.Morequestionable is theuseofDISE topredict

treatment outcome for non-surgical treatment modalities, such as MAD treatment, PT or a

combinationofboth.Chapter2formedthebasisforthestudiesdescribedinchapter3andchapter4.

WeintroducedatheoreticalmodeltoassessthepositiveeffectonUApatencyofdifferentmaneuvers

and compared these outcomeswith the effectiveness ofMAD treatment, PT and a combination of

both published in the literature. Based on the results of the study described in chapter 2, we

reassessedthesimilaritybetweentheeffectof lateralheadrotationandbothlateralheadandtrunk

positiononUAobstructioninchapter3.Inchapter4wefocusedontheroleofDISEfortheprediction

of MAD treatment outcome focusing on the potential role of a MAD simulation bite used as a

screeningtoolduringDISE.

Historically,DISEisperformedinthesupineposition,butwiththegrowingattentionfordifferencesin

UAcollapseandOSAseveritybetweenthesupineandnon-supineposition,onecouldalsoemphasize

therelevancetoperformDISE inbothpositions.TheperformanceofDISE in the lateralpositionhas

shednew lightoncollapsepatterns causingUAobstruction. Inchapter 5 thehypothesiswas tested

thataFEismainlypresentinsupinepositionandtoalesserextentwhenapatient’sheadisrotatedto

thelateralposition.Currently,OSAcausedbyaFEisdifficulttotreatandmosttreatmentoptionsfor

thistypeofcollapsearemostlylacking.Forexample,aFEhasbeenlinkedtoCPAPfailure,suggesting

that the epiglottis is pushed further backwards on application of CPAP. If our hypothesiswould be

true,PTcouldbeaddedto thearmamentariumfor the treatmentofOSAcausedbyaFE.The latter

couldalsounderlinetherelevanceofperformingDISEfornon-surgicalinterventionssinceaFEcannot

bedetectedthroughawakeendoscopy.

As previously mentioned, DISE has become an accepted tool in the diagnostic work-up for the

evaluationofsurgicalinterventionsinOSApatients.AlthoughDISEisperformedinmostsleepcentres

before initiating UA surgery, it is not mandatory in the majority of surgical interventions, with

exceptionofUAS. For this typeofUAsurgery,observationsmadeduringDISEare required, sincea

completeconcentriccollapseatpalatal levelhasbeenproventobeanegativepredictor forsurgical

success.Inchapter6theshort-termeffectivenessofUASinourcenterwasevaluated.Inaddition,we

25

General introduction and outline of thesis

1

Epiglottissurgery

Severalsurgicaltechniqueshavebeendevelopedtoresolveepiglotticcollapse,includingacompleteor

partialepiglottectomywitha(CO2)laser.104-106ManystudiesreportobjectiveimprovementoftheAHI,

but also several (major) complications—aspiration,bleedingwithandwithoutairway compromise,

dysphagiaandodynophagia—relatedtoepiglottissurgery,whichcanhaveseriousimplications.

Maxillomandibularadvancement

Maxillomandibular advancement (MMA) consists of a combination of a Le Fort I osteotomy and

bilateralsagittalsplitosteotomytoenlargethepharyngealairwayspace.Advancementofthemaxilla

andmandibleleadstoenlargementofthemedial-lateralandanteroposteriordimensionsoftheUA.107

Thistechniqueishighlyeffective intreatingsevereOSApatientswithsurgicalsuccessratesbetween

80and90%.108-112ComparedtoothersurgicaltechniquesMMAisconsideredtobemoreinvasiveand

inadditionassociatedwithconsiderablemorbidity.

OUTLINEOFTHISTHESIS

The general aim of this thesis is to assess the role of during DISE and position-dependency in the

diagnostic work-up of OSA patients to enable patient-specific treatment planning. In the end, the

ultimategoalistoimprovetreatmentoutcomeofbothsurgicalandnon-surgicaltreatmentmodalities

forOSA.

As previously mentioned, DISE has become an accepted tool in the diagnostic work-up for the

evaluationof surgical interventions inOSApatients.Morequestionable is theuseofDISE topredict

treatment outcome for non-surgical treatment modalities, such as MAD treatment, PT or a

combinationofboth.Chapter2formedthebasisforthestudiesdescribedinchapter3andchapter4.

WeintroducedatheoreticalmodeltoassessthepositiveeffectonUApatencyofdifferentmaneuvers

and compared these outcomeswith the effectiveness ofMAD treatment, PT and a combination of

both published in the literature. Based on the results of the study described in chapter 2, we

reassessedthesimilaritybetweentheeffectof lateralheadrotationandbothlateralheadandtrunk

positiononUAobstructioninchapter3.Inchapter4wefocusedontheroleofDISEfortheprediction

of MAD treatment outcome focusing on the potential role of a MAD simulation bite used as a

screeningtoolduringDISE.

Historically,DISEisperformedinthesupineposition,butwiththegrowingattentionfordifferencesin

UAcollapseandOSAseveritybetweenthesupineandnon-supineposition,onecouldalsoemphasize

therelevancetoperformDISE inbothpositions.TheperformanceofDISE in the lateralpositionhas

shednew lightoncollapsepatterns causingUAobstruction. Inchapter 5 thehypothesiswas tested

thataFEismainlypresentinsupinepositionandtoalesserextentwhenapatient’sheadisrotatedto

thelateralposition.Currently,OSAcausedbyaFEisdifficulttotreatandmosttreatmentoptionsfor

thistypeofcollapsearemostlylacking.Forexample,aFEhasbeenlinkedtoCPAPfailure,suggesting

that the epiglottis is pushed further backwards on application of CPAP. If our hypothesiswould be

true,PTcouldbeaddedto thearmamentariumfor the treatmentofOSAcausedbyaFE.The latter

couldalsounderlinetherelevanceofperformingDISEfornon-surgicalinterventionssinceaFEcannot

bedetectedthroughawakeendoscopy.

As previously mentioned, DISE has become an accepted tool in the diagnostic work-up for the

evaluationofsurgicalinterventionsinOSApatients.AlthoughDISEisperformedinmostsleepcentres

before initiating UA surgery, it is not mandatory in the majority of surgical interventions, with

exceptionofUAS. For this typeofUAsurgery,observationsmadeduringDISEare required, sincea

completeconcentriccollapseatpalatal levelhasbeenproventobeanegativepredictor forsurgical

success.Inchapter6theshort-termeffectivenessofUASinourcenterwasevaluated.Inaddition,we

26

Chapter 1

analyzed the influence of preoperative DISE findings on surgical success comparing patients with a

completemultilevelobstructionandpatientswithaprimarilycompletetonguebasecollapse.

In the second sectionof this thesis the relevanceand roleofposition-dependency in thediagnostic

work-upofOSApatientsisoutlined.First,inchapter7thehypothesiswastestedthatPSGapparatus

may influence sleeping position causing an overestimation in disease severity, especially in PP. This

couldpotentiallyleadtounnecessarytreatmentofpatients.Second,whenposition-dependencycould

be identified as a predictor for surgical success, this should be taken into consideration when

treatmentoptions,includingUAsurgery,areevaluated.Inchapter8asystematicreviewispresented

on the influence of position-dependency on surgical success of different forms of UA surgery. The

primaryaimofchapter9wastoanalyzethedifferenceinsurgicalsuccessinNPPandPPundergoing

MMA. Secondly, we evaluated the influence of position-dependency on surgical outcome and the

phenomenonofresidualPOSAinnon-responders.

Inchapter10themainfindingsofchapter2throughchapter9,generalconclusionsandsuggestions

forfutureresearcharedescribed.

Chapter11providesasummaryofthisthesisinEnglishandDutch.

REFERENCES1. WalkerMP.Theroleofsleepincognitionandemotion.AnnNYAcadSci.2009;1156:168-97.

2. WalkerMP,StickgoldR.Sleep,memory,andplasticity.AnnuRevPsychol.2006;57:139-66.

3. WalkerMP,StickgoldR,AlsopD,GaabN,SchlaugG.Sleep-dependentmotormemoryplasticity

inthehumanbrain.Neuroscience.2005;133(4):911-7.

4. Kerkhof GA. Epidemiology of sleep and sleep disorders in The Netherlands. Sleep Med.

2017;30:229-39.

5. Sateia MJ. International classification of sleep disorders-third edition: highlights and

modifications.Chest.2014;146(5):1387-94.

6. KapurVK,AuckleyDH,ChowdhuriS,etal.ClinicalPracticeGuidelineforDiagnosticTestingfor

AdultObstructiveSleepApnea:AnAmericanAcademyofSleepMedicineClinicalPracticeGuideline.J

ClinSleepMed.2017;13(3):479-504.

7. OrrJE,MalhotraA,SandsSA.Pathogenesisofcentralandcomplexsleepapnoea.Respirology.

2017;22(1):43-52.

8. BerryRB,BudhirajaR,GottliebDJ,etal.Rulesforscoringrespiratoryeventsinsleep:updateof

the 2007 AASMManual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep

Apnea Definitions Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med.

2012;8(5):597-619.

9. Force AAoSMT. Sleep-related breathing disorders in adults: recommendations for syndrome

definitionandmeasurementtechniquesinclinicalresearch.Sleep.1999;22:667-89.

10. NederlandseVerenigingvanArtsenvoorLonggeneeskundeenTuberculoseNVvK-heHvhh-hg.

Richtlijndiagnostiekenbehandelingvanobstructiefslaapapneu(OSA)bijvolwassenen.2017:1-94.

11. Heinzer R, Vat S, Marques-Vidal P, et al. Prevalence of sleep-disordered breathing in the

generalpopulation:theHypnoLausstudy.TheLancetRespiratoryMedicine.2015;3(4):310-18.

12. RichardW, Kox D, den Herder C, LamanM, van Tinteren H, de Vries N. The role of sleep

positioninobstructivesleepapneasyndrome.EurArchOtorhinolaryngol.2006;263(10):946-50.

13. vanMaanenJP,RichardW,VanKesterenER,etal.Evaluationofanewsimpletreatmentfor

positionalsleepapnoeapatients.JSleepRes.2012;21(3):322-9.

14. HeinzerR,Marti-SolerH,Haba-RubioJ.Prevalenceofsleepapnoeasyndromeinthemiddleto

oldagegeneralpopulation.LancetRespirMed.2016;4(2):e5-6.

15. MalhotraA,WhiteDP.Obstructivesleepapnoea.Lancet.2002;360(9328):237-45.

16. Pien GW, Fife D, Pack AI, Nkwuo JE, Schwab RJ. Changes in symptoms of sleep-disordered

breathingduringpregnancy.Sleep.2005;28(10):1299-305.

27

General introduction and outline of thesis

1

analyzed the influence of preoperative DISE findings on surgical success comparing patients with a

completemultilevelobstructionandpatientswithaprimarilycompletetonguebasecollapse.

In the second sectionof this thesis the relevanceand roleofposition-dependency in thediagnostic

work-upofOSApatientsisoutlined.First,inchapter7thehypothesiswastestedthatPSGapparatus

may influence sleeping position causing an overestimation in disease severity, especially in PP. This

couldpotentiallyleadtounnecessarytreatmentofpatients.Second,whenposition-dependencycould

be identified as a predictor for surgical success, this should be taken into consideration when

treatmentoptions,includingUAsurgery,areevaluated.Inchapter8asystematicreviewispresented

on the influence of position-dependency on surgical success of different forms of UA surgery. The

primaryaimofchapter9wastoanalyzethedifferenceinsurgicalsuccessinNPPandPPundergoing

MMA. Secondly, we evaluated the influence of position-dependency on surgical outcome and the

phenomenonofresidualPOSAinnon-responders.

Inchapter10themainfindingsofchapter2throughchapter9,generalconclusionsandsuggestions

forfutureresearcharedescribed.

Chapter11providesasummaryofthisthesisinEnglishandDutch.

REFERENCES1. WalkerMP.Theroleofsleepincognitionandemotion.AnnNYAcadSci.2009;1156:168-97

2. WalkerMP,StickgoldR.Sleep,memory,andplasticity.AnnuRevPsychol.2006;57:139-66

3. WalkerMP,StickgoldR,AlsopD,GaabN,SchlaugG.Sleep-dependentmotormemoryplasticity

inthehumanbrain.Neuroscience.2005;133(4):911-7

4. Kerkhof GA. Epidemiology of sleep and sleep disorders in The Netherlands. Sleep Med.

2017;30:229-39

5. Sateia MJ. International classification of sleep disorders-third edition: highlights and

modifications.Chest.2014;146(5):1387-94

6. KapurVK,AuckleyDH,ChowdhuriS,etal.ClinicalPracticeGuidelineforDiagnosticTestingfor

AdultObstructiveSleepApnea:AnAmericanAcademyofSleepMedicineClinicalPracticeGuideline.J

ClinSleepMed.2017;13(3):479-504

7. OrrJE,MalhotraA,SandsSA.Pathogenesisofcentralandcomplexsleepapnoea.Respirology.

2017;22(1):43-52

8. BerryRB,BudhirajaR,GottliebDJ,etal.Rulesforscoringrespiratoryeventsinsleep:updateof

the 2007 AASMManual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep

Apnea Definitions Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med.

2012;8(5):597-619

9. Force AAoSMT. Sleep-related breathing disorders in adults: recommendations for syndrome

definitionandmeasurementtechniquesinclinicalresearch.Sleep.1999;22:667-89

10. NederlandseVerenigingvanArtsenvoorLonggeneeskundeenTuberculoseNVvK-heHvhh-hg.

Richtlijndiagnostiekenbehandelingvanobstructiefslaapapneu(OSA)bijvolwassenen.2017:1-94

11. Heinzer R, Vat S, Marques-Vidal P, et al. Prevalence of sleep-disordered breathing in the

generalpopulation:theHypnoLausstudy.TheLancetRespiratoryMedicine.2015;3(4):310-18

12. RichardW, Kox D, den Herder C, LamanM, van Tinteren H, de Vries N. The role of sleep

positioninobstructivesleepapneasyndrome.EurArchOtorhinolaryngol.2006;263(10):946-50

13. vanMaanenJP,RichardW,VanKesterenER,etal.Evaluationofanewsimpletreatmentfor

positionalsleepapnoeapatients.JSleepRes.2012;21(3):322-9

14. HeinzerR,Marti-SolerH,Haba-RubioJ.Prevalenceofsleepapnoeasyndromeinthemiddleto

oldagegeneralpopulation.LancetRespirMed.2016;4(2):e5-6

15. MalhotraA,WhiteDP.Obstructivesleepapnoea.Lancet.2002;360(9328):237-45

16. Pien GW, Fife D, Pack AI, Nkwuo JE, Schwab RJ. Changes in symptoms of sleep-disordered

breathingduringpregnancy.Sleep.2005;28(10):1299-305

28

Chapter 1

17. Pien GW, Veasey SC. Obstructive sleep apnea and menopause. Sleep Disorders in Women.

Springer;2013:325-40

18. Pien GW, Pack AI, Jackson N, Maislin G, Macones GA, Schwab RJ. Risk factors for sleep-

disorderedbreathinginpregnancy.Thorax.2014;69(4):371-7

19. Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population

healthperspective.AmJRespirCritCareMed.2002;165(9):1217-39

20. GeorgeCF,SmileyA.Sleepapnea&automobilecrashes.Sleep.1999;22(6):790-5

21. YaggiHK,ConcatoJ,KernanWN,LichtmanJH,BrassLM,MohseninV.Obstructivesleepapnea

asariskfactorforstrokeanddeath.NewEnglandJournalofMedicine.2005;353(19):2034-41

22. ParraO,ArboixA,MontserratJ,QuintoL,BechichS,Garcia-ErolesL.Sleep-relatedbreathing

disorders: impact on mortality of cerebrovascular disease. European Respiratory Journal.

2004;24(2):267-72

23. ParraO,Sánchez-ArmengolÁ,CapoteF,etal.Efficacyofcontinuouspositiveairwaypressure

treatment on 5-year survival in patients with ischaemic stroke and obstructive sleep apnea: a

randomizedcontrolledtrial.Journalofsleepresearch.2015;24(1):47-53

24. Good DC, Henkle JQ, Gelber D, Welsh J, Verhulst S. Sleep-disordered breathing and poor

functionaloutcomeafterstroke.Stroke.1996;27(2):252-9

25. Eckert DJ. Phenotypic approaches to obstructive sleep apnoea–new pathways for targeted

therapy.Sleepmedicinereviews.2018;37:45-59

26. Eckert DJ, White DP, Jordan AS, Malhotra A, Wellman A. Defining phenotypic causes of

obstructive sleep apnea. Identification of novel therapeutic targets.American journal of respiratory

andcriticalcaremedicine.2013;188(8):996-1004

27. Schwab RJ, Gupta KB, GefterWB,Metzger LJ, Hoffman EA, Pack AI. Upper airway and soft

tissue anatomy in normal subjects and patientswith sleep-disordered breathing. Significance of the

lateralpharyngealwalls.AmJRespirCritCareMed.1995;152(5Pt1):1673-89

28. Haponik EF, Smith PL, Bohlman ME, Allen RP, Goldman SM, Bleecker ER. Computerized

tomography in obstructive sleep apnea. Correlation of airway sizewith physiology during sleep and

wakefulness.AmRevRespirDis.1983;127(2):221-6

29. Schwartz AR, Gold AR, Schubert N, Stryzak A. Effect of weight loss on upper airway

collapsibilityinobstructivesleepapnea1-3.AmRevRespirDis.1991;144(3pt1):494-98

30. SchwartzAR,SmithPL,WiseRA,GoldAR,PermuttS. Inductionofupperairwayocclusion in

sleepingindividualswithsubatmosphericnasalpressure.JApplPhysiol(1985).1988;64(2):535-42

31. Gleadhill IC, Schwartz AR, Schubert N, Wise RA, Permutt S, Smith PL. Upper airway

collapsibility in snorers and in patients with obstructive hypopnea and apnea. Am Rev Respir Dis.

1991;143(6):1300-3

32. White DP. Pathogenesis of obstructive and central sleep apnea.Am J Respir Crit CareMed.

2005;172(11):1363-70.

33. Eckert DJ, Younes MK. Arousal from sleep: implications for obstructive sleep apnea

pathogenesisandtreatment.JApplPhysiol(1985).2014;116(3):302-13.

34. YounesM.Roleof arousals in thepathogenesisofobstructive sleepapnea.Am JRespir Crit

CareMed.2004;169(5):623-33.

35. EckertDJ,MalhotraA.Pathophysiologyofadultobstructivesleepapnea.ProcAmThoracSoc.

2008;5(2):144-53.

36. OksenbergA,SilverbergDS,AronsE,RadwanH.Positionalvsnonpositionalobstructivesleep

apneapatients:anthropomorphic,nocturnalpolysomnographic,andmultiplesleep latencytestdata.

Chest.1997;112(3):629-39.

37. vanMaanenJP,RaveslootMJ,SafiruddinF,deVriesN.TheUtilityofSleepEndoscopyinAdults

with Obstructive Sleep Apnea: A Review of the Literature. Current Otorhinolaryngology Reports.

2013;1(1):1-7.

38. FrankMH,RaveslootMJ,vanMaanenJP,VerhagenE,deLangeJ,deVriesN.PositionalOSA

part1:Towardsaclinicalclassificationsystemforposition-dependentobstructivesleepapnoea.Sleep

Breath.2015;19(2):473-80.

39. CartwrightRD.Effectofsleeppositiononsleepapneaseverity.Sleep.1984;7(2):110-4.

40. Heinzer R, Petitpierre NJ, Marti-Soler H, Haba-Rubio J. Prevalence and characteristics of

positionalsleepapneaintheHypnoLauspopulation-basedcohort.(1878-5506(Electronic)).

41. MadorMJ,KufelTJ,MagalangUJ,RajeshSK,WatweV,GrantBJ.Prevalenceofpositionalsleep

apneainpatientsundergoingpolysomnography.Chest.2005;128(4):2130-7.

42. Itasaka Y,Miyazaki S, Ishikawa K, Togawa K. The influence of sleep position and obesity on

sleepapnea.PsychiatryClinNeurosci.2000;54(3):340-1.

43. Mo JH, Lee CH, Rhee CS, Yoon IY, Kim JW. Positional dependency in Asian patients with

obstructivesleepapneaanditsimplicationforhypertension.Archivesofotolaryngology--head&neck

surgery.2011;137(8):786-90.

44. Teerapraipruk B, Chirakalwasan N, Simon R, et al. Clinical and polysomnographic data of

positionalsleepapneaanditspredictors.Sleep&breathing=Schlaf&Atmung.2012;16(4):1167-72.

45. TanakaF,NakanoHFau-SudoN,SudoNFau-KuboC,KuboC.Relationshipbetweenthebody

position-specificapnea-hypopneaindexandsubjectivesleepiness.(1423-0356(Electronic)).

46. Marklund M, Persson M, Franklin KA. Treatment success with a mandibular advancement

deviceisrelatedtosupine-dependentsleepapnea.Chest.1998;114(6):1630-5.

47. PermutI,Diaz-AbadM,ChatilaW,etal.ComparisonofpositionaltherapytoCPAPinpatients

withpositionalobstructivesleepapnea.JClinSleepMed.2010;6(3):238-43.

29

General introduction and outline of thesis

1

17. Pien GW, Veasey SC. Obstructive sleep apnea and menopause. Sleep Disorders in Women.

Springer;2013:325-40.

18. Pien GW, Pack AI, Jackson N, Maislin G, Macones GA, Schwab RJ. Risk factors for sleep-

disorderedbreathinginpregnancy.Thorax.2014;69(4):371-7.

19. Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population

healthperspective.AmJRespirCritCareMed.2002;165(9):1217-39.

20. GeorgeCF,SmileyA.Sleepapnea&automobilecrashes.Sleep.1999;22(6):790-5.

21. YaggiHK,ConcatoJ,KernanWN,LichtmanJH,BrassLM,MohseninV.Obstructivesleepapnea

asariskfactorforstrokeanddeath.NewEnglandJournalofMedicine.2005;353(19):2034-41.

22. ParraO,ArboixA,MontserratJ,QuintoL,BechichS,Garcia-ErolesL.Sleep-relatedbreathing

disorders: impact on mortality of cerebrovascular disease. European Respiratory Journal.

2004;24(2):267-72.

23. ParraO,Sánchez-ArmengolÁ,CapoteF,etal.Efficacyofcontinuouspositiveairwaypressure

treatment on 5-year survival in patients with ischaemic stroke and obstructive sleep apnea: a

randomizedcontrolledtrial.Journalofsleepresearch.2015;24(1):47-53.

24. Good DC, Henkle JQ, Gelber D, Welsh J, Verhulst S. Sleep-disordered breathing and poor

functionaloutcomeafterstroke.Stroke.1996;27(2):252-9.

25. Eckert DJ. Phenotypic approaches to obstructive sleep apnoea–new pathways for targeted

therapy.Sleepmedicinereviews.2018;37:45-59.

26. Eckert DJ, White DP, Jordan AS, Malhotra A, Wellman A. Defining phenotypic causes of

obstructive sleep apnea. Identification of novel therapeutic targets.American journal of respiratory

andcriticalcaremedicine.2013;188(8):996-1004.

27. Schwab RJ, Gupta KB, GefterWB,Metzger LJ, Hoffman EA, Pack AI. Upper airway and soft

tissue anatomy in normal subjects and patientswith sleep-disordered breathing. Significance of the

lateralpharyngealwalls.AmJRespirCritCareMed.1995;152(5Pt1):1673-89.

28. Haponik EF, Smith PL, Bohlman ME, Allen RP, Goldman SM, Bleecker ER. Computerized

tomography in obstructive sleep apnea. Correlation of airway sizewith physiology during sleep and

wakefulness.AmRevRespirDis.1983;127(2):221-6.

29. Schwartz AR, Gold AR, Schubert N, Stryzak A. Effect of weight loss on upper airway

collapsibilityinobstructivesleepapnea1-3.AmRevRespirDis.1991;144(3pt1):494-98.

30. SchwartzAR,SmithPL,WiseRA,GoldAR,PermuttS. Inductionofupperairwayocclusion in

sleepingindividualswithsubatmosphericnasalpressure.JApplPhysiol(1985).1988;64(2):535-42.

31. Gleadhill IC, Schwartz AR, Schubert N, Wise RA, Permutt S, Smith PL. Upper airway

collapsibility in snorers and in patients with obstructive hypopnea and apnea. Am Rev Respir Dis.

1991;143(6):1300-3.

32. White DP. Pathogenesis of obstructive and central sleep apnea.Am J Respir Crit CareMed.

2005;172(11):1363-70

33. Eckert DJ, Younes MK. Arousal from sleep: implications for obstructive sleep apnea

pathogenesisandtreatment.JApplPhysiol(1985).2014;116(3):302-13

34. YounesM.Roleof arousals in thepathogenesisofobstructive sleepapnea.Am JRespir Crit

CareMed.2004;169(5):623-33

35. EckertDJ,MalhotraA.Pathophysiologyofadultobstructivesleepapnea.ProcAmThoracSoc.

2008;5(2):144-53

36. OksenbergA,SilverbergDS,AronsE,RadwanH.Positionalvsnonpositionalobstructivesleep

apneapatients:anthropomorphic,nocturnalpolysomnographic,andmultiplesleep latencytestdata.

Chest.1997;112(3):629-39

37. vanMaanenJP,RaveslootMJ,SafiruddinF,deVriesN.TheUtilityofSleepEndoscopyinAdults

with Obstructive Sleep Apnea: A Review of the Literature. Current Otorhinolaryngology Reports.

2013;1(1):1-7

38. FrankMH,RaveslootMJ,vanMaanenJP,VerhagenE,deLangeJ,deVriesN.PositionalOSA

part1:Towardsaclinicalclassificationsystemforposition-dependentobstructivesleepapnoea.Sleep

Breath.2015;19(2):473-80

39. CartwrightRD.Effectofsleeppositiononsleepapneaseverity.Sleep.1984;7(2):110-4

40. Heinzer R, Petitpierre NJ, Marti-Soler H, Haba-Rubio J. Prevalence and characteristics of

positionalsleepapneaintheHypnoLauspopulation-basedcohort.(1878-5506(Electronic))

41. MadorMJ,KufelTJ,MagalangUJ,RajeshSK,WatweV,GrantBJ.Prevalenceofpositionalsleep

apneainpatientsundergoingpolysomnography.Chest.2005;128(4):2130-7

42. Itasaka Y,Miyazaki S, Ishikawa K, Togawa K. The influence of sleep position and obesity on

sleepapnea.PsychiatryClinNeurosci.2000;54(3):340-1

43. Mo JH, Lee CH, Rhee CS, Yoon IY, Kim JW. Positional dependency in Asian patients with

obstructivesleepapneaanditsimplicationforhypertension.Archivesofotolaryngology--head&neck

surgery.2011;137(8):786-90

44. Teerapraipruk B, Chirakalwasan N, Simon R, et al. Clinical and polysomnographic data of

positionalsleepapneaanditspredictors.Sleep&breathing=Schlaf&Atmung.2012;16(4):1167-72

45. TanakaF,NakanoHFau-SudoN,SudoNFau-KuboC,KuboC.Relationshipbetweenthebody

position-specificapnea-hypopneaindexandsubjectivesleepiness.(1423-0356(Electronic))

46. Marklund M, Persson M, Franklin KA. Treatment success with a mandibular advancement

deviceisrelatedtosupine-dependentsleepapnea.Chest.1998;114(6):1630-5

47. PermutI,Diaz-AbadM,ChatilaW,etal.ComparisonofpositionaltherapytoCPAPinpatients

withpositionalobstructivesleepapnea.JClinSleepMed.2010;6(3):238-43

30

Chapter 1

48. BignoldJJ,MercerJD,AnticNA,McEvoyRD,CatchesidePG.Accuratepositionmonitoringand

improved supine-dependent obstructive sleep apnea with a new position recording and supine

avoidancedevice.JClinSleepMed.2011;7(4):376-83

49. Lee SA, Paek JH, Chung YS, KimWS. Clinical features in patientswith positional obstructive

sleepapneaaccordingtoitssubtypes.SleepBreath.2017;21(1):109-17

50. Kim KT, Cho YW, Kim DE, Hwang SH, Song ML, Motamedi GK. Two subtypes of positional

obstructivesleepapnea:Supine-predominantandsupine-isolated.ClinNeurophysiol.2016;127(1):565-

70

51. LeeCH,KimDK,KimSY,RheeCS,WonTB.Changesinsiteofobstructioninobstructivesleep

apneapatientsaccordingtosleepposition:aDISEstudy.TheLaryngoscope.2015;125(1):248-54

52. Victores AJ, Hamblin J, Gilbert J, Switzer C, TakashimaM.Usefulness of sleep endoscopy in

predictingpositionalobstructivesleepapnea.OtolaryngolHeadNeckSurg.2014;150(3):487-93

53. VonkPE,RaveslootMJL,KasiusKM,vanMaanenJP,deVriesN.Floppyepiglottisduringdrug-

inducedsleependoscopy:analmostcompleteresolutionbyadoptingthelateralposture.SleepBreath.

2019

54. vanKesterenER,vanMaanenJP,HilgevoordAA,LamanDM,deVriesN.Quantitativeeffectsof

trunk and head position on the apnea hypopnea index in obstructive sleep apnea. Sleep.

2011;34(8):1075-81

55. ZhuK,BradleyTD,PatelM,AlshaerH. Influenceofheadpositiononobstructivesleepapnea

severity.SleepBreath.2017;21(4):821-28

56. DonehB.EpworthSleepinessScale.OccupMed(Lond).2015;65(6):508

57. JohnsMW.A newmethod formeasuring daytime sleepiness: the Epworth sleepiness scale.

Sleep.1991;14(6):540-5

58. LopesC,EstevesAM,BittencourtLR,TufikS,MelloMT.Relationshipbetweenthequalityoflife

andtheseverityofobstructivesleepapneasyndrome.BrazJMedBiolRes.2008;41(10):908-13.

59. Weaver EM, Kapur V, Yueh B. Polysomnography vs self-reportedmeasures in patients with

sleepapnea.ArchOtolaryngolHeadNeckSurg.2004;130(4):453-8

60. Sforza E, Pichot V, Martin MS, Barthelemy JC, Roche F. Prevalence and determinants of

subjective sleepiness in healthy elderly with unrecognized obstructive sleep apnea. Sleep Med.

2015;16(8):981-6

61. RanderathW, Bassetti CL, BonsignoreMR, et al. Challenges and perspectives in obstructive

sleep apnoea: Report by an ad hocworking group of the Sleep Disordered Breathing Group of the

EuropeanRespiratorySocietyandtheEuropeanSleepResearchSociety.EurRespirJ.2018;52(3)

62. DeVitoA,Carrasco LlatasM,RaveslootMJ, et al. Europeanpositionpaperondrug-induced

sleependoscopy:2017Update.ClinicalOtolaryngology.2018;43(6):1541-52

63. Shteamer JW, Dedhia RC. Sedative choice in drug-induced sleep endoscopy: a

neuropharmacology-basedreview.TheLaryngoscope.2017;127(1):273-79.

64. HohenhorstW,RaveslootM,KezirianE,DeVriesN.Drug-inducedsleependoscopy inadults

withsleep-disorderedbreathing:techniqueandtheVOTEclassificationsystem.OperativeTechniques

inOtolaryngology-HeadandNeckSurgery.2012;23(1):11-18.

65. EichlerC,Sommer JU,StuckBA,HormannK,Maurer JT.Doesdrug-inducedsleependoscopy

change the treatment concept of patients with snoring and obstructive sleep apnea? Sleep Breath.

2013;17(1):63-8.

66. Johal A, Battagel JM, Kotecha BT. Sleep nasendoscopy: a diagnostic tool for predicting

treatment success withmandibular advancement splints in obstructive sleep apnoea. Eur J Orthod.

2005;27(6):607-14.

67. JohalA,HectorMP,BattagelJM,KotechaBT.Impactofsleepnasendoscopyontheoutcomeof

mandibularadvancementsplinttherapyinsubjectswithsleep-relatedbreathingdisorders.JLaryngol

Otol.2007;121(7):668-75.

68. VroegopAV,VandervekenOM,DieltjensM,WoutersK,SaldienV,BraemMJ.Sleependoscopy

with simulation bite for prediction of oral appliance treatment outcome. Journal of sleep research.

2013;22(3):348-55.

69. VandervekenOM,VroegopAV,vandeHeyningPH,BraemMJ.Drug-inducedsleependoscopy

completed with a simulation bite approach for the prediction of the outcome of treatment of

obstructive sleep apnea with mandibular repositioning appliances. Operative Techniques in

Otolaryngology-headandnecksurgery.2011;22(2):175-82.

70. KezirianEJ,HohenhorstW,deVriesN.Drug-inducedsleependoscopy:theVOTEclassification.

EurArchOtorhinolaryngol.2011;268(8):1233-36.

71. SarkhoshK,SwitzerNJ,El-HadiM,BirchDW,ShiX,KarmaliS.Theimpactofbariatricsurgery

onobstructivesleepapnea:asystematicreview.ObesSurg.2013;23(3):414-23.

72. SullivanC,Berthon-JonesM,IssaF,EvesL.Reversalofobstructivesleepapnoeabycontinuous

positiveairwaypressureappliedthroughthenares.TheLancet.1981;317(8225):862-65.

73. Giles TL, Lasserson TJ, Smith B, White J, Wright JJ, Cates CJ. Continuous positive airways

pressureforobstructivesleepapnoeainadults.CochraneDatabaseofSystematicReviews.2006(1).

74. Weaver TE, Grunstein RR. Adherence to continuous positive airway pressure therapy: the

challengetoeffectivetreatment.ProcAmThoracSoc.2008;5(2):173-8.

75. RichardW,Venker J,denHerderC,etal.Acceptanceand long-termcomplianceofnCPAP in

obstructivesleepapnea.EurArchOtorhinolaryngol.2007;264(9):1081-6.

31

General introduction and outline of thesis

1

48. BignoldJJ,MercerJD,AnticNA,McEvoyRD,CatchesidePG.Accuratepositionmonitoringand

improved supine-dependent obstructive sleep apnea with a new position recording and supine

avoidancedevice.JClinSleepMed.2011;7(4):376-83.

49. Lee SA, Paek JH, Chung YS, KimWS. Clinical features in patientswith positional obstructive

sleepapneaaccordingtoitssubtypes.SleepBreath.2017;21(1):109-17.

50. Kim KT, Cho YW, Kim DE, Hwang SH, Song ML, Motamedi GK. Two subtypes of positional

obstructivesleepapnea:Supine-predominantandsupine-isolated.ClinNeurophysiol.2016;127(1):565-

70.

51. LeeCH,KimDK,KimSY,RheeCS,WonTB.Changesinsiteofobstructioninobstructivesleep

apneapatientsaccordingtosleepposition:aDISEstudy.TheLaryngoscope.2015;125(1):248-54.

52. Victores AJ, Hamblin J, Gilbert J, Switzer C, TakashimaM.Usefulness of sleep endoscopy in

predictingpositionalobstructivesleepapnea.OtolaryngolHeadNeckSurg.2014;150(3):487-93.

53. VonkPE,RaveslootMJL,KasiusKM,vanMaanenJP,deVriesN.Floppyepiglottisduringdrug-

inducedsleependoscopy:analmostcompleteresolutionbyadoptingthelateralposture.SleepBreath.

2019.

54. vanKesterenER,vanMaanenJP,HilgevoordAA,LamanDM,deVriesN.Quantitativeeffectsof

trunk and head position on the apnea hypopnea index in obstructive sleep apnea. Sleep.

2011;34(8):1075-81.

55. ZhuK,BradleyTD,PatelM,AlshaerH. Influenceofheadpositiononobstructivesleepapnea

severity.SleepBreath.2017;21(4):821-28.

56. DonehB.EpworthSleepinessScale.OccupMed(Lond).2015;65(6):508.

57. JohnsMW.A newmethod formeasuring daytime sleepiness: the Epworth sleepiness scale.

Sleep.1991;14(6):540-5.

58. LopesC,EstevesAM,BittencourtLR,TufikS,MelloMT.Relationshipbetweenthequalityoflife

andtheseverityofobstructivesleepapneasyndrome.BrazJMedBiolRes.2008;41(10):908-13.

59. Weaver EM, Kapur V, Yueh B. Polysomnography vs self-reportedmeasures in patients with

sleepapnea.ArchOtolaryngolHeadNeckSurg.2004;130(4):453-8.

60. Sforza E, Pichot V, Martin MS, Barthelemy JC, Roche F. Prevalence and determinants of

subjective sleepiness in healthy elderly with unrecognized obstructive sleep apnea. Sleep Med.

2015;16(8):981-6.

61. RanderathW, Bassetti CL, BonsignoreMR, et al. Challenges and perspectives in obstructive

sleep apnoea: Report by an ad hocworking group of the Sleep Disordered Breathing Group of the

EuropeanRespiratorySocietyandtheEuropeanSleepResearchSociety.EurRespirJ.2018;52(3).

62. DeVitoA,Carrasco LlatasM,RaveslootMJ, et al. Europeanpositionpaperondrug-induced

sleependoscopy:2017Update.ClinicalOtolaryngology.2018;43(6):1541-52.

63. Shteamer JW, Dedhia RC. Sedative choice in drug-induced sleep endoscopy: a

neuropharmacology-basedreview.TheLaryngoscope.2017;127(1):273-79

64. HohenhorstW,RaveslootM,KezirianE,DeVriesN.Drug-inducedsleependoscopy inadults

withsleep-disorderedbreathing:techniqueandtheVOTEclassificationsystem.OperativeTechniques

inOtolaryngology-HeadandNeckSurgery.2012;23(1):11-18

65. EichlerC,Sommer JU,StuckBA,HormannK,Maurer JT.Doesdrug-inducedsleependoscopy

change the treatment concept of patients with snoring and obstructive sleep apnea? Sleep Breath.

2013;17(1):63-8

66. Johal A, Battagel JM, Kotecha BT. Sleep nasendoscopy: a diagnostic tool for predicting

treatment success withmandibular advancement splints in obstructive sleep apnoea. Eur J Orthod.

2005;27(6):607-14

67. JohalA,HectorMP,BattagelJM,KotechaBT.Impactofsleepnasendoscopyontheoutcomeof

mandibularadvancementsplinttherapyinsubjectswithsleep-relatedbreathingdisorders.JLaryngol

Otol.2007;121(7):668-75

68. VroegopAV,VandervekenOM,DieltjensM,WoutersK,SaldienV,BraemMJ.Sleependoscopy

with simulation bite for prediction of oral appliance treatment outcome. Journal of sleep research.

2013;22(3):348-55

69. VandervekenOM,VroegopAV,vandeHeyningPH,BraemMJ.Drug-inducedsleependoscopy

completed with a simulation bite approach for the prediction of the outcome of treatment of

obstructive sleep apnea with mandibular repositioning appliances. Operative Techniques in

Otolaryngology-headandnecksurgery.2011;22(2):175-82

70. KezirianEJ,HohenhorstW,deVriesN.Drug-inducedsleependoscopy:theVOTEclassification.

EurArchOtorhinolaryngol.2011;268(8):1233-36

71. SarkhoshK,SwitzerNJ,El-HadiM,BirchDW,ShiX,KarmaliS.Theimpactofbariatricsurgery

onobstructivesleepapnea:asystematicreview.ObesSurg.2013;23(3):414-23

72. SullivanC,Berthon-JonesM,IssaF,EvesL.Reversalofobstructivesleepapnoeabycontinuous

positiveairwaypressureappliedthroughthenares.TheLancet.1981;317(8225):862-65

73. Giles TL, Lasserson TJ, Smith B, White J, Wright JJ, Cates CJ. Continuous positive airways

pressureforobstructivesleepapnoeainadults.CochraneDatabaseofSystematicReviews.2006(1)

74. Weaver TE, Grunstein RR. Adherence to continuous positive airway pressure therapy: the

challengetoeffectivetreatment.ProcAmThoracSoc.2008;5(2):173-8

75. RichardW,Venker J,denHerderC,etal.Acceptanceand long-termcomplianceofnCPAP in

obstructivesleepapnea.EurArchOtorhinolaryngol.2007;264(9):1081-6

32

Chapter 1

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77. BignoldJJ,Deans-CostiG,GoldsworthyMR,etal.Poorlong-termpatientcompliancewiththe

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30

78. Oksenberg A, Silverberg D, Offenbach D, Arons E. Positional therapy for obstructive sleep

apneapatients:A6-monthfollow-upstudy.TheLaryngoscope.2006;116(11):1995-2000

79. Heinzer RC, Pellaton C, Rey V, et al. Positional therapy for obstructive sleep apnea: an

objectivemeasurementofpatients'usageandefficacyathome.Sleepmedicine.2012;13(4):425-8

80. Levendowski DJ, Seagraves S, Popovic D, Westbrook PR. Assessment of a neck-based

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81. RaveslootM,White D, Heinzer R, Oksenberg A, Pépin J. Efficacy of the NewGeneration of

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83. vanMaanen JP,Meester KA,Dun LN, et al. The sleep position trainer: a new treatment for

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84. vanMaanenJP,deVriesN.Long-termeffectivenessandcomplianceofpositionaltherapywith

the sleep position trainer in the treatment of positional obstructive sleep apnea syndrome. Sleep.

2014;37(7):1209-15

85. Laub RR, Tonnesen P, Jennum PJ. A Sleep Position Trainer for positional sleep apnea: a

randomized,controlledtrial.JSleepRes.2017

86. deRuiterMHT,BenoistLBL,deVriesN,deLangeJ.DurabilityoftreatmenteffectsoftheSleep

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controlledtrial.SleepBreath.2017

87. TsuikiS,LoweAA,AlmeidaFR,KawahataN,FleethamJA.Effectsofmandibularadvancement

onairwaycurvatureandobstructivesleepapnoeaseverity.EurRespirJ.2004;23(2):263-8

88. ChanAS,LeeRW,CistulliPA.Dentalappliance treatment forobstructivesleepapnea.Chest.

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89. HoekemaA,StegengaB,WijkstraPJ,vanderHoevenJH,MeineszAF,deBontLG.Obstructive

sleepapneatherapy.JDentRes.2008;87(9):882-7

90. DieltjensM,VroegopAV,VerbruggenAE,etal.Apromisingconceptofcombination therapy

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91. BenoistLB,VerhagenM,TorensmaB,vanMaanenJP,deVriesN.Positionaltherapyinpatients

withresidualpositionalobstructivesleepapneaafterupperairwaysurgery.SleepBreath.2016.

92. Stuck BA, Ravesloot MJ, Eschenhagen T, de Vet H, Sommer JU. Uvulopalatopharyngoplasty

withorwithouttonsillectomyinthetreatmentofadultobstructivesleepapnea–Asystematicreview.

Sleepmedicine.2018;50:152-65.

93. CammarotoG,MontevecchiF,D'AgostinoG,etal.Palatalsurgeryinatransoralroboticsetting

(TORS):preliminaryresultsofaretrospectivecomparisonbetweenuvulopalatopharyngoplasty(UPPP),

expansion sphincter pharyngoplasty (ESP) and barbed repositioning pharyngoplasty (BRP). Acta

otorhinolaryngologicaItalica:organoufficialedellaSocieta italianadiotorinolaringologiaechirurgia

cervico-facciale.2017.

94. Vicini C,Montevecchi F, Pang K, et al. Combined transoral robotic tongue base surgery and

palate surgery in obstructive sleep apnea-hypopnea syndrome: Expansion sphincter pharyngoplasty

versusuvulopalatopharyngoplasty.Head&neck.2014;36(1):77-83.

95. Montevecchi F, Meccariello G, Firinu E, et al. Prospective multicentre study on barbed

repositionpharyngoplastystandingaloneorasapartofmultilevelsurgery forsleepapnoea.Clinical

Otolaryngology.2018;43(2):483-88.

96. Fujita S, Woodson BT, Clark JL, Wittig R. Laser midline glossectomy as a treatment for

obstructivesleepapnea.TheLaryngoscope.1991;101(8):805-9.

97. StuckBA,KopkeJ,MaurerJT,etal.Lesionformationinradiofrequencysurgeryofthetongue

base.Laryngoscope.2003;113(9):1572-6.

98. RileyRW,PowellNB,GuilleminaultC.Obstructivesleepapneasyndrome:asurgicalprotocol

fordynamicupperairwayreconstruction.JOralMaxillofacSurg.1993;51(7):742-7;discussion48-9.

99. RileyRW,PowellNB,GuilleminaultC.Obstructivesleepapneaandthehyoid:arevisedsurgical

procedure.OtolaryngolHeadNeckSurg.1994;111(6):717-21.

100. Vicini C, Montevecchi F, Gobbi R, De Vito A, Meccariello G. Transoral robotic surgery for

obstructive sleep apnea syndrome: Principles and technique.World J Otorhinolaryngol Head Neck

Surg.2017;3(2):97-100.

101. StrolloPJ,Jr.,SooseRJ,MaurerJT,etal.Upper-airwaystimulationforobstructivesleepapnea.

NEnglJMed.2014;370(2):139-49.

102. HeiserC,EdenharterG,BasM,WirthM,HofauerB.Palatoglossuscouplinginselectiveupper

airwaystimulation.TheLaryngoscope.2017;127(10):E378-E83.

103. Mahmoud AF, Thaler ER. Outcomes of Hypoglossal Nerve Upper Airway Stimulation among

PatientswithIsolatedRetropalatalCollapse.OtolaryngolHeadNeckSurg.2019:194599819835186.

33

General introduction and outline of thesis

1

76. RaveslootMJ,BenoistL,vanMaanenP,deVriesN.Novelpositionaldevicesforthetreatment

ofpositionalobstructivesleepapnea,andhowthis relates tosleepsurgery.Sleep-RelatedBreathing

Disorders.KargerPublishers;2017:28-36.

77. BignoldJJ,Deans-CostiG,GoldsworthyMR,etal.Poorlong-termpatientcompliancewiththe

tennisballtechniquefortreatingpositionalobstructivesleepapnea.JClinSleepMed.2009;5(5):428-

30.

78. Oksenberg A, Silverberg D, Offenbach D, Arons E. Positional therapy for obstructive sleep

apneapatients:A6-monthfollow-upstudy.TheLaryngoscope.2006;116(11):1995-2000.

79. Heinzer RC, Pellaton C, Rey V, et al. Positional therapy for obstructive sleep apnea: an

objectivemeasurementofpatients'usageandefficacyathome.Sleepmedicine.2012;13(4):425-8.

80. Levendowski DJ, Seagraves S, Popovic D, Westbrook PR. Assessment of a neck-based

treatment and monitoring device for positional obstructive sleep apnea. J Clin Sleep Med.

2014;10(8):863-71.

81. RaveslootM,White D, Heinzer R, Oksenberg A, Pépin J. Efficacy of the NewGeneration of

Devices for Positional Therapy for Patients with Positional Obstructive Sleep Apnea: A Systematic

ReviewoftheLiteratureandMeta-Analysis.Journalofclinicalsleepmedicine:JCSM:officialpublication

oftheAmericanAcademyofSleepMedicine.2017.

82. EijsvogelMM,UbbinkR,DekkerJ,etal.Sleeppositiontrainerversustennisballtechniquein

positionalobstructivesleepapneasyndrome.JClinSleepMed.2015;11(2):139-47.

83. vanMaanen JP,Meester KA,Dun LN, et al. The sleep position trainer: a new treatment for

positionalobstructivesleepapnoea.SleepandBreathing.2013;17(2):771-79.

84. vanMaanenJP,deVriesN.Long-termeffectivenessandcomplianceofpositionaltherapywith

the sleep position trainer in the treatment of positional obstructive sleep apnea syndrome. Sleep.

2014;37(7):1209-15.

85. Laub RR, Tonnesen P, Jennum PJ. A Sleep Position Trainer for positional sleep apnea: a

randomized,controlledtrial.JSleepRes.2017.

86. deRuiterMHT,BenoistLBL,deVriesN,deLangeJ.DurabilityoftreatmenteffectsoftheSleep

PositionTrainerversusoralappliancetherapyinpositionalOSA:12-monthfollow-upofarandomized

controlledtrial.SleepBreath.2017.

87. TsuikiS,LoweAA,AlmeidaFR,KawahataN,FleethamJA.Effectsofmandibularadvancement

onairwaycurvatureandobstructivesleepapnoeaseverity.EurRespirJ.2004;23(2):263-8.

88. ChanAS,LeeRW,CistulliPA.Dentalappliance treatment forobstructivesleepapnea.Chest.

2007;132(2):693-9.

89. HoekemaA,StegengaB,WijkstraPJ,vanderHoevenJH,MeineszAF,deBontLG.Obstructive

sleepapneatherapy.JDentRes.2008;87(9):882-7.

90. DieltjensM,VroegopAV,VerbruggenAE,etal.Apromisingconceptofcombination therapy

forpositionalobstructivesleepapnea.SleepBreath.2015;19(2):637-44

91. BenoistLB,VerhagenM,TorensmaB,vanMaanenJP,deVriesN.Positionaltherapyinpatients

withresidualpositionalobstructivesleepapneaafterupperairwaysurgery.SleepBreath.2016

92. Stuck BA, Ravesloot MJ, Eschenhagen T, de Vet H, Sommer JU. Uvulopalatopharyngoplasty

withorwithouttonsillectomyinthetreatmentofadultobstructivesleepapnea–Asystematicreview.

Sleepmedicine.2018;50:152-65

93. CammarotoG,MontevecchiF,D'AgostinoG,etal.Palatalsurgeryinatransoralroboticsetting

(TORS):preliminaryresultsofaretrospectivecomparisonbetweenuvulopalatopharyngoplasty(UPPP),

expansion sphincter pharyngoplasty (ESP) and barbed repositioning pharyngoplasty (BRP). Acta

otorhinolaryngologicaItalica:organoufficialedellaSocieta italianadiotorinolaringologiaechirurgia

cervico-facciale.2017

94. Vicini C,Montevecchi F, Pang K, et al. Combined transoral robotic tongue base surgery and

palate surgery in obstructive sleep apnea-hypopnea syndrome: Expansion sphincter pharyngoplasty

versusuvulopalatopharyngoplasty.Head&neck.2014;36(1):77-83

95. Montevecchi F, Meccariello G, Firinu E, et al. Prospective multicentre study on barbed

repositionpharyngoplastystandingaloneorasapartofmultilevelsurgery forsleepapnoea.Clinical

Otolaryngology.2018;43(2):483-88

96. Fujita S, Woodson BT, Clark JL, Wittig R. Laser midline glossectomy as a treatment for

obstructivesleepapnea.TheLaryngoscope.1991;101(8):805-9

97. StuckBA,KopkeJ,MaurerJT,etal.Lesionformationinradiofrequencysurgeryofthetongue

base.Laryngoscope.2003;113(9):1572-6

98. RileyRW,PowellNB,GuilleminaultC.Obstructivesleepapneasyndrome:asurgicalprotocol

fordynamicupperairwayreconstruction.JOralMaxillofacSurg.1993;51(7):742-7;discussion48-9

99. RileyRW,PowellNB,GuilleminaultC.Obstructivesleepapneaandthehyoid:arevisedsurgical

procedure.OtolaryngolHeadNeckSurg.1994;111(6):717-21

100. Vicini C, Montevecchi F, Gobbi R, De Vito A, Meccariello G. Transoral robotic surgery for

obstructive sleep apnea syndrome: Principles and technique.World J Otorhinolaryngol Head Neck

Surg.2017;3(2):97-100

101. StrolloPJ,Jr.,SooseRJ,MaurerJT,etal.Upper-airwaystimulationforobstructivesleepapnea.

NEnglJMed.2014;370(2):139-49

102. HeiserC,EdenharterG,BasM,WirthM,HofauerB.Palatoglossuscouplinginselectiveupper

airwaystimulation.TheLaryngoscope.2017;127(10):E378-E83

103. Mahmoud AF, Thaler ER. Outcomes of Hypoglossal Nerve Upper Airway Stimulation among

PatientswithIsolatedRetropalatalCollapse.OtolaryngolHeadNeckSurg.2019:194599819835186

34

Chapter 1

104. CatalfumoFJ,GolzA,Westerman ST,Gilbert LM, JoachimsHZ,GoldenbergD. The epiglottis

andobstructivesleepapnoeasyndrome.JLaryngolOtol.1998;112(10):940-3

105. GolzA,GoldenbergD,WestermanST,etal.Laserpartialepiglottidectomyasatreatmentfor

obstructivesleepapneaandlaryngomalacia.AnnOtolRhinolLaryngol.2000;109(12Pt1):1140-5

106. BouroliasC,Hajiioannou J, SobolE,VelegrakisG,HelidonisE. Epiglottis reshapingusingCO2

laser:aminimallyinvasivetechniqueanditspotentapplications.HeadFaceMed.2008;4:15

107. GokceSM,GorguluS,GokceHS,BengiAO,KaracayliU,OrsF.Evaluationofpharyngealairway

space changes after bimaxillary orthognathic surgerywith a 3-dimensional simulation andmodeling

program.AmJOrthodDentofacialOrthop.2014;146(4):477-92

108. Holty JE, Guilleminault C.Maxillomandibular advancement for the treatment of obstructive

sleepapnea:asystematicreviewandmeta-analysis.SleepMedRev.2010;14(5):287-97

109. Prinsell JR.Maxillomandibularadvancementsurgery forobstructivesleepapneasyndrome. J

AmDentAssoc.2002;133(11):1489-97;quiz539-40

110. Prinsell JR.Maxillomandibularadvancementsurgery inasite-specifictreatmentapproachfor

obstructivesleepapneain50consecutivepatients.Chest.1999;116(6):1519-29

111. Hoekema A, de Lange J, Stegenga B, de Bont LG. Oral appliances and maxillomandibular

advancement surgery: an alternative treatment protocol for the obstructive sleep apnea-hypopnea

syndrome.JOralMaxillofacSurg.2006;64(6):886-91

112. Goh YH, LimKA.Modifiedmaxillomandibular advancement for the treatmentof obstructive

sleepapnea:apreliminaryreport.Laryngoscope.2003;113(9):1577-82

2Towards a prediction model fordrug-induced sleep endoscopy asselection tool for oral appliancetreatment and positional therapyinobstructivesleepapneaP.E.Vonk,A.M.E.H.Beelen,N.deVriesSleepBreath.2018Dec;22(4):901-907

2Towards a prediction model fordrug-induced sleep endoscopy asselection tool for oral appliancetreatment and positional therapyinobstructivesleepapneaP.E.Vonk,A.M.E.H.Beelen,N.deVriesSleepBreath.2018Dec;22(4):901-907

104. CatalfumoFJ,GolzA,Westerman ST,Gilbert LM, JoachimsHZ,GoldenbergD. The epiglottis

andobstructivesleepapnoeasyndrome.JLaryngolOtol.1998;112(10):940-3.

105. GolzA,GoldenbergD,WestermanST,etal.Laserpartialepiglottidectomyasatreatmentfor

obstructivesleepapneaandlaryngomalacia.AnnOtolRhinolLaryngol.2000;109(12Pt1):1140-5.

106. BouroliasC,Hajiioannou J, SobolE,VelegrakisG,HelidonisE. Epiglottis reshapingusingCO2

laser:aminimallyinvasivetechniqueanditspotentapplications.HeadFaceMed.2008;4:15.

107. GokceSM,GorguluS,GokceHS,BengiAO,KaracayliU,OrsF.Evaluationofpharyngealairway

space changes after bimaxillary orthognathic surgerywith a 3-dimensional simulation andmodeling

program.AmJOrthodDentofacialOrthop.2014;146(4):477-92.

108. Holty JE, Guilleminault C.Maxillomandibular advancement for the treatment of obstructive

sleepapnea:asystematicreviewandmeta-analysis.SleepMedRev.2010;14(5):287-97.

109. Prinsell JR.Maxillomandibularadvancementsurgery forobstructivesleepapneasyndrome. J

AmDentAssoc.2002;133(11):1489-97;quiz539-40.

110. Prinsell JR.Maxillomandibularadvancementsurgery inasite-specifictreatmentapproachfor

obstructivesleepapneain50consecutivepatients.Chest.1999;116(6):1519-29.

111. Hoekema A, de Lange J, Stegenga B, de Bont LG. Oral appliances and maxillomandibular

advancement surgery: an alternative treatment protocol for the obstructive sleep apnea-hypopnea

syndrome.JOralMaxillofacSurg.2006;64(6):886-91.

112. Goh YH, LimKA.Modifiedmaxillomandibular advancement for the treatmentof obstructive

sleepapnea:apreliminaryreport.Laryngoscope.2003;113(9):1577-82.

2Towards a prediction model fordrug-induced sleep endoscopy asselection tool for oral appliancetreatment and positional therapyinobstructivesleepapneaP.E.Vonk,A.M.E.H.Beelen,N.deVriesSleepBreath.2018Dec;22(4):901-907

2Towards a prediction model fordrug-induced sleep endoscopy asselection tool for oral appliancetreatment and positional therapyinobstructivesleepapneaP.E.Vonk,A.M.E.H.Beelen,N.deVriesSleepBreath.2018Dec;22(4):901-907

2Towards a prediction model fordrug-induced sleep endoscopy asselection tool for oral appliancetreatment and positional therapyinobstructivesleepapneaP.E.Vonk,A.M.E.H.Beelen,N.deVriesSleepBreath.2018Dec;22(4):901-907

36

Chapter 2

ABSTRACT

Purpose: To evaluate the effect of different passive maneuvers on upper airway patency during

drug-induced sleep endoscopy (DISE) compared to recent literature on treatment outcomes of

positional therapy (PT),oralappliance therapy (OAT)andcombined treatment inobstructive sleep

apnea(OSA)patients.

Methods: A retrospective, single-centre cohort study including a consecutive series of 200 OSA

patients.AllpatientsunderwentDISEwithandwithoutmanuallyperformed jaw thrustand lateral

headrotationbyusingtheVOTEclassification.Theeffectofthesemaneuverswasanalyzedbyusing

thesumVOTEscorecomparingnon-positional(NPP)andpositionalOSApatients(PP).

Results: 200Patientswere included (80.5%male)withameanageof50.1±11.7years,aBMIof

27.0±3.1kg/m2andamedianAHIof19.2eventsperhour.Forty-fourpercentofthepatientswere

NPP; of the remaining 56%, 34% was diagnosed with supine isolated and 66% with supine

predominantPOSA.ManuallyperformedjawthrustshowedareductionofsumVOTEscoreof66.7%

in all subgroups. The effect of lateral head rotation was a reduction of 33.3% in NPP and supine

predominant PP and 50% in supine isolated PP. Combining thesemaneuvers a reduction ofmore

than75%wasseeninallpatients.

Conclusions: Thepresentmodel leaves roomfor improvement.Theeffectofmanuallyperformed

jaw thrust is greater and the effect of lateral head rotation alone is less thanwhatwas expected

comparedtorecentliteratureontreatmentoutcomeofOAT,PTandcombinedtreatment.

Key words: Diagnostics, drug-induced sleep endoscopy, obstructive sleep apnea, treatmentoutcome

INTRODUCTION

Obstructive sleep apnea (OSA) is a sleep related breathing disorder characterized by recurrent

episodesofpartialorcompletecollapseoftheupperairway,whichresultsinadecreaseorcessation

in airflow during sleep.1 This can lead to fragmented sleep accompanied by snoring, excessive

daytime sleepiness or restless sleep. The prevalence of OSA is high. 49.7% in men and 23.4% in

women have an apnea-hypopnea index (AHI) ofmore than 15 per hour.When excessive daytime

sleepinessisincludedinthedefinitionwithanAHIof5ormore,theprevalenceis12.5%(men)and

5.9%(women).2,3Continuouspositiveairwaypressure(CPAP)isconsideredtobethegold-standard

therapyincaseofmoderatetosevereOSA.InpatientswithmildtomoderateOSA,othertreatment

optionsincludeoralappliancetherapy(OAT),upperairwaysurgery(UAS),positionaltherapy(PT)or

acombinationofdifferenttreatments.4-7Suchothertreatmentsarealso indicated incaseofCPAP

failure,whichoccursinapproximately35%ofpatients.8

When alternatives to CPAP are considered, in particularUAS, evaluation of the upper airway is of

paramount importance. Drug-Induced Sleep Endoscopy (DISE) is a dynamic and unique diagnostic

tool, which is gradually gaining acceptance as a selection tool in OSA patients in whom UAS is

considered. 9, 10 DISE provides information regarding the degree, level(s) and configuration of

obstructionof the collapsible segmentof theupper airway. Lesswell explored, andperhapsmore

controversial, istheroleofDISEinpatientsinwhomotherOSAtreatmentmodalities,suchasOAT,

PT,combinedtreatment(e.g.,OATandPT),andPTafterUAS,areconsidered.

Presently, in case OAT is considered, patients are mostly simply prescribed the latter without

additionalevaluationoftheupperairwaythroughDISE.Inthispragmaticapproach,OATiseffective

in30-81%.11ThealternativewouldbetoperformaDISEfirstandmimictheeffectofOAT(e.g.by

performinga jaw thrust), andonly commencewithOAT in case theairwayopenswith jaw thrust.

OpinionsconcerningtheperformanceofjawthrustduringDISEvaryamongstudiesandevidenceon

thepositiveandnegativepredictivevaluesofDISEwithjawthrustarehoweversofarlimited.12,13,14

Vroegop et al. investigated the use of simulation bites and found significant association between,positiveeffectof the simulationbite and treatment response toOAT,but at this point theuseof

simulationbitesisnotcommonpracticeandmainlyusedforresearchpurposes.15

Similarly, incasePTisconsidered, itmightbeusefultocompareDISEfindingsin lateralandsupine

position.RecentresearchfromthegroupsfromAntwerpandAmsterdamhasshownthatinmildto

37

2

Towards a prediction model for drug-induced sleep endoscopy

ABSTRACT

Purpose: To evaluate the effect of different passive maneuvers on upper airway patency during

drug-induced sleep endoscopy (DISE) compared to recent literature on treatment outcomes of

positional therapy (PT),oralappliance therapy (OAT)andcombined treatment inobstructive sleep

apnea(OSA)patients.

Methods: A retrospective, single-centre cohort study including a consecutive series of 200 OSA

patients.AllpatientsunderwentDISEwithandwithoutmanuallyperformed jaw thrustand lateral

headrotationbyusingtheVOTEclassification.Theeffectofthesemaneuverswasanalyzedbyusing

thesumVOTEscorecomparingnon-positional(NPP)andpositionalOSApatients(PP).

Results: 200Patientswere included (80.5%male)withameanageof50.1±11.7years,aBMIof

27.0±3.1kg/m2andamedianAHIof19.2eventsperhour.Forty-fourpercentofthepatientswere

NPP; of the remaining 56%, 34% was diagnosed with supine isolated and 66% with supine

predominantPOSA.ManuallyperformedjawthrustshowedareductionofsumVOTEscoreof66.7%

in all subgroups. The effect of lateral head rotation was a reduction of 33.3% in NPP and supine

predominant PP and 50% in supine isolated PP. Combining thesemaneuvers a reduction ofmore

than75%wasseeninallpatients.

Conclusions: Thepresentmodel leaves roomfor improvement.Theeffectofmanuallyperformed

jaw thrust is greater and the effect of lateral head rotation alone is less thanwhatwas expected

comparedtorecentliteratureontreatmentoutcomeofOAT,PTandcombinedtreatment.

Key words: Diagnostics, drug-induced sleep endoscopy, obstructive sleep apnea, treatmentoutcome

INTRODUCTION

Obstructive sleep apnea (OSA) is a sleep related breathing disorder characterized by recurrent

episodesofpartialorcompletecollapseoftheupperairway,whichresultsinadecreaseorcessation

in airflow during sleep.1 This can lead to fragmented sleep accompanied by snoring, excessive

daytime sleepiness or restless sleep. The prevalence of OSA is high. 49.7% in men and 23.4% in

women have an apnea-hypopnea index (AHI) ofmore than 15 per hour.When excessive daytime

sleepinessisincludedinthedefinitionwithanAHIof5ormore,theprevalenceis12.5%(men)and

5.9%(women).2,3Continuouspositiveairwaypressure(CPAP)isconsideredtobethegold-standard

therapyincaseofmoderatetosevereOSA.InpatientswithmildtomoderateOSA,othertreatment

optionsincludeoralappliancetherapy(OAT),upperairwaysurgery(UAS),positionaltherapy(PT)or

acombinationofdifferenttreatments.4-7Suchothertreatmentsarealso indicated incaseofCPAP

failure,whichoccursinapproximately35%ofpatients.8

When alternatives to CPAP are considered, in particularUAS, evaluation of the upper airway is of

paramount importance. Drug-Induced Sleep Endoscopy (DISE) is a dynamic and unique diagnostic

tool, which is gradually gaining acceptance as a selection tool in OSA patients in whom UAS is

considered. 9, 10 DISE provides information regarding the degree, level(s) and configuration of

obstructionof the collapsible segmentof theupper airway. Lesswell explored, andperhapsmore

controversial, istheroleofDISEinpatientsinwhomotherOSAtreatmentmodalities,suchasOAT,

PT,combinedtreatment(e.g.,OATandPT),andPTafterUAS,areconsidered.

Presently, in case OAT is considered, patients are mostly simply prescribed the latter without

additionalevaluationoftheupperairwaythroughDISE.Inthispragmaticapproach,OATiseffective

in30-81%.11ThealternativewouldbetoperformaDISEfirstandmimictheeffectofOAT(e.g.by

performinga jaw thrust), andonly commencewithOAT in case theairwayopenswith jaw thrust.

OpinionsconcerningtheperformanceofjawthrustduringDISEvaryamongstudiesandevidenceon

thepositiveandnegativepredictivevaluesofDISEwithjawthrustarehoweversofarlimited.12,13,14

Vroegop et al. investigated the use of simulation bites and found significant association between,positiveeffectof the simulationbite and treatment response toOAT,but at this point theuseof

simulationbitesisnotcommonpracticeandmainlyusedforresearchpurposes.15

Similarly, incasePTisconsidered, itmightbeusefultocompareDISEfindingsin lateralandsupine

position.RecentresearchfromthegroupsfromAntwerpandAmsterdamhasshownthatinmildto

38

Chapter 2

moderatelyseverepositionalOSA(POSA)theeffectofOATandPTarecomparable,withroughly50%

reductioninAHI,whilecombinedOATandPT,leadstoafurther50%reductioninAHI.7,16,17

WhenfocusingonthecorrelationbetweenAHIandobservationsmadeduringDISE,severalstudies

show similar results. In a study by Vroegop et al. they concluded that higher AHI values are

associatedwithacompletecollapseobservedduringDISE,with inparticularacompleteconcentric

collapse (CCC) at palatal level and a complete lateral hypopharyngeal collapse. Lower AHI was

associatedwithahigherprobabilityofapartialconcentriccollapseatpalatallevel.18Raveslootetal.

foundsimilarresultsandsuggestedthatamultilevelcollapse,acompletecollapseandatonguebase

collapseareassociatedwithahigherAHIinOSApatients.19

OurdepartmentservesasareferralcentreforpatientswhoseekalternativestoCPAPtreatment.In

suchpatientswepresentlyperformDISEinfourpositions:supine,supinewithjawthrust(tomimic

theeffectofOAT),lateralheadrotation(tomimictheeffectofPT),andjawthrustwithheadrotation

(tomimic combined treatmentwithOATandPT). For thepresent study,we composeda 3points

model, based on the VOTE classification system 9, in which the effects of thesemaneuvers were

retrospectively analyzed. In case of a perfect fit of themodel, the effect of jaw thrust and head

rotationwouldbeequal,(50%reductioninpoints)withanother50%reductionincaseofcombined

maneuvers.

We hypothesized that the effect of thesemaneuvers would correspond with recent literature on

treatment outcomes of PT, OAT and combined treatment and as such could serve as a tool in a

patient specific treatment planning. 7, 16, 17 When our hypothesis is correct, DISE with these

maneuvers could be of additional value to predict treatment outcome of OAT, PT or combined

treatment.

METHODS

Patients

Weperformedaretrospective,single-centrecohortstudyincludingaconsecutiveseriesof200OSA

patients,confirmedbypolysomnography,whounderwentDISEbetweenAugust2016andFebruary

2017. Patients were excluded from analysis when aged < 18 years, medical history of congenital

abnormalitiesof theupperairway,DISEperformedwithCPAPorOATandwhenDISE resultswere

inconclusiveduetomucushypersecretion.

Patientswereidentifiedasbeingnon-positional(NPP)orpositional(PP)usingamodifiedversionof

Cartwright’scriteria20,namelyadifferenceof50%ormore inAHIbetweensupineandnon-supine

positions and a total sleeping time in worse sleeping position of > 10% and < 90%. In PP the

distinctionwasmadebetweensupine isolated (non-supineAHI<5)andsupinepredominant (non-

supineAHI≥5).21

In accordance with the Declaration of Helsinki, the study protocol was approved by the Medical

EthicalCommittee.Dataonstudysubjectswascollectedandstoredanonymouslytoprotectpersonal

information.

DISEprocedure

DISEwas performed in patients inwhomalternatives to CPAPwere considered,with in particular

patientseligible forUAS,butalso toevaluate thepossibleeffectofother conservative treatments

suchasOATorPTorcombinationofboth.InsomepatientsDISEwasperformedtoidentifyreasons

forprevioustreatmentfailure(e.g.OATorCPAP).

DISE was performed in a quiet outpatient endoscopy room with dimmed lights and standard

anestheticequipment.TheprocedurewasexecutedbytwotrainedENTresidents(PVandAB),witha

nurseanesthetistmanagingsedation.Thedesiredlevelofpropofolconcentrationwascontrolledby

the nurse anesthetist by using a target-controlled infusion (TCI) pump. Prior to the propofol, 2 cc

lidocainewasgivenintravenouslytopreventpaincausedbytheinfusionofpropofol.Onindication

glycopyrrolate was administered before the procedure to avoid excessive secretions, which may

interfere with the quality of the DISE video. Propofol concentration was gradually increased until

proper sedationwas achieved. Proper sedationwas reachedwhen the patient began to snore or

showedhyporesponsivenesstoverbalandtactilestimuli.Theupperairwaywasobservedbyusinga

flexible laryngoscopy starting in supinepositionwithandwithout jaw thrust. Subsequently, lateral

headrotationtotherightwasperformed,againwithandwithoutjawthrust.

Classificationsystem

TheVOTE systemwas used to evaluate four different levels and structures that can contribute to

upperairwayobstruction,namelyvelum(V),oropharynx(O),tonguebase(T)andepiglottis(E).The

degree of obstructionwas defined by the following categories: no obstruction (collapse less than

50%),partial(collapsebetween50-75%,typicallywithvibration)orcompletecollapse(>75%)andXif

no observation could be made. The configuration of the obstruction may be anterior-posterior,

lateralorconcentric.Table1showsanoverviewofthedifferentlevels,thedegreeofobstructionand

thepossibleconfigurationsateachlevel.

39

2

Towards a prediction model for drug-induced sleep endoscopy

moderatelyseverepositionalOSA(POSA)theeffectofOATandPTarecomparable,withroughly50%

reductioninAHI,whilecombinedOATandPT,leadstoafurther50%reductioninAHI.7,16,17

WhenfocusingonthecorrelationbetweenAHIandobservationsmadeduringDISE,severalstudies

show similar results. In a study by Vroegop et al. they concluded that higher AHI values are

associatedwithacompletecollapseobservedduringDISE,with inparticularacompleteconcentric

collapse (CCC) at palatal level and a complete lateral hypopharyngeal collapse. Lower AHI was

associatedwithahigherprobabilityofapartialconcentriccollapseatpalatallevel.18Raveslootetal.

foundsimilarresultsandsuggestedthatamultilevelcollapse,acompletecollapseandatonguebase

collapseareassociatedwithahigherAHIinOSApatients.19

OurdepartmentservesasareferralcentreforpatientswhoseekalternativestoCPAPtreatment.In

suchpatientswepresentlyperformDISEinfourpositions:supine,supinewithjawthrust(tomimic

theeffectofOAT),lateralheadrotation(tomimictheeffectofPT),andjawthrustwithheadrotation

(tomimic combined treatmentwithOATandPT). For thepresent study,we composeda 3points

model, based on the VOTE classification system 9, in which the effects of thesemaneuvers were

retrospectively analyzed. In case of a perfect fit of themodel, the effect of jaw thrust and head

rotationwouldbeequal,(50%reductioninpoints)withanother50%reductionincaseofcombined

maneuvers.

We hypothesized that the effect of thesemaneuvers would correspond with recent literature on

treatment outcomes of PT, OAT and combined treatment and as such could serve as a tool in a

patient specific treatment planning. 7, 16, 17 When our hypothesis is correct, DISE with these

maneuvers could be of additional value to predict treatment outcome of OAT, PT or combined

treatment.

METHODS

Patients

Weperformedaretrospective,single-centrecohortstudyincludingaconsecutiveseriesof200OSA

patients,confirmedbypolysomnography,whounderwentDISEbetweenAugust2016andFebruary

2017. Patients were excluded from analysis when aged < 18 years, medical history of congenital

abnormalitiesof theupperairway,DISEperformedwithCPAPorOATandwhenDISE resultswere

inconclusiveduetomucushypersecretion.

Patientswereidentifiedasbeingnon-positional(NPP)orpositional(PP)usingamodifiedversionof

Cartwright’scriteria20,namelyadifferenceof50%ormore inAHIbetweensupineandnon-supine

positions and a total sleeping time in worse sleeping position of > 10% and < 90%. In PP the

distinctionwasmadebetweensupine isolated (non-supineAHI<5)andsupinepredominant (non-

supineAHI≥5).21

In accordance with the Declaration of Helsinki, the study protocol was approved by the Medical

EthicalCommittee.Dataonstudysubjectswascollectedandstoredanonymouslytoprotectpersonal

information.

DISEprocedure

DISEwas performed in patients inwhomalternatives to CPAPwere considered,with in particular

patientseligible forUAS,butalso toevaluate thepossibleeffectofother conservative treatments

suchasOATorPTorcombinationofboth.InsomepatientsDISEwasperformedtoidentifyreasons

forprevioustreatmentfailure(e.g.OATorCPAP).

DISE was performed in a quiet outpatient endoscopy room with dimmed lights and standard

anestheticequipment.TheprocedurewasexecutedbytwotrainedENTresidents(PVandAB),witha

nurseanesthetistmanagingsedation.Thedesiredlevelofpropofolconcentrationwascontrolledby

the nurse anesthetist by using a target-controlled infusion (TCI) pump. Prior to the propofol, 2 cc

lidocainewasgivenintravenouslytopreventpaincausedbytheinfusionofpropofol.Onindication

glycopyrrolate was administered before the procedure to avoid excessive secretions, which may

interfere with the quality of the DISE video. Propofol concentration was gradually increased until

proper sedationwas achieved. Proper sedationwas reachedwhen the patient began to snore or

showedhyporesponsivenesstoverbalandtactilestimuli.Theupperairwaywasobservedbyusinga

flexible laryngoscopy starting in supinepositionwithandwithout jaw thrust. Subsequently, lateral

headrotationtotherightwasperformed,againwithandwithoutjawthrust.

Classificationsystem

TheVOTE systemwas used to evaluate four different levels and structures that can contribute to

upperairwayobstruction,namelyvelum(V),oropharynx(O),tonguebase(T)andepiglottis(E).The

degree of obstructionwas defined by the following categories: no obstruction (collapse less than

50%),partial(collapsebetween50-75%,typicallywithvibration)orcompletecollapse(>75%)andXif

no observation could be made. The configuration of the obstruction may be anterior-posterior,

lateralorconcentric.Table1showsanoverviewofthedifferentlevels,thedegreeofobstructionand

thepossibleconfigurationsateachlevel.

40

Chapter 2

Table1.TheVOTEclassification9

Structure Degreeof

obstructionaConfigurationc

A-P Lateral Concentric

Velum

Oropharynxb

TongueBase

Epiglottis

A-PAntero-posterior

a. Degreeofobstruction:0noobstruction;1partialobstruction;2completeobstruction

b. Oropharynxobstructioncanbedistinguishedasrelatedsolelytothetonsilsorincludingthe

lateralwalls

c. Configurationnotedforstructureswithdegreeofobstruction>0

In thepresentmodel,weregardedobstructionat the four levelsequally important,butconcentric

collapse at velum level as more severe than lateral or antero-posterior (A-P) collapse, because

literaturehasshownthataCCCofthepalatecorrespondwithalesssuccessfultreatmentoutcome

whenapplyingOATorUAS.22,23Thereforewe introduceda3pointscale:noobstruction:0points,

partial lateral or A-P obstruction: 1 point, partial concentric obstruction at velum level: 2 points,

complete lateral or A-P obstruction: 2 points, complete concentric obstruction at velum level: 4

points.

Statisticalanalysis

StatisticalanalysiswasperformedusingSPSS (version21),SPSS Inc.,Chicago, IL).Quantitativedata

arereportedasmean±SDorasmedian(Q1,Q3)whennotnormallydistributed.

To analyze the effect of different passive maneuvers on upper airway caliber, the score that

describesthedegreeofobstruction(0,1and2)atthefourseparatestructures(V,O,TandE)was

used. For the comparison of overall effect of these maneuvers the total sum VOTE score was

calculated by summing the different scores for degree of obstruction at each site. The total sum

VOTEscoreisreportedasmedian(Q1,Q3),sinceitisasumofcategoricaldataandthereforemust

beanalyzedasordinaldata.

Comparisonofdataon total sumVOTE scores indifferentpositions,withandwithoutmaneuvers,

betweenthedifferentsubgroupswascarriedoutbyusingtheWilcoxonsignedranktest incaseof

paireddataachi-squaredtestincaseofunpaireddata.Apvalueof<0.05wasconsideredtoindicate

statisticalsignificance.

RESULTS

In total 200patientswere included in this study; 80.5%wasmale. Themeanagewas50.1 ± 11.7

years,withaBMIof27.0±3.1kg/m2andamedianAHIof19.2eventsperhour.Forty-fourpercent

ofthepatientswereNPP;oftheremaining56%,34%wasdiagnosedwithsupine isolatedand66%

withsupinepredominantPOSA.Asexpected,PPhadasignificant lowerAHI innon-supineposition

and spentmore time in supineposition.Patientswith supine isolatedPOSAshoweda significantly

lower total AHI, a lower AHI in supine and non-supine position and spent more time in supine

positioncomparedtosupinepredominantPP.Baselinecharacteristicsaregivenintables2and3.

41

2

Towards a prediction model for drug-induced sleep endoscopy

Table1.TheVOTEclassification9

Structure Degreeof

obstructionaConfigurationc

A-P Lateral Concentric

Velum

Oropharynxb

TongueBase

Epiglottis

A-PAntero-posterior

a. Degreeofobstruction:0noobstruction;1partialobstruction;2completeobstruction

b. Oropharynxobstructioncanbedistinguishedasrelatedsolelytothetonsilsorincludingthe

lateralwalls

c. Configurationnotedforstructureswithdegreeofobstruction>0

In thepresentmodel,weregardedobstructionat the four levelsequally important,butconcentric

collapse at velum level as more severe than lateral or antero-posterior (A-P) collapse, because

literaturehasshownthataCCCofthepalatecorrespondwithalesssuccessfultreatmentoutcome

whenapplyingOATorUAS.22,23Thereforewe introduceda3pointscale:noobstruction:0points,

partial lateral or A-P obstruction: 1 point, partial concentric obstruction at velum level: 2 points,

complete lateral or A-P obstruction: 2 points, complete concentric obstruction at velum level: 4

points.

Statisticalanalysis

StatisticalanalysiswasperformedusingSPSS (version21),SPSS Inc.,Chicago, IL).Quantitativedata

arereportedasmean±SDorasmedian(Q1,Q3)whennotnormallydistributed.

To analyze the effect of different passive maneuvers on upper airway caliber, the score that

describesthedegreeofobstruction(0,1and2)atthefourseparatestructures(V,O,TandE)was

used. For the comparison of overall effect of these maneuvers the total sum VOTE score was

calculated by summing the different scores for degree of obstruction at each site. The total sum

VOTEscoreisreportedasmedian(Q1,Q3),sinceitisasumofcategoricaldataandthereforemust

beanalyzedasordinaldata.

Comparisonofdataon total sumVOTE scores indifferentpositions,withandwithoutmaneuvers,

betweenthedifferentsubgroupswascarriedoutbyusingtheWilcoxonsignedranktest incaseof

paireddataachi-squaredtestincaseofunpaireddata.Apvalueof<0.05wasconsideredtoindicate

statisticalsignificance.

RESULTS

In total 200patientswere included in this study; 80.5%wasmale. Themeanagewas50.1 ± 11.7

years,withaBMIof27.0±3.1kg/m2andamedianAHIof19.2eventsperhour.Forty-fourpercent

ofthepatientswereNPP;oftheremaining56%,34%wasdiagnosedwithsupine isolatedand66%

withsupinepredominantPOSA.Asexpected,PPhadasignificant lowerAHI innon-supineposition

and spentmore time in supineposition.Patientswith supine isolatedPOSAshoweda significantly

lower total AHI, a lower AHI in supine and non-supine position and spent more time in supine

positioncomparedtosupinepredominantPP.Baselinecharacteristicsaregivenintables2and3.

42

Chapter 2

Table2.BaselinecharacteristicstotalpopulationandNPPversusPP Total NPP PP NPPversusPP

pvalue

Number(%) 200 88(44) 112(56) 88vs112

Age(years) 50.1±11.7 52.4±10.8 48.2±12.1 0.010*

Male/Female 161/39 68/20 93/19 0.307

BMI(kg/m2) 27.0±3.1 27.0±3.1 27.1±3.2 0.832

TotalAHI

(events/hour)

19.2

(11.7,31.0)°

21.0

(14.0,38.4)°

18.3

(10.7,27.3)°

0.073

SupineAHI

(events/hour)

34.5

(18.4,59.0)°

25.7

(15.9,61.4)°

37.8

(22.6,57.9)°

0.095

NonsupineAHI

(events/hour)

10.8

(5.4,22.8)°

19.4

(9.9,34.8)°

7.3

(3.4,14.7)°

0.00*

Supine sleeping time

(%)

31.5

(16.6,50.2)°

21.4

(3.7,44.4)°

35.4

(22.0,50.5)°

0.001*

NPPnon-positionalobstructivesleepapneapatientsPPpositionalobstructivesleepapneapatients

BMIBodyMassindexAHIapnea-hypopneaindex

°Median(Q1,Q3);*pvalue<0.05

Table3.BaselinecharacteristicsPPsupineisolatedversusPPsupinepredominant N=112 Supineisolated Supinepredominant Supineisolatedversus

supinepredominant

pvalue

Number(%) 38(34) 74(66) 38vs74

Age(years) 46.1±11.0 49.2±12.5 0.196

Male/Female 29/9 64/10 0.175

BMI(kg/m2) 26.3±3.2 27.4±3.2 0.087

TotalAHI

(events/hour)

8.8

(6.2,16.3)°

23.0

(15.9,33.3)°

0.00*

SupineAHI

(events/hour)

19.1

(11.4,34.0)°

47.7

(33.6,63.8)°

0.00*

NonsupineAHI

(events/hour)

2.5

(1.6,3.5)°

10.8

(7.4,19.4)°

0.00*

Supinesleepingtime

(%)

45.0

(33.6,64.9)°

30.0

(21.0,45.5)°

0.002*

PPpositionalobstructivesleepapneapatientsBMIBodyMassindexAHIapnea-hypopneaindex

°Median(Q1,Q3);*pvalue<0.05

43

2

Towards a prediction model for drug-induced sleep endoscopy

Table2.BaselinecharacteristicstotalpopulationandNPPversusPP Total NPP PP NPPversusPP

pvalue

Number(%) 200 88(44) 112(56) 88vs112

Age(years) 50.1±11.7 52.4±10.8 48.2±12.1 0.010*

Male/Female 161/39 68/20 93/19 0.307

BMI(kg/m2) 27.0±3.1 27.0±3.1 27.1±3.2 0.832

TotalAHI

(events/hour)

19.2

(11.7,31.0)°

21.0

(14.0,38.4)°

18.3

(10.7,27.3)°

0.073

SupineAHI

(events/hour)

34.5

(18.4,59.0)°

25.7

(15.9,61.4)°

37.8

(22.6,57.9)°

0.095

NonsupineAHI

(events/hour)

10.8

(5.4,22.8)°

19.4

(9.9,34.8)°

7.3

(3.4,14.7)°

0.00*

Supine sleeping time

(%)

31.5

(16.6,50.2)°

21.4

(3.7,44.4)°

35.4

(22.0,50.5)°

0.001*

NPPnon-positionalobstructivesleepapneapatientsPPpositionalobstructivesleepapneapatients

BMIBodyMassindexAHIapnea-hypopneaindex

°Median(Q1,Q3);*pvalue<0.05

Table3.BaselinecharacteristicsPPsupineisolatedversusPPsupinepredominant N=112 Supineisolated Supinepredominant Supineisolatedversus

supinepredominant

pvalue

Number(%) 38(34) 74(66) 38vs74

Age(years) 46.1±11.0 49.2±12.5 0.196

Male/Female 29/9 64/10 0.175

BMI(kg/m2) 26.3±3.2 27.4±3.2 0.087

TotalAHI

(events/hour)

8.8

(6.2,16.3)°

23.0

(15.9,33.3)°

0.00*

SupineAHI

(events/hour)

19.1

(11.4,34.0)°

47.7

(33.6,63.8)°

0.00*

NonsupineAHI

(events/hour)

2.5

(1.6,3.5)°

10.8

(7.4,19.4)°

0.00*

Supinesleepingtime

(%)

45.0

(33.6,64.9)°

30.0

(21.0,45.5)°

0.002*

PPpositionalobstructivesleepapneapatientsBMIBodyMassindexAHIapnea-hypopneaindex

°Median(Q1,Q3);*pvalue<0.05

44

Chapter 2

In all subgroups themedian total sumVOTE score in supinepositionwas 6.0 and respectively 2.0

when jaw thrust was added, a significant reduction of 66.7% (p = 0.00). In NPP and supine

predominant PP themedian total sum VOTE score of 6.0 in supine position showed a significant

reductionof2points(33.3%)whenlateralheadrotationwasperformed(p=0.00).Thisincontrastto

patientswithsupine isolatedPOSA,whereasignificantreductionwasfound(p=0.00)of50%(6.0

versus 3.0). When comparing the effect of lateral head rotation in supine isolated and supine

predominantPP,asignificantdifferencewasfoundinfavourofthesupineisolatedgroup(p=0.03).

Whenbothmaneuverswerecombined(lateralheadrotationandjawthrust)themediantotalsum

VOTE score in all subgroups changed from 6.0 in supine position to 1.0 (p = 0.00), except for the

supineisolatedPPgroup,whichshowedasignificantreductionto0.5(p=0.00),butthisdifference

wasnotsignificantcomparingsupineisolatedandsupinepredominantPP(p=0.682).

An overview of the different total sum VOTE scores in different positions with and without

maneuversispresentedintable4.

Table4.TotalsumVOTEscoreindifferentpositionswithandwithoutmaneuvers

Total

N=200

NPP

N=88

PP

N=112

PPsupine

isolated

N=38

PPsupine

predominant

N=74

Supine 6.0

(4.0,6.0)

6.0

(4.0,6.0)

6.0

(4.0,6.0)

6.0

(4.0,6.0)

6.0

(5.0,7.0)

Supine+jaw

thrust

2.0

(1.0,3.0)

2.0

(0.0,2.0)

2.0

(1.0,3.0)

2.0

(1.0,2.0)

2.0

(1.0,3.0)

Lateralhead

rotation

4.0

(3.0,6.0)

4.0

(3.0,6.0)

4.0

(3.0,6.0)

3.0

(2.0,5.5)

4.0

(3.0,6.0)

Lateralhead

rotation+jaw

thrust

1.0

(0.0,2.0)

1.0

(0.0,3.0)

1.0

(0.0,2.0)

0.5

(0.0,2.0)

1.0

(0.0,2.0)

Valuesdescribedasmedian(Q1,Q3)

NPP non-positional obstructive sleep apnea patients PP positional dependent obstructive sleep

apneapatients

45

2

Towards a prediction model for drug-induced sleep endoscopy

In all subgroups themedian total sumVOTE score in supinepositionwas 6.0 and respectively 2.0

when jaw thrust was added, a significant reduction of 66.7% (p = 0.00). In NPP and supine

predominant PP themedian total sum VOTE score of 6.0 in supine position showed a significant

reductionof2points(33.3%)whenlateralheadrotationwasperformed(p=0.00).Thisincontrastto

patientswithsupine isolatedPOSA,whereasignificantreductionwasfound(p=0.00)of50%(6.0

versus 3.0). When comparing the effect of lateral head rotation in supine isolated and supine

predominantPP,asignificantdifferencewasfoundinfavourofthesupineisolatedgroup(p=0.03).

Whenbothmaneuverswerecombined(lateralheadrotationandjawthrust)themediantotalsum

VOTE score in all subgroups changed from 6.0 in supine position to 1.0 (p = 0.00), except for the

supineisolatedPPgroup,whichshowedasignificantreductionto0.5(p=0.00),butthisdifference

wasnotsignificantcomparingsupineisolatedandsupinepredominantPP(p=0.682).

An overview of the different total sum VOTE scores in different positions with and without

maneuversispresentedintable4.

Table4.TotalsumVOTEscoreindifferentpositionswithandwithoutmaneuvers

Total

N=200

NPP

N=88

PP

N=112

PPsupine

isolated

N=38

PPsupine

predominant

N=74

Supine 6.0

(4.0,6.0)

6.0

(4.0,6.0)

6.0

(4.0,6.0)

6.0

(4.0,6.0)

6.0

(5.0,7.0)

Supine+jaw

thrust

2.0

(1.0,3.0)

2.0

(0.0,2.0)

2.0

(1.0,3.0)

2.0

(1.0,2.0)

2.0

(1.0,3.0)

Lateralhead

rotation

4.0

(3.0,6.0)

4.0

(3.0,6.0)

4.0

(3.0,6.0)

3.0

(2.0,5.5)

4.0

(3.0,6.0)

Lateralhead

rotation+jaw

thrust

1.0

(0.0,2.0)

1.0

(0.0,3.0)

1.0

(0.0,2.0)

0.5

(0.0,2.0)

1.0

(0.0,2.0)

Valuesdescribedasmedian(Q1,Q3)

NPP non-positional obstructive sleep apnea patients PP positional dependent obstructive sleep

apneapatients

46

Chapter 2

DISCUSSION

DISEisadiagnostictoolforupperairwayevaluationinpatientsdiagnosedwithOSA.Inmanycases

DISEfindingschangepatientmanagementandevidenceisaccumulatingthatDISEprovidesvaluable

informationtopredicttreatmentresponseandsurgicalsuccess.24,25Differentpassivemaneuverscan

be performed during DISE with the intent to predict treatment response of current available

treatment modalities. In the present study we evaluate the additional value of DISE including

maneuversforPT,OAToracombinationofboth.

Ameta-analysisperformedbyRaveslootetal.evaluatedtheeffectivenessofPT in improvingsleep

studyvariablesinpositionalOSA.Theresultsofsixstudieswereusedforanalysisandshowedthat

totalAHIwassignificantlyreducedwhenPTwasappliedfromameanof21.8±7.2to9.9±10.6,a

differenceof53.6%.26

SeveralstudieshaveshownthatOATiseffectiveinbothreducingAHIanddecreasingOSAsymptoms.11,27A studybyDieltjenset al. prospectively evaluated the treatment responseof a titratableoral

appliance(OA).Theyfoundasuccessrateof55.7%,adecreaseoftotalAHIofmorethan50%anda

total AHI of less than 10. The effectiveness of combined treatment with OAT + SPT has also

prospectivelybeen investigated.BothOATandSPTwere individuallyeffective inreducingAHIwith

approximately50%,whilethecombinationofSPT+OATfurtherreducedtotalAHI,withanother50%

comparedtoSPTorOATalone,leadingtointotalapproximately75%reduction.17

In themodel we tested in the present study, we regarded obstruction at the four levels (Velum,

Oropharynx,TonguebaseandEpiglottis)equallyimportant,butaconcentriccollapseasmoresevere

than lateral or antero-posterior collapse, since it has been shown that a CCC at palatal level

correspondstoaworsetreatmentoutcomethanA-Porlateralcollapse.

Vandervekenet al. found that theoverall treatment successwithhypoglossal nerve stimulation in

patientswithoutaCCCatpalatal levelwas81%,while treatmentsuccesscouldnotbeachieved in

thepresenceofaCCCofthepalate.23InastudybyKoutsourelakisetal.similarresultswerefound.

They concluded that non-responders to UAS had a higher occurrence of a CCC at palatal level

comparedtoresponders.22

When interpretingour results, itmustbe taken intoaccount that the reduction in total sumVOTE

score iscalculatedbysummingthemedianscoreof thepresenceofobstructionat the four levels.

Therefore,“reduction”actuallymustbeinterpretedasaleftshiftofthemediananddistributionof

thedata.Ifourmodelwouldhaveaperfectfit,thereductionbyeitherperformingthejawthrustand

withheadrotationwouldbothgivea50%reductioninpoints.Jawthrusthowevergaveamorethan

50%reduction.Asexpectedareductionofa50%wasseeninsupineisolatedPPwhenlateralhead

rotationwasperformed,butincontrasttowhatwashypothesized,areductionoflessthan50%was

seen in supine predominant PP. The difference in results between supine isolated and supine

predominantcouldmightbeexplainedbythegreaterdifferencebetweenthesupineandnon-supine

AHIinsupineisolatedPP.Previousstudiesalsodemonstrateanimportantinfluenceofheadposition

on theAHI, independentlyof trunkpositionand sleep stage,but at thispoint theeffectofhaving

supineisolatedorsupinepredominantPOSAneedstobefurtherunravelled.28,29

Theestimated75%reductionofthecombinationofthosetwomaneuverswasalmostaspredicted,

buthigherthanexpected,probablybasedontheerroneouslyproductoftheoverestimationof jaw

thrustandunderestimationofheadrotationinsomegroups.

Weperformedamanual jaw thrust and tried toprotrude themandible less than100%, aiming at

roughly 50-75% protrusion.We are aware that this is a very unprecisemaneuver. The predictive

value of manually performed jaw thrust on treatment response to OAT varies between different

studies.Johaletal.foundagoodcorrelationbetweenthemaneuverandtreatmentsuccessrate.12,

13Eichleretal.alsoconcludedthattheeffectofmandibularadvancementcanbeshownduringDISE.30Incontrast,Vandervekenetal.andVroegopetal.havebeenquestioningthecorrelationbetween

theeffectofthechinliftmaneuverduringDISEandtreatmentsuccessofOATandsuggestedtheuse

ofasimulationbiteduringDISE,whichtendstobetterpredictresponsetoOAT.14,15

Thepresentstudyindeedconfirmsthesuspicionthatmanualjawthrustleadstoanoverestimation

ofanOATeffect,because inthisstudywefoundareductionof66.7%whenjawthrustwasadded

insteadoftheexpectedeffectof50%.

Wepreviously reportedtwoDISEstudiesontheeffectof lateral rotationof theheadaloneandof

bothheadandtrunk.31,32Thesestudiessuggestedthattheeffectofheadrotationalone,andofhead

and trunk rotation combined were almost comparable, in terms of level(s) and direction of

obstruction.Wewerelessconvincedthatthequantitativeeffectwasequal,butforpracticalreasons

- head rotation is much easier to carry out than head and trunk rotation combined -, in clinical

practice lateral head rotation was subsequently adopted. Still, we remained critical since we are

awarethatnotallpatientsarecapableofafull90%headrotation.

InthisstudytherangeofindividualheadrotationwasnotroutinelytestedbeforeperformingDISE.

Whenthemaximumoflateralheadrotationwaslimited,anannotationwasmade,butpatientswere

notexcludedinthisstudy.Thisphysicallimitationmightleadtoanunderestimationoftheeffectof

47

2

Towards a prediction model for drug-induced sleep endoscopy

DISCUSSION

DISEisadiagnostictoolforupperairwayevaluationinpatientsdiagnosedwithOSA.Inmanycases

DISEfindingschangepatientmanagementandevidenceisaccumulatingthatDISEprovidesvaluable

informationtopredicttreatmentresponseandsurgicalsuccess.24,25Differentpassivemaneuverscan

be performed during DISE with the intent to predict treatment response of current available

treatment modalities. In the present study we evaluate the additional value of DISE including

maneuversforPT,OAToracombinationofboth.

Ameta-analysisperformedbyRaveslootetal.evaluatedtheeffectivenessofPT in improvingsleep

studyvariablesinpositionalOSA.Theresultsofsixstudieswereusedforanalysisandshowedthat

totalAHIwassignificantlyreducedwhenPTwasappliedfromameanof21.8±7.2to9.9±10.6,a

differenceof53.6%.26

SeveralstudieshaveshownthatOATiseffectiveinbothreducingAHIanddecreasingOSAsymptoms.11,27A studybyDieltjenset al. prospectively evaluated the treatment responseof a titratableoral

appliance(OA).Theyfoundasuccessrateof55.7%,adecreaseoftotalAHIofmorethan50%anda

total AHI of less than 10. The effectiveness of combined treatment with OAT + SPT has also

prospectivelybeen investigated.BothOATandSPTwere individuallyeffective inreducingAHIwith

approximately50%,whilethecombinationofSPT+OATfurtherreducedtotalAHI,withanother50%

comparedtoSPTorOATalone,leadingtointotalapproximately75%reduction.17

In themodel we tested in the present study, we regarded obstruction at the four levels (Velum,

Oropharynx,TonguebaseandEpiglottis)equallyimportant,butaconcentriccollapseasmoresevere

than lateral or antero-posterior collapse, since it has been shown that a CCC at palatal level

correspondstoaworsetreatmentoutcomethanA-Porlateralcollapse.

Vandervekenet al. found that theoverall treatment successwithhypoglossal nerve stimulation in

patientswithoutaCCCatpalatal levelwas81%,while treatmentsuccesscouldnotbeachieved in

thepresenceofaCCCofthepalate.23InastudybyKoutsourelakisetal.similarresultswerefound.

They concluded that non-responders to UAS had a higher occurrence of a CCC at palatal level

comparedtoresponders.22

When interpretingour results, itmustbe taken intoaccount that the reduction in total sumVOTE

score iscalculatedbysummingthemedianscoreof thepresenceofobstructionat the four levels.

Therefore,“reduction”actuallymustbeinterpretedasaleftshiftofthemediananddistributionof

thedata.Ifourmodelwouldhaveaperfectfit,thereductionbyeitherperformingthejawthrustand

withheadrotationwouldbothgivea50%reductioninpoints.Jawthrusthowevergaveamorethan

50%reduction.Asexpectedareductionofa50%wasseeninsupineisolatedPPwhenlateralhead

rotationwasperformed,butincontrasttowhatwashypothesized,areductionoflessthan50%was

seen in supine predominant PP. The difference in results between supine isolated and supine

predominantcouldmightbeexplainedbythegreaterdifferencebetweenthesupineandnon-supine

AHIinsupineisolatedPP.Previousstudiesalsodemonstrateanimportantinfluenceofheadposition

on theAHI, independentlyof trunkpositionand sleep stage,but at thispoint theeffectofhaving

supineisolatedorsupinepredominantPOSAneedstobefurtherunravelled.28,29

Theestimated75%reductionofthecombinationofthosetwomaneuverswasalmostaspredicted,

buthigherthanexpected,probablybasedontheerroneouslyproductoftheoverestimationof jaw

thrustandunderestimationofheadrotationinsomegroups.

Weperformedamanual jaw thrust and tried toprotrude themandible less than100%, aiming at

roughly 50-75% protrusion.We are aware that this is a very unprecisemaneuver. The predictive

value of manually performed jaw thrust on treatment response to OAT varies between different

studies.Johaletal.foundagoodcorrelationbetweenthemaneuverandtreatmentsuccessrate.12,

13Eichleretal.alsoconcludedthattheeffectofmandibularadvancementcanbeshownduringDISE.30Incontrast,Vandervekenetal.andVroegopetal.havebeenquestioningthecorrelationbetween

theeffectofthechinliftmaneuverduringDISEandtreatmentsuccessofOATandsuggestedtheuse

ofasimulationbiteduringDISE,whichtendstobetterpredictresponsetoOAT.14,15

Thepresentstudyindeedconfirmsthesuspicionthatmanualjawthrustleadstoanoverestimation

ofanOATeffect,because inthisstudywefoundareductionof66.7%whenjawthrustwasadded

insteadoftheexpectedeffectof50%.

Wepreviously reportedtwoDISEstudiesontheeffectof lateral rotationof theheadaloneandof

bothheadandtrunk.31,32Thesestudiessuggestedthattheeffectofheadrotationalone,andofhead

and trunk rotation combined were almost comparable, in terms of level(s) and direction of

obstruction.Wewerelessconvincedthatthequantitativeeffectwasequal,butforpracticalreasons

- head rotation is much easier to carry out than head and trunk rotation combined -, in clinical

practice lateral head rotation was subsequently adopted. Still, we remained critical since we are

awarethatnotallpatientsarecapableofafull90%headrotation.

InthisstudytherangeofindividualheadrotationwasnotroutinelytestedbeforeperformingDISE.

Whenthemaximumoflateralheadrotationwaslimited,anannotationwasmade,butpatientswere

notexcludedinthisstudy.Thisphysicallimitationmightleadtoanunderestimationoftheeffectof

48

Chapter 2

lateralheadrotation.Thepresentstudyconfirmsthesuspicionthatheadrotationalonemightgive

lessimprovementthanexpected.

Overall,NPP tend tohavemore severeOSA compared toPP and the incidenceof POSA increases

when the OSA severity decreases. 33-35 Previous study also showed that a multilevel collapse is

associatedwithhigherAHIandthatatonguebasecollapseorepiglottalcollapse isassociatedwith

POSA.19Basedonthesefindings,onewouldexpectahighersumVOTEscoreinNPPcomparedtoPP.

Incontrasttowhatwasexpected,similarresultswerefoundinNPPandPPwhencomparingthesum

VOTEscoreindifferentpositions.Webelieve,thatthiscouldbeexplainedbyseveralreasons.

Firstofall,patientsundergoingDISEareusuallydiagnosedwithmildtomoderateOSA,sinceCPAPis

still the gold-standard therapy in case of severe OSA. Therefore, DISE usually is not performed in

severe OSA patients, unless they experience CPAP failure/intolerance or when UAS is considered.

Thisselectioninpatientscouldinfluenceourresults,becauseasmentioned,theprevalenceofPOSA

decreasesastheseverityofOSAincreases.

Secondly, in our study population no significant difference was found in total and supine AHI.

Althoughasignificantdifferencewasfoundbetweennon-supineAHIinNPPandPP,NPPdidshowa

lowerAHIinnon-supineposition.Previousstudyshowedthatheadrotationonlycaninfluenceupper

airway collapsibility and can improve AHI compared to supine position, whether patients are

diagnosedwith POSA or not. 28, 29 On the other hand, it could also be possible that the effect of

lateralheadrotationonlyistoominimaltodifferentiatetheeffectivenessbetweenNPPandPP.

Weareawareoflimitationsofthemodel.SeveralstudieshaveshownacorrelationbetweenAHIand

observationsmadeduringDISE.Vroegopet al. found thathigherAHI valueswerebothassociated

witha complete concentric collapseatpalatal levelandcomplete lateralhypopharyngeal collapse,

whilealowerAHIwasassociatedwithapartialconcentriccollapseatpalatallevel.18Raveslootetal.

confirmed these findings and in addition suggested that amultilevel collapse, a complete collapse

andatonguebasecollapseareassociatedwithahigherAHIinOSApatients.19.Basedonthefindings

ofthisstudy,itishowevertooearlytoconcludethattheserelationsarecompletelylinear.

CONCLUSIONSANDFUTUREPERSPECTIVES

We conclude that the present model leaves room for improvement. We regard this as work in

progress and presently prospectively re-evaluate the effect of head rotation alone and head and

trunk rotation. A subsequent study will include the use of a temporary OA thatmightmimic the

effectofadefinitiveOAbetterthanmanualjawthrust.Wehopethiswilleventuallyleadtoagood

predictivemodel,whichsubsequentlycanbetestedinprospectivestudies.

49

2

Towards a prediction model for drug-induced sleep endoscopy

lateralheadrotation.Thepresentstudyconfirmsthesuspicionthatheadrotationalonemightgive

lessimprovementthanexpected.

Overall,NPP tend tohavemore severeOSA compared toPP and the incidenceof POSA increases

when the OSA severity decreases. 33-35 Previous study also showed that a multilevel collapse is

associatedwithhigherAHIandthatatonguebasecollapseorepiglottalcollapse isassociatedwith

POSA.19Basedonthesefindings,onewouldexpectahighersumVOTEscoreinNPPcomparedtoPP.

Incontrasttowhatwasexpected,similarresultswerefoundinNPPandPPwhencomparingthesum

VOTEscoreindifferentpositions.Webelieve,thatthiscouldbeexplainedbyseveralreasons.

Firstofall,patientsundergoingDISEareusuallydiagnosedwithmildtomoderateOSA,sinceCPAPis

still the gold-standard therapy in case of severe OSA. Therefore, DISE usually is not performed in

severe OSA patients, unless they experience CPAP failure/intolerance or when UAS is considered.

Thisselectioninpatientscouldinfluenceourresults,becauseasmentioned,theprevalenceofPOSA

decreasesastheseverityofOSAincreases.

Secondly, in our study population no significant difference was found in total and supine AHI.

Althoughasignificantdifferencewasfoundbetweennon-supineAHIinNPPandPP,NPPdidshowa

lowerAHIinnon-supineposition.Previousstudyshowedthatheadrotationonlycaninfluenceupper

airway collapsibility and can improve AHI compared to supine position, whether patients are

diagnosedwith POSA or not. 28, 29 On the other hand, it could also be possible that the effect of

lateralheadrotationonlyistoominimaltodifferentiatetheeffectivenessbetweenNPPandPP.

Weareawareoflimitationsofthemodel.SeveralstudieshaveshownacorrelationbetweenAHIand

observationsmadeduringDISE.Vroegopet al. found thathigherAHI valueswerebothassociated

witha complete concentric collapseatpalatal levelandcomplete lateralhypopharyngeal collapse,

whilealowerAHIwasassociatedwithapartialconcentriccollapseatpalatallevel.18Raveslootetal.

confirmed these findings and in addition suggested that amultilevel collapse, a complete collapse

andatonguebasecollapseareassociatedwithahigherAHIinOSApatients.19.Basedonthefindings

ofthisstudy,itishowevertooearlytoconcludethattheserelationsarecompletelylinear.

CONCLUSIONSANDFUTUREPERSPECTIVES

We conclude that the present model leaves room for improvement. We regard this as work in

progress and presently prospectively re-evaluate the effect of head rotation alone and head and

trunk rotation. A subsequent study will include the use of a temporary OA thatmightmimic the

effectofadefinitiveOAbetterthanmanualjawthrust.Wehopethiswilleventuallyleadtoagood

predictivemodel,whichsubsequentlycanbetestedinprospectivestudies.

50

Chapter 2

REFERENCES

1. CartwrightR,RistanovicR,DiazF,CaldarelliD,AlderG.Acomparativestudyof treatments

forpositionalsleepapnea.Sleep.1991;14(6):546-52

2. HeinzerR,Marti-SolerH,Haba-RubioJ.Prevalenceofsleepapnoeasyndromeinthemiddle

tooldagegeneralpopulation.LancetRespirMed.2016;4(2):e5-6

3. BerryRB,BudhirajaR,GottliebDJ,etal.Rulesforscoringrespiratoryeventsinsleep:update

ofthe2007AASMManualfortheScoringofSleepandAssociatedEvents.DeliberationsoftheSleep

Apnea Definitions Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med.

2012;8(5):597-619

4. Ravesloot M, Van Maanen J, Dun L, De Vries N. The undervalued potential of positional

therapyinposition-dependentsnoringandobstructivesleepapnea—areviewoftheliterature.Sleep

andBreathing.2013;17(1):39-49

5. vanMaanenJP,MeesterKA,DunLN,etal.Thesleeppositiontrainer:anewtreatmentfor

positionalobstructivesleepapnoea.SleepandBreathing.2013;17(2):771-79

6. vanMaanen JP, de VriesN. Long-term effectiveness and compliance of positional therapy

with the sleep position trainer in the treatment of positional obstructive sleep apnea syndrome.

Sleep.2014;37(7):1209-15

7. Benoist L,deRuiterM,de Lange J, deVriesN.A randomized, controlled trialofpositional

therapyversusoralappliancetherapyforposition-dependentsleepapnea.SleepMed.2017;34:109-

17

8. RichardW,VenkerJ,denHerderC,etal.Acceptanceandlong-termcomplianceofnCPAPin

obstructivesleepapnea.EurArchOtorhinolaryngol.2007;264(9):1081-6

9. Kezirian EJ, Hohenhorst W, de Vries N. Drug-induced sleep endoscopy: the VOTE

classification.EurArchOtorhinolaryngol.2011;268(8):1233-36

10. De Vito A, Llatas MC, Vanni A, et al. European position paper on drug-induced sedation

endoscopy(DISE).SleepandBreathing.2014;18(3):453-65

11. Ferguson KA, Cartwright R, Rogers R, Schmidt-NowaraW. Oral appliances for snoring and

obstructivesleepapnea:areview.Sleep.2006;29(2):244-62

12. Johal A, Battagel JM, Kotecha BT. Sleep nasendoscopy: a diagnostic tool for predicting

treatmentsuccesswithmandibularadvancementsplints inobstructivesleepapnoea.Eur JOrthod.

2005;27(6):607-14

13. JohalA,HectorMP,BattagelJM,KotechaBT.Impactofsleepnasendoscopyontheoutcome

of mandibular advancement splint therapy in subjects with sleep-related breathing disorders. J

LaryngolOtol.2007;121(7):668-75

14. Vanderveken OM, Vroegop AV, van de Heyning PH, Braem MJ. Drug-induced sleep

endoscopy completed with a simulation bite approach for the prediction of the outcome of

treatment of obstructive sleep apnea with mandibular repositioning appliances. Operative

TechniquesinOtolaryngology-headandnecksurgery.2011;22(2):175-82.

15. Vroegop AV, Vanderveken OM, Dieltjens M, Wouters K, Saldien V, Braem MJ. Sleep

endoscopywithsimulationbiteforpredictionoforalappliancetreatmentoutcome.Journalofsleep

research.2013;22(3):348-55.

16. de RuiterMHT, Benoist LBL, de VriesN, de Lange J. Durability of treatment effects of the

Sleep Position Trainer versus oral appliance therapy in positional OSA: 12-month follow-up of a

randomizedcontrolledtrial.SleepBreath.2017.

17. DieltjensM,VroegopAV,VerbruggenAE,etal.Apromisingconceptofcombinationtherapy

forpositionalobstructivesleepapnea.SleepBreath.2015;19(2):637-44.

18. VroegopAV,VandervekenOM,BoudewynsAN,etal.Drug-inducedsleependoscopyinsleep-

disorderedbreathing:reporton1,249cases.Laryngoscope.2014;124(3):797-802.

19. RaveslootMJ,deVriesN.Onehundredconsecutivepatientsundergoingdrug-inducedsleep

endoscopy:resultsandevaluation.Laryngoscope.2011;121(12):2710-6.

20. CartwrightRD.Effectofsleeppositiononsleepapneaseverity.Sleep.1984;7(2):110-4.

21. Kim KT, Cho YW, KimDE, Hwang SH, SongML,Motamedi GK. Two subtypes of positional

obstructive sleep apnea: Supine-predominant and supine-isolated. Clin Neurophysiol.

2016;127(1):565-70.

22. KoutsourelakisI,SafiruddinF,RaveslootM,ZakynthinosS,deVriesN.Surgeryforobstructive

sleepapnea:sleependoscopydeterminantsofoutcome.TheLaryngoscope.2012;122(11):2587-91.

23. Vanderveken OM, Maurer JT, Hohenhorst W, et al. Evaluation of drug-induced sleep

endoscopyasapatient selection tool for implantedupperairway stimulation forobstructive sleep

apnea.JClinSleepMed.2013;9(5):433-8.

24. Huntley C, Chou D, Doghramji K, Boon M. Preoperative Drug Induced Sleep Endoscopy

Improves the Surgical Approach to Treatment of Obstructive Sleep Apnea. Annals of Otology,

Rhinology&Laryngology.2017;126(6):478-82.

25. CertalVF,PratasR,GuimarãesL,etal.AwakeexaminationversusDISEforsurgicaldecision

makinginpatientswithOSA:asystematicreview.TheLaryngoscope.2015.

26. RaveslootM,WhiteD,HeinzerR,OksenbergA,Pépin J. Efficacyof theNewGenerationof

Devices for Positional Therapy for Patients with Positional Obstructive Sleep Apnea: A Systematic

Review of the Literature and Meta-Analysis. Journal of clinical sleep medicine: JCSM: official

publicationoftheAmericanAcademyofSleepMedicine.2017.

51

2

Towards a prediction model for drug-induced sleep endoscopy

REFERENCES

1. CartwrightR,RistanovicR,DiazF,CaldarelliD,AlderG.Acomparativestudyof treatments

forpositionalsleepapnea.Sleep.1991;14(6):546-52.

2. HeinzerR,Marti-SolerH,Haba-RubioJ.Prevalenceofsleepapnoeasyndromeinthemiddle

tooldagegeneralpopulation.LancetRespirMed.2016;4(2):e5-6.

3. BerryRB,BudhirajaR,GottliebDJ,etal.Rulesforscoringrespiratoryeventsinsleep:update

ofthe2007AASMManualfortheScoringofSleepandAssociatedEvents.DeliberationsoftheSleep

Apnea Definitions Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med.

2012;8(5):597-619.

4. Ravesloot M, Van Maanen J, Dun L, De Vries N. The undervalued potential of positional

therapyinposition-dependentsnoringandobstructivesleepapnea—areviewoftheliterature.Sleep

andBreathing.2013;17(1):39-49.

5. vanMaanenJP,MeesterKA,DunLN,etal.Thesleeppositiontrainer:anewtreatmentfor

positionalobstructivesleepapnoea.SleepandBreathing.2013;17(2):771-79.

6. vanMaanen JP, de VriesN. Long-term effectiveness and compliance of positional therapy

with the sleep position trainer in the treatment of positional obstructive sleep apnea syndrome.

Sleep.2014;37(7):1209-15.

7. Benoist L,deRuiterM,de Lange J, deVriesN.A randomized, controlled trialofpositional

therapyversusoralappliancetherapyforposition-dependentsleepapnea.SleepMed.2017;34:109-

17.

8. RichardW,VenkerJ,denHerderC,etal.Acceptanceandlong-termcomplianceofnCPAPin

obstructivesleepapnea.EurArchOtorhinolaryngol.2007;264(9):1081-6.

9. Kezirian EJ, Hohenhorst W, de Vries N. Drug-induced sleep endoscopy: the VOTE

classification.EurArchOtorhinolaryngol.2011;268(8):1233-36.

10. De Vito A, Llatas MC, Vanni A, et al. European position paper on drug-induced sedation

endoscopy(DISE).SleepandBreathing.2014;18(3):453-65.

11. Ferguson KA, Cartwright R, Rogers R, Schmidt-NowaraW. Oral appliances for snoring and

obstructivesleepapnea:areview.Sleep.2006;29(2):244-62.

12. Johal A, Battagel JM, Kotecha BT. Sleep nasendoscopy: a diagnostic tool for predicting

treatmentsuccesswithmandibularadvancementsplints inobstructivesleepapnoea.Eur JOrthod.

2005;27(6):607-14.

13. JohalA,HectorMP,BattagelJM,KotechaBT.Impactofsleepnasendoscopyontheoutcome

of mandibular advancement splint therapy in subjects with sleep-related breathing disorders. J

LaryngolOtol.2007;121(7):668-75.

14. Vanderveken OM, Vroegop AV, van de Heyning PH, Braem MJ. Drug-induced sleep

endoscopy completed with a simulation bite approach for the prediction of the outcome of

treatment of obstructive sleep apnea with mandibular repositioning appliances. Operative

TechniquesinOtolaryngology-headandnecksurgery.2011;22(2):175-82

15. Vroegop AV, Vanderveken OM, Dieltjens M, Wouters K, Saldien V, Braem MJ. Sleep

endoscopywithsimulationbiteforpredictionoforalappliancetreatmentoutcome.Journalofsleep

research.2013;22(3):348-55

16. de RuiterMHT, Benoist LBL, de VriesN, de Lange J. Durability of treatment effects of the

Sleep Position Trainer versus oral appliance therapy in positional OSA: 12-month follow-up of a

randomizedcontrolledtrial.SleepBreath.2017

17. DieltjensM,VroegopAV,VerbruggenAE,etal.Apromisingconceptofcombinationtherapy

forpositionalobstructivesleepapnea.SleepBreath.2015;19(2):637-44

18. VroegopAV,VandervekenOM,BoudewynsAN,etal.Drug-inducedsleependoscopyinsleep-

disorderedbreathing:reporton1,249cases.Laryngoscope.2014;124(3):797-802

19. RaveslootMJ,deVriesN.Onehundredconsecutivepatientsundergoingdrug-inducedsleep

endoscopy:resultsandevaluation.Laryngoscope.2011;121(12):2710-6

20. CartwrightRD.Effectofsleeppositiononsleepapneaseverity.Sleep.1984;7(2):110-4

21. Kim KT, Cho YW, KimDE, Hwang SH, SongML,Motamedi GK. Two subtypes of positional

obstructive sleep apnea: Supine-predominant and supine-isolated. Clin Neurophysiol.

2016;127(1):565-70

22. KoutsourelakisI,SafiruddinF,RaveslootM,ZakynthinosS,deVriesN.Surgeryforobstructive

sleepapnea:sleependoscopydeterminantsofoutcome.TheLaryngoscope.2012;122(11):2587-91

23. Vanderveken OM, Maurer JT, Hohenhorst W, et al. Evaluation of drug-induced sleep

endoscopyasapatient selection tool for implantedupperairway stimulation forobstructive sleep

apnea.JClinSleepMed.2013;9(5):433-8

24. Huntley C, Chou D, Doghramji K, Boon M. Preoperative Drug Induced Sleep Endoscopy

Improves the Surgical Approach to Treatment of Obstructive Sleep Apnea. Annals of Otology,

Rhinology&Laryngology.2017;126(6):478-82

25. CertalVF,PratasR,GuimarãesL,etal.AwakeexaminationversusDISEforsurgicaldecision

makinginpatientswithOSA:asystematicreview.TheLaryngoscope.2015

26. RaveslootM,WhiteD,HeinzerR,OksenbergA,Pépin J. Efficacyof theNewGenerationof

Devices for Positional Therapy for Patients with Positional Obstructive Sleep Apnea: A Systematic

Review of the Literature and Meta-Analysis. Journal of clinical sleep medicine: JCSM: official

publicationoftheAmericanAcademyofSleepMedicine.2017

52

Chapter 2

27. Hoekema A, Stegenga B, De Bont LG. Efficacy and co-morbidity of oral appliances in the

treatment of obstructive sleep apnea-hypopnea: a systematic review. Crit Rev Oral Biol Med.

2004;15(3):137-55

28. vanKesterenER,vanMaanenJP,HilgevoordAA,LamanDM,deVriesN.Quantitativeeffects

of trunk and head position on the apnea hypopnea index in obstructive sleep apnea. Sleep.

2011;34(8):1075-81

29. ZhuK,BradleyTD,PatelM,AlshaerH.Influenceofheadpositiononobstructivesleepapnea

severity.SleepBreath.2017;21(4):821-28

30. EichlerC,SommerJU,StuckBA,HormannK,MaurerJT.Doesdrug-inducedsleependoscopy

change the treatmentconceptofpatientswithsnoringandobstructivesleepapnea?SleepBreath.

2013;17(1):63-8

31. SafiruddinF,Koutsourelakis I,deVriesN.Analysisof the influenceofhead rotationduring

drug-inducedsleependoscopyinobstructivesleepapnea.TheLaryngoscope.2014;124(9):2195-99

32. SafiruddinF,Koutsourelakis I,deVriesN.Upperairwaycollapseduringdrug inducedsleep

endoscopy: head rotation in supine position compared with lateral head and trunk position.

EuropeanArchivesofOto-Rhino-Laryngology.2015;272(2):485-88

33. MadorMJ, Kufel TJ,MagalangUJ, Rajesh SK,Watwe V, Grant BJ. Prevalence of positional

sleepapneainpatientsundergoingpolysomnography.Chest.2005;128(4):2130-7

34. Oksenberg A. Positional and non-positional obstructive sleep apnea patients. Sleep Med.

2005;6(4):377-8

35. RichardW, Kox D, den Herder C, LamanM, van Tinteren H, de Vries N. The role of sleep

positioninobstructivesleepapneasyndrome.EurArchOtorhinolaryngol.2006;263(10):946-50

3Drug-induced sleep endoscopy(DISE):Newinsightsinlateralheadrotationcomparedtolateralheadand trunk rotation in (non)positionalobstructive sleepapneapatientsP.E.Vonk,M.J.vandeBeek,M.J.L.Ravesloot,N.deVriesLaryngoscope.2019Oct;129(10):2430-2435

3Drug-induced sleep endoscopy(DISE):Newinsightsinlateralheadrotationcomparedtolateralheadand trunk rotation in (non)positionalobstructive sleepapneapatientsP.E.Vonk,M.J.vandeBeek,M.J.L.Ravesloot,N.deVriesLaryngoscope.2019Oct;129(10):2430-2435

27. Hoekema A, Stegenga B, De Bont LG. Efficacy and co-morbidity of oral appliances in the

treatment of obstructive sleep apnea-hypopnea: a systematic review. Crit Rev Oral Biol Med.

2004;15(3):137-55.

28. vanKesterenER,vanMaanenJP,HilgevoordAA,LamanDM,deVriesN.Quantitativeeffects

of trunk and head position on the apnea hypopnea index in obstructive sleep apnea. Sleep.

2011;34(8):1075-81.

29. ZhuK,BradleyTD,PatelM,AlshaerH.Influenceofheadpositiononobstructivesleepapnea

severity.SleepBreath.2017;21(4):821-28.

30. EichlerC,SommerJU,StuckBA,HormannK,MaurerJT.Doesdrug-inducedsleependoscopy

change the treatmentconceptofpatientswithsnoringandobstructivesleepapnea?SleepBreath.

2013;17(1):63-8.

31. SafiruddinF,Koutsourelakis I,deVriesN.Analysisof the influenceofhead rotationduring

drug-inducedsleependoscopyinobstructivesleepapnea.TheLaryngoscope.2014;124(9):2195-99.

32. SafiruddinF,Koutsourelakis I,deVriesN.Upperairwaycollapseduringdrug inducedsleep

endoscopy: head rotation in supine position compared with lateral head and trunk position.

EuropeanArchivesofOto-Rhino-Laryngology.2015;272(2):485-88.

33. MadorMJ, Kufel TJ,MagalangUJ, Rajesh SK,Watwe V, Grant BJ. Prevalence of positional

sleepapneainpatientsundergoingpolysomnography.Chest.2005;128(4):2130-7.

34. Oksenberg A. Positional and non-positional obstructive sleep apnea patients. Sleep Med.

2005;6(4):377-8.

35. RichardW, Kox D, den Herder C, LamanM, van Tinteren H, de Vries N. The role of sleep

positioninobstructivesleepapneasyndrome.EurArchOtorhinolaryngol.2006;263(10):946-50.

3Drug-induced sleep endoscopy(DISE):Newinsightsinlateralheadrotationcomparedtolateralheadand trunk rotation in (non)positionalobstructive sleepapneapatientsP.E.Vonk,M.J.vandeBeek,M.J.L.Ravesloot,N.deVriesLaryngoscope.2019Oct;129(10):2430-2435

3Drug-induced sleep endoscopy(DISE):Newinsightsinlateralheadrotationcomparedtolateralheadand trunk rotation in (non)positionalobstructive sleepapneapatientsP.E.Vonk,M.J.vandeBeek,M.J.L.Ravesloot,N.deVriesLaryngoscope.2019Oct;129(10):2430-2435

3Drug-induced sleep endoscopy(DISE):Newinsightsinlateralheadrotationcomparedtolateralheadand trunk rotation in (non)positionalobstructive sleepapneapatientsP.E.Vonk,M.J.vandeBeek,M.J.L.Ravesloot,N.deVriesLaryngoscope.2019Oct;129(10):2430-2435

54

Chapter 3

ABSTRACT

Objective:Tocomparetheeffectoflateralheadrotationtolateralheadandtrunkrotationonupper

airway patency during drug-induced sleep endoscopy (DISE) in non-positional obstructive sleep

apnea(OSA)patients(NPP)andpositionalOSApatients(PP).

Methods:Prospectivecohortstudy

Results:Intotal92patientswereincluded.Seventy-fivepatientsweremale(82%)withameanage

of47.2±11.3years,aBMIof27.0±3.3kg/m2andamedianAHIof16.7/h(8.7,26,5).Ofallpatients,

75%werePP.LateralheadrotationandlateralheadandtrunkrotationfindingsaresimilarinNPPat

eachpossiblelevelofobstruction,withexceptionoftheoropharynx,butnotinPP.InPP,lateralhead

rotationandboth lateralheadandtrunkobservationsweredifferentateverypossibleobstruction

site.

Conclusion:Theeffectoflateralheadrotationandlateralheadandtrunkrotationonupperairway

patency during DISE is significantly different in PP. In NPP, similar results regarding the degree of

upperairwayobstructionwerefoundatthelevelofthevelum,tonguebaseandepiglottis.

Keywords:Obstructivesleepapnea,drug-inducedsleependoscopy,lateralheadrotation,positional

INTRODUCTION

Obstructivesleepapnea(OSA) isasleeprelatedconditioncharacterizedbyrecurrentepisodesofa

decrease in airflow caused by a partial or complete collapse of the upper airway. This results in

oxygendesaturation,respiratoryarousalsand insufficientsleepduetofrequentawakenings. Inthe

majorityofOSApatientsdiseaseseverityisinfluencedbybodyposition,inwhichthesupineposition

is usually the worst sleeping position (WSP). 1-6 According to Cartwright´s definition, patients are

deemedtohavepositiondependentOSA(POSA)whentheymeet the followingcriteria:anapnea-

hypopnea index (AHI) greater than 5 and an at least twofold difference between supine and non-

supineAHI. 3Over time, variousmodificationshavebeen introduced, including variousparameters

such as the overall AHI, AHI in supine and non-supine position and time spent in various body

positions.6-10

PatientswithpositionalOSA(PP)benefit fromavoidingthesupineposition,whichcanbeachieved

through positional therapy (PT). Various forms of PT exist varying from the so-called tennis-ball

technique to a new generation of PT: vibro-tactile feedback devices. A recent meta-analysis by

Raveslootetal.showedthatnewgenerationdevicesareeffectiveinreducingtheAHIduringshort-

termfollowup.11

Currently,evidenceisgrowingthatPOSAisnotonlydependentonbodyposition,butalsoonhead

position.VanKesterenetal.reportedthatthemajorityofPParetrunksupine-dependent,ofwhich

in 46.2%headpositionwasof considerable influenceon theAHI. Furthermore they reported that

6.5%oftheirstudypopulationwasheadsupinedependentalone.12Thesefindingswereendorsedby

Zhuetal.whoanalyzedtheeffectoflateralheadrotationwiththetrunkinsupinepositiononOSA

severitybyusingpolysomnography(PSG)includingvisualinspectionofthePSGvideorecording.They

concluded that therewas a significant decrease inOSA severitywhen the headwas rotated from

supinetolateralposition,inparticularinnon-obesepatients.13

AlthoughincreasingevidenceshowsthatheadrotationcaninfluenceOSAseverity,thereisactually

lack of information on the effect of head rotation on upper airway patency. Drug-induced sleep

endoscopy(DISE)isadynamicendoscopictooltoobservetheupperairwayduringpropofol-induced

sleep,whichcanbeusedtogainmoreinformationonupperairwaycollapseinOSApatients.Tothe

bestofourknowledge,onlyonepreviousstudyhasevaluatedlateralheadrotationandtheeffecton

upperairwaypatencyduringDISE.Thistwo-partstudybySafiruddinetal.firstanalyzedtheinfluence

of different head positons on upper airway collapse in 60 subjects and found a significant

improvementonupperairwaypatencywhentheheadwasrotatedto lateralpositioncomparedto

55

New insights in lateral head rotation compared to lateral head and trunk rotation

3

ABSTRACT

Objective:Tocomparetheeffectoflateralheadrotationtolateralheadandtrunkrotationonupper

airway patency during drug-induced sleep endoscopy (DISE) in non-positional obstructive sleep

apnea(OSA)patients(NPP)andpositionalOSApatients(PP).

Methods:Prospectivecohortstudy

Results:Intotal92patientswereincluded.Seventy-fivepatientsweremale(82%)withameanage

of47.2±11.3years,aBMIof27.0±3.3kg/m2andamedianAHIof16.7/h(8.7,26,5).Ofallpatients,

75%werePP.LateralheadrotationandlateralheadandtrunkrotationfindingsaresimilarinNPPat

eachpossiblelevelofobstruction,withexceptionoftheoropharynx,butnotinPP.InPP,lateralhead

rotationandboth lateralheadandtrunkobservationsweredifferentateverypossibleobstruction

site.

Conclusion:Theeffectoflateralheadrotationandlateralheadandtrunkrotationonupperairway

patency during DISE is significantly different in PP. In NPP, similar results regarding the degree of

upperairwayobstructionwerefoundatthelevelofthevelum,tonguebaseandepiglottis.

Keywords:Obstructivesleepapnea,drug-inducedsleependoscopy,lateralheadrotation,positional

INTRODUCTION

Obstructivesleepapnea(OSA) isasleeprelatedconditioncharacterizedbyrecurrentepisodesofa

decrease in airflow caused by a partial or complete collapse of the upper airway. This results in

oxygendesaturation,respiratoryarousalsand insufficientsleepduetofrequentawakenings. Inthe

majorityofOSApatientsdiseaseseverityisinfluencedbybodyposition,inwhichthesupineposition

is usually the worst sleeping position (WSP). 1-6 According to Cartwright´s definition, patients are

deemedtohavepositiondependentOSA(POSA)whentheymeet the followingcriteria:anapnea-

hypopnea index (AHI) greater than 5 and an at least twofold difference between supine and non-

supineAHI. 3Over time, variousmodificationshavebeen introduced, including variousparameters

such as the overall AHI, AHI in supine and non-supine position and time spent in various body

positions.6-10

PatientswithpositionalOSA(PP)benefit fromavoidingthesupineposition,whichcanbeachieved

through positional therapy (PT). Various forms of PT exist varying from the so-called tennis-ball

technique to a new generation of PT: vibro-tactile feedback devices. A recent meta-analysis by

Raveslootetal.showedthatnewgenerationdevicesareeffectiveinreducingtheAHIduringshort-

termfollowup.11

Currently,evidenceisgrowingthatPOSAisnotonlydependentonbodyposition,butalsoonhead

position.VanKesterenetal.reportedthatthemajorityofPParetrunksupine-dependent,ofwhich

in 46.2%headpositionwasof considerable influenceon theAHI. Furthermore they reported that

6.5%oftheirstudypopulationwasheadsupinedependentalone.12Thesefindingswereendorsedby

Zhuetal.whoanalyzedtheeffectoflateralheadrotationwiththetrunkinsupinepositiononOSA

severitybyusingpolysomnography(PSG)includingvisualinspectionofthePSGvideorecording.They

concluded that therewas a significant decrease inOSA severitywhen the headwas rotated from

supinetolateralposition,inparticularinnon-obesepatients.13

AlthoughincreasingevidenceshowsthatheadrotationcaninfluenceOSAseverity,thereisactually

lack of information on the effect of head rotation on upper airway patency. Drug-induced sleep

endoscopy(DISE)isadynamicendoscopictooltoobservetheupperairwayduringpropofol-induced

sleep,whichcanbeusedtogainmoreinformationonupperairwaycollapseinOSApatients.Tothe

bestofourknowledge,onlyonepreviousstudyhasevaluatedlateralheadrotationandtheeffecton

upperairwaypatencyduringDISE.Thistwo-partstudybySafiruddinetal.firstanalyzedtheinfluence

of different head positons on upper airway collapse in 60 subjects and found a significant

improvementonupperairwaypatencywhentheheadwasrotatedto lateralpositioncomparedto

56

Chapter 3

supineheadandtrunkposition.Nodifferenceswerefoundwhencomparingrotationtothe leftor

rightside.Inthesecondpartoftheirstudy,lateralheadrotationalonewascomparedtolateralhead

andtrunkposition.Theyconcludedthatthesetwomaneuverswerecomparable,whenfocusingon

the level(s) andconfiguration(s) involved inupperairwayobstruction inOSApatients. Therefore it

was concluded that these twopositionsare comparableduringDISE, and that there isnoneed to

assesstheupperairwayinlateralheadandtrunkposition.14,15

Inapreviousstudy,weintroduceda3-pointscaletoretrospectivelyevaluatetheeffectofdifferent

passivemaneuversduringDISEonupperairwaypatency.Oneofthesemaneuverswaslateralhead

rotation.Whencomparingtheimprovementonupperairwaypatencywhilstperforminglateralhead

rotation,theeffectwasless(<50%)thenwhatwaspreviouslyexpectedbasedoncurrentlyavailable

literatureontreatmentoutcomeofPTinPP.16

Bearing this ismind, the firstaimof this study is tocompare theeffectof lateralheadandsupine

trunkrotationtolateralheadandtrunkrotationonupperairwaypatencyduringDISEdistinguishing

betweennon-positionalOSApatients(NPP)andPPwithparticularfocusontheseverityofcollapseat

the four levels of obstruction according to theVOTE classification system.Wehypothesize that in

case of NPP lateral head rotation is similar to lateral head and trunk rotation. In case of PP, we

hypothesize that the effect on upper airway patency of lateral head rotation only will be less

comparedtobothlateralheadandtrunkrotation.WealsohypothesizethatthemoreOSAseverityis

influencedbysleepingposition,thelesscomparablelateralheadrotationistobothlateralheadand

trunkrotation.

MATERIALANDMETHODS

Patients

Weperformedaprospective, single-centre cohort study, includinga consecutive seriesofpatients

who underwent DISE in the Department of Otolaryngology, Head and Neck surgery of the OLVG

(Amsterdam, the Netherlands) between August 2017 and November 2017. All patients were

diagnosedwithOSAbyPSG.Patientswereexcludedfromthisstudywhentheywerenotwillingto

sign informedconsentor incaseofphysicaldisabilities (e.g.backand/orneckproblems)andwere

thereforeunabletorotatetheheadtolateralpositionortolieinanon-supineposition.Whenthere

was no data available of both supine and non-supine AHI or sleeping position, patientswere also

excludedfromthisstudy.

Definitions

Whenpatientsmet the inclusion criteria,patientswere classifiedasNPPorPP.POSAwasdefined

usingamodifiedversionofCartwright’scriteria:adifferenceof50%ormoreinAHIbetweensupine

andnon-supinepositions.3

DISEprocedure

DISE procedure was performed according to the practice guidelines as recommended in the

EuropeanpositionpaperonDISE(update2017).17

Indication

ThemainreasontoperformDISEwaseligibilityforupperairwaysurgery.Otherindicationsincluded

patientseligiblefororalappliancetherapy(OAT)orcombinationtherapy(e.g.OAT+PT).

Setting

All patients underwent DISE in daycare in a safe outpatient endoscopy setting with standard

anestheticequipment.

DISE was performed by one experienced ENT resident (PV), with a trained nurse anesthetist

managingsedationandmonitoringbloodpressure,electrocardiogram(ECG)andoxygenlevels.

Sedation

The drug of choice for sedation was propofol. The level of sedation was controlled by a target

controlled infusion (TCI) pump using the methods described by Schnider et al. to calculate the

effectivedose. 18,19Prior to the intravenous (IV) infusionofpropofol,2cc lidocainewasgiven IV to

preventpaincausedbytheinfusionofpropofol.InsomepatientsGlycopyrrolate(Robinul)wasgiven

IV topreventmucosalhypersecretion, since thiscould interferewith thequalityof theendoscopic

assessment.Propersedationlevelswereachievedwhenthepatientshowedhyporesponsivenessto

verbalandtactilestimuliorwhenthepatientbegantosnore.

Patientpositioning

Ideally, the patient should be positionedmimicking sleeping habits during natural, but due to the

nature of this study DISE was performed in both supine position and lateral head (and trunk)

rotation. Initially, subjects were placed in lateral head and trunk position. When proper level of

sedationwasachieved, theupperairwaywasassessedat fourdifferent levels (velum,oropharynx,

57

New insights in lateral head rotation compared to lateral head and trunk rotation

3

supineheadandtrunkposition.Nodifferenceswerefoundwhencomparingrotationtothe leftor

rightside.Inthesecondpartoftheirstudy,lateralheadrotationalonewascomparedtolateralhead

andtrunkposition.Theyconcludedthatthesetwomaneuverswerecomparable,whenfocusingon

the level(s) andconfiguration(s) involved inupperairwayobstruction inOSApatients. Therefore it

was concluded that these twopositionsare comparableduringDISE, and that there isnoneed to

assesstheupperairwayinlateralheadandtrunkposition.14,15

Inapreviousstudy,weintroduceda3-pointscaletoretrospectivelyevaluatetheeffectofdifferent

passivemaneuversduringDISEonupperairwaypatency.Oneofthesemaneuverswaslateralhead

rotation.Whencomparingtheimprovementonupperairwaypatencywhilstperforminglateralhead

rotation,theeffectwasless(<50%)thenwhatwaspreviouslyexpectedbasedoncurrentlyavailable

literatureontreatmentoutcomeofPTinPP.16

Bearing this ismind, the firstaimof this study is tocompare theeffectof lateralheadandsupine

trunkrotationtolateralheadandtrunkrotationonupperairwaypatencyduringDISEdistinguishing

betweennon-positionalOSApatients(NPP)andPPwithparticularfocusontheseverityofcollapseat

the four levels of obstruction according to theVOTE classification system.Wehypothesize that in

case of NPP lateral head rotation is similar to lateral head and trunk rotation. In case of PP, we

hypothesize that the effect on upper airway patency of lateral head rotation only will be less

comparedtobothlateralheadandtrunkrotation.WealsohypothesizethatthemoreOSAseverityis

influencedbysleepingposition,thelesscomparablelateralheadrotationistobothlateralheadand

trunkrotation.

MATERIALANDMETHODS

Patients

Weperformedaprospective, single-centre cohort study, includinga consecutive seriesofpatients

who underwent DISE in the Department of Otolaryngology, Head and Neck surgery of the OLVG

(Amsterdam, the Netherlands) between August 2017 and November 2017. All patients were

diagnosedwithOSAbyPSG.Patientswereexcludedfromthisstudywhentheywerenotwillingto

sign informedconsentor incaseofphysicaldisabilities (e.g.backand/orneckproblems)andwere

thereforeunabletorotatetheheadtolateralpositionortolieinanon-supineposition.Whenthere

was no data available of both supine and non-supine AHI or sleeping position, patientswere also

excludedfromthisstudy.

Definitions

Whenpatientsmet the inclusion criteria,patientswere classifiedasNPPorPP.POSAwasdefined

usingamodifiedversionofCartwright’scriteria:adifferenceof50%ormoreinAHIbetweensupine

andnon-supinepositions.3

DISEprocedure

DISE procedure was performed according to the practice guidelines as recommended in the

EuropeanpositionpaperonDISE(update2017).17

Indication

ThemainreasontoperformDISEwaseligibilityforupperairwaysurgery.Otherindicationsincluded

patientseligiblefororalappliancetherapy(OAT)orcombinationtherapy(e.g.OAT+PT).

Setting

All patients underwent DISE in daycare in a safe outpatient endoscopy setting with standard

anestheticequipment.

DISE was performed by one experienced ENT resident (PV), with a trained nurse anesthetist

managingsedationandmonitoringbloodpressure,electrocardiogram(ECG)andoxygenlevels.

Sedation

The drug of choice for sedation was propofol. The level of sedation was controlled by a target

controlled infusion (TCI) pump using the methods described by Schnider et al. to calculate the

effectivedose. 18,19Prior to the intravenous (IV) infusionofpropofol,2cc lidocainewasgiven IV to

preventpaincausedbytheinfusionofpropofol.InsomepatientsGlycopyrrolate(Robinul)wasgiven

IV topreventmucosalhypersecretion, since thiscould interferewith thequalityof theendoscopic

assessment.Propersedationlevelswereachievedwhenthepatientshowedhyporesponsivenessto

verbalandtactilestimuliorwhenthepatientbegantosnore.

Patientpositioning

Ideally, the patient should be positionedmimicking sleeping habits during natural, but due to the

nature of this study DISE was performed in both supine position and lateral head (and trunk)

rotation. Initially, subjects were placed in lateral head and trunk position. When proper level of

sedationwasachieved, theupperairwaywasassessedat fourdifferent levels (velum,oropharynx,

58

Chapter 3

tonguebaseandepiglottis)accordingtotheVOTEclassificationsystem.Patientswerethentiltedto

thesupinepositionwiththeheadrotatedtotherightsideandfinallytheupperairwaywasobserved

insupinepositionofbothheadandtrunk.Jawthrustwasperformedinallpositions,toevaluatethe

effect on upper airway patency; however it was not the purpose of this study to analyze this

maneuver.

Classificationsystem

Toreportontheanatomicalstructurescausingupperairwaycollapse,theVOTEclassificationsystem

was applied. The VOTE classification system distinguishes between four different levels and

structuresthatmaybeinvolvedinupperairwaycollapse,namelyvelum(V),oropharynx(O),tongue

base(T)andepiglottis(E).Todefinethedegreeofobstruction,threedifferentcategoriesareused,

namelynoobstruction,withacollapselessthan50%;apartialobstructionwithacollapsebetween

50and75%andtypicallywithvibration;oracompletecollapseinwhichacollapseisseenofmore

than 75%. An X is used when no observation can be made. Depending on the different site(s)

involved in upper airway obstruction, the configuration may be anterior-posterior, lateral or

concentric.20Intable1anoverviewisgivenofthedegreeandpossibleconfigurationsofobstruction

ateachlevel.

Table1.TheVOTEclassificationsystem20

Structure Degree of

obstructionaConfigurationc

A-P Lateral Concentric

Velum

Oropharynxb

TongueBase

Epiglottis

A-PAntero-posterior

a.Degreeofobstruction:0noobstruction;1partialobstruction;2completeobstruction

b.Oropharynxobstructioncanbedistinguishedas relatedsolely to the tonsilsor including

thelateralwalls

c.Configurationnotedforstructureswithdegreeofobstruction>0

59

New insights in lateral head rotation compared to lateral head and trunk rotation

3

tonguebaseandepiglottis)accordingtotheVOTEclassificationsystem.Patientswerethentiltedto

thesupinepositionwiththeheadrotatedtotherightsideandfinallytheupperairwaywasobserved

insupinepositionofbothheadandtrunk.Jawthrustwasperformedinallpositions,toevaluatethe

effect on upper airway patency; however it was not the purpose of this study to analyze this

maneuver.

Classificationsystem

Toreportontheanatomicalstructurescausingupperairwaycollapse,theVOTEclassificationsystem

was applied. The VOTE classification system distinguishes between four different levels and

structuresthatmaybeinvolvedinupperairwaycollapse,namelyvelum(V),oropharynx(O),tongue

base(T)andepiglottis(E).Todefinethedegreeofobstruction,threedifferentcategoriesareused,

namelynoobstruction,withacollapselessthan50%;apartialobstructionwithacollapsebetween

50and75%andtypicallywithvibration;oracompletecollapseinwhichacollapseisseenofmore

than 75%. An X is used when no observation can be made. Depending on the different site(s)

involved in upper airway obstruction, the configuration may be anterior-posterior, lateral or

concentric.20Intable1anoverviewisgivenofthedegreeandpossibleconfigurationsofobstruction

ateachlevel.

Table1.TheVOTEclassificationsystem20

Structure Degree of

obstructionaConfigurationc

A-P Lateral Concentric

Velum

Oropharynxb

TongueBase

Epiglottis

A-PAntero-posterior

a.Degreeofobstruction:0noobstruction;1partialobstruction;2completeobstruction

b.Oropharynxobstructioncanbedistinguishedas relatedsolely to the tonsilsor including

thelateralwalls

c.Configurationnotedforstructureswithdegreeofobstruction>0

60

Chapter 3

InaccordancewiththeDeclarationofHelsinki,thestudyprotocolwasapprovedbythelocalMedical

Ethical Committee. Patients signed informed consent previous to the procedure. Data on study

subjectswascollectedandstoredanonymouslytoprotectpersonalinformation.

Statisticalanalysis

StatisticalanalysiswasperformedusingSPSS (version21),SPSS Inc.,Chicago, IL).Quantitativedata

arereportedasmean±SDorasmedian(Q1,Q3)whennotnormallydistributed.Apvalueof<0.05

wasconsideredtoindicatestatisticalsignificance.Todeterminewhethertheeffectonupperairway

patency during lateral head rotation is similar to lateral head and trunk rotation, the degree of

obstructionaccordingtotheVOTEclassificationsystemwascomparedbyusingtheWilcoxonsigned

ranktest inNPPandPP.Toanalyzetheinfluenceofthedegreeofpositiondependency,aratiofor

positiondependencywascalculatedbydividingnonsupineAHIbysupineAHI;thisimplicatesthata

ratio>0.5regardsnon-positiondependentOSA.Theclosertheratioisto1,thelessOSAseverityis

influencedbybodyposition.

RESULTS

Atotalof109patientswereinvitedtoparticipateinthisstudy.Fivepatientsdeclinedafterreceiving

additional information.InfourpatientsDISEresultscouldnotbeanalyzedduetophysicalagitation

ormucosalhypersecretion,whichrenderedDISEoutcomesunreliable. Inonesubjectbodyposition

duringthePSGnightcouldnotbedeterminedduetomalfunctionofthePSGapparatusandinseven

patients supine AHI could not be determined due to a TST of zero per cent in supine position.

Therefore,onlytheresultsoftheremaining92subjectswereanalyzed.

Seventy-fivepatientsweremale(82%).Themeanagewas47.2±11.3years,withaBMIof27.0±3.3

kg/m2and a median AHI of 16.7/h (8.7, 26,5), a median supine AHI of 31.9/h (16.5, 53.5) and a

median non supine AHI of 8.1/h (3.1, 15.2). Patients spent amedian percentage of TST in supine

positionof34.0%andthemedianoxygendesaturationindex(ODI)was19.5/h(11.9,29.2).Twenty-

fivepercentofallpatientswereNPP. WhencomparingbaselinecharacteristicsbetweenNPPand

PP, PP had as expected a significantly lower non supine AHI. The supine AHI was higher in PP

comparedtoNPP,butnotstatisticallysignificant.Thepercentageofmalesubjectswassignificantly

highercomparingNPPtoPP,namely65.2%versus87.0%.Anoverviewofbaselinecharacteristicsof

thetotalpopulationandsubgroupsarepresentedintable2.

Table2.BaselinecharacteristicstotalpopulationandNPPversusPP

Total NPP PP NPPvsPP

pvalue

Number(%) 92 23(25) 69(75) 23vs69

Age(years) 47.2±11.3 44.9±13.4 48.0±10.5 0.248

Male/Female 75/17 15/8 60/9 0.019*

BMI(kg/m2) 27.0±3.3 27.3±3.8 26.9±3.1 0.664

TotalAHI

(events/hour)

16.7

(8.7,26.5)°

21.5

(8.7,33.4)°

15.7

(8.7,24.1)°

0.262

SupineAHI

(events/hour)

31.9

(16.5,53.5)°

25.2

(9.9,47.0)°

37.0

(18.4,54.7)°

0.081

NonsupineAHI

(events/hour)

8.1

(3.1,15.2)°

16.3

(9.4,34.4)°

5.7

(2.4,11.2)°

<0.001*

Supinesleepingtime

(%)

34.0

(23.1,47.5)°

37.0

(30.3,61.3)°

31.0

(20.7,46.0)°

0.050

ODI

(events/hour)

19.5

(11.9,29.2)°

19.5

(11.7,38.2)°

19.5

(11.9,27.2)°

0.317

NPP non-positional PP positional dependent patients BMI Body Mass index AHI apnea-hypopnea

indexODIoxygendesaturationindex

°Median(Q1,Q3);*pvalue<0.05

61

New insights in lateral head rotation compared to lateral head and trunk rotation

3

InaccordancewiththeDeclarationofHelsinki,thestudyprotocolwasapprovedbythelocalMedical

Ethical Committee. Patients signed informed consent previous to the procedure. Data on study

subjectswascollectedandstoredanonymouslytoprotectpersonalinformation.

Statisticalanalysis

StatisticalanalysiswasperformedusingSPSS (version21),SPSS Inc.,Chicago, IL).Quantitativedata

arereportedasmean±SDorasmedian(Q1,Q3)whennotnormallydistributed.Apvalueof<0.05

wasconsideredtoindicatestatisticalsignificance.Todeterminewhethertheeffectonupperairway

patency during lateral head rotation is similar to lateral head and trunk rotation, the degree of

obstructionaccordingtotheVOTEclassificationsystemwascomparedbyusingtheWilcoxonsigned

ranktest inNPPandPP.Toanalyzetheinfluenceofthedegreeofpositiondependency,aratiofor

positiondependencywascalculatedbydividingnonsupineAHIbysupineAHI;thisimplicatesthata

ratio>0.5regardsnon-positiondependentOSA.Theclosertheratioisto1,thelessOSAseverityis

influencedbybodyposition.

RESULTS

Atotalof109patientswereinvitedtoparticipateinthisstudy.Fivepatientsdeclinedafterreceiving

additional information.InfourpatientsDISEresultscouldnotbeanalyzedduetophysicalagitation

ormucosalhypersecretion,whichrenderedDISEoutcomesunreliable. Inonesubjectbodyposition

duringthePSGnightcouldnotbedeterminedduetomalfunctionofthePSGapparatusandinseven

patients supine AHI could not be determined due to a TST of zero per cent in supine position.

Therefore,onlytheresultsoftheremaining92subjectswereanalyzed.

Seventy-fivepatientsweremale(82%).Themeanagewas47.2±11.3years,withaBMIof27.0±3.3

kg/m2and a median AHI of 16.7/h (8.7, 26,5), a median supine AHI of 31.9/h (16.5, 53.5) and a

median non supine AHI of 8.1/h (3.1, 15.2). Patients spent amedian percentage of TST in supine

positionof34.0%andthemedianoxygendesaturationindex(ODI)was19.5/h(11.9,29.2).Twenty-

fivepercentofallpatientswereNPP. WhencomparingbaselinecharacteristicsbetweenNPPand

PP, PP had as expected a significantly lower non supine AHI. The supine AHI was higher in PP

comparedtoNPP,butnotstatisticallysignificant.Thepercentageofmalesubjectswassignificantly

highercomparingNPPtoPP,namely65.2%versus87.0%.Anoverviewofbaselinecharacteristicsof

thetotalpopulationandsubgroupsarepresentedintable2.

Table2.BaselinecharacteristicstotalpopulationandNPPversusPP

Total NPP PP NPPvsPP

pvalue

Number(%) 92 23(25) 69(75) 23vs69

Age(years) 47.2±11.3 44.9±13.4 48.0±10.5 0.248

Male/Female 75/17 15/8 60/9 0.019*

BMI(kg/m2) 27.0±3.3 27.3±3.8 26.9±3.1 0.664

TotalAHI

(events/hour)

16.7

(8.7,26.5)°

21.5

(8.7,33.4)°

15.7

(8.7,24.1)°

0.262

SupineAHI

(events/hour)

31.9

(16.5,53.5)°

25.2

(9.9,47.0)°

37.0

(18.4,54.7)°

0.081

NonsupineAHI

(events/hour)

8.1

(3.1,15.2)°

16.3

(9.4,34.4)°

5.7

(2.4,11.2)°

<0.001*

Supinesleepingtime

(%)

34.0

(23.1,47.5)°

37.0

(30.3,61.3)°

31.0

(20.7,46.0)°

0.050

ODI

(events/hour)

19.5

(11.9,29.2)°

19.5

(11.7,38.2)°

19.5

(11.9,27.2)°

0.317

NPP non-positional PP positional dependent patients BMI Body Mass index AHI apnea-hypopnea

indexODIoxygendesaturationindex

°Median(Q1,Q3);*pvalue<0.05

62

Chapter 3

InNPP,lateralheadrotationalonewascomparabletolateralheadandtrunkrotationconcerningthe

degreeofobstructionatvelum,tonguebaseandepiglottislevels.InPP,lateralheadrotationalone

significantlydifferedatalllevelsobservedduringDISEcomparedtolateralheadandtrunkrotation.

Anoverviewisgivenintable3andtable4.

Table3.DISEresultscomparinglateralheadrotationversuslateralheadandtrunkrotationinNPP

Level Configuration

(%)

Lateralheadrotation Lateralheadandtrunk

rotation

pvalueα

None Partial Complete None Partial Complete

Velum A-P 10 4 6 11 4 5 0.180

Concentric 1 2 2 1

Oropharynx Lateral 7 5 11 13 1 9 0.011*

Tonguebase A-P 13 5 5 16 5 2 0.655

Epiglottis A-P 14 5 3 19 3 1 0.058

A-PAntero-posterior

αpvaluesareWilcoxonsignedranktest

Table4.DISEresultscomparinglateralheadrotationversuslateralheadandtrunkrotationinPP

Level Configuration

(%)

Lateralheadrotation Lateralheadandtrunk

rotation

pvalueα

None Partial Complete None Partial Complete

Velum A-P 16 20 11 42 11 1 <0.001*

Concentric 8 14 11 4

Oropharynx Lateral 19 20 30 36 13 20 <0.001*

Tonguebase A-P 38 22 8 50 17 1 0.008*

Epiglottis A-P 42 15 11 60 4 4 <0.001*

A-PAntero-posterior

αpvaluesareWilcoxonsignedranktest.

Unfortunately, the data extracted to analyze the influence of the degree of position dependency

werenotreliableduetothesmallsamplesize inthedifferentsubgroups.Therefore, thestatistical

powerwasnothighenough.

DISCUSSION

Thisstudydescribestheeffectoflateralheadrotationcomparedtolateralheadandtrunkrotation

on upper airway patency during DISE in NPP and PP. The current results indicate that in NPP the

effectonupperairwaypatencywhenperforminglateralheadrotationonlyissimilartobothlateral

headandtrunkrotationateachpossiblelevelofobstruction,withexceptionoftheoropharynx.This

doesnotapplyforPP,inwhichsignificantlydifferentresultswerefoundatallfourpossiblelevelsof

obstruction.

ThepercentageofPPinourstudygroupwasrelativelyhigh,namely75%.Thiscouldbeexplainedby

thefactthattheprevalenceofPOSAdecreasesastheseverityofOSAincreasesandthatthemajority

ofthisstudypopulationwasdiagnosedwithmildtomoderateOSA. IncaseofsevereOSA,CPAP is

the first therapy of choice, which does not require DISE. The percentage of male subjects was

significantly higher in PP compared to NPP, a finding which is not described previously in the

literature.ThisdifferencecouldnotbeexplainedbyconfounderssuchasBMIorage.

The underlying pathophysiological mechanism explaining the different patterns of upper airway

collapse insupineandnon-supinepositionremains inquestion.VanKesterenetal. suggestedthat

withthehead insupineposition,thetongueandtoa lesserextentthesoftpalate, fallsbackwards

duetogravitationalforcesandmusclerelaxation.Thiseffectwouldpresumablybesmallerwhenthe

headisrotatedtolateralposition.12

ThesefindingswerestrengthenedbyastudyofLeeetal.Theyevaluatedthechangesinobstruction

siteaccording to sleepposition todeterminewhichobstructionsare responsible forobstruction in

lateralbodyposition.Theyconcludedthatobstructionduetothetonguebaseandlarynximproved

dramatically whenmoving from supine to lateral body position and that recurrent obstruction in

lateralbodypositionwasmainlycausedbylateralwallcollapsibility.Theyadditionallyassumedthat

displacementof the tonguebasealters lateralwall tensionandcausesasecondarycollapseof the

oropharyngealwalls.21Thefindingsofthesestudiescouldexplainthefactthatwefoundasignificant

differenceatoropharynxlevelwhencomparinglateralheadrotationalonetobothlateralheadand

trunkrotation,sincetheoropharyngealcollapseinNPPisenhancedbylateralbodyposition.

Theresultsofthisstudyareincontrasttowhatwaspreviouslydescribedinanearlierstudyfromour

groupbySafiruddinetal.Theyconcludedthattheoccurrenceofapartialand/orcompletecollapse

63

New insights in lateral head rotation compared to lateral head and trunk rotation

3

InNPP,lateralheadrotationalonewascomparabletolateralheadandtrunkrotationconcerningthe

degreeofobstructionatvelum,tonguebaseandepiglottislevels.InPP,lateralheadrotationalone

significantlydifferedatalllevelsobservedduringDISEcomparedtolateralheadandtrunkrotation.

Anoverviewisgivenintable3andtable4.

Table3.DISEresultscomparinglateralheadrotationversuslateralheadandtrunkrotationinNPP

Level Configuration

(%)

Lateralheadrotation Lateralheadandtrunk

rotation

pvalueα

None Partial Complete None Partial Complete

Velum A-P 10 4 6 11 4 5 0.180

Concentric 1 2 2 1

Oropharynx Lateral 7 5 11 13 1 9 0.011*

Tonguebase A-P 13 5 5 16 5 2 0.655

Epiglottis A-P 14 5 3 19 3 1 0.058

A-PAntero-posterior

αpvaluesareWilcoxonsignedranktest

Table4.DISEresultscomparinglateralheadrotationversuslateralheadandtrunkrotationinPP

Level Configuration

(%)

Lateralheadrotation Lateralheadandtrunk

rotation

pvalueα

None Partial Complete None Partial Complete

Velum A-P 16 20 11 42 11 1 <0.001*

Concentric 8 14 11 4

Oropharynx Lateral 19 20 30 36 13 20 <0.001*

Tonguebase A-P 38 22 8 50 17 1 0.008*

Epiglottis A-P 42 15 11 60 4 4 <0.001*

A-PAntero-posterior

αpvaluesareWilcoxonsignedranktest.

Unfortunately, the data extracted to analyze the influence of the degree of position dependency

werenotreliableduetothesmallsamplesize inthedifferentsubgroups.Therefore, thestatistical

powerwasnothighenough.

DISCUSSION

Thisstudydescribestheeffectoflateralheadrotationcomparedtolateralheadandtrunkrotation

on upper airway patency during DISE in NPP and PP. The current results indicate that in NPP the

effectonupperairwaypatencywhenperforminglateralheadrotationonlyissimilartobothlateral

headandtrunkrotationateachpossiblelevelofobstruction,withexceptionoftheoropharynx.This

doesnotapplyforPP,inwhichsignificantlydifferentresultswerefoundatallfourpossiblelevelsof

obstruction.

ThepercentageofPPinourstudygroupwasrelativelyhigh,namely75%.Thiscouldbeexplainedby

thefactthattheprevalenceofPOSAdecreasesastheseverityofOSAincreasesandthatthemajority

ofthisstudypopulationwasdiagnosedwithmildtomoderateOSA. IncaseofsevereOSA,CPAP is

the first therapy of choice, which does not require DISE. The percentage of male subjects was

significantly higher in PP compared to NPP, a finding which is not described previously in the

literature.ThisdifferencecouldnotbeexplainedbyconfounderssuchasBMIorage.

The underlying pathophysiological mechanism explaining the different patterns of upper airway

collapse insupineandnon-supinepositionremains inquestion.VanKesterenetal. suggestedthat

withthehead insupineposition,thetongueandtoa lesserextentthesoftpalate, fallsbackwards

duetogravitationalforcesandmusclerelaxation.Thiseffectwouldpresumablybesmallerwhenthe

headisrotatedtolateralposition.12

ThesefindingswerestrengthenedbyastudyofLeeetal.Theyevaluatedthechangesinobstruction

siteaccording to sleepposition todeterminewhichobstructionsare responsible forobstruction in

lateralbodyposition.Theyconcludedthatobstructionduetothetonguebaseandlarynximproved

dramatically whenmoving from supine to lateral body position and that recurrent obstruction in

lateralbodypositionwasmainlycausedbylateralwallcollapsibility.Theyadditionallyassumedthat

displacementof the tonguebasealters lateralwall tensionandcausesasecondarycollapseof the

oropharyngealwalls.21Thefindingsofthesestudiescouldexplainthefactthatwefoundasignificant

differenceatoropharynxlevelwhencomparinglateralheadrotationalonetobothlateralheadand

trunkrotation,sincetheoropharyngealcollapseinNPPisenhancedbylateralbodyposition.

Theresultsofthisstudyareincontrasttowhatwaspreviouslydescribedinanearlierstudyfromour

groupbySafiruddinetal.Theyconcludedthattheoccurrenceofapartialand/orcompletecollapse

64

Chapter 3

during DISE was similar comparing lateral head rotation to lateral head and trunk rotation, with

exceptionof thepalate.Nevertheless, thereare somecritical comments tobemade.Firstofall, a

smallstudypopulationwasused(N=60)ofwhichonly38%ofallpatientswasdiagnosedwithPOSA.

Thispercentage ismuch lower than theprevalenceofPOSA found in literatureand in thepresent

study.ThiscombinedwiththefactthatnodistinctionwasmadebetweenNPPandPPmightexplain

thedifferentresults.15

Limitations

This study is not without limitations. First of all, we intended to evaluate the effect of position

dependencybycalculatinga ratiodividingnonsupineAHIby supineAHI.Althoughwestillbelieve

ourhypothesisispotentiallytrue,wecouldnotconfirmthisbystatisticallyanalysisofourdata.There

wereanumberofproblemsencounteredwhenanalyzingtheresults.Whendividingthetotalstudy

population into different subgroups to compare the differences in degree of obstruction for each

different level, our sample size was too small. Secondly, the degree of obstruction during DISE

accordingtotheVOTEclassificationsystemconsistsofonlya3-pointsystem;0(<50%obstruction),1

(between 50-75% obstruction) or 2 (> 75%). In theory this could mean that although a different

degreeofobstructionisseenduringDISE(e.g.50%vs70%),thiswillbothbescoredthesame.

Thirdly, DISE can also be hampered by interobserver and intraobserver variability. 22,23 A previous

study showed that this variability seems to be less significant in experienced endoscopists. 24

Therefore,tominimizetheinfluenceofinterobserverandintraobservervariabilityinthisstudy,DISE

wasperformedbyonlyoneexperiencedENTresident(PV).Finally,nodataonheadpositionduring

thePSGnightwasavailable.Therefore,theeffectonupperairwaypatencyof lateralheadrotation

aloneandbothlateralheadandtrunkrotationcouldnotbeverifiedbyOSAseveritymeasuredwith

PSG.

Clinicalrelevance

Currently,theeffectofbodyposition,eitherheadorheadandtrunk,ondiseaseseverity isgaining

renewed attention. In addition, PT is becoming amore accepted treatment in PP as a standalone

treatmentorincombinationwithothertreatmentmodalities.Historically,recommendationswereto

performDISE in theWSP,which is usually the supineposition.But, especially in PP, inwhichOSA

severityisinfluencedbybodyposition,lateralassessmentoftheupperairwayisjustasimportantas

assessment of the supine position during DISE. For example,when PP tolerate PT, less aggressive

formsofupperairwaysurgerycanbeapplied.

Although it is clear that lateralassessmentof theupperairway isofaddedvalue inPP, itmustbe

kept inmind that notmeeting Cartwright’s criteria for position dependency, does not necessarily

mean thatOSAseverity inNPPcannotbe influencedby sleepingposition.Therefore, it isbelieved

thatlateralassessmentoftheupperairwayinNPPcanstillbeofaddedvalue.

ImpactofthesefindingsonhowtoperformDISE

Currently, inour centreDISE isperformed in supineposition followedbyassessmentof theupper

airwaywiththeheadrotatedtothelateralpositionwithandwithoutjawthrust.Theresultsofthis

studysuggestthatthismanoeuvremimicstheeffectofnon-supinesleepingpositiononupperairway

patencywithexceptionoftheleveloftheoropharynxinNPP.ThisdoesnotapplyforPP.Although

lateralheadrotationaloneismuchmorepractical,lateralheadandtrunkpositioninPPseemstobe

morerepresentativeforlateralsleepposition.

Therefore,we suggest that inNPPDISE shouldbeperformed in supine sleepingpositionwith and

without lateral head rotation tomimic non supine sleeping position. This allows the physician to

evaluate upper airway patency in both positions.We believe that thismaneuver can be of added

valueincasecombinationtherapywithOAT+PTisconsideredortoevaluatepossibilitiestoperform

lessaggressiveformsofupperairwaysurgerywhencombinedwithPT.

InPPwerecommendtoperformDISEinbothsupinepositionandlateralheadandtrunkrotationto

gainmoresufficientinformationonupperairwaycollapsepatternsinnon-supinesleepingposition.

CONCLUSION

Inconclusion,theeffectoflateralheadrotationandlateralheadandtrunkrotationonupperairway

patencyduringDISEissignificantlydifferentinPP.InNPP,similarresultswerefoundatthelevelof

the velum, tongue base and epiglottis. In NPP lateral head rotation only seems to be sufficient

enoughtomimicnonsupinesleepingposition.InPP,werecommendthatDISEisperformedinboth

lateralheadandtrunkposition.

65

New insights in lateral head rotation compared to lateral head and trunk rotation

3

during DISE was similar comparing lateral head rotation to lateral head and trunk rotation, with

exceptionof thepalate.Nevertheless, thereare somecritical comments tobemade.Firstofall, a

smallstudypopulationwasused(N=60)ofwhichonly38%ofallpatientswasdiagnosedwithPOSA.

Thispercentage ismuch lower than theprevalenceofPOSA found in literatureand in thepresent

study.ThiscombinedwiththefactthatnodistinctionwasmadebetweenNPPandPPmightexplain

thedifferentresults.15

Limitations

This study is not without limitations. First of all, we intended to evaluate the effect of position

dependencybycalculatinga ratiodividingnonsupineAHIby supineAHI.Althoughwestillbelieve

ourhypothesisispotentiallytrue,wecouldnotconfirmthisbystatisticallyanalysisofourdata.There

wereanumberofproblemsencounteredwhenanalyzingtheresults.Whendividingthetotalstudy

population into different subgroups to compare the differences in degree of obstruction for each

different level, our sample size was too small. Secondly, the degree of obstruction during DISE

accordingtotheVOTEclassificationsystemconsistsofonlya3-pointsystem;0(<50%obstruction),1

(between 50-75% obstruction) or 2 (> 75%). In theory this could mean that although a different

degreeofobstructionisseenduringDISE(e.g.50%vs70%),thiswillbothbescoredthesame.

Thirdly, DISE can also be hampered by interobserver and intraobserver variability. 22,23 A previous

study showed that this variability seems to be less significant in experienced endoscopists. 24

Therefore,tominimizetheinfluenceofinterobserverandintraobservervariabilityinthisstudy,DISE

wasperformedbyonlyoneexperiencedENTresident(PV).Finally,nodataonheadpositionduring

thePSGnightwasavailable.Therefore,theeffectonupperairwaypatencyof lateralheadrotation

aloneandbothlateralheadandtrunkrotationcouldnotbeverifiedbyOSAseveritymeasuredwith

PSG.

Clinicalrelevance

Currently,theeffectofbodyposition,eitherheadorheadandtrunk,ondiseaseseverity isgaining

renewed attention. In addition, PT is becoming amore accepted treatment in PP as a standalone

treatmentorincombinationwithothertreatmentmodalities.Historically,recommendationswereto

performDISE in theWSP,which is usually the supineposition.But, especially in PP, inwhichOSA

severityisinfluencedbybodyposition,lateralassessmentoftheupperairwayisjustasimportantas

assessment of the supine position during DISE. For example,when PP tolerate PT, less aggressive

formsofupperairwaysurgerycanbeapplied.

Although it is clear that lateralassessmentof theupperairway isofaddedvalue inPP, itmustbe

kept inmind that notmeeting Cartwright’s criteria for position dependency, does not necessarily

mean thatOSAseverity inNPPcannotbe influencedby sleepingposition.Therefore, it isbelieved

thatlateralassessmentoftheupperairwayinNPPcanstillbeofaddedvalue.

ImpactofthesefindingsonhowtoperformDISE

Currently, inour centreDISE isperformed in supineposition followedbyassessmentof theupper

airwaywiththeheadrotatedtothelateralpositionwithandwithoutjawthrust.Theresultsofthis

studysuggestthatthismanoeuvremimicstheeffectofnon-supinesleepingpositiononupperairway

patencywithexceptionoftheleveloftheoropharynxinNPP.ThisdoesnotapplyforPP.Although

lateralheadrotationaloneismuchmorepractical,lateralheadandtrunkpositioninPPseemstobe

morerepresentativeforlateralsleepposition.

Therefore,we suggest that inNPPDISE shouldbeperformed in supine sleepingpositionwith and

without lateral head rotation tomimic non supine sleeping position. This allows the physician to

evaluate upper airway patency in both positions.We believe that thismaneuver can be of added

valueincasecombinationtherapywithOAT+PTisconsideredortoevaluatepossibilitiestoperform

lessaggressiveformsofupperairwaysurgerywhencombinedwithPT.

InPPwerecommendtoperformDISEinbothsupinepositionandlateralheadandtrunkrotationto

gainmoresufficientinformationonupperairwaycollapsepatternsinnon-supinesleepingposition.

CONCLUSION

Inconclusion,theeffectoflateralheadrotationandlateralheadandtrunkrotationonupperairway

patencyduringDISEissignificantlydifferentinPP.InNPP,similarresultswerefoundatthelevelof

the velum, tongue base and epiglottis. In NPP lateral head rotation only seems to be sufficient

enoughtomimicnonsupinesleepingposition.InPP,werecommendthatDISEisperformedinboth

lateralheadandtrunkposition.

66

Chapter 3

REFERENCES

1. Ravesloot M, Van Maanen J, Dun L, De Vries N. The undervalued potential of positional

therapyinposition-dependentsnoringandobstructivesleepapnea—areviewoftheliterature.Sleep

andBreathing.2013;17(1):39-49

2. RaveslootMJ,FrankMH,vanMaanenJP,VerhagenEA,deLangeJ,deVriesN.PositionalOSA

part 2: retrospective cohort analysis with a new classification system (APOC). Sleep Breath.

2016;20(2):881-8

3. CartwrightRD.Effectofsleeppositiononsleepapneaseverity.Sleep.1984;7(2):110-4

4. OksenbergA,SilverbergDS,AronsE,RadwanH.Positionalvsnonpositionalobstructivesleep

apneapatients:anthropomorphic,nocturnalpolysomnographic,andmultiplesleeplatencytestdata.

Chest.1997;112(3):629-39

5. RichardW, Kox D, den Herder C, LamanM, van Tinteren H, de Vries N. The role of sleep

positioninobstructivesleepapneasyndrome.EurArchOtorhinolaryngol.2006;263(10):946-50

6. MadorMJ, Kufel TJ,MagalangUJ, Rajesh SK,Watwe V, Grant BJ. Prevalence of positional

sleepapneainpatientsundergoingpolysomnography.Chest.2005;128(4):2130-7

7. MarklundM, PerssonM, Franklin KA. Treatment success with amandibular advancement

deviceisrelatedtosupine-dependentsleepapnea.Chest.1998;114(6):1630-5

8. PermutI,Diaz-AbadM,ChatilaW,etal.ComparisonofpositionaltherapytoCPAPinpatients

withpositionalobstructivesleepapnea.JClinSleepMed.2010;6(3):238-43

9. Bignold JJ,Mercer JD, Antic NA,McEvoy RD, Catcheside PG. Accurate positionmonitoring

andimprovedsupine-dependentobstructivesleepapneawithanewpositionrecordingandsupine

avoidancedevice.JClinSleepMed.2011;7(4):376-83

10. Kim KT, Cho YW, KimDE, Hwang SH, SongML,Motamedi GK. Two subtypes of positional

obstructive sleep apnea: Supine-predominant and supine-isolated. Clin Neurophysiol.

2016;127(1):565-70

11. RaveslootM,WhiteD,HeinzerR,OksenbergA,Pépin J. Efficacyof theNewGenerationof

Devices for Positional Therapy for Patients with Positional Obstructive Sleep Apnea: A Systematic

Review of the Literature and Meta-Analysis. Journal of clinical sleep medicine: JCSM: official

publicationoftheAmericanAcademyofSleepMedicine.2017

12. vanKesterenER,vanMaanenJP,HilgevoordAA,LamanDM,deVriesN.Quantitativeeffects

of trunk and head position on the apnea hypopnea index in obstructive sleep apnea. Sleep.

2011;34(8):1075-81

13. ZhuK,BradleyTD,PatelM,AlshaerH.Influenceofheadpositiononobstructivesleepapnea

severity.SleepBreath.2017;21(4):821-28

14. SafiruddinF,Koutsourelakis I,deVriesN.Analysisof the influenceofhead rotationduring

drug-inducedsleependoscopyinobstructivesleepapnea.TheLaryngoscope.2014;124(9):2195-99.

15. SafiruddinF,Koutsourelakis I,deVriesN.Upperairwaycollapseduringdrug inducedsleep

endoscopy: head rotation in supine position compared with lateral head and trunk position.

EuropeanArchivesofOto-Rhino-Laryngology.2015;272(2):485-88.

16. VonkPE,BeelenA,deVriesN.Towardsapredictionmodelfordrug-inducedsleependoscopy

asselectiontoolfororalappliancetreatmentandpositionaltherapyinobstructivesleepapnea.Sleep

Breath.2018.

17. DeVitoA,CarrascoLlatasM,RavenslootM,etal.Europeanpositionpaperondrug-induced

sleependoscopy(DISE):2017update.ClinicalOtolaryngology.2018.

18. Schnider T, Minto C. Pharmacokinetic models of propofol for TCI. Anaesthesia.

2008;63(2):206-06.

19. Schnider TW,Minto CF, Gambus PL, et al. The influence ofmethod of administration and

covariateson thepharmacokineticsofpropofol in adult volunteers.Anesthesiology: The Journalof

theAmericanSocietyofAnesthesiologists.1998;88(5):1170-82.

20. Kezirian EJ, Hohenhorst W, de Vries N. Drug-induced sleep endoscopy: the VOTE

classification.EurArchOtorhinolaryngol.2011;268(8):1233-36.

21. LeeSA,PaekJH,ChungYS,KimWS.Clinical features inpatientswithpositionalobstructive

sleepapneaaccordingtoitssubtypes.SleepBreath.2017;21(1):109-17.

22. Carrasco-Llatas M, Zerpa-Zerpa V, Dalmau-Galofre J. Reliability of drug-induced sedation

endoscopy:interobserveragreement.SleepBreath.2017;21(1):173-79.

23. KezirianEJ,WhiteDP,MalhotraA,MaW,McCullochCE,GoldbergAN.Interraterreliabilityof

drug-inducedsleependoscopy.ArchOtolaryngolHeadNeckSurg.2010;136(4):393-7.

24. VroegopAV, VandervekenOM,Wouters K, et al.Observer variation in drug-induced sleep

endoscopy: experienced versus nonexperienced ear, nose, and throat surgeons. Sleep.

2013;36(6):947-53.

67

New insights in lateral head rotation compared to lateral head and trunk rotation

3

REFERENCES

1. Ravesloot M, Van Maanen J, Dun L, De Vries N. The undervalued potential of positional

therapyinposition-dependentsnoringandobstructivesleepapnea—areviewoftheliterature.Sleep

andBreathing.2013;17(1):39-49.

2. RaveslootMJ,FrankMH,vanMaanenJP,VerhagenEA,deLangeJ,deVriesN.PositionalOSA

part 2: retrospective cohort analysis with a new classification system (APOC). Sleep Breath.

2016;20(2):881-8.

3. CartwrightRD.Effectofsleeppositiononsleepapneaseverity.Sleep.1984;7(2):110-4.

4. OksenbergA,SilverbergDS,AronsE,RadwanH.Positionalvsnonpositionalobstructivesleep

apneapatients:anthropomorphic,nocturnalpolysomnographic,andmultiplesleeplatencytestdata.

Chest.1997;112(3):629-39.

5. RichardW, Kox D, den Herder C, LamanM, van Tinteren H, de Vries N. The role of sleep

positioninobstructivesleepapneasyndrome.EurArchOtorhinolaryngol.2006;263(10):946-50.

6. MadorMJ, Kufel TJ,MagalangUJ, Rajesh SK,Watwe V, Grant BJ. Prevalence of positional

sleepapneainpatientsundergoingpolysomnography.Chest.2005;128(4):2130-7.

7. MarklundM, PerssonM, Franklin KA. Treatment success with amandibular advancement

deviceisrelatedtosupine-dependentsleepapnea.Chest.1998;114(6):1630-5.

8. PermutI,Diaz-AbadM,ChatilaW,etal.ComparisonofpositionaltherapytoCPAPinpatients

withpositionalobstructivesleepapnea.JClinSleepMed.2010;6(3):238-43.

9. Bignold JJ,Mercer JD, Antic NA,McEvoy RD, Catcheside PG. Accurate positionmonitoring

andimprovedsupine-dependentobstructivesleepapneawithanewpositionrecordingandsupine

avoidancedevice.JClinSleepMed.2011;7(4):376-83.

10. Kim KT, Cho YW, KimDE, Hwang SH, SongML,Motamedi GK. Two subtypes of positional

obstructive sleep apnea: Supine-predominant and supine-isolated. Clin Neurophysiol.

2016;127(1):565-70.

11. RaveslootM,WhiteD,HeinzerR,OksenbergA,Pépin J. Efficacyof theNewGenerationof

Devices for Positional Therapy for Patients with Positional Obstructive Sleep Apnea: A Systematic

Review of the Literature and Meta-Analysis. Journal of clinical sleep medicine: JCSM: official

publicationoftheAmericanAcademyofSleepMedicine.2017.

12. vanKesterenER,vanMaanenJP,HilgevoordAA,LamanDM,deVriesN.Quantitativeeffects

of trunk and head position on the apnea hypopnea index in obstructive sleep apnea. Sleep.

2011;34(8):1075-81.

13. ZhuK,BradleyTD,PatelM,AlshaerH.Influenceofheadpositiononobstructivesleepapnea

severity.SleepBreath.2017;21(4):821-28.

14. SafiruddinF,Koutsourelakis I,deVriesN.Analysisof the influenceofhead rotationduring

drug-inducedsleependoscopyinobstructivesleepapnea.TheLaryngoscope.2014;124(9):2195-99

15. SafiruddinF,Koutsourelakis I,deVriesN.Upperairwaycollapseduringdrug inducedsleep

endoscopy: head rotation in supine position compared with lateral head and trunk position.

EuropeanArchivesofOto-Rhino-Laryngology.2015;272(2):485-88

16. VonkPE,BeelenA,deVriesN.Towardsapredictionmodelfordrug-inducedsleependoscopy

asselectiontoolfororalappliancetreatmentandpositionaltherapyinobstructivesleepapnea.Sleep

Breath.2018

17. DeVitoA,CarrascoLlatasM,RavenslootM,etal.Europeanpositionpaperondrug-induced

sleependoscopy(DISE):2017update.ClinicalOtolaryngology.2018

18. Schnider T, Minto C. Pharmacokinetic models of propofol for TCI. Anaesthesia.

2008;63(2):206-06

19. Schnider TW,Minto CF, Gambus PL, et al. The influence ofmethod of administration and

covariateson thepharmacokineticsofpropofol in adult volunteers.Anesthesiology: The Journalof

theAmericanSocietyofAnesthesiologists.1998;88(5):1170-82

20. Kezirian EJ, Hohenhorst W, de Vries N. Drug-induced sleep endoscopy: the VOTE

classification.EurArchOtorhinolaryngol.2011;268(8):1233-36

21. LeeSA,PaekJH,ChungYS,KimWS.Clinical features inpatientswithpositionalobstructive

sleepapneaaccordingtoitssubtypes.SleepBreath.2017;21(1):109-17

22. Carrasco-Llatas M, Zerpa-Zerpa V, Dalmau-Galofre J. Reliability of drug-induced sedation

endoscopy:interobserveragreement.SleepBreath.2017;21(1):173-79

23. KezirianEJ,WhiteDP,MalhotraA,MaW,McCullochCE,GoldbergAN.Interraterreliabilityof

drug-inducedsleependoscopy.ArchOtolaryngolHeadNeckSurg.2010;136(4):393-7

24. VroegopAV, VandervekenOM,Wouters K, et al.Observer variation in drug-induced sleep

endoscopy: experienced versus nonexperienced ear, nose, and throat surgeons. Sleep.

2013;36(6):947-53

4Jawthrustversustheuseofaboil-and-bitemandibularadvancementdevice as a screening tool duringdrug-inducedsleependoscopyP.E.Vonk,J.A.M.UnikenVenema,M.J.L.Ravesloot,A.Hoekema,J.A.vandeVelde–Muusers,N.deVriesSubmitted

4Jawthrustversustheuseofaboil-and-bitemandibularadvancementdevice as a screening tool duringdrug-inducedsleependoscopyP.E.Vonk,J.A.M.UnikenVenema,M.J.L.Ravesloot,A.Hoekema,J.A.vandeVelde–Muusers,N.deVriesSubmitted

4Jawthrustversustheuseofaboil-and-bitemandibularadvancementdevice as a screening tool duringdrug-inducedsleependoscopyP.E.Vonk,J.A.M.UnikenVenema,M.J.L.Ravesloot,A.Hoekema,J.A.vandeVelde–Muusers,N.deVriesSubmitted

4Jawthrustversustheuseofaboil-and-bitemandibularadvancementdevice as a screening tool duringdrug-inducedsleependoscopyP.E.Vonk,J.A.M.UnikenVenema,M.J.L.Ravesloot,A.Hoekema,J.A.vandeVelde–Muusers,N.deVriesSubmitted

4Jawthrustversustheuseofaboil-and-bitemandibularadvancementdevice as a screening tool duringdrug-inducedsleependoscopyP.E.Vonk,J.A.M.UnikenVenema,M.J.L.Ravesloot,A.Hoekema,J.A.vandeVelde–Muusers,N.deVriesSubmitted

70

Chapter 4

ABSTRACT

Studyobjectives:1)toanalyseagreementindegreeofobstructionandconfigurationoftheupper

airway (UA) between jaw thrust and an oral device in situ during drug-induced sleep endoscopy

(DISE)2)toevaluateclinicaldecisionmakingusingjawthrustoraboil-and-biteMAD,theMyTAP.

Methods: single-centre prospective cohort study in obstructive sleep apnea patients who

underwentDISEbetweenJanuary-July2019.

Results:Sixty-threepatientswereincluded.Agreementamongstobservationsinthesupineposition

fordegreeofobstructionwas60%(N=36,k=0.41)atthelevelofthevelum,68.3%(N=41,k=0.35)for

oropharynx,58.3%(N=35,k=0.28)fortonguebase,56.7%(N=34,k=0.14)forepiglottis;inthelateral

position 81.7% (N=49, k=0.32), 71.7% (N=43, k=0.36), 90.0% (N=54, k=0.23) and 96.7% (N=58, k=

could not be determined) respectively. In the supine position agreement for configuration of

obstruction at level of the velum was found in 20 of 29 patients (69.0%, k=0.41), in the lateral

position100%.ThirtypatientswouldhavebeenprescribedaMADusingjawthrust,34usingtheboil-

and-biteMAD as a screening instrument. Themain reason for being labelled as non-suitablewas

completeresidualretropalatalcollapseduringjawthrust.Usingtheboil-and-biteMAD,thiswasboth

duetocompleteretropalatalorhypopharyngealcollapse.

Conclusion:Thereisonlyslighttomoderateagreementindegreeofobstructionforjawthrustanda

new-generation boil-and-bite MAD during DISE. Greater improvement of UA patency at

hypopharyngeal level was observed during jaw thrust, but this manoeuvre was less effective in

improvingUAobstructionatretropalatallevel.

Key words: obstructive sleep apnea, sleep-disordered breathing, jaw thrust, drug-induced sleep

endoscopy,mandibularadvancementdevice,treatmentoutcome

Briefsummary

Incasesofmildormoderateobstructivesleepapnea(OSA)oriftreatmentwithcontinuouspositive

airway pressure fails, treatment with a mandibular advancement device (MAD) can be a viable

alternative. Unfortunately, identification of suitable candidates can be challenging. Relevant

variablesusedtopredicttreatmentoutcomeincludebodymassindex,totalapnea-hypopneaindex,

age, gender and cephalometric outcomes. Another, more controversial, way to predict MAD

treatmentoutcome is theuseof jaw thrustduringdrug-induced sleependoscopy (DISE).Although

alternatives to jaw thrust (e.g., simulation bite) have been proposed, there is still a demand for

readilyavailable,quickandeasytousesystemsthatmimictheeffectofaMADduringDISEtopredict

andimproveMADtreatmentoutcome.

71

4

Jaw thrust versus the use of a boil-and-bite mandibular advancement device

ABSTRACT

Studyobjectives:1)toanalyseagreementindegreeofobstructionandconfigurationoftheupper

airway (UA) between jaw thrust and an oral device in situ during drug-induced sleep endoscopy

(DISE)2)toevaluateclinicaldecisionmakingusingjawthrustoraboil-and-biteMAD,theMyTAP.

Methods: single-centre prospective cohort study in obstructive sleep apnea patients who

underwentDISEbetweenJanuary-July2019.

Results:Sixty-threepatientswereincluded.Agreementamongstobservationsinthesupineposition

fordegreeofobstructionwas60%(N=36,k=0.41)atthelevelofthevelum,68.3%(N=41,k=0.35)for

oropharynx,58.3%(N=35,k=0.28)fortonguebase,56.7%(N=34,k=0.14)forepiglottis;inthelateral

position 81.7% (N=49, k=0.32), 71.7% (N=43, k=0.36), 90.0% (N=54, k=0.23) and 96.7% (N=58, k=

could not be determined) respectively. In the supine position agreement for configuration of

obstruction at level of the velum was found in 20 of 29 patients (69.0%, k=0.41), in the lateral

position100%.ThirtypatientswouldhavebeenprescribedaMADusingjawthrust,34usingtheboil-

and-biteMAD as a screening instrument. Themain reason for being labelled as non-suitablewas

completeresidualretropalatalcollapseduringjawthrust.Usingtheboil-and-biteMAD,thiswasboth

duetocompleteretropalatalorhypopharyngealcollapse.

Conclusion:Thereisonlyslighttomoderateagreementindegreeofobstructionforjawthrustanda

new-generation boil-and-bite MAD during DISE. Greater improvement of UA patency at

hypopharyngeal level was observed during jaw thrust, but this manoeuvre was less effective in

improvingUAobstructionatretropalatallevel.

Key words: obstructive sleep apnea, sleep-disordered breathing, jaw thrust, drug-induced sleep

endoscopy,mandibularadvancementdevice,treatmentoutcome

Briefsummary

Incasesofmildormoderateobstructivesleepapnea(OSA)oriftreatmentwithcontinuouspositive

airway pressure fails, treatment with a mandibular advancement device (MAD) can be a viable

alternative. Unfortunately, identification of suitable candidates can be challenging. Relevant

variablesusedtopredicttreatmentoutcomeincludebodymassindex,totalapnea-hypopneaindex,

age, gender and cephalometric outcomes. Another, more controversial, way to predict MAD

treatmentoutcome is theuseof jaw thrustduringdrug-induced sleependoscopy (DISE).Although

alternatives to jaw thrust (e.g., simulation bite) have been proposed, there is still a demand for

readilyavailable,quickandeasytousesystemsthatmimictheeffectofaMADduringDISEtopredict

andimproveMADtreatmentoutcome.

72

Chapter 4

INTRODUCTION

Obstructive sleep apnea (OSA) is the most prevalent sleep-related breathing disorder caused by

episodes of partial or complete obstruction of the upper airway (UA) during sleep. Currently,

continuouspositiveairwaypressure(CPAP)isthestandardtherapyformoderatetosevereOSA,but

duetopoortoleranceandlowacceptance,non-complianceratesareoftenhigh.1Incasesofmildor

moderate OSA or if CPAP treatment fails, UA surgery, positional therapy and mandibular

advancementdevices(MADs)canbeviablealternatives.

MADsaredesignedtoadvancethemandible, suchthat the tonguebase,epiglottisandsoftpalate

areprotruded.ThisimprovesUApatencyandstability.2PreviousstudieshaveshownthatMADsare

successful in84%ofpatientswithmildtomoderateOSAand69.2%ofsevereOSApatients.3MAD

treatmentfailuremightbeexplainedbythefactthatitisdifficulttoidentifysuitablecandidatesfor

this treatment. Relevant variables that are used to predict treatment outcome include bodymass

index(BMI),totalapnea-hypopneaindex(AHI),age,genderandcephalometricoutcomes.4

Another,more controversial, tool that is used topredictMAD treatmentoutcome isdrug-induced

sleependoscopy(DISE).Thistoolprovidesadditional informationontheanatomicalsites intheUA

relatedtoobstruction.SeveralstudieshaveshownthatMADsarelesseffectiveincasesinvolvinga

completeconcentriccollapseatthelevelofthevelum.5,6Inaddition,DISEhastheuniqueadvantage

of allowing the physician to perform different passivemaneuvers that are considered to serve as

predictors for surgical or non-surgical treatment outcomes. 7 One of these maneuvers is the jaw

thrust.Throughjawthrust,thephysicianactivelyprotrudesthemandible.Themandibleisprotruded

uptoapproximately5-10mmor75%ofmaximalprotrusion,thusmimickingtheprotrusiveposition

ofthemandiblewithMADtreatment.8

However,thejawthrustmaneuverduringDISEhasbeencriticized,andthepositivepredictivevalue

ofmaximal passiveprotrusionof themandibleduringDISEhas variedbetween studies. 9-13 This is

probablybecausethismaneuverdoesnotaccountforthethicknessofaMAD,therebyoverlooking

thefactthattheverticalopening(VO)ofthemandible isnotsimilartoaMAD.Secondly,aMADis

often set at 60-75% of maximum mandibular protrusion. The degree of advancement of the

mandibleduringjawthrustisgenerallylessprecisethanapre-setdegreeofprotrusionwithaMAD.

As a result, it is difficult to mimic the real life effect of aMAD during DISE using the jaw thrust

maneuver. In addition, there is probably variability in the performance of jaw thrust during DISE

amongsurgeonsand insomecases jawthrust isnotperformedbythesurgeon,but forexamplea

trainednurseanesthetist.

Overrecentyears,severalalternativestojawthrusthavebeenproposed.In2008Vandervekenetal.

comparedtheefficacyofathermoplasticappliancewithaclassiccustom-madeMADasascreening

toolinsearchofgoodcandidatesforadefinitivecustom-madeMADduring4monthsoffollow-up.It

wasconcludedthatacustom-madeMADwasmoreeffectivethanathermoplasticmonoblocdevice

and that it couldnotbe recommendedasa screeningmethod.Thiswasmainlydue to the lackof

retentionandpoorcomfortofthethermoplasticappliance.14 In2013,Vroegopetal.evaluatedthe

useofasimulationbiteduringDISE.TheyconcludedthatapositiveeffectonUApatencywiththe

simulation bite inmaximal comfortable protrusion during DISEwas significantly associatedwith a

favorabletreatmentresponsetoMAD.13

Althoughtheuseofasimulationbiteseemstobepromising,itiswiththeexceptionofafewcentres,

notpartofdailypractice.Therefore,readilyavailable,quickandeasytousesystemsthatmimicthe

effectofaMADduringDISEneedtobedevelopedtopredictandimproveMADtreatmentoutcome.

Since2008newthermoplasticMADshavebeenintroduced,whicharethinner,havebetterretention

andareeasiertouse.Duetobetterretention,thesedevicesmayalsobeusedinanin-homesetting

afterusingthemforUAevaluationduringDISE.

The primary aim of the present study was to improve insight in agreement in the degree of

obstructionandconfigurationof theUAbetween jaw thrustandanoraldevice in situduringDISE

withtheultimategoaltoimprovethepredictivevalueofDISEasaselectiontoolforMADtreatment

in OSA. Secondly, we wanted to evaluate the theoretical implications on clinical decision making

using either the jaw thrust or a new generation boil-and-bite MAD as potential screening

instruments.

METHODS

Studyparticipants

Weperformeda single-centreprospective cohort study includingpatientswhounderwentDISE at

the Department of Otolaryngology, Head and Neck surgery of the OLVG (Amsterdam, the

Netherlands)betweenJanuary2019andJuly2019.Patientswereincludedwhenaged18yearsand

older,diagnosedwithOSAconfirmedbypolysomnography(PSG,AHI≥5eventsperhour)andifthey

wereabletogivewritteninformedconsent.Patientswereexcludedincaseofpoordentalcondition

(e.g.,partialorcompleteedentulism,extensiveperiodontaldiseaseortoothdecay)orwhenpatients

werediagnosedwithcentralsleepapnea(>50%ofcentralapneas).

73

4

Jaw thrust versus the use of a boil-and-bite mandibular advancement device

INTRODUCTION

Obstructive sleep apnea (OSA) is the most prevalent sleep-related breathing disorder caused by

episodes of partial or complete obstruction of the upper airway (UA) during sleep. Currently,

continuouspositiveairwaypressure(CPAP)isthestandardtherapyformoderatetosevereOSA,but

duetopoortoleranceandlowacceptance,non-complianceratesareoftenhigh.1Incasesofmildor

moderate OSA or if CPAP treatment fails, UA surgery, positional therapy and mandibular

advancementdevices(MADs)canbeviablealternatives.

MADsaredesignedtoadvancethemandible, suchthat the tonguebase,epiglottisandsoftpalate

areprotruded.ThisimprovesUApatencyandstability.2PreviousstudieshaveshownthatMADsare

successful in84%ofpatientswithmildtomoderateOSAand69.2%ofsevereOSApatients.3MAD

treatmentfailuremightbeexplainedbythefactthatitisdifficulttoidentifysuitablecandidatesfor

this treatment. Relevant variables that are used to predict treatment outcome include bodymass

index(BMI),totalapnea-hypopneaindex(AHI),age,genderandcephalometricoutcomes.4

Another,more controversial, tool that is used topredictMAD treatmentoutcome isdrug-induced

sleependoscopy(DISE).Thistoolprovidesadditional informationontheanatomicalsites intheUA

relatedtoobstruction.SeveralstudieshaveshownthatMADsarelesseffectiveincasesinvolvinga

completeconcentriccollapseatthelevelofthevelum.5,6Inaddition,DISEhastheuniqueadvantage

of allowing the physician to perform different passivemaneuvers that are considered to serve as

predictors for surgical or non-surgical treatment outcomes. 7 One of these maneuvers is the jaw

thrust.Throughjawthrust,thephysicianactivelyprotrudesthemandible.Themandibleisprotruded

uptoapproximately5-10mmor75%ofmaximalprotrusion,thusmimickingtheprotrusiveposition

ofthemandiblewithMADtreatment.8

However,thejawthrustmaneuverduringDISEhasbeencriticized,andthepositivepredictivevalue

ofmaximal passiveprotrusionof themandibleduringDISEhas variedbetween studies. 9-13 This is

probablybecausethismaneuverdoesnotaccountforthethicknessofaMAD,therebyoverlooking

thefactthattheverticalopening(VO)ofthemandible isnotsimilartoaMAD.Secondly,aMADis

often set at 60-75% of maximum mandibular protrusion. The degree of advancement of the

mandibleduringjawthrustisgenerallylessprecisethanapre-setdegreeofprotrusionwithaMAD.

As a result, it is difficult to mimic the real life effect of aMAD during DISE using the jaw thrust

maneuver. In addition, there is probably variability in the performance of jaw thrust during DISE

amongsurgeonsand insomecases jawthrust isnotperformedbythesurgeon,but forexamplea

trainednurseanesthetist.

Overrecentyears,severalalternativestojawthrusthavebeenproposed.In2008Vandervekenetal.

comparedtheefficacyofathermoplasticappliancewithaclassiccustom-madeMADasascreening

toolinsearchofgoodcandidatesforadefinitivecustom-madeMADduring4monthsoffollow-up.It

wasconcludedthatacustom-madeMADwasmoreeffectivethanathermoplasticmonoblocdevice

and that it couldnotbe recommendedasa screeningmethod.Thiswasmainlydue to the lackof

retentionandpoorcomfortofthethermoplasticappliance.14 In2013,Vroegopetal.evaluatedthe

useofasimulationbiteduringDISE.TheyconcludedthatapositiveeffectonUApatencywiththe

simulation bite inmaximal comfortable protrusion during DISEwas significantly associatedwith a

favorabletreatmentresponsetoMAD.13

Althoughtheuseofasimulationbiteseemstobepromising,itiswiththeexceptionofafewcentres,

notpartofdailypractice.Therefore,readilyavailable,quickandeasytousesystemsthatmimicthe

effectofaMADduringDISEneedtobedevelopedtopredictandimproveMADtreatmentoutcome.

Since2008newthermoplasticMADshavebeenintroduced,whicharethinner,havebetterretention

andareeasiertouse.Duetobetterretention,thesedevicesmayalsobeusedinanin-homesetting

afterusingthemforUAevaluationduringDISE.

The primary aim of the present study was to improve insight in agreement in the degree of

obstructionandconfigurationof theUAbetween jaw thrustandanoraldevice in situduringDISE

withtheultimategoaltoimprovethepredictivevalueofDISEasaselectiontoolforMADtreatment

in OSA. Secondly, we wanted to evaluate the theoretical implications on clinical decision making

using either the jaw thrust or a new generation boil-and-bite MAD as potential screening

instruments.

METHODS

Studyparticipants

Weperformeda single-centreprospective cohort study includingpatientswhounderwentDISE at

the Department of Otolaryngology, Head and Neck surgery of the OLVG (Amsterdam, the

Netherlands)betweenJanuary2019andJuly2019.Patientswereincludedwhenaged18yearsand

older,diagnosedwithOSAconfirmedbypolysomnography(PSG,AHI≥5eventsperhour)andifthey

wereabletogivewritteninformedconsent.Patientswereexcludedincaseofpoordentalcondition

(e.g.,partialorcompleteedentulism,extensiveperiodontaldiseaseortoothdecay)orwhenpatients

werediagnosedwithcentralsleepapnea(>50%ofcentralapneas).

74

Chapter 4

Ethicalconsiderations

Allproceduresfollowedwereinaccordancewiththeethicalstandardsoftheresponsiblecommittee

onhumanexperimentationandwiththeDeclarationofHelsinkiof1975.Dataonstudysubjectswas

collected and stored encoded to protect personal information. All patients gavewritten informed

consent.

Study-relatedprocedures

Polysomnography

The results of a full-night diagnostic PSG (EMBLA® A10/Titanium, Medcare Flaga, Iceland, and

SomnoscreenTM,SOMNOmedicsGmbH,Randersacker,Germany)werecollected ineachsubjectat

baseline. To determine the stages of sleep, an electroencephalogram (Fp1, Fp2, C3 C4, O1, O2),

electro-oculogramandelectromyogramof thesubmentalmusclewereobtained.Nasalairflowwas

measured by a nasal cannula/pressure transducer inserted in the opening of the nostrils. Arterial

blood oxyhemoglobin was recorded with the use of a finger pulse oximeter. Thoracoabdominal

excursions were measured qualitatively by respiratory effort belts placed over the rib cage and

abdomen. Body position was determined by a position sensor, which differentiated between the

upright,leftside,rightside,proneandsupineposition.

Sleep stages were scored using 30-s epochs according to American Academy of Sleep Medicine

(AASM) criteria,withN3 reflecting slowwave sleep.Obstructive respiratory eventswere analysed

accordingto theAASMcriteria201715Anobstructiverespiratoryevent inadultswasscoredasan

apnea if therewas a drop in the peak signal excursion by ≥ 90%with a duration of at least ≥ 10

seconds.Ahypopneawasdefinedasadecreaseofairflowby≥30%duringaperiodof≥10seconds

combinedwith anoxygendesaturationof ≥ 3%. Thenumberof apneicor hypopneic episodesper

hourofsleepwasreferredastheAHI.

FittingoftheMyTAP

TheMyTAP(MyThorntonAdjustablePositioner,AirwayManagementInc.,Dallas,TX,USA)isanew-

generation thermoplastic boil-and-bite MAD, which consists of two separate trays of polymeric

material.TheMyTAPfullycoverstheupperandlowerdentalarchesandcanbefixedinaprotrusive

positionbyasinglescrewinthefrontalareaoftheappliance.Theappliancewasadjustedforeach

patient according to the manufacturer’s recommendations and instructions. First, both trays are

heatedinboilingwateruntilthematerialturnedtransparent.Second,thetrayswere—onebyone

—placedcoveringtheupperorlowerdentalarchwhereuponthepatientwasinstructedtobiteinto

habitualocclusion,byactivelyclosing themouth for threeminutes.After fittingboth trays,a shim

wasplacedbetween the trays resulting inaverticalopeningallowingmovementof the tongue. In

patientswith a BMI <30 kg/m2a 6mm shim and in patientswith BMI >30 kg/m2a 9mm shimwas

used.Subsequently,themandiblewasadvancedbytighteningthescrewinthefrontalareauntilthe

patient indicated an uncomfortable sensation. This was followed by a 1mm retraction of the

mandible,describedasthemaximalcomfortableprotrusion(MCP).

Drug-inducedsleependoscopy

DISE procedure was performed according to the practice guidelines as recommended in the

EuropeanpositionpaperonDISE(update2017).16DISEproceduretookplaceinadaycaresettingin

aoutpatientendoscopyroomwithstandardanaestheticequipment.Thedrugofchoiceforsedation

waspropofol. The level of sedationwas controlledby a target controlled infusionpumpusing the

methodsdescribedbySchnideretal.tocalculatetheeffectivedose.17,18Priortotheintravenous(IV)

infusionofpropofol,2cclidocainewasgivenIVtopreventpaincausedbytheinfusionofpropofol.In

allpatientsglycopyrrolate(Robinul)wasgivenIVtopreventmucosalhypersecretion,sincethiscould

interferewiththequalityoftheendoscopicassessment.Propersedationlevelswereachievedwhen

thepatient showedhyporesponsiveness toverbaland tactile stimuliorwhen thepatientbegan to

snore.

Initially,subjectswereplacedinthelateralpositionwiththeboil-and-biteMADinsitu.Theboil-and-

biteMADwas adjusted toMCP after proper sedation levels were achieved. Adequate and stable

sedation levelswere retainedduring thewholeprocedure.Patientswere then tilted to the supine

position—bothheadandtrunk—withtheboil-and-biteMADstillinsitu.InbothpositionstheUA

was assessed at four different levels (velum,oropharynx, tonguebase andepiglottis) according to

theVOTEclassificationsystem.Subsequently, theboil-and-biteMADwasremoved,afterwhichthe

UAwasobservedinthelateralandthesupineposition,withandwithoutamanuallyperformedjaw

thrustaimingat65-75%protrusionofthemandible.

Classificationsystem

To report on the anatomical structures causing UA collapse, the VOTE classification system was

applied.19TheVOTEclassificationsystemdistinguishesbetweenfourdifferentlevelsandstructures

thatmaybeinvolvedinUAcollapse:velum(V),oropharynx(O),tonguebase(T)andepiglottis(E).To

define thedegreeof obstruction, threedifferent categories areused: noobstruction in casesof a

collapse less than 50% (scored as 0); a partial obstruction with a collapse between 50-75% and

typically with vibration (scored as 1); or a complete collapse with a collapse of more than 75%

75

4

Jaw thrust versus the use of a boil-and-bite mandibular advancement device

Ethicalconsiderations

Allproceduresfollowedwereinaccordancewiththeethicalstandardsoftheresponsiblecommittee

onhumanexperimentationandwiththeDeclarationofHelsinkiof1975.Dataonstudysubjectswas

collected and stored encoded to protect personal information. All patients gavewritten informed

consent.

Study-relatedprocedures

Polysomnography

The results of a full-night diagnostic PSG (EMBLA® A10/Titanium, Medcare Flaga, Iceland, and

SomnoscreenTM,SOMNOmedicsGmbH,Randersacker,Germany)werecollected ineachsubjectat

baseline. To determine the stages of sleep, an electroencephalogram (Fp1, Fp2, C3 C4, O1, O2),

electro-oculogramandelectromyogramof thesubmentalmusclewereobtained.Nasalairflowwas

measured by a nasal cannula/pressure transducer inserted in the opening of the nostrils. Arterial

blood oxyhemoglobin was recorded with the use of a finger pulse oximeter. Thoracoabdominal

excursions were measured qualitatively by respiratory effort belts placed over the rib cage and

abdomen. Body position was determined by a position sensor, which differentiated between the

upright,leftside,rightside,proneandsupineposition.

Sleep stages were scored using 30-s epochs according to American Academy of Sleep Medicine

(AASM) criteria,withN3 reflecting slowwave sleep.Obstructive respiratory eventswere analysed

accordingto theAASMcriteria201715Anobstructiverespiratoryevent inadultswasscoredasan

apnea if therewas a drop in the peak signal excursion by ≥ 90%with a duration of at least ≥ 10

seconds.Ahypopneawasdefinedasadecreaseofairflowby≥30%duringaperiodof≥10seconds

combinedwith anoxygendesaturationof ≥ 3%. Thenumberof apneicor hypopneic episodesper

hourofsleepwasreferredastheAHI.

FittingoftheMyTAP

TheMyTAP(MyThorntonAdjustablePositioner,AirwayManagementInc.,Dallas,TX,USA)isanew-

generation thermoplastic boil-and-bite MAD, which consists of two separate trays of polymeric

material.TheMyTAPfullycoverstheupperandlowerdentalarchesandcanbefixedinaprotrusive

positionbyasinglescrewinthefrontalareaoftheappliance.Theappliancewasadjustedforeach

patient according to the manufacturer’s recommendations and instructions. First, both trays are

heatedinboilingwateruntilthematerialturnedtransparent.Second,thetrayswere—onebyone

—placedcoveringtheupperorlowerdentalarchwhereuponthepatientwasinstructedtobiteinto

habitualocclusion,byactivelyclosing themouth for threeminutes.After fittingboth trays,a shim

wasplacedbetween the trays resulting inaverticalopeningallowingmovementof the tongue. In

patientswith a BMI <30 kg/m2a 6mm shim and in patientswith BMI >30 kg/m2a 9mm shimwas

used.Subsequently,themandiblewasadvancedbytighteningthescrewinthefrontalareauntilthe

patient indicated an uncomfortable sensation. This was followed by a 1mm retraction of the

mandible,describedasthemaximalcomfortableprotrusion(MCP).

Drug-inducedsleependoscopy

DISE procedure was performed according to the practice guidelines as recommended in the

EuropeanpositionpaperonDISE(update2017).16DISEproceduretookplaceinadaycaresettingin

aoutpatientendoscopyroomwithstandardanaestheticequipment.Thedrugofchoiceforsedation

waspropofol. The level of sedationwas controlledby a target controlled infusionpumpusing the

methodsdescribedbySchnideretal.tocalculatetheeffectivedose.17,18Priortotheintravenous(IV)

infusionofpropofol,2cclidocainewasgivenIVtopreventpaincausedbytheinfusionofpropofol.In

allpatientsglycopyrrolate(Robinul)wasgivenIVtopreventmucosalhypersecretion,sincethiscould

interferewiththequalityoftheendoscopicassessment.Propersedationlevelswereachievedwhen

thepatient showedhyporesponsiveness toverbaland tactile stimuliorwhen thepatientbegan to

snore.

Initially,subjectswereplacedinthelateralpositionwiththeboil-and-biteMADinsitu.Theboil-and-

biteMADwas adjusted toMCP after proper sedation levels were achieved. Adequate and stable

sedation levelswere retainedduring thewholeprocedure.Patientswere then tilted to the supine

position—bothheadandtrunk—withtheboil-and-biteMADstillinsitu.InbothpositionstheUA

was assessed at four different levels (velum,oropharynx, tonguebase andepiglottis) according to

theVOTEclassificationsystem.Subsequently, theboil-and-biteMADwasremoved,afterwhichthe

UAwasobservedinthelateralandthesupineposition,withandwithoutamanuallyperformedjaw

thrustaimingat65-75%protrusionofthemandible.

Classificationsystem

To report on the anatomical structures causing UA collapse, the VOTE classification system was

applied.19TheVOTEclassificationsystemdistinguishesbetweenfourdifferentlevelsandstructures

thatmaybeinvolvedinUAcollapse:velum(V),oropharynx(O),tonguebase(T)andepiglottis(E).To

define thedegreeof obstruction, threedifferent categories areused: noobstruction in casesof a

collapse less than 50% (scored as 0); a partial obstruction with a collapse between 50-75% and

typically with vibration (scored as 1); or a complete collapse with a collapse of more than 75%

76

Chapter 4

(scored as 2). An X is usedwhen no observation can bemade. Depending on the different site(s)

involvedinUAobstruction,theconfigurationmaybeanteroposterior(A-P),lateralorconcentric.

Definitions

PatientswereconsideredasbeingsuitablecandidatesforMADtreatmentwhenadecreaseindegree

of obstruction was observed of at least 1 point at each potential level of obstruction, leading to

absenceofacompletecollapseatV,O,TorElevel.

Statisticalanalysis

StatisticalanalysiswasperformedusingSPSS (version22),SPSS Inc.,Chicago, IL).Quantitativedata

were reported asmean and standard deviation (SD) or asmedian andQ1-Q3when not normally

distributed.Apvalueof<0.05wasconsideredtoindicatestatisticalsignificance.

Agreementamongobservationsmadebyusingthetwodifferentscreeninginstruments—jawthrust

andtheboil-and-biteMAD—werecalculatedbydividingthenumberofagreementswithregardto

thedegreeofobstructionbythenumberofdisagreementsbetweenbothmeasurements.Tocorrect

for chance agreement and due the use of an ordinal scale, a weighted, Cohen’s kappa was

determined.Kappavalueswereinterpretedasfollowing:k<0poor;k0to0.20slight;0.21–0.4fair;

0.41to0.60moderate;k0.61to0.8substantialandk>0.81almostperfectagreement.

Samplesize

Theaimof this studywas to reject thenull hypothesis that theeffectonUApatencyofmanually

performedjawthrustissimilartotheeffectoftheboil-and-biteMADduringDISE.Tocomparetwo

measureinstrumentsaminimumof50subjectshadtobeincluded.20

RESULTS

Atotal63patientswereincludedinthisstudy.Inthreepatientsmeasurementwiththeboil-and-bite

MADinsitufailedduetotechnicalproblemswiththefittingofthedevice.Thereforetheresultsof60

patientswereusedforanalysis.

Of the 60 patients, 50 patientsweremale (83.3%) and 45 patientswere diagnosedwith position-

dependentOSA(POSA)accordingtoCartwright’scriteria.21Themeanageofallpatientswas46.9±

11.8years,withaBMIof27.9±2.7kg/m2andaneckcircumferenceof40.8±3.0cm.Themedian

AHIwas15.9/h(12.1,26.0),themediansupineAHI36.4/h(19.4,65.3)andthemediannon-supine

AHI7.1/h(2.8,19.9).Patientsspentamedianpercentageoftotalsleepingtimeinthesupineposition

of39.3%(12.5,51.5).Themedianoxygendesaturationindex(ODI)was21.9/h(15.5,28.6).TheMCP

was84.2±13.2%of themaximalprotrusionof themandible.Table 1providesanoverviewof the

baselinecharacteristicsofthetotalstudygroup.

Table1.Baselinecharacteristics

Patientcharacteristic

Total

N=60

Age(years) 46.9±11.8

Male/Female 50/10

BMI(kg/m2) 27.9±2.7

Neckcircumference(cm) 40.8±3.0

TotalAHI(events/hour) 15.9(12.1,26.0)°

SupineAHI(events/hour) 36.4(19.4,65.3)°

Non-supineAHI(events/hour) 9.9(3.9,18.2)°

TSTinthesupineposition(%) 39.3(12.5,51.5)°

ODI(events/hour) 21.9(15.5,28.6)°

MCP(%)* 84.2±13.8

Datapresentedasmean±standarddeviationor°median(Q1,Q3)

BMIbodymassindex,AHIapnea-hypopneaindex,TSTtotalsleepingtime,ODIoxygendesaturation

index,MCPmaximalcomfortableprotrusion

*MCPasapercentageofthemaximalprotrusionofthemandibleduringwakefulness

77

4

Jaw thrust versus the use of a boil-and-bite mandibular advancement device

(scored as 2). An X is usedwhen no observation can bemade. Depending on the different site(s)

involvedinUAobstruction,theconfigurationmaybeanteroposterior(A-P),lateralorconcentric.

Definitions

PatientswereconsideredasbeingsuitablecandidatesforMADtreatmentwhenadecreaseindegree

of obstruction was observed of at least 1 point at each potential level of obstruction, leading to

absenceofacompletecollapseatV,O,TorElevel.

Statisticalanalysis

StatisticalanalysiswasperformedusingSPSS (version22),SPSS Inc.,Chicago, IL).Quantitativedata

were reported asmean and standard deviation (SD) or asmedian andQ1-Q3when not normally

distributed.Apvalueof<0.05wasconsideredtoindicatestatisticalsignificance.

Agreementamongobservationsmadebyusingthetwodifferentscreeninginstruments—jawthrust

andtheboil-and-biteMAD—werecalculatedbydividingthenumberofagreementswithregardto

thedegreeofobstructionbythenumberofdisagreementsbetweenbothmeasurements.Tocorrect

for chance agreement and due the use of an ordinal scale, a weighted, Cohen’s kappa was

determined.Kappavalueswereinterpretedasfollowing:k<0poor;k0to0.20slight;0.21–0.4fair;

0.41to0.60moderate;k0.61to0.8substantialandk>0.81almostperfectagreement.

Samplesize

Theaimof this studywas to reject thenull hypothesis that theeffectonUApatencyofmanually

performedjawthrustissimilartotheeffectoftheboil-and-biteMADduringDISE.Tocomparetwo

measureinstrumentsaminimumof50subjectshadtobeincluded.20

RESULTS

Atotal63patientswereincludedinthisstudy.Inthreepatientsmeasurementwiththeboil-and-bite

MADinsitufailedduetotechnicalproblemswiththefittingofthedevice.Thereforetheresultsof60

patientswereusedforanalysis.

Of the 60 patients, 50 patientsweremale (83.3%) and 45 patientswere diagnosedwith position-

dependentOSA(POSA)accordingtoCartwright’scriteria.21Themeanageofallpatientswas46.9±

11.8years,withaBMIof27.9±2.7kg/m2andaneckcircumferenceof40.8±3.0cm.Themedian

AHIwas15.9/h(12.1,26.0),themediansupineAHI36.4/h(19.4,65.3)andthemediannon-supine

AHI7.1/h(2.8,19.9).Patientsspentamedianpercentageoftotalsleepingtimeinthesupineposition

of39.3%(12.5,51.5).Themedianoxygendesaturationindex(ODI)was21.9/h(15.5,28.6).TheMCP

was84.2±13.2%of themaximalprotrusionof themandible.Table 1providesanoverviewof the

baselinecharacteristicsofthetotalstudygroup.

Table1.Baselinecharacteristics

Patientcharacteristic

Total

N=60

Age(years) 46.9±11.8

Male/Female 50/10

BMI(kg/m2) 27.9±2.7

Neckcircumference(cm) 40.8±3.0

TotalAHI(events/hour) 15.9(12.1,26.0)°

SupineAHI(events/hour) 36.4(19.4,65.3)°

Non-supineAHI(events/hour) 9.9(3.9,18.2)°

TSTinthesupineposition(%) 39.3(12.5,51.5)°

ODI(events/hour) 21.9(15.5,28.6)°

MCP(%)* 84.2±13.8

Datapresentedasmean±standarddeviationor°median(Q1,Q3)

BMIbodymassindex,AHIapnea-hypopneaindex,TSTtotalsleepingtime,ODIoxygendesaturation

index,MCPmaximalcomfortableprotrusion

*MCPasapercentageofthemaximalprotrusionofthemandibleduringwakefulness

78

Chapter 4

Agreement in degree of obstruction in the supine position comparing jaw

thrustandboil-and-biteMAD

Agreement amongst observations in the supinepositionwith regard to degreeof obstructionwas

60%(N=36,k=0.41)atthe levelofthevelum,68.3%(N=41,k=0.35)atthe leveloftheoropharynx,

58.3% (N=35,k=0.28)at the levelof the tonguebaseand56.7% (N=34,k=0.14)at the levelof the

epiglottis.Anoverviewcanbefoundintable2.

Agreementindegreeofobstructioninthelateralpositioncomparingjawthrust

andboil-and-biteMAD

Agreement amongst observations in the lateral positionwith regard to degree of obstructionwas

81.7%(N=49,k=0.32)atthelevelofthevelum,71.7%(N=43,k=0.36)attheleveloftheoropharynx,

90.0% (N=54, k=0.23) at the level of the tongue base and in 96.7% (N=58, k= could not be

determined)attheleveloftheepiglottis.Table3providesanoverviewoftheagreementindegree

ofobstructioncomparingjawthrustandboil-and-biteMAD.

Table2.AgreementindegreeofobstructioninthesupinepositioncomparingjawthrustandMyTAPLevel Degreeof

obstruction

Supine

position

Jaw

thrust

(N)

Boil-and-

biteMAD

(N)

Overall

percentageof

agreement

Kappa Interpretation

kappa

V 0 7 18 29 60% 0.41 Moderate

1 9 22 16

2 44 20 15

O 0 30 35 49 68.3% 0.35 Fair

1 4 13 8

2 26 12 3

T 0 18 43 28 58.3% 0.28 Fair

1 16 12 23

2 26 5 9

E 0 25 52 32 56.7% 0.14 Slight

1 12 6 15

2 13 2 13

Vvelum,Ooropharynx,Ttonguebase,Eepiglottis

0=<50%ofobstruction,1=50-75%ofobstruction,2=>75%ofobstruction

79

4

Jaw thrust versus the use of a boil-and-bite mandibular advancement device

Agreement in degree of obstruction in the supine position comparing jaw

thrustandboil-and-biteMAD

Agreement amongst observations in the supinepositionwith regard to degreeof obstructionwas

60%(N=36,k=0.41)atthe levelofthevelum,68.3%(N=41,k=0.35)atthe leveloftheoropharynx,

58.3% (N=35,k=0.28)at the levelof the tonguebaseand56.7% (N=34,k=0.14)at the levelof the

epiglottis.Anoverviewcanbefoundintable2.

Agreementindegreeofobstructioninthelateralpositioncomparingjawthrust

andboil-and-biteMAD

Agreement amongst observations in the lateral positionwith regard to degree of obstructionwas

81.7%(N=49,k=0.32)atthelevelofthevelum,71.7%(N=43,k=0.36)attheleveloftheoropharynx,

90.0% (N=54, k=0.23) at the level of the tongue base and in 96.7% (N=58, k= could not be

determined)attheleveloftheepiglottis.Table3providesanoverviewoftheagreementindegree

ofobstructioncomparingjawthrustandboil-and-biteMAD.

Table2.AgreementindegreeofobstructioninthesupinepositioncomparingjawthrustandMyTAPLevel Degreeof

obstruction

Supine

position

Jaw

thrust

(N)

Boil-and-

biteMAD

(N)

Overall

percentageof

agreement

Kappa Interpretation

kappa

V 0 7 18 29 60% 0.41 Moderate

1 9 22 16

2 44 20 15

O 0 30 35 49 68.3% 0.35 Fair

1 4 13 8

2 26 12 3

T 0 18 43 28 58.3% 0.28 Fair

1 16 12 23

2 26 5 9

E 0 25 52 32 56.7% 0.14 Slight

1 12 6 15

2 13 2 13

Vvelum,Ooropharynx,Ttonguebase,Eepiglottis

0=<50%ofobstruction,1=50-75%ofobstruction,2=>75%ofobstruction

80

Chapter 4

Table3.Agreementindegreeofobstructioninthelateralpositioncomparingtheboil-and-biteMAD

andjawthrust

Level Degreeof

obstruction

Lateral

position

Jaw

thrust

(N)

Boil-and-

biteMAD

(N)

Overall

percentageof

agreement

Kappa Interpretation

kappa

V 0 27 50 52 81.7% 0.32 Fair

1 17 4 6

2 16 6 2

O 0 21 44 42 71.7% 0.36 Fair

1 9 10 10

2 30 6 8

T 0 44 59 53 90% 0.23 Fair

1 11 1 7

2 5 0 0

E 0 51 60 58 96.7% CND N/A

1 8 0 2

2 1 0 0

MADmandibularadvancementdevice,Vvelum,Ooropharynx,Ttonguebase,Eepiglottis

0=<50%ofobstruction,1=50-75%ofobstruction,2=>75%ofobstruction

CNDcouldnotbedetermined,N/Anotapplicable

Agreement of the configuration of collapse in the supine and the lateral

positioncomparingboil-and-biteMADandjawthrust

Inthesupinepositionagreementwithregardtotheconfigurationofobstructionatthelevelofthe

velum was found in 20 out of 29 patients (69.0%), with a kappa of 0.41. In seven patients a

concentriccollapsewasfoundwhenapplyingjawthrust,whichwasmodifiedtoanA-Pcollapsewith

the boil-and-bite MAD in situ. In two patients a lateral collapse was observed during jaw thrust,

which changed to a concentric collapse with the boil-and-bite MAD in place. Agreement on

configurationofobstructioninthelateralpositionwasfoundinallpatients(seetable4and5)

81

4

Jaw thrust versus the use of a boil-and-bite mandibular advancement device

Table3.Agreementindegreeofobstructioninthelateralpositioncomparingtheboil-and-biteMAD

andjawthrust

Level Degreeof

obstruction

Lateral

position

Jaw

thrust

(N)

Boil-and-

biteMAD

(N)

Overall

percentageof

agreement

Kappa Interpretation

kappa

V 0 27 50 52 81.7% 0.32 Fair

1 17 4 6

2 16 6 2

O 0 21 44 42 71.7% 0.36 Fair

1 9 10 10

2 30 6 8

T 0 44 59 53 90% 0.23 Fair

1 11 1 7

2 5 0 0

E 0 51 60 58 96.7% CND N/A

1 8 0 2

2 1 0 0

MADmandibularadvancementdevice,Vvelum,Ooropharynx,Ttonguebase,Eepiglottis

0=<50%ofobstruction,1=50-75%ofobstruction,2=>75%ofobstruction

CNDcouldnotbedetermined,N/Anotapplicable

Agreement of the configuration of collapse in the supine and the lateral

positioncomparingboil-and-biteMADandjawthrust

Inthesupinepositionagreementwithregardtotheconfigurationofobstructionatthelevelofthe

velum was found in 20 out of 29 patients (69.0%), with a kappa of 0.41. In seven patients a

concentriccollapsewasfoundwhenapplyingjawthrust,whichwasmodifiedtoanA-Pcollapsewith

the boil-and-bite MAD in situ. In two patients a lateral collapse was observed during jaw thrust,

which changed to a concentric collapse with the boil-and-bite MAD in place. Agreement on

configurationofobstructioninthelateralpositionwasfoundinallpatients(seetable4and5)

82

Chapter 4

Table4.Agreementinconfigurationinthesupinepositioncomparingtheboil-and-biteMADandjaw

thrust

Level Configuration Jaw

thrust

(N)

Boil-and-bite

MAD(N)

Overall

percentageof

agreement

Kappa Interpretation

kappa

V A-P 23 24 69.0% 0.41 Moderate

Lateral 3 1

Concentric 16 6

O Lateral 25 11 100% N/A N/A

T A-P 17 32 100% N/A N/A

E A-P 8 28 100% N/A N/A

Lateral 0 0

MADmandibularadvancementdevice,Vvelum,Ooropharynx,Ttonguebase,Eepiglottis,

A-PAnteroposterior,N/Anotapplicable

Table5.Agreementinconfigurationinthelateralpositioncomparingtheboil-and-biteMADandjaw

thrust

Level Configuration Jaw

thrust

(N)

Boil-and-bite

MAD(N)

Overall

percentageof

agreement

Kappa Interpretation

kappa

V A-P 2 3 100% 1.00 Perfect

Lateral 4 3

Concentric 4 2

O Lateral 16 17 100% N/A N/A

T A-P 1 7 100% N/A N/A

E A-P 0 2 CND N/A N/A

Lateral 0 0

MADmandibularadvancementdevice,Vvelum,Ooropharynx,Ttonguebase,Eepiglottis,

A-PAnteroposterior,CNDcouldnotbedetermined,N/Anotapplicable

TheoreticalidentificationofsuitablecandidatesforMADtreatment

Jawthrust

Assuming that jaw thrust is a valid screening instrument forMAD treatmentoutcome,30patients

wouldhavebeenprescribedaMADbasedontheeffectofamanuallyperformedjawthrust.Ofthe

30patientsthatwouldhavebeen labelledasnon-suitablecandidates forMADtreatment, thiswas

duetoacompleteresidualretropalatalcollapsein24patients.Intwopatientsacompletecollapseat

hypopharyngeallevelwasobservedandinfourpatientsaresidualmultilevelcollapsewaspresent.

Boil-and-biteMAD

Whentheboil-and-biteMADwouldhavebeenused,34patientswouldhavebeenselectedforMAD

treatment.Inthatcase,11patientswouldhavebeenidentifiedasnon-suitablecandidatesduetoa

complete residual retropalatal collapse, 11 patients due to a complete residual hypopharyngeal

collapseandinthreepatientsapersistentmultilevelcollapsewasfound.

Afloppyepiglottiswaspresentinonlyonepatientwhenapplyingjawthrustandinfivepatientswith

theboil-and-biteMADinsitu.

DISCUSSION

Currently,theuseofDISEtopredictMADtreatmentoutcomeiscontroversialandthereisalackin

consensusontheuseofamanuallyperformedjawthrustmimickingthereallifeeffectofaMAD.To

best of our knowledge this is the first study to describe the use and comparison of two potential

screening instruments duringDISE— jaw thrust and a new-generation thermoplastic boil-and-bite

MAD—topredicttheeffectofMADtreatment.Theresultsofthisstudyindicatethatthereisonlya

slighttomoderateagreementonthedegreeofobstructionmeasuredwithjawthrustandtheboil-

and-biteMAD, especially in the supine position. The latter is not surprising, since themajority of

patientswasposition-dependentwithonly fewUAobstructions inthe lateralposition.Overall, jaw

thrustseemstobemoreeffectiveinresolvingobstructionsathypopharyngeallevel—tonguebase

and epiglottis— than the boil-and-biteMAD during DISE. In contrast, obstructions at retropalatal

level—velumandoropharynx—weremoreoftenimprovedwiththeboil-and-biteMADinsituthan

whenjawthrustwasapplied.

Whencomparingthetwoscreening instruments,twomajordifferencescanbeidentified.First,the

degreeofadvancementofthemandibleduringjawthrustislessprecisethanthepre-setdegreeof

protrusionoftheboil-and-biteMAD,whichissetattheMCP.Second,jawthrusttakesnoaccountfor

83

4

Jaw thrust versus the use of a boil-and-bite mandibular advancement device

Table4.Agreementinconfigurationinthesupinepositioncomparingtheboil-and-biteMADandjaw

thrust

Level Configuration Jaw

thrust

(N)

Boil-and-bite

MAD(N)

Overall

percentageof

agreement

Kappa Interpretation

kappa

V A-P 23 24 69.0% 0.41 Moderate

Lateral 3 1

Concentric 16 6

O Lateral 25 11 100% N/A N/A

T A-P 17 32 100% N/A N/A

E A-P 8 28 100% N/A N/A

Lateral 0 0

MADmandibularadvancementdevice,Vvelum,Ooropharynx,Ttonguebase,Eepiglottis,

A-PAnteroposterior,N/Anotapplicable

Table5.Agreementinconfigurationinthelateralpositioncomparingtheboil-and-biteMADandjaw

thrust

Level Configuration Jaw

thrust

(N)

Boil-and-bite

MAD(N)

Overall

percentageof

agreement

Kappa Interpretation

kappa

V A-P 2 3 100% 1.00 Perfect

Lateral 4 3

Concentric 4 2

O Lateral 16 17 100% N/A N/A

T A-P 1 7 100% N/A N/A

E A-P 0 2 CND N/A N/A

Lateral 0 0

MADmandibularadvancementdevice,Vvelum,Ooropharynx,Ttonguebase,Eepiglottis,

A-PAnteroposterior,CNDcouldnotbedetermined,N/Anotapplicable

TheoreticalidentificationofsuitablecandidatesforMADtreatment

Jawthrust

Assuming that jaw thrust is a valid screening instrument forMAD treatmentoutcome,30patients

wouldhavebeenprescribedaMADbasedontheeffectofamanuallyperformedjawthrust.Ofthe

30patientsthatwouldhavebeen labelledasnon-suitablecandidates forMADtreatment, thiswas

duetoacompleteresidualretropalatalcollapsein24patients.Intwopatientsacompletecollapseat

hypopharyngeallevelwasobservedandinfourpatientsaresidualmultilevelcollapsewaspresent.

Boil-and-biteMAD

Whentheboil-and-biteMADwouldhavebeenused,34patientswouldhavebeenselectedforMAD

treatment.Inthatcase,11patientswouldhavebeenidentifiedasnon-suitablecandidatesduetoa

complete residual retropalatal collapse, 11 patients due to a complete residual hypopharyngeal

collapseandinthreepatientsapersistentmultilevelcollapsewasfound.

Afloppyepiglottiswaspresentinonlyonepatientwhenapplyingjawthrustandinfivepatientswith

theboil-and-biteMADinsitu.

DISCUSSION

Currently,theuseofDISEtopredictMADtreatmentoutcomeiscontroversialandthereisalackin

consensusontheuseofamanuallyperformedjawthrustmimickingthereallifeeffectofaMAD.To

best of our knowledge this is the first study to describe the use and comparison of two potential

screening instruments duringDISE— jaw thrust and a new-generation thermoplastic boil-and-bite

MAD—topredicttheeffectofMADtreatment.Theresultsofthisstudyindicatethatthereisonlya

slighttomoderateagreementonthedegreeofobstructionmeasuredwithjawthrustandtheboil-

and-biteMAD, especially in the supine position. The latter is not surprising, since themajority of

patientswasposition-dependentwithonly fewUAobstructions inthe lateralposition.Overall, jaw

thrustseemstobemoreeffectiveinresolvingobstructionsathypopharyngeallevel—tonguebase

and epiglottis— than the boil-and-biteMAD during DISE. In contrast, obstructions at retropalatal

level—velumandoropharynx—weremoreoftenimprovedwiththeboil-and-biteMADinsituthan

whenjawthrustwasapplied.

Whencomparingthetwoscreening instruments,twomajordifferencescanbeidentified.First,the

degreeofadvancementofthemandibleduringjawthrustislessprecisethanthepre-setdegreeof

protrusionoftheboil-and-biteMAD,whichissetattheMCP.Second,jawthrusttakesnoaccountfor

84

Chapter 4

thethicknessofaMADandthereforedoesnotincludeVO,whichisgeneratedbytheboil-and-bite

MAD.

ThegreaterimprovementofUApatencyathypopharyngeallevelwithjawthrustisslightlysurprising,

since theMCPused for thepre-setdegreeofprotrusion for theboil-and-biteMADwas ingeneral

morethan65-75%.Thedegreeofprotrusionwithjawthrustwasestimatedtobe65-75%,whilethe

degreeofprotrusionwith theboil-and-biteMADwasonaverage84.2%of themaximalprotrusion

duringwakefulness.Onewould therefore expect to find greater improvementofUApatencywith

boil-and-biteMAD in situ. On the other,we assume that the estimated 65-75% protrusion of the

mandibleisprobablyanunderestimation,whichcouldexplainthedifferenceinresults.Furthermore,

we hypothesize that the maximum amount of mandibular protrusion during DISE is more

pronouncedwhencomparedwiththeawakestate.Firstlybecauseoftheneuromuscularboundaries

that patients experiencewhen they are not sedated. Secondly, onemust keep inmind that the

percentageofprotrusionduringdeterminedduringDISEisasubjectiveandestimatedvalue,whichis

not objectively determined. Thesephenomenaprobably explainwhy thepercentageof protrusion

determinedduringthejawthrustmanoeuvreisanunderestimatewhencomparedtothedegreeof

protrusionasdeterminedwiththeboil-and-biteMAD.

Thedifferenceineffectatretropalatallevelisanovelfinding.Wehypothesizethatthegreatereffect

oftheboil-and-biteMADonUApatencyatthislevelisprobablycausedbytheVOofthemouththat

is createdwith the oral device in place. By addingVO, stretching forces on the lateralwall of the

pharynxincrease,leadingtoadecreaseinUAcollapsibilityandstabilizationoftheairway.Ifcorrect,

this would also explain the differences in configuration of obstruction at palatal level. In seven

patientsaconcentriccollapsewasobservedwhenapplyingjawthrust,whichwasalteredtoanA-P

configurationwiththeboil-and-biteMADinsitu(i.e.openingofthepharynxinthelateral,butnotA-

Pdimension).

SeveralstudiesintheliteraturefocusontheeffectofVOonMADeffectivenessandUAcollapsibility.

Unfortunately,theresultsvaryamongstudies.Pitsisetal.concludedthatVOofthemouthinduced

by aMADdoes not significantly influence treatment efficacy 22,while Rose et al. found thatMAD

treatmentwasmoreeffectivewithincreasedVO.23 Inaddition,Fergusonetal.concludedthatthe

effectofVOontheefficacyofMADremainsundecided.24TheeffectofVOonUApatencywithouta

MAD in situ was previously studied by Vroegop et al. Their results indicated that increased VO,

without advancement of the mandible, had an adverse effect on pharyngeal dimensions in the

majorityofpatientsathypopharyngeallevel.25Unfortunately,theydidnotreportonoutcomeswith

regardtoobstructionatretropalatallevelmakingadequatecomparisonwiththeresultsofthisstudy

difficult.

Limitations

DISE was performed by one experienced endoscopist (PV), but were not reassessed by a second

observer.Thiscouldpotentiallyhave influenced interpretationofDISE.Nevertheless,byusingonly

one observer interobserver variability was avoided. In addition, the majority of patients were

diagnosed with mild to moderate position-dependent OSA, which might make the results of this

studylessapplicabletomoreseverenon-positionalOSApatients.

Clinicalimplicationsandfutureresearch

Theresultsofthisstudyemphasizetheneedforanalternativetojawthrustasascreeningmethod

and prediction tool for MAD treatment outcome used during DISE. Jaw thrust seems to be less

effectiveinimprovingUAcollapseatretropalatallevelthantheboilandbiteMAD,whichwasusedin

thisstudy.Inseveralpatients,thiscouldhaveledtoanoverestimationofassessmentof´notsuitable

for MAD treatment’. Furthermore, advancement of the mandible using jaw thrust during DISE is

probablygreater than theMCPduringwakefulness in themajorityofpatients.Therefore theMCP

seemstobemorerepresentativewheniscomestotheexpectedadvancementofthemandiblethat

canbeachievedwheninitiatingMADtreatment.

CONCLUSIONSANDFUTURERESEARCH

The results of this study indicate that there is only a slight tomoderate agreement in degree of

obstructionmeasuredwith jaw thrust and a new-generation boil–and-biteMAD— theMyTAP—

duringDISE.Overall, a greater improvementofUApatency at hypopharyngeal levelwasobserved

whenapplying jawthrust. Incontrast, jawthrustwas lesseffective in improvingUAobstructionat

retropalatallevelthantheMyTAP.Thereisstillaneedforanalterativetojawthrustthatcanbeused

asascreeningmethodandpredictiontoolforMADtreatmentoutcomeduringDISE.Thisisthefirst

partofatwo-partstudy.InthesecondpartofthisstudythecorrelationbetweenDISEfindingsand

MAD treatment outcome will be evaluated to further unravel the predictive value on MAD

effectiveness.

85

4

Jaw thrust versus the use of a boil-and-bite mandibular advancement device

thethicknessofaMADandthereforedoesnotincludeVO,whichisgeneratedbytheboil-and-bite

MAD.

ThegreaterimprovementofUApatencyathypopharyngeallevelwithjawthrustisslightlysurprising,

since theMCPused for thepre-setdegreeofprotrusion for theboil-and-biteMADwas ingeneral

morethan65-75%.Thedegreeofprotrusionwithjawthrustwasestimatedtobe65-75%,whilethe

degreeofprotrusionwith theboil-and-biteMADwasonaverage84.2%of themaximalprotrusion

duringwakefulness.Onewould therefore expect to find greater improvementofUApatencywith

boil-and-biteMAD in situ. On the other,we assume that the estimated 65-75% protrusion of the

mandibleisprobablyanunderestimation,whichcouldexplainthedifferenceinresults.Furthermore,

we hypothesize that the maximum amount of mandibular protrusion during DISE is more

pronouncedwhencomparedwiththeawakestate.Firstlybecauseoftheneuromuscularboundaries

that patients experiencewhen they are not sedated. Secondly, onemust keep inmind that the

percentageofprotrusionduringdeterminedduringDISEisasubjectiveandestimatedvalue,whichis

not objectively determined. Thesephenomenaprobably explainwhy thepercentageof protrusion

determinedduringthejawthrustmanoeuvreisanunderestimatewhencomparedtothedegreeof

protrusionasdeterminedwiththeboil-and-biteMAD.

Thedifferenceineffectatretropalatallevelisanovelfinding.Wehypothesizethatthegreatereffect

oftheboil-and-biteMADonUApatencyatthislevelisprobablycausedbytheVOofthemouththat

is createdwith the oral device in place. By addingVO, stretching forces on the lateralwall of the

pharynxincrease,leadingtoadecreaseinUAcollapsibilityandstabilizationoftheairway.Ifcorrect,

this would also explain the differences in configuration of obstruction at palatal level. In seven

patientsaconcentriccollapsewasobservedwhenapplyingjawthrust,whichwasalteredtoanA-P

configurationwiththeboil-and-biteMADinsitu(i.e.openingofthepharynxinthelateral,butnotA-

Pdimension).

SeveralstudiesintheliteraturefocusontheeffectofVOonMADeffectivenessandUAcollapsibility.

Unfortunately,theresultsvaryamongstudies.Pitsisetal.concludedthatVOofthemouthinduced

by aMADdoes not significantly influence treatment efficacy 22,while Rose et al. found thatMAD

treatmentwasmoreeffectivewithincreasedVO.23 Inaddition,Fergusonetal.concludedthatthe

effectofVOontheefficacyofMADremainsundecided.24TheeffectofVOonUApatencywithouta

MAD in situ was previously studied by Vroegop et al. Their results indicated that increased VO,

without advancement of the mandible, had an adverse effect on pharyngeal dimensions in the

majorityofpatientsathypopharyngeallevel.25Unfortunately,theydidnotreportonoutcomeswith

regardtoobstructionatretropalatallevelmakingadequatecomparisonwiththeresultsofthisstudy

difficult.

Limitations

DISE was performed by one experienced endoscopist (PV), but were not reassessed by a second

observer.Thiscouldpotentiallyhave influenced interpretationofDISE.Nevertheless,byusingonly

one observer interobserver variability was avoided. In addition, the majority of patients were

diagnosed with mild to moderate position-dependent OSA, which might make the results of this

studylessapplicabletomoreseverenon-positionalOSApatients.

Clinicalimplicationsandfutureresearch

Theresultsofthisstudyemphasizetheneedforanalternativetojawthrustasascreeningmethod

and prediction tool for MAD treatment outcome used during DISE. Jaw thrust seems to be less

effectiveinimprovingUAcollapseatretropalatallevelthantheboilandbiteMAD,whichwasusedin

thisstudy.Inseveralpatients,thiscouldhaveledtoanoverestimationofassessmentof´notsuitable

for MAD treatment’. Furthermore, advancement of the mandible using jaw thrust during DISE is

probablygreater than theMCPduringwakefulness in themajorityofpatients.Therefore theMCP

seemstobemorerepresentativewheniscomestotheexpectedadvancementofthemandiblethat

canbeachievedwheninitiatingMADtreatment.

CONCLUSIONSANDFUTURERESEARCH

The results of this study indicate that there is only a slight tomoderate agreement in degree of

obstructionmeasuredwith jaw thrust and a new-generation boil–and-biteMAD— theMyTAP—

duringDISE.Overall, a greater improvementofUApatency at hypopharyngeal levelwasobserved

whenapplying jawthrust. Incontrast, jawthrustwas lesseffective in improvingUAobstructionat

retropalatallevelthantheMyTAP.Thereisstillaneedforanalterativetojawthrustthatcanbeused

asascreeningmethodandpredictiontoolforMADtreatmentoutcomeduringDISE.Thisisthefirst

partofatwo-partstudy.InthesecondpartofthisstudythecorrelationbetweenDISEfindingsand

MAD treatment outcome will be evaluated to further unravel the predictive value on MAD

effectiveness.

86

Chapter 4

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sleepapneatherapy.JDentRes.2008;87(9):882-7

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repositioningapplianceinobstructivesleepapneasyndrome.BrazOralRes.2017;31:e37

5. Dieltjens M, Wouters K, Verbruggen A, et al. Drug-induced Sedation Endoscopy (DISE)

findingscorrelatewithtreatmentoutcomeinOSApatientstreatedwithoralappliancetherapyina

fixedmandibularprotrusion.AmJRespirCritCareMed.2015;191:A2474

6. OpdeBeeckSDM,VerbruggenAE,etal.OpdeBeeckS,DieltjensM,VerbruggenAE,etal.

PhenotypicLabelingusingDrug-InducedSleepEndoscopyImprovesPatientSelectionforMandibular

Advancement Device Outcome. American journal of respiratory and critical care medicine. 2018

(submitted)

7. De Vito A, Llatas MC, Vanni A, et al. European position paper on drug-induced sedation

endoscopy(DISE).SleepandBreathing.2014;18(3):453-65

8. HohenhorstW,RaveslootM,KezirianE,DeVriesN.Drug-inducedsleependoscopyinadults

withsleep-disorderedbreathing:techniqueandtheVOTEclassificationsystem.OperativeTechniques

inOtolaryngology-HeadandNeckSurgery.2012;23(1):11-18

9. Johal A, Battagel JM, Kotecha BT. Sleep nasendoscopy: a diagnostic tool for predicting

treatmentsuccesswithmandibularadvancementsplints inobstructivesleepapnoea.Eur JOrthod.

2005;27(6):607-14

10. JohalA,HectorMP,BattagelJM,KotechaBT.Impactofsleepnasendoscopyontheoutcome

of mandibular advancement splint therapy in subjects with sleep-related breathing disorders. J

LaryngolOtol.2007;121(7):668-75

11. EichlerC,SommerJU,StuckBA,HormannK,MaurerJT.Doesdrug-inducedsleependoscopy

change the treatmentconceptofpatientswithsnoringandobstructivesleepapnea?SleepBreath.

2013;17(1):63-8

12. Vanderveken OM, Vroegop AV, van de Heyning PH, Braem MJ. Drug-induced sleep

endoscopy completed with a simulation bite approach for the prediction of the outcome of

treatment of obstructive sleep apnea with mandibular repositioning appliances. Operative

TechniquesinOtolaryngology-headandnecksurgery.2011;22(2):175-82

13. Vroegop AV, Vanderveken OM, Dieltjens M, Wouters K, Saldien V, Braem MJ. Sleep

endoscopywithsimulationbiteforpredictionoforalappliancetreatmentoutcome.Journalofsleep

research.2013;22(3):348-55.

14. Vanderveken OM, Devolder A, Marklund M, et al. Comparison of a custom-made and a

thermoplastic oral appliance for the treatment of mild sleep apnea. Am J Respir Crit Care Med.

2008;178(2):197-202.

15. BerryRB,BudhirajaR,GottliebDJ,etal.Rulesforscoringrespiratoryeventsinsleep:update

ofthe2007AASMmanualforthescoringofsleepandassociatedevents:deliberationsofthesleep

apnea definitions task force of the American Academy of SleepMedicine. Journal of clinical sleep

medicine:JCSM:officialpublicationoftheAmericanAcademyofSleepMedicine.2012;8(5):597.

16. DeVitoA,CarrascoLlatasM,RaveslootMJ,etal.Europeanpositionpaperondrug-induced

sleependoscopy:2017Update.ClinicalOtolaryngology.2018;43(6):1541-52.

17. Schnider T, Minto C. Pharmacokinetic models of propofol for TCI. Anaesthesia.

2008;63(2):206-06.

18. Schnider TW,Minto CF, Gambus PL, et al. The influence ofmethod of administration and

covariateson thepharmacokineticsofpropofol in adult volunteers.Anesthesiology: The Journalof

theAmericanSocietyofAnesthesiologists.1998;88(5):1170-82.

19. Kezirian EJ, Hohenhorst W, de Vries N. Drug-induced sleep endoscopy: the VOTE

classification.EurArchOtorhinolaryngol.2011;268(8):1233-36.

20. DeVetHC, Terwee CB,Mokkink LB, Knol DL.Measurement inmedicine: a practical guide.

CambridgeUniversityPress;2011.

21. CartwrightRD.Effectofsleeppositiononsleepapneaseverity.Sleep.1984;7(2):110-4.

22. PitsisAJ,DarendelilerMA,GotsopoulosH,PetoczP,CistulliPA.Effectofverticaldimension

on efficacy of oral appliance therapy in obstructive sleep apnea. Am J Respir Crit Care Med.

2002;166(6):860-4.

23. RoseE,StaatsR,VirchowC,JonasIE.Acomparativestudyoftwomandibularadvancement

appliancesforthetreatmentofobstructivesleepapnoea.EurJOrthod.2002;24(2):191-8.

24. Ferguson KA, Cartwright R, Rogers R, Schmidt-NowaraW. Oral appliances for snoring and

obstructivesleepapnea:areview.Sleep.2006;29(2):244-62.

25. VroegopAV,VandervekenOM,VandeHeyningPH,BraemMJ.Effectsofverticalopeningon

pharyngealdimensionsinpatientswithobstructivesleepapnoea.SleepMed.2012;13(3):314-6.

87

4

Jaw thrust versus the use of a boil-and-bite mandibular advancement device

REFERENCES1. RotenbergBW,ViciniC,PangEB,PangKP.Reconsideringfirst-linetreatmentforobstructive

sleepapnea:asystematicreviewoftheliterature.JOtolaryngolHeadNeckSurg.2016;45:23.

2. ChanAS,LeeRW,CistulliPA.Dentalappliancetreatmentforobstructivesleepapnea.Chest.

2007;132(2):693-9.

3. HoekemaA,StegengaB,WijkstraPJ,vanderHoevenJH,MeineszAF,deBontLG.Obstructive

sleepapneatherapy.JDentRes.2008;87(9):882-7.

4. Cunha TCA, Guimaraes TM, Schultz TCB, et al. Predictors of success for mandibular

repositioningapplianceinobstructivesleepapneasyndrome.BrazOralRes.2017;31:e37.

5. Dieltjens M, Wouters K, Verbruggen A, et al. Drug-induced Sedation Endoscopy (DISE)

findingscorrelatewithtreatmentoutcomeinOSApatientstreatedwithoralappliancetherapyina

fixedmandibularprotrusion.AmJRespirCritCareMed.2015;191:A2474.

6. OpdeBeeckSDM,VerbruggenAE,etal.OpdeBeeckS,DieltjensM,VerbruggenAE,etal.

PhenotypicLabelingusingDrug-InducedSleepEndoscopyImprovesPatientSelectionforMandibular

Advancement Device Outcome. American journal of respiratory and critical care medicine. 2018

(submitted).

7. De Vito A, Llatas MC, Vanni A, et al. European position paper on drug-induced sedation

endoscopy(DISE).SleepandBreathing.2014;18(3):453-65.

8. HohenhorstW,RaveslootM,KezirianE,DeVriesN.Drug-inducedsleependoscopyinadults

withsleep-disorderedbreathing:techniqueandtheVOTEclassificationsystem.OperativeTechniques

inOtolaryngology-HeadandNeckSurgery.2012;23(1):11-18.

9. Johal A, Battagel JM, Kotecha BT. Sleep nasendoscopy: a diagnostic tool for predicting

treatmentsuccesswithmandibularadvancementsplints inobstructivesleepapnoea.Eur JOrthod.

2005;27(6):607-14.

10. JohalA,HectorMP,BattagelJM,KotechaBT.Impactofsleepnasendoscopyontheoutcome

of mandibular advancement splint therapy in subjects with sleep-related breathing disorders. J

LaryngolOtol.2007;121(7):668-75.

11. EichlerC,SommerJU,StuckBA,HormannK,MaurerJT.Doesdrug-inducedsleependoscopy

change the treatmentconceptofpatientswithsnoringandobstructivesleepapnea?SleepBreath.

2013;17(1):63-8.

12. Vanderveken OM, Vroegop AV, van de Heyning PH, Braem MJ. Drug-induced sleep

endoscopy completed with a simulation bite approach for the prediction of the outcome of

treatment of obstructive sleep apnea with mandibular repositioning appliances. Operative

TechniquesinOtolaryngology-headandnecksurgery.2011;22(2):175-82.

13. Vroegop AV, Vanderveken OM, Dieltjens M, Wouters K, Saldien V, Braem MJ. Sleep

endoscopywithsimulationbiteforpredictionoforalappliancetreatmentoutcome.Journalofsleep

research.2013;22(3):348-55

14. Vanderveken OM, Devolder A, Marklund M, et al. Comparison of a custom-made and a

thermoplastic oral appliance for the treatment of mild sleep apnea. Am J Respir Crit Care Med.

2008;178(2):197-202

15. BerryRB,BudhirajaR,GottliebDJ,etal.Rulesforscoringrespiratoryeventsinsleep:update

ofthe2007AASMmanualforthescoringofsleepandassociatedevents:deliberationsofthesleep

apnea definitions task force of the American Academy of SleepMedicine. Journal of clinical sleep

medicine:JCSM:officialpublicationoftheAmericanAcademyofSleepMedicine.2012;8(5):597

16. DeVitoA,CarrascoLlatasM,RaveslootMJ,etal.Europeanpositionpaperondrug-induced

sleependoscopy:2017Update.ClinicalOtolaryngology.2018;43(6):1541-52

17. Schnider T, Minto C. Pharmacokinetic models of propofol for TCI. Anaesthesia.

2008;63(2):206-06

18. Schnider TW,Minto CF, Gambus PL, et al. The influence ofmethod of administration and

covariateson thepharmacokineticsofpropofol in adult volunteers.Anesthesiology: The Journalof

theAmericanSocietyofAnesthesiologists.1998;88(5):1170-82

19. Kezirian EJ, Hohenhorst W, de Vries N. Drug-induced sleep endoscopy: the VOTE

classification.EurArchOtorhinolaryngol.2011;268(8):1233-36

20. DeVetHC, Terwee CB,Mokkink LB, Knol DL.Measurement inmedicine: a practical guide.

CambridgeUniversityPress;2011

21. CartwrightRD.Effectofsleeppositiononsleepapneaseverity.Sleep.1984;7(2):110-4

22. PitsisAJ,DarendelilerMA,GotsopoulosH,PetoczP,CistulliPA.Effectofverticaldimension

on efficacy of oral appliance therapy in obstructive sleep apnea. Am J Respir Crit Care Med.

2002;166(6):860-4

23. RoseE,StaatsR,VirchowC,JonasIE.Acomparativestudyoftwomandibularadvancement

appliancesforthetreatmentofobstructivesleepapnoea.EurJOrthod.2002;24(2):191-8

24. Ferguson KA, Cartwright R, Rogers R, Schmidt-NowaraW. Oral appliances for snoring and

obstructivesleepapnea:areview.Sleep.2006;29(2):244-62

25. VroegopAV,VandervekenOM,VandeHeyningPH,BraemMJ.Effectsofverticalopeningon

pharyngealdimensionsinpatientswithobstructivesleepapnoea.SleepMed.2012;13(3):314-6

52

Floppyepiglottisduringdrug-induced sleep endoscopy: analmost complete resolution byadoptingthelateralpostureP.E.Vonk,M.J.L.Ravesloot,K.M.Kasius,J.P.vanMaanen,N.deVriesSleepBreath.2019Apr24.doi:10.1007/s11325-019-01847-x.

52

Floppyepiglottisduringdrug-induced sleep endoscopy: analmost complete resolution byadoptingthelateralpostureP.E.Vonk,M.J.L.Ravesloot,K.M.Kasius,J.P.vanMaanen,N.deVriesSleepBreath.2019Apr24.doi:10.1007/s11325-019-01847-x.

52

Floppyepiglottisduringdrug-induced sleep endoscopy: analmost complete resolution byadoptingthelateralpostureP.E.Vonk,M.J.L.Ravesloot,K.M.Kasius,J.P.vanMaanen,N.deVriesSleepBreath.2019Apr24.doi:10.1007/s11325-019-01847-x

52

Floppyepiglottisduringdrug-induced sleep endoscopy: analmost complete resolution byadoptingthelateralpostureP.E.Vonk,M.J.L.Ravesloot,K.M.Kasius,J.P.vanMaanen,N.deVriesSleepBreath.2019Apr24.doi:10.1007/s11325-019-01847.

52

Floppyepiglottisduringdrug-induced sleep endoscopy: analmost complete resolution byadoptingthelateralpostureP.E.Vonk,M.J.L.Ravesloot,K.M.Kasius,J.P.vanMaanen,N.deVriesSleepBreath.2019Apr24.doi:10.1007/s11325-019-01847-x.

90

Chapter 5

ABSTRACT

Purpose:Toanalyzethepresenceofafloppyepiglottis(FE)duringdrug-inducedsleependoscopyin

non-apneic snoring patients, non-positional obstructive sleep apnea (OSA) patients (NPP) and

position-dependentOSApatients (PP)and toevaluate the impactofmaneuversandbodyposition

duringDISE,includingjawthrust,supineandlateralhead(andtrunk)position.

Methods:Retrospectivecohortstudy.

Results: In total 324 patients were included. In 60 patients (18.5%) a FE was found in supine

position; seven non-apneic snoring patients and 53 OSA patients. When performing lateral head

rotationonly,aFEwaspresent infourpatients(NPP,N=0;PP,N=4).Whenpatientsweretiltedto

bothlateralheadandtrunkpositionaFEwasfoundinonlyonesubject.Afterapplyingjawthrust,a

FEwasstillpresentin10patients.TheprevalenceofaFEdidnotdifferbetweenNPPandPP.When

comparing baseline characteristics between patients with and without a FE in supine position no

significantdifferenceswerefound.

Conclusion: A FE appears almost exclusively in supine position. In patients with a FE, positional

therapycanbeapromisingalternativeasa standalone treatment,butalsoaspartofcombination

therapywith for examplemandibular advancementdevicesor less invasive formsofupper airway

surgery.

Keywords: obstructive sleep apnea, epiglottic collapse, floppy epiglottis, drug-induced sleep

endoscopy,positional

INTRODUCTION

Obstructive sleep apnea (OSA) is characterized by recurrent episodes of upper airway collapse

causingoxygendesaturationsandfragmentedsleep.InthemajorityofOSApatients,theseverityof

upperairway collapse is influencedbybodyposition, inwhich supineposition isusually theworst

sleepingposition.1-6

The underlying pathophysiologicalmechanism explaining different collapse patterns in supine and

non-supine sleepingposition remainspoorly understood.Oneof the structureswhich is known to

causeupperairwayobstructionandapneasistheepiglottis.Ithasbeensuggestedthatacollapseat

this level of the upper airway is enhancedby sleeping position and seems to occurmoreoften in

supinecomparedtonon-supineposition.7,8

Currently, diagnosis of an epiglottic collapse requires invasive studies, since as a rule it cannot be

established by physical examination or awake endoscopy. One of these invasive studies is drug-

inducedsleependoscopy (DISE). DISE isanuniqueanddynamicdiagnostic toolusedtogainmore

informationonupperairwaycollapsepatterns inorderto improvepatientselectionandtreatment

planning inOSApatients. InastudybyAzarbazinetal.analgorithmhasbeenproposedto identify

airflowpatternsanditsrelationtoepiglotticcollapseasdistinctfromothersitesofcollapseleading

tolessinvasivestudies.9Unfortunately,thesealgorithmsarenotexternallyvalidatedoryetpartof

daily practice. In literature many definitions have been used to define an epiglottic collapse: 1)

secondarytoananterior-posteriorcollapseofthetonguebasepushingtheepiglottisbackwards;2)

lateral collapseof theepiglottis forexampledue tounderdevelopmentof theepiglottis itself;3)a

completeisolatedanterior-posteriorepiglotticcollapse,alsocalledfloppyepiglottis(FE)ortrapdoor

phenomenon.

Focusing on the latter, treatment remains challenging. Previous studies showed that conventional

treatmentforthistypeofcollapseisdifficultandoftennotsuccessful.AFEhasbeenlinkedtoCPAP

failure, suggesting that the epiglottis is pushed further backwards on application of CPAP. 10-12

Treatmentwithmandibular advancement devices (MADs), designed to advance themandible in a

forward position and protruding several structures in the upper airway including the epiglottis,

regardedastherapyofchoice,isnotalwayssuccessful.13

BesidesconventionalOSAtreatment,severalsurgicaltechniqueshavebeendescribedinliteratureto

resolveepiglottic collapse, including (partial)epiglottectomywitha (CO2)laser. 14-16Althoughmany

studies report objective improvement of the apnea-hypopnea index (AHI), there are also several

(major)complications-aspiration,bleedingwhetherornotcompromisingtheairway,dysphagiaand

odynophagia-relatedtoepiglottissurgery,whichcanhaveseriousimplications.Inaddition,arecent

91

5

Floppy epiglottis during drug-induced sleep endoscopy

ABSTRACT

Purpose:Toanalyzethepresenceofafloppyepiglottis(FE)duringdrug-inducedsleependoscopyin

non-apneic snoring patients, non-positional obstructive sleep apnea (OSA) patients (NPP) and

position-dependentOSApatients (PP)and toevaluate the impactofmaneuversandbodyposition

duringDISE,includingjawthrust,supineandlateralhead(andtrunk)position.

Methods:Retrospectivecohortstudy.

Results: In total 324 patients were included. In 60 patients (18.5%) a FE was found in supine

position; seven non-apneic snoring patients and 53 OSA patients. When performing lateral head

rotationonly,aFEwaspresent infourpatients(NPP,N=0;PP,N=4).Whenpatientsweretiltedto

bothlateralheadandtrunkpositionaFEwasfoundinonlyonesubject.Afterapplyingjawthrust,a

FEwasstillpresentin10patients.TheprevalenceofaFEdidnotdifferbetweenNPPandPP.When

comparing baseline characteristics between patients with and without a FE in supine position no

significantdifferenceswerefound.

Conclusion: A FE appears almost exclusively in supine position. In patients with a FE, positional

therapycanbeapromisingalternativeasa standalone treatment,butalsoaspartofcombination

therapywith for examplemandibular advancementdevicesor less invasive formsofupper airway

surgery.

Keywords: obstructive sleep apnea, epiglottic collapse, floppy epiglottis, drug-induced sleep

endoscopy,positional

INTRODUCTION

Obstructive sleep apnea (OSA) is characterized by recurrent episodes of upper airway collapse

causingoxygendesaturationsandfragmentedsleep.InthemajorityofOSApatients,theseverityof

upperairway collapse is influencedbybodyposition, inwhich supineposition isusually theworst

sleepingposition.1-6

The underlying pathophysiologicalmechanism explaining different collapse patterns in supine and

non-supine sleepingposition remainspoorly understood.Oneof the structureswhich is known to

causeupperairwayobstructionandapneasistheepiglottis.Ithasbeensuggestedthatacollapseat

this level of the upper airway is enhancedby sleeping position and seems to occurmoreoften in

supinecomparedtonon-supineposition.7,8

Currently, diagnosis of an epiglottic collapse requires invasive studies, since as a rule it cannot be

established by physical examination or awake endoscopy. One of these invasive studies is drug-

inducedsleependoscopy (DISE). DISE isanuniqueanddynamicdiagnostic toolusedtogainmore

informationonupperairwaycollapsepatterns inorderto improvepatientselectionandtreatment

planning inOSApatients. InastudybyAzarbazinetal.analgorithmhasbeenproposedto identify

airflowpatternsanditsrelationtoepiglotticcollapseasdistinctfromothersitesofcollapseleading

tolessinvasivestudies.9Unfortunately,thesealgorithmsarenotexternallyvalidatedoryetpartof

daily practice. In literature many definitions have been used to define an epiglottic collapse: 1)

secondarytoananterior-posteriorcollapseofthetonguebasepushingtheepiglottisbackwards;2)

lateral collapseof theepiglottis forexampledue tounderdevelopmentof theepiglottis itself;3)a

completeisolatedanterior-posteriorepiglotticcollapse,alsocalledfloppyepiglottis(FE)ortrapdoor

phenomenon.

Focusing on the latter, treatment remains challenging. Previous studies showed that conventional

treatmentforthistypeofcollapseisdifficultandoftennotsuccessful.AFEhasbeenlinkedtoCPAP

failure, suggesting that the epiglottis is pushed further backwards on application of CPAP. 10-12

Treatmentwithmandibular advancement devices (MADs), designed to advance themandible in a

forward position and protruding several structures in the upper airway including the epiglottis,

regardedastherapyofchoice,isnotalwayssuccessful.13

BesidesconventionalOSAtreatment,severalsurgicaltechniqueshavebeendescribedinliteratureto

resolveepiglottic collapse, including (partial)epiglottectomywitha (CO2)laser. 14-16Althoughmany

studies report objective improvement of the apnea-hypopnea index (AHI), there are also several

(major)complications-aspiration,bleedingwhetherornotcompromisingtheairway,dysphagiaand

odynophagia-relatedtoepiglottissurgery,whichcanhaveseriousimplications.Inaddition,arecent

92

Chapter 5

casereportshowedthatupperairwaystimulationalsohadabeneficialeffectonthepresenceofaFE

observedduringDISE.17

Inourcenter,DISE isperformedindifferentbodypositions, i.e. insupinepositionand lateralhead

(and trunk) position, andwhen applying jaw thrust. Based on observationsmade duringDISE,we

hypothesize that a FE is in particular present in supine position and to a lesser extent when the

patient is lying in lateral bodyposition.Wewere interested to seewhetherwe could confirmour

hypothesis by retrospectively analyze if a FE ismore common in position-dependentOSApatients

(PP)comparedtonon-positionalOSApatients(NPP)duringDISE.Furthermore,wewereinterestedin

evaluating the impact ofmaneuvers and body position during DISE on a FE, including jaw thrust,

supineandlateralhead(andtrunk)position.

MATERIALANDMETHODS

Patients

Weperformedaretrospectivestudy,includingaconsecutiveseriesofpatientswhounderwentDISE

in theDepartmentofOtorhinolaryngology -HeadandNeck surgeryof theOLVG (Amsterdam, the

Netherlands)betweenthe14thofAugust2017andthe6thofAugust2018.Bothnon-apneicsnoring

patients and OSA patients were included. Patients were excluded from this study when

polysomnography (PSG) data concerning supine and non-supine AHI and sleeping position was

missingorwhenpatients slept < 10%or > 90%of the total sleeping time (TST) in supine sleeping

position,becausesubsequentlysupineornon-supineAHIcouldnotbedeterminedreliably.Patients

were also excludedwhenDISE resultswere inconclusive (e.g. due tomucosal hypersecretion) and

couldthereforenotbeinterpreted.

Definitions

Patientswere diagnosedwith position-dependentOSA (POSA) using Cartwright’s criteria: a supine

AHIofat least twiceashighasnon-supineAHI. 3 In this studywewereonly interested inpatients

with a complete anterior-posterior epiglottic collapse, not secondary to a collapse of the tongue

base,furtherreferredtoasaFE.

DISEprocedure

DISEwasperformedaccordingtothepracticeguidelinesasrecommendedintheEuropeanposition

paper on DISE (update 2017). 18 The procedure was performed in a quiet outpatient endoscopy

settingusingpropofol.ThemainreasontoperformDISEwastoevaluatesurgicaltreatmentoptions.

Otherindicationsincludedpatients’eligibilityforMADtreatmentorcombinationtherapy(e.g.MAD

+positionaltherapy(PT)).

DISE was performed by one experienced ENT resident (PV), with a trained nurse anesthetist

managingsedationandmonitoringbloodpressure,electrocardiogramandoxygenlevels.Thelevelof

sedation was controlled by a target controlled infusion pump using the methods described by

Schnideretal.tocalculatetheeffectivedose.19,20Priortotheintravenous(IV)infusionofpropofol,

2cc lidocaine was given IV to prevent pain caused by the infusion of propofol. In some patients

Glycopyrrolate (Robinul)wasgiven IVtopreventmucosalhypersecretion,sincethiscould interfere

withthequalityoftheendoscopicassessment.

Patientpositioning

Initially,DISEevaluationwascommencedinsupineposition.Subsequently,theheadwasrotatedto

the lateral position, to mimic the effect of non-supine sleeping position. 21 A jaw thrust was

performed to mimic the effect of a MAD by gently protruding the mandible up to 65-75% of

maximumprotrusion.Thismaneuverwasperformedinbothpositions.

Incontrasttowhatwaspreviouslythought,newstudyfindingsshowedthattheeffectoflateralhead

rotationonupperairwaypatencyinPPisnotsimilartolateralheadandtrunkposition.22Asaresult,

ourDISEprocedureremainedunchangedinNPP,butinPPDISEwascommencedinlateralheadand

trunkposition.Afteradequateevaluationpatientsweremaneuveredtosupineposition.Jawthrust

wasperformedinbothpositions.Theheadwasnotrotatedtolateralposition.Subsequently,results

inNPParepresentedusingobservationsmadeinsupinepositionandwiththeheadrotatedtolateral

position. In PP results are described either using lateral head rotation or lateral head and trunk

position.

VOTEclassificationsystem

Toreportontheanatomicalstructurescausingupperairwaycollapse,theVOTEclassificationsystem

was applied. The VOTE classification system distinguishes between four different levels and

structuresthatmaybeinvolvedinupperairwaycollapse,i.e.velum(V),oropharynx(O),tonguebase

(T) and epiglottis (E). To define the degree of obstruction, three different categories are used: no

obstruction,withacollapseof50%and less;apartialobstructionwithacollapsebetween50-75%

andtypicallywithvibration;oracompletecollapseinwhichacollapseisseenthatcomprisesmore

93

5

Floppy epiglottis during drug-induced sleep endoscopy

casereportshowedthatupperairwaystimulationalsohadabeneficialeffectonthepresenceofaFE

observedduringDISE.17

Inourcenter,DISE isperformedindifferentbodypositions, i.e. insupinepositionand lateralhead

(and trunk) position, andwhen applying jaw thrust. Based on observationsmade duringDISE,we

hypothesize that a FE is in particular present in supine position and to a lesser extent when the

patient is lying in lateral bodyposition.Wewere interested to seewhetherwe could confirmour

hypothesis by retrospectively analyze if a FE ismore common in position-dependentOSApatients

(PP)comparedtonon-positionalOSApatients(NPP)duringDISE.Furthermore,wewereinterestedin

evaluating the impact ofmaneuvers and body position during DISE on a FE, including jaw thrust,

supineandlateralhead(andtrunk)position.

MATERIALANDMETHODS

Patients

Weperformedaretrospectivestudy,includingaconsecutiveseriesofpatientswhounderwentDISE

in theDepartmentofOtorhinolaryngology -HeadandNeck surgeryof theOLVG (Amsterdam, the

Netherlands)betweenthe14thofAugust2017andthe6thofAugust2018.Bothnon-apneicsnoring

patients and OSA patients were included. Patients were excluded from this study when

polysomnography (PSG) data concerning supine and non-supine AHI and sleeping position was

missingorwhenpatients slept < 10%or > 90%of the total sleeping time (TST) in supine sleeping

position,becausesubsequentlysupineornon-supineAHIcouldnotbedeterminedreliably.Patients

were also excludedwhenDISE resultswere inconclusive (e.g. due tomucosal hypersecretion) and

couldthereforenotbeinterpreted.

Definitions

Patientswere diagnosedwith position-dependentOSA (POSA) using Cartwright’s criteria: a supine

AHIofat least twiceashighasnon-supineAHI. 3 In this studywewereonly interested inpatients

with a complete anterior-posterior epiglottic collapse, not secondary to a collapse of the tongue

base,furtherreferredtoasaFE.

DISEprocedure

DISEwasperformedaccordingtothepracticeguidelinesasrecommendedintheEuropeanposition

paper on DISE (update 2017). 18 The procedure was performed in a quiet outpatient endoscopy

settingusingpropofol.ThemainreasontoperformDISEwastoevaluatesurgicaltreatmentoptions.

Otherindicationsincludedpatients’eligibilityforMADtreatmentorcombinationtherapy(e.g.MAD

+positionaltherapy(PT)).

DISE was performed by one experienced ENT resident (PV), with a trained nurse anesthetist

managingsedationandmonitoringbloodpressure,electrocardiogramandoxygenlevels.Thelevelof

sedation was controlled by a target controlled infusion pump using the methods described by

Schnideretal.tocalculatetheeffectivedose.19,20Priortotheintravenous(IV)infusionofpropofol,

2cc lidocaine was given IV to prevent pain caused by the infusion of propofol. In some patients

Glycopyrrolate (Robinul)wasgiven IVtopreventmucosalhypersecretion,sincethiscould interfere

withthequalityoftheendoscopicassessment.

Patientpositioning

Initially,DISEevaluationwascommencedinsupineposition.Subsequently,theheadwasrotatedto

the lateral position, to mimic the effect of non-supine sleeping position. 21 A jaw thrust was

performed to mimic the effect of a MAD by gently protruding the mandible up to 65-75% of

maximumprotrusion.Thismaneuverwasperformedinbothpositions.

Incontrasttowhatwaspreviouslythought,newstudyfindingsshowedthattheeffectoflateralhead

rotationonupperairwaypatencyinPPisnotsimilartolateralheadandtrunkposition.22Asaresult,

ourDISEprocedureremainedunchangedinNPP,butinPPDISEwascommencedinlateralheadand

trunkposition.Afteradequateevaluationpatientsweremaneuveredtosupineposition.Jawthrust

wasperformedinbothpositions.Theheadwasnotrotatedtolateralposition.Subsequently,results

inNPParepresentedusingobservationsmadeinsupinepositionandwiththeheadrotatedtolateral

position. In PP results are described either using lateral head rotation or lateral head and trunk

position.

VOTEclassificationsystem

Toreportontheanatomicalstructurescausingupperairwaycollapse,theVOTEclassificationsystem

was applied. The VOTE classification system distinguishes between four different levels and

structuresthatmaybeinvolvedinupperairwaycollapse,i.e.velum(V),oropharynx(O),tonguebase

(T) and epiglottis (E). To define the degree of obstruction, three different categories are used: no

obstruction,withacollapseof50%and less;apartialobstructionwithacollapsebetween50-75%

andtypicallywithvibration;oracompletecollapseinwhichacollapseisseenthatcomprisesmore

94

Chapter 5

than75%oftheupperairwaylumen.AnXisusedwhennoobservationcanbemade.Dependingon

the different site(s) involved in upper airway obstruction, the configuration may be anterior-

posterior,lateralorconcentric.23

Ethicalconsiderations

InaccordancewiththeDeclarationofHelsinki,thestudyprotocolwasapprovedbythelocalMedical

EthicalCommittee.Informedconsentwasnotrequiredforthistypeofstudy.Dataonstudysubjects

wascollectedandstoredanonymouslytoprotectpersonalinformation.

Statisticalanalysis

StatisticalanalysiswasperformedusingSPSS (version21),SPSS Inc.,Chicago, IL).Quantitativedata

arereportedasmean±SDorasmedian(Q1,Q3)whennotnormallydistributed.Apvalueof<0.05is

consideredtoindicatestatisticalsignificance.Tocomparebaselinecharacteristicsbetweenpatients

with andwithout a FE the unpaired T testwas used in case of normally distributed data and the

Mann-WhitneyTestwhendatawasnotnormallydistributed.Thechi-squaretestwasusedtoanalyze

categoricaldata.Achi-squaretestwasalsousedtoanalyzethecorrelationbetweenthepresenceof

a FE and POSA. To compareDISE findings in different body positions andwhen applying different

maneuverstheWilcoxonsignedranktestwasused.

RESULTS

Atotalof428patientswerescreenedforthisstudy. In87patientsPSGresultsshowed<10%or>

90%oftheTSTinworstsleepingposition.In17patientsthedegreeandconfigurationofobstruction

attheleveloftheepiglottiscouldnotbeobserved.Therefore,onlytheresultsof324patientswere

used.

Patientcharacteristics-totalpopulation

Ofthe324patients,269patientsweremale(83.0%)and291patients(89.8%)werediagnosedwith

OSA(AHI≥5eventsperhour).OfallOSApatients,211(72.5%)werePP.Themeanageofallpatients

was48.4±24.4years,withameanBMIof27.1±3.3kg/m2andamedianAHIof17.7/h(8.3,31.1)a

mediansupineAHIof33.5/h(15.3,56.6)andamediannon-supineAHIof7.1/h(2.8,19.9)Patients

spentamedianpercentageof theTST insupinepositionof38.3%(25.9,52.2), themedianoxygen

desaturationindex(ODI)was19.8/h(10.3,34.2).Anoverviewcomparingbaselinecharacteristics in

non-apneicsnoringpatients,NPPandPPcanbefoundintable1.

Patientcharacteristics-FEversusnoFEinsupineposition

Nosignificantdifferenceswerefoundbetweenbaselinecharacteristicsinpatientswithorwithouta

FE.InPP,19.4%werediagnosedwithaFEcomparedto16.8%inNPP,butnosignificantcorrelation

was found between the presence of a FE and the presence of position dependency (p=0.183). An

overviewofthebaselinecharacteristicsinpatientswithandwithoutaFEinsupinepositionisgiven

intable2.

95

5

Floppy epiglottis during drug-induced sleep endoscopy

than75%oftheupperairwaylumen.AnXisusedwhennoobservationcanbemade.Dependingon

the different site(s) involved in upper airway obstruction, the configuration may be anterior-

posterior,lateralorconcentric.23

Ethicalconsiderations

InaccordancewiththeDeclarationofHelsinki,thestudyprotocolwasapprovedbythelocalMedical

EthicalCommittee.Informedconsentwasnotrequiredforthistypeofstudy.Dataonstudysubjects

wascollectedandstoredanonymouslytoprotectpersonalinformation.

Statisticalanalysis

StatisticalanalysiswasperformedusingSPSS (version21),SPSS Inc.,Chicago, IL).Quantitativedata

arereportedasmean±SDorasmedian(Q1,Q3)whennotnormallydistributed.Apvalueof<0.05is

consideredtoindicatestatisticalsignificance.Tocomparebaselinecharacteristicsbetweenpatients

with andwithout a FE the unpaired T testwas used in case of normally distributed data and the

Mann-WhitneyTestwhendatawasnotnormallydistributed.Thechi-squaretestwasusedtoanalyze

categoricaldata.Achi-squaretestwasalsousedtoanalyzethecorrelationbetweenthepresenceof

a FE and POSA. To compareDISE findings in different body positions andwhen applying different

maneuverstheWilcoxonsignedranktestwasused.

RESULTS

Atotalof428patientswerescreenedforthisstudy. In87patientsPSGresultsshowed<10%or>

90%oftheTSTinworstsleepingposition.In17patientsthedegreeandconfigurationofobstruction

attheleveloftheepiglottiscouldnotbeobserved.Therefore,onlytheresultsof324patientswere

used.

Patientcharacteristics-totalpopulation

Ofthe324patients,269patientsweremale(83.0%)and291patients(89.8%)werediagnosedwith

OSA(AHI≥5eventsperhour).OfallOSApatients,211(72.5%)werePP.Themeanageofallpatients

was48.4±24.4years,withameanBMIof27.1±3.3kg/m2andamedianAHIof17.7/h(8.3,31.1)a

mediansupineAHIof33.5/h(15.3,56.6)andamediannon-supineAHIof7.1/h(2.8,19.9)Patients

spentamedianpercentageof theTST insupinepositionof38.3%(25.9,52.2), themedianoxygen

desaturationindex(ODI)was19.8/h(10.3,34.2).Anoverviewcomparingbaselinecharacteristics in

non-apneicsnoringpatients,NPPandPPcanbefoundintable1.

Patientcharacteristics-FEversusnoFEinsupineposition

Nosignificantdifferenceswerefoundbetweenbaselinecharacteristicsinpatientswithorwithouta

FE.InPP,19.4%werediagnosedwithaFEcomparedto16.8%inNPP,butnosignificantcorrelation

was found between the presence of a FE and the presence of position dependency (p=0.183). An

overviewofthebaselinecharacteristicsinpatientswithandwithoutaFEinsupinepositionisgiven

intable2.

96

Chapter 5

Table1.Baselinecharacteristicstotalpopulation,noOSA,NPPandPP

Datapresentedasmean±standarddeviationor°median(Q1,Q3)

*pvalue<0.05comparingNPPandPP

OSA obstructive sleep apnea, NPP non-positional obstructive sleep apnea patients, PP positional

obstructive sleep apnea patients, BMI body mass index, AHI apnea-hypopnea index, TST total

sleepingtime,ODIoxygendesaturationindex

Patient

characteristic

Total

N=324

NoOSA

N=33

NPP

N=80

PP

N=211

pvalue

Age

(years)

48.4±24.4 40.2±10.0 48.3±12.3 49.6±28.8 0.688

Male/Female 269/55 22/11 61/19 186/25 0.002*

BMI

(kg/m2)

27.1±3.3 25.8±3.6 27.2±3.5 27.2±3.5 0.991

TotalAHI

(events/hour)

17.7

(8.3,31.1)°

2.8

(1.6,4.0)°

28.1

(13.1,48.9)°

17.7

(10.3,28.9)°

0.001*

SupineAHI

(events/hour)

33.3

(15.3,56.5)°

5.0

(2.0,8.3)°

30.3

(15.9,59.9)°

37.5

(22.6,58.5)°

0.124

Non-supineAHI

(events/hour)

7.1

(2.8,19.8)°

1.1

(0.6,2.2)°

25.4

(10.4,41.0)°

6.1

(2.8,14.0)°

<0.001*

TSTinsupine

position(%)

40.2±18.8

42.3±18.0 42.6±18.2 38.9±19.1

0.134

ODI

(events/hour)

19.8

(10.3,34.2)°

3.9

(2.7,7.0)°

30.2

(15.1,51.6)°

20.2

(12.3,32.0)°

<0.001*

Table2.BaselinecharacteristicsinpatientswithandwithoutaFE

Patientcharacteristic FE NoFE FEvsnoFE

pvalue

Number(%) 60(18.5) 264(81.5) 48vs228

Age(years) 47.5±11.9 48.6±26.4 0.756

Male/Female 53/7 216/48 0.914

BMI(kg/m2) 27.0±3.6 27.1±3.3 0.787

TotalAHI(events/hour) 14.4(8.2,25.0)° 18.3(8.3,32.4)° 0.317

SupineAHI(events/hour) 28.9(14.3,56.6)° 35.0(15.5,57.0)° 0.260

Non-supineAHI(events/hour) 5.9(2.7,16.0)° 8.1(2.8,20.1)° 0.173

TSTinsupineposition(%) 41.1(28.2,63.1)° 37.6(25.8,51.5)° 0.475

ODI(events/hour) 20.0(10.2,31.3)° 19.8(10.3,34.8)° 0.949

Datapresentedasmean±standarddeviationor°median(Q1,Q3)

*pvalue<0.05

BMIbodymassindex;AHIapnea-hypopneaindex;TSTtotalsleepingtime;ODIoxygendesaturation

index

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5

Floppy epiglottis during drug-induced sleep endoscopy

Table1.Baselinecharacteristicstotalpopulation,noOSA,NPPandPP

Datapresentedasmean±standarddeviationor°median(Q1,Q3)

*pvalue<0.05comparingNPPandPP

OSA obstructive sleep apnea, NPP non-positional obstructive sleep apnea patients, PP positional

obstructive sleep apnea patients, BMI body mass index, AHI apnea-hypopnea index, TST total

sleepingtime,ODIoxygendesaturationindex

Patient

characteristic

Total

N=324

NoOSA

N=33

NPP

N=80

PP

N=211

pvalue

Age

(years)

48.4±24.4 40.2±10.0 48.3±12.3 49.6±28.8 0.688

Male/Female 269/55 22/11 61/19 186/25 0.002*

BMI

(kg/m2)

27.1±3.3 25.8±3.6 27.2±3.5 27.2±3.5 0.991

TotalAHI

(events/hour)

17.7

(8.3,31.1)°

2.8

(1.6,4.0)°

28.1

(13.1,48.9)°

17.7

(10.3,28.9)°

0.001*

SupineAHI

(events/hour)

33.3

(15.3,56.5)°

5.0

(2.0,8.3)°

30.3

(15.9,59.9)°

37.5

(22.6,58.5)°

0.124

Non-supineAHI

(events/hour)

7.1

(2.8,19.8)°

1.1

(0.6,2.2)°

25.4

(10.4,41.0)°

6.1

(2.8,14.0)°

<0.001*

TSTinsupine

position(%)

40.2±18.8

42.3±18.0 42.6±18.2 38.9±19.1

0.134

ODI

(events/hour)

19.8

(10.3,34.2)°

3.9

(2.7,7.0)°

30.2

(15.1,51.6)°

20.2

(12.3,32.0)°

<0.001*

Table2.BaselinecharacteristicsinpatientswithandwithoutaFE

Patientcharacteristic FE NoFE FEvsnoFE

pvalue

Number(%) 60(18.5) 264(81.5) 48vs228

Age(years) 47.5±11.9 48.6±26.4 0.756

Male/Female 53/7 216/48 0.914

BMI(kg/m2) 27.0±3.6 27.1±3.3 0.787

TotalAHI(events/hour) 14.4(8.2,25.0)° 18.3(8.3,32.4)° 0.317

SupineAHI(events/hour) 28.9(14.3,56.6)° 35.0(15.5,57.0)° 0.260

Non-supineAHI(events/hour) 5.9(2.7,16.0)° 8.1(2.8,20.1)° 0.173

TSTinsupineposition(%) 41.1(28.2,63.1)° 37.6(25.8,51.5)° 0.475

ODI(events/hour) 20.0(10.2,31.3)° 19.8(10.3,34.8)° 0.949

Datapresentedasmean±standarddeviationor°median(Q1,Q3)

*pvalue<0.05

BMIbodymassindex;AHIapnea-hypopneaindex;TSTtotalsleepingtime;ODIoxygendesaturation

index

98

Chapter 5

DISEfindings

In60patients(18.5%)aFEwasfoundinsupineposition;sevennonapneicsnoringpatients(21.2%)

and53wereOSApatients(18.2%).In58patientsaFEwaspartofamultilevelcollapseoftheupper

airway.InonlytwopatientsaFEwaspresentasanisolatedcollapse.

When performing jaw thrust in supine position, a FEwas still present in 10 patients; a significant

decrease (p<0.001). In one patient jaw thrust could not be performeddue to temporomandibular

jointproblems.TomimicnonsupinesleepingpositioninNPPlateralheadrotationwasperformed.In

one patient this maneuver could not be applied due to preexistent neck injury. In none of the

remaining79patientsaFEwasstillpresentafterperformingthismaneuver(p<0.001).InPP,lateral

head rotation was performed in 89 patients and lateral head and trunk position in 121 patients.

When performing lateral head rotation only, a FE was persistent in four patients.When patients

wereturnedtolateralheadandtrunkpositionaFEwasfoundtobepersistentinonlyonesubject.In

lateralhead(andtrunk)positionthisimprovementwasstatisticallysignificant(p<0.001).Anoverview

ofDISEfindingscanbefoundintable3.

Table3.OverviewofthepresenceofaFEindifferentbodypositions,withandwithoutmaneuversin

patientswithnoOSA,NPPandPP

Bodyposition

(+maneuver)

FE(N)

NoOSA NPP PP Total

Supine 7 12 41 60*

Supine+jawthrust 0 2 8 10*

Lateralhead

rotation

0 0 4 4*

Lateralheadand

trunkrotation

N/A N/A 1 1*

FE floppy epiglottis;OSA obstructive sleep apnea;NPP non-positional OSA patients; PP positional

OSApatients;N/Anotapplicable

*pvalue<0.05

DISCUSSION

ThisstudydescribestheeffectofbodypositionandjawthrustonthepresenceofaFEduringDISE.

To thebestofourknowledge, this is the first study thatanalyzes thisphenomenonduringDISE in

non-apneic snoringpatients andOSApatients. The results of this study indicate that a FE appears

almostexclusivelyinsupinepositionandtoalesserextentduringlateralhead(andtrunk)rotation.

Despite this phenomenon, the prevalence of a FE did not differ between NPP and PP. When

comparing baseline characteristics between patients with and without a FE in supine position no

significantdifferenceswerefound.

The fact that we did not find a correlation between the presence of a FE and POSA might be

explainedbythefindingthat inthemajorityof includedpatientsamultilevelcollapseoftheupper

airwaywasobservedduringDISE.InthreepatientsanisolatedFEwasfound.Onepatientwasindeed

found to beposition-dependentwithobstructive events almost exclusively in supineposition. The

twootherpatientswithanisolatedFEwerephenotypicallydifferent:theywereyounger,hadalow

BMIandhadasupineAHItwiceashighasthenon-supineAHI.Thesecharacteristicsarecomparable

tothoseofPP.2,5,24,25

TheprevalenceofaFEinthisstudywas18.5%.Inliteratureawidevariationoftheprevalenceofan

epiglotticcollapsecanbefoundvaryingfrom9.7%to73.5%.26Asmentionedbefore,thisvariation

couldbeexplainedbythedifferentdefinitionsusedinliteraturetodescribeanepiglotticcollapse.It

mustbekeptinmindthatthereisanimportantdifferencebetweenaFEandanepiglotticcollapse

secondarytoananterior-posteriorcollapseofthetonguebase.

Inthisstudy,72.5%ofallpatientswerePP.Thisisrelativelyhighcomparedtotheprevalencefound

in literature. This high prevalence could be explained by the fact that the prevalence of POSA

decreaseswhenOSAseverityincreases.3-6,27,28IncaseofsevereOSA,CPAPisthefirsttreatmentof

choice and does not requireDISE. Therefore, patients undergoingDISE aremainly diagnosedwith

mildtomoderateOSA.

Previousfindings

ThefindingsofthisstudyaresupportedbytheresultsofastudybyMarquesetal.inwhich23OSA

patients underwent upper airway endoscopy during natural sleep. The aim of this study was to

evaluate the effect of sleepingposition and the correlationwithpharyngeal structures involved in

upperairwaycollapse.Additionalrecordingsofairflowandpharyngealpressureweresimultaneously

99

5

Floppy epiglottis during drug-induced sleep endoscopy

DISEfindings

In60patients(18.5%)aFEwasfoundinsupineposition;sevennonapneicsnoringpatients(21.2%)

and53wereOSApatients(18.2%).In58patientsaFEwaspartofamultilevelcollapseoftheupper

airway.InonlytwopatientsaFEwaspresentasanisolatedcollapse.

When performing jaw thrust in supine position, a FEwas still present in 10 patients; a significant

decrease (p<0.001). In one patient jaw thrust could not be performeddue to temporomandibular

jointproblems.TomimicnonsupinesleepingpositioninNPPlateralheadrotationwasperformed.In

one patient this maneuver could not be applied due to preexistent neck injury. In none of the

remaining79patientsaFEwasstillpresentafterperformingthismaneuver(p<0.001).InPP,lateral

head rotation was performed in 89 patients and lateral head and trunk position in 121 patients.

When performing lateral head rotation only, a FE was persistent in four patients.When patients

wereturnedtolateralheadandtrunkpositionaFEwasfoundtobepersistentinonlyonesubject.In

lateralhead(andtrunk)positionthisimprovementwasstatisticallysignificant(p<0.001).Anoverview

ofDISEfindingscanbefoundintable3.

Table3.OverviewofthepresenceofaFEindifferentbodypositions,withandwithoutmaneuversin

patientswithnoOSA,NPPandPP

Bodyposition

(+maneuver)

FE(N)

NoOSA NPP PP Total

Supine 7 12 41 60*

Supine+jawthrust 0 2 8 10*

Lateralhead

rotation

0 0 4 4*

Lateralheadand

trunkrotation

N/A N/A 1 1*

FE floppy epiglottis;OSA obstructive sleep apnea;NPP non-positional OSA patients; PP positional

OSApatients;N/Anotapplicable

*pvalue<0.05

DISCUSSION

ThisstudydescribestheeffectofbodypositionandjawthrustonthepresenceofaFEduringDISE.

To thebestofourknowledge, this is the first study thatanalyzes thisphenomenonduringDISE in

non-apneic snoringpatients andOSApatients. The results of this study indicate that a FE appears

almostexclusivelyinsupinepositionandtoalesserextentduringlateralhead(andtrunk)rotation.

Despite this phenomenon, the prevalence of a FE did not differ between NPP and PP. When

comparing baseline characteristics between patients with and without a FE in supine position no

significantdifferenceswerefound.

The fact that we did not find a correlation between the presence of a FE and POSA might be

explainedbythefindingthat inthemajorityof includedpatientsamultilevelcollapseoftheupper

airwaywasobservedduringDISE.InthreepatientsanisolatedFEwasfound.Onepatientwasindeed

found to beposition-dependentwithobstructive events almost exclusively in supineposition. The

twootherpatientswithanisolatedFEwerephenotypicallydifferent:theywereyounger,hadalow

BMIandhadasupineAHItwiceashighasthenon-supineAHI.Thesecharacteristicsarecomparable

tothoseofPP.2,5,24,25

TheprevalenceofaFEinthisstudywas18.5%.Inliteratureawidevariationoftheprevalenceofan

epiglotticcollapsecanbefoundvaryingfrom9.7%to73.5%.26Asmentionedbefore,thisvariation

couldbeexplainedbythedifferentdefinitionsusedinliteraturetodescribeanepiglotticcollapse.It

mustbekeptinmindthatthereisanimportantdifferencebetweenaFEandanepiglotticcollapse

secondarytoananterior-posteriorcollapseofthetonguebase.

Inthisstudy,72.5%ofallpatientswerePP.Thisisrelativelyhighcomparedtotheprevalencefound

in literature. This high prevalence could be explained by the fact that the prevalence of POSA

decreaseswhenOSAseverityincreases.3-6,27,28IncaseofsevereOSA,CPAPisthefirsttreatmentof

choice and does not requireDISE. Therefore, patients undergoingDISE aremainly diagnosedwith

mildtomoderateOSA.

Previousfindings

ThefindingsofthisstudyaresupportedbytheresultsofastudybyMarquesetal.inwhich23OSA

patients underwent upper airway endoscopy during natural sleep. The aim of this study was to

evaluate the effect of sleepingposition and the correlationwithpharyngeal structures involved in

upperairwaycollapse.Additionalrecordingsofairflowandpharyngealpressureweresimultaneously

100

Chapter 5

executed.Anepiglotticcollapsewas found insix subjectswhoshowedsubstantial improvement in

upperairwaypatencywhenturnedtolateralbodyposition.Objectivemeasurementsalsoshoweda

decrease in percentage of breaths exhibiting an epiglottic collapse (from 66.5% to 12.3%) and an

increase inventilationby45%comparingsupineto lateralbodyposition.Surprisingly,noeffecton

upperairwaycollapsewasfoundinpatientswithtongue-relatedobstruction.7

In another studybyVictores et al. similar resultswere foundwith regard to thepositive effect of

bodypositiononupperairwaypatencyattheleveloftheepiglottis.8Interestingly,Safiruddinetal.

found that lateral head rotation only was also associated with a decreased frequency of a

partial/completecollapseatepiglottislevelcomparedtosupineposition.29

Physiologicalaspects

Azarbarzinetal.analyzedflowcharacteristicscorrelatedwiththepresenceofaFE.Theyfoundthata

FEwasassociatedwith flowfeaturescharacterizedbydiscontinuityand jaggedness.Unfortunately,

changes in body position were not included. 9When trying to understand the pathophysiological

mechanism behind the correlation of body position and the presence of a FE, several hypotheses

couldbetakenintoconsideration.

Firstofall, ithasbeenthoughtthatoropharyngealstructuresrespondtogravitationalforces inthe

upperairway. InastudybySutthiprapapornetal.sevensubjectswereevaluatedbyconebeamCT

while theywere in upright or in supine position. They found that gravity enhancesmovement of

oropharyngeal structures, such as the epiglottis and palatewhen changing fromupright to supine

position.Surprisingly,thehyoidbonedidnotmoveposteriorlybutcaudally.30

Onecouldalsoarguethatalteringbodypositioncouldleadtochangesinthenegativeintrathoracic

pressure, which as a result causes an increase in intraluminal pressure. This could hypothetically

influencethecriticalclosingpressureoftheepiglottis.Unfortunately,noevidenceonthistopicisyet

availableinliterature.

Limitations

Thereareseverallimitationsinthisstudy.First,datawasretrospectivelycollectedusinganinclusion

periodduringwhichnewresultswereavailableshowingthat theeffectof lateralheadrotationon

upperairwaypatencyinPPisnotsimilartobothlateralheadandtrunkposition,incontrasttoNPP.22Consequently,theresultsinPParedescribedeitherusinglateralheadrotationorlateralheadand

trunkposition.Nevertheless,noFEwasfoundinNPPduringlateralheadrotationincontrasttoPP,

whichemphasizesthatlateralheadrotationinNPPiscomparabletolateralheadandtrunkposition

andthataFEisapositiondependentphenomenon.

Second,DISEwas scored according to theVOTE classification system,which is a simplified system

withknownintra-andinterobserverreliability.31Butinthisstudy,DISEwasperformedbyonlyone

endoscopist, clearly describing an epiglottic collapse caused by a complete anterior-posterior

collapseof the tonguebaseorasan isolatedcompleteanterior-posteriorcollapseof theepiglottis

(e.g.FE),which,toouropinion,enhancesintraobserverreliability.

Clinicalrelevance

Currently, treatment inOSApatientswitha FE remains challengingandevidencebased treatment

options inthispopulationare lacking. Inthepast,severalsurgicaltechniquesoftheepiglottishave

been described, which are not without risks. CPAP might even worsen a FE resulting in low

compliance and treatment failure and also MAD treatment is not always successful. It can be

concluded that there isademand forother treatmentoptions inpatientswithaFE.Basedon the

resultsofthisstudy,PTcouldbeapromisingalternativeinpatientswithaFE,despitethefactthat

theymightnotsufferfromPOSA.Itcanbeusedasastandalonetreatment,butduetothefactthata

FEisusuallypartofamultilevelproblemitcanalsobecombinedwithMADorlessinvasiveformsof

upperairwaysurgerylimitingrisksandcomplications.32-35

CONCLUSION

The results of this study indicate that a FE is a position dependent phenomenon, which appears

almostexclusivelyinsupineposition.Despitethisphenomenon,thecorrelationwiththeunderlying

pathophysiologicalmechanisminNPPandPPremainsyetunclear.

Treatment planning in OSA patientswith a FE remains challenging and evidence based treatment

options in this population are lacking. Further studies are needed to show if PT can be a viable

alternative as standalone treatment or as part of combination therapy (e.g.MAD or less invasive

formsofupperairwaysurgery).

101

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Floppy epiglottis during drug-induced sleep endoscopy

executed.Anepiglotticcollapsewas found insix subjectswhoshowedsubstantial improvement in

upperairwaypatencywhenturnedtolateralbodyposition.Objectivemeasurementsalsoshoweda

decrease in percentage of breaths exhibiting an epiglottic collapse (from 66.5% to 12.3%) and an

increase inventilationby45%comparingsupineto lateralbodyposition.Surprisingly,noeffecton

upperairwaycollapsewasfoundinpatientswithtongue-relatedobstruction.7

In another studybyVictores et al. similar resultswere foundwith regard to thepositive effect of

bodypositiononupperairwaypatencyattheleveloftheepiglottis.8Interestingly,Safiruddinetal.

found that lateral head rotation only was also associated with a decreased frequency of a

partial/completecollapseatepiglottislevelcomparedtosupineposition.29

Physiologicalaspects

Azarbarzinetal.analyzedflowcharacteristicscorrelatedwiththepresenceofaFE.Theyfoundthata

FEwasassociatedwith flowfeaturescharacterizedbydiscontinuityand jaggedness.Unfortunately,

changes in body position were not included. 9When trying to understand the pathophysiological

mechanism behind the correlation of body position and the presence of a FE, several hypotheses

couldbetakenintoconsideration.

Firstofall, ithasbeenthoughtthatoropharyngealstructuresrespondtogravitationalforces inthe

upperairway. InastudybySutthiprapapornetal.sevensubjectswereevaluatedbyconebeamCT

while theywere in upright or in supine position. They found that gravity enhancesmovement of

oropharyngeal structures, such as the epiglottis and palatewhen changing fromupright to supine

position.Surprisingly,thehyoidbonedidnotmoveposteriorlybutcaudally.30

Onecouldalsoarguethatalteringbodypositioncouldleadtochangesinthenegativeintrathoracic

pressure, which as a result causes an increase in intraluminal pressure. This could hypothetically

influencethecriticalclosingpressureoftheepiglottis.Unfortunately,noevidenceonthistopicisyet

availableinliterature.

Limitations

Thereareseverallimitationsinthisstudy.First,datawasretrospectivelycollectedusinganinclusion

periodduringwhichnewresultswereavailableshowingthat theeffectof lateralheadrotationon

upperairwaypatencyinPPisnotsimilartobothlateralheadandtrunkposition,incontrasttoNPP.22Consequently,theresultsinPParedescribedeitherusinglateralheadrotationorlateralheadand

trunkposition.Nevertheless,noFEwasfoundinNPPduringlateralheadrotationincontrasttoPP,

whichemphasizesthatlateralheadrotationinNPPiscomparabletolateralheadandtrunkposition

andthataFEisapositiondependentphenomenon.

Second,DISEwas scored according to theVOTE classification system,which is a simplified system

withknownintra-andinterobserverreliability.31Butinthisstudy,DISEwasperformedbyonlyone

endoscopist, clearly describing an epiglottic collapse caused by a complete anterior-posterior

collapseof the tonguebaseorasan isolatedcompleteanterior-posteriorcollapseof theepiglottis

(e.g.FE),which,toouropinion,enhancesintraobserverreliability.

Clinicalrelevance

Currently, treatment inOSApatientswitha FE remains challengingandevidencebased treatment

options inthispopulationare lacking. Inthepast,severalsurgicaltechniquesoftheepiglottishave

been described, which are not without risks. CPAP might even worsen a FE resulting in low

compliance and treatment failure and also MAD treatment is not always successful. It can be

concluded that there isademand forother treatmentoptions inpatientswithaFE.Basedon the

resultsofthisstudy,PTcouldbeapromisingalternativeinpatientswithaFE,despitethefactthat

theymightnotsufferfromPOSA.Itcanbeusedasastandalonetreatment,butduetothefactthata

FEisusuallypartofamultilevelproblemitcanalsobecombinedwithMADorlessinvasiveformsof

upperairwaysurgerylimitingrisksandcomplications.32-35

CONCLUSION

The results of this study indicate that a FE is a position dependent phenomenon, which appears

almostexclusivelyinsupineposition.Despitethisphenomenon,thecorrelationwiththeunderlying

pathophysiologicalmechanisminNPPandPPremainsyetunclear.

Treatment planning in OSA patientswith a FE remains challenging and evidence based treatment

options in this population are lacking. Further studies are needed to show if PT can be a viable

alternative as standalone treatment or as part of combination therapy (e.g.MAD or less invasive

formsofupperairwaysurgery).

102

Chapter 5

REFERENCES

1. Ravesloot M, Van Maanen J, Dun L, De Vries N. The undervalued potential of positional

therapyinposition-dependentsnoringandobstructivesleepapnea—areviewoftheliterature.Sleep

andBreathing.2013;17(1):39-49

2. RaveslootMJ,FrankMH,vanMaanenJP,VerhagenEA,deLangeJ,deVriesN.PositionalOSA

part 2: retrospective cohort analysis with a new classification system (APOC). Sleep Breath.

2016;20(2):881-8

3. CartwrightRD.Effectofsleeppositiononsleepapneaseverity.Sleep.1984;7(2):110-4.

4. Oksenberg A. Positional and non-positional obstructive sleep apnea patients. Sleep Med.

2005;6(4):377-8

5. RichardW, Kox D, den Herder C, LamanM, van Tinteren H, de Vries N. The role of sleep

positioninobstructivesleepapneasyndrome.EurArchOtorhinolaryngol.2006;263(10):946-50

6. MadorMJ, Kufel TJ,MagalangUJ, Rajesh SK,Watwe V, Grant BJ. Prevalence of positional

sleepapneainpatientsundergoingpolysomnography.Chest.2005;128(4):2130-7

7. MarquesM,GentaPR,SandsSA,etal.EffectofSleepingPositiononUpperAirwayPatencyin

Obstructive Sleep Apnea Is Determined by the Pharyngeal Structure Causing Collapse. Sleep.

2017;40(3)

8. VictoresAJ,Hamblin J,Gilbert J,SwitzerC,TakashimaM.Usefulnessofsleependoscopy in

predictingpositionalobstructivesleepapnea.OtolaryngolHeadNeckSurg.2014;150(3):487-93

9. Azarbarzin A, Marques M, Sands SA, et al. Predicting epiglottic collapse in patients with

obstructivesleepapnoea.EurRespirJ.2017;50(3)

10. Verse T, PirsigW.Age-related changes in the epiglottis causing failureof nasal continuous

positiveairwaypressuretherapy.JLaryngolOtol.1999;113(11):1022-5

11. Dedhia RC, Rosen CA, Soose RJ. What is the role of the larynx in adult obstructive sleep

apnea?Laryngoscope.2014;124(4):1029-34

12. ShimohataT,TomitaM,NakayamaH,AizawaN,OzawaT,NishizawaM.Floppyepiglottisasa

contraindicationofCPAPinpatientswithmultiplesystematrophy.Neurology.2011;76(21):1841-2

13. Kent DT, Rogers R, Soose RJ. Drug-Induced Sedation Endoscopy in the Evaluation of OSA

Patients with Incomplete Oral Appliance Therapy Response. Otolaryngol Head Neck Surg.

2015;153(2):302-7

14. CatalfumoFJ,GolzA,WestermanST,GilbertLM,JoachimsHZ,GoldenbergD.Theepiglottis

andobstructivesleepapnoeasyndrome.JLaryngolOtol.1998;112(10):940-3

15. GolzA,GoldenbergD,WestermanST,etal.Laserpartialepiglottidectomyasatreatmentfor

obstructivesleepapneaandlaryngomalacia.AnnOtolRhinolLaryngol.2000;109(12Pt1):1140-5

16. BouroliasC,HajiioannouJ,SobolE,VelegrakisG,HelidonisE.EpiglottisreshapingusingCO2

laser:aminimallyinvasivetechniqueanditspotentapplications.HeadFaceMed.2008;4:15.

17. HeiserC.Advancedtitrationtotreatafloppyepiglottisinselectiveupperairwaystimulation.

Laryngoscope.2016;126Suppl7:S22-4.

18. DeVitoA,CarrascoLlatasM,RaveslootMJ,etal.Europeanpositionpaperondrug-induced

sleependoscopy:2017Update.ClinicalOtolaryngology.2018;43(6):1541-52.

19. Schnider T, Minto C. Pharmacokinetic models of propofol for TCI. Anaesthesia.

2008;63(2):206-06.

20. Schnider TW,Minto CF, Gambus PL, et al. The influence ofmethod of administration and

covariateson thepharmacokineticsofpropofol in adult volunteers.Anesthesiology: The Journalof

theAmericanSocietyofAnesthesiologists.1998;88(5):1170-82.

21. SafiruddinF,Koutsourelakis I,deVriesN.Upperairwaycollapseduringdrug inducedsleep

endoscopy: head rotation in supine position compared with lateral head and trunk position.

EuropeanArchivesofOto-Rhino-Laryngology.2015;272(2):485-88.

22. VonkPE,vandeBeekMJ,RaveslootMJL,deVriesN.Drug-inducedsleependoscopy(DISE):

Newinsightsinlateralheadrotationcomparedtolateralheadandtrunkrotationin(non)positional

obstructivesleepapneapatients.TheLaryngoscope.2018.

23. Kezirian EJ, Hohenhorst W, de Vries N. Drug-induced sleep endoscopy: the VOTE

classification.EurArchOtorhinolaryngol.2011;268(8):1233-36.

24. OksenbergA,SilverbergDS,AronsE,RadwanH.Positionalvsnonpositionalobstructivesleep

apneapatients:anthropomorphic,nocturnalpolysomnographic,andmultiplesleeplatencytestdata.

Chest.1997;112(3):629-39.

25. ItasakaY,MiyazakiS, IshikawaK,TogawaK.The influenceofsleeppositionandobesityon

sleepapnea.PsychiatryClinNeurosci.2000;54(3):340-1.

26. TorreC,CamachoM,LiuSY,HuonLK,CapassoR.Epiglottiscollapseinadultobstructivesleep

apnea:Asystematicreview.Laryngoscope.2016;126(2):515-23.

27. FrankMH,RaveslootMJ,vanMaanenJP,VerhagenE,deLangeJ,deVriesN.PositionalOSA

part 1: Towards a clinical classification system for position-dependent obstructive sleep apnoea.

SleepBreath.2015;19(2):473-80.

28. RaveslootMJ, vanMaanen JP, Dun L, de Vries N. The undervalued potential of positional

therapyinposition-dependentsnoringandobstructivesleepapnea-areviewoftheliterature.Sleep

Breath.2013;17(1):39-49.

29. SafiruddinF,Koutsourelakis I,deVriesN.Analysisof the influenceofhead rotationduring

drug-inducedsleependoscopyinobstructivesleepapnea.TheLaryngoscope.2014;124(9):2195-99.

103

5

Floppy epiglottis during drug-induced sleep endoscopy

REFERENCES

1. Ravesloot M, Van Maanen J, Dun L, De Vries N. The undervalued potential of positional

therapyinposition-dependentsnoringandobstructivesleepapnea—areviewoftheliterature.Sleep

andBreathing.2013;17(1):39-49.

2. RaveslootMJ,FrankMH,vanMaanenJP,VerhagenEA,deLangeJ,deVriesN.PositionalOSA

part 2: retrospective cohort analysis with a new classification system (APOC). Sleep Breath.

2016;20(2):881-8.

3. CartwrightRD.Effectofsleeppositiononsleepapneaseverity.Sleep.1984;7(2):110-4.

4. Oksenberg A. Positional and non-positional obstructive sleep apnea patients. Sleep Med.

2005;6(4):377-8.

5. RichardW, Kox D, den Herder C, LamanM, van Tinteren H, de Vries N. The role of sleep

positioninobstructivesleepapneasyndrome.EurArchOtorhinolaryngol.2006;263(10):946-50.

6. MadorMJ, Kufel TJ,MagalangUJ, Rajesh SK,Watwe V, Grant BJ. Prevalence of positional

sleepapneainpatientsundergoingpolysomnography.Chest.2005;128(4):2130-7.

7. MarquesM,GentaPR,SandsSA,etal.EffectofSleepingPositiononUpperAirwayPatencyin

Obstructive Sleep Apnea Is Determined by the Pharyngeal Structure Causing Collapse. Sleep.

2017;40(3).

8. VictoresAJ,Hamblin J,Gilbert J,SwitzerC,TakashimaM.Usefulnessofsleependoscopy in

predictingpositionalobstructivesleepapnea.OtolaryngolHeadNeckSurg.2014;150(3):487-93.

9. Azarbarzin A, Marques M, Sands SA, et al. Predicting epiglottic collapse in patients with

obstructivesleepapnoea.EurRespirJ.2017;50(3).

10. Verse T, PirsigW.Age-related changes in the epiglottis causing failureof nasal continuous

positiveairwaypressuretherapy.JLaryngolOtol.1999;113(11):1022-5.

11. Dedhia RC, Rosen CA, Soose RJ. What is the role of the larynx in adult obstructive sleep

apnea?Laryngoscope.2014;124(4):1029-34.

12. ShimohataT,TomitaM,NakayamaH,AizawaN,OzawaT,NishizawaM.Floppyepiglottisasa

contraindicationofCPAPinpatientswithmultiplesystematrophy.Neurology.2011;76(21):1841-2.

13. Kent DT, Rogers R, Soose RJ. Drug-Induced Sedation Endoscopy in the Evaluation of OSA

Patients with Incomplete Oral Appliance Therapy Response. Otolaryngol Head Neck Surg.

2015;153(2):302-7.

14. CatalfumoFJ,GolzA,WestermanST,GilbertLM,JoachimsHZ,GoldenbergD.Theepiglottis

andobstructivesleepapnoeasyndrome.JLaryngolOtol.1998;112(10):940-3.

15. GolzA,GoldenbergD,WestermanST,etal.Laserpartialepiglottidectomyasatreatmentfor

obstructivesleepapneaandlaryngomalacia.AnnOtolRhinolLaryngol.2000;109(12Pt1):1140-5.

16. BouroliasC,HajiioannouJ,SobolE,VelegrakisG,HelidonisE.EpiglottisreshapingusingCO2

laser:aminimallyinvasivetechniqueanditspotentapplications.HeadFaceMed.2008;4:15

17. HeiserC.Advancedtitrationtotreatafloppyepiglottisinselectiveupperairwaystimulation.

Laryngoscope.2016;126Suppl7:S22-4

18. DeVitoA,CarrascoLlatasM,RaveslootMJ,etal.Europeanpositionpaperondrug-induced

sleependoscopy:2017Update.ClinicalOtolaryngology.2018;43(6):1541-52

19. Schnider T, Minto C. Pharmacokinetic models of propofol for TCI. Anaesthesia.

2008;63(2):206-06

20. Schnider TW,Minto CF, Gambus PL, et al. The influence ofmethod of administration and

covariateson thepharmacokineticsofpropofol in adult volunteers.Anesthesiology: The Journalof

theAmericanSocietyofAnesthesiologists.1998;88(5):1170-82

21. SafiruddinF,Koutsourelakis I,deVriesN.Upperairwaycollapseduringdrug inducedsleep

endoscopy: head rotation in supine position compared with lateral head and trunk position.

EuropeanArchivesofOto-Rhino-Laryngology.2015;272(2):485-88

22. VonkPE,vandeBeekMJ,RaveslootMJL,deVriesN.Drug-inducedsleependoscopy(DISE):

Newinsightsinlateralheadrotationcomparedtolateralheadandtrunkrotationin(non)positional

obstructivesleepapneapatients.TheLaryngoscope.2018

23. Kezirian EJ, Hohenhorst W, de Vries N. Drug-induced sleep endoscopy: the VOTE

classification.EurArchOtorhinolaryngol.2011;268(8):1233-36

24. OksenbergA,SilverbergDS,AronsE,RadwanH.Positionalvsnonpositionalobstructivesleep

apneapatients:anthropomorphic,nocturnalpolysomnographic,andmultiplesleeplatencytestdata.

Chest.1997;112(3):629-39

25. ItasakaY,MiyazakiS, IshikawaK,TogawaK.The influenceofsleeppositionandobesityon

sleepapnea.PsychiatryClinNeurosci.2000;54(3):340-1

26. TorreC,CamachoM,LiuSY,HuonLK,CapassoR.Epiglottiscollapseinadultobstructivesleep

apnea:Asystematicreview.Laryngoscope.2016;126(2):515-23

27. FrankMH,RaveslootMJ,vanMaanenJP,VerhagenE,deLangeJ,deVriesN.PositionalOSA

part 1: Towards a clinical classification system for position-dependent obstructive sleep apnoea.

SleepBreath.2015;19(2):473-80

28. RaveslootMJ, vanMaanen JP, Dun L, de Vries N. The undervalued potential of positional

therapyinposition-dependentsnoringandobstructivesleepapnea-areviewoftheliterature.Sleep

Breath.2013;17(1):39-49

29. SafiruddinF,Koutsourelakis I,deVriesN.Analysisof the influenceofhead rotationduring

drug-inducedsleependoscopyinobstructivesleepapnea.TheLaryngoscope.2014;124(9):2195-99

104

Chapter 5

30. Sutthiprapaporn P, Tanimoto K, Ohtsuka M, Nagasaki T, Iida Y, Katsumata A. Positional

changes of oropharyngeal structures due to gravity in the upright and supine positions.

DentomaxillofacialRadiology.2008;37(3):130-35

31. VroegopAV, VandervekenOM,Wouters K, et al.Observer variation in drug-induced sleep

endoscopy: experienced versus nonexperienced ear, nose, and throat surgeons. Sleep.

2013;36(6):947-53

32. Benoist LB, Verhagen M, Torensma B, van Maanen JP, de Vries N. Positional therapy in

patientswith residual positional obstructive sleep apnea after upper airway surgery.SleepBreath.

2016

33. vanMaanen JP, de VriesN. Long-term effectiveness and compliance of positional therapy

with the sleep position trainer in the treatment of positional obstructive sleep apnea syndrome.

Sleep.2014;37(7):1209-15

34. vanMaanenJP,MeesterKA,DunLN,etal.Thesleeppositiontrainer:anewtreatmentfor

positionalobstructivesleepapnoea.SleepandBreathing.2013;17(2):771-79

35. RaveslootM,WhiteD,HeinzerR,OksenbergA,Pépin J. Efficacyof theNewGenerationof

Devices for Positional Therapy for Patients with Positional Obstructive Sleep Apnea: A Systematic

Review of the Literature and Meta-Analysis. Journal of clinical sleep medicine: JCSM: official

publicationoftheAmericanAcademyofSleepMedicine.2017

6Short-termresultsofupperairwaystimulation in obstructive sleepapnea patients: the AmsterdamexperienceP.E.Vonk,M.J.L.Ravesloot,J.P.vanMaanen,N.deVriesSubmitted

6Short-termresultsofupperairwaystimulation in obstructive sleepapnea patients: the AmsterdamexperienceP.E.Vonk,M.J.L.Ravesloot,J.P.vanMaanen,N.deVriesSubmitted

30. Sutthiprapaporn P, Tanimoto K, Ohtsuka M, Nagasaki T, Iida Y, Katsumata A. Positional

changes of oropharyngeal structures due to gravity in the upright and supine positions.

DentomaxillofacialRadiology.2008;37(3):130-35.

31. VroegopAV, VandervekenOM,Wouters K, et al.Observer variation in drug-induced sleep

endoscopy: experienced versus nonexperienced ear, nose, and throat surgeons. Sleep.

2013;36(6):947-53.

32. Benoist LB, Verhagen M, Torensma B, van Maanen JP, de Vries N. Positional therapy in

patientswith residual positional obstructive sleep apnea after upper airway surgery.SleepBreath.

2016.

33. vanMaanen JP, de VriesN. Long-term effectiveness and compliance of positional therapy

with the sleep position trainer in the treatment of positional obstructive sleep apnea syndrome.

Sleep.2014;37(7):1209-15.

34. vanMaanenJP,MeesterKA,DunLN,etal.Thesleeppositiontrainer:anewtreatmentfor

positionalobstructivesleepapnoea.SleepandBreathing.2013;17(2):771-79.

35. RaveslootM,WhiteD,HeinzerR,OksenbergA,Pépin J. Efficacyof theNewGenerationof

Devices for Positional Therapy for Patients with Positional Obstructive Sleep Apnea: A Systematic

Review of the Literature and Meta-Analysis. Journal of clinical sleep medicine: JCSM: official

publicationoftheAmericanAcademyofSleepMedicine.2017.

6Short-termresultsofupperairwaystimulation in obstructive sleepapnea patients: the AmsterdamexperienceP.E.Vonk,M.J.L.Ravesloot,J.P.vanMaanen,N.deVriesSubmitted

6Short-termresultsofupperairwaystimulation in obstructive sleepapnea patients: the AmsterdamexperienceP.E.Vonk,M.J.L.Ravesloot,J.P.vanMaanen,N.deVriesSubmitted

6Short-termresultsofupperairwaystimulation in obstructive sleepapnea patients: the AmsterdamexperienceP.E.Vonk,M.J.L.Ravesloot,J.P.vanMaanen,N.deVriesSubmitted

106

Chapter 6

ABSTRACT

Objectives: 1) To retrospectively analyse single-centre results in means of surgical success,

respiratoryoutcomesandadverseeventsaftershort-termfollow-upinobstructivesleepapnea(OSA)

patients treated with upper airway stimulation (UAS). 2) To evaluate the correlation between

preoperativedrug-inducedsleependoscopy(DISE)findingsandsurgicalsuccess.

Material andmethods: retrospective descriptive cohort study, including a consecutive series of

OSApatientsundergoingUASimplantation.

Results: Forty-four patients were included. The total median AHI and oxygen desaturation index

significantly decreased from37.6 (30.4; 43.4) events/h to 8.3 (5.3; 12.0) events/h (p < 0.001) and

37.1 (28.4; 42.6) events/h to 15.9 (11.1; 21.6) events/h. Surgical success was 88.6% and did not

significantly differ between patients with or without a complete collapse at retropalatal level

(p=0.784).Themostcommontherapy-relatedadverseeventreportedwas(temporary)stimulation-

relateddiscomfort.

Conclusions: UAS has proven to be an effective and safe treatment in OSA patients with CPAP

intoleranceorfailure.Therewasnosignificantdifferenceinsurgicaloutcomebetweenpatientswith

atonguebasecollapsewithorwithoutacompleteanteroposteriorcollapseatthelevelofthepalate.

Keywords:obstructivesleepapnea,upperairwaystimulation,hypoglossalnervestimulation,drug-

inducedsleependoscopy

INTRODUCTION

Obstructive sleep apnea (OSA) is the most prevalent sleep-related breathing disorder caused by

episodesofpartialorcompleteobstructionoftheupperairwayduringsleep.Currently,continuous

positive airway pressure (CPAP) is the gold-standard therapy formoderate to severe OSA, but its

non-compliancerateisoftenhighduetopoortoleranceandlowacceptance.1

AlternativetreatmentstoCPAPincludemandibularadvancementdevices(MAD),positionaltherapy

(PT)orupperairwaysurgery.The latteraimsto improveupperairwaypatency inordertoprevent

obstruction during sleep. Conventional surgical approaches to the upper airway for treatment for

moderate to severe OSA have mediocre results, are often painful, with potential serious

complicationsandsideeffects.Therefore,newsurgical techniques,whicharepatient friendly, safe

andhaveahigh surgical success, are inhighdemand,especially in severeOSApatientswithCPAP

failure.

A recent development is hypoglossal nerve stimulation, also referred to as selective upper airway

stimulation(UAS).Byusingaunilateralstimulation,selectivefibres,whicharemainlyinnervatingthe

tongue protrusors, are stimulated during every breathing cycle. Furthermore, by including the

cervical spine nerve (C1) the hyoid bone is displaced in an anterosuperior direction during

stimulation.Althoughstimulationactivatesthetongueprotrusors,previousstudieshavealsoshown

thattheeffectofUASisnotlimitedtothelevelofthetonguebase,butalsoimprovesupperairway

patency at the level of the palate. It has been suggested that this multilevel effect is caused by

palatoglossalcoupling.2

UAShasshowntobeeffectiveinreducingobjectiverespiratoryparameters,suchastheAHI,oxygen

desaturation index (ODI) and subjective symptoms related to OSA, such as excessive daytime

sleepiness. Adequate patient selection is of paramount importance. Previous studies have shown

thatUAS iseffective inpatientswithanAHI≥15events/hand≤65events/h,aBMI≤32kg/m2,a

non-supineAHI≥10events/h, less than25%centralapneasandabsenceof concentric collapseat

palatal level during drug-induced sleep endoscopy (DISE). 3-13 Some studies also show a good

responseinpatientswithaBMI≤35kg/m2.4,7

TheUSFoodandDrugAdministration(FDA)approvedthisnewformofupperairwaysurgeryinApril

2014. During the first years after FDA approval, this procedure was only performed in cases of

patient-specific reimbursementor in a commercial setting. In addition, sinceApril 2017,UAS for a

selective group of OSA patients with an AHI between 30 and 50 events/h and CPAP failure, or

107

6

Short-term results of upper airway stimulation in obstructive sleep apnea patients

ABSTRACT

Objectives: 1) To retrospectively analyse single-centre results in means of surgical success,

respiratoryoutcomesandadverseeventsaftershort-termfollow-upinobstructivesleepapnea(OSA)

patients treated with upper airway stimulation (UAS). 2) To evaluate the correlation between

preoperativedrug-inducedsleependoscopy(DISE)findingsandsurgicalsuccess.

Material andmethods: retrospective descriptive cohort study, including a consecutive series of

OSApatientsundergoingUASimplantation.

Results: Forty-four patients were included. The total median AHI and oxygen desaturation index

significantly decreased from37.6 (30.4; 43.4) events/h to 8.3 (5.3; 12.0) events/h (p < 0.001) and

37.1 (28.4; 42.6) events/h to 15.9 (11.1; 21.6) events/h. Surgical success was 88.6% and did not

significantly differ between patients with or without a complete collapse at retropalatal level

(p=0.784).Themostcommontherapy-relatedadverseeventreportedwas(temporary)stimulation-

relateddiscomfort.

Conclusions: UAS has proven to be an effective and safe treatment in OSA patients with CPAP

intoleranceorfailure.Therewasnosignificantdifferenceinsurgicaloutcomebetweenpatientswith

atonguebasecollapsewithorwithoutacompleteanteroposteriorcollapseatthelevelofthepalate.

Keywords:obstructivesleepapnea,upperairwaystimulation,hypoglossalnervestimulation,drug-

inducedsleependoscopy

INTRODUCTION

Obstructive sleep apnea (OSA) is the most prevalent sleep-related breathing disorder caused by

episodesofpartialorcompleteobstructionoftheupperairwayduringsleep.Currently,continuous

positive airway pressure (CPAP) is the gold-standard therapy formoderate to severe OSA, but its

non-compliancerateisoftenhighduetopoortoleranceandlowacceptance.1

AlternativetreatmentstoCPAPincludemandibularadvancementdevices(MAD),positionaltherapy

(PT)orupperairwaysurgery.The latteraimsto improveupperairwaypatency inordertoprevent

obstruction during sleep. Conventional surgical approaches to the upper airway for treatment for

moderate to severe OSA have mediocre results, are often painful, with potential serious

complicationsandsideeffects.Therefore,newsurgical techniques,whicharepatient friendly, safe

andhaveahigh surgical success, are inhighdemand,especially in severeOSApatientswithCPAP

failure.

A recent development is hypoglossal nerve stimulation, also referred to as selective upper airway

stimulation(UAS).Byusingaunilateralstimulation,selectivefibres,whicharemainlyinnervatingthe

tongue protrusors, are stimulated during every breathing cycle. Furthermore, by including the

cervical spine nerve (C1) the hyoid bone is displaced in an anterosuperior direction during

stimulation.Althoughstimulationactivatesthetongueprotrusors,previousstudieshavealsoshown

thattheeffectofUASisnotlimitedtothelevelofthetonguebase,butalsoimprovesupperairway

patency at the level of the palate. It has been suggested that this multilevel effect is caused by

palatoglossalcoupling.2

UAShasshowntobeeffectiveinreducingobjectiverespiratoryparameters,suchastheAHI,oxygen

desaturation index (ODI) and subjective symptoms related to OSA, such as excessive daytime

sleepiness. Adequate patient selection is of paramount importance. Previous studies have shown

thatUAS iseffective inpatientswithanAHI≥15events/hand≤65events/h,aBMI≤32kg/m2,a

non-supineAHI≥10events/h, less than25%centralapneasandabsenceof concentric collapseat

palatal level during drug-induced sleep endoscopy (DISE). 3-13 Some studies also show a good

responseinpatientswithaBMI≤35kg/m2.4,7

TheUSFoodandDrugAdministration(FDA)approvedthisnewformofupperairwaysurgeryinApril

2014. During the first years after FDA approval, this procedure was only performed in cases of

patient-specific reimbursementor in a commercial setting. In addition, sinceApril 2017,UAS for a

selective group of OSA patients with an AHI between 30 and 50 events/h and CPAP failure, or

108

Chapter 6

intolerance,hasbeenreimbursedaspartofthebasichealthcaresystemintheNetherlandsaswell.

Currently, this surgicalprocedure isonlyperformed in twocentres in theNetherlands.Oneof the

twocentresisOLVG,Amsterdam.Theprimaryaimofthisstudywastoretrospectivelyanalysesingle-

centre results inmeans of surgical success, respiratory outcomes and adverse events after short-

termfollow-upinOSApatientstreatedwithUAS.ThesecondaimwastodescribepreoperativeDISE

findingsandevaluatewhetherpatientswithanisolatedtonguebasecollapsepriortosurgeryhada

higherchanceofsurgicalsuccessincomparisontoOSApatientswithbothacompletecollapseofthe

tonguebaseandatretropalatallevel.

METHODS

Studyparticipants

WeperformedaretrospectivedescriptivecohortstudyincludingaconsecutiveseriesofOSApatients

undergoing UAS at the Department of Otorhinolaryngology Head and Neck Surgery, OLVG,

Amsterdam, the Netherlands between January 2017 and April 2019. Patients were excluded if

preoperativeorpostoperativepolysomnography(PSG)datawerenotavailable.

ThemaincriteriaforimplantationoftheUASsystemwereanAHI≥15events/hand≤65events/h,a

centralapneaindex<25%ofthetotalAHI,anon-supineAHI<10eventsperhour,aBMI<32kg/m2,

CPAPfailureorintolerance,andtheabsenceofacompleteconcentriccollapse(CCC)atthelevelof

thevelumobservedduringDISE.

DISEprocedureandclassificationsystem

DISEwasperformedbyoneexperiencedENT(PV)resident inaquietoutpatientendoscopysetting

usingpropofol,toevaluatesurgicaltreatmentoptions.Sedationandmonitoringofbloodpressure,

electrocardiogram and oxygen levels was managed by a trained nurse anaesthesist. The level of

sedation was controlled by a target controlled infusion pump using the methods described by

Schnideretal.tocalculatetheeffectivedose.14,15Priortotheintravenous(IV)infusionofpropofol,

2cc lidocainewasgiven IVand in themajorityofpatients glycopyrrolate (Robinul)wasgiven IV to

preventmucosalhypersecretion.

Toreportontheanatomicalstructurescausingupperairwaycollapse,theVOTEclassificationsystem

wasused.TheVOTEclassificationsystemdistinguishesbetweenfourdifferentlevelsandstructures

thatmaybe involved inupperairwaycollapse, i.e.velum(V),oropharynx (O), tonguebase (T)and

epiglottis(E).Threecategorieswereusedtodefinethedegreeofobstruction:noobstruction,witha

collapse of 50% and less; a partial obstructionwith a collapse between 50-75% and typicallywith

vibration;oracompletecollapseinwhichacollapsewasfoundthatcomprisesmorethan75%ofthe

upper airway lumen. Depending on the different site(s) involved in upper airway obstruction, the

configurationmaybeanteroposterior,lateralorconcentric.16

Implantation,activationandtitration

Approximatelyonemonthafter implantationthedevicewasactivatedduringaconsultationat the

outpatientclinicofthedepartmentofOtorhinolaryngology-HeadandNeckSurgery.Afteractivation

of thedevice, patients gradually increase the stimulation amplitude tooptimizeboth comfort and

subjectiveeffectiveness.Twomonthspostoperatively,apost-titrationvisittookplaceconsistingofa

consultationandanin-labtitrationusingPSGtooptimizetherapeuticsettings.Althoughthemajority

ofpatientsonlyneededonetitrationnight,asecondtitrationnightwasindicatedwhentheclinical

laboratory technician was not able to titrate the therapy to an effective setting during the first

titrationnight.Thiscouldbedueto,forexample,device-relatedissuesorlowsleepefficiency,which

made sufficient titration not possible. When a second titration night was needed, data collected

during this night was used in our analysis. Since respiratory parameters were collected during a

titrationPSG,theresultsusedwerefromtheportionofsleepwhentherapywasundertherapeutic

settings,alsocalledthetreatmentAHI.

Ethicalconsiderations

Allproceduresfollowedwereinaccordancewiththeethicalstandardsoftheresponsiblecommittee

onhumanexperimentationandwiththeDeclarationofHelsinkiof1975.Dataonstudysubjectswas

collected and stored encoded to protect personal information. For this type of study informed

consentwasnotrequired.

Definitions

SurgicalsuccessisdefinedaccordingtoSher’scriteria:areductioninpreoperativeAHIofmorethan

50% and a postoperative AHI < 20 events/h. 17 Patientswho do notmeet the criteria for surgical

successafter(advanced)titration,arefurtherreferredtoasnon-responders.

Obstructive respiratory events are analyzed according to the AASM criteria. An obstructive

respiratoryeventinadultsisscoredasanapneaifthereisadropinthepeaksignalexcursionby≥

90%withadurationofatleast≥10seconds.Ahypopneaisdefinedasadecreaseofairflowby≥30%

duringaperiodof≥10secondscombinedwithanoxygendesaturationof≥3%.18

109

6

Short-term results of upper airway stimulation in obstructive sleep apnea patients

intolerance,hasbeenreimbursedaspartofthebasichealthcaresystemintheNetherlandsaswell.

Currently, this surgicalprocedure isonlyperformed in twocentres in theNetherlands.Oneof the

twocentresisOLVG,Amsterdam.Theprimaryaimofthisstudywastoretrospectivelyanalysesingle-

centre results inmeans of surgical success, respiratory outcomes and adverse events after short-

termfollow-upinOSApatientstreatedwithUAS.ThesecondaimwastodescribepreoperativeDISE

findingsandevaluatewhetherpatientswithanisolatedtonguebasecollapsepriortosurgeryhada

higherchanceofsurgicalsuccessincomparisontoOSApatientswithbothacompletecollapseofthe

tonguebaseandatretropalatallevel.

METHODS

Studyparticipants

WeperformedaretrospectivedescriptivecohortstudyincludingaconsecutiveseriesofOSApatients

undergoing UAS at the Department of Otorhinolaryngology Head and Neck Surgery, OLVG,

Amsterdam, the Netherlands between January 2017 and April 2019. Patients were excluded if

preoperativeorpostoperativepolysomnography(PSG)datawerenotavailable.

ThemaincriteriaforimplantationoftheUASsystemwereanAHI≥15events/hand≤65events/h,a

centralapneaindex<25%ofthetotalAHI,anon-supineAHI<10eventsperhour,aBMI<32kg/m2,

CPAPfailureorintolerance,andtheabsenceofacompleteconcentriccollapse(CCC)atthelevelof

thevelumobservedduringDISE.

DISEprocedureandclassificationsystem

DISEwasperformedbyoneexperiencedENT(PV)resident inaquietoutpatientendoscopysetting

usingpropofol,toevaluatesurgicaltreatmentoptions.Sedationandmonitoringofbloodpressure,

electrocardiogram and oxygen levels was managed by a trained nurse anaesthesist. The level of

sedation was controlled by a target controlled infusion pump using the methods described by

Schnideretal.tocalculatetheeffectivedose.14,15Priortotheintravenous(IV)infusionofpropofol,

2cc lidocainewasgiven IVand in themajorityofpatients glycopyrrolate (Robinul)wasgiven IV to

preventmucosalhypersecretion.

Toreportontheanatomicalstructurescausingupperairwaycollapse,theVOTEclassificationsystem

wasused.TheVOTEclassificationsystemdistinguishesbetweenfourdifferentlevelsandstructures

thatmaybe involved inupperairwaycollapse, i.e.velum(V),oropharynx (O), tonguebase (T)and

epiglottis(E).Threecategorieswereusedtodefinethedegreeofobstruction:noobstruction,witha

collapse of 50% and less; a partial obstructionwith a collapse between 50-75% and typicallywith

vibration;oracompletecollapseinwhichacollapsewasfoundthatcomprisesmorethan75%ofthe

upper airway lumen. Depending on the different site(s) involved in upper airway obstruction, the

configurationmaybeanteroposterior,lateralorconcentric.16

Implantation,activationandtitration

Approximatelyonemonthafter implantationthedevicewasactivatedduringaconsultationat the

outpatientclinicofthedepartmentofOtorhinolaryngology-HeadandNeckSurgery.Afteractivation

of thedevice, patients gradually increase the stimulation amplitude tooptimizeboth comfort and

subjectiveeffectiveness.Twomonthspostoperatively,apost-titrationvisittookplaceconsistingofa

consultationandanin-labtitrationusingPSGtooptimizetherapeuticsettings.Althoughthemajority

ofpatientsonlyneededonetitrationnight,asecondtitrationnightwasindicatedwhentheclinical

laboratory technician was not able to titrate the therapy to an effective setting during the first

titrationnight.Thiscouldbedueto,forexample,device-relatedissuesorlowsleepefficiency,which

made sufficient titration not possible. When a second titration night was needed, data collected

during this night was used in our analysis. Since respiratory parameters were collected during a

titrationPSG,theresultsusedwerefromtheportionofsleepwhentherapywasundertherapeutic

settings,alsocalledthetreatmentAHI.

Ethicalconsiderations

Allproceduresfollowedwereinaccordancewiththeethicalstandardsoftheresponsiblecommittee

onhumanexperimentationandwiththeDeclarationofHelsinkiof1975.Dataonstudysubjectswas

collected and stored encoded to protect personal information. For this type of study informed

consentwasnotrequired.

Definitions

SurgicalsuccessisdefinedaccordingtoSher’scriteria:areductioninpreoperativeAHIofmorethan

50% and a postoperative AHI < 20 events/h. 17 Patientswho do notmeet the criteria for surgical

successafter(advanced)titration,arefurtherreferredtoasnon-responders.

Obstructive respiratory events are analyzed according to the AASM criteria. An obstructive

respiratoryeventinadultsisscoredasanapneaifthereisadropinthepeaksignalexcursionby≥

90%withadurationofatleast≥10seconds.Ahypopneaisdefinedasadecreaseofairflowby≥30%

duringaperiodof≥10secondscombinedwithanoxygendesaturationof≥3%.18

110

Chapter 6

Statisticalanalysis

Statistical analysiswasperformedusing SPSS (version22), SPSS Inc., Chicago, IL.Quantitativedata

werereportedasmeanandstandarddeviation(SD)orasmedianand(Q1,Q3)whennotnormally

distributed.TocomparepreoperativeandpostoperativePSGvalues,apairedTtestwasperformed

in case of normally distributed data. AWilcoxon signed rank testwas appliedwhen datawas not

normally distributed. To identify a possible correlation between surgical success and collapse

patternsobservedduringDISE,patientsweredividedintotwosubgroups.Thefirstgroupconsisted

of patientswith a complete collapse of the tongue basewith orwithout a partial collapse of the

palate.Inthesecondsubgroup,patientswithbothapartialorcompletecollapseofthetonguebase,

and a complete collapse of the palate were included. To compare the surgical success in both

subgroupsachi-squaredtestwasapplied.Apvalueof<0.05wasconsideredto indicatestatistical

significance.

RESULTS

Baselinecharacteristics

In total, 47 patients underwent UAS implantation between January 2017 and April 2019. Two

patientsdidnotwant toundergoa titrationnightand inonepatienta titrationnightwasnot yet

performedduetoadelayedhealingprocess.Therefore,theresultsof44patientswereincludedfor

analysis.Thirty-eightpatientsweremale(86.4%).Themeanagewas58.5±9.6yearsoldwithamean

BMI of 27.2 ± 2.4 kg/m2. Patients had a preoperativemedianAHI of 37.6 (30.4; 43.4) events/h, a

mediansupineAHIof45.8 (34.1;65.0)events/handamediannon-supineAHIof26.2 (17.5;35.9)

events/h.Thepercentageoftotalsleepingtime(TST)insupinepositionwas26.9%(910.2;51.2)and

themedian oxygen desaturation index (ODI, ≥3%)was 37.1 (28.4; 42.6) events/h. An overview of

baselinecharacteristicscanbefoundintable1.

Table1.Baselinecharacteristics

Total

N=44

Gender(M/F) 38/6

Age(years) 58.5±9.6

BMI(kg/m2) 27.2±2.4

AHI(events/h) 37.6(30.4;43.4)*

ODI(events/h,≥3%) 37.1(28.4;42.6)*

Datapresentedasmean±SDor*median(Q1;Q3)

BMIbodymassindex,AHIapnea-hypopneaindex,ODIoxygendesaturationindex

PreoperativeandpostoperativeUASoutcomes

Respiratoryparameters

The total median AHI significantly decreased from 37.6 (30.4; 43.4) events/h to 8.3 (5.3; 12.0)

events/h,pvalue<0.001.BoththesupineAHIandthenon-supinesignificantlydecreasedfrom45.8

(34.1; 65.0) events/h to15.4 (7.2; 27.8) events/hand26.2 (17.5;35.9) events/h to5.2 (2.4; 10.0),

respectively.Alsoasignificantreduction inODI from37.1(28.4;42.6)events/hto15.9 (11.1;21.6)

events/h, and significant increase in theminimumO2was found.Anoverviewofpreoperativeand

postoperative PSG parameters can be found in table 2. Figure 1 and 2 provide a boxplot of the

preoperativeAHIvs.thetreatmentAHIandODIvs.treatmentODI.

111

6

Short-term results of upper airway stimulation in obstructive sleep apnea patients

Statisticalanalysis

Statistical analysiswasperformedusing SPSS (version22), SPSS Inc., Chicago, IL.Quantitativedata

werereportedasmeanandstandarddeviation(SD)orasmedianand(Q1,Q3)whennotnormally

distributed.TocomparepreoperativeandpostoperativePSGvalues,apairedTtestwasperformed

in case of normally distributed data. AWilcoxon signed rank testwas appliedwhen datawas not

normally distributed. To identify a possible correlation between surgical success and collapse

patternsobservedduringDISE,patientsweredividedintotwosubgroups.Thefirstgroupconsisted

of patientswith a complete collapse of the tongue basewith orwithout a partial collapse of the

palate.Inthesecondsubgroup,patientswithbothapartialorcompletecollapseofthetonguebase,

and a complete collapse of the palate were included. To compare the surgical success in both

subgroupsachi-squaredtestwasapplied.Apvalueof<0.05wasconsideredto indicatestatistical

significance.

RESULTS

Baselinecharacteristics

In total, 47 patients underwent UAS implantation between January 2017 and April 2019. Two

patientsdidnotwant toundergoa titrationnightand inonepatienta titrationnightwasnot yet

performedduetoadelayedhealingprocess.Therefore,theresultsof44patientswereincludedfor

analysis.Thirty-eightpatientsweremale(86.4%).Themeanagewas58.5±9.6yearsoldwithamean

BMI of 27.2 ± 2.4 kg/m2. Patients had a preoperativemedianAHI of 37.6 (30.4; 43.4) events/h, a

mediansupineAHIof45.8 (34.1;65.0)events/handamediannon-supineAHIof26.2 (17.5;35.9)

events/h.Thepercentageoftotalsleepingtime(TST)insupinepositionwas26.9%(910.2;51.2)and

themedian oxygen desaturation index (ODI, ≥3%)was 37.1 (28.4; 42.6) events/h. An overview of

baselinecharacteristicscanbefoundintable1.

Table1.Baselinecharacteristics

Total

N=44

Gender(M/F) 38/6

Age(years) 58.5±9.6

BMI(kg/m2) 27.2±2.4

AHI(events/h) 37.6(30.4;43.4)*

ODI(events/h,≥3%) 37.1(28.4;42.6)*

Datapresentedasmean±SDor*median(Q1;Q3)

BMIbodymassindex,AHIapnea-hypopneaindex,ODIoxygendesaturationindex

PreoperativeandpostoperativeUASoutcomes

Respiratoryparameters

The total median AHI significantly decreased from 37.6 (30.4; 43.4) events/h to 8.3 (5.3; 12.0)

events/h,pvalue<0.001.BoththesupineAHIandthenon-supinesignificantlydecreasedfrom45.8

(34.1; 65.0) events/h to15.4 (7.2; 27.8) events/hand26.2 (17.5;35.9) events/h to5.2 (2.4; 10.0),

respectively.Alsoasignificantreduction inODI from37.1(28.4;42.6)events/hto15.9 (11.1;21.6)

events/h, and significant increase in theminimumO2was found.Anoverviewofpreoperativeand

postoperative PSG parameters can be found in table 2. Figure 1 and 2 provide a boxplot of the

preoperativeAHIvs.thetreatmentAHIandODIvs.treatmentODI.

112

Chapter 6

Table2.PreoperativeandpostoperativePSGvalues

Preoperative Postoperative pvalue

Total

N=44

Total

N=44

AHI

(events/h)

37.6

(30.4;43.4)

8.3

(5.3;12.0)

<0.001*

ObstructiveAI

(events/h)

11.8

(2.7;18.9)

0.8

(0.0;2.2)

<0.001*

SupineAHI

(events/h)

45.8

(34.1;65.0)

15.4

(7.2;27.8)

<0.001*

Non-supineAHI

(events/h)

26.2

(17.5;35.9)

5.2

(2.4;10.0)

<0.001*

%TSTinsupine 26.9

(10.2;51.2)

11.9

(0.0;41.3)

0.021*

MinimumO2(%) 84.0

(81.0;87.0)

88.0

(87.0;90.0)

<0.001*

ODI

(events/h,≥3%)

37.1

(28.4;42.6)

15.9

(11.3;21.6)

<0.001*

Datapresentedasmedian(Q1;Q3)

*pvalue<0.05(Wilcoxonsignedranktest)

PSG polysomnography, AHI apnea-hypopnea index, AI apnea index, TST total sleeping time, ODI

oxygendesaturationindex(≥3%)

Figure1.BoxplotofthepreoperativeandtreatmentAHI

AHIapnea-hypopneaindex

*outlier

113

6

Short-term results of upper airway stimulation in obstructive sleep apnea patients

Table2.PreoperativeandpostoperativePSGvalues

Preoperative Postoperative pvalue

Total

N=44

Total

N=44

AHI

(events/h)

37.6

(30.4;43.4)

8.3

(5.3;12.0)

<0.001*

ObstructiveAI

(events/h)

11.8

(2.7;18.9)

0.8

(0.0;2.2)

<0.001*

SupineAHI

(events/h)

45.8

(34.1;65.0)

15.4

(7.2;27.8)

<0.001*

Non-supineAHI

(events/h)

26.2

(17.5;35.9)

5.2

(2.4;10.0)

<0.001*

%TSTinsupine 26.9

(10.2;51.2)

11.9

(0.0;41.3)

0.021*

MinimumO2(%) 84.0

(81.0;87.0)

88.0

(87.0;90.0)

<0.001*

ODI

(events/h,≥3%)

37.1

(28.4;42.6)

15.9

(11.3;21.6)

<0.001*

Datapresentedasmedian(Q1;Q3)

*pvalue<0.05(Wilcoxonsignedranktest)

PSG polysomnography, AHI apnea-hypopnea index, AI apnea index, TST total sleeping time, ODI

oxygendesaturationindex(≥3%)

Figure1.BoxplotofthepreoperativeandtreatmentAHI

AHIapnea-hypopneaindex

*outlier

114

Chapter 6

Figure2.BoxplotofpreoperativeandtreatmentODI

ODIoxygendesaturationindex(≥3%)

*outlier

Surgicalsuccess

The surgical success in our study population was 88.6% (N=39). Reasons for not meeting Sher’s

criteriaforsurgicalsuccesswerean(temporary)increaseofmixedandcentralapneas(N=1)andthe

inability toperforma sufficient titrationdue to frequentawakening causedby the strengthof the

stimulation (N=3). In one patient proper titration of the therapy was not yet possible due to

neuropraxiaofthehypoglossalnerveafterapostoperativebleedingintheareaoftheneckincision.

PreoperativeDISEfindings

InallpatientsacompleteanteroposteriorcollapseofthetonguebasewasobservedduringDISE.In

43patientsanadditionalpartialcollapse(N=9)orcompletecollapse(N=33)atthelevelofthevelum

wasobserved.Anisolatedtonguebasecollapsewasfoundinonlyonepatient.

Inthemajorityofpatientswithanepiglotticcollapse,thiswassecondarytoacompletecollapseof

the tongue base. A floppy epiglottis was present in five patients. A partial or complete lateral

collapseat the levelof theoropharynxwas lesscommon.Adetailedoverviewofcollapsepatterns

canbefoundintable3.

Table3.PreoperativeDISEfindings

Level Configuration Supineposition

N=44 Nocollapse

<50%

Partialcollapse

50-75%

Complete

collapse

>75%

Velum A-P 2 9 33

Oropharynx Lateral 33 10 1

Tonguebase A-P 0 0 44

Epiglottis A-P 2 4 36

Lateral 0 1 1

DISEdrug-inducedsleependoscopy,A-Pantero-posterior

115

6

Short-term results of upper airway stimulation in obstructive sleep apnea patients

Figure2.BoxplotofpreoperativeandtreatmentODI

ODIoxygendesaturationindex(≥3%)

*outlier

Surgicalsuccess

The surgical success in our study population was 88.6% (N=39). Reasons for not meeting Sher’s

criteriaforsurgicalsuccesswerean(temporary)increaseofmixedandcentralapneas(N=1)andthe

inability toperforma sufficient titrationdue to frequentawakening causedby the strengthof the

stimulation (N=3). In one patient proper titration of the therapy was not yet possible due to

neuropraxiaofthehypoglossalnerveafterapostoperativebleedingintheareaoftheneckincision.

PreoperativeDISEfindings

InallpatientsacompleteanteroposteriorcollapseofthetonguebasewasobservedduringDISE.In

43patientsanadditionalpartialcollapse(N=9)orcompletecollapse(N=33)atthelevelofthevelum

wasobserved.Anisolatedtonguebasecollapsewasfoundinonlyonepatient.

Inthemajorityofpatientswithanepiglotticcollapse,thiswassecondarytoacompletecollapseof

the tongue base. A floppy epiglottis was present in five patients. A partial or complete lateral

collapseat the levelof theoropharynxwas lesscommon.Adetailedoverviewofcollapsepatterns

canbefoundintable3.

Table3.PreoperativeDISEfindings

Level Configuration Supineposition

N=44 Nocollapse

<50%

Partialcollapse

50-75%

Complete

collapse

>75%

Velum A-P 2 9 33

Oropharynx Lateral 33 10 1

Tonguebase A-P 0 0 44

Epiglottis A-P 2 4 36

Lateral 0 1 1

DISEdrug-inducedsleependoscopy,A-Pantero-posterior

116

Chapter 6

Aspreviouslymentioned,33patientshadacompletecollapseatmultiplelevelsintheupperairway

consistingofacompleteanteroposteriorcollapseof thepalateand tonguebase.Whencomparing

differences in surgicaloutcomebetweenpatientswitha completemultilevel collapseandpatients

with an anteroposterior tongue base collapsewith orwithout a partial collapse of the palate, no

significantdifferenceinsurgicalsuccesswasfound(p=0.784).

Adverseevents

In total,26patients reported therapy-relatedadverseevents.With45.5%, frequentawakeningsor

insomniaduetodiscomfortofthestimulationwasthemostcommontherapy-relatedadverseevent

reported.Postoperativebleedingandproblemswithswallowingwerebothobservedinonepatient.

In five patients a revision of the sensor leadwas needed, probably due to damage of the sensor

during implantation. Temporary tongueweaknesswas found in twopatients and in eight patients

abrasionofthetongueoradrymouthwasseen.Table4providesanoverviewofpatient-reported

therapy-relatedadverseevents.

Table4.Therapy-relatedadverseevents

N=26* Events(n) %oftotalpopulation

Postoperativebleeding 1 2.3%

Revisioninterventionsofthe

sensorlead

5 11.4%

Stimulation-relateddiscomfort

(includinginsomnia/arousal)

20 45.5%

Infection 0 0%

Tongueweakness/neuropraxia 2 4.5%

Tongueabrasion,drymouth 8 18.2%

Problemswithswallowing 1 2.3%

Buzzingnoiseduring

stimulation

2 4.5%

Total 39

*Intotal26outof44patientsreportedtherapy-relatedadverseevents

117

6

Short-term results of upper airway stimulation in obstructive sleep apnea patients

Aspreviouslymentioned,33patientshadacompletecollapseatmultiplelevelsintheupperairway

consistingofacompleteanteroposteriorcollapseof thepalateand tonguebase.Whencomparing

differences in surgicaloutcomebetweenpatientswitha completemultilevel collapseandpatients

with an anteroposterior tongue base collapsewith orwithout a partial collapse of the palate, no

significantdifferenceinsurgicalsuccesswasfound(p=0.784).

Adverseevents

In total,26patients reported therapy-relatedadverseevents.With45.5%, frequentawakeningsor

insomniaduetodiscomfortofthestimulationwasthemostcommontherapy-relatedadverseevent

reported.Postoperativebleedingandproblemswithswallowingwerebothobservedinonepatient.

In five patients a revision of the sensor leadwas needed, probably due to damage of the sensor

during implantation. Temporary tongueweaknesswas found in twopatients and in eight patients

abrasionofthetongueoradrymouthwasseen.Table4providesanoverviewofpatient-reported

therapy-relatedadverseevents.

Table4.Therapy-relatedadverseevents

N=26* Events(n) %oftotalpopulation

Postoperativebleeding 1 2.3%

Revisioninterventionsofthe

sensorlead

5 11.4%

Stimulation-relateddiscomfort

(includinginsomnia/arousal)

20 45.5%

Infection 0 0%

Tongueweakness/neuropraxia 2 4.5%

Tongueabrasion,drymouth 8 18.2%

Problemswithswallowing 1 2.3%

Buzzingnoiseduring

stimulation

2 4.5%

Total 39

*Intotal26outof44patientsreportedtherapy-relatedadverseevents

118

Chapter 6

DISCUSSIONThe aimof this studywas to retrospectively analyse postoperative outcomes ofUAS treatment in

OSApatients (AHIbetween15and65events/h)withCPAP failureor intolerance.UASsignificantly

improvedrespiratoryparameters.At88.6%,theoverallsurgicalsuccessinourstudypopulationwas

high.Therewasnosignificantdifference insurgicaloutcomebetweenpatientswitha tonguebase

collapsewithorwithoutacompleteanteroposteriorcollapseatthelevelofthepalate.

Ourresultsareinlinewiththosepreviouslypublishedintheliterature.DuringtheSTARtrial,a5-year

follow-upstudy,Strolloetal.alsofoundasignificantreductioninAHI(29.3to9.0events/h)andODI

(25.4 to 7.4 events/h) in moderate to severe OSA patients 12 months after implantation with a

surgicalsuccessof66%.9Theseresultsweremaintainedduringlong-termfollowup.11,12

SinceFDAapproval,severalstudiesontheobjectiveandsubjectiveoutcomesofUAStreatmenthave

beenpublished.Heiseretal.reportedadecreaseinmedianAHIfrom28.6events/hto8.3events/h

after six months of follow-up. Boon et al. found similar results. Post-titration patient-outcomes

showeda significantdecrease inmeanAHI from35.6 ± 15.3 to 10.2 ± 12.9 events/h. The surgical

success in this studywas78%. 3 Inanother small-scale studybyKentet al., post-titrationAHIalso

significantlydecreasedand found thatAHIwas reducedwithinnormal range (AHI<5events/h) in

70%ofallpatients.5

Asstatedabove,ourstudyfoundsimilarresults.Thehighersurgicalsuccessinourstudycomparedto

the 12-months results of the STAR trial could be due to differences in length of follow-up, and

increasedknowledgewithregardtopatientselectionandtitrationsinceFDAapproval.Nevertheless,

one could argue that the decrease of the AHI in our studywas even greater than that in several

previouspublished studies, sincebaselineAHI (37.6 events/h) inour studypopulationwashigher.

ThehighbaselineAHIinthisstudypopulationcanbeexplainedbythefactthat,intheNetherlands,

treatmentwithUASisonlyreimbursedinpatientswhoseAHIliesbetween30and50events/h.

Althoughitmustbetakenintoaccountthatoursampleforthisanalysiswassmall,nodifferencesin

surgicalsuccesswerefoundwhencomparingpatientswithacompletecollapseofthetonguebase

with or without a complete anteroposterior collapse at the level of the palate. This finding is

supportedbytwopreviouslypublishedstudies.Heiseretal.describedtheprincipleofpalatoglossal

coupling in patients treated with UAS. It was concluded that by selective stimulation of the

hypoglossal nerve,more than 80%of all implanted patients had both a significant opening of the

upper airway at retropalatal level and the level of the tongue base. 2 In another study the

postoperative results of patients with an isolated retropalatal collapse, or multilevel collapse

undergoingUAS,were compared. Postoperative results showed that the reduction inAHI, success

andcureratewerecomparablebetweenthetwogroups.20

Clinicalrelevance

OSA is associated with increased risk of developing cardiovascular disease, high morbidity, and

mortality.InsomestudiesithasalsobeensuggestedthatOSAservesasariskfactorforstrokeandas

an independentpredictor for functionalrecoveryandmortality instrokepatients. 21-24Especially in

patientswithmoderatetosevereOSAandCPAPintolerance,orfailure,adequateOSAtreatmentisof

paramountimportance.Manyformsofupperairwaysurgeryhavebeendescribedintheliterature.

Manyarehamperedby lowsurgicalsuccessratesand it isknownthatahighpreoperativeAHI isa

negative predictor for surgical success. Although patients selected for UAS have often failed both

conservative and surgical treatment for their OSA, the surgical success rate of UAS is higher

compared to other types of upper airway surgery. 25 Nevertheless, it must be kept in mind that

properpatientselectionandanadequateandspecializedfollow-upbyateam,trainedforthistype

ofsurgery,isthekeytotreatmentsuccess.

Limitations

Thisstudyisnotwithoutlimitations.Firstofall,thisstudycontainsdatacollectedduringatitration

night,wherebyinthemajorityofincludedpatientsanadjustedAHI,alsoreferredtoasthetreatment

AHI,wasusedforanalysis.Secondly,interpretationofUASresultsisnotonlydependentonitseffect

on respiratory events, but also on its compliance. 26 The results of this study show thatUAS is an

effectivetreatmentinpatientswithmoderatetosevereOSApatients,buttherapyusageisnottaken

intoaccount.Hence, the resultsof this study canbeanoverestimationof treatmenteffectiveness

whencomparedtoanactualin-homesituation.Long-termfollow-upofbothobjectiveandsubjective

outcomes including therapy usage are therefore required. Thirdly, subjective outcomes were not

includedinthisstudy.Thiswasduetolackofdatamakingsufficientanalysisofthedatanotreliable.

CONCLUSION

UAShasproventobeaneffectivetreatment inOSApatients(rangeAHI20.8-55.8events/h)with

CPAPintoleranceorfailure,intermsofrespiratoryoutcomes,withasurgicalsuccessof88.6%.There

wasnosignificantdifferenceinsurgicaloutcomebetweenpatientswithatonguebasecollapsewith

orwithoutacompleteanteroposteriorcollapseatthelevelofthepalate.Themostcommontherapy-

related adverse event reported was (temporary) stimulation-related discomfort often leading to

frequentawakeningsorinsomnia.AlthoughUASseemstobeapromisingalternativeformoderateto

119

6

Short-term results of upper airway stimulation in obstructive sleep apnea patients

DISCUSSIONThe aimof this studywas to retrospectively analyse postoperative outcomes ofUAS treatment in

OSApatients (AHIbetween15and65events/h)withCPAP failureor intolerance.UASsignificantly

improvedrespiratoryparameters.At88.6%,theoverallsurgicalsuccessinourstudypopulationwas

high.Therewasnosignificantdifference insurgicaloutcomebetweenpatientswitha tonguebase

collapsewithorwithoutacompleteanteroposteriorcollapseatthelevelofthepalate.

Ourresultsareinlinewiththosepreviouslypublishedintheliterature.DuringtheSTARtrial,a5-year

follow-upstudy,Strolloetal.alsofoundasignificantreductioninAHI(29.3to9.0events/h)andODI

(25.4 to 7.4 events/h) in moderate to severe OSA patients 12 months after implantation with a

surgicalsuccessof66%.9Theseresultsweremaintainedduringlong-termfollowup.11,12

SinceFDAapproval,severalstudiesontheobjectiveandsubjectiveoutcomesofUAStreatmenthave

beenpublished.Heiseretal.reportedadecreaseinmedianAHIfrom28.6events/hto8.3events/h

after six months of follow-up. Boon et al. found similar results. Post-titration patient-outcomes

showeda significantdecrease inmeanAHI from35.6 ± 15.3 to 10.2 ± 12.9 events/h. The surgical

success in this studywas78%. 3 Inanother small-scale studybyKentet al., post-titrationAHIalso

significantlydecreasedand found thatAHIwas reducedwithinnormal range (AHI<5events/h) in

70%ofallpatients.5

Asstatedabove,ourstudyfoundsimilarresults.Thehighersurgicalsuccessinourstudycomparedto

the 12-months results of the STAR trial could be due to differences in length of follow-up, and

increasedknowledgewithregardtopatientselectionandtitrationsinceFDAapproval.Nevertheless,

one could argue that the decrease of the AHI in our studywas even greater than that in several

previouspublished studies, sincebaselineAHI (37.6 events/h) inour studypopulationwashigher.

ThehighbaselineAHIinthisstudypopulationcanbeexplainedbythefactthat,intheNetherlands,

treatmentwithUASisonlyreimbursedinpatientswhoseAHIliesbetween30and50events/h.

Althoughitmustbetakenintoaccountthatoursampleforthisanalysiswassmall,nodifferencesin

surgicalsuccesswerefoundwhencomparingpatientswithacompletecollapseofthetonguebase

with or without a complete anteroposterior collapse at the level of the palate. This finding is

supportedbytwopreviouslypublishedstudies.Heiseretal.describedtheprincipleofpalatoglossal

coupling in patients treated with UAS. It was concluded that by selective stimulation of the

hypoglossal nerve,more than 80%of all implanted patients had both a significant opening of the

upper airway at retropalatal level and the level of the tongue base. 2 In another study the

postoperative results of patients with an isolated retropalatal collapse, or multilevel collapse

undergoingUAS,were compared. Postoperative results showed that the reduction inAHI, success

andcureratewerecomparablebetweenthetwogroups.20

Clinicalrelevance

OSA is associated with increased risk of developing cardiovascular disease, high morbidity, and

mortality.InsomestudiesithasalsobeensuggestedthatOSAservesasariskfactorforstrokeandas

an independentpredictor for functionalrecoveryandmortality instrokepatients. 21-24Especially in

patientswithmoderatetosevereOSAandCPAPintolerance,orfailure,adequateOSAtreatmentisof

paramountimportance.Manyformsofupperairwaysurgeryhavebeendescribedintheliterature.

Manyarehamperedby lowsurgicalsuccessratesand it isknownthatahighpreoperativeAHI isa

negative predictor for surgical success. Although patients selected for UAS have often failed both

conservative and surgical treatment for their OSA, the surgical success rate of UAS is higher

compared to other types of upper airway surgery. 25 Nevertheless, it must be kept in mind that

properpatientselectionandanadequateandspecializedfollow-upbyateam,trainedforthistype

ofsurgery,isthekeytotreatmentsuccess.

Limitations

Thisstudyisnotwithoutlimitations.Firstofall,thisstudycontainsdatacollectedduringatitration

night,wherebyinthemajorityofincludedpatientsanadjustedAHI,alsoreferredtoasthetreatment

AHI,wasusedforanalysis.Secondly,interpretationofUASresultsisnotonlydependentonitseffect

on respiratory events, but also on its compliance. 26 The results of this study show thatUAS is an

effectivetreatmentinpatientswithmoderatetosevereOSApatients,buttherapyusageisnottaken

intoaccount.Hence, the resultsof this study canbeanoverestimationof treatmenteffectiveness

whencomparedtoanactualin-homesituation.Long-termfollow-upofbothobjectiveandsubjective

outcomes including therapy usage are therefore required. Thirdly, subjective outcomes were not

includedinthisstudy.Thiswasduetolackofdatamakingsufficientanalysisofthedatanotreliable.

CONCLUSION

UAShasproventobeaneffectivetreatment inOSApatients(rangeAHI20.8-55.8events/h)with

CPAPintoleranceorfailure,intermsofrespiratoryoutcomes,withasurgicalsuccessof88.6%.There

wasnosignificantdifferenceinsurgicaloutcomebetweenpatientswithatonguebasecollapsewith

orwithoutacompleteanteroposteriorcollapseatthelevelofthepalate.Themostcommontherapy-

related adverse event reported was (temporary) stimulation-related discomfort often leading to

frequentawakeningsorinsomnia.AlthoughUASseemstobeapromisingalternativeformoderateto

120

Chapter 6

severe OSA patients with CPAP intolerance or failure, proper patient selection, adequate

implantationoftheUASsystemandfollow-upbytrainedpersonnelarethekeytotreatmentsuccess.

Acknowledgements: The authors would like to thank Michella Klitsie – Olie (UAS coordinator,

OLVG), Jonate van den Oever (UAS coordinator, OLVG) and Anja van de Velde-Muusers (research

coordinator,OLVG)fortheextensiveworkandsupportwithconductingthisstudy.

REFERENCES

1. RotenbergBW,ViciniC,PangEB,PangKP.Reconsideringfirst-linetreatmentforobstructive

sleepapnea:asystematicreviewoftheliterature.JOtolaryngolHeadNeckSurg.2016;45:23.

2. HeiserC,EdenharterG,BasM,WirthM,HofauerB.Palatoglossuscouplinginselectiveupper

airwaystimulation.Laryngoscope.2017;127(10):E378-E83.

3. BoonM,HuntleyC,SteffenA,etal.UpperAirwayStimulationforObstructiveSleepApnea:

ResultsfromtheADHERERegistry.OtolaryngolHeadNeckSurg.2018;159(2):379-85.

4. Heiser C, Knopf A, BasM, Gahleitner C, Hofauer B. Selective upper airway stimulation for

obstructive sleep apnea: a single center clinical experience. European archives of oto-rhino-

laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies

(EUFOS) : affiliatedwith the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery.

2017;274(3):1727-34.

5. KentDT,LeeJJ,StrolloPJ,SooseRJ.UpperAirwayStimulationforOSA:EarlyAdherenceand

OutcomeResultsofOneCenter.Otolaryngology--headandnecksurgery:officialjournalofAmerican

AcademyofOtolaryngology-HeadandNeckSurgery.2016;155(1):188-93.

6. Steffen A, Hartmann JT, Konig IR, RaveslootMJL, Hofauer B, Heiser C. Evaluation of body

position in upper airway stimulation for obstructive sleep apnea-is continuous voltage sufficient

enough?SleepBreath.2018;22(4):1207-12.

7. SteffenA,Sommer JU,HofauerB,Maurer JT,HasselbacherK,HeiserC.Outcomeafterone

yearofupperairwaystimulation forobstructivesleepapnea inamulticenterGermanpost-market

study.Laryngoscope.2018;128(2):509-15.

8. Strollo PJ, Gillespie MB, Soose RJ, et al. Upper Airway Stimulation for Obstructive Sleep

Apnea:DurabilityoftheTreatmentEffectat18Months.2015.

9. Strollo PJ, Jr., Soose RJ, Maurer JT, et al. Upper-airway stimulation for obstructive sleep

apnea.NEnglJMed.2014;370(2):139-49.

10. WoodsonBT,GillespieMB,SooseRJ,etal.Randomizedcontrolledwithdrawalstudyofupper

airway stimulation on OSA: short-and long-term effect. Otolaryngology--Head and Neck Surgery.

2014;151(5):880-87.

11. WoodsonBT,SooseRJ,GillespieMB,etal.Three-yearoutcomesofcranialnervestimulation

for obstructive sleep apnea: the STAR trial. Otolaryngology--Head and Neck Surgery.

2016;154(1):181-88.

12. Woodson BT, Strohl KP, Soose RJ, et al. Upper Airway Stimulation for Obstructive Sleep

Apnea:5-YearOutcomes.OtolaryngolHeadNeckSurg.2018;159(1):194-202.

121

6

Short-term results of upper airway stimulation in obstructive sleep apnea patients

severe OSA patients with CPAP intolerance or failure, proper patient selection, adequate

implantationoftheUASsystemandfollow-upbytrainedpersonnelarethekeytotreatmentsuccess.

Acknowledgements: The authors would like to thank Michella Klitsie – Olie (UAS coordinator,

OLVG), Jonate van den Oever (UAS coordinator, OLVG) and Anja van de Velde-Muusers (research

coordinator,OLVG)fortheextensiveworkandsupportwithconductingthisstudy.

REFERENCES

1. RotenbergBW,ViciniC,PangEB,PangKP.Reconsideringfirst-linetreatmentforobstructive

sleepapnea:asystematicreviewoftheliterature.JOtolaryngolHeadNeckSurg.2016;45:23

2. HeiserC,EdenharterG,BasM,WirthM,HofauerB.Palatoglossuscouplinginselectiveupper

airwaystimulation.Laryngoscope.2017;127(10):E378-E83

3. BoonM,HuntleyC,SteffenA,etal.UpperAirwayStimulationforObstructiveSleepApnea:

ResultsfromtheADHERERegistry.OtolaryngolHeadNeckSurg.2018;159(2):379-85

4. Heiser C, Knopf A, BasM, Gahleitner C, Hofauer B. Selective upper airway stimulation for

obstructive sleep apnea: a single center clinical experience. European archives of oto-rhino-

laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies

(EUFOS) : affiliatedwith the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery.

2017;274(3):1727-34

5. KentDT,LeeJJ,StrolloPJ,SooseRJ.UpperAirwayStimulationforOSA:EarlyAdherenceand

OutcomeResultsofOneCenter.Otolaryngology--headandnecksurgery:officialjournalofAmerican

AcademyofOtolaryngology-HeadandNeckSurgery.2016;155(1):188-93

6. Steffen A, Hartmann JT, Konig IR, RaveslootMJL, Hofauer B, Heiser C. Evaluation of body

position in upper airway stimulation for obstructive sleep apnea-is continuous voltage sufficient

enough?SleepBreath.2018;22(4):1207-12

7. SteffenA,Sommer JU,HofauerB,Maurer JT,HasselbacherK,HeiserC.Outcomeafterone

yearofupperairwaystimulation forobstructivesleepapnea inamulticenterGermanpost-market

study.Laryngoscope.2018;128(2):509-15

8. Strollo PJ, Gillespie MB, Soose RJ, et al. Upper Airway Stimulation for Obstructive Sleep

Apnea:DurabilityoftheTreatmentEffectat18Months.2015

9. Strollo PJ, Jr., Soose RJ, Maurer JT, et al. Upper-airway stimulation for obstructive sleep

apnea.NEnglJMed.2014;370(2):139-49

10. WoodsonBT,GillespieMB,SooseRJ,etal.Randomizedcontrolledwithdrawalstudyofupper

airway stimulation on OSA: short-and long-term effect. Otolaryngology--Head and Neck Surgery.

2014;151(5):880-87

11. WoodsonBT,SooseRJ,GillespieMB,etal.Three-yearoutcomesofcranialnervestimulation

for obstructive sleep apnea: the STAR trial. Otolaryngology--Head and Neck Surgery.

2016;154(1):181-88

12. Woodson BT, Strohl KP, Soose RJ, et al. Upper Airway Stimulation for Obstructive Sleep

Apnea:5-YearOutcomes.OtolaryngolHeadNeckSurg.2018;159(1):194-202

122

Chapter 6

13. Vanderveken OM, Maurer JT, Hohenhorst W, et al. Evaluation of drug-induced sleep

endoscopyasapatient selection tool for implantedupperairway stimulation forobstructive sleep

apnea.JClinSleepMed.2013;9(5):433-8

14. Schnider T, Minto C. Pharmacokinetic models of propofol for TCI. Anaesthesia.

2008;63(2):206-06

15. Schnider TW,Minto CF, Gambus PL, et al. The influence ofmethod of administration and

covariateson thepharmacokineticsofpropofol in adult volunteers.Anesthesiology: The Journalof

theAmericanSocietyofAnesthesiologists.1998;88(5):1170-82

16. Kezirian EJ, Hohenhorst W, de Vries N. Drug-induced sleep endoscopy: the VOTE

classification.EurArchOtorhinolaryngol.2011;268(8):1233-36

17. Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifications of the upper

airwayinadultswithobstructivesleepapneasyndrome.Sleep.1996;19(2):156-77

18. BerryRB,BudhirajaR,GottliebDJ,etal.Rulesforscoringrespiratoryeventsinsleep:update

ofthe2007AASMManualfortheScoringofSleepandAssociatedEvents.DeliberationsoftheSleep

Apnea Definitions Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med.

2012;8(5):597-619

19. Heiser C, Maurer JT, Hofauer B, Sommer JU, Seitz A, Steffen A. Outcomes of Upper Airway

Stimulation for Obstructive Sleep Apnea in a Multicenter German Postmarket Study.Otolaryngol

HeadNeckSurg156(2):378-384.doi:10.1177/0194599816683378

20. MahmoudAF,ThalerER.OutcomesofHypoglossalNerveUpperAirwayStimulationamong

PatientswithIsolatedRetropalatalCollapse.OtolaryngolHeadNeckSurg.2019:194599819835186.

21. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep

apneaasariskfactorforstrokeanddeath.NEnglJMed.2005;353(19):2034-41

22. Good DC, Henkle JQ, Gelber D,Welsh J, Verhulst S. Sleep-disordered breathing and poor

functionaloutcomeafterstroke.Stroke.1996;27(2):252-9

23. Parra O, Arboix A, Montserrat JM, Quinto L, Bechich S, Garcia-Eroles L. Sleep-related

breathingdisorders:impactonmortalityofcerebrovasculardisease.EurRespirJ.2004;24(2):267-72

24. ParraO,Sanchez-ArmengolA,CapoteF,etal.Efficacyofcontinuouspositiveairwaypressure

treatment on 5-year survival in patients with ischaemic stroke and obstructive sleep apnea: a

randomizedcontrolledtrial.JSleepRes.2015;24(1):47-53

25. KezirianEJ,GoldbergAN.Hypopharyngealsurgery inobstructivesleepapnea:anevidence-

basedmedicinereview.ArchOtolaryngolHeadNeckSurg.2006;132(2):206-13

26. Ravesloot MJ, de Vries N. Reliable calculation of the efficacy of non-surgical and surgical

treatment of obstructive sleep apnea revisited. Sleep. 2011;34(1):105

72

Polysomnography and sleepposition, an Heisenbergphenomenon?-alargescaleseriesP.E.Vonk,N.deVries,M.J.L.RaveslootHNO.2019Sep;67(9):679-684.

72

Polysomnography and sleepposition, an Heisenbergphenomenon?-alargescaleseriesP.E.Vonk,N.deVries,M.J.L.RaveslootHNO.2019Sep;67(9):679-684.

13. Vanderveken OM, Maurer JT, Hohenhorst W, et al. Evaluation of drug-induced sleep

endoscopyasapatient selection tool for implantedupperairway stimulation forobstructive sleep

apnea.JClinSleepMed.2013;9(5):433-8.

14. Schnider T, Minto C. Pharmacokinetic models of propofol for TCI. Anaesthesia.

2008;63(2):206-06.

15. Schnider TW,Minto CF, Gambus PL, et al. The influence ofmethod of administration and

covariateson thepharmacokineticsofpropofol in adult volunteers.Anesthesiology: The Journalof

theAmericanSocietyofAnesthesiologists.1998;88(5):1170-82.

16. Kezirian EJ, Hohenhorst W, de Vries N. Drug-induced sleep endoscopy: the VOTE

classification.EurArchOtorhinolaryngol.2011;268(8):1233-36.

17. Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifications of the upper

airwayinadultswithobstructivesleepapneasyndrome.Sleep.1996;19(2):156-77.

18. BerryRB,BudhirajaR,GottliebDJ,etal.Rulesforscoringrespiratoryeventsinsleep:update

ofthe2007AASMManualfortheScoringofSleepandAssociatedEvents.DeliberationsoftheSleep

Apnea Definitions Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med.

2012;8(5):597-619.

19. Heiser C, Maurer JT, Hofauer B, Sommer JU, Seitz A, Steffen A. Outcomes of Upper Airway

Stimulation for Obstructive Sleep Apnea in a Multicenter German Postmarket Study.Otolaryngol

HeadNeckSurg156(2):378-384.doi:10.1177/0194599816683378

20. MahmoudAF,ThalerER.OutcomesofHypoglossalNerveUpperAirwayStimulationamong

PatientswithIsolatedRetropalatalCollapse.OtolaryngolHeadNeckSurg.2019:194599819835186.

21. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep

apneaasariskfactorforstrokeanddeath.NEnglJMed.2005;353(19):2034-41.

22. Good DC, Henkle JQ, Gelber D,Welsh J, Verhulst S. Sleep-disordered breathing and poor

functionaloutcomeafterstroke.Stroke.1996;27(2):252-9.

23. Parra O, Arboix A, Montserrat JM, Quinto L, Bechich S, Garcia-Eroles L. Sleep-related

breathingdisorders:impactonmortalityofcerebrovasculardisease.EurRespirJ.2004;24(2):267-72.

24. ParraO,Sanchez-ArmengolA,CapoteF,etal.Efficacyofcontinuouspositiveairwaypressure

treatment on 5-year survival in patients with ischaemic stroke and obstructive sleep apnea: a

randomizedcontrolledtrial.JSleepRes.2015;24(1):47-53.

25. KezirianEJ,GoldbergAN.Hypopharyngealsurgery inobstructivesleepapnea:anevidence-

basedmedicinereview.ArchOtolaryngolHeadNeckSurg.2006;132(2):206-13.

26. Ravesloot MJ, de Vries N. Reliable calculation of the efficacy of non-surgical and surgical

treatment of obstructive sleep apnea revisited. Sleep. 2011;34(1):105

72

Polysomnography and sleepposition, an Heisenbergphenomenon?-alargescaleseriesP.E.Vonk,N.deVries,M.J.L.RaveslootHNO.2019Sep;67(9):679-684

72

Polysomnography and sleepposition, an Heisenbergphenomenon?-alargescaleseriesP.E.Vonk,N.deVries,M.J.L.RaveslootHNO.2019Sep;67(9):679-684.

124

Chapter 7

ABSTRACT

Background: The severity of position-dependent obstructive sleep apnea (POSA) depends on the

non-supine and supine apnea-hypopnea index (AHI) as well as the time spent in supine position.

Especially, the latter is susceptible to variation. Several small-scale studies suggest that wearing

polysomnography(PSG)apparatusleadstoanincreaseinsupinesleepingposition.

Objectives:TheaimofthisstudywastoevaluatetheeffectofwearingPSGapparatusonsleeping

positionandtoassesstheinfluenceonOSAseverity.

Materialandmethods:A largescale,retrospectivestudywasperformed, includingaconsecutive

series of POSA and non-apneic snoring patients who were prescribed positional therapy [Sleep

PositionTrainer (SPT)].TheeffectofwearingPSGapparatusonsleepingpositionwasevaluatedby

comparingbodypositionduringthePSGnightandinactive(diagnostic)phaseofSPT.

Results:Themeanpercentageoftotalrecordingtime(TRT)insupinepositionwas43.1%duringthe

PSGnightcomparedto28.6%ofTRTduringinactive(diagnostic)phaseofSPT;asignificantdecrease

of33.6%(p<0.001).WhenadjustingtheAHIusingTRTindifferentsleepingpositionsmeasuredwith

theSPT,medianAHIdecreasedfrom13.3/h(9.0,20.4)to10.3/h(6.8,16.2);p<0.001.Whenusing

theadjustedAHI,33%(N=66)ofallpatientshadachangeinOSAseverity.

Conclusions: Theresultsof this study indicate thatwearingPSGapparatus leads toan increase in

percentage of supine sleeping position causing an overestimation of OSA severity, especially in

patientswithPOSA.Thiscanhavesignificantimpactinbothclinicalandscientificpractice.

Keywords:severity,sleepapnea,obstructive,sleepwakedisorders,snoring,supineposition

INTRODUCTIONANDBACKGROUND

Position-dependentobstructivesleepapnea(POSA)constitutesaconsiderableproportionofpatients

diagnosedwithobstructivesleepapnea(OSA).In56-75%OSAseverityisinfluencedbybodyposition,

inwhichthesupinepositionisusuallytheworstsleepingposition(WSP).1-6

Currently,avarietyofdefinitionsforPOSAhavebeensuggestedintheliterature.Themostcommon

classificationmakes a distinction between two groups; positional patients (PP) and non-positional

patients(NPP).1,5,7InPP,thefrequencyanddurationofhypopneicandapneiceventsareincreased

inthesupinesleepingposition.InsomePP,theseeventsoccursolelyinthesupinesleepingposition.8Cartwrightfirstdescribedthearbitrarycut-offpointofadifferenceof50%ormoreinapneaindex

betweensupineandnon-supinepositions.1

PP can be treatedwith positional therapy (PT) as a standalone treatment or in combinationwith

othertreatmentmodalitiesforOSA(e.g.mandibularadvancementdevices).9,10PTisusedtoprevent

patientsfromlyinginthesupineposition.3Inarecentmeta-analysisstrongevidencewasfoundthat

thenewgenerationofvibro-tactiledevicesforPTiseffectiveinreducingtheapnea-hypopneaindex

(AHI)duringshort-termfollow-up.Thesesmalldevices,attachedtoeitherthetrunkorneck,provide

a subtlevibrating stimulus thatpreventspatients fromadopting the supineposition. Furthermore,

thesedevicesaresimpletouseandreversible.Thecomplianceduringshort-termfollow-upishigh,

butdataonlong-termfollow-upislimited.11

TheseverityofOSAinPPdependsontheAHIinsupineandnon-supinepositionaswellasthetime

spent in supineposition. Especially, the time spent in supineposition is susceptible to variation.A

pivotalmatter,withconsiderableimpactonbothclinicalandscientificworkonPP.Oneparameter,

whichcouldinfluencetimespentinvariousbodypositions,ispolysomnography(PSG).

Three small-scale studies have evaluated the effect of PSG apparatus on sleeping position. The

results of these studies suggest that through wearing PSG apparatus patients are likely to spend

more time in thesupineposition. 12-14Wewere interested toseewhetherwecouldconfirmthese

findings in a larger scale study. We hypothesize that PSG apparatus leads to an increase in

percentageoftotaltimespentinsupinepositionandsubsequentlyinfluencesOSAseveritymeasured

byPSG,especiallyinPP.

125

7

Polysomnography and sleep position, an Heisenberg phenomenon?

ABSTRACT

Background: The severity of position-dependent obstructive sleep apnea (POSA) depends on the

non-supine and supine apnea-hypopnea index (AHI) as well as the time spent in supine position.

Especially, the latter is susceptible to variation. Several small-scale studies suggest that wearing

polysomnography(PSG)apparatusleadstoanincreaseinsupinesleepingposition.

Objectives:TheaimofthisstudywastoevaluatetheeffectofwearingPSGapparatusonsleeping

positionandtoassesstheinfluenceonOSAseverity.

Materialandmethods:A largescale,retrospectivestudywasperformed, includingaconsecutive

series of POSA and non-apneic snoring patients who were prescribed positional therapy [Sleep

PositionTrainer (SPT)].TheeffectofwearingPSGapparatusonsleepingpositionwasevaluatedby

comparingbodypositionduringthePSGnightandinactive(diagnostic)phaseofSPT.

Results:Themeanpercentageoftotalrecordingtime(TRT)insupinepositionwas43.1%duringthe

PSGnightcomparedto28.6%ofTRTduringinactive(diagnostic)phaseofSPT;asignificantdecrease

of33.6%(p<0.001).WhenadjustingtheAHIusingTRTindifferentsleepingpositionsmeasuredwith

theSPT,medianAHIdecreasedfrom13.3/h(9.0,20.4)to10.3/h(6.8,16.2);p<0.001.Whenusing

theadjustedAHI,33%(N=66)ofallpatientshadachangeinOSAseverity.

Conclusions: Theresultsof this study indicate thatwearingPSGapparatus leads toan increase in

percentage of supine sleeping position causing an overestimation of OSA severity, especially in

patientswithPOSA.Thiscanhavesignificantimpactinbothclinicalandscientificpractice.

Keywords:severity,sleepapnea,obstructive,sleepwakedisorders,snoring,supineposition

INTRODUCTIONANDBACKGROUND

Position-dependentobstructivesleepapnea(POSA)constitutesaconsiderableproportionofpatients

diagnosedwithobstructivesleepapnea(OSA).In56-75%OSAseverityisinfluencedbybodyposition,

inwhichthesupinepositionisusuallytheworstsleepingposition(WSP).1-6

Currently,avarietyofdefinitionsforPOSAhavebeensuggestedintheliterature.Themostcommon

classificationmakes a distinction between two groups; positional patients (PP) and non-positional

patients(NPP).1,5,7InPP,thefrequencyanddurationofhypopneicandapneiceventsareincreased

inthesupinesleepingposition.InsomePP,theseeventsoccursolelyinthesupinesleepingposition.8Cartwrightfirstdescribedthearbitrarycut-offpointofadifferenceof50%ormoreinapneaindex

betweensupineandnon-supinepositions.1

PP can be treatedwith positional therapy (PT) as a standalone treatment or in combinationwith

othertreatmentmodalitiesforOSA(e.g.mandibularadvancementdevices).9,10PTisusedtoprevent

patientsfromlyinginthesupineposition.3Inarecentmeta-analysisstrongevidencewasfoundthat

thenewgenerationofvibro-tactiledevicesforPTiseffectiveinreducingtheapnea-hypopneaindex

(AHI)duringshort-termfollow-up.Thesesmalldevices,attachedtoeitherthetrunkorneck,provide

a subtlevibrating stimulus thatpreventspatients fromadopting the supineposition. Furthermore,

thesedevicesaresimpletouseandreversible.Thecomplianceduringshort-termfollow-upishigh,

butdataonlong-termfollow-upislimited.11

TheseverityofOSAinPPdependsontheAHIinsupineandnon-supinepositionaswellasthetime

spent in supineposition. Especially, the time spent in supineposition is susceptible to variation.A

pivotalmatter,withconsiderableimpactonbothclinicalandscientificworkonPP.Oneparameter,

whichcouldinfluencetimespentinvariousbodypositions,ispolysomnography(PSG).

Three small-scale studies have evaluated the effect of PSG apparatus on sleeping position. The

results of these studies suggest that through wearing PSG apparatus patients are likely to spend

more time in thesupineposition. 12-14Wewere interested toseewhetherwecouldconfirmthese

findings in a larger scale study. We hypothesize that PSG apparatus leads to an increase in

percentageoftotaltimespentinsupinepositionandsubsequentlyinfluencesOSAseveritymeasured

byPSG,especiallyinPP.

126

Chapter 7

MATERIALANDMETHODS

Weperformedaretrospective,single-centercohortstudyincludingaconsecutiveseriesofpatients

who were prescribed PT between January 2016 and June 2017. Inclusion criteria included the

availabilityofafull-nightpolysomnography.PatientswereeligiblefortreatmentwithPTwhenthey

metamodifiedversionofCartwright’scriteriaforPOSAdefinedasasupineAHIat leasttwotimes

greaterthanthenon-supineAHI,combinedwithanon-supineAHI<10/h.1InpatientswithoutOSA,

AHI<5/h,patientswereprescribedPTincaseoftheoccurrenceofsnoringmerelyinsupineposition

basedonclinicalhistory.Patientswereexcludedwhendatawasmissingconcerningthepercentage

ofTSTorTRTinvariousbodypositionsduringthePSGnight.

Ethicalconsiderations

Allproceduresfollowedwereinaccordancewiththeethicalstandardsoftheresponsiblecommittee

onhumanexperimentationandwiththeDeclarationofHelsinkiof1975.Dataonstudysubjectswas

collected and stored encoded to protect personal information. For this type of study informed

consentwasnotrequired.

SleepPositionTrainer(SPT)

PP eligible for PT were prescribed the Sleep Position Trainer (SPT; NightBalance, Delft, the

Netherlands),anewgenerationvibro-tactiledevice.Itweighs25gandhasthefollowingdimensions:

72X35X10mm,respectively.Thedeviceisfastenedtothechestwithastrap,sothatthedeviceis

locatedonthesternum.TheSPTisplacedinapocketofthestrap,whichisclosedwithaVelcrotab.

Thedeviceprovidesavibratingstimulusifthesupinepositionisidentified,whichismeasuredusinga

3-dimensional digital accelerometer. 9, 15-17 When no turning movement is detected, the stimulus

graduallyincreasesuntilthepatientturnstoanon-supineposition.Ifnoreactionismonitored,the

vibrationsarepausedandreinitiatedafter2minutes.InitiationoftreatmentwiththeSPTisdivided

intothreephases:adiagnosticphase,atrainingphaseandatherapyphase.Thefirsttwonightsare

definedasthediagnosticphase,wheretheSPTmonitorsandrecordssleepingpositions.Duringthis

phase,noactivefeedbackisgiventothepatient.Thedeviceisinactive.Anaverageisprovidedofthe

variousbodypositionsmeasuredoverthefirsttwonights.

Polysomnography

Eachsubjectunderwentafull-night,unattendedPSG(typeII).Todeterminethestagesofsleep,an

electroencephalogram (Fp1, Fp2, C3, C4, O1, O2), electro-oculogram and electromyogram of the

submental muscle were obtained. To measure the nasal airflow a nasal cannula with a pressure

transducerwas inserted in theopeningof thenostrils.A fingerpulseoximeterwasused to record

arterialbloodoxyhaemoglobin.Respiratoryeffortbeltswereplaceovertheabdomenandribcageto

measurethoracoabdominalexcursions.Todeterminebodyposition,differentiationbetweenupright,

right side, left side,proneandsupineposition,apositionsensorwasused.Limbmovementswere

detectedwithananteriortibialelectromyogramwithsurfaceelectrodes.

ForeachpatientthedataweremanuallyscoredaccordingtoAmericanAcademyofSleepMedicine

(AASM)scoringmanualbyanexperiencedsleepinvestigator.18

Sleepingpositionmeasurements

ToevaluatetheeffectofPSGapparatusonsleepingposition,wecompareddatacollectedduringthe

PSG night to data collected with the SPT during the first two nights of therapy usage (diagnostic

phase).Asmentionedbefore,theSPTisinactiveduringthisphase,butdoesrecordsleepingposition.

SincetheSPT is inactive,sleepposition isnot influencedbyavibratingstimulusof thedevice.The

distribution of different body positionsmeasured by the SPT are described as percentage of total

recordingtime(TRT).TheTRToftheSPTisnotpreset,butisinitiatedwhentheSPTisswitchedonby

thepatientwhengoingtobed.

ItisclearthattheSPTcannotdistinguishbetweensleepandawakestates.Toenablecomparisonof

the distribution of body positions during the PSG night, percentages in different body positions

during time in bed (TIB) was used. TIB is the TRT from lights out to lights on and therefore

comparabletotheTRToftheSPT.

AdjustedAHI

ThetotalAHIdependsonseveralparameters,consistingofthesupineAHI,non-supineAHIandthe

percentageofTSTspendinsupineandnon-supineposition.ToevaluatethepossibleinfluenceofPSG

apparatusonthepercentageofsupinebodyposition,andsubsequentlyOSAseveritymeasuredwith

PSG,aseparateanalysiswillbeperformedusinganadjustedAHI.TheadjustedAHIwillbecalculated

using the percentage of TRT in supine position asmeasured with the inactive SPT instead of the

percentageofTRTduringthePSGnight.

Statisticalanalysis

StatisticalanalysiswasperformedusingSPSS (version21),SPSS Inc.,Chicago, IL).Quantitativedata

are reported as mean ± standard deviation (SD) or as median (Q1; Q3) when not normally

distributed.ComparisonofdatacollectedduringthePSGnightandinactive(diagnostic)phaseofthe

SPTwascarriedoutusingthepairedT-testinthecaseofnormallydistributeddataandtheWilcoxon

127

7

Polysomnography and sleep position, an Heisenberg phenomenon?

MATERIALANDMETHODS

Weperformedaretrospective,single-centercohortstudyincludingaconsecutiveseriesofpatients

who were prescribed PT between January 2016 and June 2017. Inclusion criteria included the

availabilityofafull-nightpolysomnography.PatientswereeligiblefortreatmentwithPTwhenthey

metamodifiedversionofCartwright’scriteriaforPOSAdefinedasasupineAHIat leasttwotimes

greaterthanthenon-supineAHI,combinedwithanon-supineAHI<10/h.1InpatientswithoutOSA,

AHI<5/h,patientswereprescribedPTincaseoftheoccurrenceofsnoringmerelyinsupineposition

basedonclinicalhistory.Patientswereexcludedwhendatawasmissingconcerningthepercentage

ofTSTorTRTinvariousbodypositionsduringthePSGnight.

Ethicalconsiderations

Allproceduresfollowedwereinaccordancewiththeethicalstandardsoftheresponsiblecommittee

onhumanexperimentationandwiththeDeclarationofHelsinkiof1975.Dataonstudysubjectswas

collected and stored encoded to protect personal information. For this type of study informed

consentwasnotrequired.

SleepPositionTrainer(SPT)

PP eligible for PT were prescribed the Sleep Position Trainer (SPT; NightBalance, Delft, the

Netherlands),anewgenerationvibro-tactiledevice.Itweighs25gandhasthefollowingdimensions:

72X35X10mm,respectively.Thedeviceisfastenedtothechestwithastrap,sothatthedeviceis

locatedonthesternum.TheSPTisplacedinapocketofthestrap,whichisclosedwithaVelcrotab.

Thedeviceprovidesavibratingstimulusifthesupinepositionisidentified,whichismeasuredusinga

3-dimensional digital accelerometer. 9, 15-17 When no turning movement is detected, the stimulus

graduallyincreasesuntilthepatientturnstoanon-supineposition.Ifnoreactionismonitored,the

vibrationsarepausedandreinitiatedafter2minutes.InitiationoftreatmentwiththeSPTisdivided

intothreephases:adiagnosticphase,atrainingphaseandatherapyphase.Thefirsttwonightsare

definedasthediagnosticphase,wheretheSPTmonitorsandrecordssleepingpositions.Duringthis

phase,noactivefeedbackisgiventothepatient.Thedeviceisinactive.Anaverageisprovidedofthe

variousbodypositionsmeasuredoverthefirsttwonights.

Polysomnography

Eachsubjectunderwentafull-night,unattendedPSG(typeII).Todeterminethestagesofsleep,an

electroencephalogram (Fp1, Fp2, C3, C4, O1, O2), electro-oculogram and electromyogram of the

submental muscle were obtained. To measure the nasal airflow a nasal cannula with a pressure

transducerwas inserted in theopeningof thenostrils.A fingerpulseoximeterwasused to record

arterialbloodoxyhaemoglobin.Respiratoryeffortbeltswereplaceovertheabdomenandribcageto

measurethoracoabdominalexcursions.Todeterminebodyposition,differentiationbetweenupright,

right side, left side,proneandsupineposition,apositionsensorwasused.Limbmovementswere

detectedwithananteriortibialelectromyogramwithsurfaceelectrodes.

ForeachpatientthedataweremanuallyscoredaccordingtoAmericanAcademyofSleepMedicine

(AASM)scoringmanualbyanexperiencedsleepinvestigator.18

Sleepingpositionmeasurements

ToevaluatetheeffectofPSGapparatusonsleepingposition,wecompareddatacollectedduringthe

PSG night to data collected with the SPT during the first two nights of therapy usage (diagnostic

phase).Asmentionedbefore,theSPTisinactiveduringthisphase,butdoesrecordsleepingposition.

SincetheSPT is inactive,sleepposition isnot influencedbyavibratingstimulusof thedevice.The

distribution of different body positionsmeasured by the SPT are described as percentage of total

recordingtime(TRT).TheTRToftheSPTisnotpreset,butisinitiatedwhentheSPTisswitchedonby

thepatientwhengoingtobed.

ItisclearthattheSPTcannotdistinguishbetweensleepandawakestates.Toenablecomparisonof

the distribution of body positions during the PSG night, percentages in different body positions

during time in bed (TIB) was used. TIB is the TRT from lights out to lights on and therefore

comparabletotheTRToftheSPT.

AdjustedAHI

ThetotalAHIdependsonseveralparameters,consistingofthesupineAHI,non-supineAHIandthe

percentageofTSTspendinsupineandnon-supineposition.ToevaluatethepossibleinfluenceofPSG

apparatusonthepercentageofsupinebodyposition,andsubsequentlyOSAseveritymeasuredwith

PSG,aseparateanalysiswillbeperformedusinganadjustedAHI.TheadjustedAHIwillbecalculated

using the percentage of TRT in supine position asmeasured with the inactive SPT instead of the

percentageofTRTduringthePSGnight.

Statisticalanalysis

StatisticalanalysiswasperformedusingSPSS (version21),SPSS Inc.,Chicago, IL).Quantitativedata

are reported as mean ± standard deviation (SD) or as median (Q1; Q3) when not normally

distributed.ComparisonofdatacollectedduringthePSGnightandinactive(diagnostic)phaseofthe

SPTwascarriedoutusingthepairedT-testinthecaseofnormallydistributeddataandtheWilcoxon

128

Chapter 7

signed rank test in case of not normally distributed data. A p value of < 0.05 was considered to

indicatestatisticalsignificance.

RESULTS

Thedataof168patientswereavailableforanalysis.Ineightpatients(4.8%)theSPTwasprescribed

becauseofnon-apneicposition-dependentsnoring.Themajorityof thestudypopulationwasmale

(67.9%).Themeanagewas51.7±12.4years.Anoverviewofbaselinecharacteristicsispresentedin

table 1.Patientsspentamean43.8±22.3%ofTST insupinepositioncomparedtoamean43.1±

20.8%oftheTRTwhileundergoingPSG,whichwasnotsignificantlydifferent(p=0.132).Duringthe

inactive(diagnostic)phaseofSPTpatientsspent28.6±15.5%ofTRTinsupineposition;asignificant

decrease of 33.6% compared to the TRT in supine position during the PSG night; p < 0.001. No

significantdifferenceswerefoundbetweenmaleandfemalepatients.Figure1showsthepercentage

ofTRTinsupinepositionduringthePSGnightandinactive(diagnostic)phaseofSPT.

Table1.Baselinecharacteristics

Patientcharacteristic

N=168

Mean±SD

Age(year) 51.7±12.4

Sex(male/female) 114/54

BMI(kg/m2) 26.8±4.0

AHI(perhour) 13.2(9.1,20.3)†

AHIinsupineposition(perhour) 28.8(17.2,47.2)†

AHIinnon-supineposition(perhour) 4.0(2.0,6.5)†

%TSTinsupineposition 43.8±22.3

%TRTinsupineposition 43.1±20.8

†median(Q1,Q3)

SDstandarddeviationBMIbodymassindexAHIapnea-hypopneaindexTSTtotalsleeptimeTRT

totalrecordingtime

129

7

Polysomnography and sleep position, an Heisenberg phenomenon?

signed rank test in case of not normally distributed data. A p value of < 0.05 was considered to

indicatestatisticalsignificance.

RESULTS

Thedataof168patientswereavailableforanalysis.Ineightpatients(4.8%)theSPTwasprescribed

becauseofnon-apneicposition-dependentsnoring.Themajorityof thestudypopulationwasmale

(67.9%).Themeanagewas51.7±12.4years.Anoverviewofbaselinecharacteristicsispresentedin

table 1.Patientsspentamean43.8±22.3%ofTST insupinepositioncomparedtoamean43.1±

20.8%oftheTRTwhileundergoingPSG,whichwasnotsignificantlydifferent(p=0.132).Duringthe

inactive(diagnostic)phaseofSPTpatientsspent28.6±15.5%ofTRTinsupineposition;asignificant

decrease of 33.6% compared to the TRT in supine position during the PSG night; p < 0.001. No

significantdifferenceswerefoundbetweenmaleandfemalepatients.Figure1showsthepercentage

ofTRTinsupinepositionduringthePSGnightandinactive(diagnostic)phaseofSPT.

Table1.Baselinecharacteristics

Patientcharacteristic

N=168

Mean±SD

Age(year) 51.7±12.4

Sex(male/female) 114/54

BMI(kg/m2) 26.8±4.0

AHI(perhour) 13.2(9.1,20.3)†

AHIinsupineposition(perhour) 28.8(17.2,47.2)†

AHIinnon-supineposition(perhour) 4.0(2.0,6.5)†

%TSTinsupineposition 43.8±22.3

%TRTinsupineposition 43.1±20.8

†median(Q1,Q3)

SDstandarddeviationBMIbodymassindexAHIapnea-hypopneaindexTSTtotalsleeptimeTRT

totalrecordingtime

130

Chapter 7

Figure1.PercentageofTRTinsupinepositionmeasuredwithPSGandinactiveSPT

TRTtotalrecordingtime,PSGpolysomnography,SPTSleepPositionTrainer

OSAseverity

Eight patients (4.8%) were diagnosed with non-apneic position-dependent snoring, 87 patients

(51.8%)withmildOSA(AHI≥5/hand<15/h),53patients(31.5%)withmoderateOSA(AHI≥15/h

and<30/h)and20patients(11.9%)withsevereOSA(AHI≥30/h).

TheAHIwascorrected for thepercentageofTRT in supinepositionasmeasuredwith the inactive

SPT–theadjustedAHI.TheadjustedmedianAHIdecreasedfrom13.3/h(9.0,20.4) to10.3/h(6.8,

16.2) (see figure 2). Sixty-six patients (39.2%) had a change in severity of OSA when using the

adjusted AHI. In theory, 17 patients (10.1%) would not have been diagnosedwith OSAwhen the

adjustedAHIisused(seefigure3).

Figure2.TotalAHImeasuredwithtypeIIPSGversustheadjustedAHI

AHIapnea-hypopneaindex,PSGpolysomnography

131

7

Polysomnography and sleep position, an Heisenberg phenomenon?

Figure1.PercentageofTRTinsupinepositionmeasuredwithPSGandinactiveSPT

TRTtotalrecordingtime,PSGpolysomnography,SPTSleepPositionTrainer

OSAseverity

Eight patients (4.8%) were diagnosed with non-apneic position-dependent snoring, 87 patients

(51.8%)withmildOSA(AHI≥5/hand<15/h),53patients(31.5%)withmoderateOSA(AHI≥15/h

and<30/h)and20patients(11.9%)withsevereOSA(AHI≥30/h).

TheAHIwascorrected for thepercentageofTRT in supinepositionasmeasuredwith the inactive

SPT–theadjustedAHI.TheadjustedmedianAHIdecreasedfrom13.3/h(9.0,20.4) to10.3/h(6.8,

16.2) (see figure 2). Sixty-six patients (39.2%) had a change in severity of OSA when using the

adjusted AHI. In theory, 17 patients (10.1%) would not have been diagnosedwith OSAwhen the

adjustedAHIisused(seefigure3).

Figure2.TotalAHImeasuredwithtypeIIPSGversustheadjustedAHI

AHIapnea-hypopneaindex,PSGpolysomnography

132

Chapter 7

Figure3.DistributionofOSAseveritymeasuredwithtypeIIPSGandduringtheinactive(diagnostic)

phaseofSPT

DISCUSSION

Heisenbergiscreditedfortheuncertaintyprinciple,thefactthattheperformanceofatestinfluences

itsoutcome.TheresultsofthisstudysuggestthatthisphenomenonoccurswhenPPundergoaPSG.

TodatethisisthelargestcohortstudyobjectivelyevaluatingtheeffectofPSGapparatusonsleeping

position.Ourresultssuggestthatpatientsspendsignificantlymoretimeinthesupinepositionwhilst

undergoing a PSG, which could result in overestimation of OSA in severity in PP. Supporting this

hypothesis,ourresultsareconsistentwithfoursimilar,small-scalestudies.12-14,19

Loganetal. includedsixteenpatients,whounderwenttypeIPSGfollowedbyathometypeIIPSG.

The sensors were attached to a device situated above the bed, not on the chest. Patients spent

significantlylesstimeinthebackpostureduringthesecondathomePSGcomparedtoin-laboratory

PSG.12InthestudybyMeterskyetal.twelvePPwhounderwentanadditionalPSGduringwhichno

PSG leadswere attached. Time spent in supinepositionwas56%greaterduring thePSGnight in

comparison to the non-PSG night. 13 Two studies used a similar study design as described in this

paper, comparingobjectivemeasurementof timespent invarious sleepingpositionsbetweenPSG

andanon-activevibro-tactileneck-worndevice.14,19InthestudybyBignoldetal.patientsreceived

oneweekactiveandoneweekinactivetreatmentseparatedbyoneweekandinrandomizedorder.

They found that the supine sleeping time during the in-laboratory sleep study was significantly

greatercomparedtothein-homesupinesleepingtimemeasuredduringinactivetreatment.(36.6%

±5.7%vs.19.3%±4.3%,p=0.002).14Wimaleswarenetal.reported35.1%±25.1%supinesleeping

timeduringPSGvs.25%±21.4%athome,p=0.007in18patients.19Bothstudiesconcludethatthe

in-laboratorybiastowardssupinesleepmightcauseoverestimationofOSAseverity.Figure2clearly

illustrates a significant reduction inmedianAHI,whenadjusted, calculated in accordancewith the

supine sleep time at homewith inactive SPT. These results emphasize the vigilance neededwhen

interpreting sleep study results inPP. There is a riskofoverestimatingOSA severity, resulting in a

significantimpactinclinicalpractice,withconsequencesfortreatmentrecommendations.

Besidesthesupinetrunkbodyposition,thepositionofthehead,andpronesleepingpositionhave

impact on OSA severity as well. Van Kesteren et al. reported that in 46.2% of supine position-

dependentpatients,headpositionwasofconsiderableinfluenceontheAHI.20Bidarion-Monirietal.

studiedtheeffectofpronepositioninOSAandconcludedthatupperairwaycollapsewasreducedin

pronepositionwithsignificantimprovementoftheAHIandoxygendesaturationindexcomparedto

bothlateralassupineposition.Thesefindingsindicatethatlesstimespentinproneposition,leadsto

anincreaseofOSAseverity.21Diseaseseveritymayinfluencetimespentinthesupineposition.Kaur

et al. found an inverse correlation between the supine AHI and the percentage of TST in supine

133

7

Polysomnography and sleep position, an Heisenberg phenomenon?

Figure3.DistributionofOSAseveritymeasuredwithtypeIIPSGandduringtheinactive(diagnostic)

phaseofSPT

DISCUSSION

Heisenbergiscreditedfortheuncertaintyprinciple,thefactthattheperformanceofatestinfluences

itsoutcome.TheresultsofthisstudysuggestthatthisphenomenonoccurswhenPPundergoaPSG.

TodatethisisthelargestcohortstudyobjectivelyevaluatingtheeffectofPSGapparatusonsleeping

position.Ourresultssuggestthatpatientsspendsignificantlymoretimeinthesupinepositionwhilst

undergoing a PSG, which could result in overestimation of OSA in severity in PP. Supporting this

hypothesis,ourresultsareconsistentwithfoursimilar,small-scalestudies.12-14,19

Loganetal. includedsixteenpatients,whounderwenttypeIPSGfollowedbyathometypeIIPSG.

The sensors were attached to a device situated above the bed, not on the chest. Patients spent

significantlylesstimeinthebackpostureduringthesecondathomePSGcomparedtoin-laboratory

PSG.12InthestudybyMeterskyetal.twelvePPwhounderwentanadditionalPSGduringwhichno

PSG leadswere attached. Time spent in supinepositionwas56%greaterduring thePSGnight in

comparison to the non-PSG night. 13 Two studies used a similar study design as described in this

paper, comparingobjectivemeasurementof timespent invarious sleepingpositionsbetweenPSG

andanon-activevibro-tactileneck-worndevice.14,19InthestudybyBignoldetal.patientsreceived

oneweekactiveandoneweekinactivetreatmentseparatedbyoneweekandinrandomizedorder.

They found that the supine sleeping time during the in-laboratory sleep study was significantly

greatercomparedtothein-homesupinesleepingtimemeasuredduringinactivetreatment.(36.6%

±5.7%vs.19.3%±4.3%,p=0.002).14Wimaleswarenetal.reported35.1%±25.1%supinesleeping

timeduringPSGvs.25%±21.4%athome,p=0.007in18patients.19Bothstudiesconcludethatthe

in-laboratorybiastowardssupinesleepmightcauseoverestimationofOSAseverity.Figure2clearly

illustrates a significant reduction inmedianAHI,whenadjusted, calculated in accordancewith the

supine sleep time at homewith inactive SPT. These results emphasize the vigilance neededwhen

interpreting sleep study results inPP. There is a riskofoverestimatingOSA severity, resulting in a

significantimpactinclinicalpractice,withconsequencesfortreatmentrecommendations.

Besidesthesupinetrunkbodyposition,thepositionofthehead,andpronesleepingpositionhave

impact on OSA severity as well. Van Kesteren et al. reported that in 46.2% of supine position-

dependentpatients,headpositionwasofconsiderableinfluenceontheAHI.20Bidarion-Monirietal.

studiedtheeffectofpronepositioninOSAandconcludedthatupperairwaycollapsewasreducedin

pronepositionwithsignificantimprovementoftheAHIandoxygendesaturationindexcomparedto

bothlateralassupineposition.Thesefindingsindicatethatlesstimespentinproneposition,leadsto

anincreaseofOSAseverity.21Diseaseseveritymayinfluencetimespentinthesupineposition.Kaur

et al. found an inverse correlation between the supine AHI and the percentage of TST in supine

134

Chapter 7

position.Theauthorshypothesizeaself-correctingeffect inPPwithmoreseveredisease insupine

position.22

Limitations

Therearesomelimitationstothisstudy.Firstofall, theSPT isnotadiagnosticmodality;therefore

thedatamustbeinterpretedwithcare.Allpatientsincludedinthisstudywerepositional.Onecould

argue that this could be of influence, nevertheless studies report no difference in time spent in

supinepositionbetweenNPPandPP.23Secondly,itmustbetakenintoaccountthattheSPTcannot

distinguishwhetherapatient is awakeor asleep. Toenable statistical comparisonwe recalculated

the percentage of total time spend in supine position as part of the TRT during the PSG night.

Althoughtheuseofcomparableequipmentispreferred,thedifferenceofsupinebodypositionusing

TRTorTSTwasnotstatisticallydifferent.

Twovery small caseseries (N=4andN=15) reported that followingactiveverbal instructions to

avoid adopting the supine position, patients spent less time in the supine position. 4, 24 Before

initiationofSPT,patientshadreceivedtheresultsoftheirPSGandwereawareofthefactthatthey

shouldavoidthesupineposition.PatientsareinformedthattheSPThasastartdelayof30minutes

andthatiftheyprefertofallasleepinsupinepositioncandoso.Althoughthismightlimittheeffect

oftheverbal instructiongiventothepatient,onemustconsiderthatpatientsmayhavespent less

timeinsupinepositionduringtheinactive(diagnostic)phaseofSPTduetothefactthattheywere

awaretheyshouldavoidthesupineposition.

Finally,previousstudiesreportthatOSAseverityisnotonlyinfluencedbytrunkposition,butalsoby

thepositionoftheheadduringsleep.20HeadpositionwasnotrecordedduringthePSG.Thisisnot

onlyalimitationofthisstudybutalsoinclinicalpracticeingeneralsinceheadpositionmonitoringis

as yet not common practice. An advantage of our study is that during the PSG and inactive

(diagnostic)phaseofSPTthepositionsensorwasattachedtothetrunkenablingcomparison.There

isasignificantriskofbiaswhenthepositionsensorsarelocatedondifferentbodypositions.

Previousmentionedlimitationsmayimpactourresults,causinganoverestimationoftheinfluenceof

PSGapparatusonbodysleepingposition.Infuture,thereisaneedforlessinvasivePSGapparatus,

withlessornoimpactonsleepingposition.

Clinicalrelevance

Inclinicalpracticedifferenttreatmentmodalitiesareconsideredbasedon,amongotherthings,OSA

severity.WhileCPAPisthetherapyofchoiceincaseofsevereOSA,othertreatmentoptions,suchas

PTormandibularadvancementdevicesorupperairwaysurgery,canbeconsideredincaseofmildor

moderateOSA.Theresultsof this studysuggest thatbodyposition is influencedbyPSGapparatus

andasaresultmaycauseashiftinOSAseverityinPP.Whenevaluatingourresults,17patients(N=

9versusN=26)wouldnothavebeendiagnosedwithOSAwhenusingthepercentageofsupinebody

positionmeasured during the inactive (diagnostic) phase of SPT. Thismay have consequences for

treatmentrecommendationsandinsomecasesmightleadtoovertreatment.

CONCLUSION

ThisstudyshowsthatwearingPSGapparatusmaycausepatientstospendmoretimeinthesupine

sleepingposition.ThisleadstoanincreaseinOSAseveritymeasuredbyPSGinPP,whichcouldhave

significant impact on both clinical practice and research. There is a need for less invasive PSG

apparatus,withlessimpactonsleepingposition.

135

7

Polysomnography and sleep position, an Heisenberg phenomenon?

position.Theauthorshypothesizeaself-correctingeffect inPPwithmoreseveredisease insupine

position.22

Limitations

Therearesomelimitationstothisstudy.Firstofall, theSPT isnotadiagnosticmodality;therefore

thedatamustbeinterpretedwithcare.Allpatientsincludedinthisstudywerepositional.Onecould

argue that this could be of influence, nevertheless studies report no difference in time spent in

supinepositionbetweenNPPandPP.23Secondly,itmustbetakenintoaccountthattheSPTcannot

distinguishwhetherapatient is awakeor asleep. Toenable statistical comparisonwe recalculated

the percentage of total time spend in supine position as part of the TRT during the PSG night.

Althoughtheuseofcomparableequipmentispreferred,thedifferenceofsupinebodypositionusing

TRTorTSTwasnotstatisticallydifferent.

Twovery small caseseries (N=4andN=15) reported that followingactiveverbal instructions to

avoid adopting the supine position, patients spent less time in the supine position. 4, 24 Before

initiationofSPT,patientshadreceivedtheresultsoftheirPSGandwereawareofthefactthatthey

shouldavoidthesupineposition.PatientsareinformedthattheSPThasastartdelayof30minutes

andthatiftheyprefertofallasleepinsupinepositioncandoso.Althoughthismightlimittheeffect

oftheverbal instructiongiventothepatient,onemustconsiderthatpatientsmayhavespent less

timeinsupinepositionduringtheinactive(diagnostic)phaseofSPTduetothefactthattheywere

awaretheyshouldavoidthesupineposition.

Finally,previousstudiesreportthatOSAseverityisnotonlyinfluencedbytrunkposition,butalsoby

thepositionoftheheadduringsleep.20HeadpositionwasnotrecordedduringthePSG.Thisisnot

onlyalimitationofthisstudybutalsoinclinicalpracticeingeneralsinceheadpositionmonitoringis

as yet not common practice. An advantage of our study is that during the PSG and inactive

(diagnostic)phaseofSPTthepositionsensorwasattachedtothetrunkenablingcomparison.There

isasignificantriskofbiaswhenthepositionsensorsarelocatedondifferentbodypositions.

Previousmentionedlimitationsmayimpactourresults,causinganoverestimationoftheinfluenceof

PSGapparatusonbodysleepingposition.Infuture,thereisaneedforlessinvasivePSGapparatus,

withlessornoimpactonsleepingposition.

Clinicalrelevance

Inclinicalpracticedifferenttreatmentmodalitiesareconsideredbasedon,amongotherthings,OSA

severity.WhileCPAPisthetherapyofchoiceincaseofsevereOSA,othertreatmentoptions,suchas

PTormandibularadvancementdevicesorupperairwaysurgery,canbeconsideredincaseofmildor

moderateOSA.Theresultsof this studysuggest thatbodyposition is influencedbyPSGapparatus

andasaresultmaycauseashiftinOSAseverityinPP.Whenevaluatingourresults,17patients(N=

9versusN=26)wouldnothavebeendiagnosedwithOSAwhenusingthepercentageofsupinebody

positionmeasured during the inactive (diagnostic) phase of SPT. Thismay have consequences for

treatmentrecommendationsandinsomecasesmightleadtoovertreatment.

CONCLUSION

ThisstudyshowsthatwearingPSGapparatusmaycausepatientstospendmoretimeinthesupine

sleepingposition.ThisleadstoanincreaseinOSAseveritymeasuredbyPSGinPP,whichcouldhave

significant impact on both clinical practice and research. There is a need for less invasive PSG

apparatus,withlessimpactonsleepingposition.

136

Chapter 7

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2. vanMaanen JP, RaveslootMJ, Safiruddin F, de Vries N. The Utility of Sleep Endoscopy in

Adults with Obstructive Sleep Apnea: A Review of the Literature. Current Otorhinolaryngology

Reports.2013;1(1):1-7

3. FrankMH,RaveslootMJ,vanMaanenJP,VerhagenE,deLangeJ,deVriesN.PositionalOSA

part 1: Towards a clinical classification system for position-dependent obstructive sleep apnoea.

SleepBreath.2015;19(2):473-80

4. CartwrightR,RistanovicR,DiazF,CaldarelliD,AlderG.Acomparativestudyof treatments

forpositionalsleepapnea.Sleep.1991;14(6):546-52

5. Oksenberg A. Positional and non-positional obstructive sleep apnea patients. Sleep Med.

2005;6(4):377-8

6. RichardW, Kox D, den Herder C, LamanM, van Tinteren H, de Vries N. The role of sleep

positioninobstructivesleepapneasyndrome.EurArchOtorhinolaryngol.2006;263(10):946-50

7. MarklundM, PerssonM, Franklin KA. Treatment success with amandibular advancement

deviceisrelatedtosupine-dependentsleepapnea.Chest.1998;114(6):1630-5

8. Oksenberg A, Gadoth N. Are we missing a simple treatment for most adult sleep apnea

patients?Theavoidanceofthesupinesleepposition.JSleepRes.2014;23(2):204-10

9. DieltjensM,VroegopAV,VerbruggenAE,etal.Apromisingconceptofcombinationtherapy

forpositionalobstructivesleepapnea.SleepBreath.2015;19(2):637-44

10. Benoist LB, Verhagen M, Torensma B, van Maanen JP, de Vries N. Positional therapy in

patientswith residual positional obstructive sleep apnea after upper airway surgery.SleepBreath.

2016

11. RaveslootMJL,WhiteD,HeinzerR,OksenbergA,PepinJL.EfficacyoftheNewGenerationof

Devices for Positional Therapy for PatientsWith Positional Obstructive Sleep Apnea: A Systematic

ReviewoftheLiteratureandMeta-Analysis.JClinSleepMed.2017;13(6):813-24

12. Logan MB, Branham GH, Eisenbeis JF, Hartse K. Unattended Home Monitoring in the

Evaluationof SleepApnea: Is it Equal toFormalPolysomnograph?Otolaryngology--HeadandNeck

Surgery.1996;115(2):P156-P56

13. Metersky ML, Castriotta RJ. The effect of polysomnography on sleep position: possible

implicationsonthediagnosisofpositionalobstructivesleepapnea.Respiration.1996;63(5):283-87

14. Bignold JJ,Mercer JD, Antic NA,McEvoy RD, Catcheside PG. Accurate positionmonitoring

andimprovedsupine-dependentobstructivesleepapneawithanewpositionrecordingandsupine

avoidancedevice.JClinSleepMed.2011;7(4):376-83

15. EijsvogelMM,UbbinkR,DekkerJ,etal.Sleeppositiontrainerversustennisballtechniquein

positionalobstructivesleepapneasyndrome.JClinSleepMed.2015;11(2):139-47.

16. vanMaanenJP,MeesterKA,DunLN,etal.Thesleeppositiontrainer:anewtreatmentfor

positionalobstructivesleepapnoea.SleepBreath.2013;17(2):771-9.

17. vanMaanen JP, de VriesN. Long-term effectiveness and compliance of positional therapy

with the sleep position trainer in the treatment of positional obstructive sleep apnea syndrome.

Sleep.2014;37(7):1209-15.

18. BerryRB,BudhirajaR,GottliebDJ,etal.Rulesforscoringrespiratoryeventsinsleep:update

ofthe2007AASMmanualforthescoringofsleepandassociatedevents:deliberationsofthesleep

apnea definitions task force of the American Academy of SleepMedicine. Journal of clinical sleep

medicine:JCSM:officialpublicationoftheAmericanAcademyofSleepMedicine.2012;8(5):597.

19. Wimaleswaran H, Yo S, Buzacott H, et al. Sleeping position during laboratory

polysomnography compared to habitual sleeping position at home In: Editor, ed.^eds. Sleeping

positionduring laboratorypolysomnographycompared tohabitual sleepingpositionathome.City,

2018.

20. vanKesterenER,vanMaanenJP,HilgevoordAA,LamanDM,deVriesN.Quantitativeeffects

of trunk and head position on the apnea hypopnea index in obstructive sleep apnea. Sleep.

2011;34(8):1075-81.

21. Bidarian-MoniriA,NilssonM,RasmussonL,AttiaJ,EjnellH.Theeffectofthepronesleeping

positiononobstructivesleepapnoea.Actaoto-laryngologica.2015;135(1):79-84.

22. Kaur A, Verma R, Gandhi A, et al. Effect of disease severity on determining body position

duringsleepinpatientswithpositionalobstructivesleepapnea.JournalofSleepandSleepDisorders

Research.2017;40(suppl_1):A233-A33.

23. JoostenSA,O'DriscollDM,BergerPJ,HamiltonGS.Supinepositionrelatedobstructivesleep

apneainadults:pathogenesisandtreatment.Sleepmedicinereviews.2014;18(1):7-17.

24. KaveyNB,BlitzerA,Gidro-FrankS,KorstanjeK.Sleepingpositionandsleepapneasyndrome.

Americanjournalofotolaryngology.1985;6(5):373-77.

137

7

Polysomnography and sleep position, an Heisenberg phenomenon?

REFERENCES

1. CartwrightRD.Effectofsleeppositiononsleepapneaseverity.Sleep.1984;7(2):110-4.

2. vanMaanen JP, RaveslootMJ, Safiruddin F, de Vries N. The Utility of Sleep Endoscopy in

Adults with Obstructive Sleep Apnea: A Review of the Literature. Current Otorhinolaryngology

Reports.2013;1(1):1-7.

3. FrankMH,RaveslootMJ,vanMaanenJP,VerhagenE,deLangeJ,deVriesN.PositionalOSA

part 1: Towards a clinical classification system for position-dependent obstructive sleep apnoea.

SleepBreath.2015;19(2):473-80.

4. CartwrightR,RistanovicR,DiazF,CaldarelliD,AlderG.Acomparativestudyof treatments

forpositionalsleepapnea.Sleep.1991;14(6):546-52.

5. Oksenberg A. Positional and non-positional obstructive sleep apnea patients. Sleep Med.

2005;6(4):377-8.

6. RichardW, Kox D, den Herder C, LamanM, van Tinteren H, de Vries N. The role of sleep

positioninobstructivesleepapneasyndrome.EurArchOtorhinolaryngol.2006;263(10):946-50.

7. MarklundM, PerssonM, Franklin KA. Treatment success with amandibular advancement

deviceisrelatedtosupine-dependentsleepapnea.Chest.1998;114(6):1630-5.

8. Oksenberg A, Gadoth N. Are we missing a simple treatment for most adult sleep apnea

patients?Theavoidanceofthesupinesleepposition.JSleepRes.2014;23(2):204-10.

9. DieltjensM,VroegopAV,VerbruggenAE,etal.Apromisingconceptofcombinationtherapy

forpositionalobstructivesleepapnea.SleepBreath.2015;19(2):637-44.

10. Benoist LB, Verhagen M, Torensma B, van Maanen JP, de Vries N. Positional therapy in

patientswith residual positional obstructive sleep apnea after upper airway surgery.SleepBreath.

2016.

11. RaveslootMJL,WhiteD,HeinzerR,OksenbergA,PepinJL.EfficacyoftheNewGenerationof

Devices for Positional Therapy for PatientsWith Positional Obstructive Sleep Apnea: A Systematic

ReviewoftheLiteratureandMeta-Analysis.JClinSleepMed.2017;13(6):813-24.

12. Logan MB, Branham GH, Eisenbeis JF, Hartse K. Unattended Home Monitoring in the

Evaluationof SleepApnea: Is it Equal toFormalPolysomnograph?Otolaryngology--HeadandNeck

Surgery.1996;115(2):P156-P56.

13. Metersky ML, Castriotta RJ. The effect of polysomnography on sleep position: possible

implicationsonthediagnosisofpositionalobstructivesleepapnea.Respiration.1996;63(5):283-87.

14. Bignold JJ,Mercer JD, Antic NA,McEvoy RD, Catcheside PG. Accurate positionmonitoring

andimprovedsupine-dependentobstructivesleepapneawithanewpositionrecordingandsupine

avoidancedevice.JClinSleepMed.2011;7(4):376-83.

15. EijsvogelMM,UbbinkR,DekkerJ,etal.Sleeppositiontrainerversustennisballtechniquein

positionalobstructivesleepapneasyndrome.JClinSleepMed.2015;11(2):139-47

16. vanMaanenJP,MeesterKA,DunLN,etal.Thesleeppositiontrainer:anewtreatmentfor

positionalobstructivesleepapnoea.SleepBreath.2013;17(2):771-9

17. vanMaanen JP, de VriesN. Long-term effectiveness and compliance of positional therapy

with the sleep position trainer in the treatment of positional obstructive sleep apnea syndrome.

Sleep.2014;37(7):1209-15

18. BerryRB,BudhirajaR,GottliebDJ,etal.Rulesforscoringrespiratoryeventsinsleep:update

ofthe2007AASMmanualforthescoringofsleepandassociatedevents:deliberationsofthesleep

apnea definitions task force of the American Academy of SleepMedicine. Journal of clinical sleep

medicine:JCSM:officialpublicationoftheAmericanAcademyofSleepMedicine.2012;8(5):597

19. Wimaleswaran H, Yo S, Buzacott H, et al. Sleeping position during laboratory

polysomnography compared to habitual sleeping position at home In: Editor, ed.^eds. Sleeping

positionduring laboratorypolysomnographycompared tohabitual sleepingpositionathome.City,

2018

20. vanKesterenER,vanMaanenJP,HilgevoordAA,LamanDM,deVriesN.Quantitativeeffects

of trunk and head position on the apnea hypopnea index in obstructive sleep apnea. Sleep.

2011;34(8):1075-81

21. Bidarian-MoniriA,NilssonM,RasmussonL,AttiaJ,EjnellH.Theeffectofthepronesleeping

positiononobstructivesleepapnoea.Actaoto-laryngologica.2015;135(1):79-84

22. Kaur A, Verma R, Gandhi A, et al. Effect of disease severity on determining body position

duringsleepinpatientswithpositionalobstructivesleepapnea.JournalofSleepandSleepDisorders

Research.2017;40(suppl_1):A233-A33

23. JoostenSA,O'DriscollDM,BergerPJ,HamiltonGS.Supinepositionrelatedobstructivesleep

apneainadults:pathogenesisandtreatment.Sleepmedicinereviews.2014;18(1):7-17

24. KaveyNB,BlitzerA,Gidro-FrankS,KorstanjeK.Sleepingpositionandsleepapneasyndrome.

Americanjournalofotolaryngology.1985;6(5):373-77

8Influence of position-dependencyon surgical success in sleep apneasurgery-asystematicreviewP.E.Vonk,P.J.Rotteveel,M.J.L.Ravesloot,C.denHaan,N.deVriesSleepBreath.2019Oct17.doi:10.1007/s11325-019-01935-y.

8Influence of position-dependencyon surgical success in sleep apneasurgery-asystematicreviewP.E.Vonk,P.J.Rotteveel,M.J.L.Ravesloot,C.denHaan,N.deVriesSleepBreath.2019Oct17.doi:10.1007/s11325-019-01935-y.

8Influence of position-dependencyon surgical success in sleep apneasurgery-asystematicreviewP.E.Vonk,P.J.Rotteveel,M.J.L.Ravesloot,C.denHaan,N.deVriesSleepBreath.2019Oct17.doi:10.1007/s11325-019-01935-y

8Influence of position-dependencyon surgical success in sleep apneasurgery-asystematicreviewP.E.Vonk,P.J.Rotteveel,M.J.L.Ravesloot,C.denHaan,N.deVriesSleepBreath.2019Oct17.doi:10.1007/s11325-019-01935-y.

140

Chapter 8

ABSTRACT

Purpose:Toevaluatetheinfluenceofposition-dependencyonsurgicalsuccessofupperairway(UA)

surgeryinobstructivesleepapnea(OSA)patients.

Methods:Systematicreview.

Results:Twoprospectivecohortstudiesandsevenretrospectivecohortstudieswereincludedinthis

review.Despitetheimportanceofthesubject,itremainsunclearwhetherposition-dependencyisa

predictor for surgical success. No differences were found in surgical success rate between non-

positional (NPP) and positional (PP) OSA patients undergoing uvulopalatopharyngoplasty/Z-

palatoplastywith orwithout radiofrequent thermotherapy of the tongue, isolated tongue base or

multilevel surgery and hypoglossal nerve stimulation. In one study PP undergoing relocation

pharyngoplasty had a greater chance of surgical success. In themajority of the remaining studies

surgicalsuccesswas infavorofNPP.Furthermore, inthevastpartof includedstudiestheeffectof

UAsurgerywassuggestedtobegreaterinthelateralpositionthansupineposition.

Conclusion:AlthoughpreoperativecharacteristicsinPP(e.g.lowerBMIandAHI)seemtobeinfavor

forhigher surgical success compared toNPP, it remainsunclearwhetherposition-dependency is a

predictorforsurgicaloutcome.Itissuggestedthatthelargestdifferencesandexpectedpreoperative

andpostoperativechangesoccurinnon-supineAHI.InPPthepreoperativenon-supineAHIisalready

lowercomparedtoNPPsuggestingalowerchanceofsurgicalsuccessinPP.

Keywords:obstructivesleepapnea,position-dependency,upperairwaysurgery,surgicalsuccess

INTRODUCTIONObstructivesleepapnea(OSA) is themostcommonsleep-relatedbreathingdisorder,characterized

by repetitive collapse of the upper airway (UA) causing desaturations due to cessation of airflow

during sleep. The prevalence of OSA is estimated at 12.5% in men and 5.9% in women.1 In the

majority of OSA patients respiratory obstructive events are more ascribed to supine sleeping

position. 2-7 A variety of definitions have been applied in the literature to describe position-

dependentOSA(POSA).CartwrightwasthefirsttodescribePOSAasthearbitrarycut-offpointofa

difference of 50% or more in apnea index between supine and non-supine positions.4 Overall,

positionalpatients(PP)tendtohavea lowertotalapneahypopneaindex(AHI),a lowerbodymass

index (BMI), fewersymptoms,areyoungerandhave lessco-morbiditycompared tonon-positional

patients (NPP).3,5,6,8,9OSA treatmentcomprises severaloptionssuchasconservative treatmentor

surgical interventions of the UA. Non-surgical interventions traditionally include weight loss,

treatment with mandibular advancement devices (MAD) or continuous positive airway pressure

(CPAP).10 Recently positional therapy (PT), with new generation devices has been added to the

conservative armamentarium.11-14 When alternatives for conservative treatment are required,

differentformsofUAsurgerycanbeconsideredwiththeaim,amongotherthings,to increasethe

surfaceareaoftheUAbytargetingstructuresrelatedtoobstruction.15

Thereareseveralknownfactorscontributingtolowersurgicalsuccess,suchasahighBMI,hightotal

AHI and a complete concentric collapse at palatal level observed during drug-induced sleep

endoscopy (DISE). 16-19 Likewise NPP tend to have more severe disease and a higher BMI in

comparisontoPP.Basedonthisinformation,onecouldhypothesizethatNPPhavealowerchanceof

surgicalsuccess.Ontheotherhand,onemightarguethatsincethenon-supineAHIinPPislowpre-

operatively,NPPhaveahigherchanceofsurgicalsuccesssincean improvementoftheAHI inboth

supineandnon-supinepositioncanbeachieved,thisincontrasttoPP.Althoughvariousarticleshave

beenwrittenonthissubjectmatter,theverdictremainsundecided.

Therefore, the aim of this studywas to perform a systematic review to evaluate the influence of

position-dependency on surgical success of UA surgery in OSA patients. We hypothesize that

position-dependency is a predictive factor for surgical success in OSA patients undergoing UA

surgery.

METHODS

Searchstrategyandinformationsources

A systematic review was performed according to the Preferred Reporting Items for Systematic

Reviews and Meta-Analyses (PRISMA).20 Studies were identified by searching PubMed, EMBASE,

141

8

Influence of position-dependency on surgical succes in sleep apnea surgery

ABSTRACT

Purpose:Toevaluatetheinfluenceofposition-dependencyonsurgicalsuccessofupperairway(UA)

surgeryinobstructivesleepapnea(OSA)patients.

Methods:Systematicreview.

Results:Twoprospectivecohortstudiesandsevenretrospectivecohortstudieswereincludedinthis

review.Despitetheimportanceofthesubject,itremainsunclearwhetherposition-dependencyisa

predictor for surgical success. No differences were found in surgical success rate between non-

positional (NPP) and positional (PP) OSA patients undergoing uvulopalatopharyngoplasty/Z-

palatoplastywith orwithout radiofrequent thermotherapy of the tongue, isolated tongue base or

multilevel surgery and hypoglossal nerve stimulation. In one study PP undergoing relocation

pharyngoplasty had a greater chance of surgical success. In themajority of the remaining studies

surgicalsuccesswas infavorofNPP.Furthermore, inthevastpartof includedstudiestheeffectof

UAsurgerywassuggestedtobegreaterinthelateralpositionthansupineposition.

Conclusion:AlthoughpreoperativecharacteristicsinPP(e.g.lowerBMIandAHI)seemtobeinfavor

forhigher surgical success compared toNPP, it remainsunclearwhetherposition-dependency is a

predictorforsurgicaloutcome.Itissuggestedthatthelargestdifferencesandexpectedpreoperative

andpostoperativechangesoccurinnon-supineAHI.InPPthepreoperativenon-supineAHIisalready

lowercomparedtoNPPsuggestingalowerchanceofsurgicalsuccessinPP.

Keywords:obstructivesleepapnea,position-dependency,upperairwaysurgery,surgicalsuccess

INTRODUCTIONObstructivesleepapnea(OSA) is themostcommonsleep-relatedbreathingdisorder,characterized

by repetitive collapse of the upper airway (UA) causing desaturations due to cessation of airflow

during sleep. The prevalence of OSA is estimated at 12.5% in men and 5.9% in women.1 In the

majority of OSA patients respiratory obstructive events are more ascribed to supine sleeping

position. 2-7 A variety of definitions have been applied in the literature to describe position-

dependentOSA(POSA).CartwrightwasthefirsttodescribePOSAasthearbitrarycut-offpointofa

difference of 50% or more in apnea index between supine and non-supine positions.4 Overall,

positionalpatients(PP)tendtohavea lowertotalapneahypopneaindex(AHI),a lowerbodymass

index (BMI), fewersymptoms,areyoungerandhave lessco-morbiditycompared tonon-positional

patients (NPP).3,5,6,8,9OSA treatmentcomprises severaloptionssuchasconservative treatmentor

surgical interventions of the UA. Non-surgical interventions traditionally include weight loss,

treatment with mandibular advancement devices (MAD) or continuous positive airway pressure

(CPAP).10 Recently positional therapy (PT), with new generation devices has been added to the

conservative armamentarium.11-14 When alternatives for conservative treatment are required,

differentformsofUAsurgerycanbeconsideredwiththeaim,amongotherthings,to increasethe

surfaceareaoftheUAbytargetingstructuresrelatedtoobstruction.15

Thereareseveralknownfactorscontributingtolowersurgicalsuccess,suchasahighBMI,hightotal

AHI and a complete concentric collapse at palatal level observed during drug-induced sleep

endoscopy (DISE). 16-19 Likewise NPP tend to have more severe disease and a higher BMI in

comparisontoPP.Basedonthisinformation,onecouldhypothesizethatNPPhavealowerchanceof

surgicalsuccess.Ontheotherhand,onemightarguethatsincethenon-supineAHIinPPislowpre-

operatively,NPPhaveahigherchanceofsurgicalsuccesssincean improvementoftheAHI inboth

supineandnon-supinepositioncanbeachieved,thisincontrasttoPP.Althoughvariousarticleshave

beenwrittenonthissubjectmatter,theverdictremainsundecided.

Therefore, the aim of this studywas to perform a systematic review to evaluate the influence of

position-dependency on surgical success of UA surgery in OSA patients. We hypothesize that

position-dependency is a predictive factor for surgical success in OSA patients undergoing UA

surgery.

METHODS

Searchstrategyandinformationsources

A systematic review was performed according to the Preferred Reporting Items for Systematic

Reviews and Meta-Analyses (PRISMA).20 Studies were identified by searching PubMed, EMBASE,

142

Chapter 8

Cochrane Database of Systematic Reviews/Wiley, Cochrane Central Register of Controlled

Trials/Wiley,CINAHL/EbscoandWebofScience/ClarivateAnalyticsupto24September2018(PRand

CdH). A search strategy was used with a combination of Medical Subject Headings (MeSH) and

keywords. Full search strategies for all databases are available as supplementary information

(Appendix1).

Studyselection

Duplicatearticleswereexcluded.Theremainingresultswerescreenedbasedontitleandabstractby

twoindependentinvestigators(PVandPR).Thefulltextofpotentiallyrelevantarticleswasretrieved

andexaminedbythesameresearchers.Disagreementineligibilitywasresolvedbyathirdresearcher

(MR).Referencelistsofeligiblestudieswerecheckedforadditionalreferences.

Eligibilitycriteria

StudiesreportingonsurgicalsuccessofUAsurgeryinOSApatients(confirmedbypolysomnography

(PSG)), specifically evaluating the role of position-dependency on surgical success, were included,

when (a modified version of) Cartwright’s criteria were applied to define position-dependency.4

Studies reporting on non-surgical interventions only, conference abstracts, editorials, posters,

protocolsandcasereportswereexcluded.Non-Englishstudieswereonlyincludedandtranslatedif

found to be of high priority (e.g. randomized trials or trials with superior number of patients or

follow-up).

OutcomeMeasures

TheprimaryoutcomemeasureofthisreviewwassurgicalsuccessinNPPandPP.Secondaryoutcome

measuresincludedpreoperativeandpostoperativetotalAHI,supineAHIandnon-supineAHI.

Datacollection

A standardized formwas used to extract data from the included studies for assessment of study

qualityandevidencesynthesis.Extractedinformationincluded:

-Source:author,publicationdata;

-Methods:studydesign,intervention;

-Participants:samplesize,gender,meanage,BMI,numberofNPPandPP;

-Primaryoutcomemeasures:surgicalsuccessinNPPandPP;

-Secondaryoutcomemeasure:preoperativeandpostoperativetotalAHI,supineAHIandnon-supine

AHI,asmeasuredbyPSGinNPPandPP.

Datawasextractedindependentlyanddiscrepancieswereidentifiedandresolvedthroughdiscussion

(with a third author if necessary). The flowof citations reviewed in the course of this reviewwas

recordedasdescribedbythePRISMAstatementseefigure1.

Levelofevidenceandqualityassessmentofincludedstudies

Level of evidencewas provided for all articles according to theOxford Centre for Evidence-based

Medicine.21 Quality assessment of the included studies was performed by two independent

reviewers (PVandPR)using theNIHQualityAssessmentTool forObservationalCohort andCross-

SectionalStudies.22

RESULTS

Theresultsofthesearchstrategyareshowninfigure1.Atotalof1791articleswereidentifiedafter

theinitialsearchandremovalofduplicates.Twoadditionalarticleswereidentifiedviareferencelists.

Based on title and abstract, 39 full text articleswere checked for eligibility. Nine articlesmet the

inclusioncriteriaforthissystematicreview:twoprospectivestudiesandsevenretrospectivestudies.

The main reason for exclusion was not reporting surgical success separately in NPP and PP. A

summaryoftheincludedstudiescanbefoundintable1.

143

8

Influence of position-dependency on surgical succes in sleep apnea surgery

Cochrane Database of Systematic Reviews/Wiley, Cochrane Central Register of Controlled

Trials/Wiley,CINAHL/EbscoandWebofScience/ClarivateAnalyticsupto24September2018(PRand

CdH). A search strategy was used with a combination of Medical Subject Headings (MeSH) and

keywords. Full search strategies for all databases are available as supplementary information

(Appendix1).

Studyselection

Duplicatearticleswereexcluded.Theremainingresultswerescreenedbasedontitleandabstractby

twoindependentinvestigators(PVandPR).Thefulltextofpotentiallyrelevantarticleswasretrieved

andexaminedbythesameresearchers.Disagreementineligibilitywasresolvedbyathirdresearcher

(MR).Referencelistsofeligiblestudieswerecheckedforadditionalreferences.

Eligibilitycriteria

StudiesreportingonsurgicalsuccessofUAsurgeryinOSApatients(confirmedbypolysomnography

(PSG)), specifically evaluating the role of position-dependency on surgical success, were included,

when (a modified version of) Cartwright’s criteria were applied to define position-dependency.4

Studies reporting on non-surgical interventions only, conference abstracts, editorials, posters,

protocolsandcasereportswereexcluded.Non-Englishstudieswereonlyincludedandtranslatedif

found to be of high priority (e.g. randomized trials or trials with superior number of patients or

follow-up).

OutcomeMeasures

TheprimaryoutcomemeasureofthisreviewwassurgicalsuccessinNPPandPP.Secondaryoutcome

measuresincludedpreoperativeandpostoperativetotalAHI,supineAHIandnon-supineAHI.

Datacollection

A standardized formwas used to extract data from the included studies for assessment of study

qualityandevidencesynthesis.Extractedinformationincluded:

-Source:author,publicationdata;

-Methods:studydesign,intervention;

-Participants:samplesize,gender,meanage,BMI,numberofNPPandPP;

-Primaryoutcomemeasures:surgicalsuccessinNPPandPP;

-Secondaryoutcomemeasure:preoperativeandpostoperativetotalAHI,supineAHIandnon-supine

AHI,asmeasuredbyPSGinNPPandPP.

Datawasextractedindependentlyanddiscrepancieswereidentifiedandresolvedthroughdiscussion

(with a third author if necessary). The flowof citations reviewed in the course of this reviewwas

recordedasdescribedbythePRISMAstatementseefigure1.

Levelofevidenceandqualityassessmentofincludedstudies

Level of evidencewas provided for all articles according to theOxford Centre for Evidence-based

Medicine.21 Quality assessment of the included studies was performed by two independent

reviewers (PVandPR)using theNIHQualityAssessmentTool forObservationalCohort andCross-

SectionalStudies.22

RESULTS

Theresultsofthesearchstrategyareshowninfigure1.Atotalof1791articleswereidentifiedafter

theinitialsearchandremovalofduplicates.Twoadditionalarticleswereidentifiedviareferencelists.

Based on title and abstract, 39 full text articleswere checked for eligibility. Nine articlesmet the

inclusioncriteriaforthissystematicreview:twoprospectivestudiesandsevenretrospectivestudies.

The main reason for exclusion was not reporting surgical success separately in NPP and PP. A

summaryoftheincludedstudiescanbefoundintable1.

144

Chapter 8

Figure1.Resultsofliteraturesearch

From: MoherD, Liberati A, Tetzlaff J, AltmanDG, The PRISMAGroup (2009).PreferredReporting

ItemsforSystematicReviewsandMeta-Analyses:ThePRISMAStatement.PLoSMed6(7):e1000097.

doi:10.1371/journal.pmed1000097

Recordsidentifiedthroughdatabasesearching

(n=2976)

Screening

Additionalrecordsidentifiedthroughothersources

(n=2)

Recordsscreenedafterduplicatesremoved(n=1791)

Recordsexcluded(n=1752)

Full-textarticlesassessedforeligibility(n=39)

Full-textarticlesexcluded(n=29)

Reasonsforexclusion:

-NoPOSA(n=25)

-NoOSA(n=2)

-Nosurgery(n=1)

-NosurgicalsuccessNPPvsPP(n=2)

Studiesincludedinqualitativesynthesis

(n=9)

Eligibility

Includ

ed

Identification

145

8

Influence of position-dependency on surgical succes in sleep apnea surgery

Figure1.Resultsofliteraturesearch

From: MoherD, Liberati A, Tetzlaff J, AltmanDG, The PRISMAGroup (2009).PreferredReporting

ItemsforSystematicReviewsandMeta-Analyses:ThePRISMAStatement.PLoSMed6(7):e1000097.

doi:10.1371/journal.pmed1000097

Recordsidentifiedthroughdatabasesearching

(n=2976)

Screening

Additionalrecordsidentifiedthroughothersources

(n=2)

Recordsscreenedafterduplicatesremoved(n=1791)

Recordsexcluded(n=1752)

Full-textarticlesassessedforeligibility(n=39)

Full-textarticlesexcluded(n=29)

Reasonsforexclusion:

-NoPOSA(n=25)

-NoOSA(n=2)

-Nosurgery(n=1)

-NosurgicalsuccessNPPvsPP(n=2)

Studiesincludedinqualitativesynthesis

(n=9)

Eligibility

Includ

ed

Identification

Table1.Sum

maryofin

clud

edst

udies

Author

Year

Coun

try

Design

Interventio

nLO

ESamplesize*

N(%

)Ag

e(years)

Male

N(%

)BM

I(m

2/kg)

Total

NPP

PP

To

tal

NPP

PP

Ka

stoe

ret

al.2

3

2018

Nethe

rland

sRe

trospe

ctive

Diffe

renttyp

esofUA

surgery

463

*(100

)24

(38.1)

39

(61.9)

--

--

-

Steffen

et

al.2

4

2018

German

yProspe

ctive

Hyp

oglossal

nerve

stim

ulation

344

(100

)13

(29.5)

31

(70.5)

58.2

±10

.0

44

(100

)

28.8

(19.7;

36.6)

28.7

(27.7;

34.1)

28.7

(25.6;

31.0)

Van

Maa

nen

etal.

25

2014

Nethe

rland

sRe

trospe

ctive

UPP

P/ZP

P(+/-RFT

B)

413

9(100

)71

(51.1)

68

(48.9)

45.0

[25 -

69]

127

(91.4)

27.4

[20.4 -

38.2]

--

Lieta

l.26

2013

Ta

iwan

Re

trospe

ctive

Relocatio

nph

aryn

goplasty

447

(100

)20

(42.6)

27

(57.4)

38.8

±9.0

44

(93.6)

27.3

±3.0

27.4

±3.4

27.2

±2.5

Van

Maa

nen

etal.

27

2012

Nethe

rland

sRe

trospe

ctive

Hyo

idsu

spen

sion

(+/-UPP

P/ZP

Pan

dRF

TB)

413

0(100

)60

(46.2)

70

(53.8)

49.9

±9.7

116

(72.5)

27.3

±2.8

--

Leeetal.

28

2011

So

uthKo

rea

Retrospe

ctive

UPP

P4

74

(100

)22

(29.7)

52

(70.3)

47

[21 -

71]

72

(97.3)

-26

.5

26.0

Kwon

eta

l.29

2010

So

uthKo

rea

Retrospe

ctive

Uvu

la-preserving

UPP

P 4

20*

(100

)3 (15)

17

(85)

40.0

±9.4

20

(100

.0)

27.2

±2.5

--

Leeetal.

30

2009

So

uthKo

rea

Retrospe

ctive

UPP

P4

69

(100

)25

(36.2)

44

(63.8)

45.4

[29 -

67]

69

(100

.0)

--

-

Stuc

ketal.

31

2005

German

yProspe

ctive

Isolated

hy

oid

suspen

sion

315

(100

)9 (60)

6 (40)

47.3

±12

.4

-27

.5

±3.3

--

Datapresented

asm

ean±stan

darddev

iatio

n,m

ean[ran

ge]o

rmed

ian(Q

25;Q

75)

LOELeve

lofE

vide

nce,NPPnon

-position

alobstruc

tiveslee

pap

neapa

tients,PPpo

sitio

nalo

bstruc

tiveslee

pap

neapa

tients,BMIb

odymassinde

x,UAup

per

airw

ay,U

PPPuv

ulop

alatop

haryng

oplasty,RFTBradiofreq

uentth

ermothe

rapy

ofthe

tong

uebase,ZPP

Z-palatop

lasty,LTFUlo

ssto

follo

w-up

*Su

bgroup

con

sistin

gofOSA

patientsu

ndergo

ingUAsurgerywith

preop

erativean

dpo

stop

erativepo

lysomno

grap

hy

146

Chapter 8

Table2.Qua

lityassessmen

tind

ividua

lstudies

Kastoer

etal.2

3 Steffen

etal.24

Van

Maanen

etal.2

5

Lieta

l.26

Van

Maanen

etal.2

7

Leeetal.2

8 Kw

onet

al.29

Leeetal.3

0 Stucket

al.31

1.W

asth

eresearch

que

stionorobjectiv

einth

ispap

erclearlyst

ated

?

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

2.W

asth

estud

ypo

pulatio

nclea

rly

specified

and

defined

?Ye

sYe

s*

Yes

Yes

Yes

Yes

Yes

Yes

Yes*

3.W

asth

epa

rticipationrateofe

ligible

person

satlea

st50%

?CD

∞

Yes

Yes

Yes

Yes

Yes

No

Yes

Yes

4.W

ereallthe

subjectsse

lected

or

recruitedfrom

thesameorsimila

rpo

pulatio

ns(inc

luding

thesametim

epe

riod)?Wereinclusionan

dex

clusion

crite

riafo

rbeing

inth

estud

yprespe

cifie

dan

dap

pliedun

iform

lyto

allpa

rticipan

ts?

Yes

Yes

Yes

Yes

Yes

No

Yes

No

Yes

5.W

asasa

mplesiz

ejustificatio

n,pow

er

descrip

tion,orv

arianc

ean

deffect

estim

atesprovide

d?

No

No

No

No

No

No

No

No

No

6.Forth

ean

alysesin

thispa

per,werethe

expo

sure(s)o

finterestm

easuredpriorto

theou

tcom

e(s)being

mea

sured?

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

7.W

asth

etim

eframesufficien

tsothat

oneco

uldreason

ablyexp

ecttoseean

associationbe

twee

nex

posureand

ou

tcom

eifitex

isted?

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

8.Forexp

osuresth

atcan

varyinamou

nt

orle

vel,didthestud

yex

aminediffe

rent

leve

lsofthe

exp

osureasre

latedtoth

eou

tcom

e(e.g.,catego

rieso

fexp

osure,or

expo

surem

easuredascon

tinuo

us

varia

ble)?

NA

NA

NA

NA

NA

NA

NA

NA

NA

Descriptionofstudies

VarioustypesofsurgicalinterventionsforOSAoftheUAwereevaluatedintheincludedstudies;the

vastmajorityreportedon(amodifiedversionof)uvulopalatopharyngoplasty(UPPP)withorwithout

radiofrequent thermotherapy of the tongue base (RFTB).23-27 The remaining studies evaluated

surgical success rate in OSA patients who underwent hypoglossal nerve stimulation and hyoid

suspensionwithorwithoutUPPPorZ-palatoplasty (ZPP)andRFTB.28-30Onestudydidnot focuson

onetypeofsurgerybutreportedonavarietyofdifferenttypesofsurgicalinterventions.31

InsevenstudiessurgicalsuccesswasdefinedaccordingtoSher’scriteria:apostoperativedecreaseof

thetotalAHIofatleast50%andreductionbelow20events/hourinpatientswhosepreoperativeAHI

was > 20/h.32 One study reported the respiratory disturbance index (RDI) instead of the AHI.29 In

anotherstudysurgicalsuccesswasdefinedasareductioninAHIofmorethan50%and/orcomplete

therapeuticresponse(AHI≤5events/hour).31

InsevenstudiesPOSAwasdefinedaccordingtoCartwright’scriteria;adifferenceof50%ormorein

AHIbetweensupineandnon-supinepositions.Twostudiesusedamodifiedversionwithadditional

criteriaconcerningminimumsleepingtimespentinsupineposition.29,31

Qualityassessmentindividualstudies

Overall, studies clearly specified their study population and selection criteria were adequately

reported except for one study.25 The vast part of included studies used a retrospective, but

consecutiverecruitmentofstudyparticipants.IntwostudiesapostoperativePSGwasperformedin

only a small numberofpatients,whichmakes the resultsof these studies susceptible to selection

bias.26, 31 In all studies the diagnosis of OSA was confirmed prior to UA surgery using PSG a

postoperative PSG after acceptable follow-up. Question 8was not applicable for all studies, since

patients were only included in the studies if they received a form of UA surgery. Measurement

instruments used for primary outcome measures were good; all studies used preoperative and

postoperativePSG.Allstudiesreportedonprognostic factors forsurgicalsuccess,suchasBMI,but

onlyafewstudiesmentionedchangesinBMIorpercentageofTSTinsupinepositionpreoperatively

and postoperatively. In only one study, logistic regression analysis was performed to assess the

influence of possible confounders.24 Therefore it is unclearwhether the surgical intervention(s) in

thesestudieswereindependentofotherchangesandfreeofbias.Table2showsadetailedoverview

ofthequalityassessmentofindividualstudies.

147

8

Influence of position-dependency on surgical succes in sleep apnea surgery

Table2.Qua

lityassessmen

tind

ividua

lstudies

Kastoer

etal.2

3 Steffen

etal.24

Van

Maanen

etal.2

5

Lieta

l.26

Van

Maanen

etal.2

7

Leeetal.2

8 Kw

onet

al.29

Leeetal.3

0 Stucket

al.31

1.W

asth

eresearch

que

stionorobjectiv

einth

ispap

erclearlyst

ated

?

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

2.W

asth

estud

ypo

pulatio

nclea

rly

specified

and

defined

?Ye

sYe

s*

Yes

Yes

Yes

Yes

Yes

Yes

Yes*

3.W

asth

epa

rticipationrateofe

ligible

person

satlea

st50%

?CD

∞

Yes

Yes

Yes

Yes

Yes

No

Yes

Yes

4.W

ereallthe

subjectsse

lected

or

recruitedfrom

thesameorsimila

rpo

pulatio

ns(inc

luding

thesametim

epe

riod)?Wereinclusionan

dex

clusion

crite

riafo

rbeing

inth

estud

yprespe

cifie

dan

dap

pliedun

iform

lyto

allpa

rticipan

ts?

Yes

Yes

Yes

Yes

Yes

No

Yes

No

Yes

5.W

asasa

mplesiz

ejustificatio

n,pow

er

descrip

tion,orv

arianc

ean

deffect

estim

atesprovide

d?

No

No

No

No

No

No

No

No

No

6.Forth

ean

alysesin

thispa

per,werethe

expo

sure(s)o

finterestm

easuredpriorto

theou

tcom

e(s)being

mea

sured?

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

7.W

asth

etim

eframesufficien

tsothat

oneco

uldreason

ablyexp

ecttoseean

associationbe

twee

nex

posureand

ou

tcom

eifitex

isted?

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

8.Forexp

osuresth

atcan

varyinamou

nt

orle

vel,didthestud

yex

aminediffe

rent

leve

lsofthe

exp

osureasre

latedtoth

eou

tcom

e(e.g.,catego

rieso

fexp

osure,or

expo

surem

easuredascon

tinuo

us

varia

ble)?

NA

NA

NA

NA

NA

NA

NA

NA

NA

Descriptionofstudies

VarioustypesofsurgicalinterventionsforOSAoftheUAwereevaluatedintheincludedstudies;the

vastmajorityreportedon(amodifiedversionof)uvulopalatopharyngoplasty(UPPP)withorwithout

radiofrequent thermotherapy of the tongue base (RFTB).23-27 The remaining studies evaluated

surgical success rate in OSA patients who underwent hypoglossal nerve stimulation and hyoid

suspensionwithorwithoutUPPPorZ-palatoplasty (ZPP)andRFTB.28-30Onestudydidnot focuson

onetypeofsurgerybutreportedonavarietyofdifferenttypesofsurgicalinterventions.31

InsevenstudiessurgicalsuccesswasdefinedaccordingtoSher’scriteria:apostoperativedecreaseof

thetotalAHIofatleast50%andreductionbelow20events/hourinpatientswhosepreoperativeAHI

was > 20/h.32 One study reported the respiratory disturbance index (RDI) instead of the AHI.29 In

anotherstudysurgicalsuccesswasdefinedasareductioninAHIofmorethan50%and/orcomplete

therapeuticresponse(AHI≤5events/hour).31

InsevenstudiesPOSAwasdefinedaccordingtoCartwright’scriteria;adifferenceof50%ormorein

AHIbetweensupineandnon-supinepositions.Twostudiesusedamodifiedversionwithadditional

criteriaconcerningminimumsleepingtimespentinsupineposition.29,31

Qualityassessmentindividualstudies

Overall, studies clearly specified their study population and selection criteria were adequately

reported except for one study.25 The vast part of included studies used a retrospective, but

consecutiverecruitmentofstudyparticipants.IntwostudiesapostoperativePSGwasperformedin

only a small numberofpatients,whichmakes the resultsof these studies susceptible to selection

bias.26, 31 In all studies the diagnosis of OSA was confirmed prior to UA surgery using PSG a

postoperative PSG after acceptable follow-up. Question 8was not applicable for all studies, since

patients were only included in the studies if they received a form of UA surgery. Measurement

instruments used for primary outcome measures were good; all studies used preoperative and

postoperativePSG.Allstudiesreportedonprognostic factors forsurgicalsuccess,suchasBMI,but

onlyafewstudiesmentionedchangesinBMIorpercentageofTSTinsupinepositionpreoperatively

and postoperatively. In only one study, logistic regression analysis was performed to assess the

influence of possible confounders.24 Therefore it is unclearwhether the surgical intervention(s) in

thesestudieswereindependentofotherchangesandfreeofbias.Table2showsadetailedoverview

ofthequalityassessmentofindividualstudies.

148

Chapter 8

9.W

eretheex

posurem

easures

(inde

pend

entv

ariables)c

learlydefined

,va

lid,reliable,and

implem

ented

consistentlyacrossa

llstud

ypa

rticipan

ts?

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

10.W

asth

eex

posure(s)a

ssessedmore

than

onc

eov

ertime?

No

Yes

No

No

No

No

No

No

No

11.W

eretheou

tcom

emea

sures

(dep

ende

ntvariables)c

learlydefined

,va

lid,reliable,and

implem

ented

consistentlyacrossa

llstud

ypa

rticipan

ts?

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

12.W

eretheou

tcom

eassessorsb

linde

dtoth

eex

posurest

atusofp

artic

ipan

ts?

NA

NA

NA

NA

NA

NA

NA

NA

NA

13.W

aslo

ssto

follo

w-upafterb

aseline

20%orless?

NA

Yes

NA

NA

NA

NA

NA

NA

Yes

14.W

ereke

ypo

tentialcon

foun

ding

va

riablesm

easuredan

dad

justed

statist

icallyfo

rthe

irim

pactonthe

relatio

nshipbe

twee

n ex

posure(s)a

nd

outcom

e(s)?

No

No

No

Yes

No

No

No

No

No

(+)=

yes,(-)=no

,CDcann

otdetermine,NAno

tapp

licab

le,N

Rno

trep

orted

*Stud

ypo

pulatio

nclea

rlysp

ecified

with

excep

tionofagiven

timeframe

∞Unc

learw

hetheracon

secu

tiveserie

sofo

nlyOSA

patientsu

ndergo

ingup

pera

irway

surgerywasin

clud

ed

Primaryoutcomemeasures

Prospectivestudies

Twoprospectivestudieswereidentified.Steffenetal.reportedtreatmentoutcomeinOSApatients

undergoing hypoglossal nerve stimulation. Surgical success rate was comparable in NPP and PP,

namely 83.3% versus 90.3%; p=0.608. An AHI < 5 events/hourwas seenmore often in PP (N=14)

compared toNPP (N=1),whichwas significantly higher (p=0.033).30 In a second prospective study

Stuck et al. found surgical success of isolated hyoid suspension in favor of NPP, namely 35.7%

comparedto16.7%inPP.29

Retrospectivestudies

Seven retrospectivestudieswere identified.Nosignificantdifferencewas found in surgical success

ratebetweenNPPandPPundergoinghyoidsuspensionwithorwithoutadditionalUPPPorZPPand

RFTB (40.0% versus 35.7%, p=0.615) 28 or UPPP/ZPP (with orwithout RFTB) (43.7% versus 35.3%;

p=0.313).23Inaddition,twootherstudiesanalysingtheresultsof(amodifiedversion)ofUPPPalso

foundcomparableresultsinsurgicalsuccess,butdidnottestourhypothesiswithstatisticaltesting.25,

26 Li et al. found that severe PP undergoing relocation pharyngoplasty had a greater chance of

surgicalsuccesscomparedtoNPP(67%vs.25%;p=0.008).24OtherstudieswereinfavorofNPP.

Kastoeretal.reportedalowerefficacyofUAsurgeryinPPascomparedtoNPP(33.3%vs62.5%).31

Lee et al. reported that patientswho failedUPPPwerepredominantly PP. Surgical success rate in

NPPandPPwas40%and22.7%,respectively.27Anoverviewofprimaryoutcomemeasurescanbe

foundintable3.

Because of the heterogeneity amongst the studies (i.e. medians vs. means, differences in scoring

criteria,surgicalinterventionsandoutcomesreported),ameta-analysiswasnotperformed.

149

8

Influence of position-dependency on surgical succes in sleep apnea surgery

Primaryoutcomemeasures

Prospectivestudies

Twoprospectivestudieswereidentified.Steffenetal.reportedtreatmentoutcomeinOSApatients

undergoing hypoglossal nerve stimulation. Surgical success rate was comparable in NPP and PP,

namely 83.3% versus 90.3%; p=0.608. An AHI < 5 events/hourwas seenmore often in PP (N=14)

compared toNPP (N=1),whichwas significantly higher (p=0.033).30 In a second prospective study

Stuck et al. found surgical success of isolated hyoid suspension in favor of NPP, namely 35.7%

comparedto16.7%inPP.29

Retrospectivestudies

Seven retrospectivestudieswere identified.Nosignificantdifferencewas found in surgical success

ratebetweenNPPandPPundergoinghyoidsuspensionwithorwithoutadditionalUPPPorZPPand

RFTB (40.0% versus 35.7%, p=0.615) 28 or UPPP/ZPP (with orwithout RFTB) (43.7% versus 35.3%;

p=0.313).23Inaddition,twootherstudiesanalysingtheresultsof(amodifiedversion)ofUPPPalso

foundcomparableresultsinsurgicalsuccess,butdidnottestourhypothesiswithstatisticaltesting.25,

26 Li et al. found that severe PP undergoing relocation pharyngoplasty had a greater chance of

surgicalsuccesscomparedtoNPP(67%vs.25%;p=0.008).24OtherstudieswereinfavorofNPP.

Kastoeretal.reportedalowerefficacyofUAsurgeryinPPascomparedtoNPP(33.3%vs62.5%).31

Lee et al. reported that patientswho failedUPPPwerepredominantly PP. Surgical success rate in

NPPandPPwas40%and22.7%,respectively.27Anoverviewofprimaryoutcomemeasurescanbe

foundintable3.

Because of the heterogeneity amongst the studies (i.e. medians vs. means, differences in scoring

criteria,surgicalinterventionsandoutcomesreported),ameta-analysiswasnotperformed.

150

Chapter 8

Table3.Prim

aryou

tcom

emea

sure:com

paris

onofsurgicalsuc

cessbetwee

nNPP

and

PP

Author

Year

Interventio

nSurgicalsuccess

pvalue

Surgicalsuccess

comparin

gNPP

and

PP

To

tal

NPP

PP

Kastoe

reta

l.23

20

18

Diffe

rentty

peso

fUA

surgery

44.4%

62.5%

33.3%

-Infa

voro

fNPP

Steffenetal.

24

2018

Hyp

oglossalnerve

stim

ulation

88.4%

83.3%

90.3%

0.60

8Nosig

nific

antd

ifferen

ce

VanMaa

nenetal.

25

2014

UPP

P/ZP

P(+/-RFT

B)

39.6%

43.7%

35.3%

0.31

3Nosig

nific

antd

ifferen

ce

Lieta

l.26

2013

Relocatio

n

pharyn

goplasty

49%

25%

67%

0.00

8*

Infa

voro

fPP

VanMaa

nenetal.

27

2012

Hyo

idsu

spen

sion

(+/-UPP

P/ZP

Pan

dRF

TB)

37.7%

40.0%

35.7%

0.61

5Nosig

nific

antd

ifferen

ce

Leeetal.

28

2011

UPP

P33

.8%

31.8%

34.6%

-Su

ggestiv

etobesimila

r

Kwon

eta

l.29

2010

Uvu

la-preservingUPP

P40

%

33.3%

41.1%

-Su

ggestiv

etobesimila

r

Leeetal.

30

2009

UPP

P29

%

40.0%

22.7%

-Infa

voro

fNPP

Stuc

ketal.

31

2005

Isolated

hyo

id

suspen

sion

42.8%

35.7%

16.7%

-Infa

voro

fNPP

NPPnon

-position

alobstruc

tiveslee

pap

neapa

tients,PPpo

sitio

nalo

bstruc

tiveslee

pap

neapa

tients,UAup

perairw

ay,U

PPPuv

ulop

alatop

haryng

oplasty,

RFTB

radiofreq

uentth

ermothe

rapy

ofthe

tong

uebase,ZPP

Z-palatop

lasty,

Table4.Secon

daryoutco

memea

sures:preop

erativean

dpo

stop

erativePSGparam

eterso

fstudy

pop

ulationasst

ratifiedbe

twee

nNPP

and

PP

Secondaryoutcomemeasures

Fiveoutofnine includedstudies reportedonall secondaryoutcomemeasuresstratifyingbetween

NPPandPP.TwostudiesonlyreportedontotalAHI.

Sixstudies23-25,27,28,33reportedareductionintotalAHIinbothNPPandPP,whilstonestudyonlyin

NPP.31 In NPP, the supine AHI significantly decreased in two studies.34, 35 Four studies reported a

significantdecreaseinsupineAHIinPPpostoperatively.23-25,28Inonestudy,supineAHIonlyslightly

reducedfrom49.8±19.9to44.2±31.2events/hour.27InNPP,adecreaseinthenon-supineAHIwas

foundinfivestudies.24,25,27,28,35 InPP,asignificantdecreaseofthenon-supineAHIwasreportedin

onlyonestudy.24Anoverviewofavailablesecondaryoutcomemeasurescanbefoundintable4.

151

8

Influence of position-dependency on surgical succes in sleep apnea surgery

Secondaryoutcomemeasures

Fiveoutofnine includedstudies reportedonall secondaryoutcomemeasuresstratifyingbetween

NPPandPP.TwostudiesonlyreportedontotalAHI.

Sixstudies23-25,27,28,33reportedareductionintotalAHIinbothNPPandPP,whilstonestudyonlyin

NPP.31 In NPP, the supine AHI significantly decreased in two studies.34, 35 Four studies reported a

significantdecreaseinsupineAHIinPPpostoperatively.23-25,28Inonestudy,supineAHIonlyslightly

reducedfrom49.8±19.9to44.2±31.2events/hour.27InNPP,adecreaseinthenon-supineAHIwas

foundinfivestudies.24,25,27,28,35 InPP,asignificantdecreaseofthenon-supineAHIwasreportedin

onlyonestudy.24Anoverviewofavailablesecondaryoutcomemeasurescanbefoundintable4.

152

Chapter 8

Author

Year

Preoperativ

ePSGparam

eters

Postop

erativePSGparam

eters

TotalA

HI

Supine

AHI

Non

-sup

ineAH

ITo

talA

HI

Supine

AHI

Non

-sup

ineAH

ITo

tal

NPP

PP

To

tal

NPP

PP

To

tal

NPP

PP

To

tal

NPP

PP

To

tal

NPP

PP

To

tal

NPP

PP

Kastoe

retal.

23

2018

-

38.5

(25.6,

52.5)

19.0

(14.3,

27.4)

--

--

--

-17

.8*

(5.3,

25.2)

13.1

(7.2,

28.5)

--

--

--

Steffen

etal.

24

2018

27

.5

(18.4,42

.3)

26.5

(17.5,

37.0)

30.0

(19.5,

54.5)

38.3

(21.6,

55.3)

--

--

-9.0*

(4.0,

17.5)

11.3

(5.0,

18.5)

8.5

(3.0,

14.0)

12.5

* (5.0,

24.1)

--

--

-

Van

Maa

nen

etal.

25

2014

18

.0(5.1,

69.6)

23.0

(14.3,

31.0)

15.5

(10.9,

21.7)

30.2

(19.1,

49.5)

27.2

(15.0,

49.5)

33.9

(22.2,

50.6)

12.5

29.2

5.6

11.2

* (5.6,

20.2)

11.0

* (6.1,

20.1)

11.5

* (5.0,

21.2)

20.5

* (8.3,

39.9)

20.5

* (7.8,

42.2)

20.9

* (8.4,

38.3)

5.7*

9.1*

3.6

Lie

tal.

26

2013

59

.5±18

.2

68.9

**

±17.4

52.5

**

±15.7

63.4

±22.5

65.4

±28.6

61.9

±17.1

33.7

±27.7

61.4

**

±14.8

13.3

**

±13.1

22.6

* ±1

9.6

31.0

* ±1

9.6

16.4

* ±1

2.8

27.6

* ±2

1.5

40.6

* ±2

4.4

17.9

* ±1

2.4

10.7

* ±1

6.7

15.8

* ±2

0.3

6.9*

±12.6

Van

Maa

nen

etal.

27

2012

36

.7±14

.4

41.3

32.7

51.2

±24.8

43.5

57.9

25.9

38.8

14.9

25.1

* 26

.6*

23.7

* 39

.3*

35.6

42.2

* 16

.8*

20.8

* 13

.3

Lee

et

al.28

20

11

-50

.0**

±19.2

30.9

**

±13.7

-53

.0

±20.9

51.1

±21.6

-46

.3**

±21.8

9.7**

±8

.4

-35

.4*

±23.7

22.9

* ±1

8.1

-46

.1

±30.1

35.3

* ±2

6.2

-18

.5*

±22.9

8.2

±10.8

Kwon

et

al.29

20

10

34.7±20

.0

--

51.2

--

18.4

--

24.2

* ±1

7.2

--

31.5

--

10.5

--

Lee

et

al.30

20

09

-48

.8**

±18.3

35.6

**

±16.9

-49

.8

±19.9

53.0

±20.9

-45

.1**

±19.2

8.2**

±8

.5

-33

.3

±25.1

27.4

±19.5

-44

.2

±31.2

38.7

±26.4

-15

.6

±21.6

10.0

±12.4

Stuc

ket

al.3

1 20

05

35.2°

±19.1

--

--

--

--

27.4°*

±26.2

--

--

--

--

Datapresented

asm

ean±stan

darddev

iatio

norm

edian(Q

1,Q3),°re

spira

torydist

urba

nceinde

x(RDI)

AHIa

pnea

-hyp

opne

ainde

x,NPP

non

-position

alobstruc

tivesle

epapn

eapatients,PPpo

sitiona

lobstruc

tivesle

epapn

eapatients

* pvalue

<0.05co

mpa

ringpreo

perativ

ean

dpo

stop

erativePS

Gparam

etersinsepa

rategroup

s(total,NPP

and

PP)

**pvalue

<0.05co

mpa

ringdiffe

renc

esin

PSG

param

etersb

etwee

nNPP

and

PP

Table3.Prim

aryou

tcom

emea

sure:com

paris

onofsurgicalsuc

cessbetwee

nNPP

and

PP

Author

Year

Interventio

nSurgicalsuccess

pvalue

Surgicalsuccess

comparin

gNPP

and

PP

To

tal

NPP

PP

Kastoe

reta

l.23

20

18

Diffe

rentty

peso

fUA

surgery

44.4%

62.5%

33.3%

-Infa

voro

fNPP

Steffenetal.

24

2018

Hyp

oglossalnerve

stim

ulation

88.4%

83.3%

90.3%

0.60

8Nosig

nific

antd

ifferen

ce

VanMaa

nenetal.

25

2014

UPP

P/ZP

P(+/-RFT

B)

39.6%

43.7%

35.3%

0.31

3Nosig

nific

antd

ifferen

ce

Lieta

l.26

2013

Relocatio

n

pharyn

goplasty

49%

25%

67%

0.00

8*

Infa

voro

fPP

VanMaa

nenetal.

27

2012

Hyo

idsu

spen

sion

(+/-UPP

P/ZP

Pan

dRF

TB)

37.7%

40.0%

35.7%

0.61

5Nosig

nific

antd

ifferen

ce

Leeetal.

28

2011

UPP

P33

.8%

31.8%

34.6%

-Su

ggestiv

etobesimila

r

Kwon

eta

l.29

2010

Uvu

la-preservingUPP

P40

%

33.3%

41.1%

-Su

ggestiv

etobesimila

r

Leeetal.

30

2009

UPP

P29

%

40.0%

22.7%

-Infa

voro

fNPP

Stuc

ketal.

31

2005

Isolated

hyo

id

suspen

sion

42.8%

35.7%

16.7%

-Infa

voro

fNPP

NPPnon

-position

alobstruc

tiveslee

pap

neapa

tients,PPpo

sitio

nalo

bstruc

tiveslee

pap

neapa

tients,UAup

perairw

ay,U

PPPuv

ulop

alatop

haryng

oplasty,

RFTB

radiofreq

uentth

ermothe

rapy

ofthe

tong

uebase,ZPP

Z-palatop

lasty,

Table4.Secon

daryoutco

memea

sures:preop

erativean

dpo

stop

erativePSGparam

eterso

fstudy

pop

ulationasst

ratifiedbe

twee

nNPP

and

PP

DISCUSSION

Theaimofthissystematicreviewwastoevaluatetheinfluenceofposition-dependencyonsurgical

successofUAsurgeryinOSApatients.Wehypothesizedthatthereisadifferenceinsurgicalsuccess

in NPP and PP undergoing UA surgery. Despite the importance of the subject, it remains unclear

whether position-dependency is a predictor for surgical success. Various small-scale studies,

evaluatingdifferentsurgicalmodalitiesreportonthismatter.Themajorityofstudiesreportedonthe

surgicaloutcomesofdifferentformsofpalatalsurgery,inparticularUPPP.UPPPaimstoincreasethe

retropalatal lumenandreducethecollapsibilityofthepharynxbyresectionofthefreeedgeofthe

soft palate and uvula, in combination with a tonsillectomy. In some studies palatal surgery was

combinedwithRFTB—a temperature-controlled reductionof the tissueof the tonguebase—or

hyoid suspension, consisting of a dissection of the hyoid bone at both sides of themidline, after

whichsuturesareplacedthroughthethyroidcartilageandaroundthehyoidbone.29Thelatteraims

atcreatingagreaterairwaydimensionatthelevelofthetonguebaseandepiglottis.Inonestudythe

resultsofhypoglossalnervestimulationwerediscussed,whichisanoveldevelopmentfortreatment

of moderate to severe OSA patients with CPAP intolerance or failure. By using a unilateral

stimulation, selective fibres, which are mainly innervating the tongue protrusors, are stimulated

causingopeningoftheUAduringeverybreathingcycle.

When evaluating the influence of position-dependency on the surgical success of these different

forms of UA surgery, no differences were found in surgical success rate between NPP and PP

undergoing UPPP/ZPP (+/- RFTB)23, isolated tongue base or multilevel surgery28 and hypoglossal

nerve stimulation.30 One study found that PP undergoing relocation pharyngoplasty had a greater

chanceofsurgicalsuccess.24Inthemajorityoftheremainingstudiessurgicalsuccesswasinfavorof

NPP.27,29,31Furthermore,inthevastpartofincludedstudiestheeffectofUAsurgerywassuggested

tobegreater in the lateralposition thansupineposition. In studies reportingonpreoperativeand

postoperativePSGparametersinNPPandPPasignificantreductionofthenon-supineAHIwasfound

inNPP,butnotinPP.

Thereisasignificantclinicaldiversityinthesestudies,complicatinginterpretationoftheresults,such

asdifferent formsofUAsurgeryanddifferentdefinitionsofsurgicalsuccessand insomestudiesa

modifiedversionsofCartwright’scriteriaforPOSAwasapplied.Levelofevidenceislow;studiesare

generally small-scale and retrospective. Another important consideration is that the inverse

relationshipwith BMI and AHI, is not only related to PP, but also to surgical success. Considering

these confounders is of utmost importance. Last but not least, studies did not correct for

153

8

Influence of position-dependency on surgical succes in sleep apnea surgery

Author

Year

Preoperativ

ePSGparam

eters

Postop

erativePSGparam

eters

TotalA

HI

Supine

AHI

Non

-sup

ineAH

ITo

talA

HI

Supine

AHI

Non

-sup

ineAH

ITo

tal

NPP

PP

To

tal

NPP

PP

To

tal

NPP

PP

To

tal

NPP

PP

To

tal

NPP

PP

To

tal

NPP

PP

Kastoe

retal.

23

2018

-

38.5

(25.6,

52.5)

19.0

(14.3,

27.4)

--

--

--

-17

.8*

(5.3,

25.2)

13.1

(7.2,

28.5)

--

--

--

Steffen

etal.

24

2018

27

.5

(18.4,42

.3)

26.5

(17.5,

37.0)

30.0

(19.5,

54.5)

38.3

(21.6,

55.3)

--

--

-9.0*

(4.0,

17.5)

11.3

(5.0,

18.5)

8.5

(3.0,

14.0)

12.5

* (5.0,

24.1)

--

--

-

Van

Maa

nen

etal.

25

2014

18

.0(5.1,

69.6)

23.0

(14.3,

31.0)

15.5

(10.9,

21.7)

30.2

(19.1,

49.5)

27.2

(15.0,

49.5)

33.9

(22.2,

50.6)

12.5

29.2

5.6

11.2

* (5.6,

20.2)

11.0

* (6.1,

20.1)

11.5

* (5.0,

21.2)

20.5

* (8.3,

39.9)

20.5

* (7.8,

42.2)

20.9

* (8.4,

38.3)

5.7*

9.1*

3.6

Lie

tal.

26

2013

59

.5±18

.2

68.9

**

±17.4

52.5

**

±15.7

63.4

±22.5

65.4

±28.6

61.9

±17.1

33.7

±27.7

61.4

**

±14.8

13.3

**

±13.1

22.6

* ±1

9.6

31.0

* ±1

9.6

16.4

* ±1

2.8

27.6

* ±2

1.5

40.6

* ±2

4.4

17.9

* ±1

2.4

10.7

* ±1

6.7

15.8

* ±2

0.3

6.9*

±12.6

Van

Maa

nen

etal.

27

2012

36

.7±14

.4

41.3

32.7

51.2

±24.8

43.5

57.9

25.9

38.8

14.9

25.1

* 26

.6*

23.7

* 39

.3*

35.6

42.2

* 16

.8*

20.8

* 13

.3

Lee

et

al.28

20

11

-50

.0**

±19.2

30.9

**

±13.7

-53

.0

±20.9

51.1

±21.6

-46

.3**

±21.8

9.7**

±8

.4

-35

.4*

±23.7

22.9

* ±1

8.1

-46

.1

±30.1

35.3

* ±2

6.2

-18

.5*

±22.9

8.2

±10.8

Kwon

et

al.29

20

10

34.7±20

.0

--

51.2

--

18.4

--

24.2

* ±1

7.2

--

31.5

--

10.5

--

Lee

et

al.30

20

09

-48

.8**

±18.3

35.6

**

±16.9

-49

.8

±19.9

53.0

±20.9

-45

.1**

±19.2

8.2**

±8

.5

-33

.3

±25.1

27.4

±19.5

-44

.2

±31.2

38.7

±26.4

-15

.6

±21.6

10.0

±12.4

Stuc

ket

al.3

1 20

05

35.2°

±19.1

--

--

--

--

27.4°*

±26.2

--

--

--

--

Datapresented

asm

ean±stan

darddev

iatio

norm

edian(Q

1,Q3),°re

spira

torydist

urba

nceinde

x(RDI)

AHIa

pnea

-hyp

opne

ainde

x,NPP

non

-position

alobstruc

tivesle

epapn

eapatients,PPpo

sitiona

lobstruc

tivesle

epapn

eapatients

* pvalue

<0.05co

mpa

ringpreo

perativ

ean

dpo

stop

erativePS

Gparam

etersinsepa

rategroup

s(total,NPP

and

PP)

**pvalue

<0.05co

mpa

ringdiffe

renc

esin

PSG

param

etersb

etwee

nNPP

and

PP

DISCUSSION

Theaimofthissystematicreviewwastoevaluatetheinfluenceofposition-dependencyonsurgical

successofUAsurgeryinOSApatients.Wehypothesizedthatthereisadifferenceinsurgicalsuccess

in NPP and PP undergoing UA surgery. Despite the importance of the subject, it remains unclear

whether position-dependency is a predictor for surgical success. Various small-scale studies,

evaluatingdifferentsurgicalmodalitiesreportonthismatter.Themajorityofstudiesreportedonthe

surgicaloutcomesofdifferentformsofpalatalsurgery,inparticularUPPP.UPPPaimstoincreasethe

retropalatal lumenandreducethecollapsibilityofthepharynxbyresectionofthefreeedgeofthe

soft palate and uvula, in combination with a tonsillectomy. In some studies palatal surgery was

combinedwithRFTB—a temperature-controlled reductionof the tissueof the tonguebase—or

hyoid suspension, consisting of a dissection of the hyoid bone at both sides of themidline, after

whichsuturesareplacedthroughthethyroidcartilageandaroundthehyoidbone.29Thelatteraims

atcreatingagreaterairwaydimensionatthelevelofthetonguebaseandepiglottis.Inonestudythe

resultsofhypoglossalnervestimulationwerediscussed,whichisanoveldevelopmentfortreatment

of moderate to severe OSA patients with CPAP intolerance or failure. By using a unilateral

stimulation, selective fibres, which are mainly innervating the tongue protrusors, are stimulated

causingopeningoftheUAduringeverybreathingcycle.

When evaluating the influence of position-dependency on the surgical success of these different

forms of UA surgery, no differences were found in surgical success rate between NPP and PP

undergoing UPPP/ZPP (+/- RFTB)23, isolated tongue base or multilevel surgery28 and hypoglossal

nerve stimulation.30 One study found that PP undergoing relocation pharyngoplasty had a greater

chanceofsurgicalsuccess.24Inthemajorityoftheremainingstudiessurgicalsuccesswasinfavorof

NPP.27,29,31Furthermore,inthevastpartofincludedstudiestheeffectofUAsurgerywassuggested

tobegreater in the lateralposition thansupineposition. In studies reportingonpreoperativeand

postoperativePSGparametersinNPPandPPasignificantreductionofthenon-supineAHIwasfound

inNPP,butnotinPP.

Thereisasignificantclinicaldiversityinthesestudies,complicatinginterpretationoftheresults,such

asdifferent formsofUAsurgeryanddifferentdefinitionsofsurgicalsuccessand insomestudiesa

modifiedversionsofCartwright’scriteriaforPOSAwasapplied.Levelofevidenceislow;studiesare

generally small-scale and retrospective. Another important consideration is that the inverse

relationshipwith BMI and AHI, is not only related to PP, but also to surgical success. Considering

these confounders is of utmost importance. Last but not least, studies did not correct for

154

Chapter 8

postoperativechangesinthetimespentinsupineposition.EspeciallyinPP,OSAseverityisstrongly

dependentonthisfactorandsubsequentlymayalsohaveinfluencedsurgicalsuccess.

Althoughtheresultsofthisstudyareinconclusive,thereareseveralfindingsthatareofimportance

whenevaluatingthepossibilityofUAsurgeryinOSApatients.Aspreviouslymentioned,thedecrease

innon-supineAHIissignificantlygreaterinNPPcomparedtoPP.23,25,27,28Thisisnotsurprising,since

inPP,thenon-supineAHIisusuallylowandthereforeonedoesnotexpectasignificantdecrease,this

incontrasttoNPP.ThesefindingsarestrengthenedbyastudybyBabademezetal.includingonlyPP.

They founda significantdecrease in supineAHI,butno significant changeswereobserved innon-

supineAHI postoperatively. The surgical cure rate of supine andnon-supineAHI in this studywas

87.5%comparedto56.3%,respectively.36

Furthermore, another interesting finding is that NPP often improve to less severe PP after UA

surgery;thedropinAHIismorepronouncedinnon-supineascomparedtosupineposition.Leeetal.

reportedthat64%ofNPPundergoingUPPPchangedtolessseverePP.25Inasecondstudyevaluating

OSApatients,42%ofallNPPchangedtolessseverePP.31Inathirdstudysimilarresultswerefound;

66.7%ofallNPPchangedtoPPaftermultilevelsurgery.InthePPgrouponly9.1%shiftedtoNPP.37

Clinicalrelevance

Recent developments have seen the introduction of a new, effective treatment modality for PP,

assistingpatientsinavoidingthesupineposition.38,39PPeffectivelytreatedwithPT,withpersistent

milder OSA,may need less aggressive secondary treatment.40 Furthermore, previous studies have

shownbeneficialeffectsinpatientswithpostoperativepersistentPOSA.InastudybyBenoistetal.

patientswere includedwithpartialeffectiveUAsurgery, totalAHIdecreasedfrom28.5 (18.0-52.8)

events/hourbeforesurgeryto18.3(13.7-24.0)events/houraftersurgery.Afteradditionaltreatment

withPTafurtherdecreaseto12.5(4.5–21.8)events/hourwasfound.41Similarresultswerefoundin

a studyby the samegroup inpatientswith residualPOSAaftermaxillomandibularadvancement.42

TheseresultsarestrengthenedbyastudyusingatheoreticalapproachofconcomitantPTinPPafter

UPPP/ZPP(+/-RFTB).Mathematicalcalculationssuggestedthat insuchpatientswithadditionalPT,

medianAHIwoulddecreasefrom18.0events/hourto4.5events/hour(p<0.001).23

Futureperspectives

Currenthighqualitydataislackingevaluatingtheimpactofposition-dependencyonsurgicalsuccess.

Thereisademandforhigh-qualityevidencefromlargerprospectivestudiesevaluatingdifferencesin

surgical success betweenNPP and PP, especially since themajority of OSA patient are PP.4,6,11,43

Thereshouldbeafocusonconfoundersinfluencingsurgicalsuccess,suchastheBMIandtotalAHI.

Evaluating surgical success in NPP and PP is also hindered by the fact that different types of UA

surgeryhavebeenappliedandnogeneralconsensushasbeenreachedontheusageofPOSAcriteria

and surgical success. To enable accurate comparison of surgical success in NPP and PP universal

definitionsshouldbeusedandsubanalysismustbeperformedfocusingonthedifferenttypesofUA

surgeryinOSApatients.

CONCLUSION

This systematic review evaluates the influence of position-dependency on surgical success of UA

surgeryinOSApatients.AlthoughpatientcharacteristicsinPPseemtobeinfavorforhighersurgical

successcomparedtoNPP,itremainsunclearwhetherposition-dependencyisapredictorforsurgical

outcome. Previous studies suggest that the largest differences and expected preoperative and

postoperativechangesoccurinthenon-supineAHI.InPPthepreoperativenon-supineAHIisalready

lowercomparedtoNPPsuggestingalowerchanceofsurgicalsuccessinPP.Furthermore,inpatients

withpartialeffectivesurgery(improvement,butnotcured),atransitionofNPPtolessseverePPis

often seen. In these patients additional treatment with PT can be offered as additional therapy.

155

8

Influence of position-dependency on surgical succes in sleep apnea surgery

postoperativechangesinthetimespentinsupineposition.EspeciallyinPP,OSAseverityisstrongly

dependentonthisfactorandsubsequentlymayalsohaveinfluencedsurgicalsuccess.

Althoughtheresultsofthisstudyareinconclusive,thereareseveralfindingsthatareofimportance

whenevaluatingthepossibilityofUAsurgeryinOSApatients.Aspreviouslymentioned,thedecrease

innon-supineAHIissignificantlygreaterinNPPcomparedtoPP.23,25,27,28Thisisnotsurprising,since

inPP,thenon-supineAHIisusuallylowandthereforeonedoesnotexpectasignificantdecrease,this

incontrasttoNPP.ThesefindingsarestrengthenedbyastudybyBabademezetal.includingonlyPP.

They founda significantdecrease in supineAHI,butno significant changeswereobserved innon-

supineAHI postoperatively. The surgical cure rate of supine andnon-supineAHI in this studywas

87.5%comparedto56.3%,respectively.36

Furthermore, another interesting finding is that NPP often improve to less severe PP after UA

surgery;thedropinAHIismorepronouncedinnon-supineascomparedtosupineposition.Leeetal.

reportedthat64%ofNPPundergoingUPPPchangedtolessseverePP.25Inasecondstudyevaluating

OSApatients,42%ofallNPPchangedtolessseverePP.31Inathirdstudysimilarresultswerefound;

66.7%ofallNPPchangedtoPPaftermultilevelsurgery.InthePPgrouponly9.1%shiftedtoNPP.37

Clinicalrelevance

Recent developments have seen the introduction of a new, effective treatment modality for PP,

assistingpatientsinavoidingthesupineposition.38,39PPeffectivelytreatedwithPT,withpersistent

milder OSA,may need less aggressive secondary treatment.40 Furthermore, previous studies have

shownbeneficialeffectsinpatientswithpostoperativepersistentPOSA.InastudybyBenoistetal.

patientswere includedwithpartialeffectiveUAsurgery, totalAHIdecreasedfrom28.5 (18.0-52.8)

events/hourbeforesurgeryto18.3(13.7-24.0)events/houraftersurgery.Afteradditionaltreatment

withPTafurtherdecreaseto12.5(4.5–21.8)events/hourwasfound.41Similarresultswerefoundin

a studyby the samegroup inpatientswith residualPOSAaftermaxillomandibularadvancement.42

TheseresultsarestrengthenedbyastudyusingatheoreticalapproachofconcomitantPTinPPafter

UPPP/ZPP(+/-RFTB).Mathematicalcalculationssuggestedthat insuchpatientswithadditionalPT,

medianAHIwoulddecreasefrom18.0events/hourto4.5events/hour(p<0.001).23

Futureperspectives

Currenthighqualitydataislackingevaluatingtheimpactofposition-dependencyonsurgicalsuccess.

Thereisademandforhigh-qualityevidencefromlargerprospectivestudiesevaluatingdifferencesin

surgical success betweenNPP and PP, especially since themajority of OSA patient are PP.4,6,11,43

Thereshouldbeafocusonconfoundersinfluencingsurgicalsuccess,suchastheBMIandtotalAHI.

Evaluating surgical success in NPP and PP is also hindered by the fact that different types of UA

surgeryhavebeenappliedandnogeneralconsensushasbeenreachedontheusageofPOSAcriteria

and surgical success. To enable accurate comparison of surgical success in NPP and PP universal

definitionsshouldbeusedandsubanalysismustbeperformedfocusingonthedifferenttypesofUA

surgeryinOSApatients.

CONCLUSION

This systematic review evaluates the influence of position-dependency on surgical success of UA

surgeryinOSApatients.AlthoughpatientcharacteristicsinPPseemtobeinfavorforhighersurgical

successcomparedtoNPP,itremainsunclearwhetherposition-dependencyisapredictorforsurgical

outcome. Previous studies suggest that the largest differences and expected preoperative and

postoperativechangesoccurinthenon-supineAHI.InPPthepreoperativenon-supineAHIisalready

lowercomparedtoNPPsuggestingalowerchanceofsurgicalsuccessinPP.Furthermore,inpatients

withpartialeffectivesurgery(improvement,butnotcured),atransitionofNPPtolessseverePPis

often seen. In these patients additional treatment with PT can be offered as additional therapy.

156

Chapter 8

Appendix1.Supplementaryinformation–fullsearchstrategies

PubMed,24-9-2018

Search Query Results#9 #1AND#2AND#8 644#8 #3OR#4OR#5OR#6OR#7 189576#7 ((velopharyn*[tiab] OR palat*[tiab] OR "Palate"[Mesh] OR "Tongue"[Mesh] OR

tongue*[tiab] OR gloss*[tiab] OR "Oropharynx"[Mesh] OR oropharyn*[tiab] ORlaryngopharyn*[tiab] OR tonsil*[tiab] OR "Hypopharynx"[Mesh] OR hypopharyn*[tiab] OR"Maxilla"[Mesh]ORmaxill*[tiab]ORbimaxill*[tiab]ORmandib*[tiab]OR“Mandible”[Mesh]OR "Nose"[Mesh] OR nose[tiab] OR nasal[tiab] OR upper airway[tiab]) AND ("SurgicalProcedures,Operative"[Mesh]OR"surgery"[Subheading]ORsurge*[tiab]ORsurgical*[tiab]ORoperati*[tiab]ORoperate*[tiab]ORprocedure*[tiab]))

184062

#6 ((Genioglossus[tiab] OR genioglossal) AND (advancement*[tiab])) OR (("MandibularAdvancement"[Mesh] OR "Surgical Procedures, Operative"[Mesh] OR "surgery"[Subheading] OR surge*[tiab] OR surgical*[tiab] OR operati*[tiab] OR operate*[tiab] ORprocedure*[tiab]ORadvancement*[tiab]ORosteotom*[tiab]OR“Osteotomy”[Mesh])AND("Maxilla"[Mesh] OR maxill*[tiab] OR bimaxill*[tiab] OR mandib*[tiab] OR“Mandible”[Mesh])) OR (("Osteogenesis, Distraction"[Mesh] OR distractionosteogenes*[tiab] ) AND ("Maxilla"[Mesh] OR maxill*[tiab] OR bimaxill*[tiab] ORmandib*[tiab]OR“Mandible”[Mesh]))

85296

#5 Hyoid suspension*[tiab] OR Hyoidthyroidpexi*[tiab] OR glossectom*[tiab] OR (("HyoidBone"[Mesh] OR hyoid*[tiab] OR “Hypopharynx”[Mesh] OR hypopharyn*[tiab] ORlaryngopharyn*[tiab] OR Lower pharyngeal airway*[tiab] OR "Tongue"[Mesh] ORtongue*[tiab])AND("SurgicalProcedures,Operative"[Mesh]OR"surgery"[Subheading]ORsurge*[tiab]ORsurgical*[tiab]ORoperati*[tiab]ORoperate*[tiab]ORprocedure*[tiab]ORresect*[tiab]))ORtonguesuspension*[tiab]ORtonguebasesuspension*[tiab]ORTransoralroboticsurg*[tiab]ORtrans-oralroboticsurg*[tiab]ORTORS[tiab]

20942

#4 "Tonsillectomy"[Mesh] OR adenotonsillectom*[tiab] OR tonsillectom*[tiab] ORTonsillotom*[tiab] OR palatopharyngoplast* [tiab] OR palatoplast* [tiab] OR palateplast*[tiab] OR pharyngoplast* [tiab] OR uvulopalatopharyngoplast* [tiab] ORuvulopharyngoplast* [tiab] OR pharyngouvulopalatoplast*[tiab] OR velopharyngoplast*[tiab]ORUPP[tiab]ORUPPP[tiab]ORUVPP*[tiab]ORUP3[tiab]

14784

#3 LAUP[tiab] OR laser assisted uvulop*[tiab] OR laser uvulop*[tiab] OR (("PulsedRadiofrequency Treatment"[Mesh] OR radiofrequency[tiab]) AND ("Palate"[Mesh] ORpalat*[tiab]OR"Tongue"[Mesh]ORtongue*[tiab]))ORPalatalstiffening[tiab]ORinjectionsnoreplast*[tiab]

494

#2 "Posture"[Mesh]ORposition*[tiab]ORpostur*[tiab]ORsupine*[tiab] 625134#1 "Sleep Apnea, Obstructive"[Mesh] OR OSA[tiab] OR OSAS[tiab] OR OSAHS[tiab] OR

apnoea[tiab]OR apnea[tiab]OR hypopnea[tiab]OR hypopnoea[tiab]OR apneic*[tiab]ORapnoeic*[tiab] OR sdb[tiab] OR sleep disordered[tiab] OR obesity hypoventilat*[tiab] ORpickwickian[tiab]ORupperairwayresistancesyndrom*[tiab]

51649

Embase.com,24-9-2018Search Query Results

#16 #1AND#2AND#15 1064#15 #3OR#4OR#8OR#13OR#14 219060#14 ('palate'/exp OR'tongue'/exp OR'oropharynx'/exp OR'velopharynx'/exp

OR'hypopharynx'/exp OR'maxilla'/exp OR'mandible'/exp OR'nose'/expORvelopharyn*:ab,ti ORpalat*:ab,ti ORtongue*:ab,ti ORgloss*:ab,tiORoropharyn*:ab,ti ORlaryngopharyn*:ab,ti ORtonsil*:ab,tiORhypopharyn*:ab,ti ORmaxill*:ab,ti ORbimaxill*:ab,ti ORmandib*:ab,tiORnose:ab,ti ORnasal:ab,ti OR'upper airway':ab,ti) AND ('surgery'/expOR'surgery'/lnk ORsurge*:ab,ti ORsurgical*:ab,ti ORoperati*:ab,tiORoperate*:ab,tiORprocedure*:ab,ti)

209245

#13 #9OR#10OR#11OR#12 93845#12 ('distractionosteogenesis'/expOR(distraction:ab,tiANDosteogenes*:ab,ti))AND

('maxilla'/exp OR'mandible'/exp ORmaxill*:ab,ti ORbimaxill*:ab,tiORmandib*:ab,ti)

2896

#11 ('surgery'/exp OR'surgery'/lnk ORsurge*:ab,ti ORsurgical*:ab,tiORoperati*:ab,ti ORoperate*:ab,ti ORprocedure*:ab,ti ORadvancement*:ab,tiORosteotom*:ab,ti) AND ('maxilla'/exp OR'mandible'/exp ORmaxill*:ab,tiORbimaxill*:ab,tiORmandib*:ab,ti)

92919

#10 'mandibular advancement'/exp OR'mandible osteotomy'/exp OR'maxillaosteotomy'/exp

4935

#9 'genioglossus advancement'/exp OR (((genioglossusORgenioglossal)NEAR/9advancement*):ab,ti)

157

#8 #5OR#6OR#7 28400#7 'tongue surgery'/exp OR'transoral robotic surgery'/exp OR'tongue

suspension*':ab,ti OR'tongue base suspension*':ab,ti OR'transoral roboticsurg*':ab,tiOR'transoralroboticsurg*':ab,tiORtors:ab,ti

1419

#6 ('hyoid bone'/exp OR'hypopharynx'/exp OR'tongue'/exp ORhyoid*:ab,tiORhypopharyn*:ab,ti ORlaryngopharyn*:ab,ti OR'lower pharyngealairway*':ab,ti ORtongue*:ab,ti) AND ('surgery'/exp OR'surgery'/lnkORsurge*:ab,ti ORsurgical*:ab,ti ORoperati*:ab,ti ORoperate*:ab,tiORprocedure*:ab,tiORresect*:ab,ti)

26666

#5 'hyoid suspension'/exp OR'glossectomy'/exp ORhyoidthyroidpexi*:ab,tiORglossectom*:ab,ti

2113

#4 'tonsillectomy'/exp OR'palatopharyngoplasty'/exp OR'palatoplasty'/expOR'uvulopalatal flap'/exp OR'uvulopalatopharyngoplasty'/exp OR'pharynxreconstruction'/exp ORadenotonsillectom*:ab,ti ORtonsillectom*:ab,tiORtonsillotom*:ab,ti ORpalatopharyngoplast*:ab,ti ORpalatoplast*:ab,tiOR'palate plast*':ab,ti ORpharyngoplast*:ab,tiORuvulopalatopharyngoplast*:ab,ti ORuvulopharyngoplast*:ab,tiORpharyngouvulopalatoplast*:ab,ti ORvelopharyngoplast*:ab,ti ORupp:ab,tiORuppp:ab,tiORuvpp*:ab,tiORup3:ab,ti

22065

#3 (laup:ab,ti OR'laser assisted uvulop*':ab,ti OR'laser uvulop*':ab,ti OR'palatalstiffening':ab,ti OR'injection snoreplast*':ab,ti OR'pulsed radiofrequencytreatment'/exp ORradiofrequency:ab,ti) AND ('palate'/exp OR'tongue'/expORpalat*:ab,tiORtongue*:ab,ti)

506

#2 'position'/expORposition*:ab,tiORpostur*:ab,tiORsupine*:ab,ti 764917#1 'sleep disordered breathing'/exp ORosa:ab,ti ORosas:ab,ti ORosahs:ab,ti

ORapnoea:ab,ti ORapnea:ab,ti ORhypopnea:ab,ti ORhypopnoea:ab,tiORapneic*:ab,ti ORapnoeic*:ab,ti ORsdb:ab,ti OR'sleep disordered':ab,ti OR((obesityNEXT/1hypoventilat*):ab,ti) ORpickwickian:ab,ti OR (('upper airwayresistance'NEXT/1syndrom*):ab,ti)OR'upperairwayresistancesyndrome'/exp

90375

CochraneLibrary,24-9-2018OnlyCENTRALhadresultsSearch Query Results

#1 (osaORosasORosahsORapnoeaORapneaORhypopneaORhypopnoeaORapneic*OR apnoeic* OR sdb OR “sleep disordered” OR (obesity NEXT hypoventilat*) ORpickwickianOR(“upperairwayresistance”NEXTsyndrom*)):ti,ab,kw

7677

#2 (LAUP OR (“laser assisted” NEXT uvulop*) OR (laser NEXT uvulop*) OR “Palatalstiffening” OR (injection NEXT snoreplast*) OR (radiofrequency AND (palat* ORtongue*))):ti,ab,kw

91

#3 (adenotonsillectom* OR tonsillectom* OR Tonsillotom* OR palatopharyngoplast* ORpalatoplast*OR(palateNEXTplast*)ORpharyngoplast*ORuvulopalatopharyngoplast*ORuvulopharyngoplast*ORpharyngouvulopalatoplast*ORvelopharyngoplast*ORUPPORUPPPORUVPP*ORUP3):ti,ab,kw

2534

#4 (Hyoidthyroidpexi*ORglossectom*OR(tongueNEXTsuspension*)OR(“tonguebase” 1016

157

8

Influence of position-dependency on surgical succes in sleep apnea surgery

Appendix1.Supplementaryinformation–fullsearchstrategies

PubMed,24-9-2018

Search Query Results#9 #1AND#2AND#8 644#8 #3OR#4OR#5OR#6OR#7 189576#7 ((velopharyn*[tiab] OR palat*[tiab] OR "Palate"[Mesh] OR "Tongue"[Mesh] OR

tongue*[tiab] OR gloss*[tiab] OR "Oropharynx"[Mesh] OR oropharyn*[tiab] ORlaryngopharyn*[tiab] OR tonsil*[tiab] OR "Hypopharynx"[Mesh] OR hypopharyn*[tiab] OR"Maxilla"[Mesh]ORmaxill*[tiab]ORbimaxill*[tiab]ORmandib*[tiab]OR“Mandible”[Mesh]OR "Nose"[Mesh] OR nose[tiab] OR nasal[tiab] OR upper airway[tiab]) AND ("SurgicalProcedures,Operative"[Mesh]OR"surgery"[Subheading]ORsurge*[tiab]ORsurgical*[tiab]ORoperati*[tiab]ORoperate*[tiab]ORprocedure*[tiab]))

184062

#6 ((Genioglossus[tiab] OR genioglossal) AND (advancement*[tiab])) OR (("MandibularAdvancement"[Mesh] OR "Surgical Procedures, Operative"[Mesh] OR "surgery"[Subheading] OR surge*[tiab] OR surgical*[tiab] OR operati*[tiab] OR operate*[tiab] ORprocedure*[tiab]ORadvancement*[tiab]ORosteotom*[tiab]OR“Osteotomy”[Mesh])AND("Maxilla"[Mesh] OR maxill*[tiab] OR bimaxill*[tiab] OR mandib*[tiab] OR“Mandible”[Mesh])) OR (("Osteogenesis, Distraction"[Mesh] OR distractionosteogenes*[tiab] ) AND ("Maxilla"[Mesh] OR maxill*[tiab] OR bimaxill*[tiab] ORmandib*[tiab]OR“Mandible”[Mesh]))

85296

#5 Hyoid suspension*[tiab] OR Hyoidthyroidpexi*[tiab] OR glossectom*[tiab] OR (("HyoidBone"[Mesh] OR hyoid*[tiab] OR “Hypopharynx”[Mesh] OR hypopharyn*[tiab] ORlaryngopharyn*[tiab] OR Lower pharyngeal airway*[tiab] OR "Tongue"[Mesh] ORtongue*[tiab])AND("SurgicalProcedures,Operative"[Mesh]OR"surgery"[Subheading]ORsurge*[tiab]ORsurgical*[tiab]ORoperati*[tiab]ORoperate*[tiab]ORprocedure*[tiab]ORresect*[tiab]))ORtonguesuspension*[tiab]ORtonguebasesuspension*[tiab]ORTransoralroboticsurg*[tiab]ORtrans-oralroboticsurg*[tiab]ORTORS[tiab]

20942

#4 "Tonsillectomy"[Mesh] OR adenotonsillectom*[tiab] OR tonsillectom*[tiab] ORTonsillotom*[tiab] OR palatopharyngoplast* [tiab] OR palatoplast* [tiab] OR palateplast*[tiab] OR pharyngoplast* [tiab] OR uvulopalatopharyngoplast* [tiab] ORuvulopharyngoplast* [tiab] OR pharyngouvulopalatoplast*[tiab] OR velopharyngoplast*[tiab]ORUPP[tiab]ORUPPP[tiab]ORUVPP*[tiab]ORUP3[tiab]

14784

#3 LAUP[tiab] OR laser assisted uvulop*[tiab] OR laser uvulop*[tiab] OR (("PulsedRadiofrequency Treatment"[Mesh] OR radiofrequency[tiab]) AND ("Palate"[Mesh] ORpalat*[tiab]OR"Tongue"[Mesh]ORtongue*[tiab]))ORPalatalstiffening[tiab]ORinjectionsnoreplast*[tiab]

494

#2 "Posture"[Mesh]ORposition*[tiab]ORpostur*[tiab]ORsupine*[tiab] 625134#1 "Sleep Apnea, Obstructive"[Mesh] OR OSA[tiab] OR OSAS[tiab] OR OSAHS[tiab] OR

apnoea[tiab]OR apnea[tiab]OR hypopnea[tiab]OR hypopnoea[tiab]OR apneic*[tiab]ORapnoeic*[tiab] OR sdb[tiab] OR sleep disordered[tiab] OR obesity hypoventilat*[tiab] ORpickwickian[tiab]ORupperairwayresistancesyndrom*[tiab]

51649

Embase.com,24-9-2018Search Query Results

#16 #1AND#2AND#15 1064#15 #3OR#4OR#8OR#13OR#14 219060#14 ('palate'/exp OR'tongue'/exp OR'oropharynx'/exp OR'velopharynx'/exp

OR'hypopharynx'/exp OR'maxilla'/exp OR'mandible'/exp OR'nose'/expORvelopharyn*:ab,ti ORpalat*:ab,ti ORtongue*:ab,ti ORgloss*:ab,tiORoropharyn*:ab,ti ORlaryngopharyn*:ab,ti ORtonsil*:ab,tiORhypopharyn*:ab,ti ORmaxill*:ab,ti ORbimaxill*:ab,ti ORmandib*:ab,tiORnose:ab,ti ORnasal:ab,ti OR'upper airway':ab,ti) AND ('surgery'/expOR'surgery'/lnk ORsurge*:ab,ti ORsurgical*:ab,ti ORoperati*:ab,tiORoperate*:ab,tiORprocedure*:ab,ti)

209245

#13 #9OR#10OR#11OR#12 93845#12 ('distractionosteogenesis'/expOR(distraction:ab,tiANDosteogenes*:ab,ti))AND

('maxilla'/exp OR'mandible'/exp ORmaxill*:ab,ti ORbimaxill*:ab,tiORmandib*:ab,ti)

2896

#11 ('surgery'/exp OR'surgery'/lnk ORsurge*:ab,ti ORsurgical*:ab,tiORoperati*:ab,ti ORoperate*:ab,ti ORprocedure*:ab,ti ORadvancement*:ab,tiORosteotom*:ab,ti) AND ('maxilla'/exp OR'mandible'/exp ORmaxill*:ab,tiORbimaxill*:ab,tiORmandib*:ab,ti)

92919

#10 'mandibular advancement'/exp OR'mandible osteotomy'/exp OR'maxillaosteotomy'/exp

4935

#9 'genioglossus advancement'/exp OR (((genioglossusORgenioglossal)NEAR/9advancement*):ab,ti)

157

#8 #5OR#6OR#7 28400#7 'tongue surgery'/exp OR'transoral robotic surgery'/exp OR'tongue

suspension*':ab,ti OR'tongue base suspension*':ab,ti OR'transoral roboticsurg*':ab,tiOR'transoralroboticsurg*':ab,tiORtors:ab,ti

1419

#6 ('hyoid bone'/exp OR'hypopharynx'/exp OR'tongue'/exp ORhyoid*:ab,tiORhypopharyn*:ab,ti ORlaryngopharyn*:ab,ti OR'lower pharyngealairway*':ab,ti ORtongue*:ab,ti) AND ('surgery'/exp OR'surgery'/lnkORsurge*:ab,ti ORsurgical*:ab,ti ORoperati*:ab,ti ORoperate*:ab,tiORprocedure*:ab,tiORresect*:ab,ti)

26666

#5 'hyoid suspension'/exp OR'glossectomy'/exp ORhyoidthyroidpexi*:ab,tiORglossectom*:ab,ti

2113

#4 'tonsillectomy'/exp OR'palatopharyngoplasty'/exp OR'palatoplasty'/expOR'uvulopalatal flap'/exp OR'uvulopalatopharyngoplasty'/exp OR'pharynxreconstruction'/exp ORadenotonsillectom*:ab,ti ORtonsillectom*:ab,tiORtonsillotom*:ab,ti ORpalatopharyngoplast*:ab,ti ORpalatoplast*:ab,tiOR'palate plast*':ab,ti ORpharyngoplast*:ab,tiORuvulopalatopharyngoplast*:ab,ti ORuvulopharyngoplast*:ab,tiORpharyngouvulopalatoplast*:ab,ti ORvelopharyngoplast*:ab,ti ORupp:ab,tiORuppp:ab,tiORuvpp*:ab,tiORup3:ab,ti

22065

#3 (laup:ab,ti OR'laser assisted uvulop*':ab,ti OR'laser uvulop*':ab,ti OR'palatalstiffening':ab,ti OR'injection snoreplast*':ab,ti OR'pulsed radiofrequencytreatment'/exp ORradiofrequency:ab,ti) AND ('palate'/exp OR'tongue'/expORpalat*:ab,tiORtongue*:ab,ti)

506

#2 'position'/expORposition*:ab,tiORpostur*:ab,tiORsupine*:ab,ti 764917#1 'sleep disordered breathing'/exp ORosa:ab,ti ORosas:ab,ti ORosahs:ab,ti

ORapnoea:ab,ti ORapnea:ab,ti ORhypopnea:ab,ti ORhypopnoea:ab,tiORapneic*:ab,ti ORapnoeic*:ab,ti ORsdb:ab,ti OR'sleep disordered':ab,ti OR((obesityNEXT/1hypoventilat*):ab,ti) ORpickwickian:ab,ti OR (('upper airwayresistance'NEXT/1syndrom*):ab,ti)OR'upperairwayresistancesyndrome'/exp

90375

CochraneLibrary,24-9-2018OnlyCENTRALhadresultsSearch Query Results

#1 (osaORosasORosahsORapnoeaORapneaORhypopneaORhypopnoeaORapneic*OR apnoeic* OR sdb OR “sleep disordered” OR (obesity NEXT hypoventilat*) ORpickwickianOR(“upperairwayresistance”NEXTsyndrom*)):ti,ab,kw

7677

#2 (LAUP OR (“laser assisted” NEXT uvulop*) OR (laser NEXT uvulop*) OR “Palatalstiffening” OR (injection NEXT snoreplast*) OR (radiofrequency AND (palat* ORtongue*))):ti,ab,kw

91

#3 (adenotonsillectom* OR tonsillectom* OR Tonsillotom* OR palatopharyngoplast* ORpalatoplast*OR(palateNEXTplast*)ORpharyngoplast*ORuvulopalatopharyngoplast*ORuvulopharyngoplast*ORpharyngouvulopalatoplast*ORvelopharyngoplast*ORUPPORUPPPORUVPP*ORUP3):ti,ab,kw

2534

#4 (Hyoidthyroidpexi*ORglossectom*OR(tongueNEXTsuspension*)OR(“tonguebase” 1016

158

Chapter 8

NEXTsuspension*)OR (“Transoral robotic”NEXTsurg*)OR (“transoral robotic”NEXTsurg*) OR TORS OR ((hyoid* OR hypopharyn* OR laryngopharyn* OR (“lowerpharyngeal” NEXT airway*) OR tongue*) AND (surge* OR surgical* OR operati* ORoperate*ORprocedure*ORresect*))):ti,ab,kw

#5 ((GenioglossusNEXTadvancement*)OR(genioglossalNEXTadvancement*)OR((surge*OR surgical* OR operati* OR operate* OR procedure* OR advancement* ORosteotom*) AND (maxill* OR bimaxill* OR mandib*)) OR ((distraction NEXTosteogenes*)AND(maxill*ORbimaxill*ORmandib*))):ti,ab,kw

5050

#6 ((velopharyn*ORpalat*ORtongue*ORgloss*ORoropharyn*ORlaryngopharyn*ORtonsil* OR hypopharyn* ORmaxill* OR bimaxill* ORmandib* OR nose OR nasal OR“upper airway”) AND (surge* OR surgical* OR operati* OR operate* ORprocedure*)):ti,ab,kw

13853

#7 #2OR#3OR#4OR#5OR#6 15220#8 (position*ORpostur*ORsupine*):ti,ab,kw 28653#9 #1AND#7AND#8 114

CINAHLviaEbscohost,24-9-2018Search Query ResultsS5 S3ANDS4 402S4 (MH"BodyPositions+")OR(TI(position*ORpostur*ORsupine*))OR(AB

(position*ORpostur*ORsupine*))70,431

S3 ( TI (OSA OR OSAS OR OSAHS OR apnoea OR apnea OR hypopnea ORhypopnoea OR apneic* OR apnoeic* OR sdb OR “sleep disordered” OR“obesity hypoventilat*” OR pickwickian OR “upper airway resistancesyndrom*”) OR AB (OSA OR OSAS OR OSAHS OR apnoea OR apnea ORhypopnea OR hypopnoea OR apneic* OR apnoeic* OR sdb OR “sleepdisordered”OR“obesityhypoventilat*”ORpickwickianOR“upperairwayresistancesyndrom*”))OR(S1ORS2)

8,867

S2 (MH"PickwickianSyndrome") 94S1 (MH"SleepApnea,Obstructive") 3,575

WebofScience,24-9-2018Search

Query

Results

#9 #8AND#2AND#1Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

752

#8 #7OR#6OR#5OR#4OR#3Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

115,558

#7 TOPIC:(((velopharyn* OR palat* OR tongue* OR gloss* OR oropharyn* ORlaryngopharyn*ORtonsil*ORhypopharyn*ORmaxill*ORbimaxill*ORmandib*ORnoseORnasalOR“upperairway”)AND(surge*ORsurgical*ORoperati*ORoperate*ORprocedure*)))Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

93,966

#6 TOPIC:(((GenioglossusORgenioglossal)NEAR/5advancement*)OR((surge*ORsurgical* OR operati* OR operate* OR procedure* OR advancement* ORosteotom*) AND (maxill* OR bimaxill* OR mandib*)) OR (“distractionosteogenes*”AND(maxill*ORbimaxill*ORmandib*)))Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

48,130

#5 TOPIC:(Hyoidthyroidpexi* OR glossectom* OR “tongue suspension*” OR“tonguebasesuspension*”OR“Transoral roboticsurg*”OR“transoral roboticsurg*” OR TORS OR ((hyoid* OR hypopharyn* OR laryngopharyn* OR “lowerpharyngeal airway*” OR tongue*) AND (surge* OR surgical* OR operati* ORoperate*ORprocedure*ORresect*)))Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

22,918

#4 TOPIC:(adenotonsillectom* OR tonsillectom* OR Tonsillotom* ORpalatopharyngoplast*ORpalatoplast*OR“palateplast*”ORpharyngoplast*ORuvulopalatopharyngoplast* OR uvulopharyngoplast* ORpharyngouvulopalatoplast*ORvelopharyngoplast*ORUPPORUPPPORUVPP*ORUP3)Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

12,164

#3 TOPIC:(LAUP OR “laser assisted uvulop*” OR “laser uvulop*” OR “Palatalstiffening” OR “injection snoreplast*”OR (radiofrequency AND (palat* ORtongue*)))Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

554

#2 TOPIC:(position*ORpostur*ORsupine*)Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

1,007,448

#1 TOPIC:(osaORosasORosahsORapnoeaORapneaORhypopneaORhypopnoeaOR apneic* OR apnoeic* OR sdb OR “sleep disordered” OR “obesityhypoventilat*”ORpickwickianOR“upperairwayresistancesyndrom*”)Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

67,157

159

8

Influence of position-dependency on surgical succes in sleep apnea surgery

NEXTsuspension*)OR (“Transoral robotic”NEXTsurg*)OR (“transoral robotic”NEXTsurg*) OR TORS OR ((hyoid* OR hypopharyn* OR laryngopharyn* OR (“lowerpharyngeal” NEXT airway*) OR tongue*) AND (surge* OR surgical* OR operati* ORoperate*ORprocedure*ORresect*))):ti,ab,kw

#5 ((GenioglossusNEXTadvancement*)OR(genioglossalNEXTadvancement*)OR((surge*OR surgical* OR operati* OR operate* OR procedure* OR advancement* ORosteotom*) AND (maxill* OR bimaxill* OR mandib*)) OR ((distraction NEXTosteogenes*)AND(maxill*ORbimaxill*ORmandib*))):ti,ab,kw

5050

#6 ((velopharyn*ORpalat*ORtongue*ORgloss*ORoropharyn*ORlaryngopharyn*ORtonsil* OR hypopharyn* ORmaxill* OR bimaxill* ORmandib* OR nose OR nasal OR“upper airway”) AND (surge* OR surgical* OR operati* OR operate* ORprocedure*)):ti,ab,kw

13853

#7 #2OR#3OR#4OR#5OR#6 15220#8 (position*ORpostur*ORsupine*):ti,ab,kw 28653#9 #1AND#7AND#8 114

CINAHLviaEbscohost,24-9-2018Search Query ResultsS5 S3ANDS4 402S4 (MH"BodyPositions+")OR(TI(position*ORpostur*ORsupine*))OR(AB

(position*ORpostur*ORsupine*))70,431

S3 ( TI (OSA OR OSAS OR OSAHS OR apnoea OR apnea OR hypopnea ORhypopnoea OR apneic* OR apnoeic* OR sdb OR “sleep disordered” OR“obesity hypoventilat*” OR pickwickian OR “upper airway resistancesyndrom*”) OR AB (OSA OR OSAS OR OSAHS OR apnoea OR apnea ORhypopnea OR hypopnoea OR apneic* OR apnoeic* OR sdb OR “sleepdisordered”OR“obesityhypoventilat*”ORpickwickianOR“upperairwayresistancesyndrom*”))OR(S1ORS2)

8,867

S2 (MH"PickwickianSyndrome") 94S1 (MH"SleepApnea,Obstructive") 3,575

WebofScience,24-9-2018Search

Query

Results

#9 #8AND#2AND#1Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

752

#8 #7OR#6OR#5OR#4OR#3Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

115,558

#7 TOPIC:(((velopharyn* OR palat* OR tongue* OR gloss* OR oropharyn* ORlaryngopharyn*ORtonsil*ORhypopharyn*ORmaxill*ORbimaxill*ORmandib*ORnoseORnasalOR“upperairway”)AND(surge*ORsurgical*ORoperati*ORoperate*ORprocedure*)))Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

93,966

#6 TOPIC:(((GenioglossusORgenioglossal)NEAR/5advancement*)OR((surge*ORsurgical* OR operati* OR operate* OR procedure* OR advancement* ORosteotom*) AND (maxill* OR bimaxill* OR mandib*)) OR (“distractionosteogenes*”AND(maxill*ORbimaxill*ORmandib*)))Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

48,130

#5 TOPIC:(Hyoidthyroidpexi* OR glossectom* OR “tongue suspension*” OR“tonguebasesuspension*”OR“Transoral roboticsurg*”OR“transoral roboticsurg*” OR TORS OR ((hyoid* OR hypopharyn* OR laryngopharyn* OR “lowerpharyngeal airway*” OR tongue*) AND (surge* OR surgical* OR operati* ORoperate*ORprocedure*ORresect*)))Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

22,918

#4 TOPIC:(adenotonsillectom* OR tonsillectom* OR Tonsillotom* ORpalatopharyngoplast*ORpalatoplast*OR“palateplast*”ORpharyngoplast*ORuvulopalatopharyngoplast* OR uvulopharyngoplast* ORpharyngouvulopalatoplast*ORvelopharyngoplast*ORUPPORUPPPORUVPP*ORUP3)Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

12,164

#3 TOPIC:(LAUP OR “laser assisted uvulop*” OR “laser uvulop*” OR “Palatalstiffening” OR “injection snoreplast*”OR (radiofrequency AND (palat* ORtongue*)))Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

554

#2 TOPIC:(position*ORpostur*ORsupine*)Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

1,007,448

#1 TOPIC:(osaORosasORosahsORapnoeaORapneaORhypopneaORhypopnoeaOR apneic* OR apnoeic* OR sdb OR “sleep disordered” OR “obesityhypoventilat*”ORpickwickianOR“upperairwayresistancesyndrom*”)Indexes=SCI-EXPANDED,SSCI,ESCITimespan=Allyears

67,157

160

Chapter 8

REFERENCES

1. HeinzerR,Marti-SolerH,Haba-RubioJ.Prevalenceofsleepapnoeasyndromeinthemiddle

tooldagegeneralpopulation.LancetRespirMed.2016;4(2):e5-6

2. vanMaanen JP, RaveslootMJ, Safiruddin F, de Vries N. The Utility of Sleep Endoscopy in

Adults with Obstructive Sleep Apnea: A Review of the Literature. Current Otorhinolaryngology

Reports.2013;1(1):1-7

3. FrankMH,RaveslootMJ,vanMaanenJP,VerhagenE,deLangeJ,deVriesN.PositionalOSA

part 1: Towards a clinical classification system for position-dependent obstructive sleep apnoea.

SleepBreath.2015;19(2):473-80

4. CartwrightRD.Effectofsleeppositiononsleepapneaseverity.Sleep.1984;7(2):110-4

5. OksenbergA,SilverbergDS,AronsE,RadwanH.Positionalvsnonpositionalobstructivesleep

apneapatients:anthropomorphic,nocturnalpolysomnographic,andmultiplesleeplatencytestdata.

Chest.1997;112(3):629-39

6. RichardW, Kox D, den Herder C, LamanM, van Tinteren H, de Vries N. The role of sleep

positioninobstructivesleepapneasyndrome.EurArchOtorhinolaryngol.2006;263(10):946-50

7. Heinzer R, Petitpierre NJ, Marti-Soler H, Haba-Rubio J. Prevalence and characteristics of

positionalsleepapneaintheHypnoLauspopulation-basedcohort.(1878-5506(Electronic))

8. MadorMJ, Kufel TJ,MagalangUJ, Rajesh SK,Watwe V, Grant BJ. Prevalence of positional

sleepapneainpatientsundergoingpolysomnography.Chest.2005;128(4):2130-7

9. ItasakaY,MiyazakiS, IshikawaK,TogawaK.The influenceofsleeppositionandobesityon

sleepapnea.PsychiatryClinNeurosci.2000;54(3):340-1

10. EpsteinLJ,KristoD,StrolloPJ,Jr.,etal.Clinicalguidelinefortheevaluation,managementand

long-termcareofobstructivesleepapneainadults.JClinSleepMed.2009;5(3):263-76

11. RaveslootMJ, vanMaanen JP, Dun L, de Vries N. The undervalued potential of positional

therapyinposition-dependentsnoringandobstructivesleepapnea-areviewoftheliterature.Sleep

Breath.2013;17(1):39-49

12. vanMaanen JP, de VriesN. Long-term effectiveness and compliance of positional therapy

with the sleep position trainer in the treatment of positional obstructive sleep apnea syndrome.

Sleep.2014;37(7):1209-15

13. vanMaanenJP,MeesterKA,DunLN,etal.Thesleeppositiontrainer:anewtreatmentfor

positionalobstructivesleepapnoea.SleepandBreathing.2013;17(2):771-79

14. RaveslootM,WhiteD,HeinzerR,OksenbergA,Pépin J. Efficacyof theNewGenerationof

Devices for Positional Therapy for Patients with Positional Obstructive Sleep Apnea: A Systematic

Review of the Literature and Meta-Analysis. Journal of clinical sleep medicine: JCSM: official

publicationoftheAmericanAcademyofSleepMedicine.2017.

15. Sundaram S, Bridgman SA, Lim J, Lasserson TJ. Surgery for obstructive sleep apnoea.

CochraneDatabaseSystRev.2005(4):CD001004.

16. ShieDY,TsouYA,TaiCJ,TsaiMH.Impactofobesityonuvulopalatopharyngoplastysuccessin

patients with severe obstructive sleep apnea: a retrospective single-center study in Taiwan. Acta

Otolaryngol.2013;133(3):261-9.

17. Liu SA, Li HY, Tsai WC, Chang KM. Associated factors to predict outcomes of

uvulopharyngopalatoplasty plus genioglossal advancement for obstructive sleep apnea.

Laryngoscope.2005;115(11):2046-50.

18. Vanderveken OM, Maurer JT, Hohenhorst W, et al. Evaluation of drug-induced sleep

endoscopyasapatient selection tool for implantedupperairway stimulation forobstructive sleep

apnea.JClinSleepMed.2013;9(5):433-8.

19. KoutsourelakisI,SafiruddinF,RaveslootM,ZakynthinosS,deVriesN.Surgeryforobstructive

sleepapnea:sleependoscopydeterminantsofoutcome.TheLaryngoscope.2012;122(11):2587-91.

20. MoherD,LiberatiA,TetzlaffJ,AltmanDG,GroupP.Preferredreportingitemsforsystematic

reviewsandmeta-analyses:thePRISMAstatement.BMJ.2009;339:b2535.

21. OCEBM Levels of EvidenceWorking Group. "The Oxford 2011 Levels of Evidence". Oxford

CentreforEvidence-BasedMedicine.http://www.cebm.net/index.aspx?o=5653.

22. Quality assessment tool for observational cohort and cross-sectional studies – NHLBI N.

https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools.

23. vanMaanenJ,WitteB,deVriesN.Theoreticalapproachtowardsincreasingeffectivenessof

palatal surgery in obstructive sleep apnea: role for concomitant positional therapy? Sleep and

Breathing.2014;18(2):341-49.

24. LiHY,ChengWN,ChuangLP,etal.Positionaldependencyandsurgicalsuccessofrelocation

pharyngoplasty amongpatientswith severe obstructive sleep apnea.OtolaryngolHeadNeck Surg.

2013;149(3):506-12.

25. LeeCH,KimSW,HanK,etal.Effectofuvulopalatopharyngoplastyonpositionaldependency

inobstructivesleepapnea.ArchOtolaryngolHeadNeckSurg.2011;137(7):675-9.

26. KwonM, JangYJ, LeeBJ,ChungYS.Theeffectofuvula-preservingpalatopharyngoplasty in

obstructive sleep apnea on globus sense and positional dependency. Clin Exp Otorhinolaryngol.

2010;3(3):141-6.

27. LeeCH,ShinHW,HanDH,etal.Theimplicationofsleeppositionintheevaluationofsurgical

outcomesinobstructivesleepapnea.OtolaryngolHeadNeckSurg.2009;140(4):531-5.

161

8

Influence of position-dependency on surgical succes in sleep apnea surgery

REFERENCES

1. HeinzerR,Marti-SolerH,Haba-RubioJ.Prevalenceofsleepapnoeasyndromeinthemiddle

tooldagegeneralpopulation.LancetRespirMed.2016;4(2):e5-6.

2. vanMaanen JP, RaveslootMJ, Safiruddin F, de Vries N. The Utility of Sleep Endoscopy in

Adults with Obstructive Sleep Apnea: A Review of the Literature. Current Otorhinolaryngology

Reports.2013;1(1):1-7.

3. FrankMH,RaveslootMJ,vanMaanenJP,VerhagenE,deLangeJ,deVriesN.PositionalOSA

part 1: Towards a clinical classification system for position-dependent obstructive sleep apnoea.

SleepBreath.2015;19(2):473-80.

4. CartwrightRD.Effectofsleeppositiononsleepapneaseverity.Sleep.1984;7(2):110-4.

5. OksenbergA,SilverbergDS,AronsE,RadwanH.Positionalvsnonpositionalobstructivesleep

apneapatients:anthropomorphic,nocturnalpolysomnographic,andmultiplesleeplatencytestdata.

Chest.1997;112(3):629-39.

6. RichardW, Kox D, den Herder C, LamanM, van Tinteren H, de Vries N. The role of sleep

positioninobstructivesleepapneasyndrome.EurArchOtorhinolaryngol.2006;263(10):946-50.

7. Heinzer R, Petitpierre NJ, Marti-Soler H, Haba-Rubio J. Prevalence and characteristics of

positionalsleepapneaintheHypnoLauspopulation-basedcohort.(1878-5506(Electronic)).

8. MadorMJ, Kufel TJ,MagalangUJ, Rajesh SK,Watwe V, Grant BJ. Prevalence of positional

sleepapneainpatientsundergoingpolysomnography.Chest.2005;128(4):2130-7.

9. ItasakaY,MiyazakiS, IshikawaK,TogawaK.The influenceofsleeppositionandobesityon

sleepapnea.PsychiatryClinNeurosci.2000;54(3):340-1.

10. EpsteinLJ,KristoD,StrolloPJ,Jr.,etal.Clinicalguidelinefortheevaluation,managementand

long-termcareofobstructivesleepapneainadults.JClinSleepMed.2009;5(3):263-76.

11. RaveslootMJ, vanMaanen JP, Dun L, de Vries N. The undervalued potential of positional

therapyinposition-dependentsnoringandobstructivesleepapnea-areviewoftheliterature.Sleep

Breath.2013;17(1):39-49.

12. vanMaanen JP, de VriesN. Long-term effectiveness and compliance of positional therapy

with the sleep position trainer in the treatment of positional obstructive sleep apnea syndrome.

Sleep.2014;37(7):1209-15.

13. vanMaanenJP,MeesterKA,DunLN,etal.Thesleeppositiontrainer:anewtreatmentfor

positionalobstructivesleepapnoea.SleepandBreathing.2013;17(2):771-79.

14. RaveslootM,WhiteD,HeinzerR,OksenbergA,Pépin J. Efficacyof theNewGenerationof

Devices for Positional Therapy for Patients with Positional Obstructive Sleep Apnea: A Systematic

Review of the Literature and Meta-Analysis. Journal of clinical sleep medicine: JCSM: official

publicationoftheAmericanAcademyofSleepMedicine.2017

15. Sundaram S, Bridgman SA, Lim J, Lasserson TJ. Surgery for obstructive sleep apnoea.

CochraneDatabaseSystRev.2005(4):CD001004

16. ShieDY,TsouYA,TaiCJ,TsaiMH.Impactofobesityonuvulopalatopharyngoplastysuccessin

patients with severe obstructive sleep apnea: a retrospective single-center study in Taiwan. Acta

Otolaryngol.2013;133(3):261-9

17. Liu SA, Li HY, Tsai WC, Chang KM. Associated factors to predict outcomes of

uvulopharyngopalatoplasty plus genioglossal advancement for obstructive sleep apnea.

Laryngoscope.2005;115(11):2046-50

18. Vanderveken OM, Maurer JT, Hohenhorst W, et al. Evaluation of drug-induced sleep

endoscopyasapatient selection tool for implantedupperairway stimulation forobstructive sleep

apnea.JClinSleepMed.2013;9(5):433-8

19. KoutsourelakisI,SafiruddinF,RaveslootM,ZakynthinosS,deVriesN.Surgeryforobstructive

sleepapnea:sleependoscopydeterminantsofoutcome.TheLaryngoscope.2012;122(11):2587-91

20. MoherD,LiberatiA,TetzlaffJ,AltmanDG,GroupP.Preferredreportingitemsforsystematic

reviewsandmeta-analyses:thePRISMAstatement.BMJ.2009;339:b2535

21. OCEBM Levels of EvidenceWorking Group. "The Oxford 2011 Levels of Evidence". Oxford

CentreforEvidence-BasedMedicine.http://www.cebm.net/index.aspx?o=5653

22. Quality assessment tool for observational cohort and cross-sectional studies – NHLBI N.

https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools

23. vanMaanenJ,WitteB,deVriesN.Theoreticalapproachtowardsincreasingeffectivenessof

palatal surgery in obstructive sleep apnea: role for concomitant positional therapy? Sleep and

Breathing.2014;18(2):341-49

24. LiHY,ChengWN,ChuangLP,etal.Positionaldependencyandsurgicalsuccessofrelocation

pharyngoplasty amongpatientswith severe obstructive sleep apnea.OtolaryngolHeadNeck Surg.

2013;149(3):506-12

25. LeeCH,KimSW,HanK,etal.Effectofuvulopalatopharyngoplastyonpositionaldependency

inobstructivesleepapnea.ArchOtolaryngolHeadNeckSurg.2011;137(7):675-9

26. KwonM, JangYJ, LeeBJ,ChungYS.Theeffectofuvula-preservingpalatopharyngoplasty in

obstructive sleep apnea on globus sense and positional dependency. Clin Exp Otorhinolaryngol.

2010;3(3):141-6

27. LeeCH,ShinHW,HanDH,etal.Theimplicationofsleeppositionintheevaluationofsurgical

outcomesinobstructivesleepapnea.OtolaryngolHeadNeckSurg.2009;140(4):531-5

162

Chapter 8

28. van Maanen JP, Ravesloot MJ, Witte BI, Grijseels M, de Vries N. Exploration of the

relationship between sleep position and isolated tongue base ormultilevel surgery in obstructive

sleepapnea.EurArchOtorhinolaryngol.2012;269(9):2129-36

29. StuckBA,NeffW,HormannK,etal.Anatomicchangesafterhyoidsuspensionforobstructive

sleepapnea:anMRIstudy.OtolaryngolHeadNeckSurg.2005;133(3):397-402

30. Steffen A, Hartmann JT, Konig IR, RaveslootMJL, Hofauer B, Heiser C. Evaluation of body

position in upper airway stimulation for obstructive sleep apnea-is continuous voltage sufficient

enough?SleepBreath.2018;22(4):1207-12

31. KastoerC,BenoistLBL,DieltjensM,etal.Comparisonofupperairwaycollapsepatternsand

its clinical significance: drug-induced sleependoscopy inpatientswithoutobstructive sleep apnea,

positionalandnon-positionalobstructivesleepapnea.SleepBreath.2018;22(4):939-48

32. Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifications of the upper

airwayinadultswithobstructivesleepapneasyndrome.Sleep.1996;19(2):156-77

33. Steffen A, Hartmann JT, König IR, Ravesloot MJ, Hofauer B, Heiser C. Evaluation of body

position in upper airway stimulation for obstructive sleep apnea—is continuous voltage sufficient

enough?SleepandBreathing.2018;22(4):1207-12

34. BakerAB, Xiao CC,O'Connell BP, Cline JM,GillespieMB.Uvulopalatopharyngoplasty:Does

Multilevel Surgery Increase Risk? Otolaryngology--head and neck surgery : official journal of

AmericanAcademyofOtolaryngology-HeadandNeckSurgery.2016;155(6):1053-58

35. vanMaanenJP,WitteBI,deVriesN.Theoreticalapproachtowardsincreasingeffectiveness

ofpalatalsurgeryinobstructivesleepapnea:roleforconcomitantpositionaltherapy?SleepBreath.

2014;18(2):341-9

36. Babademez MA, Ciftci B, Acar B, et al. Low-temperature bipolar radiofrequency ablation

(coblation) of the tongue base for supine-position-associated obstructive sleep apnea. ORL J

OtorhinolaryngolRelatSpec.2010;72(1):51-5

37. Lee YC, Eun YG, Shin SY, Kim SW. Change in position dependency in non-responders after

multilevel surgery for obstructive sleep apnea: analysis of polysomnographic parameters.EurArch

Otorhinolaryngol.2014;271(5):1081-5

38. RaveslootMJL,WhiteD,HeinzerR,OksenbergA,PepinJL.EfficacyoftheNewGenerationof

Devices for Positional Therapy for PatientsWith Positional Obstructive Sleep Apnea: A Systematic

ReviewoftheLiteratureandMeta-Analysis.JClinSleepMed.2017;13(6):813-24

39. VonkP,RaveslootM.Positionalobstructivesleepapnea.Somnologie.2018:1-6

40. RaveslootMJ,FrankMH,vanMaanenJP,VerhagenEA,deLangeJ,deVriesN.PositionalOSA

part 2: retrospective cohort analysis with a new classification system (APOC). Sleep Breath.

2016;20(2):881-8

41. Benoist LB, Verhagen M, Torensma B, van Maanen JP, de Vries N. Positional therapy in

patientswith residual positional obstructive sleep apnea after upper airway surgery.SleepBreath.

2016.

42. Benoist LBLdR, M.H.T.; de Lange, J.; de Vries, N. Residual POSA After Maxillomandibular

AdvancementinPatientswithSevereOSA.In:deVriesNR,M.;vanMaanen,J.,ed.PositionalTherapy

inObstructiveSleepApnea.Springer,Cham;2015:321-29.

43. Oksenberg A. Positional and non-positional obstructive sleep apnea patients. Sleep Med.

2005;6(4):377-8.

163

8

Influence of position-dependency on surgical succes in sleep apnea surgery

28. van Maanen JP, Ravesloot MJ, Witte BI, Grijseels M, de Vries N. Exploration of the

relationship between sleep position and isolated tongue base ormultilevel surgery in obstructive

sleepapnea.EurArchOtorhinolaryngol.2012;269(9):2129-36.

29. StuckBA,NeffW,HormannK,etal.Anatomicchangesafterhyoidsuspensionforobstructive

sleepapnea:anMRIstudy.OtolaryngolHeadNeckSurg.2005;133(3):397-402.

30. Steffen A, Hartmann JT, Konig IR, RaveslootMJL, Hofauer B, Heiser C. Evaluation of body

position in upper airway stimulation for obstructive sleep apnea-is continuous voltage sufficient

enough?SleepBreath.2018;22(4):1207-12.

31. KastoerC,BenoistLBL,DieltjensM,etal.Comparisonofupperairwaycollapsepatternsand

its clinical significance: drug-induced sleependoscopy inpatientswithoutobstructive sleep apnea,

positionalandnon-positionalobstructivesleepapnea.SleepBreath.2018;22(4):939-48.

32. Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifications of the upper

airwayinadultswithobstructivesleepapneasyndrome.Sleep.1996;19(2):156-77.

33. Steffen A, Hartmann JT, König IR, Ravesloot MJ, Hofauer B, Heiser C. Evaluation of body

position in upper airway stimulation for obstructive sleep apnea—is continuous voltage sufficient

enough?SleepandBreathing.2018;22(4):1207-12.

34. BakerAB, Xiao CC,O'Connell BP, Cline JM,GillespieMB.Uvulopalatopharyngoplasty:Does

Multilevel Surgery Increase Risk? Otolaryngology--head and neck surgery : official journal of

AmericanAcademyofOtolaryngology-HeadandNeckSurgery.2016;155(6):1053-58.

35. vanMaanenJP,WitteBI,deVriesN.Theoreticalapproachtowardsincreasingeffectiveness

ofpalatalsurgeryinobstructivesleepapnea:roleforconcomitantpositionaltherapy?SleepBreath.

2014;18(2):341-9.

36. Babademez MA, Ciftci B, Acar B, et al. Low-temperature bipolar radiofrequency ablation

(coblation) of the tongue base for supine-position-associated obstructive sleep apnea. ORL J

OtorhinolaryngolRelatSpec.2010;72(1):51-5.

37. Lee YC, Eun YG, Shin SY, Kim SW. Change in position dependency in non-responders after

multilevel surgery for obstructive sleep apnea: analysis of polysomnographic parameters.EurArch

Otorhinolaryngol.2014;271(5):1081-5.

38. RaveslootMJL,WhiteD,HeinzerR,OksenbergA,PepinJL.EfficacyoftheNewGenerationof

Devices for Positional Therapy for PatientsWith Positional Obstructive Sleep Apnea: A Systematic

ReviewoftheLiteratureandMeta-Analysis.JClinSleepMed.2017;13(6):813-24.

39. VonkP,RaveslootM.Positionalobstructivesleepapnea.Somnologie.2018:1-6.

40. RaveslootMJ,FrankMH,vanMaanenJP,VerhagenEA,deLangeJ,deVriesN.PositionalOSA

part 2: retrospective cohort analysis with a new classification system (APOC). Sleep Breath.

2016;20(2):881-8.

41. Benoist LB, Verhagen M, Torensma B, van Maanen JP, de Vries N. Positional therapy in

patientswith residual positional obstructive sleep apnea after upper airway surgery.SleepBreath.

2016

42. Benoist LBLdR, M.H.T.; de Lange, J.; de Vries, N. Residual POSA After Maxillomandibular

AdvancementinPatientswithSevereOSA.In:deVriesNR,M.;vanMaanen,J.,ed.PositionalTherapy

inObstructiveSleepApnea.Springer,Cham;2015:321-29

43. Oksenberg A. Positional and non-positional obstructive sleep apnea patients. Sleep Med.

2005;6(4):377-8

9The influence of position-dependency on surgical success inobstructive sleep apnea patientsundergoing maxillomandibularadvancementP.E.Vonk,P.J.Rotteveel,M.J.L.Ravesloot,J.P.T.F.Ho,J.deLange,N.deVriesJClinSleepMed.2019Nov27.pii:jc-19-00306.

9The influence of position-dependency on surgical success inobstructive sleep apnea patientsundergoing maxillomandibularadvancementP.E.Vonk,P.J.Rotteveel,M.J.L.Ravesloot,J.P.T.F.Ho,J.deLange,N.deVriesJClinSleepMed.2019Nov27.pii:jc-19-00306.

9The influence of position-dependency on surgical success inobstructive sleep apnea patientsundergoing maxillomandibularadvancementP.E.Vonk,P.J.Rotteveel,M.J.L.Ravesloot,J.P.T.F.Ho,J.deLange,N.deVriesJClinSleepMed.2019Nov27.pii:jc-19-00306

9The influence of position-dependency on surgical success inobstructive sleep apnea patientsundergoing maxillomandibularadvancementP.E.Vonk,P.J.Rotteveel,M.J.L.Ravesloot,J.P.T.F.Ho,J.deLange,N.deVriesJClinSleepMed.2019Nov27.pii:jc-19-0030.

166

Chapter 9

ABSTRACT

Study objectives: 1) to evaluate surgical success in obstructive sleep apnea (OSA) patients

undergoingmaxillomandibular advancement (MMA) stratifying for the reduction of both the total

apnea-hypopnea index (AHI) and the AHI in supine and non-supine position 2) to evaluate the

influence of position-dependency on surgical outcome 3) to analyze the prevalence of residual

position-dependentOSAinnon-respondersafterMMA.

Methods: a single-centre retrospective study including a consecutive series of OSA patients

undergoingMMAbetweenAugust2011andFebruary2019.

Results: In total,57patientswere included.Theoverall surgical successwas52.6%.Nosignificant

difference in surgical success between non-positional (NPP) and positional (PP) OSA patients was

found. Surgical success of the supineAHIwasnot significantly different betweenNPPandPP, but

surgical success of the non-supine AHI was significantly greater in NPP than in PP. Of the 17

preoperativeNPP,13patientsshiftedtolessseverePPpostoperatively.Intotal,21outof27(77.8%)

non-responderswerePPpostoperatively.

Conclusion:NosignificantdifferenceinsurgicalsuccessbetweenNPPandPPundergoingMMAwas

found. However, the improvement of total and non-supine AHI in NPP was significantly greater

compared to PP. In non-responders, a postoperative shift from severe NPP to less severe PPwas

found,causedbyagreaterreductionofthenon-supineAHIthanthesupineAHIpostoperatively.In

patientswith residualOSA in the supineposition afterMMA, additional treatmentwith positional

therapycanbeindicated.

Keywords: obstructive sleep apnea, sleep-disordered breathing,maxillomandibular advancement,

surgicalsuccess,positional,position-dependency

166

Briefsummary

Preoperative evaluation of possible predictors for surgical success is of paramount importance

before initiatingupper airway surgery. Currently, the influenceof position-dependencyon surgical

success in obstructive sleep apnea (OSA) patients undergoing MMA is unknown. We found that

surgical successwas similar in non-positional (NPP) and positionalOSA patients (PP), but that the

decrease in non-supine AHI was significantly greater in NPP than in PP, often resulting in a

postoperativeshiftfromsevereNPPtolessseverePP.Additionaltreatmentwithpositionaltherapy

canbeofaddedvalueinnon-responderswithresidualOSAinthesupineposition.

167

9

The influence of position-dependency on surgical success in obstructive sleep apnea patients

ABSTRACT

Study objectives: 1) to evaluate surgical success in obstructive sleep apnea (OSA) patients

undergoingmaxillomandibular advancement (MMA) stratifying for the reduction of both the total

apnea-hypopnea index (AHI) and the AHI in supine and non-supine position 2) to evaluate the

influence of position-dependency on surgical outcome 3) to analyze the prevalence of residual

position-dependentOSAinnon-respondersafterMMA.

Methods: a single-centre retrospective study including a consecutive series of OSA patients

undergoingMMAbetweenAugust2011andFebruary2019.

Results: In total,57patientswere included.Theoverall surgical successwas52.6%.Nosignificant

difference in surgical success between non-positional (NPP) and positional (PP) OSA patients was

found. Surgical success of the supineAHIwasnot significantly different betweenNPPandPP, but

surgical success of the non-supine AHI was significantly greater in NPP than in PP. Of the 17

preoperativeNPP,13patientsshiftedtolessseverePPpostoperatively.Intotal,21outof27(77.8%)

non-responderswerePPpostoperatively.

Conclusion:NosignificantdifferenceinsurgicalsuccessbetweenNPPandPPundergoingMMAwas

found. However, the improvement of total and non-supine AHI in NPP was significantly greater

compared to PP. In non-responders, a postoperative shift from severe NPP to less severe PPwas

found,causedbyagreaterreductionofthenon-supineAHIthanthesupineAHIpostoperatively.In

patientswith residualOSA in the supineposition afterMMA, additional treatmentwith positional

therapycanbeindicated.

Keywords: obstructive sleep apnea, sleep-disordered breathing,maxillomandibular advancement,

surgicalsuccess,positional,position-dependency

166

Briefsummary

Preoperative evaluation of possible predictors for surgical success is of paramount importance

before initiatingupper airway surgery. Currently, the influenceof position-dependencyon surgical

success in obstructive sleep apnea (OSA) patients undergoing MMA is unknown. We found that

surgical successwas similar in non-positional (NPP) and positionalOSA patients (PP), but that the

decrease in non-supine AHI was significantly greater in NPP than in PP, often resulting in a

postoperativeshiftfromsevereNPPtolessseverePP.Additionaltreatmentwithpositionaltherapy

canbeofaddedvalueinnon-responderswithresidualOSAinthesupineposition.

168

Chapter 9

INTRODUCTION

In patients with moderate to severe obstructive sleep apnea (OSA), Continuous Positive Airway

Pressure (CPAP) is considered the “gold-standard” therapy, but this therapy is often hamperedby

poortoleranceandlowacceptance.1-3InpatientswithsevereOSA(apnea-hypopneaindex(AHI)>30

events/h) and failure of CPAP treatment, several surgical therapies are available aiming to target

structuresrelatedtoupperairway(UA)collapseinordertoreduceobstructionsduringsleep.Oneof

thesesurgicaltechniquesismaxillomandibularadvancement(MMA).MMAconsistsofacombination

of a Le Fort I osteotomy and a bilateral sagittal split osteotomy to enlarge the pharyngeal airway

space. By advancement of the maxilla and mandible the medial-lateral and anteroposterior

dimensionsoftheUAareenlarged.4ThistechniqueishighlyeffectiveintreatingsevereOSApatients

withsurgicalsuccessratesvaryingfrom80to90%.5-9Comparedtoothersurgicaltechniques,MMA

isconsideredtobemoreinvasiveandinadditionithasconsiderablemorbidity.Therefore,patients

areusuallyreferredincasesofseveretoextremeOSA,andwhenthechanceofsurgicalsuccessof

lessinvasiveformsofUAsurgeryisconsideredtobelow.

There are several known negative predictors for the surgical success ofMMA.Older patients and

those with an increased neck circumference are at a greater risk of surgical failure. 10 Another

potential predictor is position-dependency. In a small-scale study, results showed that in partially

effectiveMMA(responsebutnotcured),ashiftwasoftenseenfromseverenon-positionalOSAto

lessseverepositionalOSA.Insuchcases,thereisasuccessfuldecreaseoftheAHIinthenon-supine

position,butinsufficientreductionoftheAHIinthesupineposition.11Althoughthisfindingsuggests

acorrelationbetweenposition-dependencyandsurgicalsuccess,furtherevidenceisneeded.

Therefore, theaimof thisstudywastoevaluatesurgicalsuccess inOSApatientsundergoingMMA

stratifying for the reduction of both the total AHI and the AHI in supine and non-supine position.

Secondly,wewantedtoevaluatetheinfluenceofposition-dependencyonsurgicaloutcome.Thirdly,

wewantedtoanalyzetheprevalenceofresidualposition-dependentOSA(POSA)innon-responders

afterMMA. Our hypothesis is that there is a difference in surgical success in non-positional OSA

patients (NPP) and positional OSA patients (PP). Secondly, we hypothesize that surgical failure is

causedbyinsufficientreductionoftheAHIinthesupinepositionratherthannon-supineAHI.

METHODS

Studyparticipants

We performed a single-centre retrospective study including a consecutive series of OSA patients

undergoing MMA between August 2011 and February 2019. Patients were only included if

preoperativeandpostoperativepolysomnography(PSG)dataafter3to6monthsoffollow-upwere

available. When patients slept 0% of the total sleeping time (TST) in the supine or non-supine

position, position-dependency could not be adequately determined. In that case, patients were

excludedfromfurtheranalysis.

Cephalometricwork-upandMMAprocedure

Preoperative and postoperative cephalometric data was collected including the following skeletal

landmarks: center of sella turnica (S), nasion (N), subspinal (A-point) and supramentale (B-point).

Sella-nasion–A-pointangle(SNA-angle)indicateswhetherornotthemaxillaisnormal,prognatic,or

retrognatic.Sella–nasion–B-pointangle(SNB-angle)assessesthemandibleinasimilarwayandtheA-

point toB-Point angle (ANB-angle) describes the sagittal discrepancybetween themaxilla and the

mandible(figure1).12

Figure1.Skeletallandmarks

Scenterofsellaturnica,Nnasion,AA-point(subspinal),BB-point(supramentale)

169

9

The influence of position-dependency on surgical success in obstructive sleep apnea patients

INTRODUCTION

In patients with moderate to severe obstructive sleep apnea (OSA), Continuous Positive Airway

Pressure (CPAP) is considered the “gold-standard” therapy, but this therapy is often hamperedby

poortoleranceandlowacceptance.1-3InpatientswithsevereOSA(apnea-hypopneaindex(AHI)>30

events/h) and failure of CPAP treatment, several surgical therapies are available aiming to target

structuresrelatedtoupperairway(UA)collapseinordertoreduceobstructionsduringsleep.Oneof

thesesurgicaltechniquesismaxillomandibularadvancement(MMA).MMAconsistsofacombination

of a Le Fort I osteotomy and a bilateral sagittal split osteotomy to enlarge the pharyngeal airway

space. By advancement of the maxilla and mandible the medial-lateral and anteroposterior

dimensionsoftheUAareenlarged.4ThistechniqueishighlyeffectiveintreatingsevereOSApatients

withsurgicalsuccessratesvaryingfrom80to90%.5-9Comparedtoothersurgicaltechniques,MMA

isconsideredtobemoreinvasiveandinadditionithasconsiderablemorbidity.Therefore,patients

areusuallyreferredincasesofseveretoextremeOSA,andwhenthechanceofsurgicalsuccessof

lessinvasiveformsofUAsurgeryisconsideredtobelow.

There are several known negative predictors for the surgical success ofMMA.Older patients and

those with an increased neck circumference are at a greater risk of surgical failure. 10 Another

potential predictor is position-dependency. In a small-scale study, results showed that in partially

effectiveMMA(responsebutnotcured),ashiftwasoftenseenfromseverenon-positionalOSAto

lessseverepositionalOSA.Insuchcases,thereisasuccessfuldecreaseoftheAHIinthenon-supine

position,butinsufficientreductionoftheAHIinthesupineposition.11Althoughthisfindingsuggests

acorrelationbetweenposition-dependencyandsurgicalsuccess,furtherevidenceisneeded.

Therefore, theaimof thisstudywastoevaluatesurgicalsuccess inOSApatientsundergoingMMA

stratifying for the reduction of both the total AHI and the AHI in supine and non-supine position.

Secondly,wewantedtoevaluatetheinfluenceofposition-dependencyonsurgicaloutcome.Thirdly,

wewantedtoanalyzetheprevalenceofresidualposition-dependentOSA(POSA)innon-responders

afterMMA. Our hypothesis is that there is a difference in surgical success in non-positional OSA

patients (NPP) and positional OSA patients (PP). Secondly, we hypothesize that surgical failure is

causedbyinsufficientreductionoftheAHIinthesupinepositionratherthannon-supineAHI.

METHODS

Studyparticipants

We performed a single-centre retrospective study including a consecutive series of OSA patients

undergoing MMA between August 2011 and February 2019. Patients were only included if

preoperativeandpostoperativepolysomnography(PSG)dataafter3to6monthsoffollow-upwere

available. When patients slept 0% of the total sleeping time (TST) in the supine or non-supine

position, position-dependency could not be adequately determined. In that case, patients were

excludedfromfurtheranalysis.

Cephalometricwork-upandMMAprocedure

Preoperative and postoperative cephalometric data was collected including the following skeletal

landmarks: center of sella turnica (S), nasion (N), subspinal (A-point) and supramentale (B-point).

Sella-nasion–A-pointangle(SNA-angle)indicateswhetherornotthemaxillaisnormal,prognatic,or

retrognatic.Sella–nasion–B-pointangle(SNB-angle)assessesthemandibleinasimilarwayandtheA-

point toB-Point angle (ANB-angle) describes the sagittal discrepancybetween themaxilla and the

mandible(figure1).12

Figure1.Skeletallandmarks

Scenterofsellaturnica,Nnasion,AA-point(subspinal),BB-point(supramentale)

170

Chapter 9

AllMMAprocedureswereperformedbytwodedicatedmaxillofacialsurgeonsandconsistedofaLe

Fort I osteotomyandaBSSO toadvance themaxillaryandmandibular facial skeleton. Themaxilla

was advanced to the preoperatively planned position (~8-10mm anteriorly) and an acrylic

intermediate splint was used to guarantee correct alignment and fixation of the maxilla in the

intendedplannedposition.

Definitions

SurgicalsuccesswasdefinedaccordingtoSher’scriteria,whichmeansthatMMAwasconsideredto

be successful when a postoperative reduction of more than 50% of the preoperative AHI was

achieved combinedwith a postoperative AHI below 20 events/h. 13 To determine surgical success

stratifiedtosupineandnon-supinepositionamodifiedversionsofSher’scriteriawasappliedusing

supineandnon-supineAHIinsteadoftotalAHI.

PatientsnotmeetingSher’scriteriaforsurgicalsuccesswerereferredtoasnon-responders.Surgical

successfortotalAHI,supineAHIandnon-supineAHIwasdeterminedinthetotalstudypopulation,

NPP,PP,responders,andinnon-responders.

Patientswere identifiedasbeingposition-dependentusingCartwright’s criteria,a supineAHIofat

leasttwiceashighasnon-supineAHI.14

Ethicalconsiderations

Allproceduresfollowedwereinaccordancewiththeethicalstandardsoftheresponsiblecommittee

onhumanexperimentationandwiththeDeclarationofHelsinkiof1975.Dataonstudysubjectswas

collected and stored encoded to protect personal information. For this type of study informed

consentwasnotrequired.

Statisticalanalysis

Statistical analysiswasperformedusing SPSS (version22), SPSS Inc., Chicago, IL.Quantitativedata

werereportedasmeanandstandarddeviation(SD)orasmedianand(Q1,Q3)whennotnormally

distributed.Todeterminewhethercontinuousvariableswerenormallydistributed,theShapiro-Wilk

Testwas used. A p value of < 0.05was considered to indicate statistical significance. To compare

baseline characteristics between NPP and PP the unpaired t test was used in case of normally

distributeddataandtheMann-WhitneyUtestwhendatawasnotnormallydistributed.APearson’s

chi-squared test was used to determine whether there was a correlation between position-

dependency and surgical success. To compare preoperative and postoperative values in total

population,NPPandPPapairedttestwasusedwhendatawasnormallydistributed.Incaseofnot

normallydistributeddataaWilcoxonsignedranktestwasapplied.Whencomparingdifferences in

surgicaloutcomebetweengroupsanunpairedTtestortheMann-WhitneyUtestwasusedincaseof

normally or not normally distributed data respectively. To correct for possible confounders a

multivariate logistic regressionanalyseswasperformed.Descriptive statisticswereused toanalyze

theoccurrenceofashiftinposition-dependencyafterMMA.

RESULTS

In total 68 patients underwent MMA for OSA. Eight patients were excluded because (partial)

preoperative or postoperative PSG datawasmissing. In three patients position-dependency could

notbedeterminedduetoaTSTof0%inthesupineposition.Therefore,57patientswereincluded

foranalysis.Forty-eightpatientsweremale(84.2%).Themeanagewas51.3±8.6yearswithabody

mass index (BMI) of 28.6 ± 4.0 kg/m2. Twenty-four patients were daily smokers (42.1%) and 23

patients(40.4%)werepreviouslydiagnosedwithcardiovascularproblems(myocardialinfarctionN=9,

hypertensionN=9,atrialfibrillationN=2,otherN=2).Fifty-fivepatients(96.5%)hadCPAPintolerance

or failure and 23 patients (40.4%) received another form of UA surgery prior to MMA (e.g.

uvulopalatopharyngoplasty(UPPP),thermotherapyofthetonguebaseorhyoidthyroidpexia).

PatientshadatotalmeanAHIof51.4±22.2events/h,ameansupineAHIof68.1±20.7events/hand

anon-supineAHIof44.4±24.5events/h.Themeanoxygendesaturationindex(ODI≥3%)was46.9±

22.3 events/h and themedian averagewas SpO293.0% (92.0; 95.0).Of all patients, 38wereNPP

preoperatively(66.7%).Adetailedoverviewofbaselinecharacteristicscanbefoundintable1.

171

9

The influence of position-dependency on surgical success in obstructive sleep apnea patients

AllMMAprocedureswereperformedbytwodedicatedmaxillofacialsurgeonsandconsistedofaLe

Fort I osteotomyandaBSSO toadvance themaxillaryandmandibular facial skeleton. Themaxilla

was advanced to the preoperatively planned position (~8-10mm anteriorly) and an acrylic

intermediate splint was used to guarantee correct alignment and fixation of the maxilla in the

intendedplannedposition.

Definitions

SurgicalsuccesswasdefinedaccordingtoSher’scriteria,whichmeansthatMMAwasconsideredto

be successful when a postoperative reduction of more than 50% of the preoperative AHI was

achieved combinedwith a postoperative AHI below 20 events/h. 13 To determine surgical success

stratifiedtosupineandnon-supinepositionamodifiedversionsofSher’scriteriawasappliedusing

supineandnon-supineAHIinsteadoftotalAHI.

PatientsnotmeetingSher’scriteriaforsurgicalsuccesswerereferredtoasnon-responders.Surgical

successfortotalAHI,supineAHIandnon-supineAHIwasdeterminedinthetotalstudypopulation,

NPP,PP,responders,andinnon-responders.

Patientswere identifiedasbeingposition-dependentusingCartwright’s criteria,a supineAHIofat

leasttwiceashighasnon-supineAHI.14

Ethicalconsiderations

Allproceduresfollowedwereinaccordancewiththeethicalstandardsoftheresponsiblecommittee

onhumanexperimentationandwiththeDeclarationofHelsinkiof1975.Dataonstudysubjectswas

collected and stored encoded to protect personal information. For this type of study informed

consentwasnotrequired.

Statisticalanalysis

Statistical analysiswasperformedusing SPSS (version22), SPSS Inc., Chicago, IL.Quantitativedata

werereportedasmeanandstandarddeviation(SD)orasmedianand(Q1,Q3)whennotnormally

distributed.Todeterminewhethercontinuousvariableswerenormallydistributed,theShapiro-Wilk

Testwas used. A p value of < 0.05was considered to indicate statistical significance. To compare

baseline characteristics between NPP and PP the unpaired t test was used in case of normally

distributeddataandtheMann-WhitneyUtestwhendatawasnotnormallydistributed.APearson’s

chi-squared test was used to determine whether there was a correlation between position-

dependency and surgical success. To compare preoperative and postoperative values in total

population,NPPandPPapairedttestwasusedwhendatawasnormallydistributed.Incaseofnot

normallydistributeddataaWilcoxonsignedranktestwasapplied.Whencomparingdifferences in

surgicaloutcomebetweengroupsanunpairedTtestortheMann-WhitneyUtestwasusedincaseof

normally or not normally distributed data respectively. To correct for possible confounders a

multivariate logistic regressionanalyseswasperformed.Descriptive statisticswereused toanalyze

theoccurrenceofashiftinposition-dependencyafterMMA.

RESULTS

In total 68 patients underwent MMA for OSA. Eight patients were excluded because (partial)

preoperative or postoperative PSG datawasmissing. In three patients position-dependency could

notbedeterminedduetoaTSTof0%inthesupineposition.Therefore,57patientswereincluded

foranalysis.Forty-eightpatientsweremale(84.2%).Themeanagewas51.3±8.6yearswithabody

mass index (BMI) of 28.6 ± 4.0 kg/m2. Twenty-four patients were daily smokers (42.1%) and 23

patients(40.4%)werepreviouslydiagnosedwithcardiovascularproblems(myocardialinfarctionN=9,

hypertensionN=9,atrialfibrillationN=2,otherN=2).Fifty-fivepatients(96.5%)hadCPAPintolerance

or failure and 23 patients (40.4%) received another form of UA surgery prior to MMA (e.g.

uvulopalatopharyngoplasty(UPPP),thermotherapyofthetonguebaseorhyoidthyroidpexia).

PatientshadatotalmeanAHIof51.4±22.2events/h,ameansupineAHIof68.1±20.7events/hand

anon-supineAHIof44.4±24.5events/h.Themeanoxygendesaturationindex(ODI≥3%)was46.9±

22.3 events/h and themedian averagewas SpO293.0% (92.0; 95.0).Of all patients, 38wereNPP

preoperatively(66.7%).Adetailedoverviewofbaselinecharacteristicscanbefoundintable1.

172

Chapter 9

Table1.Baselinecharacteristicsofthetotalpopulation,NPPandPP

Total NPP PP pvalue

Numberofpatients(N) 57 38 19 -

Male:female 48:9 32:6 16:3 1.000

Age(years) 51.3±8.6 51.2±9.1 51.6±7.8 0.872

BMI(kg/m2) 28.6±4.0 29.0±3.9 27.8±4.2 0.302

TotalAHI(events/h) 51.4±22.2 61.9±17.5 30.4±14.5 <0.001*

ObstructiveAI(events/h) 21.7

[10.4,44.3]

33.5

[19.5,54.8]

11.0

[3.8,18.2]

<0.001*

MixedAI(events/h) 3.9

[0.3,15.3]

4.4

[1.5,21.9]

1.3

[0.3,10.3]

0.257

CentralAI(events/h) 0.8

[0.2,3.0]

0.8

[0.2,2.5]

0.9

[0.1,3.3]

0.739

SupineAHI(events/h) 68.1±20.7 70.7±17.6 63.0±25.6 0.188

Non-supineAHI(events/h) 44.4±24.5 57.0±19.1 19.3±10.9 <0.001*

%ofTSTinthesupineposition 35.2±19.6 39.2±18.2 27.4±20.5 0.031*

ODI(events/h) 46.9±22.3 56.4±19.1 28.5±15.9 <0.001*

MedianaverageSpO2(%) 93.0

[92.0,95.0]

95.0

[91.0,94.5]

94.0

[93.0,95.3]

0.079

Datapresentedasmean±standarddeviationormedian[Q1,Q3]

*pvalue<0.05comparingNPPandPP

NPPnon-positionalobstructivesleepapneapatients,PPpositionalobstructivesleepapneapatients,

BMI body mass index, AHI apnea-hypopnea index, AI apnea index, TST total sleeping time, ODI

oxygendesaturationindex,SpO2saturationofperipheraloxygen

BaselinecharacteristicsNPPversusPP

WhencomparingbaselinecharacteristicsbetweenNPPandPP,meanage,thedistributionofgender,

meanBMIand supineAHIdidnot significantlydiffer.TotalAHI (p<0.001),obstructiveapnea index

(AI;p<0.001),non-supineAHI(p<0.001),percentageofTSTinthesupineposition(p=0.036)andODI

(p<0.001)were significantly higher inNPP. Themedian average SpO2 did not significantly differ in

NPPfromthatinPP(p=0.079)(table2).

Table2.ResultsbeforeandafterMMAintotalpopulation

Datapresentedasmean±standarddeviationormedian[Q1,Q3],*pvalue<0.05

MMA maxillomandibular advancement, NPP non-positional obstructive sleep apnea patients, PP

positional obstructive sleep apnea patients,BMI bodymass index,AHI apnea-hypopnea index,AI

apnea index,TST total sleeping time,ODIoxygendesaturation index,SpO2 saturationofperipheral

oxygen

Totalpopulation(N=57)

Preoperative Postoperative pvalue

BMI(kg/m2) 28.6±4.0 28.1±3.8 0.125

TotalAHI(events/h) 51.4±22.2 19.9±15.3 <0.001*

ObstructiveAI(events/h) 21.7

[10.4,44.3]

5.0

[1.4,10.1]

<0.001*

MixedAI(events/h) 3.9

[0.3,15.3]

0.6

[0.1,4.1]

0.004*

CentralAI(events/h) 0.8

[0.2,3.0]

0.3

[0.1,1.1]

0.021*

SupineAHI(events/h) 68.1±20.7 35.2±25.9 <0.001*

Non-supineAHI(events/h) 44.4±24.5 11.2±11.8 <0.001*

%ofTSTinsupinesleepingposition 35.2±19.6 38.3±21.8 0.236

ODI(events/h) 46.9±22.3 25.1±15.8 <0.001*

MedianaverageSpO2(%) 93.0

[92.0,95.0]

95.0

[93.0,96.0]

<0.001*

173

9

The influence of position-dependency on surgical success in obstructive sleep apnea patients

Table1.Baselinecharacteristicsofthetotalpopulation,NPPandPP

Total NPP PP pvalue

Numberofpatients(N) 57 38 19 -

Male:female 48:9 32:6 16:3 1.000

Age(years) 51.3±8.6 51.2±9.1 51.6±7.8 0.872

BMI(kg/m2) 28.6±4.0 29.0±3.9 27.8±4.2 0.302

TotalAHI(events/h) 51.4±22.2 61.9±17.5 30.4±14.5 <0.001*

ObstructiveAI(events/h) 21.7

[10.4,44.3]

33.5

[19.5,54.8]

11.0

[3.8,18.2]

<0.001*

MixedAI(events/h) 3.9

[0.3,15.3]

4.4

[1.5,21.9]

1.3

[0.3,10.3]

0.257

CentralAI(events/h) 0.8

[0.2,3.0]

0.8

[0.2,2.5]

0.9

[0.1,3.3]

0.739

SupineAHI(events/h) 68.1±20.7 70.7±17.6 63.0±25.6 0.188

Non-supineAHI(events/h) 44.4±24.5 57.0±19.1 19.3±10.9 <0.001*

%ofTSTinthesupineposition 35.2±19.6 39.2±18.2 27.4±20.5 0.031*

ODI(events/h) 46.9±22.3 56.4±19.1 28.5±15.9 <0.001*

MedianaverageSpO2(%) 93.0

[92.0,95.0]

95.0

[91.0,94.5]

94.0

[93.0,95.3]

0.079

Datapresentedasmean±standarddeviationormedian[Q1,Q3]

*pvalue<0.05comparingNPPandPP

NPPnon-positionalobstructivesleepapneapatients,PPpositionalobstructivesleepapneapatients,

BMI body mass index, AHI apnea-hypopnea index, AI apnea index, TST total sleeping time, ODI

oxygendesaturationindex,SpO2saturationofperipheraloxygen

BaselinecharacteristicsNPPversusPP

WhencomparingbaselinecharacteristicsbetweenNPPandPP,meanage,thedistributionofgender,

meanBMIand supineAHIdidnot significantlydiffer.TotalAHI (p<0.001),obstructiveapnea index

(AI;p<0.001),non-supineAHI(p<0.001),percentageofTSTinthesupineposition(p=0.036)andODI

(p<0.001)were significantly higher inNPP. Themedian average SpO2 did not significantly differ in

NPPfromthatinPP(p=0.079)(table2).

Table2.ResultsbeforeandafterMMAintotalpopulation

Datapresentedasmean±standarddeviationormedian[Q1,Q3],*pvalue<0.05

MMA maxillomandibular advancement, NPP non-positional obstructive sleep apnea patients, PP

positional obstructive sleep apnea patients,BMI bodymass index,AHI apnea-hypopnea index,AI

apnea index,TST total sleeping time,ODIoxygendesaturation index,SpO2 saturationofperipheral

oxygen

Totalpopulation(N=57)

Preoperative Postoperative pvalue

BMI(kg/m2) 28.6±4.0 28.1±3.8 0.125

TotalAHI(events/h) 51.4±22.2 19.9±15.3 <0.001*

ObstructiveAI(events/h) 21.7

[10.4,44.3]

5.0

[1.4,10.1]

<0.001*

MixedAI(events/h) 3.9

[0.3,15.3]

0.6

[0.1,4.1]

0.004*

CentralAI(events/h) 0.8

[0.2,3.0]

0.3

[0.1,1.1]

0.021*

SupineAHI(events/h) 68.1±20.7 35.2±25.9 <0.001*

Non-supineAHI(events/h) 44.4±24.5 11.2±11.8 <0.001*

%ofTSTinsupinesleepingposition 35.2±19.6 38.3±21.8 0.236

ODI(events/h) 46.9±22.3 25.1±15.8 <0.001*

MedianaverageSpO2(%) 93.0

[92.0,95.0]

95.0

[93.0,96.0]

<0.001*

174

Chapter 9

PreoperativeandpostoperativeMMAresults

The median advancement of the maxillomandibular complex was 10mm (range 8-12mm). The

preoperativeandpostoperativeskeletalrelationshipbasedontheSNA,SNBandANBareshownin

table3.

Table3.Cephalometricanalysis

SNA SNB ANB

Preoperative 81.0(79.5-85.2) 77.4(73.1-81.8) 5.0(2.7-7.7)

Postoperative 87.0(84.2-91.7) 80.2(76.7-85.6) 6.8(5.1-11.1)

Datapresentedasmedian(IQRinterquartilerange)

SNAS-NlineandA-point,SNBS-NlineandB-point

ThetotalmeanAHIwassignificantlyreducedfrom51.4±22.2to19.9±15.3events/h(p<0.001).In

NPP,thetotalmeanAHIdecreasedfrom61.9±17.5to21.9±16.8events/hcomparedtoadecrease

from30.4±14.5to16.1±11.0events/hinPP.

Inthetotalpopulation,supineAHIwassignificantlyreducedfrom68.1±20.7to35.2±25.9events/h

(p<0.001). InNPP, supineAHIwas reduced from70.6±17.6 to38.2±28.9events/h compared to

63.0±25.6to29.2±17.6events/hinPP.

Thenon-supineAHI inallpatientssignificantlydecreased from44.4±24.5 to11.2±11.8events/h

(p<0.001).Areductioninnon-supineAHIfrom57.0±19.1to12.0±13.0events/hand19.3±10.9to

9.7±9.3events/hwasfoundinNPPandPPrespectively(seefigure2).Anoverviewofpreoperative

andpostoperativePSGparametersinthetotalpopulation,andinbothNPPandPPcanbefoundin

table2andtable4.

Figure 2.Boxplot of thepreoperative andpostoperativeMMA supine andnon-supineAHI in total

population

*pvalue<0.05comparingthepreoperativeandpostoperativesupineandnon-supineAHI

MMAmaxillomandibularadvancement,AHIapnea-hypopneaindex

*

*

175

9

The influence of position-dependency on surgical success in obstructive sleep apnea patients

PreoperativeandpostoperativeMMAresults

The median advancement of the maxillomandibular complex was 10mm (range 8-12mm). The

preoperativeandpostoperativeskeletalrelationshipbasedontheSNA,SNBandANBareshownin

table3.

Table3.Cephalometricanalysis

SNA SNB ANB

Preoperative 81.0(79.5-85.2) 77.4(73.1-81.8) 5.0(2.7-7.7)

Postoperative 87.0(84.2-91.7) 80.2(76.7-85.6) 6.8(5.1-11.1)

Datapresentedasmedian(IQRinterquartilerange)

SNAS-NlineandA-point,SNBS-NlineandB-point

ThetotalmeanAHIwassignificantlyreducedfrom51.4±22.2to19.9±15.3events/h(p<0.001).In

NPP,thetotalmeanAHIdecreasedfrom61.9±17.5to21.9±16.8events/hcomparedtoadecrease

from30.4±14.5to16.1±11.0events/hinPP.

Inthetotalpopulation,supineAHIwassignificantlyreducedfrom68.1±20.7to35.2±25.9events/h

(p<0.001). InNPP, supineAHIwas reduced from70.6±17.6 to38.2±28.9events/h compared to

63.0±25.6to29.2±17.6events/hinPP.

Thenon-supineAHI inallpatientssignificantlydecreased from44.4±24.5 to11.2±11.8events/h

(p<0.001).Areductioninnon-supineAHIfrom57.0±19.1to12.0±13.0events/hand19.3±10.9to

9.7±9.3events/hwasfoundinNPPandPPrespectively(seefigure2).Anoverviewofpreoperative

andpostoperativePSGparametersinthetotalpopulation,andinbothNPPandPPcanbefoundin

table2andtable4.

Figure 2.Boxplot of thepreoperative andpostoperativeMMA supine andnon-supineAHI in total

population

*pvalue<0.05comparingthepreoperativeandpostoperativesupineandnon-supineAHI

MMAmaxillomandibularadvancement,AHIapnea-hypopneaindex

*

*

176

Chapter 9

SurgicalsuccessofthetotalAHI,supineAHIandnon-supineAHI

Surgicalsuccesswasachievedin30outof57patients(52.6%);55.3%(N=21)inNPPand47.4%(N=9)

in PP. This difference was not statistically significant (p=0.574). Multivariate logistic regression

analysis showednosignificant correlationbetweensurgical successandage (OR0.96CI95%0.90-

1.02;p=0.198),preoperativeBMI(OR1.0CI95%0.90-1.20;p=0.561)orpreoperativetotalAHI (OR

0.99CI95%0.97-1.01);p=0.630).

Surgicalsuccessinthesupinepositionwasachievedin19patients(33.3%)ofthetotalpopulation,in

13NPP(34.2%)andin6PP(31.6%).Nosignificantdifferencewasfoundbetweenthesurgicalsuccess

inthesupinepositioncomparingpreoperativeNPPandPP(p=0.843).

In the non-supine position surgical success was achieved in 41 patients (71.9%) of the total

population,in31NPP(81.6%)andin10PP(52.6%).Surgicalsuccessinthenon-supinepositionswas

significantly greater inNPP than in PP (p=0.022).Table 5 provides anoverviewof surgical success

percentages stratified for the total AHI, the supine AHI and the non-supine AHI in the total

populationandcomparingNPPwithPP.

Table5.SurgicalsuccessofAHI,supineAHIandnon-supineAHIintotalpopulation,NPPandPP

Surgicalsuccess Totalpopulation

(N=57)

NPP

(N=38)

PP

(N=19)

pvalue

TotalAHI 52.6% 55.3% 47.4% 0.574

SupineAHI 50.9% 34.2% 31.6% 0.843

Non-supineAHI 75.4% 81.6% 52.6% 0.022*

*pvalue<0.05comparingNPPandPP

AHI apnea-hypopnea index, NPP non-positional obstructive sleep apnea patients, PP positional

obstructivesleepapneapatients

Table4.Pre

oper

ativean

dpo

stop

erat

ivePS

Gvalue

scom

parin

gNPP

and

PP

Data

pre

sent

edasm

ean±stan

dard

dev

iatio

nor

med

ian[Q

1,Q

3]

*pva

lue<0

.05co

mpa

ringpr

eope

rativ

ean

dpo

stop

erat

ivePS

Gvalue

s

**pvalue

<0.05

com

parin

gΔ

(pre

oper

ativean

dpo

stop

erat

ivech

ange

)inNPP

and

PP

PSGp

olys

omno

grap

hy,N

PPn

on-p

ositi

onalo

bstruc

tive

slee

pap

nea

patie

nts,PP

positio

nalo

bstruc

tive

slee

pap

nea

patie

nts,BMIb

ody

mas

sinde

x,AHI

apne

a-hy

popn

ea

inde

x,AI

apne

ainde

x,TST

tota

lsle

eping

time,ODI

ox

ygen

de

satu

ratio

ninde

x,SpO

2sa

tura

tion

of

perip

hera

lox

ygen

NPP

(N=3

8)

PP(N

=19)

NPP

vsPP

Preo

pera

tive

Postop

erat

ive

pva

lue

ΔPr

eope

rativ

ePo

stop

erat

ive

pva

lue

Δpva

lue

BMI(

kg/m

2 )

29.0±3.9

28.6±3.7

0.40

10.3±2.4

27.8±4.2

27.1±3.9

0.08

20.7±1.6

0.57

7To

talA

HI(

even

ts/h

)61

.9±17.5

21.9±16.8

<0.001

*40

.0±20.3

30.4±14.5

16.1±11.0

0.00

2*

14.3±17.7

<0.001

**

Obs

truc

tiveAI

(eve

nts/

h)

33.5

[19.5,54.8]

6.3

[2.1,1

0.7]

<0

.001

*23

.1

[11.3,45.2]

11

.0

[3.8,1

8.2]

3.3

[0.3,7

.5]

0.01

7*

7.0

[-1.0,1

4.0]

0.00

1*

Mixed

AI(

even

ts/h

)4.4

[1.5,2

1.9]

0.8

[0.0,7

.0]

0.01

7*

2.0

[-1.5,1

8.2]

1.3

[0.3,1

0.3]

0.6

[0.1,1

.8]

0.04

4*

0.6

[-0.2,9

.7]

0.86

5

Cent

ralA

I(ev

ents/h

)0.8

[0.2,2

.5]

0.3

[0.0,1

.0]

0.03

3*

0.3

[-0.3,2

.4]

0.9

[0.1,3

.3]

0.4

[0.1,1

.3]

0.43

40.1

[-0.3,2

.3]

0.18

2

Supine

AHI(

even

ts/h

)70

.6±17.6

38.2±28.9

<0.001

*32

.5±30.9

63.0±25.6

29.2±17.6

<0.001

*33

.8±32.2

0.88

4Non

-sup

ineAH

I(ev

ents/h

)57

.0±19.1

12.0±13.0

<0.001

*44

.9±20.6

19.3±10.9

9.7±9.3

0.02

0*

9.6±16

.4

<0.001

**

%

of

TST

in

the

supine

po

sitio

n39

.2±18.2

41.0±22.6

<0.001

*1.8±21

.5

27.4±20.5

32.9±19.6

0.10

45.4±14

.3

0.50

9

ODI

(eve

nts/

h)

56.4±19.1

27.4±17.4

0.60

828

.9±20.0

28.5±15.9

20.5±11.1

0.07

37.9±18

.2

<0.001

**

Med

ianav

erag

eSp

O2(

%)

93.0

[91.0,94.5]

95

.0

[93.0,96.0]

<0

.001

*1.0

0.0,2.0]

94.0

[93.0,95.3]

95

.0

[94.0,96.0]

0.01

8*

0.5

[0.0,2

.0]

0.11

9

177

9

The influence of position-dependency on surgical success in obstructive sleep apnea patients

SurgicalsuccessofthetotalAHI,supineAHIandnon-supineAHI

Surgicalsuccesswasachievedin30outof57patients(52.6%);55.3%(N=21)inNPPand47.4%(N=9)

in PP. This difference was not statistically significant (p=0.574). Multivariate logistic regression

analysis showednosignificant correlationbetweensurgical successandage (OR0.96CI95%0.90-

1.02;p=0.198),preoperativeBMI(OR1.0CI95%0.90-1.20;p=0.561)orpreoperativetotalAHI (OR

0.99CI95%0.97-1.01);p=0.630).

Surgicalsuccessinthesupinepositionwasachievedin19patients(33.3%)ofthetotalpopulation,in

13NPP(34.2%)andin6PP(31.6%).Nosignificantdifferencewasfoundbetweenthesurgicalsuccess

inthesupinepositioncomparingpreoperativeNPPandPP(p=0.843).

In the non-supine position surgical success was achieved in 41 patients (71.9%) of the total

population,in31NPP(81.6%)andin10PP(52.6%).Surgicalsuccessinthenon-supinepositionswas

significantly greater inNPP than in PP (p=0.022).Table 5 provides anoverviewof surgical success

percentages stratified for the total AHI, the supine AHI and the non-supine AHI in the total

populationandcomparingNPPwithPP.

Table5.SurgicalsuccessofAHI,supineAHIandnon-supineAHIintotalpopulation,NPPandPP

Surgicalsuccess Totalpopulation

(N=57)

NPP

(N=38)

PP

(N=19)

pvalue

TotalAHI 52.6% 55.3% 47.4% 0.574

SupineAHI 50.9% 34.2% 31.6% 0.843

Non-supineAHI 75.4% 81.6% 52.6% 0.022*

*pvalue<0.05comparingNPPandPP

AHI apnea-hypopnea index, NPP non-positional obstructive sleep apnea patients, PP positional

obstructivesleepapneapatients

178

Chapter 9

Postoperativeshiftinposition-dependency

Of all patients, 38 patients (66.7%) were NPP preoperatively. Twenty-five NPP shifted to PP

postoperatively(65.8%).Nineteenpatients(33.3%)werePPpreoperatively.AfterMMA14patients

remained PP, 5 shifted to NPP (26.3%), see figure 3. In total, 39 out of 57 patients were PP

postoperatively(68.4%).

Respondersversusnon-responders

In the non-responder group, 10 out of 27 patients (37.0%) were PP preoperatively. Eight

preoperative PP remainedposition-dependent.Of the 17 preoperativeNPP, 13 patients shifted to

less severe PP postoperatively. In total, 21 out of 27 (77.8%) non-responders were PP

postoperatively.ThesurgicalsuccessofthesupineAHIwas83.3%inrespondersversus14.8%innon-

responders (p<0.001). When comparing the surgical success of the non-supine AHI we found a

surgical success of 93.3% compared to 55.6% in responders and non-responders respectively

(p<0.001).Table6providesanoverviewofsurgicalsuccesspercentagesofthetotal,supineandnon-

supineAHIcomparingresponderswithnon-responders.

Table6.SurgicalsuccessintotalAHI,supineAHIandnon-supineAHIcomparingrespondersandnon-

responders

Surgicalsuccess Responders

(N=30)

Non-responders

(N=27)

pvalue

TotalAHI 100% N/A -

SupineAHI 83.3% 14.8% <0.001*

Non-supineAHI 93.3% 55.6% <0.001*

*pvalue<0.05comparingsurgicalsuccessofthesupineandnon-supineAHIinrespondersandnon-

responders

AHIapnea-hypopneaindex

DISCUSSION

Most studies on MMA show success rates of approximately 85%. 15 This is the first series that

focussesonnon-responderstoMMA.Incontrasttowhatwasexpected,ourresultsdidnotshowa

significantdifferenceinsurgicalsuccessbetweenNPPandPP,suggestingtheabsenceofacorrelation

betweenposition-dependencyandsurgicaloutcomeinpatientsundergoingMMA.Whenstratifying

for surgical success of the supine and non-supine AHI no significant difference was found in the

surgical success of the supine AHI, but surgical success of the non-supine AHI was significantly

greaterinNPPthaninPP.Inthemajorityofnon-responders,ashiftfromsevereNPPtolesssevere

PPwasseencausedbyamorepronouncedreductionofthenon-supineAHIthanthesupineAHI.

When interpretingtheresults, thereareseveral factorsthatmustbetaken intoconsideration.Our

overallsuccessrate is lowerthanreported inthe literature.15This isprobablyduetothefactthat

MMA in our institute is strictly reserved for severe to extremeOSA (mean AHI of 51.5 events/h),

whilemanyotherseriesalsoincludemoderateandevenmildpathology.FortypercentofourMMA

patients underwent previous, unsuccessful UA surgery, or were considered poor candidates for

standardUAsurgeryorupperairwaystimulationforavarietyofreasons(e.g.,unfavorablefindings

during drug-induced sleep endoscopy, such as complete concentric palatal collapse or multilevel

totalcollapse),whichmighthaveinterferedwithapositivesurgicaloutcome.Lastly,theaverageage

inthisstudywashigherthaninotherstudiesreportingonthesurgicaloutcomeofMMA.Itisknown

thatahigheragehasanegativeimpactonthesurgicalsuccessofUAsurgeryandMMA.10

Nevertheless,wedidnotfindasignificantcorrelationbetweenageandsurgicalsuccessinourstudy

population. When evaluating the possible relation of REM–related OSA and the increase of the

percentage of REM sleep postoperatively, we did not find a significant correlation between the

presence of REM-relatedOSA and surgical success (p=0.136) Furthermore, the high percentage of

NPP is not surprising, due to the fact that the prevalence of positional OSA decreaseswhenOSA

severityincreases.16-20

AsignificantdecreaseofthetotalAHI,supineAHIandnon-supineAHIwasfoundinbothNPPandPP

afterMMA.ODIandaverageSpO2alsosignificantly improved inNPP,butnot inPP.Althoughtotal

and non-supine AHI significantly decreased in both NPP and PP, the decrease was significantly

greaterinNPPthaninPP.NosignificantdifferencewasfoundinthedecreaseofthesupineAHI.This

findingmight be explainedby the fact that thepreoperative total AHI andnon-supineAHI inNPP

weresignificantlyhigher.Asaresult,agreaterreductioninnon-supineAHIwaspossible.

The finding of a postoperative shift from severe NPP to less severe PP is not new. In previously

publishedstudies,similarresultswerefoundinpatientsundergoinguvulopalatopharyngoplastyorZ-

palatoplasty with or without radiofrequency thermotherapy of the tongue base and multilevel

179

9

The influence of position-dependency on surgical success in obstructive sleep apnea patients

Postoperativeshiftinposition-dependency

Of all patients, 38 patients (66.7%) were NPP preoperatively. Twenty-five NPP shifted to PP

postoperatively(65.8%).Nineteenpatients(33.3%)werePPpreoperatively.AfterMMA14patients

remained PP, 5 shifted to NPP (26.3%), see figure 3. In total, 39 out of 57 patients were PP

postoperatively(68.4%).

Respondersversusnon-responders

In the non-responder group, 10 out of 27 patients (37.0%) were PP preoperatively. Eight

preoperative PP remainedposition-dependent.Of the 17 preoperativeNPP, 13 patients shifted to

less severe PP postoperatively. In total, 21 out of 27 (77.8%) non-responders were PP

postoperatively.ThesurgicalsuccessofthesupineAHIwas83.3%inrespondersversus14.8%innon-

responders (p<0.001). When comparing the surgical success of the non-supine AHI we found a

surgical success of 93.3% compared to 55.6% in responders and non-responders respectively

(p<0.001).Table6providesanoverviewofsurgicalsuccesspercentagesofthetotal,supineandnon-

supineAHIcomparingresponderswithnon-responders.

Table6.SurgicalsuccessintotalAHI,supineAHIandnon-supineAHIcomparingrespondersandnon-

responders

Surgicalsuccess Responders

(N=30)

Non-responders

(N=27)

pvalue

TotalAHI 100% N/A -

SupineAHI 83.3% 14.8% <0.001*

Non-supineAHI 93.3% 55.6% <0.001*

*pvalue<0.05comparingsurgicalsuccessofthesupineandnon-supineAHIinrespondersandnon-

responders

AHIapnea-hypopneaindex

DISCUSSION

Most studies on MMA show success rates of approximately 85%. 15 This is the first series that

focussesonnon-responderstoMMA.Incontrasttowhatwasexpected,ourresultsdidnotshowa

significantdifferenceinsurgicalsuccessbetweenNPPandPP,suggestingtheabsenceofacorrelation

betweenposition-dependencyandsurgicaloutcomeinpatientsundergoingMMA.Whenstratifying

for surgical success of the supine and non-supine AHI no significant difference was found in the

surgical success of the supine AHI, but surgical success of the non-supine AHI was significantly

greaterinNPPthaninPP.Inthemajorityofnon-responders,ashiftfromsevereNPPtolesssevere

PPwasseencausedbyamorepronouncedreductionofthenon-supineAHIthanthesupineAHI.

When interpretingtheresults, thereareseveral factorsthatmustbetaken intoconsideration.Our

overallsuccessrate is lowerthanreported inthe literature.15This isprobablyduetothefactthat

MMA in our institute is strictly reserved for severe to extremeOSA (mean AHI of 51.5 events/h),

whilemanyotherseriesalsoincludemoderateandevenmildpathology.FortypercentofourMMA

patients underwent previous, unsuccessful UA surgery, or were considered poor candidates for

standardUAsurgeryorupperairwaystimulationforavarietyofreasons(e.g.,unfavorablefindings

during drug-induced sleep endoscopy, such as complete concentric palatal collapse or multilevel

totalcollapse),whichmighthaveinterferedwithapositivesurgicaloutcome.Lastly,theaverageage

inthisstudywashigherthaninotherstudiesreportingonthesurgicaloutcomeofMMA.Itisknown

thatahigheragehasanegativeimpactonthesurgicalsuccessofUAsurgeryandMMA.10

Nevertheless,wedidnotfindasignificantcorrelationbetweenageandsurgicalsuccessinourstudy

population. When evaluating the possible relation of REM–related OSA and the increase of the

percentage of REM sleep postoperatively, we did not find a significant correlation between the

presence of REM-relatedOSA and surgical success (p=0.136) Furthermore, the high percentage of

NPP is not surprising, due to the fact that the prevalence of positional OSA decreaseswhenOSA

severityincreases.16-20

AsignificantdecreaseofthetotalAHI,supineAHIandnon-supineAHIwasfoundinbothNPPandPP

afterMMA.ODIandaverageSpO2alsosignificantly improved inNPP,butnot inPP.Althoughtotal

and non-supine AHI significantly decreased in both NPP and PP, the decrease was significantly

greaterinNPPthaninPP.NosignificantdifferencewasfoundinthedecreaseofthesupineAHI.This

findingmight be explainedby the fact that thepreoperative total AHI andnon-supineAHI inNPP

weresignificantlyhigher.Asaresult,agreaterreductioninnon-supineAHIwaspossible.

The finding of a postoperative shift from severe NPP to less severe PP is not new. In previously

publishedstudies,similarresultswerefoundinpatientsundergoinguvulopalatopharyngoplastyorZ-

palatoplasty with or without radiofrequency thermotherapy of the tongue base and multilevel

180

Chapter 9

surgery.21-24Thisphenomenonalsooccursinthecaseofextensiveweightlossafterbariatricsurgery

inOSApatients 25,while unpublisheddata suggests that treatmentwithmandibular advancement

devicescanalsoleadtomorereductionofthelateralAHIthanthesupineAHI.

Clinicalrelevance

SinceMMA is oftenpositioned as a last resort and taking into account its considerablemorbidity,

surgicalfailureisaverydisappointingoutcome.ItisoftenseenthattheAHIinnon-supinepositions

issuccessfullyreduced,thisincontrasttothesupineAHI.Asaresult,apneiceventsmaystilloccurin

thesupineposition,whichcanhaveanegativeeffectontheoutcomeofMMA.However,additional

positional therapy (PT) using either the so-called tennis ball technique – inwhich a bulkymass is

attachedtotheback–,orwithnew-generationvibro-tactiledevicesattachedtothechestortrunk

aimingtopreventpatientsfromlyinginthesupineposition.Inthatcase,PTcanbeofaddedvaluein

non-responders with residual OSA in the supine position. 23, 26, 27 Furthermore, hypoglossal nerve

stimulationhasbeenaddedtothetreatmentarmamentariumofOSA.Severalpatientstreatedwith

MMA could in theory also have benefitted from this form of UA surgery, whichmay explain the

decrease innumberofMMAproceduresover thepast fewyears.Nevertheless,hypoglossalnerve

stimulation is currently only performed in patients with an AHI between 15 and 65 events/h,

therefore almost half of our study population would not have been selected for this therapeutic

option.

Limitations

This study is not without limitations. First, a retrospective study design was used, where a

prospectivestudywouldhavebeenpreferred.Second,whencomparingNPPandPPonemusttake

severalconfoundersintoconsideration.PPtendtohavelowertotalAHI, lowerBMIandareusually

younger as compared to NPP. These factors are also related to surgical outcome. 15, 28, 29

Nevertheless, after correcting for confounders such as age, preoperative total AHI and BMI, no

significantdifferenceinsurgicalsuccessbetweenNPPandPPwasfound.Third,especiallyinPP,total

AHI is influenced by the time spent in the supine position. Although this could have influenced

differencesinsurgicalsuccesswhencomparingNPPandPP,wedidnotfindasignificantdifferencein

percentageofTST inthesupineposition.Therefore, inouropiniontheeffectofthis limitationwas

negligible.

CONCLUSION

No significant difference in surgical success between NPP and PP undergoing MMA was found.

However,theimprovementoftotalandnon-supineAHIinNPPwassignificantlygreatercomparedto

PP.Innon-responders,apostoperativeshiftfromsevereNPPtolessseverePPwasseen,causedbya

greater reductionof thenon-supineAHI than thesupineAHI. Inpatientswith residualOSA in the

supinepositionafterMMA,additionaltreatmentwithPTcanbeindicated.

181

9

The influence of position-dependency on surgical success in obstructive sleep apnea patients

surgery.21-24Thisphenomenonalsooccursinthecaseofextensiveweightlossafterbariatricsurgery

inOSApatients 25,while unpublisheddata suggests that treatmentwithmandibular advancement

devicescanalsoleadtomorereductionofthelateralAHIthanthesupineAHI.

Clinicalrelevance

SinceMMA is oftenpositioned as a last resort and taking into account its considerablemorbidity,

surgicalfailureisaverydisappointingoutcome.ItisoftenseenthattheAHIinnon-supinepositions

issuccessfullyreduced,thisincontrasttothesupineAHI.Asaresult,apneiceventsmaystilloccurin

thesupineposition,whichcanhaveanegativeeffectontheoutcomeofMMA.However,additional

positional therapy (PT) using either the so-called tennis ball technique – inwhich a bulkymass is

attachedtotheback–,orwithnew-generationvibro-tactiledevicesattachedtothechestortrunk

aimingtopreventpatientsfromlyinginthesupineposition.Inthatcase,PTcanbeofaddedvaluein

non-responders with residual OSA in the supine position. 23, 26, 27 Furthermore, hypoglossal nerve

stimulationhasbeenaddedtothetreatmentarmamentariumofOSA.Severalpatientstreatedwith

MMA could in theory also have benefitted from this form of UA surgery, whichmay explain the

decrease innumberofMMAproceduresover thepast fewyears.Nevertheless,hypoglossalnerve

stimulation is currently only performed in patients with an AHI between 15 and 65 events/h,

therefore almost half of our study population would not have been selected for this therapeutic

option.

Limitations

This study is not without limitations. First, a retrospective study design was used, where a

prospectivestudywouldhavebeenpreferred.Second,whencomparingNPPandPPonemusttake

severalconfoundersintoconsideration.PPtendtohavelowertotalAHI, lowerBMIandareusually

younger as compared to NPP. These factors are also related to surgical outcome. 15, 28, 29

Nevertheless, after correcting for confounders such as age, preoperative total AHI and BMI, no

significantdifferenceinsurgicalsuccessbetweenNPPandPPwasfound.Third,especiallyinPP,total

AHI is influenced by the time spent in the supine position. Although this could have influenced

differencesinsurgicalsuccesswhencomparingNPPandPP,wedidnotfindasignificantdifferencein

percentageofTST inthesupineposition.Therefore, inouropiniontheeffectofthis limitationwas

negligible.

CONCLUSION

No significant difference in surgical success between NPP and PP undergoing MMA was found.

However,theimprovementoftotalandnon-supineAHIinNPPwassignificantlygreatercomparedto

PP.Innon-responders,apostoperativeshiftfromsevereNPPtolessseverePPwasseen,causedbya

greater reductionof thenon-supineAHI than thesupineAHI. Inpatientswith residualOSA in the

supinepositionafterMMA,additionaltreatmentwithPTcanbeindicated.

182

Chapter 9

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sleepapneainpatientsundergoingpolysomnography.Chest.2005;128(4):2130-7.

20. ItasakaY,MiyazakiS, IshikawaK,TogawaK.The influenceofsleeppositionandobesityon

sleepapnea.PsychiatryClinNeurosci.2000;54(3):340-1.

21. LeeCH,ShinHW,HanDH,etal.Theimplicationofsleeppositionintheevaluationofsurgical

outcomesinobstructivesleepapnea.OtolaryngolHeadNeckSurg.2009;140(4):531-5.

22. KastoerC,BenoistLBL,DieltjensM,etal.Comparisonofupperairwaycollapsepatternsand

its clinical significance: drug-induced sleependoscopy inpatientswithoutobstructive sleep apnea,

positionalandnon-positionalobstructivesleepapnea.SleepBreath.2018;22(4):939-48.

23. vanMaanenJ,WitteB,deVriesN.Theoreticalapproachtowardsincreasingeffectivenessof

palatal surgery in obstructive sleep apnea: role for concomitant positional therapy? Sleep and

Breathing.2014;18(2):341-49.

24. van Maanen JP, Ravesloot MJ, Witte BI, Grijseels M, de Vries N. Exploration of the

relationship between sleep position and isolated tongue base ormultilevel surgery in obstructive

sleepapnea.EurArchOtorhinolaryngol.2012;269(9):2129-36.

25. deRaaffCAL,Gorter-StamMAW,deVriesN,etal.Perioperativemanagementofobstructive

sleepapneainbariatricsurgery:aconsensusguideline.SurgObesRelatDis.2017;13(7):1095-109.

26. Benoist LB, Verhagen M, Torensma B, van Maanen JP, de Vries N. Positional therapy in

patientswith residual positional obstructive sleep apnea after upper airway surgery.SleepBreath.

2016.

27. RaveslootMJL,WhiteD,HeinzerR,OksenbergA,PepinJL.EfficacyoftheNewGenerationof

Devices for Positional Therapy for PatientsWith Positional Obstructive Sleep Apnea: A Systematic

ReviewoftheLiteratureandMeta-Analysis.JClinSleepMed.2017;13(6):813-24.

183

9

The influence of position-dependency on surgical success in obstructive sleep apnea patients

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syndrome.JOralMaxillofacSurg.2006;64(6):886-91.

9. GohYH,LimKA.Modifiedmaxillomandibularadvancementforthetreatmentofobstructive

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10. de Ruiter MHT, Apperloo RC, Milstein DMJ, de Lange J. Assessment of obstructive sleep

apnoea treatment success or failure after maxillomandibular advancement. Int J Oral Maxillofac

Surg.2017;46(11):1357-62.

11. Benoist LBLdR, M.H.T.; de Lange, J.; de Vries, N. Residual POSA After Maxillomandibular

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inObstructiveSleepApnea.Springer,Cham;2015:321-29.

12. Paoli JR, LauwersF, LacassagneL, TibergeM,Dodart L,Boutault F.Craniofacialdifferences

according to the body mass index of patients with obstructive sleep apnoea syndrome:

cephalometricstudyin85patients.BrJOralMaxillofacSurg.2001;39(1):40-5.

13. Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifications of the upper

airwayinadultswithobstructivesleepapneasyndrome.Sleep.1996;19(2):156-77.

14. Cartwright RD, Diaz F, Lloyd S. The effects of sleep posture and sleep stage on apnea

frequency.Sleep.1991;14(4):351-3

15. Zaghi S, Holty JE, Certal V, et al. Maxillomandibular Advancement for Treatment of

ObstructiveSleepApnea:AMeta-analysis.JAMAOtolaryngolHeadNeckSurg.2016;142(1):58-66

16. FrankMH,RaveslootMJ,vanMaanenJP,VerhagenE,deLangeJ,deVriesN.PositionalOSA

part 1: Towards a clinical classification system for position-dependent obstructive sleep apnoea.

SleepBreath.2015;19(2):473-80

17. OksenbergA,SilverbergDS,AronsE,RadwanH.Positionalvsnonpositionalobstructivesleep

apneapatients:anthropomorphic,nocturnalpolysomnographic,andmultiplesleeplatencytestdata.

Chest.1997;112(3):629-39

18. RichardW, Kox D, den Herder C, LamanM, van Tinteren H, de Vries N. The role of sleep

positioninobstructivesleepapneasyndrome.EurArchOtorhinolaryngol.2006;263(10):946-50

19. MadorMJ, Kufel TJ,MagalangUJ, Rajesh SK,Watwe V, Grant BJ. Prevalence of positional

sleepapneainpatientsundergoingpolysomnography.Chest.2005;128(4):2130-7

20. ItasakaY,MiyazakiS, IshikawaK,TogawaK.The influenceofsleeppositionandobesityon

sleepapnea.PsychiatryClinNeurosci.2000;54(3):340-1

21. LeeCH,ShinHW,HanDH,etal.Theimplicationofsleeppositionintheevaluationofsurgical

outcomesinobstructivesleepapnea.OtolaryngolHeadNeckSurg.2009;140(4):531-5

22. KastoerC,BenoistLBL,DieltjensM,etal.Comparisonofupperairwaycollapsepatternsand

its clinical significance: drug-induced sleependoscopy inpatientswithoutobstructive sleep apnea,

positionalandnon-positionalobstructivesleepapnea.SleepBreath.2018;22(4):939-48

23. vanMaanenJ,WitteB,deVriesN.Theoreticalapproachtowardsincreasingeffectivenessof

palatal surgery in obstructive sleep apnea: role for concomitant positional therapy? Sleep and

Breathing.2014;18(2):341-49

24. van Maanen JP, Ravesloot MJ, Witte BI, Grijseels M, de Vries N. Exploration of the

relationship between sleep position and isolated tongue base ormultilevel surgery in obstructive

sleepapnea.EurArchOtorhinolaryngol.2012;269(9):2129-36

25. deRaaffCAL,Gorter-StamMAW,deVriesN,etal.Perioperativemanagementofobstructive

sleepapneainbariatricsurgery:aconsensusguideline.SurgObesRelatDis.2017;13(7):1095-109

26. Benoist LB, Verhagen M, Torensma B, van Maanen JP, de Vries N. Positional therapy in

patientswith residual positional obstructive sleep apnea after upper airway surgery.SleepBreath.

2016

27. RaveslootMJL,WhiteD,HeinzerR,OksenbergA,PepinJL.EfficacyoftheNewGenerationof

Devices for Positional Therapy for PatientsWith Positional Obstructive Sleep Apnea: A Systematic

ReviewoftheLiteratureandMeta-Analysis.JClinSleepMed.2017;13(6):813-24

184

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4

28. ShieDY,TsouYA,TaiCJ,TsaiMH.Impactofobesityonuvulopalatopharyngoplastysuccessin

patients with severe obstructive sleep apnea: a retrospective single-center study in Taiwan. Acta

Otolaryngol.2013;133(3):261-9

29. Liu SA, Li HY, Tsai WC, Chang KM. Associated factors to predict outcomes of

uvulopharyngopalatoplasty plus genioglossal advancement for obstructive sleep apnea.

Laryngoscope.2005;115(11):2046-50

10Discussionandfutureperspectives

10Discussionandfutureperspectives

4

28. ShieDY,TsouYA,TaiCJ,TsaiMH.Impactofobesityonuvulopalatopharyngoplastysuccessin

patients with severe obstructive sleep apnea: a retrospective single-center study in Taiwan. Acta

Otolaryngol.2013;133(3):261-9.

29. Liu SA, Li HY, Tsai WC, Chang KM. Associated factors to predict outcomes of

uvulopharyngopalatoplasty plus genioglossal advancement for obstructive sleep apnea.

Laryngoscope.2005;115(11):2046-50.

10Discussionandfutureperspectives

10Discussionandfutureperspectives

186

Chapter 10

DISCUSSIONANDFUTUREPERSEPECTIVES

The general aim of this thesis is to assess the role of drug-induced sleep endoscopy (DISE) and

position-dependency inthediagnosticwork-up inobstructivesleepapnea(OSA)patientstoenable

patient-specifictreatmentplanning.

DISE isanacceptedtool inthediagnosticwork-upforsurgicalcandidatesto identifythestructures

involvedinupperairway(UA)obstruction.MorecontroversialistheapplicationofDISEinthework-

up for non-surgical interventions, such as a mandibular advancement device (MAD), positional

therapy(PT)orcombinationtreatment(i.e.,MADandPTorPTandUAsurgery).Basedontheresults

ofchapter4andchapter5,weadvocatethatDISEcanbeofaddedvaluepriortothesenon-surgical

interventions since this procedure in combination with the maneuvers described can provide

valuableinformation.

Thefoundationforthestudies leadingtotheseconclusionswaspresentedinchapter2.Byusinga

theoreticalmodelweconcludedthattheeffectofjawthrustonUApatencyisprobablygreaterthan

the effect ofMAD treatment. Secondly,we suggested that lateral head rotation is not similar to

lateralheadandtrunkposition,especiallynotinpatientswithposition-dependentOSA(PP).Weare

awareof the fact that thepresentmodel leaves roomfor improvementandwestill regard thisas

work inprogress.But, theoutcomesofthisstudygeneratedtheaimsandhypothesesevaluated in

thesubsequentchapters.

TheuseofjawthrustduringDISEtopredictMADtreatmentoutcome

Ideally,bymimicking theeffectofMADthroughpassivemaneuversduringDISEonecould reliably

predict its actual effect resulting in greater cost-effectiveness. The predictive value of passive

maneuvers remains under discussion. In recent years, several alternatives to the jaw thrust have

been proposed varying from thermoplastic appliances — a mono-bloc splint — to the use of a

simulationbite—consistingofaregistrationforkinmaximalcomfortableprotrusion(MCP)—during

DISE.Althoughthe latterseemstobepromising, it istime-consumingand inalmostallcentresnot

partofdailypractice.Inchapter4theeffectonUApatencyoftwopotentialscreeningmethodswas

compared.Unfortunately, theagreement indegreeofobstructionmeasuredwith jawthrustanda

new-generation thermoplastic boil-and-bite MAD — the MyTAP —was only slight to moderate.

Overall,agreaterimprovementofUApatencyathypopharyngeallevelwasobservedwhenapplying

jawthrust.Incontrast,jawthrustwaslesseffectiveinimprovingUAobstructionatretropalatallevel

thantheMyTAPduringDISE.Theresultsofthisstudyemphasizetheneedforanalternativetojaw

thrustasascreeningmethodandpredictiontoolforMADtreatmentthatcanbeusedduringDISE.

Chapter4describesthefirstpartofatwo-partstudy.Inthefuture,itwillbeessentialtoassessthe

correlation between the screening methods previously described and actual MAD treatment

outcome.ThiswillbenecessarytofurtherunravelthepredictivevalueonMADeffectivenessusing

DISEasscreeningtool.

BodypositionandDISE

Historically,DISE is performed in theworst sleepingposition,which is usually the supineposition.

Withthegrowingattentionfortheeffectofbodyposition—either lateralheadrotationor lateral

headand trunkposition—onOSA severity, one could argue that assessmentof theUA in lateral

positionisatleastasimportantasobservationsmadeinthesupineposition.Theresultsdescribedin

chapter3 indicatethatinnon-positionalOSApatients(NPP)theeffectoflateralheadrotationonly

onUApatencyiscomparabletolateralheadandtrunkpositionateachpossiblelevelofobstruction,

withexceptionoftheoropharynx.Thelatterisprobablycausedbydisplacementofthetonguebase,

which alters lateral oropharyngeal wall tension causing a secondary collapse of the lateral

oropharyngealwalls.ThiscollapsibilityispresumablyhigherinNPP,sinceNPPtendtohaveahigher

body mass index (BMI) in combination with a greater neck circumference. In PP, the degree of

obstructionduringlateralheadrotationwassignificantlydifferentfromtheobservationsmadewhen

patients were lying in lateral position, at every possible obstruction site. Therefore, in NPP DISE

should be performed in supine position with and without lateral head rotation, which suffices to

imitate lateral sleeping position. In PP, it is recommended to perform DISE in supine and lateral

positiontogainmoreinformationonUAcollapsepatterns.Thiscanprovideabroaderperspectiveon

possible treatmentoptions, especially sincePT is becoming amore accepted treatment in PP as a

standalonetreatment,or incombinationwithothertreatmentmodalities(e.g.,MADorUAsurgery

orUAstimulation).

Another finding that underlines the relevance of performing DISE — also when non-surgical

interventionsare considered— is thephenomenonof a floppyepiglottis (FE). Thediagnosisof an

epiglotticcollapsestill requires invasivestudies,sinceasarule itcannotbeestablishedbyphysical

examinationorawakeindirectorflexiblelaryngoscopy.Althoughalgorithmshavebeenproposedto

identify airflow patterns and its relation to epiglottic collapse, these studies are not externally

validated or yet part of daily practice. Nevertheless it is important to evaluate whether a FE is

involved in the underlying pathology ofOSA, since it has been linked to CPAP failure. In addition,

treatmentwithMADs—which is often recommended as therapy of choice— is also not always

successful. In chapter 5we tested thehypothesis that thepresenceof a FE is influencedbybody

187

10

Discussion and future perspective

DISCUSSIONANDFUTUREPERSEPECTIVES

The general aim of this thesis is to assess the role of drug-induced sleep endoscopy (DISE) and

position-dependency inthediagnosticwork-up inobstructivesleepapnea(OSA)patientstoenable

patient-specifictreatmentplanning.

DISE isanacceptedtool inthediagnosticwork-upforsurgicalcandidatesto identifythestructures

involvedinupperairway(UA)obstruction.MorecontroversialistheapplicationofDISEinthework-

up for non-surgical interventions, such as a mandibular advancement device (MAD), positional

therapy(PT)orcombinationtreatment(i.e.,MADandPTorPTandUAsurgery).Basedontheresults

ofchapter4andchapter5,weadvocatethatDISEcanbeofaddedvaluepriortothesenon-surgical

interventions since this procedure in combination with the maneuvers described can provide

valuableinformation.

Thefoundationforthestudies leadingtotheseconclusionswaspresentedinchapter2.Byusinga

theoreticalmodelweconcludedthattheeffectofjawthrustonUApatencyisprobablygreaterthan

the effect ofMAD treatment. Secondly,we suggested that lateral head rotation is not similar to

lateralheadandtrunkposition,especiallynotinpatientswithposition-dependentOSA(PP).Weare

awareof the fact that thepresentmodel leaves roomfor improvementandwestill regard thisas

work inprogress.But, theoutcomesofthisstudygeneratedtheaimsandhypothesesevaluated in

thesubsequentchapters.

TheuseofjawthrustduringDISEtopredictMADtreatmentoutcome

Ideally,bymimicking theeffectofMADthroughpassivemaneuversduringDISEonecould reliably

predict its actual effect resulting in greater cost-effectiveness. The predictive value of passive

maneuvers remains under discussion. In recent years, several alternatives to the jaw thrust have

been proposed varying from thermoplastic appliances — a mono-bloc splint — to the use of a

simulationbite—consistingofaregistrationforkinmaximalcomfortableprotrusion(MCP)—during

DISE.Althoughthe latterseemstobepromising, it istime-consumingand inalmostallcentresnot

partofdailypractice.Inchapter4theeffectonUApatencyoftwopotentialscreeningmethodswas

compared.Unfortunately, theagreement indegreeofobstructionmeasuredwith jawthrustanda

new-generation thermoplastic boil-and-bite MAD — the MyTAP —was only slight to moderate.

Overall,agreaterimprovementofUApatencyathypopharyngeallevelwasobservedwhenapplying

jawthrust.Incontrast,jawthrustwaslesseffectiveinimprovingUAobstructionatretropalatallevel

thantheMyTAPduringDISE.Theresultsofthisstudyemphasizetheneedforanalternativetojaw

thrustasascreeningmethodandpredictiontoolforMADtreatmentthatcanbeusedduringDISE.

Chapter4describesthefirstpartofatwo-partstudy.Inthefuture,itwillbeessentialtoassessthe

correlation between the screening methods previously described and actual MAD treatment

outcome.ThiswillbenecessarytofurtherunravelthepredictivevalueonMADeffectivenessusing

DISEasscreeningtool.

BodypositionandDISE

Historically,DISE is performed in theworst sleepingposition,which is usually the supineposition.

Withthegrowingattentionfortheeffectofbodyposition—either lateralheadrotationor lateral

headand trunkposition—onOSA severity, one could argue that assessmentof theUA in lateral

positionisatleastasimportantasobservationsmadeinthesupineposition.Theresultsdescribedin

chapter3 indicatethatinnon-positionalOSApatients(NPP)theeffectoflateralheadrotationonly

onUApatencyiscomparabletolateralheadandtrunkpositionateachpossiblelevelofobstruction,

withexceptionoftheoropharynx.Thelatterisprobablycausedbydisplacementofthetonguebase,

which alters lateral oropharyngeal wall tension causing a secondary collapse of the lateral

oropharyngealwalls.ThiscollapsibilityispresumablyhigherinNPP,sinceNPPtendtohaveahigher

body mass index (BMI) in combination with a greater neck circumference. In PP, the degree of

obstructionduringlateralheadrotationwassignificantlydifferentfromtheobservationsmadewhen

patients were lying in lateral position, at every possible obstruction site. Therefore, in NPP DISE

should be performed in supine position with and without lateral head rotation, which suffices to

imitate lateral sleeping position. In PP, it is recommended to perform DISE in supine and lateral

positiontogainmoreinformationonUAcollapsepatterns.Thiscanprovideabroaderperspectiveon

possible treatmentoptions, especially sincePT is becoming amore accepted treatment in PP as a

standalonetreatment,or incombinationwithothertreatmentmodalities(e.g.,MADorUAsurgery

orUAstimulation).

Another finding that underlines the relevance of performing DISE — also when non-surgical

interventionsare considered— is thephenomenonof a floppyepiglottis (FE). Thediagnosisof an

epiglotticcollapsestill requires invasivestudies,sinceasarule itcannotbeestablishedbyphysical

examinationorawakeindirectorflexiblelaryngoscopy.Althoughalgorithmshavebeenproposedto

identify airflow patterns and its relation to epiglottic collapse, these studies are not externally

validated or yet part of daily practice. Nevertheless it is important to evaluate whether a FE is

involved in the underlying pathology ofOSA, since it has been linked to CPAP failure. In addition,

treatmentwithMADs—which is often recommended as therapy of choice— is also not always

successful. In chapter 5we tested thehypothesis that thepresenceof a FE is influencedbybody

188

Chapter 10

positionandjawthrust.TheresultsofthisstudyindicatedthataFEappearsalmostexclusivelyinthe

supineposition.AFEwasstillpresentintheminorityofpatientswhenjawthrustwasapplied.

Aspreviouslystated, treatmentofaFE remainschallengingandevidencebasedtreatmentoptions

arelacking.Inthepast,severalsurgicaltechniquesoftheepiglottishavebeendescribed,whichare

unfortunately not without any risks. Based on the results described in chapter 5, PT could be a

promisingalternativeinpatientswithaFE,despitethefactthattheymightnotsufferfromposition-

dependentOSA(POSA).Itcanbeusedasastandalonetreatment,butsinceaFEisusuallypartofa

multilevelproblem,itcanalsobecombinedwithaMADorlessinvasiveformsofUAsurgerylimiting

risksandcomplications.

Polysomnographyandsleepposition

Inchapter8theinfluenceofwearingtypeIIpolysomnography(PSG)apparatusonsleepingposition

was analyzed. The results suggested that patients spend significantly more time in the supine

position whilst undergoing a PSG. This leads to an increase in OSA severity measured by PSG,

especially in PP, which could have significant impact on both clinical practice and research. As a

matter of fact, several patients would not even have been diagnosed with OSA when using the

percentage of supine body positionmeasured during the inactive (diagnostic) phase of the Sleep

Position Trainer (SPT). We are aware of the fact that the presented study leaves room for

improvement. First we only included PP who were aware of the fact that they were position-

dependentandthattheyshouldavoidthesupineposition.Nevertheless,similarresultswerefound

in a few previously published small-scale studies. In clinical practice, therapeutic options are

evaluatedbasedon,amongotherthings,OSAseverity.WhileCPAPisthetherapyofchoiceincaseof

severeOSA,othertreatmentoptions,suchasPT,MADsorUAsurgerycanbeconsideredincaseof

mildormoderateOSA. IfwearingPSGapparatustrulycausinganoverestimationOSAseverity,this

hasanimportantimpactondiagnosisandtreatment,sincemanyrecommendationsinguidelinesare

basedon the totalAHI. In the future, there isademand for less invasivePSGapparatus,with less

impactonsleepingposition.

Position-dependencyandsleepapneasurgery

Thereareseveralknownfactorscontributingtolowersurgicalsuccessrates,suchasahighBMI,high

totalAHIandacompleteconcentriccollapseatpalatallevelobservedduringDISE.LikewiseNPPtend

tohavemoreseverediseaseandahigherBMIincomparisontoPP.Basedonthisinformation,one

couldhypothesizethatNPPhavea lowerchanceofsurgicalsuccess.Ontheotherhand,onemight

arguethatsincethenon-supineAHIinPPislowpre-operatively,NPPhaveahigherchanceofsurgical

successsincean improvementof theAHI inbothsupineandnon-supinepositioncanbeachieved,

thisincontrasttoPP.

Toevaluatewhetherposition-dependencyisapredictorforsurgicalsuccessofsleepapneasurgery,a

systematic reviewwas performed including nine studies; two prospective and seven retrospective

cohort studies (chapter 9). Despite the importance of the subject, the results of this study were

inconclusive.Thesignificantclinicaldiversityamongstudies(e.g.,differentformsofUAsurgeryand

variations in the definition of surgical success) complicated the interpretation of the results.

Furthermore,noneoftheincludedstudiescorrectedforpostoperativechangesinthetimespendin

supine position. As previously mentioned, OSA severity is strongly dependent on this factor —

especially in PP—and subsequently thismay also have influenced surgical success. These factors

couldhavecontributedtothefactthatwedidnotfindadifferenceinsurgicalsuccessbetweenNPP

andPP.WedidfindthatinthevastpartofincludedstudiestheeffectofUAsurgerywassuggested

tobegreater in the lateral position than the supineposition. In studies reportingonpreoperative

andpostoperativePSGparametersinNPPandPP,asignificantreductionofthenon-supineAHIwas

foundinNPP,butnotinPP.AnotherinterestingfindingwasthatNPPoftenimprovetolessseverePP

afterUAsurgery;thedropinAHIismorepronouncedinnon-supineascomparedtosupineposition.

Whenevaluatingthesurgicalsuccessofmaxillomandibularadvancement(MMA) inmoredetail,no

difference in surgical successwas found comparingNPPandPP (chapter 10).When stratifying for

surgicalsuccessofthesupineandnon-supineAHInosignificantdifferencewasfoundinthesurgical

successofthesupineAHI,butsurgicalsuccessofthenon-supineAHIwassignificantlygreaterinNPP

than inPP. In themajorityofnon-responders, a shift fromsevereNPP to less severePPwas seen

causedbyamorepronouncedreductionofthenon-supineAHIthanthesupineAHI.

Insummary, it remainsundecidedwhetherposition-dependency isapredictor forsurgicalsuccess.

But, since themajority of OSA patients are PP, there is a demand for high-quality evidence from

largerprospectivestudiesevaluatingdifferencesinsurgicalsuccessbetweenNPPandPP.Toenable

accuratecomparisonofsurgicalsuccessinNPPandPPuniversaldefinitionsforposition-dependency

and surgical success should be used. Furthermore, we believe that it is recommended to use a

standardizedframeworktoreportontheroleofbodypositioninthemanagementofOSApatients.

189

10

Discussion and future perspective

positionandjawthrust.TheresultsofthisstudyindicatedthataFEappearsalmostexclusivelyinthe

supineposition.AFEwasstillpresentintheminorityofpatientswhenjawthrustwasapplied.

Aspreviouslystated, treatmentofaFE remainschallengingandevidencebasedtreatmentoptions

arelacking.Inthepast,severalsurgicaltechniquesoftheepiglottishavebeendescribed,whichare

unfortunately not without any risks. Based on the results described in chapter 5, PT could be a

promisingalternativeinpatientswithaFE,despitethefactthattheymightnotsufferfromposition-

dependentOSA(POSA).Itcanbeusedasastandalonetreatment,butsinceaFEisusuallypartofa

multilevelproblem,itcanalsobecombinedwithaMADorlessinvasiveformsofUAsurgerylimiting

risksandcomplications.

Polysomnographyandsleepposition

Inchapter8theinfluenceofwearingtypeIIpolysomnography(PSG)apparatusonsleepingposition

was analyzed. The results suggested that patients spend significantly more time in the supine

position whilst undergoing a PSG. This leads to an increase in OSA severity measured by PSG,

especially in PP, which could have significant impact on both clinical practice and research. As a

matter of fact, several patients would not even have been diagnosed with OSA when using the

percentage of supine body positionmeasured during the inactive (diagnostic) phase of the Sleep

Position Trainer (SPT). We are aware of the fact that the presented study leaves room for

improvement. First we only included PP who were aware of the fact that they were position-

dependentandthattheyshouldavoidthesupineposition.Nevertheless,similarresultswerefound

in a few previously published small-scale studies. In clinical practice, therapeutic options are

evaluatedbasedon,amongotherthings,OSAseverity.WhileCPAPisthetherapyofchoiceincaseof

severeOSA,othertreatmentoptions,suchasPT,MADsorUAsurgerycanbeconsideredincaseof

mildormoderateOSA. IfwearingPSGapparatustrulycausinganoverestimationOSAseverity,this

hasanimportantimpactondiagnosisandtreatment,sincemanyrecommendationsinguidelinesare

basedon the totalAHI. In the future, there isademand for less invasivePSGapparatus,with less

impactonsleepingposition.

Position-dependencyandsleepapneasurgery

Thereareseveralknownfactorscontributingtolowersurgicalsuccessrates,suchasahighBMI,high

totalAHIandacompleteconcentriccollapseatpalatallevelobservedduringDISE.LikewiseNPPtend

tohavemoreseverediseaseandahigherBMIincomparisontoPP.Basedonthisinformation,one

couldhypothesizethatNPPhavea lowerchanceofsurgicalsuccess.Ontheotherhand,onemight

arguethatsincethenon-supineAHIinPPislowpre-operatively,NPPhaveahigherchanceofsurgical

successsincean improvementof theAHI inbothsupineandnon-supinepositioncanbeachieved,

thisincontrasttoPP.

Toevaluatewhetherposition-dependencyisapredictorforsurgicalsuccessofsleepapneasurgery,a

systematic reviewwas performed including nine studies; two prospective and seven retrospective

cohort studies (chapter 9). Despite the importance of the subject, the results of this study were

inconclusive.Thesignificantclinicaldiversityamongstudies(e.g.,differentformsofUAsurgeryand

variations in the definition of surgical success) complicated the interpretation of the results.

Furthermore,noneoftheincludedstudiescorrectedforpostoperativechangesinthetimespendin

supine position. As previously mentioned, OSA severity is strongly dependent on this factor —

especially in PP—and subsequently thismay also have influenced surgical success. These factors

couldhavecontributedtothefactthatwedidnotfindadifferenceinsurgicalsuccessbetweenNPP

andPP.WedidfindthatinthevastpartofincludedstudiestheeffectofUAsurgerywassuggested

tobegreater in the lateral position than the supineposition. In studies reportingonpreoperative

andpostoperativePSGparametersinNPPandPP,asignificantreductionofthenon-supineAHIwas

foundinNPP,butnotinPP.AnotherinterestingfindingwasthatNPPoftenimprovetolessseverePP

afterUAsurgery;thedropinAHIismorepronouncedinnon-supineascomparedtosupineposition.

Whenevaluatingthesurgicalsuccessofmaxillomandibularadvancement(MMA) inmoredetail,no

difference in surgical successwas found comparingNPPandPP (chapter 10).When stratifying for

surgicalsuccessofthesupineandnon-supineAHInosignificantdifferencewasfoundinthesurgical

successofthesupineAHI,butsurgicalsuccessofthenon-supineAHIwassignificantlygreaterinNPP

than inPP. In themajorityofnon-responders, a shift fromsevereNPP to less severePPwas seen

causedbyamorepronouncedreductionofthenon-supineAHIthanthesupineAHI.

Insummary, it remainsundecidedwhetherposition-dependency isapredictor forsurgicalsuccess.

But, since themajority of OSA patients are PP, there is a demand for high-quality evidence from

largerprospectivestudiesevaluatingdifferencesinsurgicalsuccessbetweenNPPandPP.Toenable

accuratecomparisonofsurgicalsuccessinNPPandPPuniversaldefinitionsforposition-dependency

and surgical success should be used. Furthermore, we believe that it is recommended to use a

standardizedframeworktoreportontheroleofbodypositioninthemanagementofOSApatients.

190

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190

11Summary/Samenvatting

190

11Summary/Samenvatting

190

11Summary/Samenvatting

192

Chapter 11

SUMMARY

Studiesenclosedinthisthesisfocusedontheroleofpostureanddifferentpassivemaneuversduring

drug-inducedsleependoscopy(DISE)anditsrelevancewithregardtoobstructivesleepapnea(OSA)

treatment outcome and patient-specific treatment planning. Chapter 1 provides a general

introductiontoOSA.

Inchapter2aretrospective,single-centercohortstudyincludingaconsecutiveseriesofOSApatients

whounderwentDISEwaspresented.Wecomposeda3-pointsmodel,basedon theVOTE (Velum,

Oropharynx,Tonguebase,Epiglottis)classificationsystem,evaluatingtheeffectofdifferentpassive

maneuvers—manuallyperformedjawthrust,lateralheadrotation,andacombinationofboth—on

upper airway (UA) patency. The effect of thesemaneuvers was analyzed by using the sum VOTE

scorecomparingnon-positionalOSApatients(NPP)andpositionalOSApatients(PP)andcompared

to the expected effect based on treatment outcomeof amandibular advancement device (MAD),

positionaltherapy(PT),andcombinedtreatmentasreportedintheliterature.Itwasconcludedthat

theeffectofmanuallyperformedjawthrustwasgreaterandtheeffectoflateralheadrotationalone

duringDISElessthanwhatwasexpected.

Basedonthefindingsdescribedinchapter2,weprospectivelycomparedtheeffectof lateralhead

rotationonlyandboth lateralheadandtrunkpositiononUAobstruction inchapter 3. In total,92

patientsunderwentDISE intrunkandheadsupine,trunkandheadlateralandwhenonlythehead

wasrotatedtolateralpositionbuttrunkremainedinthesupineposition.Theeffectoflateralhead

rotationandlateralheadandtrunkrotationonUApatencyduringDISEwassignificantlydifferentin

PP. In NPP, similar results regarding the degree of UA obstructionwere found at the level of the

velum,tonguebaseandepiglottis.

Inthestudydescribedinchapter2wealsofoundthatjawthrusthadagreatereffectonUApatency

thanexpectedbasedondatapublished in the literatureonMADtreatmentoutcome. Inchapter 4

theagreementbetweenjawthrustandanoraldeviceinsituduringDISE—inmeansofopeningof

thecollapsiblesegmentoftheUA—wasassessed.Secondly,thetheoreticalimplicationsonclinical

decision-making using either jaw thrust or a new generation boil-and-bite MAD (MyTAP, Airway

Management Inc.) as potential screening instruments were evaluated. The results of this study

indicated that therewas only a slight tomoderate agreement in degree of obstructionmeasured

withjawthrustandtheMyTAPinsituduringDISE.Overall,agreaterimprovementofUApatencyat

hypopharyngeal level was observed when applying jaw thrust. In contrast, jaw thrust was less

effective in improvingUAobstruction at retropalatal level than theMyTAP. Itwas concluded that

thereisstillaneedforanalternativetojawthrustthatcanbeusedasascreeningmethodandserve

asabetterpredictiontoolfortheeffectofMADtreatmentoutcomeduringDISE.

Inchapter5thepresenceofafloppyepiglottis(FE)duringDISEinnon-apneicsnoringpatients,NPP

andPPwasassessedandtheimpactofmaneuversandposturewasevaluated.Inthisretrospective

study324patientswere included. In60patients (18.5%)aFEwas found in supineposition.When

performinglateralheadrotationonly,aFEwaspresentinfourpatients,whileinlateralpositionaFE

was found inonlyonesubject.Afterapplying jaw thrust,aFEwas stillpresent in10patients.The

prevalenceofaFEdidnotsignificantlydifferbetweenNPPandPP.InpatientswithaFE,PTcanbea

promising alternative as a standalone treatment, but also aspart of combination therapywith for

exampleMADsorlessinvasiveformsofUAsurgery.

Chapter 6 presents theobjectiveoutcomesand safetyof upper airway stimulation (UAS), and the

influenceofpreoperativeDISE findingsonsurgicalsuccess.Aconsecutiveseriesof44moderateto

severe OSA patients with continuous positive airway pressure (CPAP) intolerance or failure were

included. The total median apnea-hypopnea index (AHI) significantly decreased from 37.6 (30.4;

43.4)events/hto8.3(5.3;12.0)events/h(p<0.001),theoxygendesaturationindexwassignificantly

reducedfrom37.1(28.4;42.6)events/hto15.9(11.1;21.6)events/h.With88.6%,surgicalsuccess

was high. UAS has proven to be an effective and safe treatment in OSA patients with CPAP

intoleranceor failure, inwhichproperpatient selection,adequate implantationof theUASsystem

andfollow-upbytrainedpersonnelarekeytotreatmentsuccess.Therewasnosignificantdifference

in surgical outcome between patients with a tongue base collapse with or without a complete

anteroposteriorcollapseatthelevelofthepalate.

PastyearsnotonlythenumberofstudiesonDISEhasrapidlyincreased,alsotheinfluenceofbody

postureonOSAseverityhasgainedgrowingattention.EspeciallyinPP,OSAseveritydependsonthe

supine and non-supine AHI, as well as the time spent in supine position. Especially, the latter is

susceptible to variation. In chapter 7, the effect ofwearing polysomnography (PSG) apparatus on

sleeping position and the influence on OSA severity was evaluated. One hundred and sixty-eight

position-dependent OSA (POSA) and non-apneic snoring patients who were prescribed PT (Sleep

Position Trainer [SPT]) were retrospectively included. The effect of wearing PSG apparatus on

sleeping position was analyzed by comparing body position during the PSG night and inactive

(diagnostic)phaseoftheSPT.TheresultsofthisstudyindicatedthatwearingPSGapparatusleadto

anincreaseinsupinesleepof33.6%causinganoverestimationofOSAseverity,especiallyinPP.

193

11

Summary / samenvatting

SUMMARY

Studiesenclosedinthisthesisfocusedontheroleofpostureanddifferentpassivemaneuversduring

drug-inducedsleependoscopy(DISE)anditsrelevancewithregardtoobstructivesleepapnea(OSA)

treatment outcome and patient-specific treatment planning. Chapter 1 provides a general

introductiontoOSA.

Inchapter2aretrospective,single-centercohortstudyincludingaconsecutiveseriesofOSApatients

whounderwentDISEwaspresented.Wecomposeda3-pointsmodel,basedon theVOTE (Velum,

Oropharynx,Tonguebase,Epiglottis)classificationsystem,evaluatingtheeffectofdifferentpassive

maneuvers—manuallyperformedjawthrust,lateralheadrotation,andacombinationofboth—on

upper airway (UA) patency. The effect of thesemaneuvers was analyzed by using the sum VOTE

scorecomparingnon-positionalOSApatients(NPP)andpositionalOSApatients(PP)andcompared

to the expected effect based on treatment outcomeof amandibular advancement device (MAD),

positionaltherapy(PT),andcombinedtreatmentasreportedintheliterature.Itwasconcludedthat

theeffectofmanuallyperformedjawthrustwasgreaterandtheeffectoflateralheadrotationalone

duringDISElessthanwhatwasexpected.

Basedonthefindingsdescribedinchapter2,weprospectivelycomparedtheeffectof lateralhead

rotationonlyandboth lateralheadandtrunkpositiononUAobstruction inchapter 3. In total,92

patientsunderwentDISE intrunkandheadsupine,trunkandheadlateralandwhenonlythehead

wasrotatedtolateralpositionbuttrunkremainedinthesupineposition.Theeffectoflateralhead

rotationandlateralheadandtrunkrotationonUApatencyduringDISEwassignificantlydifferentin

PP. In NPP, similar results regarding the degree of UA obstructionwere found at the level of the

velum,tonguebaseandepiglottis.

Inthestudydescribedinchapter2wealsofoundthatjawthrusthadagreatereffectonUApatency

thanexpectedbasedondatapublished in the literatureonMADtreatmentoutcome. Inchapter 4

theagreementbetweenjawthrustandanoraldeviceinsituduringDISE—inmeansofopeningof

thecollapsiblesegmentoftheUA—wasassessed.Secondly,thetheoreticalimplicationsonclinical

decision-making using either jaw thrust or a new generation boil-and-bite MAD (MyTAP, Airway

Management Inc.) as potential screening instruments were evaluated. The results of this study

indicated that therewas only a slight tomoderate agreement in degree of obstructionmeasured

withjawthrustandtheMyTAPinsituduringDISE.Overall,agreaterimprovementofUApatencyat

hypopharyngeal level was observed when applying jaw thrust. In contrast, jaw thrust was less

effective in improvingUAobstruction at retropalatal level than theMyTAP. Itwas concluded that

thereisstillaneedforanalternativetojawthrustthatcanbeusedasascreeningmethodandserve

asabetterpredictiontoolfortheeffectofMADtreatmentoutcomeduringDISE.

Inchapter5thepresenceofafloppyepiglottis(FE)duringDISEinnon-apneicsnoringpatients,NPP

andPPwasassessedandtheimpactofmaneuversandposturewasevaluated.Inthisretrospective

study324patientswere included. In60patients (18.5%)aFEwas found in supineposition.When

performinglateralheadrotationonly,aFEwaspresentinfourpatients,whileinlateralpositionaFE

was found inonlyonesubject.Afterapplying jaw thrust,aFEwas stillpresent in10patients.The

prevalenceofaFEdidnotsignificantlydifferbetweenNPPandPP.InpatientswithaFE,PTcanbea

promising alternative as a standalone treatment, but also aspart of combination therapywith for

exampleMADsorlessinvasiveformsofUAsurgery.

Chapter 6 presents theobjectiveoutcomesand safetyof upper airway stimulation (UAS), and the

influenceofpreoperativeDISE findingsonsurgicalsuccess.Aconsecutiveseriesof44moderateto

severe OSA patients with continuous positive airway pressure (CPAP) intolerance or failure were

included. The total median apnea-hypopnea index (AHI) significantly decreased from 37.6 (30.4;

43.4)events/hto8.3(5.3;12.0)events/h(p<0.001),theoxygendesaturationindexwassignificantly

reducedfrom37.1(28.4;42.6)events/hto15.9(11.1;21.6)events/h.With88.6%,surgicalsuccess

was high. UAS has proven to be an effective and safe treatment in OSA patients with CPAP

intoleranceor failure, inwhichproperpatient selection,adequate implantationof theUASsystem

andfollow-upbytrainedpersonnelarekeytotreatmentsuccess.Therewasnosignificantdifference

in surgical outcome between patients with a tongue base collapse with or without a complete

anteroposteriorcollapseatthelevelofthepalate.

PastyearsnotonlythenumberofstudiesonDISEhasrapidlyincreased,alsotheinfluenceofbody

postureonOSAseverityhasgainedgrowingattention.EspeciallyinPP,OSAseveritydependsonthe

supine and non-supine AHI, as well as the time spent in supine position. Especially, the latter is

susceptible to variation. In chapter 7, the effect ofwearing polysomnography (PSG) apparatus on

sleeping position and the influence on OSA severity was evaluated. One hundred and sixty-eight

position-dependent OSA (POSA) and non-apneic snoring patients who were prescribed PT (Sleep

Position Trainer [SPT]) were retrospectively included. The effect of wearing PSG apparatus on

sleeping position was analyzed by comparing body position during the PSG night and inactive

(diagnostic)phaseoftheSPT.TheresultsofthisstudyindicatedthatwearingPSGapparatusleadto

anincreaseinsupinesleepof33.6%causinganoverestimationofOSAseverity,especiallyinPP.

194

Chapter 11

Chapter8describedasystematicreviewontheinfluenceofposition-dependencyonsurgicalsuccess

of different forms of UA surgery. In total, nine studies were included. Although preoperative

characteristics inPP (e.g., lowerbodymass index andAHI) seem tobe in favor forhigher surgical

successcomparedtoNPP,itremainsunclearwhetherornotposition-dependencyisapredictorfor

surgical outcome. It is suggested that the largest differences and expected preoperative and

postoperative changes occur in non-supineAHI. In PP, the preoperative non-supineAHI is already

lowercomparedtoNPPsuggestingalowerchanceofsurgicalsuccessinPP.

Chapter9focusesonthedifferencesinsurgicalsuccessinNPPandPPundergoingmaxillomandibular

advancement (MMA).Furthermore, the influenceofposition-dependencyonsurgicaloutcomeand

thephenomenonofresidualPOSAinnon-responderstoMMAwereevaluated.Aconsecutiveseries

of 57 patients undergoing MMA were retrospectively included. The overall surgical success was

52.6%. No significant difference in surgical success between NPP and PP undergoing MMA was

found. However, the improvement of total and non-supine AHI in NPP was significantly greater

compared to PP. In non-responders, a postoperative shift from severe NPP to less severe PPwas

found,causedbyagreaterreductionofthenon-supineAHIthanthesupineAHIpostoperatively.

SAMENVATTING

De studies in dit proefschrift zijn gericht op de rol van lichaamshouding en verschillende passieve

manoeuvres toegepast tijdens een medicamenteus-geïnduceerde slaapendoscopie (drug-induced

sleep endoscopy, DISE) bij patiënten met obstructieve slaapapneu (OSA). Hierbij ging het in het

bijzonder om de relevantie ervanmet betrekking tot behandeluitkomsten en patiëntselectie voor

diversevormenvantherapie.Inhoofdstuk1werdeenalgemeneintroductiegegeven.

Hoofdstuk 2 gaf deuitkomsten vaneen retrospectieve cohort studieweer,waarbijOSA-patiënten

werden geïncludeerddie eenDISE hebbenondergaan. Erwerd een 3-punten systeemontwikkeld,

gebaseerdophetVOTE(Velum,Orofarynx,Tongbasis,Epiglottis)classificatiesysteem.Doormiddel

vanditsysteemwerdheteffectopdeopeningvandebovensteluchtwegvanverschillendepassieve

manoeuvres,tewetenjawthrust,lateralehoofdrotatieeneencombinatievanbeide,geanalyseerd.

Hiervoorwerddetotalesomberekendvandescorediegegevenwerdvoordematevanbovenste

luchtwegobstructie in zowel niet-positionele (NPP) als positionele OSA patiënten (PP). Er werd

geconcludeerd dat het effect van jaw thrust op bovenste luchtwegobstructie groter was dan wat

verwacht werd op basis van het behandeleffect van een mandibulair repositie apparaat (MRA)

beschrevenindeliteratuur.Ditintegenstellingtotheteffectvanlateralehoofdrotatie:diteffectwas

minderdanverwachtinvergelijkingmethetbehandeleffectvanpositietherapie(PT)gerapporteerd

indeliteratuur.

Deresultatenbeschreveninhoofdstuk2hebbendebasisgevormdvoordestudiesweergegevenin

hoofdstuk3enhoofdstuk4.Hoofdstuk3behandeldeeenprospectievestudiewaarbijheteffectop

bovensteluchtwegobstructievanlateralehoofdrotatiewerdvergelekenmetheteffectvanvolledige

zijligging(rompenhoofd).Intotaalwerden92patiëntengeïncludeerd.Dezepatiëntenondergingen

eenDISE in rugligging, zijligging enmet het hoofd geroteerd naar lateraal. Het effect van laterale

hoofdrotatie op bovenste luchtwegobstructie verschilde significant van het effect van volledige

zijligging bij PP. Bij NPP was het effect vergelijkbaar op het niveau van het velum, tongbasis en

epiglottis,maarnietoporofarynxniveau.

Inhoofdstuk4werddeovereenstemmingtussenbovensteluchtwegobstructietijdensjawthrusten

eenboilandbiteMRA(MyTAP) insitu tijdensDISEbeoordeeld.Daarnaastwerdendetheoretische

gevolgenmetbetrekkingtotklinischebesluitvorminggeanalyseerdbijhetgebruiktvandejawthrust

ofdeMyTAPalspotentieelscreeninginstrument.Deresultatenvandezestudietoondenslechtseen

lichtetotmatigeovereenstemmingindematevanobstructiegemetenmetjawthrustendeMyTAP

195

11

Summary / samenvatting

Chapter8describedasystematicreviewontheinfluenceofposition-dependencyonsurgicalsuccess

of different forms of UA surgery. In total, nine studies were included. Although preoperative

characteristics inPP (e.g., lowerbodymass index andAHI) seem tobe in favor forhigher surgical

successcomparedtoNPP,itremainsunclearwhetherornotposition-dependencyisapredictorfor

surgical outcome. It is suggested that the largest differences and expected preoperative and

postoperative changes occur in non-supineAHI. In PP, the preoperative non-supineAHI is already

lowercomparedtoNPPsuggestingalowerchanceofsurgicalsuccessinPP.

Chapter9focusesonthedifferencesinsurgicalsuccessinNPPandPPundergoingmaxillomandibular

advancement (MMA).Furthermore, the influenceofposition-dependencyonsurgicaloutcomeand

thephenomenonofresidualPOSAinnon-responderstoMMAwereevaluated.Aconsecutiveseries

of 57 patients undergoing MMA were retrospectively included. The overall surgical success was

52.6%. No significant difference in surgical success between NPP and PP undergoing MMA was

found. However, the improvement of total and non-supine AHI in NPP was significantly greater

compared to PP. In non-responders, a postoperative shift from severe NPP to less severe PPwas

found,causedbyagreaterreductionofthenon-supineAHIthanthesupineAHIpostoperatively.

SAMENVATTING

De studies in dit proefschrift zijn gericht op de rol van lichaamshouding en verschillende passieve

manoeuvres toegepast tijdens een medicamenteus-geïnduceerde slaapendoscopie (drug-induced

sleep endoscopy, DISE) bij patiënten met obstructieve slaapapneu (OSA). Hierbij ging het in het

bijzonder om de relevantie ervanmet betrekking tot behandeluitkomsten en patiëntselectie voor

diversevormenvantherapie.Inhoofdstuk1werdeenalgemeneintroductiegegeven.

Hoofdstuk 2 gaf deuitkomsten vaneen retrospectieve cohort studieweer,waarbijOSA-patiënten

werden geïncludeerd die eenDISE hebbenondergaan. Erwerd een 3-punten systeemontwikkeld,

gebaseerdophetVOTE(Velum,Orofarynx,Tongbasis,Epiglottis)classificatiesysteem.Doormiddel

vanditsysteemwerdheteffectopdeopeningvandebovensteluchtwegvanverschillendepassieve

manoeuvres,tewetenjawthrust,lateralehoofdrotatieeneencombinatievanbeide,geanalyseerd.

Hiervoorwerddetotalesomberekendvandescorediegegevenwerdvoordematevanbovenste

luchtwegobstructie in zowel niet-positionele (NPP) als positionele OSA patiënten (PP). Er werd

geconcludeerd dat het effect van jaw thrust op bovenste luchtwegobstructie groter was dan wat

verwacht werd op basis van het behandeleffect van een mandibulair repositie apparaat (MRA)

beschrevenindeliteratuur.Ditintegenstellingtotheteffectvanlateralehoofdrotatie:diteffectwas

minderdanverwachtinvergelijkingmethetbehandeleffectvanpositietherapie(PT)gerapporteerd

indeliteratuur.

Deresultatenbeschreveninhoofdstuk2hebbendebasisgevormdvoordestudiesweergegevenin

hoofdstuk3enhoofdstuk4.Hoofdstuk3behandeldeeenprospectievestudiewaarbijheteffectop

bovensteluchtwegobstructievanlateralehoofdrotatiewerdvergelekenmetheteffectvanvolledige

zijligging(rompenhoofd).Intotaalwerden92patiëntengeïncludeerd.Dezepatiëntenondergingen

eenDISE in rugligging, zijligging enmet het hoofd geroteerd naar lateraal. Het effect van laterale

hoofdrotatie op bovenste luchtwegobstructie verschilde significant van het effect van volledige

zijligging bij PP. Bij NPP was het effect vergelijkbaar op het niveau van het velum, tongbasis en

epiglottis,maarnietoporofarynxniveau.

Inhoofdstuk4werddeovereenstemmingtussenbovensteluchtwegobstructietijdensjawthrusten

eenboilandbiteMRA(MyTAP) insitu tijdensDISEbeoordeeld.Daarnaastwerdendetheoretische

gevolgenmetbetrekkingtotklinischebesluitvorminggeanalyseerdbijhetgebruiktvandejawthrust

ofdeMyTAPalspotentieelscreeninginstrument.Deresultatenvandezestudietoondenslechtseen

lichtetotmatigeovereenstemmingindematevanobstructiegemetenmetjawthrustendeMyTAP

196

Chapter 11

in situ tijdens DISE. Over het algemeen werd een aanzienlijke verbetering van bovenste

luchtwegobstructie op hypofarynxaal niveau gezien tijdens jaw thrust. Jaw thrust was minder

effectief alshet gingomhetopheffenvanbovenste luchtwegobstructieop retropalataalniveau in

vergelijkingmetdeMyTAP.Deresultatenbevestigendenoodzaakvooreenalternatiefvoorde jaw

thrust, dat kanwordengebruikt als screeningmethode tijdensDISEomheteffect vanbehandeling

meteenMRAtevoorspellen.

Inhoofdstuk5werddeaanwezigheidvaneenfloppyepiglottis(FE)tijdensDISEbijsnurkers,NPPen

PPbeoordeeldenwerddeimpactvanverschillendemanoeuvresenlichaamshoudinggeëvalueerd.In

dezeretrospectievestudiewerden324patiëntengeïncludeerd.Bij60patiënten(18,5%)werdeenFE

in rugligging gevonden. Bij het uitvoeren van alleen laterale hoofdrotatiewas een FE aanwezig bij

vierpatiënten, terwijl in zijligging slechtsbijéénpatiënteenFEwerdgevonden.Nahet toepassen

van jawthrustwaseenFEaanwezigbij10patiënten.DeprevalentievaneenFEbijNPPenPPwas

niet significant verschillend. Bij patiëntenmet een FE kan PT een veelbelovend alternatief zijn als

monotherapie,maarookalsonderdeelvancombinatietherapiemetbijvoorbeeldeenMADofminder

invasievevormenvanbovensteluchtwegchirurgie.

In hoofdstuk 6 werden de objectieve resultaten en veiligheid van nervus hypoglossus stimulatie

(NHS)ende invloedvanpreoperatieveDISE-bevindingenopchirurgisch succesgepresenteerd.Een

opeenvolgendereeksvan44matigetoternstigeOSA-patiëntenmetcontinuepositieveluchtwegdruk

(CPAP) intolerantieof–falenwerdgeïncludeerd.Deapneu-hypopneu-index(AHI)daaldeaanzienlijk

van37,6(30,4;43,4)events/unaar8,3(5,3;12,0)events/u(p<0,001),dezuurstofverzadigingsindex

daaldevan37,1(28,4;42.6)events/unaar15.9(11.1;21.6)events/u.Hetchirurgischesuccesvande

behandeling was hoog, namelijk 88,6%. NHS is een bewezen effectieve en veilige behandeling bij

OSA-patiënten met CPAP-intolerantie of –falen. Hierbij is goede patiëntselectie, adequate

implantatie van het NHS-systeem en follow-up door hiertoe opgeleid personeel cruciaal voor het

slagenvandebehandeling. Erwerdgeenverschil gevonden in chirurgisch succes tussenpatiënten

metenkeleentongbasiscollapsofeenvolledigecollapsopzoweltongbasis-alsvelumniveau.

Deafgelopen jaren isnietalleenhetaantalpublicatiesoverDISEsnel toegenomen,ookde invloed

vanlichaamshoudingopdeernstvanOSAheeftsteedsmeeraandachtgekregen.VooralinPPisde

ernstvanOSAsterkafhankelijkvandeAHIinrugliggingenAHIinniet-rugligging,evenalsdetijddiein

rugliggingwordtdoorgebracht.Vooraldetijdinrugliggingisonderhevigaanvariatie.Inhoofdstuk7

werd het effect van het dragen van polysomnografie (PSG)-apparatuur op de slaaphouding en

hiermeede invloedopdeernstvandeOSAgeëvalueerd.HonderdachtenzestigPPensnurkersaan

wie PT [Sleep Position Trainer (SPT)] werd voorgeschreven, werden retrospectief geïncludeerd in

dezestudie.HeteffectvanhetdragenvanPSG-apparatuuropdeslaaphoudingwerdgeanalyseerd

doordelichaamspositietijdensdePSG-nachtentijdensdeinactieve(diagnostische)fasevanSPTte

vergelijken.DeresultatenvandezestudielietenziendathetdragenvanPSG-apparatuurleiddetot

eentoenamevanderugliggingmet33,6%.MetnameinPPkanditleidentoteenoverschattingvan

deernstvanOSA.

Inhoofdstuk9werdenderesultatenvaneensystematischereviewvandeliteratuurmetbetrekking

totde invloedvanpositie-afhankelijkheidophetchirurgischesuccesvanverschillendevormenvan

bovenste luchtwegchirurgie beschreven. In totaal werden negen studies geïncludeerd. Hoewel de

preoperatievekenmerkenvanPP(bijv.lagerebodymassindexenAHI)geassocieerdlijkentezijnmet

hogere kans op chirurgisch succes in vergelijking met NPP, blijft het onduidelijk of positie-

afhankelijkheid een positieve of negatieve voorspeller is voor chirurgisch succes. Het grootste

verschil tussen pre- en postoperatieve waardes lijkt op te treden bij de AHI in niet-rugligging.

AangezieninPPdepreoperatieveAHIinniet-rugliggingbijvoorbaatallaagis,lijkthetdesalniettemin

aannemelijkdathettebehalenchirurgischsuccesinNPPhogerligtdaninPP.

Hoofdstuk 10 richtte zich op de verschillen in chirurgisch succes tussen NPP en PP die

maxillomandibular advancement (MMA) hebben ondergaan. Daarnaast werden de invloed van

positie-afhankelijkheid op chirurgische succes en het fenomeen van residueel POSA bij non-

respondersgeëvalueerd.Erwerdenretrospectief57patiëntengeïncludeerd.Hetchirurgischesucces

bijhenwas52,6%.ErwerdgeensignificantverschilinchirurgischsuccesgevondentussenNPPenPP.

De verbetering van totale AHI en AHI in niet-rugligging in NPP was echter aanzienlijk groter in

vergelijkingmetPP.Bijnon-responderswerdeenpostoperatieveverschuivingvanernstigeNPPnaar

minder ernstige PP gevonden. Ditwerdwaarschijnlijk veroorzaakt door een grotere daling van de

postoperatieveAHIinniet-rugligginginvergelijkingmetdedalingvandeAHIinrugligging.

197

11

Summary / samenvatting

in situ tijdens DISE. Over het algemeen werd een aanzienlijke verbetering van bovenste

luchtwegobstructie op hypofarynxaal niveau gezien tijdens jaw thrust. Jaw thrust was minder

effectief alshet gingomhetopheffenvanbovenste luchtwegobstructieop retropalataalniveau in

vergelijkingmetdeMyTAP.Deresultatenbevestigendenoodzaakvooreenalternatiefvoorde jaw

thrust, dat kanwordengebruikt als screeningmethode tijdensDISEomheteffect vanbehandeling

meteenMRAtevoorspellen.

Inhoofdstuk5werddeaanwezigheidvaneenfloppyepiglottis(FE)tijdensDISEbijsnurkers,NPPen

PPbeoordeeldenwerddeimpactvanverschillendemanoeuvresenlichaamshoudinggeëvalueerd.In

dezeretrospectievestudiewerden324patiëntengeïncludeerd.Bij60patiënten(18,5%)werdeenFE

in rugligging gevonden. Bij het uitvoeren van alleen laterale hoofdrotatiewas een FE aanwezig bij

vierpatiënten, terwijl in zijligging slechtsbijéénpatiënteenFEwerdgevonden.Nahet toepassen

van jawthrustwaseenFEaanwezigbij10patiënten.DeprevalentievaneenFEbijNPPenPPwas

niet significant verschillend. Bij patiëntenmet een FE kan PT een veelbelovend alternatief zijn als

monotherapie,maarookalsonderdeelvancombinatietherapiemetbijvoorbeeldeenMADofminder

invasievevormenvanbovensteluchtwegchirurgie.

In hoofdstuk 6 werden de objectieve resultaten en veiligheid van nervus hypoglossus stimulatie

(NHS)ende invloedvanpreoperatieveDISE-bevindingenopchirurgisch succesgepresenteerd.Een

opeenvolgendereeksvan44matigetoternstigeOSA-patiëntenmetcontinuepositieveluchtwegdruk

(CPAP) intolerantieof–falenwerdgeïncludeerd.Deapneu-hypopneu-index(AHI)daaldeaanzienlijk

van37,6(30,4;43,4)events/unaar8,3(5,3;12,0)events/u(p<0,001),dezuurstofverzadigingsindex

daaldevan37,1(28,4;42.6)events/unaar15.9(11.1;21.6)events/u.Hetchirurgischesuccesvande

behandeling was hoog, namelijk 88,6%. NHS is een bewezen effectieve en veilige behandeling bij

OSA-patiënten met CPAP-intolerantie of –falen. Hierbij is goede patiëntselectie, adequate

implantatie van het NHS-systeem en follow-up door hiertoe opgeleid personeel cruciaal voor het

slagenvandebehandeling. Erwerdgeenverschil gevonden in chirurgisch succes tussenpatiënten

metenkeleentongbasiscollapsofeenvolledigecollapsopzoweltongbasis-alsvelumniveau.

Deafgelopen jaren isnietalleenhetaantalpublicatiesoverDISEsnel toegenomen,ookde invloed

vanlichaamshoudingopdeernstvanOSAheeftsteedsmeeraandachtgekregen.VooralinPPisde

ernstvanOSAsterkafhankelijkvandeAHIinrugliggingenAHIinniet-rugligging,evenalsdetijddiein

rugliggingwordtdoorgebracht.Vooraldetijdinrugliggingisonderhevigaanvariatie.Inhoofdstuk7

werd het effect van het dragen van polysomnografie (PSG)-apparatuur op de slaaphouding en

hiermeede invloedopdeernstvandeOSAgeëvalueerd.HonderdachtenzestigPPensnurkersaan

wie PT [Sleep Position Trainer (SPT)] werd voorgeschreven, werden retrospectief geïncludeerd in

dezestudie.HeteffectvanhetdragenvanPSG-apparatuuropdeslaaphoudingwerdgeanalyseerd

doordelichaamspositietijdensdePSG-nachtentijdensdeinactieve(diagnostische)fasevanSPTte

vergelijken.DeresultatenvandezestudielietenziendathetdragenvanPSG-apparatuurleiddetot

eentoenamevanderugliggingmet33,6%.MetnameinPPkanditleidentoteenoverschattingvan

deernstvanOSA.

Inhoofdstuk9werdenderesultatenvaneensystematischereviewvandeliteratuurmetbetrekking

totde invloedvanpositie-afhankelijkheidophetchirurgischesuccesvanverschillendevormenvan

bovenste luchtwegchirurgie beschreven. In totaal werden negen studies geïncludeerd. Hoewel de

preoperatievekenmerkenvanPP(bijv.lagerebodymassindexenAHI)geassocieerdlijkentezijnmet

hogere kans op chirurgisch succes in vergelijking met NPP, blijft het onduidelijk of positie-

afhankelijkheid een positieve of negatieve voorspeller is voor chirurgisch succes. Het grootste

verschil tussen pre- en postoperatieve waardes lijkt op te treden bij de AHI in niet-rugligging.

AangezieninPPdepreoperatieveAHIinniet-rugliggingbijvoorbaatallaagis,lijkthetdesalniettemin

aannemelijkdathettebehalenchirurgischsuccesinNPPhogerligtdaninPP.

Hoofdstuk 10 richtte zich op de verschillen in chirurgisch succes tussen NPP en PP die

maxillomandibular advancement (MMA) hebben ondergaan. Daarnaast werden de invloed van

positie-afhankelijkheid op chirurgische succes en het fenomeen van residueel POSA bij non-

respondersgeëvalueerd.Erwerdenretrospectief57patiëntengeïncludeerd.Hetchirurgischesucces

bijhenwas52,6%.ErwerdgeensignificantverschilinchirurgischsuccesgevondentussenNPPenPP.

De verbetering van totale AHI en AHI in niet-rugligging in NPP was echter aanzienlijk groter in

vergelijkingmetPP.Bijnon-responderswerdeenpostoperatieveverschuivingvanernstigeNPPnaar

minder ernstige PP gevonden. Ditwerdwaarschijnlijk veroorzaakt door een grotere daling van de

postoperatieveAHIinniet-rugligginginvergelijkingmetdedalingvandeAHIinrugligging.

APPENDICES

LISTOFPUBLICATIONSANDPRESENTATIONS

PHDPORTFOLIO

CURRICULUMVITAE

DANKWOORD

APPENDICES

LISTOFPUBLICATIONSANDPRESENTATIONS

PHDPORTFOLIO

CURRICULUMVITAE

DANKWOORD

APPENDICES

LISTOFPUBLICATIONSANDPRESENTATIONS

PHDPORTFOLIO

CURRICULUMVITAE

DANKWOORD

APPENDICES

LISTOFPUBLICATIONSANDPRESENTATIONS

PHDPORTFOLIO

CURRICULUMVITAE

DANKWOORD

200

PEER-REVIEWEDPUBLICATIONSP.E.Vonk,M.J.L.Ravesloot.Positionalobstructivesleepapnea:anunderestimatedphenomenon?

Somnologie,June2018,Volume22,Issue2,pp79–84

P.E. Vonk, A.M.E.H. Beelen, N. de Vries. Towards a prediction model for Drug-Induced Sleep

EndoscopyasselectiontoolforOralApplianceTreatmentandPositionalTherapyinObstructiveSleep

Apnea.SleepBreath.2018Mar9.11325-018-1649

C.Kastoer,L.B.L.Benoist,M.Dieltjens,B.Torensma,L.H.deVries,P.E.Vonk,M.J.L.Ravesloot,N.de

Vries.Comparisonofupperairwaycollapsepatternsanditsclinicalsignificance:

drug-induced sleep endoscopy in patients without obstructive sleep apnea, positional and non-

positionalobstructivesleepapnea.SleepBreath.2018Dec;22(4):939-948.doi:10.1007/s11325-018-

1702-y

A. deVito,M.Carrasco Llatas,M.J. Ravesloot, B. KotechaB,NdeVries, E.Hamans, J.Maurer,M.

Bosi, M. Blumen, C. Heiser, M. Herzog, F. Montevecchi, R.M. Corso, A. Braghiroli, R. Gobbi, A.

Vroegop,P.E. Vonk,W.Hohenhorst,O. Piccin,G. Sorrenti,O.M. Vanderveken, C. Vicini. European

Position Paper On Drug-Induced Sleep Endoscopy (DISE): 2017 Update. Clin Otolaryngol. 2018

Dec;43(6):1541-1552.doi:10.1111/coa.13213

A.M.E.H.Beelen,P.E.Vonk,N.deVries.Drug-InducedSleepEndoscopy:Theeffectof

different passive maneuvers on the distribution of collapse patterns of the upper airway in

obstructive sleep apneapatients. SleepBreath. 2018Dec;22(4):909-917. doi: 10.1007/s11325-018-

1732-5

P.E.Vonk,M.J.vandeBeek,M.J.L.Ravesloot,N.deVries.Drug-inducedsleependoscopy

(DISE): New insights in the influence of lateral head position compared to lateral head and trunk

rotation innon-positionalandpositionalobstructivesleepapneapatients.Laryngoscope.2018Dec

24.doi:10.1002/lary.27703

P.E. Vonk, N. de Vries, M.J.L. Ravesloot. Polysomnography and sleep position, a Heisenberg

phenomenon?-Alarge-scaleseries.HNO.2019Jun4.doi:10.1007/s00106-019-0678-7

P.E.Vonk,L.B.L.Benoist,J.P.vanMaanen,M.J.L.Ravesloot,H.J.Reesink,

K.Kasius,N.deVries.Stimulatievantongzenuwbijobstructieveslaapapneu.Techniek, indicatieen

toekomst.NedTijdschrGeneeskd.2019May3;163.:D3286.

P.E.Vonk,M.J.L.Ravesloot,K.M.Kasius,J.P.vanMaanen,N.deVries.Floppyepiglottisduringdrug-

induced sleep endoscopy: an almost complete resolution by adopting the lateral posture. Sleep

Breath.2019Apr24.doi:10.1007/s11325-019-01847-x

M.J.L.Ravesloot,C.A.L.deRaaff,M.vandeBeek,L.B.L.Benoist,J.Beyers,R.M.

Corso,G.Edenharter,C.denHaan,J.Hedari-Azad1,J.T.F.Ho,B.Hofauer,E.J.Kezirian,J.P.van

Maanen,S.Maes,J.P.Mulier,W.Randerath,O.M.Vanderveken,J.Verbraecken,P.E.Vonk,E.M.

Weaver,N.deVries.PerioperativeCareofPatientsWithObstructiveSleepApneaUndergoingUpper

Airway Surgery: A Review and Consensus Recommendations. JAMA Otolaryngol Head Neck Surg,

2019Jun27.doi:10.1001/jamaoto.2019.1448.

L.B.L. Benoist, P.E. Vonk, N. de Vries, H.C.J.P. Janssen, J. Verbraecken. New-generation positional

therapyinpatientswithpositionalcentralsleepapnea.EurArchOtorhinolaryngol.2019Jul13.doi:

10.1007/s00405-019-05545-y

M.J. van de Beek,P.E. Vonk, J.P. vanMaanen,M.J.L. Ravesloot,N. deVries. Tongzenuwstimulatie

voorobstructiefslaapapneuenbenodigdecapaciteitinNederland.NederlandsTijdschriftvoorKeel-

Neus-Oorheelkunde,jaargang25,nummer4,november2019

P.E. Vonk, P.J. Rotteveel, M.J.L. Ravesloot, C. den Haan, N. de Vries. The influence of position-

dependencyonsurgicalsuccessinsleepapneasurgery-asystematicreview.SleepBreath.2019Oct

17.doi:10.1007/s11325-019-01935-y.

P.E. Vonk, P.J. Rotteveel, M.J.L. Ravesloot, J.P.T.F. Ho, J. de Lange, N. de Vries, The influence of

position-dependency on surgical success in OSA patients undergoing maxillomandibular

advancement.JClinSleepMed.2019Nov27.pii:jc-19-00306.

P.E. Vonk, M.J.L. Ravesloot, J.P. van Maanen, N. de Vries. Short-term results of upper airway

stimulationinobstructivesleepapneapatients:theAmsterdamexperience.Submitted

P.E.Vonk,M.J.L.Ravesloot,J.P.vanMaanen,N.deVries.Kortetermijnresultatenvanstimulatievan

debovensteluchtwegbijobstructieveslaapapneupatiënten:deAmsterdamseervaring.Submitted

201

PEER-REVIEWEDPUBLICATIONSP.E.Vonk,M.J.L.Ravesloot.Positionalobstructivesleepapnea:anunderestimatedphenomenon?

Somnologie,June2018,Volume22,Issue2,pp79–84

P.E. Vonk, A.M.E.H. Beelen, N. de Vries. Towards a prediction model for Drug-Induced Sleep

EndoscopyasselectiontoolforOralApplianceTreatmentandPositionalTherapyinObstructiveSleep

Apnea.SleepBreath.2018Mar9.11325-018-1649

C.Kastoer,L.B.L.Benoist,M.Dieltjens,B.Torensma,L.H.deVries,P.E.Vonk,M.J.L.Ravesloot,N.de

Vries.Comparisonofupperairwaycollapsepatternsanditsclinicalsignificance:

drug-induced sleep endoscopy in patients without obstructive sleep apnea, positional and non-

positionalobstructivesleepapnea.SleepBreath.2018Dec;22(4):939-948.doi:10.1007/s11325-018-

1702-y.

A. deVito,M.Carrasco Llatas,M.J. Ravesloot, B. KotechaB,NdeVries, E.Hamans, J.Maurer,M.

Bosi, M. Blumen, C. Heiser, M. Herzog, F. Montevecchi, R.M. Corso, A. Braghiroli, R. Gobbi, A.

Vroegop,P.E. Vonk,W.Hohenhorst,O. Piccin,G. Sorrenti,O.M. Vanderveken, C. Vicini. European

Position Paper On Drug-Induced Sleep Endoscopy (DISE): 2017 Update. Clin Otolaryngol. 2018

Dec;43(6):1541-1552.doi:10.1111/coa.13213.

A.M.E.H.Beelen,P.E.Vonk,N.deVries.Drug-InducedSleepEndoscopy:Theeffectof

different passive maneuvers on the distribution of collapse patterns of the upper airway in

obstructive sleep apneapatients. SleepBreath. 2018Dec;22(4):909-917. doi: 10.1007/s11325-018-

1732-5.

P.E.Vonk,M.J.vandeBeek,M.J.L.Ravesloot,N.deVries.Drug-inducedsleependoscopy

(DISE): New insights in the influence of lateral head position compared to lateral head and trunk

rotation innon-positionalandpositionalobstructivesleepapneapatients.Laryngoscope.2018Dec

24.doi:10.1002/lary.27703.

P.E. Vonk, N. de Vries, M.J.L. Ravesloot. Polysomnography and sleep position, a Heisenberg

phenomenon?-Alarge-scaleseries.HNO.2019Jun4.doi:10.1007/s00106-019-0678-7.

P.E.Vonk,L.B.L.Benoist,J.P.vanMaanen,M.J.L.Ravesloot,H.J.Reesink,

K.Kasius,N.deVries.Stimulatievantongzenuwbijobstructieveslaapapneu.Techniek, indicatieen

toekomst.NedTijdschrGeneeskd.2019May3;163.:D3286

P.E.Vonk,M.J.L.Ravesloot,K.M.Kasius,J.P.vanMaanen,N.deVries.Floppyepiglottisduringdrug-

induced sleep endoscopy: an almost complete resolution by adopting the lateral posture. Sleep

Breath.2019Apr24.doi:10.1007/s11325-019-01847-x

M.J.L.Ravesloot,C.A.L.deRaaff,M.vandeBeek,L.B.L.Benoist,J.Beyers,R.M.

Corso,G.Edenharter,C.denHaan,J.Hedari-Azad1,J.T.F.Ho,B.Hofauer,E.J.Kezirian,J.P.van

Maanen,S.Maes,J.P.Mulier,W.Randerath,O.M.Vanderveken,J.Verbraecken,P.E.Vonk,E.M.

Weaver,N.deVries.PerioperativeCareofPatientsWithObstructiveSleepApneaUndergoingUpper

Airway Surgery: A Review and Consensus Recommendations. JAMA Otolaryngol Head Neck Surg,

2019Jun27.doi:10.1001/jamaoto.2019.1448

L.B.L. Benoist, P.E. Vonk, N. de Vries, H.C.J.P. Janssen, J. Verbraecken. New-generation positional

therapyinpatientswithpositionalcentralsleepapnea.EurArchOtorhinolaryngol.2019Jul13.doi:

10.1007/s00405-019-05545-y

M.J. van de Beek,P.E. Vonk, J.P. vanMaanen,M.J.L. Ravesloot,N. deVries. Tongzenuwstimulatie

voorobstructiefslaapapneuenbenodigdecapaciteitinNederland.NederlandsTijdschriftvoorKeel-

Neus-Oorheelkunde,jaargang25,nummer4,november2019

P.E. Vonk, P.J. Rotteveel, M.J.L. Ravesloot, C. den Haan, N. de Vries. The influence of position-

dependencyonsurgicalsuccessinsleepapneasurgery-asystematicreview.SleepBreath.2019Oct

17.doi:10.1007/s11325-019-01935-y

P.E. Vonk, P.J. Rotteveel, M.J.L. Ravesloot, J.P.T.F. Ho, J. de Lange, N. de Vries, The influence of

position-dependency on surgical success in OSA patients undergoing maxillomandibular

advancement.JClinSleepMed.2019Nov27.pii:jc-19-00306

P.E. Vonk, M.J.L. Ravesloot, J.P. van Maanen, N. de Vries. Short-term results of upper airway

stimulationinobstructivesleepapneapatients:theAmsterdamexperience.Submitted

P.E.Vonk,M.J.L.Ravesloot,J.P.vanMaanen,N.deVries.Kortetermijnresultatenvanstimulatievan

debovensteluchtwegbijobstructieveslaapapneupatiënten:deAmsterdamseervaring.Submitted

202

OTHERNON-PEERREVIEWEDPUBLICATIONS

P.E.Vonk,M.J.L.Ravesloot,N.deVries.Positionaltherapyforpositionalobstructivesleepapnea:

what’snew?CurrentSleepMedicineReports,September2017,Volume3,Issue3,pp113–121

P.E.Vonk,M.J.L.Ravesloot,N.deVries.Advancesintheroleofdruginducedsleependoscopyin

Investigatingsleepapnea.CurrentOtorhinolaryngologyReports,September2017,Volume5,Issue3,

pp187–190

CONTRIBUTIONSTOTEXTBOOKS

SleepandSleepdisorders.Apracticalhandbook.

Editors: JohanVerbraecken,BertienBuyse,HansHamburgen,VivianevanKasteel,Reindert

vanSteenwijk

Hoofdstuk21.9.2.2:PattyVonk,NicodeVries,NinaMichiels,MarcWillemen,JohanVerbraecken.

BehandelingvanOSA:positietherapie

Drug-induced Sleep Endoscopy: Diagnostic and Therapeutic Applications: A

GuideforClinicalPractices.

Editors:DeVries,Piccin,Vanderveken&Vicini

Chapter14:P.E.Vonk,A.M.E.H.Beelen,N.deVries.Workinprogress:apredictionmodelforDISEas

selectiontoolforMADandpositionaltherapy

Chapter18:P.E.Vonk,M.J.L.Ravesloot,N.deVries,Epiglotticcollapse

Chapter21:M.J.L.Ravesloot,P.E.Vonk,N.deVries,DISEandPosition-DependentOSA

Chapter22:P.E.Vonk,M.J.L.Ravesloot,O.M.Vanderveken,A.V.M.T.Vroegop,N.deVries,DISEand

OralApplianceTreatmentinObstructiveSleepApnea

PHDPORTFOLIO

PhDperiod:January2017–January2020

PhDsupervisors:Prof.dr.N.deVries,dr.M.J.L.Ravesloot,dr.J.P.vanMaanen

Year ECTS

Generalcourses

GoodClinicalPractice 2018 1

Introductioninstatisticsand

methodology

2018 3

Advancedbiostatistics 1.5

ScientificWritingandEnglish

presenting

2019 4

ScientificIntegrity 2019 2

Seminars,workshopsand

masterclasses

Refereeravondenen

intercollegialeoverleggen(>15x)

2017-2020 2

OrganisatieRefereermiddag

“OSAeninnovatiesindiagnostiek

enbehandeling”

2017 1

OrganisatieendeelnameMini-

OSAScursus

2017 1

Oralpresentations

RefereermiddagOLVG,

Amsterdam,theNetherlands

2017 1

231eKNO-ledenvergadering,

Nieuwegein,theNetherlands

Mini-OSAScursus(2x)

2017

2017

1

1

9thInternationalSurgicalSleep

SocietyMeeting,Munich,

Germany(3x)

2018 3

Sleepless2019,Amersfoort,the 2019 1

203

OTHERNON-PEERREVIEWEDPUBLICATIONS

P.E.Vonk,M.J.L.Ravesloot,N.deVries.Positionaltherapyforpositionalobstructivesleepapnea:

what’snew?CurrentSleepMedicineReports,September2017,Volume3,Issue3,pp113–121

P.E.Vonk,M.J.L.Ravesloot,N.deVries.Advancesintheroleofdruginducedsleependoscopyin

Investigatingsleepapnea.CurrentOtorhinolaryngologyReports,September2017,Volume5,Issue3,

pp187–190

CONTRIBUTIONSTOTEXTBOOKS

SleepandSleepdisorders.Apracticalhandbook.

Editors: JohanVerbraecken,BertienBuyse,HansHamburgen,VivianevanKasteel,Reindert

vanSteenwijk.

Hoofdstuk21.9.2.2:PattyVonk,NicodeVries,NinaMichiels,MarcWillemen,JohanVerbraecken.

BehandelingvanOSA:positietherapie

Drug-induced Sleep Endoscopy: Diagnostic and Therapeutic Applications: A

GuideforClinicalPractices.

Editors:DeVries,Piccin,Vanderveken&Vicini

Chapter14:P.E.Vonk,A.M.E.H.Beelen,N.deVries.Workinprogress:apredictionmodelforDISEas

selectiontoolforMADandpositionaltherapy

Chapter18:P.E.Vonk,M.J.L.Ravesloot,N.deVries,Epiglotticcollapse

Chapter21:M.J.L.Ravesloot,P.E.Vonk,N.deVries,DISEandPosition-DependentOSA

Chapter22:P.E.Vonk,M.J.L.Ravesloot,O.M.Vanderveken,A.V.M.T.Vroegop,N.deVries,DISEand

OralApplianceTreatmentinObstructiveSleepApnea

PHDPORTFOLIO

PhDperiod:January2017–January2020

PhDsupervisors:Prof.dr.N.deVries,dr.M.J.L.Ravesloot,dr.J.P.vanMaanen

Year ECTS

Generalcourses

GoodClinicalPractice 2018 1

Introductioninstatisticsand

methodology

2018 3

Advancedbiostatistics 1.5

ScientificWritingandEnglish

presenting

2019 4

ScientificIntegrity 2019 2

Seminars,workshopsand

masterclasses

Refereeravondenen

intercollegialeoverleggen(>15x)

2017-2020 2

OrganisatieRefereermiddag

“OSAeninnovatiesindiagnostiek

enbehandeling”

2017 1

OrganisatieendeelnameMini-

OSAScursus

2017 1

Oralpresentations

RefereermiddagOLVG,

Amsterdam,theNetherlands

2017 1

231eKNO-ledenvergadering,

Nieuwegein,theNetherlands

Mini-OSAScursus(2x)

2017

2017

1

1

9thInternationalSurgicalSleep

SocietyMeeting,Munich,

Germany(3x)

2018 3

Sleepless2019,Amersfoort,the 2019 1

204

Netherlands

iBEDSMA2019,Knokke,Belgium 2019 1

SLAAP2019,Ermelo,the

Netherlands

2019 1

Posterpresentations

WetenschapsdagOLVG2018,

Amsterdam,theNetherlands

2018 0.5

WetenschapsdagOLVG2019,

Amsterdam,theNetherlands

2019 0.5

10thInternationalSurgicalSleep

SocietyMeeting,NewYork,USA

2019 0.5

Conferences

IFOSENTworldcongress 2017 1

231steKNO-ledenvergadering,

Nieuwegein,theNetherlands

2017 1

WetenschapsdagOLVG 2018 1

9thInternationalSurgicalSleep

SocietyMeeting

2018 1

233steKNO-ledenvergadering,

Nieuwegein,theNetherlands

2019 1

EuropeanSleepResearchSociety

(ESRS)congress

2018 1

10thInternationalSurgicalSleep

SocietyMeeting

2019 1

WetenschapsdagOLVG 2019 1

iBEDSMA 2019 1

SLAAP2019 2019 1

Teaching

Lecturesformedicalstudents–

Diagnosticsandtreatmentin

obstructivesleepapneapatients

2017-2019

2

Supervisingmedicalstudents(3x) 2017-2019 4

Guidanceandsupervisionbythe 2017-20120 6

supervisor

Other

CompletionC-SSRSTraining 2017 0.5

TitratietrainingInspire 2017 2

KadaverlabtrainingInspire 2018 1

Researcherandattendee

consensusmeeting

“PerioperativecareinOSA

patientundergoingupperairway

surgery”

2018 3

Authoroffivebookchapters 2018-2019 -

TotalECTS 51

205

Netherlands

iBEDSMA2019,Knokke,Belgium 2019 1

SLAAP2019,Ermelo,the

Netherlands

2019 1

Posterpresentations

WetenschapsdagOLVG2018,

Amsterdam,theNetherlands

2018 0.5

WetenschapsdagOLVG2019,

Amsterdam,theNetherlands

2019 0.5

10thInternationalSurgicalSleep

SocietyMeeting,NewYork,USA

2019 0.5

Conferences

IFOSENTworldcongress 2017 1

231steKNO-ledenvergadering,

Nieuwegein,theNetherlands

2017 1

WetenschapsdagOLVG 2018 1

9thInternationalSurgicalSleep

SocietyMeeting

2018 1

233steKNO-ledenvergadering,

Nieuwegein,theNetherlands

2019 1

EuropeanSleepResearchSociety

(ESRS)congress

2018 1

10thInternationalSurgicalSleep

SocietyMeeting

2019 1

WetenschapsdagOLVG 2019 1

iBEDSMA 2019 1

SLAAP2019 2019 1

Teaching

Lecturesformedicalstudents–

Diagnosticsandtreatmentin

obstructivesleepapneapatients

2017-2019

2

Supervisingmedicalstudents(3x) 2017-2019 4

Guidanceandsupervisionbythe 2017-20120 6

supervisor

Other

CompletionC-SSRSTraining 2017 0.5

TitratietrainingInspire 2017 2

KadaverlabtrainingInspire 2018 1

Researcherandattendee

consensusmeeting

“PerioperativecareinOSA

patientundergoingupperairway

surgery”

2018 3

Authoroffivebookchapters 2018-2019 -

TotalECTS 51

206

CURRICULUMVITAE

PattyVonkwerdgeborenop20januari1991inGeldrop.Vanaf2009

studeerdezijGeneeskundeaandeUniversiteitvanMaastricht.Nahet

behalen van haar artsenexamen in augustus 2016 begon zij, onder

begeleiding van Prof. dr.N. deVries, dr.M.J.L. Ravesloot en dr. J.P.

vanMaanen,methetonderzoekdatgeleidheefttotditproefschrift.

Daarnaastwaszijtijdensdezeperiodewerkzaamalsarts-assistentop

deafdelingKeel-,Neus-enOorheelkundevanhetOLVG,Amsterdam.

Zij wasmedeverantwoordelijk voor het opzetten en implementeren

van het zorgtrajact rondom OSA-patiënten die behandeld worden

doormiddelvannervushypoglossusstimulatie.Inaugustus2019iszij

begonnenmetdeopleidingtotKNO-artsinhetAmsterdamUMC,locatieAMC(Prof.dr.F.G.Dikkers).

DANKWOORD

Detotstandkomingvanditproefschriftwasmenooitalleengelukt.Inditdankwoordwilikgraagmijn

dankuitsprekennaarallecollegae,vrienden,familieendepatiëntendiehieraanhebbenbijgedragen.

Erzijneenaantalmensendieikinhetbijzonderwilbedanken.

Mijnpromotor,Prof.dr.N.DeVries.

LieveNico,ikweetnoggoeddatik3.5jaargeledennaeenopensollicitatiebijjouopgesprekmocht

komen.Werkeneenplekvoormehadjezeker,gelddaarentegenwasnogeenpuntjevanaandacht.

Gelukkigkwamdat,zoalsjeoverigensaldietijdgeroepenhebt,goedenkondenwesamendittraject

aangaan.Watikaltijdinjoubewonderdheb,isdemanierwaaropjijmensenweettestimulerenen

meeweettenemeninjouwenthousiasme.Wehebbenvaaklopensparrenalseenvanonsweereen

hersenspinselhadwatinonzeogenweereenmooiprojectzoukunnenopleveren(ookalliepeneral

20).Detrotswaarmeejijmensenomjeheennaarvorenduwtenindeschijnwerpersweettezetten,

waardeerikenorm.Dankvoorallekansendiejemehebtgegevenendemanierwaaropjemeonder

jehoedehebtgenomen.

Mijnco-promotores,dr.M.J.L.Raveslootendr.J.P.vanMaanen.

LieveMadeline, waar was ik zonder jou geweest in deze onderzoekswereld en hetmannenteam,

zoalsjijzouzeggen.Naasthetfeitdatjemeonwijsgeholpenhebtomdeinhoudenkwaliteitvandit

proefschrift naar een hoger niveau te tillen, zijnwe de afgelopen jaren naast goede collega’s ook

vriendinnengeworden.Ikbewonderjealspersoonmetinhetbijzonderjegedrevenheidenzorgdie

jedraagtvoordemensenomjeheen.Enlatenweeerlijkzijn:ikkenniemanddiezoattentisalsjij.

Dankjewel.

LievePeter,mijnsteunentoeverlaatalshetgaatomrelativering.Endatwasafentoezekernodig.

Denuchteremanierwaaropjijinhetlevenstaat,daarzouiknogwatvankunnenleren.Deafgelopen

jarenhebikveelvanjegeleerdalsdokterenhebikmetpleziermetjesamengewerkt.Gelukkigzijn

wenaastcollega’sookvriendengeworden,dusikhoopdatwenahetafrondenvanditproefschrift

contactblijvenhouden.

Deledenvandeleescommissieenoppositie.

Prof.dr.O.M.Vanderveken,besteOlivier,dankvoordesteundieuopafstanddeafgelopen jaren

heeftgebodenenhetprettigecontactopdevelecongressenwaarwijelkaarhebbengetroffen.Ook

benikdankbaarvoordebezoekenaanhetUZAwaarNicoenikkeeropkeerweerhartelijkwerden

ontvangen.

207

CURRICULUMVITAE

PattyVonkwerdgeborenop20januari1991inGeldrop.Vanaf2009

studeerdezijGeneeskundeaandeUniversiteitvanMaastricht.Nahet

behalen van haar artsenexamen in augustus 2016 begon zij, onder

begeleiding van Prof. dr.N. deVries, dr.M.J.L. Ravesloot en dr. J.P.

vanMaanen,methetonderzoekdatgeleidheefttotditproefschrift.

Daarnaastwaszijtijdensdezeperiodewerkzaamalsarts-assistentop

deafdelingKeel-,Neus-enOorheelkundevanhetOLVG,Amsterdam.

Zij wasmedeverantwoordelijk voor het opzetten en implementeren

van het zorgtrajact rondom OSA-patiënten die behandeld worden

doormiddelvannervushypoglossusstimulatie.Inaugustus2019iszij

begonnenmetdeopleidingtotKNO-artsinhetAmsterdamUMC,locatieAMC(Prof.dr.F.G.Dikkers).

DANKWOORD

Detotstandkomingvanditproefschriftwasmenooitalleengelukt.Inditdankwoordwilikgraagmijn

dankuitsprekennaarallecollegae,vrienden,familieendepatiëntendiehieraanhebbenbijgedragen.

Erzijneenaantalmensendieikinhetbijzonderwilbedanken.

Mijnpromotor,Prof.dr.N.DeVries.

LieveNico,ikweetnoggoeddatik3.5jaargeledennaeenopensollicitatiebijjouopgesprekmocht

komen.Werkeneenplekvoormehadjezeker,gelddaarentegenwasnogeenpuntjevanaandacht.

Gelukkigkwamdat,zoalsjeoverigensaldietijdgeroepenhebt,goedenkondenwesamendittraject

aangaan.Watikaltijdinjoubewonderdheb,isdemanierwaaropjijmensenweettestimulerenen

meeweettenemeninjouwenthousiasme.Wehebbenvaaklopensparrenalseenvanonsweereen

hersenspinselhadwatinonzeogenweereenmooiprojectzoukunnenopleveren(ookalliepeneral

20).Detrotswaarmeejijmensenomjeheennaarvorenduwtenindeschijnwerpersweettezetten,

waardeerikenorm.Dankvoorallekansendiejemehebtgegevenendemanierwaaropjemeonder

jehoedehebtgenomen.

Mijnco-promotores,dr.M.J.L.Raveslootendr.J.P.vanMaanen.

LieveMadeline, waar was ik zonder jou geweest in deze onderzoekswereld en hetmannenteam,

zoalsjijzouzeggen.Naasthetfeitdatjemeonwijsgeholpenhebtomdeinhoudenkwaliteitvandit

proefschrift naar een hoger niveau te tillen, zijnwe de afgelopen jaren naast goede collega’s ook

vriendinnengeworden.Ikbewonderjealspersoonmetinhetbijzonderjegedrevenheidenzorgdie

jedraagtvoordemensenomjeheen.Enlatenweeerlijkzijn:ikkenniemanddiezoattentisalsjij.

Dankjewel.

LievePeter,mijnsteunentoeverlaatalshetgaatomrelativering.Endatwasafentoezekernodig.

Denuchteremanierwaaropjijinhetlevenstaat,daarzouiknogwatvankunnenleren.Deafgelopen

jarenhebikveelvanjegeleerdalsdokterenhebikmetpleziermetjesamengewerkt.Gelukkigzijn

wenaastcollega’sookvriendengeworden,dusikhoopdatwenahetafrondenvanditproefschrift

contactblijvenhouden.

Deledenvandeleescommissieenoppositie.

Prof.dr.O.M.Vanderveken,besteOlivier,dankvoordesteundieuopafstanddeafgelopen jaren

heeftgebodenenhetprettigecontactopdevelecongressenwaarwijelkaarhebbengetroffen.Ook

benikdankbaarvoordebezoekenaanhetUZAwaarNicoenikkeeropkeerweerhartelijkwerden

ontvangen.

208

Prof.dr.F.G.Dikkers,besteFreek,dankvoorjedeelnameinmijnleescommissieendekansdiejeme

hebtgebodenommijndroomKNO-artsteworden,teverwezenlijken.

Prof.dr. J.deLange,prof.dr.F. Lobbezoo,prof.dr.B.G.Loos,prof.dr.F.R.Rozemaenprof.dr. J.

Verbraecken, dank voor het accepteren van de uitnodiging om zitting te nemen in mijn

leescommissieendezorgvuldigeenkritischebeoordelingvanmijnproefschrift.

DaarnaastwilikdedamesvandepoliKNO,MarijeenDavidbedankenvooralhunsteunenzorgdie

zemij hebben geboden in de soms roerige tijdwaarinwemet z’n allen zaten,met name op het

einde.Wathadiktochzonderjulliegemoeten.Hetisnietdeeerstekeerdatditgezegdwordt,maar

watbenikdankbaardatikbenopgenomenindeKNO-familievanhetOLVGWest.

Dr.P.M.vanRijn,lievePeter.OokalhadjehelemaalniksmetdeOSA-onderzoekenenhadjesoms

geenideewaarikmeebezigwas,jehebtaltijdvoormeklaargestaanenjeommijbekommerd.Jouw

enthousiasme omme dingen te leren en jouw vertrouwen hebbenme absoluut doen groeien als

dokter.Deloyaliteitdiejijhebttegenoverjecollega’senonuitputbareinzethebbenmijkeeropkeer

weerdoenverbazen.Dankjewelvoordefijneenleerzametijd.

Dr.M.A.J.vanLooij,lieveMarjolein,watvondikhetleukdatjijhetlaatstejaarvanmijnpromotiein

hetOLVGkwamwerken.Dankvoorjeluisterendoorenfijnetijdsamen!

Ookwil ik graag de collega’s van de KNF, Longgeneeskunde enMKA-chirurgie bedanken. De vele

overlegmomenten,nauwesamenwerkingenhetvasteMDOSlaaplatenziendatslaap-gerelateerde

ademhalingsstoornissen,metinhetbijzonderobstructieveencentraleslaapapneu,multidisciplinaire

ziektebeelden zijn, waarbij samenwerking centraal moet staan. Dank voor de vele inzichten en

verdiepinggedurendemijntijdinhetOLVGWest.

LieveLinda,hetwasgeenmakkelijketaakominjouwvoetsporentetreden.Gelukkigwasjetenallen

tijdebereidommetehelpenwaarnodigenhebjememeerderemaleneenluisterendoorgeboden.

Ikbenblijdatweelkaarbeterhebbenlerenkennenenelkaaropheteindehebbenkunnenaanvullen

enhelpenmetallezakendiegeregeldmoestenwordenrondomhethelepromotietraject.Behalve

“het stappenplan” hadden we namelijk niet heel veel om op te varen. Inmiddels ben jij ook

gepromoveerdenishetonsallemaalgelukt.Ikbentrotsopje.

Lieve Pien, ik had me geen betere opvolger kunnen wensen. Dank voor de hulp die je me hebt

gebodenbijhetafrondenvanalleprojecten.Hopelijkgaanernogeenaantalgezamenlijkeprojecten

enborrelsvolgen,ikkijkernaaruit.

Mijn liefste vriendinnetjes, ik mag van geluk spreken dat ik de afgelopen jaren zo’n fijne groep

mensenommeheenhebwetenteverzamelen.Dankvoordeafleiding,steunendosispositiviteitdie

julliemijhebbengeboden.Ikhoopdaternogveelhoogtepuntengaankomen,metomtebeginnen

hetfeestvanvanavond.Laatdiedanspasjesenhitjesmaarkomen!

LieveMarleen, ik hoor je nóg zeggen “jemoetmeniet vragen, omdat ik jou gevraagdheb”. En ik

maardenken,dieisgek..Ikdenkdatermaarweinigmensenzijndiemeéchtzogoedkennenalsjij.

Erisdanookgeenmomentgeweestdatikeraanhebgetwijfeldomjoualsmijnparanimftevragen.

Dankvooraljehulpenfijnegesprekken.Onzevriendschapisheelbelangrijkvoormij!

Lieve Fen,mijnmaatje. YOLO is onsmottoendatheb ikde afgelopen tijdbijzonder goedkunnen

gebruiken. Inmiddelskennenweelkaaralbijnaeendecadeen ikkanmenietvoorstellendatonze

vriendschapnogstukkan.Vanzelfsprekendentrotsbenikdatjijmijnparanimfbent!

Lievepapenmam,watzouikzonderjulliemoeten.Waarikzelfsomshetvertrouwenwasverloren,

hebben jullienooitaanmijgetwijfeld. Jullieonvoorwaardelijkesteunenvrijheiddie julliemijaltijd

hebben gegeven, hebben me gemaakt tot de persoon die ik nu ben. Ik weet niet hoe ik jullie

daarvoorkanbedanken,woordenschietentekort.Dankvooralles.

LieveXanenDeb,mijnzusjes,deafgelopenjarenzijnwesteedshechtergeworden,ietswatmijheel

veelgoedheeftgedaan.Julliezijnmeheeldierbaarenookalzijnwealledrieverschillend,degoede

banddiewehebbenopgebouwd,neemtniemandonsmeeraf.LieveGijsenDon,watbenikblijdat

julliedeelzijngaanuitmakenvanonzefamilie, iedereen isnucompleet.LieveMiaLuna,mijn lieve

nichtje,watben je tocheendropje. Ikbenknettergekop jeentrotsdat ikmijzelf jouwtantemag

noemen!

Allerliefste Mark, leukerd, jij bent mijn steun en toeverlaat. Dank voor je eindeloze geduld,

relativeringsvermogenen afleidingwanneer ik het nodig had. Jijwas enbent er altijd voormij. Jij

houdtmemetbeidebenenopdegrondensteuntmeinalleswat ikdoe.Watbenikblijdat ikdit

avontuursamenmetjouhebmogenbeleven.Zonderjouwashetmenietgelukt.

209

Prof.dr.F.G.Dikkers,besteFreek,dankvoorjedeelnameinmijnleescommissieendekansdiejeme

hebtgebodenommijndroomKNO-artsteworden,teverwezenlijken.

Prof.dr. J.deLange,prof.dr.F. Lobbezoo,prof.dr.B.G.Loos,prof.dr.F.R.Rozemaenprof.dr. J.

Verbraecken, dank voor het accepteren van de uitnodiging om zitting te nemen in mijn

leescommissieendezorgvuldigeenkritischebeoordelingvanmijnproefschrift.

DaarnaastwilikdedamesvandepoliKNO,MarijeenDavidbedankenvooralhunsteunenzorgdie

zemij hebben geboden in de soms roerige tijdwaarinwemet z’n allen zaten,met name op het

einde.Wathadiktochzonderjulliegemoeten.Hetisnietdeeerstekeerdatditgezegdwordt,maar

watbenikdankbaardatikbenopgenomenindeKNO-familievanhetOLVGWest.

Dr.P.M.vanRijn,lievePeter.OokalhadjehelemaalniksmetdeOSA-onderzoekenenhadjesoms

geenideewaarikmeebezigwas,jehebtaltijdvoormeklaargestaanenjeommijbekommerd.Jouw

enthousiasme omme dingen te leren en jouw vertrouwen hebbenme absoluut doen groeien als

dokter.Deloyaliteitdiejijhebttegenoverjecollega’senonuitputbareinzethebbenmijkeeropkeer

weerdoenverbazen.Dankjewelvoordefijneenleerzametijd.

Dr.M.A.J.vanLooij,lieveMarjolein,watvondikhetleukdatjijhetlaatstejaarvanmijnpromotiein

hetOLVGkwamwerken.Dankvoorjeluisterendoorenfijnetijdsamen!

Ookwil ik graag de collega’s van de KNF, Longgeneeskunde enMKA-chirurgie bedanken. De vele

overlegmomenten,nauwesamenwerkingenhetvasteMDOSlaaplatenziendatslaap-gerelateerde

ademhalingsstoornissen,metinhetbijzonderobstructieveencentraleslaapapneu,multidisciplinaire

ziektebeelden zijn, waarbij samenwerking centraal moet staan. Dank voor de vele inzichten en

verdiepinggedurendemijntijdinhetOLVGWest.

LieveLinda,hetwasgeenmakkelijketaakominjouwvoetsporentetreden.Gelukkigwasjetenallen

tijdebereidommetehelpenwaarnodigenhebjememeerderemaleneenluisterendoorgeboden.

Ikbenblijdatweelkaarbeterhebbenlerenkennenenelkaaropheteindehebbenkunnenaanvullen

enhelpenmetallezakendiegeregeldmoestenwordenrondomhethelepromotietraject.Behalve

“het stappenplan” hadden we namelijk niet heel veel om op te varen. Inmiddels ben jij ook

gepromoveerdenishetonsallemaalgelukt.Ikbentrotsopje.

Lieve Pien, ik had me geen betere opvolger kunnen wensen. Dank voor de hulp die je me hebt

gebodenbijhetafrondenvanalleprojecten.Hopelijkgaanernogeenaantalgezamenlijkeprojecten

enborrelsvolgen,ikkijkernaaruit.

Mijn liefste vriendinnetjes, ik mag van geluk spreken dat ik de afgelopen jaren zo’n fijne groep

mensenommeheenhebwetenteverzamelen.Dankvoordeafleiding,steunendosispositiviteitdie

julliemijhebbengeboden.Ikhoopdaternogveelhoogtepuntengaankomen,metomtebeginnen

hetfeestvanvanavond.Laatdiedanspasjesenhitjesmaarkomen!

LieveMarleen, ik hoor je nóg zeggen “jemoetmeniet vragen, omdat ik jou gevraagdheb”. En ik

maardenken,dieisgek..Ikdenkdatermaarweinigmensenzijndiemeéchtzogoedkennenalsjij.

Erisdanookgeenmomentgeweestdatikeraanhebgetwijfeldomjoualsmijnparanimftevragen.

Dankvooraljehulpenfijnegesprekken.Onzevriendschapisheelbelangrijkvoormij!

Lieve Fen,mijnmaatje. YOLO is onsmottoendatheb ikde afgelopen tijdbijzonder goedkunnen

gebruiken. Inmiddelskennenweelkaaralbijnaeendecadeen ikkanmenietvoorstellendatonze

vriendschapnogstukkan.Vanzelfsprekendentrotsbenikdatjijmijnparanimfbent!

Lievepapenmam,watzouikzonderjulliemoeten.Waarikzelfsomshetvertrouwenwasverloren,

hebben jullienooitaanmijgetwijfeld. Jullieonvoorwaardelijkesteunenvrijheiddie julliemijaltijd

hebben gegeven, hebben me gemaakt tot de persoon die ik nu ben. Ik weet niet hoe ik jullie

daarvoorkanbedanken,woordenschietentekort.Dankvooralles.

LieveXanenDeb,mijnzusjes,deafgelopenjarenzijnwesteedshechtergeworden,ietswatmijheel

veelgoedheeftgedaan.Julliezijnmeheeldierbaarenookalzijnwealledrieverschillend,degoede

banddiewehebbenopgebouwd,neemtniemandonsmeeraf.LieveGijsenDon,watbenikblijdat

julliedeelzijngaanuitmakenvanonzefamilie, iedereen isnucompleet.LieveMiaLuna,mijn lieve

nichtje,watben je tocheendropje. Ikbenknettergekop jeentrotsdat ikmijzelf jouwtantemag

noemen!

Allerliefste Mark, leukerd, jij bent mijn steun en toeverlaat. Dank voor je eindeloze geduld,

relativeringsvermogenen afleidingwanneer ik het nodig had. Jijwas enbent er altijd voormij. Jij

houdtmemetbeidebenenopdegrondensteuntmeinalleswat ikdoe.Watbenikblijdat ikdit

avontuursamenmetjouhebmogenbeleven.Zonderjouwashetmenietgelukt.

210

SPONSOREN

Dezeuitgavewerkmedemogelijkgemaaktdoor:

AirwayManagement

AuroraMedicalSupportBelgium(AMSB)

ApneuVereniging

InspireMedicalSystems

NederlandseVerenigingvoorSlaap-enWaakonderzoek(NSWO)

Nyxoah

Vivisol

OLVG

SlaapgeneeskundeVerenigingNederland

211

SPONSOREN

Dezeuitgavewerkmedemogelijkgemaaktdoor:

AirwayManagement

AuroraMedicalSupportBelgium(AMSB)

ApneuVereniging

InspireMedicalSystems

NederlandseVerenigingvoorSlaap-enWaakonderzoek(NSWO)

Nyxoah

Vivisol

OLVG

SlaapgeneeskundeVerenigingNederland

The role of drug-induced sleep endoscopy and

position-dependency in the diagnostic work-up of

obstructive sleep apnea

Patty E. Vonk

The role of drug-induced sleep endoscopy and position-dependency in the diagnostic w

ork-up of obstructive sleep apneaPatt

y E. Vonk

Uitnodigingvoor het bijwonen van de openbare

verdediging van het proefschrift

THE ROLE OF DRUG-INDUCED SLEEP ENDOSCOPY AND

POSITION-DEPENDENCY IN THE DIAGNOSTIC WORK-

UP OF OBSTRUCTIVE SLEEP APNEA

door

Patty Vonk

op vrijdag 24 januari 2020 om 13.00 uur

in de Aula der Universiteit, Singel 411 (hoek Spui), 1012 WN

Amsterdam

Na afloop bent u van harte uitgenodigd voor de receptie in

de Tetterode Bibliotheek

Patty VonkWichersstraat 72

1051 ML Amsterdam06-42853615

p.e.vonk@outlook.com

PARANIMFENMarleen van Tetering

06-30107053mvantetering@outlook.com

Fenna Peper06-23102428

fennapeper@hotmail.com