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Preprint:Pleasenotethatthisarticlehasnotcompletedpeerreview.
RiskScreeningofObstructiveSleepApneaSyndrome
byBodyProfilesviaRandomForestsModel
CURRENTSTATUS:UNDERREVIEW
Cheng-YuTsai
ImperialCollegeLondonDepartmentofCivilandEnvironmentalEngineering
Wen-TeLiu
ShuangHoHospital
Yin-TzuLin
ShuangHoHospital
Shang-YangLin
TaipeiMedicalUniversityCollegeofMedicine
ArnabMajumdar
ImperialCollegeLondon
a.majumdar@imperial.ac.ukCorrespondingAuthor
ORCiD:https://orcid.org/0000-0002-6332-7858
RobertHoughton
ImperialCollegeLondonDepartmentofCivilandEnvironmentalEngineering
DeanWu
ShuangHoHospital
Hsin-ChienLee
TaipeiMedicalUniversityCollegeofMedicine
Cheng-JungWu
ShuangHoHospital
LokYeeJoyceLi
ShinKongWuHoSuMemorialHospital
Jer-NanJuang
NationalChengKungUniversity
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Yi-ShanTsai
TaipeiMedicalUniversityCollegeofPharmacy
Shin-MeiHsu
ShuangHoHospital
Chen-ChenLo
ShuangHoHospital
KangLo
ShuangHoHospital
You-RongChen
ShuangHoHospital
Feng-ChingLin
NationalTaiwanUniversity
DOI:
10.21203/rs.3.rs-22545/v1
SUBJECTAREAS
MedicalInformatics
KEYWORDS
Obstructivesleepapneasyndrome,Polysomnography,anthropometricfeatures,
sleepdisorderindexes,randomforestsmodel
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Abstract
Background
ObstructiveSleepApneaSyndrome(OSAS)isamajorglobalhealthconcernandistypicallydiagnosed
byin-labpolysomnography(PSG).Thisexaminationthoughhashighmedicalmanpowercostsand
alternativeportablemethodshavefurtherlimitations.Thispaperdevelopsanewmodelforscreening
theriskofOSASindifferentagegroupsandgenderbyusingbodyprofiles.Theeffectsofbody
profilesfordifferentsubgroupsinsleepstagealterationandOSASseverityarealsoinvestigated.
Methods
Thedataisderivedfrom6614Han-TaiwanesesubjectswhohavepreviouslyundergonePSGinorder
toassesstheseverityofOSASinthesleepcenterofTaipeiMedicalUniversityShuang-HoHospital
betweenMarch2015andOctober2019.Characteristicsofsubjects,includingage,gender,bodymass
index(BMI),neckcircumference,andwaistcircumference,wereobtainedfromaquestionnaire.
Pearsonregressionwasusedtoevaluatethecorrelationsbetweenbodyprofilesandsleepstagesas
wellassleepdisorderindexes.Todevelopanageandgenderindependentmodel,randomforests
(RF),whichisanensemblelearningmethodwithhighexplainability,weretrainedbythefourgroups
bygenderandage(olderoryoungerthan50yearsold)withratiosof70%(trainingdataset)and30%
(testingdataset),respectively.Predictionperformancewasevaluatedbysensitivity,specificityand
accuracy.Variableimportancewasassessedbyaveragingtheimpuritydecreasetoaccountforthe
effectofdifferentfactors.
Results
ResultsindicatethathighBMI,neckcircumferenceandwaistcircumferencedecreasedthedurationof
slow-wavesleepandincreasedthesleepdisorderindicesandthepercentageofwakeandN1.
Additionally,screeningmodelsfordifferentgenderandageutilizinganthropometricfeaturesas
predictorsviaRFwereestablishedanddemonstratedtohavehighaccuracy(75.63%foryounger
males,74.72%foreldermales,78.81%foryoungerfemales,and72.10%forelderfemales).Feature
importanceindicatedthatwaistcircumferencewasthehighestcontributingfactorinfemalesand
eldermales,whereastheBMIwasthehighestcontributioninyoungermales.
Conclusions
TheauthorsrecommendtheuseofthepredictionmodelsforthosewithHan-Taiwanesecraniofacial
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features.
Background
Inrecentyears,ObstructiveSleepApneaSyndrome(OSAS)hasbecomeasourceofmajorhealth
concernsglobally(1).Astudyby(2)reportedthattheestimatedprevalenceofOSAS(moderateto
severedegree)intheUnitedStateswas10%inmalesbetween30and49yearsofage,risingto17%
inelderlymales(between50and70yearsold).Thesamestudynotedthatforfemales,theestimated
prevalencewas3%ofmoderate-to-severeOSASbetweentheage30and49years,againincreasing
to9%between50and70years.Withrespecttocomorbidity,OSASisalsoconsideredasan
independentriskfactorforawiderangeofailments,including:cardiovasculardiseases,systemic
hypertension,stroke,abnormalglucosemetabolismandevencancer(3,4).Furthermore,previous
studieshaveobservedthatOSAScorrelatesto:braindamage,cognitiveimpairment,anddementia
(5–7).Therefore,withoutdoubt,OSASsignificantlyaffectsanindividual’squalityoflife.
TodiagnosetheseverityofOSASandtherebydeveloptherapeuticstrategies,thein-lab
polysomnography(PSG)isthestandardexamination(8).However,thisexaminationhasassociated
highresourcecostsintermsofmedicalmanpowerforcontinuoussleepmonitoring(9).Givenboth
thattheexaminationmodalitiesareexpensiveandthatthereisoftenalackofspaceinasleep
laboratory,thewaitinglistsforanindividualtoreceiveaPSGareusuallylong,e.g.,typically,the
averagewaittimeforreceivingmedicaltherapyafteraPSGintheUnitedStatesis11.6months(10).
Thislimitedavailabilityresultsindelaysinthetimerequiredtodiagnosesleepdisorders(11).To
overcometheselimitations,theHomeSleepTest(HST)hasbeenconsideredasanalternative
portableexaminationfordiagnosingtheseverityofOSAS.However,thistesttoohasnumerous
limitationsregardingitsuse.Forinstance,theaccuratediagnosisofOSASthroughaHSTiscurtailedif
thepatientsuffersfromothercomorbidities(12).Forexample,forsubjectswhosebodymassindex
(BMI)aremorethan40andelderlysubjects(overthe65yearsofage),therearenoestablishedHST
clinicalguidelines(13).Inadditiontothesetests,thereareavarietyofquestionnairesdesignedon
thebasisoftheclinicalpredictionrules,suchas:theBerlinquestionnaire,EpworthSleepinessScale,
andtheSTOP-Bangquestionnaire(14).Althoughthesequestionnaireshavebeenvalidatedashigh
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sensitivitytoolsforscreeningOSAS,lowspecificityhasbeenobservedineachoftheseveritygroups
(15).Hence,giventheseshortcomingsofthecurrentmethodsofevaluatingOSAS,thereisaneedto
developanewmethodforanaccurateexaminationoftheriskofOSAS.
Inordertodothis,itisworthwhiletoinvestigatethesignificantpredictorsrelatedtoOSASseverity.
Onesuchpredictorisgender,e.g.(16)notedthattheprevalenceofOSASinsouthernPennsylvaniais
nearlythreetimeshigherinmalescomparedtofemales.ThesamestudyreportedthatOSAS
prevalenceinpostmenopausalfemaleswas2.7%andsignificantlyhigherthanthe0.6%prevalencein
premenopausalfemales.Withrespecttoanthropometricprofiles,ahighermeanBMIandalarger
meanneckcircumferencehasbeenobservedinsevereOSASsubjects(N = 25)comparedwithnormal
subjects(N = 14)inTurkey(BMI:34.55kg/m2versus29.83kg/m2,p = 0.021;Neck:40.84cmversus
36.11cm,p < 0.001)(17).AnotherstudyindicatedthatforTurkishadults,theoddsratioforOSAS
was1.09(95%confidenceinterval(CI):1.014–1.17,p < 0.05)witheachincreaseof3.5cminneck
circumference(18).Inanotherstudy,thesignificantmeanlargerwaistcircumferencewasobservedin
asevereOSASgroup(N = 437)comparedwithacontrolgroup(N = 72)intheTurkishsubjects(OSAS
group:111.74 ± 12.47cm;controlgroup:91.67 ± 12.00cm,p < 0.001)(19).Inafurtherstudy,which
involvedOSASsubjects(N = 59)recruitedintheUSA,significantassociationswereobservedbetween
theapnea-hypopneaindex(AHI)andBMI(r = 0.349,p = 0.008),neckcircumference(r = 0.276,p =
0.038),andwaistcircumference(r = 0.459,p < 0.001)(20).Despiteepidemiologicalreportsshowing
thatexcessbodyprofilesareassociatedwiththeseverityofOSAS,tothebestoftheauthors’
knowledge,thereisstillnoapplicablescreeningmodelforaccessingOSASriskbyconsideringthe
anthropometricdata,genderandageeffects.Furthermore,theassociationsbetweenanthropometric
features,alternationsofsleepstructureandsleep-disorderedindexesfordifferentagegroupsand
gendersalsoremainunclear.
Therefore,thispaperexaminesthehypothesisthatbodyprofiles,asindicatorsofOSASseverity,can
beusedtoperformOSASriskscreening.TheprimaryobjectiveistoestablishOSASriskscreening
modelsfordifferentageandgendergroupsbasedonbodyprofiles.Thesemodelsareestablished
usingtherandomforests(RF)methodwhichhasanumberofadvantageswhencomparedtocurrent
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methodsofanalysis.Furthermore,thispaperinvestigatedtheeffectsofanthropometricfeaturesin
relationtosleepstagealternationsandsleep-disorderedindexesinsubgroupsbyusingthe
regressionmodel.Thepaperisorganizedasfollows.Section2describesthecollectionofthedataset,
statisticalanalysisandtheestablishmentofthescreeningmodel.Section3presentsthebaseline
characteristicsofthesubjects,thestatisticaloutcomesbetweenbodyprofilesandPSGparameters
andtheclassifyingperformanceofthetrainedmodel.Section4discussestheresultsandcompares
thefindingswithotherrelatedstudies.ThepaperconcludesinSect.5.
Methods
Ethics
ThestudyprotocolwasapprovedbytheEthicsCommitteeoftheTaipeiMedicalUniversity-Joint
InstitutionalReviewBoard(SHH:N201911007).Theexaminationinstitution(SleepcenterofShuang-
HoHospital)wasqualifiedbytheTaiwanSocietyofSleepMedicine.Themethodswereconductedin
accordancewiththeapprovedguidelines.
Studypopulation
ThedataisderivedfromsubjectswhohavepreviouslyundergonePSGinordertoassesstheseverity
ofOSASinthesleepcenterofTaipeiMedicalUniversityShuang-HoHospital(SHH,NewTaipeiCity,
Taiwan)betweenMarch2015andOctober2019.Thecriteriaforparticipantselectionwereasfollows:
(1)theywerebetween18yearsand80yearsofage(2)nonehadreceivedanyinvasivesurgeryfor
OSAStreatment(3)nonehadregularlytakenhypnoticorpsychotropicmedications,andfinally(4)the
totalrecordingtimeofthePSGwasmorethansixhours.Abaselinescreeningquestionnairewas
administeredtoassessthefollowing:age,gender,BMI,neckcircumference,andwaistcircumference.
Additionally,theusageofmedicationandthesurgicalhistoryofeachparticipantwereobtainedfrom
theirclinicalregistration.ItisworthnotingthatallparticipantswereHan-Taiwaneseinethnicorigin,
andcraniofacialfeaturesareconsideredastheeffectivefactorsrelatedtotheOSASseverityforHan
ethnicitycomparedwithotherethnicities(21).However,thesefactorswerenotusedaspredictors
sincethispaperonlyrecruitedHan-Taiwanesesubjects.
Polysomnography
Thefull-nightPSGexaminationwasperformedbyusingResMedEmblaN7000andEmblaMPRinthe
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sleepcenterofSHH.TherecordedPSGdatainvolvedthefollowing:electroencephalography(EEG),
electrooculography(EOG),chinandlegelectromyography(EMG),electrocardiography(ECG),nasal
andoralairflow,thoracicandabdominalbands,snoringsensor,bodypositionmeter,andoxygen
saturation.ThesedatawerescoredbycertifiedpolysomnographictechnologistsusingRemLogic
(version3.4.1)software.ThesleepstagesandrespiratoryeventswerescoredusingtheAmerican
AcademyofSleepMedicinescoringmanualfor2017(22).ThediagnosisofOSASwasdeterminedby
thefrequencyofapneaandhypopneaevents(23).TheAHIforeachsubjectwascalculatedbythe
totaleventnumbersofapneaandhypopneadividedbythetotalsleepingtime(TST).Infollowingwith
clinicalpractice,subjectswererecommendedtoundertaketheactiveinterventionwhentheirAHIwas
higherthan15timesperhour,whichistheclinicalthresholdformoderatetosevereOSAS(24).
StatisticalAnalysis
AllthestatisticalanalyseswereconductedbyusingPythonstatisticsmodule:Scikit-learn(version:
0.21.2).ThecollectedPSGdata,whichqualifiedwithinclusioncriteria,weredividedintotwogroups
bygender.Thecharacteristicsofthetwogroupswerecomparedbyusingtheindependentstudentt-
testforcontinuousvariablesorthechi-squaretestforcategoricalvariables.Inordertodeterminethe
correlationsbetweenanthropometricfeatures,sleepstructurealternationsandsleep-disordered
indicesconsideringgenderandmenopauseeffects,themaleandfemalegroupsweredividedinto
subgroupsbytheage(overtheageof50yearsorunder)(25).Linearregressionmodelswereusedto
associatethebodyprofilestotheparametersofPSGreportamongfourgroups.Thelevelof
significancewassettop < 0.05.
RandomForests
Previousstudieshaveusedclassificationmethodssuchasgeneticalgorithm(26)andsupportvector
machine(27).Inthispaper,weusedRF,whichisanensemblelearningmodelthatcanbeusedto
performclassification(28).Comparedwithotherclassificationmethods,thismethodhasthefollowing
advantages:fastresultcomputation,highexplainabilityoffeatureimportance,betteranti-noise
ability,stableperformancewithhighaccuracyandtheavoidanceofoverfitting.Therefore,theRF
methodhasbeenwidelyusedtoperformdiagnosisordecisionsupportinthemedicalfield(29,30).In
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thisstudy,consideringtheamountofdatacollected,whichiseasilyoverfitted,andtoinvestigatethe
importanceofpredictorseffectingtheseverityofOSAS,theRFwasusedtodevelopscreeningmodels
foreachsubgroup.
TheprocedurefortrainingandtestingmodelisillustratedinFig.1.ThePSGdataofthefourgroups
weredividedintheratioof70–30%topreparethetrainingandtestingdatasetrespectively.The
structureofthemodelconsistsofanumberofclassificationandregressiontrees(CART)whichare
trainedonselecteddatausingthebootstraptechnique(28).Thistechniquerandomlysamplesa
subsetateachinternalpartfromthetrainingdatasettodecreasetrainingtimeandtoprevent
overfitting.ThetrainingdatawasinputinamodeliterativelyfortrainingeachCARTinRFwith
bootstrapping.ThenumberofCARTwasdecidedbyout-of-bag(OOB)samplesestimationwhichcan
beusedtoevaluatetheconvergenceofthepredictionerror(31,32).Inthisstudy,themaximum
numberofCARTwasdefinedas800forstabilityandresourceimplication.SinceeachCARTwas
trainedbyavarietyofsubsetdata,overfittingsituationscanbeavoidedandcanbeassembledfor
votingtoperformtheclassification.Furthermore,featureimportancewascomputedbyaveragingthe
impuritydecreasefordeterminingtheeffectbydifferentfactors(33–35).
AccuracyEvaluation
Uponcompletionofthetrainingprocess,thetestingdatasetwasinputintotheRFmodeltoaccess
themodelsensitivity,specificityanditsaccuracy.Theconfusionmatrix,whichisameasurementfor
theperformanceoftheclassification,wascomputed.Thevaluesoftrue-positive(TP),true-negative
(TN),false-positive(FP),andfalse-negative(FN)weredetermined.Inaddition,severalindexes,
includingsensitivity(TP/(TP + FN)),specificity(TN/(TP + FN)),andaccuracy((TP + TN)/(TP + TN + FP
+ FN))werecalculatedtovalidatetheaccuracyofthetrainedmodel.TheReceiverOperating
Characteristic(ROC)curvewascalculatedtodeterminetheoptimalpoint,whichservedasthemost
balancedsensitivityandspecificitypoint.TheAreaUndertheROCcurve(AUC)measuresthe
separabilityofthemodel.Thecloserthisvalueisto1,thebettertheseparabilityofthemodel.In
addition,thepositivelikelihoodratioandthenegativelikelihoodratiowerecalculatedtovalidatethe
performance.
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Results
Characterizationofstudysubjects
Atotalof6614subjects,ofwhom69.9%(4632)weremale,wereenrolledinthisstudy,andtheir
baselinecharacteristicsaredemonstratedinTable1.Severalfeaturesareworthyofnoteinthis
sample.TherewasasignificantdifferenceinnumbersofdifferentOSASseveritiesbetweenthemale
andfemalegroups(p < 0.01).Theaverageagesofthesubjectsinthemalegroups(48.47 ±
12.81years)weresignificantlylowerthanthevalueofthesubjectsinthenormalgroup(51.94 ±
12.67years;p < 0.01).Foranthropometricfeatures,themeanBMI(26.97 ± 3.96kg/m2),themean
neckcircumference(39.25 ± 3.14cm),andthemeanwaistcircumference(93.73 ± 10.46cm)inthe
malegroupweresignificantlyhigherthanthemeanvaluesinthenormalgroup(p < 0.01).
Table1
Baselinecharacteristicsofsubjectsdividedbygender.
CategoricalVariables Male Female Total P
Number(total) 4623 1991 6614
Number(age ≥ 50) 2096 1205 3141
Number(age < 50) 2527 786 3473
Age(years) 48.47 ± 12.81 51.94 ± 12.67 49.52 ± 12.87 < 0.01
BMI(kg/m2)26.97 ± 3.96 25.46 ± 4.72 26.52 ± 4.26 < 0.01
Neckcircumference
(cm) 39.25 ± 3.14 34.13 ± 3.09 37.71 ± 3.91 < 0.01
Waistcircumference
(cm) 93.73 ± 10.46 84.38 ± 11.74 90.92 ± 11.68 < 0.01
AHI(events/hour) 32.18 ± 23.01 17.29 ± 18.94 27.70 ± 22.91 < 0.01
OSASSeveritya < 0.01
AHI < 15,n(%) 1399(30.26%) 1199(60.22%) 2598(39.28%)
AHI ≥ 15,n(%) 3224(69.74%) 792(39.78%) 4016(60.72%)
Dataareexpressedasameanwithstandarddeviation
BMI:Bodymassindex;OSAS:Obstructivesleepapneasyndrome
aChi-squaredtest
PSGresultsofstudysubjects
ThemeanvaluesofPSGresultsamongthesubjectsarelistedinTable2.Inthemales,theaverageof
sleepefficiency(SE)intheyoungergroups(9.68 ± 15.54%)weresignificantlyhigherthantheelderly
groups(73.00 ± 16.37%;p < 0.01).Similarresultswereobservedinthefemalegroups(younger:
79.92 ± 15.20%;elder:74.41 ± 16.37%;p < 0.01).Foreachsleepstage,themeanpercentageofthe
wakeandthestageone(N1)inbothgenders,thevaluesoftheyounggroupsweresignificantlylower
thantheelderlygroupsrespectively(allp < 0.01).Incontrast,themeanpercentageofthestagetwo
(N2)andtherapid-eye-movement(REM)stageintheyoungergroupswerehigherthanthevaluesof
elderlygroups(allp < 0.01).Theaverageminutesofthewakeaftersleeponset(WASO)inthe
youngergroupsofbothgenders(male:53.33 ± 48.43min;female:46.13 ± 43.18min)were
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significantlylowerthanthevaluesoftheelderlygroups(male:76.41 ± 50.33min;female:65.92 ±
47.89min;p < 0.01).
Table2
PSGresultsofsubjectsdividedbygender.
CategoricalVariables Male ≤ 50y/o Male > 50y/o Female ≤ 50y/o Female > 50y/o
SE(%) 79.68 ± 15.54%*73.00 ± 16.37%*$ 79.92 ± 15.20%#74.41 ± 16.37%#$
Wake(%ofSPT) 15.71 ± 14.65%*& 22.67 ± 15.46%*$ 13.96 ± 13.67%#& 19.86 ± 14.85%#$
N1(%ofSPT) 11.75 ± 8.18%*& 14.10 ± 10.18%*$ 8.40 ± 5.88%#& 9.34 ± 6.85%#$
N2(%ofSPT) 57.88 ± 14.81%*52.89 ± 16.15%*$ 59.03 ± 14.56%#57.50 ± 15.06%#$
REM(%ofSPT) 10.99 ± 6.28%*& 9.41 ± 6.26%*$ 12.31 ± 6.71%#& 10.35 ± 6.44%#$
WASO(mins) 53.33 ± 48.43*& 76.41 ± 50.33*$ 46.13 ± 43.18#& 65.92 ± 47.89#$
AHI(events/hour) 31.06 ± 23.71*& 33.53 ± 22.09*$ 11.34 ± 16.16#& 21.16 ± 19.62#$
Desaturationsindex
(events/hour) 29.92 ± 23.98*& 31.97 ± 22.40*$ 10.48 ± 16.05#& 20.29 ± 19.62#$
Snoringindex
(events/hour) 259.62 ± 212.69&253.51 ± 217.72$149.04 ± 193.74#& 176.49 ± 202.58#$
Arousalsindex
(events/hour) 25.47 ± 16.78*& 28.89 ± 16.56*$ 16.42 ± 10.80#& 20.72 ± 13.01#$
Dataareexpressedasameanwithstandarddeviation
SE:Sleepefficiency;SPT:Sleepperiodtime;N1:Sleepstageone;N2:Sleepstagetwo;REM:Rapideyemovement
stage;WASO:Wakeaftersleeponset;AHI:Apneahypopneaindex.
*:thep-valueislessthan0.05betweenyoungandelderwithinmales.
#:thep-valueislessthan0.05betweenyoungandelderwithinfemales.
&:thep-valueislessthan0.05betweenmalesandfemaleswithinsubjectsyoungerthan50yearsold.
$:thep-valueislessthan0.05betweenmalesandfemaleswithinsubjectsolderthan50yearsold.
Intermsofthesleepqualityindexes,themeanvaluesofAHIanddesaturationindexintheelderly
groupsinbothgendersweresignificantlyhigherthanthevaluesoftheyoungergroups(AHI:p < 0.01;
desaturationindex:p < 0.05).Therewasnosignificantdifferenceinthesnoringindexinmalegroups,
whereasasignificantdifferencewasfoundinthefemalegroups(male:149.04 ± 193.74events/hour;
female:176.49 ± 202.58events/hour,p < 0.01).Also,thereweresignificantdifferencesinarousal
indexbetweenyoungerandeldergroupsinbothgenders(allp < 0.01).Additionally,thepercentage
ofwakeandN1,WASO,AHI,desaturationindex,snoringindex,andarousalindexinmaleswas
significantlyhigherthanvaluesinfemalesinbothyoungerandelderagegroups(allp < 0.05).
Conversely,thepercentageofREMinyoungermalesweresignificantlylowerthanvaluesinyounger
females(allp < 0.05).ThelowerSE,thelowerpercentageofN2,andthelowerpercentageofREMin
eldermaleswereobservedcomparedwithelderfemales(allp < 0.05).
PSGresultsandanthropometricfeatures
TheassociationsbetweentheparametersofPSGresultsandbodyprofilesinthedifferentagegroups
andgendersareillustratedinTable3andTable4respectively.Thesleepefficiency(SE)inelder
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malesassociatednegativelywiththewaistcircumference,whereasthepercentageofwakestage
associatedpositively(p < 0.05).Similarly,thepercentageofwakestageassociatedpositivelywith
neckandwaistcircumferenceinyoungermales(p < 0.05).Thereweresignificantpositivecorrelations
betweenthepercentageofN1stageandallbodyprofilesamongallgroupsexcepttheBMIofyounger
females.Additionally,significantnegativecorrelationsbetweenthepercentageofN2,neck
circumference,andwaistcircumferenceinmaleswereobserved.ThepercentageofREMnegatively
correlatedtoallbodyprofilesinmales(p < 0.05)andnegativelycorrelatedtotheBMIaswellaswaist
circumferenceinelderfemales(p < 0.05).WhiletherewerepositivecorrelationsbetweenWASOand
allbodyprofilesamongallgroup,theylackedstatisticalsignificance.TheindexesofOSASseverity,
AHI,desaturationindex,snoringindexandarousalsindexallcorrelatedpositivelywithBMI,neck
circumferenceaswellaswaistcircumferenceinallgroups(allp < 0.05).
Table3
Pearson’scorrelationcoefficientsforvariablesofPSGresultsandanthropometricfeaturesinmales
Categorical
Variables Male ≤ 50y/o Male > 50y/o
BMI NC(cm) WC(cm) BMI NC(cm) WC(cm)
Sleepefficiency
(%) 0.0001 -0.0013 -0.0003 -0.0001 -0.0005 -0.0007*
Wake(%of
SPT) 0.0005 0.0020*0.0005*0.0004 0.0013 0.0007*
N1(%ofSPT) 0.0032*0.0047*0.0013*0.0036*0.0061*0.0014*
N2(%ofSPT) -0.0007 -0.0027*-0.0006*-0.0019 -0.0051*-0.0014*
REM(%ofSPT) -0.0017*-0.0014*-0.0006*-0.0017*-0.0015*-0.0006*
WASO(mins) 0.1346 0.5788 0.1553 0.0670 0.3069 0.2041
AHI
(events/hour) 2.7538*3.3725*1.0994*2.5695*2.8574*0.9283*
Desaturations
index
(events/hour)
2.8501*3.4735*1.1196*2.6869*2.9548*0.9587*
Snoringindex
(events/hour) 12.8627*18.0209*5.5982*18.5562*21.5843*6.6324*
Arousalsindex
(events/hour) 0.9191*1.5281*0.3946*0.9420*1.3266*0.3601*
SE:Sleepefficiency;SPT:Sleepperiodtime;N1:Sleepstageone;N2:Sleepstagetwo;REM:Rapideyemovement
stage;WASO:Wakeaftersleeponset;AHI:Apneahypopneaindex;BMI:Bodymassindex;NC:Neck
circumference;WC:Waistcircumference.
*:thep-valueislessthan0.05.
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Table4
Pearson’scorrelationcoefficientsforvariablesofPSGresultsandanthropometricfeaturesinfemales
Categorical
Variables Female ≤ 50y/o Female > 50y/o
BMI NC(cm) WC(cm) BMI NC(cm) WC(cm)
SE(%) < 0.0001 -0.001 -0.0003 -0.0009 -0.0017 -0.0005
Wake(%of
SPT) 0.0006 0.0019 0.0005 0.001 0.0024 0.0005
N1(%ofSPT) 0.0005 0.0016*0.0004*0.0018*0.0030*0.0007*
N2(%ofSPT) -0.0001 -0.0004 -0.0002 -0.0003 -0.0027 -0.0004
REM(%ofSPT) -0.0001 < 0.0001 -0.0003 -0.0014*-0.0012 -0.0004*
WASO(mins) 0.2924 0.7094 0.1976 0.1876 0.7309 0.11
AHI
(events/hour) 1.4414*2.3677*0.6746*2.0423*2.6475*0.7909*
Desaturations
index
(events/hour)
1.4971*2.4165*0.6904*2.1067*2.6857*0.8024*
Snoringindex
(events/hour) 10.4552*17.5522*4.5551*14.8561*18.7307*5.9572*
Arousalsindex
(events/hour) 0.2342*0.4529*0.1350*0.5117*0.9050*0.2279*
SE:Sleepefficiency;SPT:Sleepperiodtime;N1:Sleepstageone;N2:Sleepstagetwo;REM:Rapideyemovement
stage;WASO:Wakeaftersleeponset;AHI:Apneahypopneaindex;BMI:Bodymassindex;NC:Neck
circumference;WC:Waistcircumference.
*:thep-valueislessthan0.05
AccuracyPerformanceandparameterimportance
TheresultsoftheclassificationandvariableimportanceforeachmodelarepresentedinTable5.The
predictionaccuraciesfordifferentgroupswererangedfrom72.10–78.81%.TheAUCofROCwas
arrangedfrom76.80–81.61%.Forvariableimportance,theBMIcontributedthehighestimpact,of
38.10%inthemodelforyoungermales.However,themostimpactingfactorinothergroups,wasthe
waistcircumference:39.16%foreldermales,39.90%foryoungerfemales,and39.08%forelder
females.
Table5
Theclassificationresultsoftheage-dependentbodyprofilemodelonfoursubgroups.
CategoricalVariables Male ≤ 50y/o Male > 50y/o Female ≤ 50y/o Female > 50y/o
Casenumber(AHI ≥
15vsAHI < 15) 1676vs851 1548vs548 596vs190 603vs602
Sensitivity,% 66.84 ± 6.54 62.90 ± 13.21 83.96 ± 6.06 80.12 ± 5.87
Specificity,% 78.69 ± 3.62 76.01 ± 3.73 59.18 ± 14.97 65.67 ± 7.01
Accuracy,% 75.63 ± 3.22 74.72 ± 3.59 78.81 ± 5.77 72.10 ± 4.56
LR+ 3.14 ± 0.54 2.62 ± 0.56 2.06 ± 0.84 2.33 ± 0.43
LR- 0.42 ± 0.08 0.49 ± 0.14 0.27 ± 0.14 0.27 ± 0.12
AUC,% 81.61 ± 2.7 77.11 ± 3.01 79.30 ± 5.86 76.80 ± 4.19
Featureimportance
(100%)
BMI(%) 38.10% 38.84% 33.71% 37.00%
Neckcircumference
(%) 24.87% 23.00% 26.39% 23.92%
Waistcircumference
(%) 37.03% 39.16% 39.90% 39.08%
Dataareexpressedasameanwithstandarddeviation
AHI:Apneahypopneaindex;LR+:Positivelikelihoodratio;LR-:Negativelikelihoodratio;AUC:Areaunderthe
curve.
Discussion
Inthisstudy,theassociationsbetweenPSGparametersandanthropometricfeatureshavebeen
13
determinedconsideringageandgendereffect.Thegenderandage-independentmodelsbasedon
theanthropometricfeatureswereestablishedsuccessfullytoassesstheriskofOSAS.Theapplicable
modelsweredemonstratedtopossesshighpredictionaccuracyforclassifyingAHIhigherorlower
than15,inparticularforHan-Taiwanesesubjects.Theanthropometricfeatureimportancefor
effectingOSASseveritywasobtainedforeachsubgroup.Thelarge-scalestatistics,includingHan-
Taiwaneseanthropometricfeatures,sleepstagedetailsandPSGresultswerealsoprovided.
Forbothgenders,betteraccuracycanbeobservedintheyoungergroups,andthewaist
circumferenceshowedthehighestimportanceforitsaffectsontheAHIexceptforthecaseof
youngermales.Itisknownthatvisceralfat,whichisatypeofbodyfatdepositedaroundinternal
organs,isrelatedtotheAHIandwaistcircumferenceisauniqueindicatorforindicatingvisceralfat
distribution.Similarly,apriorstudy,whichusedtraditionalstatisticalmethods,reportedthe
observationthatwaistcircumferencewasabetterpredictorfortheseverityofOSAScomparedwith
theBMIandneckcircumference(36).AnotherstudyrevealedthatOSASprevalencewasexacerbated
inmenopausalfemalesandwaistcircumferenceservedasthemainfactor(37).Additionally,theBMI
andwaistcircumferenceshowedsimilarimportanceforeffectingtheAHIinthemalesandelderly
femalegroups,butthereisadifferenceinyoungerfemales.Therewerestatisticallysignificant
correlationsbetweentheBMI,waistcircumferenceandsleepstagepercentage,forthemalesand
elderlyfemalegroups,butnotforyoungerfemales.Theseresultsmaybeinducedbythemenopause
effect.Thiseffectmaynotleadtoweightgaindirectly,butitmaybecorrelatedtothefatdistribution
changes.Inperimenopausefemales,theincreasedabdominaladipositydepositionanddecreased
leanbodymasswereobserved.Thischangeissimilartothefatdistributionofmaleswhichtendsto
developagreaterdegreeofupperbodyobesity.
Withrespecttoneckcircumference,whichisanindicatoroffatdistributionintheupperairway,there
arethesignificantcorrelationsbetweenthesnoringindexandarousalindex.Increasedneck
circumferencemaynarrowtheupperairwayandincreasetheturbulenceofairflow,therebycausing
snoring.Besides,thecollapsibleupperairwayandtheincreasedupperairwayresistancemay
increaseintherespiratoryeffortinordertokeepventilating.Thisisthemechanismbywhich
14
increasingrespiratoryeffortmaystimulatetransientarousalinanindividualandleadtosleep
fragmentation.Similarfindingsweredemonstratedinpreviousstudies.Largeneckcircumferencehas
beenreportedasafactorinsnoring(38).
Furthermore,forbothgenders,theyoungergroupsreportedbetteroverallsleepqualityandlower
sleepdisorderindices.Theseresultsmaybeduetothecollagenlossofupperairwayconnective
tissuewithageing.Withthedecreaseinneuromusculartension,theupperairwayeasilycollapses
duringsleep.Forelderlyfemales,thedecreasedhormonelevelsduringmenopausealsoresult
increasedsleepdisorderindexesandaffectsleepquality.Similarly,numerousstudieshaveshown
thatobstructioneventsandtheseverityofOSASaresignificantlymorelikelyinelderlypatients(39,
40).Collectively,theobservationsofthisstudyareconsistentwithpreviousstudiesdemonstrating
thattheriskofOSASwasaffectedbyage,gender,andbodyprofiles.
Therearesomelimitationstothisstudy,whichshouldbeaddressedinthefuture.Firstofall,inthis
study,thedatasetwaslimitedtoaSouth-EastAsianpopulation,withcraniofacialfactors,ratherthan
fromdiversebodyprofileswithawidergeographicaldistribution.Hencetheresultsofthispaper
shouldbeviewedwiththisinmind,sincecraniofacialfactors,whichalsoaffectssleep-disordered
breathingshouldbeconsideredaspredictors(41).Next,theclinicalstandardforclassifyingOSAS
severityrequiresaPSGtodeterminetheAHI.Thissleepexaminationisstillconductedbymanual
interpretation,andsincethePSGresultswerescoredbydifferenttechnologists,thescoringvariability
canaffecttheaccuracy(42).Althoughthedatawasderivedfromonesleepcenter,whichregularly
performedinter-scoringtraining,scoringvariabilitycouldstillhaveaffectedtheresults.Furthermore,
thefirstnighteffect,whichisaphenomenononthefirstnightoftestingcharacterizedbyanaltered
sleepcycleandimpactedsleepphysiology,canalsocauseinaccuraciesofPSGresults(43).To
minimizethiseffect,somePSGparameters,suchassleepefficiency,shouldbeusedtoruleout
subjectsandrearrangethePSGforavoidingthebias.
AnotherlimitationconcernsthelackofsomeinteractingfactorsofOSAS,whileOSAShasbeen
recognizedasmultifactorialsleep-disorderedbreathing.Somebehaviors,includingsmoking,alcohol
use,environmentalparameters,andmenopausalstatusarehighlyassociatedwithOSAS(44,45).To
15
understandinfluenceofbackgrounddetails,thequestionnairecanbeusedtoobtainpersonalhabits.
OSASalsoinfluencedbydifferentdiseases(44).Thesituationofcomorbidityalsoaffectstheresultsof
PSG.Thedisease-relatedparametersthatarealreadyavailablefromclinicalinformationcanbe
obtainedandserveassignificantvariablesforpreformingpre-screenclassification.
Infuturework,adatasetwithcomprehensivedimensions,whichincludepersonalhabits,personal
comorbidity,moreanthropometricfeatures,andbodycompositions,willbecollectedfortraininga
novelmodel.
Conclusion
GiventheconcernsgloballyabouttheimpactsofOSAS,thispapernotedtheneedforamethodof
measuringOSASgiventhelimitationsofcurrentmethods.Inordertodothis,OSASriskscreening
modelsfordifferentageandgendergroupsbasedonbodyprofilesweredevelopedbasedupondata
from6614participantsfromTaiwan.
ResultsindicatethathighBMI,neckcircumferenceandwaistcircumferencedecreasedthedurationof
slow-wavesleepandincreasedthesleepdisorderindicesandthepercentageofwakeandN1.
Additionally,predictionmodelsfordifferentgenderandageutilizinganthropometricfeaturesas
predictorsviaRFwereestablishedanddemonstratedtohavehighaccuracy.Featureimportancewas
explored,withwaistcircumferencethehighestcontributingfactorinfemalesandeldermales,
whereastheBMIwasthehighestcontributioninyoungermales.
TheauthorsrecommendtheuseofthepredictionmodelsforTaiwanandindeedforthosewithHan-
Taiwanesecraniofacialfeatures.
Abbreviations
OSAS:Obstructivesleepapneasyndrome;PSG:polysomnography;HST:HomeSleepTest;AHI:
Apnea-hypopneaindex;BMI:Bodymassindex;NC:Neckcircumference;WC:Waistcircumference;
SE:Sleepefficiency;SPT:Sleepperiodtime;N1:Sleepstageone;N2:Sleepstagetwo;REM:Rapid
eyemovementstage;WASO:Wakeaftersleeponset;AUC:Areaunderthecurve;RF:Randomforest
Declarations
Availabilityofdataandmaterials
Alldatageneratedoranalyzedduringthisstudyareincludedinthispublishedarticleand
16
supplementaryinformationfiles.
Ethicsapprovalandconsenttoparticipate
Ourstudyusedexistingrecordstoconductaretrospectivestudy.Allnecessaryapprovalsanda
waiverofinformedconsentwereobtainedfromtheEthicsCommitteeoftheTaipeiMedicalUniversity-
JointInstitutionalReviewBoard(SHH:N201911007).
Acknowledgments
Wewouldliketoappreciatealltheparticipantsfortheircontributiontothisresearch.
Authors’contributions
AMandWTLguidedthewholeresearchwork;CYTandWTLmadesubstantialcontributionsto
conceptionanddesignofthestudy;LYJL,YST,SMH,CCL,KL,YRC,andFCLcollectedandorganized
thedata;CYT,YTL,SYLandRHperformedtheanalysisandinterpretationofdata;CYTdraftedthe
article;WTL,AM,DW,HCL,CJW,andJNJrevisedthemanuscriptcriticallyforimportantintellectual
content.Allauthorshavereadandapprovedthefinalversionofthemanuscriptforpublication.
Funding
ThisstudywasfundedbytheMinistryofScienceandTechnologyofTaiwan(MOST108-2634-F-038-
003).Thefunderhadnoroleinthestudydesign,datacollectionandanalysis,orinwritingofthe
manuscript.
Consenttopublication
Notapplicable.
Competinginterest
Theauthorsdeclarethattheyhavenocompetinginterest.
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SupplementaryInformation
Additionalfile1.TheDatasetfromSHHSleepCenter
Figures
Figure1
ThetrainingprocessofRFmodelwithbootstrappingtechniqueToincreasetheefficiency
andpreventtheoverfittinghappened,bootstrappingcanbeappliedtosamplethesubset
fromtheoriginaldataset.Thetechniqueistorepeatedlysampletoacquiresub-training
datawithreplacementfromtheoriginaldatasettogeneratemultipleseparatedatasetsfor
trainingeachclassificationandregressiontrees(CART).Abbreviations:RF,randomforests