ResearchPDF Available

Proposal: A crossover study comparing the efficacy of the Buteyko breathing method with continuous positive airway pressure (CPAP) in obstructive sleep apnea

Authors:
  • Healthy Pixels LLC

Abstract

This proposed study aims to evaluate the success of Buteyko Breathing Method (BBM) for sleep apnea considering BBM's positive effects on asthma
Acrossoverstudycomparingtheefficacy
oftheButeykobreathingmethodwith
continuouspositiveairwaypressure(CPAP)
inobstructivesleepapnea
ShariCheves,StacyMorrow,JohnBienvenida
PH206Epidemiology•December2,2014
UniversityofCalifornia,Irvine
2
Abstract
Prevalenceofsleepapneaaffectsbetween2and10%oftheglobalpopulation,showingstrong
associationswithobesity,hypertension,cardiovascularmorbidityandmortality.Whileitisnot
clearifsleepapneaplaysacausalroleindisease,treatmentwithCPAPhasimprovedcertain
aspectsofOSAanddiseaseriskinsomecases.Yetduetocomplexfactorsincluding
convenienceandcomfort,patientadherencetoCPAPtreatmentispooracrossallages,and
successinfindingeffectivealternativetherapieshasbeenlimited.
Asdiscoveredinathletictrainingandmyofunctionaltherapy,nasalbreathingandverymild,
controlledhypoxiacanpotentiallyimproverespiratoryfunctionandperformance.Buteyko
BreathingMethod(BBM)isasimpletechniquethatfeaturesdaily“underbreathing”thathas
beenclinicallyshowntoimproveasthma,aconditioncomorbidwithOSA.Observationalstudies
haveindicatedthatBBMmayimprovesymptomsofsleepapnea,thoughpotentialmechanisms
ofsuccessareunclear.
ThiscrossoverstudyaimstoevaluatetheefficacyofBBMonindicatorsofobstructivesleep
apnea(OSA)comparedtobaselineandstandardtreatmentwithcontinuouspositiveairway
pressure(CPAP).InthisSouthernCaliforniastudy,subjectswithnewlydiagnosedmildto
moderatesleepapneawillberandomlyassignedtooneoftwosequencesoftreatments.
Measurementsofpolysomnography,respiratoryplasticity,andcapnometrywillhelpquantify
resultsofeachtreatment.Qualitativeanalysisincludingselfreportedhealthchangesand
experienceswithtreatmentswillalsobecompared.
3
Overview
Obstructivesleepapnea(OSA)isthemostcommonsleepdisorderedbreathingconditionthat
preventsadequateairflowduringsleep.Upperairwaysareblockedwhensoftmusclescollapse
duringsleepbetween10and30seconds.Thesepausesresultinintermittenthypoxiawith
significantdropsinbloodoxygenlevelsthatassociatewithmanydifferentdiseases.Individuals
withuntreatedsleepdisorderedbreathingexperienceare5.2timesmorelikelythanothersto
experiencecardiovascularmortalityindependentofsex,gender,orBMI.(1)PrevalenceofOSA
issimilarbetweenmajorcountries,rangingbetween3and7%formenand2to5%for
women.(2)AvastmajorityofOSAcasesremainundiagnosed.
AlthoughOSAmostsignificantlyassociateswiththeriskofheartdisease,researchhasrevealed
otherassociationswithdiabetes(3),cancer(4),stroke(5),dementiainolderwomen(6),adverse
pregnancyoutcomes(7),pneumonia(8),certainautoimmunediseases(9),andmotorvehicle
crashes.ThepresenceofOSAinREMsleepsignificantlyassociateswiththedevelopmentof
hypertensioninlongitudinalanalysis.(10)Anincreasingnumberofstudieslinksleepdisordersto
ADHDinchildren.(11)Weightgainappearstoincreasemarkersofsleepapneawhileweight
lossseemstodecreasethem.(12)PatientswithOSAalsohavemorecomplicationsaftersurgery.
(13)
BackgroundandRationale
Themostcommontreatmentforsleepapneaiscontinuouspositiveairwaypressure(CPAP).Use
ofCPAPassociateswithlowerriskofcardiovasculardisease,withastrongereffectformen.(14)
TreatmentwithCPAPmayalsorelievedaytimesleepinessandsubsequentriskoftraffic
accidents.(15)Inwomen,CPAPappearstoreducetheriskofstroke.(16)CPAPtherapyalso
4
reducestheriskofhypertensioninOSApatients,(17)thoughresearchindicatesthatitmayonly
protectcardiovascularpatientswhoalsoundergoprimarypreventiontherapy.(18)
WhileCPAPhasbeentherecommendedtreatmentforsleepapneainmostindividuals,the
devicescanbeuncomfortableandinconvenient.Approximately1530%ofpatientsdonot
acceptCPAPtreatment,while2040%discontinueafterthreemonths.Recentstudiessuggest
increasednasalinflammationinsomeCPAPpatientsthatassociateswithdaytimesleepiness.(19)
OthermetabolicfactorsinCPAPcompliancemayincludelowlevelsmalonyldialdehydethat
playanimportantroleinnitricoxideproduction.(20)Furthermore,whileCPAPimproves
measurementsofOSA,itdoesnotappeartoimprovemetabolicorinflammatorymarkers
associatedwithOSA(21)andmortalityrisksarenotconsistentlyimproved.Findingsare
complicatedbyfactorsofcompliance,age,andcomorbidityamongCPAPusers.Alackof
protectionisparticularlynotableinmoreseverecasesofOSAsuchasobesityhypoventilation
syndrome.(22)Newresearchsuggeststhattheindividualdifferencesinphysiologicalresponses
toOSAandhypoxiamayplayanimportantrole.(23)
DozensofmeasurementshelpdiagnoseOSAthroughpolysomnography,theindustry’s
resourceintensive“goldstandard.”TheseverityofOSAisdeterminedbythepopular
apneahypopneaindex(AHI)whichdividestheapneabreathingpausesbythehoursofsleep.
NormalAHIlevelsarefrom04.Insomecases,severityofhypoxiaismorecloselyassociated
withdiseaseoutcomethantheAHI.(24)
5
UnderlyingconditionsplayasignificantroleinOSAandlikelyinfluencetheeffectivenessof
anyOSAtreatment.Inonestudy,asthmapredictedan8yearriskofdevelopingOSA,(25)while
anotherstudyshowed38%ofOSApatientswithunderdiagnosedallergicrhinitis.(26)
Nasalobstructionisofteninvolvedinallergicconditions,possiblycontributingtopoortolerance
ofCPAP.Nasalobstructionalsoleadstomouthbreathing.Interestingly,onestudyfoundthat
nasalbreathingwasmorecommoninwomenthanmen.(27)Sleepdisordershavelongbeen
associatedwithmouthbreathingandstudiestypicallyignoreitspresentation.(28)
Mouthbreathingcanresultfromnasalobstructionsaswellasabnormalorofacialmuscletone.
Myofunctionaltherapyhasbeenusedtoimprovemusclefunctionofthetongue,lips,andjaw.In
fact,myofunctionaltherapytoretrainmusclesofthefaceandtonguedecreasesAHIby50%in
adultsand62%inchildren.(29)Onemajorgoalofmyofunctionaltherapyispropernasal
breathing.Whilethecompletemechanismsremainunclear,nasalbreathingencouragesthe
importantreleaseofnitricoxide(NO)inthenasalpassages.Extremelyhighconcentrationsare
releasedintheepithelialcellsofupperairways,andprotectiveeffectsinvolvebloodpressure,
tumorsuppression,andvasculartone.Serumandalveolarlevelsofnitricoxidemaybereduced
inOSA(30),whilefractionalexhalednitricoxide(FeNO)maybeincreased.(31)Lownasalnitric
oxidelevelsalsoassociatewithuncontrolledasthma.(31)CPAPtreatmentmayresolvecertain
FeNOlevels,evenaftershorttermtreatment,(32)(31)butotherfactorsofNOproductionareat
work.ResearchersspeculatethatreducedexpressionofendothelialNOsynthase(eNOS),the
enzymesupportingNOproduction,contributestoendothelialdysfunctionunderlyingsleep
apnea.(33)GeneticpolymorphismsthatcontrolNOproductionmayexplainthisdeficiencyand
untreatablesusceptibilityinmanycases.(34)ItisnotablethatdecreasedNOproductionand
6
assumedcardiovascularriskarelinkedtopolymorphismsintheeNOSgeneassociatedwith
methylmercuryexposure.(35)
Trainingthatincorporatesslowernasalbreathingwithreducedventilationhasbeenreportedto
improveasthmasymptoms.(36)(37)Onestudyoncontrolledbreathingshowedimprovementsin
certainaspectsofsleepqualityandbloodpressure.(38)Controlledbreathing,particularly
throughbreathholding,forcesamildhypoxicstatewhichappearstobebothprotectiveand
damagingbasedonshortorlongtermexposure,respectively.Hypoxictraining,forinstance,is
commonlyusedwithcertainathletes.Onestudyproposedthatbenefitswereconferredbymodest
amountsofhypoxiaequatedto916%inspiredoxygen,andlowcyclesequatedto3to15
episodesperday.(39)ModerateaerobicexercisealsoreducesAHI,thoughmoreresearchis
neededtodeterminelevelsofhypoxiaachievedfordifferenttypesandintensitiesof
exercise.(40)
Thedualityofhypoxiaiscomplicatedbythebody’sfunctionofrespiratoryplasticity,theability
fortheupperairwaytoadjustitselfandavoidcollapseduringsleep.Measuresofrespiratory
plasticityincludehypoxicventilatoryresponse(HVR)andventilatorylongtermfacilitation
(LTF).ResearchershavedeterminedthatintermittenthypoxiaenhancesthemagnitudeofHVR
andLTF,thoughthelongtermhealthconsequencesofthesechangesareunclear.(41)Recent
investigationsofrespiratoryplasticityinOSAcautionthatintermittenthypoxiamayresultin
detrimentaltypesofrespiratoryplasticitywhencarbondioxidelevelsarenotmaintained.(42)
Consequently,therapiesthatcanmanipulaterespiratoryplasticitybasedonindividualconditions
mightproducebetteroutcomes.
7
Controlledbreathingexerciseshavebeenusedforthousandsofyearstotreatrespiratory
conditions.Onetechniquewasdefinedinthe1950swhenaUkrainianphysicianKonstantin
Buteykonotedthatasthmawasworsenedwithhyperventilationandimprovedwithexercises
featuring“underbreathing.”TheButeykoBreathingMethod(BBM)slowlyspreadtodifferent
countrieswithclaimsofbenefittingsleepdisorders,anxiety,andfatigue.ThebenefitsofBBM
onasthmahavebeenpublishedinclinicaltrials,butsupportforOSAislimitedtoacase
study(43),smallsurvey,(44)andobservationsamongtrainingpractitioners.Thesimple
techniquesinBBMincludebreathholdingandnasalbreathingthroughcontrolledexercises.
Indeed,breathholdingaswellasnasalbreathinghavebeenassociatedwithsignificantlyhigher
levelsofNOreleasedfromnasalpassages.(45)ItissuggestedthatBBMelicitsaverymild
intermittenthypoxiaandhasbeensuccessfullyusedtocontrolasthmasymptoms.(46)Studiesare
neededtoidentifyhowBBMcompareswithCPAPtreatmentinbothquantitativeandqualitative
aspectsofsleepapnea.
Hypothesis
Ourapriorihypothesisisthatshortterm,dailyuseofBBMcansignificantlyimprovebaseline
AHIandothermeasurementsofrespiratoryplasticityinmildtomoderatecasesofOSA.Also,
wehypothesizethatshortterm,dailyuseofBBMtreatmentwillhavethesametreatmenteffects
asshortterm,dailyuseofCPAPtreatment.
Method
StudyDesign
ThirtytwosubjectswithnewlydiagnosedmildtomoderateOSAwillbeanalyzedusinga2x2
crossoverstudydesignwithtwotreatments,twoperiodsand2sequencestoanalyzetheefficacy
8
ofBBMtreatmentandtocompareitsefficacywithCPAPtreatment.Thecrossoverstudydesign
willreducethepatientvariabilitythatappearstoimpactOSAandCPAPtreatmentandallowfor
acomparisonoftreatmentswhilecontrollingforvariablessuchasgender,age,BMI,anddisease
severity(47).Thesequence(XorY)willberandomlyassignedtoeachpatient.Thetablebelow
illustratesourstudydesign:
2x2Design
Period1
(2Weeks)
Period2
(2Weeks)
SequenceX
CPAP
BBM
SequenceY
BBM
CPAP
ForBBMtreatment,subjectswillreceiverealtimeoneononedailyBBMvideotraining
interventionwiththefollowingfeatures:trainingsessionsconductedfor20minutesinthe
morningeverydayforatotalof14sessionswithinthetreatmentperiodmeasuringthesubjects’
controlpauseslowlyincreasingeachsubjects’controlpauseovertime,withanidealdurationof
40+secondsandawarenessandparticipationinexclusivenasalbreathing.Thecontrolpauseis
definedastheamountoftimeapersoncancomfortablyholdtheirbreathafterexhaling,andthis
canincreaseby34secondsperweekwithregulartraining.AccordingtotheButeykoClinic,the
mostaccuratereadingofthecontrolpauseistakenrightafterwaking.Physicalexercisewith
correct,nasal,calmbreathingisnecessaryforincreasingthecontrolpausefrom2040seconds.
SubjectsusingBBMtreatmentwillnotbeabletocrossovertoCPAPtreatmentduringthestudy
withoutdroppingoutofthestudy.
9
ForCPAPtreatment,subjectswillreceiveadeviceandmaskthat,whenproperlyworn,createa
positivepressurethatpreventsairwaysfromcollapsingincasesofOSA.TheCPAPdevicewill
betitratedfortheproperpressureforeachsubjectbasedontheinitialbaselineevaluation.
EachofthetwotreatmentperiodswillspanfortwofullweeksstartingonaTuesday,and
measurementsofsleepquality(polysomnography)andrespiratoryfunction(AHI,capnometry,
oxygensaturation)willbeobtainedatthebeginningandendofeachstudyperiod.Qualitative
evaluationswillalsobeconductedusingsurveystoevaluatetheparticipants’experienceand
symptomsattheendofeachperiod.
Awashoutperiodofoneweekwillseparateeachperiod,andparticipantswillbeinstructedto
terminateallBBMtechniquesandCPAPusagetopreventcarryovereffects.Thiswashoutperiod
wasdeterminedbasedonresearchindicatingthatmildormoderateOSApatientsusingCPAP
treatmentfor4monthswillreturntopretreatmentlevelsexcludingoxygendesaturationand
airflowobstructionaftertwodaysofCPAPwithdrawal.(48)Theoutcomevariablesinthisstudy
willbethepolysomnography,capnometry,andrespirationmeasurementsforeachmethod.
Thoughacrossoverdesignrequirestwiceasmanymeasurementsperpatientasaparallelgroup
study,thesamplesizeismuchlessinordertomeetcriteriainavoidingtypeIandtypeIIerrors.
Participantswillalsobenefitfromtheexperienceofcomparingtwotreatments,andthe
measurementswillbesharedafterthestudyiscomplete. 
10
StudyPopulation
UponapprovalbytheHumanSubjectsInstitutionalReviewBoardatUCIrvine,subjectswillbe
recruitedfromlocalcareprovidersaswellasonlineadvertisementsandnewsletterpostings.
CandidateswillbefirstscreenedbyphoneinterviewtoconfirminterestandOSAsymptoms
suchasdaytimesleepiness,daytimefatigue,andsnoring.Durationoftherecruitmentphasewill
befromthefirstofthemonthtothelastdayofthemonth.Participantsmaybeasthmaticbutthey
mustindicatetheirasthmaticconditionatthebeginningofthestudy.Additionalcriteriawill
include:successfulcompletionofanightlongpolysomnographywithresultsindicativeofOSA
aqualifiedotolaryngologistmustassesstheparticipant’snasalairflowcapacityandapprovethe
participantfortreatmentstablemedicalhistoryasevidencedbymedicalrecordsnohistoryof
treatmentforsnoringwillingnesstoengageinbothtreatmentscurrentmedicationregimenmust
notcontainnarcoticorpsychedelicdrugsandabstinencefromdailyalcoholuse.
ContraindicationsfortheButeykomethodinclude:cancerbraintumorkidneydiseasediabetes
chestpainsicklecellanemiaepilepsyschizophreniahyperthyroidismrecentheartproblems
(withinthelastsixmonths)arterialaneurysmandthrombosis.ContraindicationsfortheCPAP
(continuouspositiveairwaypreassure)include:persistentnauseaand/orvomitinghypotension
uppergastrointestinalbleedingorrecentsurgerysuspectedpneumothoraxandanyserious
allergyorblockageofnasalpassages.
Allpotentialparticipantswillfilloutconsentforms,demographicquestionnaires,andsleep
qualityquestionnairesassessingbothnighttimeanddaytimesleepcomplaints.Aphysicianwill
intervieweachsubjectformedicalandotolaryngologichistoryandperformmedicaland
otolaryngologicexaminations.Medicationhistorywillbeassessedforpertinentprescription
11
drugsandherbalsupplements.Thepolysomnographusedtomeetcriteriaforthestudywillalso
serveasbaselinemeasurementstocomparetoposttreatmentAandpretreatmentB
measurements.Furthermore,duringthispolysomnograph,technicianswillalsoperformCPAP
titrationtodeterminethecorrectairpressuresettingsforCPAPtherapy.Titrationinvolves
gradualincreasesinairpressureuntilmanifestationsofapneadisappear.Technicianswill
monitorforchangesassociatedwithadjustmentofbodypositionorprogressionofsleepcycle
andregulateairpressureasneeded.
DuetodifferencesinCPAPefficacyinolderadults,onlyadultsnewlydiagnosedwithmildand
moderateOSAages2165willbeincluded.
ProposedMeasures
Polysomnogramsandmeanapneahypopneaindex(AHI)readingswillbetakenatthebeginning
andendofeachtreatmentatthesleepcenter.IntegratednocturnalCO2(capnometry)willbe
measuredaswell.Datawillbescoredbyapolysomnographerinablindtotreatmentfashion,
meaningsleeptechniciansandpolysomnographerswillhavenoknowledgeoftheparticipant’s
assignedsequence.
Polysomnographs(PSGs)willbeperformedusingthefollowing:respiratoryinductive
plethysmograph(RIP)electroencephalography(referredtoasEEG,C3A2)an
electrooculogram(EOG)chinelectromyogram(EMG)electrocardiogram(EKG)oraland
nasalairflowmeasures(thermistors)andpulseoximeter(rightindexfinger).Equipment
operationandcalibrationwillbeperformedbytrainedvasculartechniciansandexperienced
12
polysomnographers.Recordingswillbedigitizedusinga44channelpolygraph(Compumedics
44Eseries,Australia).
Arespiratoryinductiveplethysmographrecordsdisplacementofsensorbandsandthisrepresents
changesintidalvolume.Thisdata,expressedaspercentageofbaselinetidalvolume,willbe
usedtomeasurerespiratoryplasticity(vLTFandHVR).Ventilatorylongtermfacilitationis
definedasdeeperbreathsafterareturntonormaloxygenlevelswhereasHVRischaracterized
bydeeperbreathsduringhypoxia(49).EEGsinvolvecarefulplacementofelectrodesonthe
scalptorecordbrainwaveswhicharemeasuredinHertz(Hz)orcyclespersecond.Deltawaves
(<4Hz),thetawaves(47Hz),alphawaves(813Hz),andbetawaves(>13Hz)correspondto
differentstagesofthesleepcycle(50).EOGsrecordeyemovementsbydetectingvoltage
changesthatoccurwhentheeyemovesinrelationtotheattachedEOGelectrode(51).Eye
movementslastinglessthan500millisecondsthatareirregularandhavedrasticpeaksare
indicativeofREMsleep(52).EMGsmonitormusclemovementsasinfrequentchinmuscle
movementsthatcorrespondtotheonsetofREMsleep(53).
EKGswillmonitorheartrateandrhythmthroughelectrodesplacedonthechestwhichdetect
electricalsignalsemittedfromtheheart.Thermistors(Alice2builtinoral/nasalthermistor)will
trackairflowbysensingchangesintemperaturearoundthenoseandmouth.Inhalationis
indicatedbyalowtemperaturewhilewarmertemperaturesareassociatedwithexhalation,anda
lackofvariationintemperaturewillbeindicativeofanapneaevent(54).Bloodoxygenlevels
willbeassessedusingapulseoximeter.Thisdevicewillbeattachedtotherightindexfinger,
utilizingredandinfraredlighttodeterminebloodoxygenation.Anoxygenlevelof95100%is
considerednormalwhereasalevelbelow90%isconsideredhypoxemic(55).Finally,a
13
capnometerdevicewillmeasuretheamountofcarbondioxideinthesubject’sexhaledbreaths.
Thismeasurementisknownasendtidalcarbondioxide(ETCO2).AnETCO2valuebetween
3545mmHgisconsiderednormalwhereasavaluebelow35mmHGisindicativeofhypocapnia
(56).IntegratednocturnalCO2willbecalculatedbysumminguptheproductsoftheaverage
ETCO2ineachtimeintervalandthepercentsleepofeachtimeinterval.
Polysomnographerswillmeasuresleeprecordingsin30secondepochs.OSAeventswillbe
describedasairflowcessationofthenoseandmouthwithaminimum10secondduration.
Eventsresultinginaminimum50%decreaseinairflowandassociatedwithelectrophysiologic
evidenceofarousalwillbeconsideredhypopneic.CombinedAHIs,apneaindexes,and
hypopneaindexeswillbecalculatedbydividingthenumberofeventsbythehoursofsleep
experienced.Participantswillbeaskedtonotsmokeatleast30minutespriortothebeginningof
testingasthismaycorrupttestresults.At9pm,participantswillreporttothesleepcenterafter
consumingalightmeal.SedativesandhypnoticswillnotbeadministeredasthismayalterPSG
measurements.Subjectswillbeallowedtorelaxintheirroomandreadanovelorenjoy
televisionentertainmentonthescreenprovided.Oncetheyarereadytobeginsleep,the
participantwillnotifythesleeptechnician.
Apulseoximeterwillthenbeattachedtotherightindexfingerinordertomonitorbloodoxygen
levelsduringtesting.RIPbandswillbesecuredtothethorax(nipplelevel)andabdomen
(umbilicuslevel)usingadhesivetape.EEGelectrodeswillbeplacedaccordingtothe1020
system.TwoEOGelectrodeswillbeattachedtoeachsubject.Anelectrodewillbelocated
approximately1cmupand1cmoutfromtheoutercanthusoftherighteye.Theotherelectrode
willbeplaced1cmdownandonecmoutfromtheoutercanthusofthelefteye.Adhesivetape
14
willbeusedtoattachatotalofthreeEMGelectrodestothementalisandsubmentalismusclesof
thechintomonitormusclemovement.ThesixEKGleadswillbeattachedtothechestaccording
tostandardprocedure.Oronasalthermistorsensors(Compumedics,Melbourne,Australia)will
beattachedaroundthenoseandmouth.Acapillarytubewillbeattachedtothesubject’sairway
andwillcontinuouslycollectairsamples.Theseairsampleswilltravelupthetubetothe
sidestreamcapnometerwhereH2Oparticleswillberemovedinawatertrap.Theremaininggas
willthenbeassessedwithaninfraredlightforETCO2levels.Interviewswilltakeplaceatthe
beginningandendofeachtreatmenttoallowforqualitativeanalysisincludingselfobserved
changesinhealth,sleepinessandfatigue,adherencetotreatment,preconceptionsoftreatments,
andchallengeswithtreatments.
Statisticalmethods
Wefirstperformatesttovalidatetheassumptionsofourcrossoverdesign.Inorderforthis
methodtobevalid,wemustruleoutthepossibilityofacarryovereffectbetweenthetwo
treatments.Wewilltestthisusingatwosidedunpairedttestsofthewithinsubjectsums(47).
Wewillusean =0.05levelofsignificancetodetermineiftherearesignificantdifferencesα
betweentheperiods.Alowpvalue(p<0.05)foreithertstatisticwillbeevidenceofa
significantcarryovereffect.
WeuseaonesidedpairedttesttotestthehypothesisthatBBMwillsignificantlydecreasethe
outcomemeasurements.
Ho: =0μBBM
Ha:  <0μBBM
where isthemeaneffectofBBMtreatmentμBBM
15
ThetstatisticisastandardizedmeasureoftheaverageeffectoftheBBMtreatmentonthe
outcomemeasure.Weusean =0.05levelofsignificancetodetermineifthereisasignificantα
decreaseforeachmeasure.Alowpvalue(p<0.05)willbeevidenceofasignificantdifference
andthatBBMtreatmentsignificantlydecreasestheoutcomemeasure.
WeuseatwosidedpairedttesttotestthehypothesisthattheBBMtreatmentwillhavethesame
treatmenteffectsasCPAPtreatment.Wewanttotestforanysignificantdifferencebetweenthe
twotreatments.
Ho: =0μCPAP − μBBM
Ha: 0μCPAP − μBBM =/
where isthemeaneffectofCPAP,andμCPAP
isthemeaneffectofBBM.μBBM
ThetstatisticisastandardizedmeasureofthedifferenceinaverageeffectoftheBBMtreatment
andtheCPAPtreatmentontheoutcomemeasure.Wewillusean =0.05levelofsignificanceα
todetermineifthereisasignificantdifferencebetweenthetwotreatments.Alowpvalue(p<
0.05)willbeevidencesupportingthealternativehypothesisthatthereisasignificantdifference
betweenthetwotreatments.Ahighpvalue(p>0.05)wouldgivenoevidenceagainstthenull
hypothesisthatthetreatmenteffectsarethesame.
Inthecasethatourdataarenotnormallydistributed,thenanonparametricWilcoxonranksum
testwillbeusedtotestforcarryovereffectsandthehypothesis(47).AWilcoxonranksumtest
firstrankstheoutcomemeasurementsforeachtreatmentandthensumstheranksforeach
16
treatment.TheWstatisticifthesmallerofthetwosums.WecompareWstatistictoWcritical
whichcanbefoundusingaWilcoxonranksumtableusingan =0.05levelofsignificance(forα
twotailtest).If|Wstatistic|isgreaterthanWcritical,thenwerejectthenullhypothesisand
concludethatthereissignificantevidenceinfavorofthenull.(57)
Wedeterminedasamplesizeofapproximately32participantsbasedonasamplesizecalculation
forouronesamplepairedttestforthesecondhypothesistest(58).Thiscalculationusedan
estimatedmeandifferenceinoutcomeofAHIof6.6withanestimatedstandarddeviationof9.3
basedonapreviousstudycomparingtheefficacyofCPAPwithmandibularadvancementdevice
(MAD)therapy(59).Weusean =0.05levelofsignificanceand =0.80statisticalpower.α β
Belowistheequationusedforcalculatingthesamplesizeusing(59).
N= )(
sd
μdiff
2(Z+Z)
β 1−α 2
where =estimatedmeandifferenceinAHIoutcomevariableandμdiff 
sd=estimatedstandarddeviationofthereductionintheAHIoutcomevariable
LimitationsandAlternateApproaches
Thereareafewlimitationswhenusingacrossoverdesign.First,itisverydifficulttoassume
absolutelynocarryovereffectbetweenthesequencesandthatthewashoutperiodwill
completelyabolishanyeffect.Itisalsodifficulttoassumethatthereisnodifferenceineffect
betweensequenceXandsequenceY(47).Lastly,acrossoverstudydesignwiththreeorfour
periodsisrecommendedforgreaterefficiency(60).
17
ArandomizedcontrolledparallelgroupdesignforcomparingBMMandCPAPwouldavoidany
carryovereffectsinthecrossoverdesign,butvariabilitybetweensubjectscouldstrongly
influencetheresults.Sufficientrandomizationinsubjectswouldberequiredyetchallengingwith
thesmallersamplesizesdesiredwithsleepstudiesthatinvolvenumerous,costly
polysomnographs.Evenwiththiscrossoverstudy,therelianceonmeasurementsof
polysomnography,capnometry,andrespirationmaynotbeadequatetofullyevaluatethe
effectivenessofBMMorevenCPAPwithrespecttoOSAandsubsequentriskofdiseaseand
mortality.ElevatedlevelsofFeNOinOSA,forexample,requirelongtermuseofCPAPto
decline.Longerstudyperiodsmighthelpconfirmefficacyoftreatments.
TheprospectofusingdailybreathingexerciseswithBMMasasupplementarytreatmentfor
CPAPisalsonotexaminedinthisstudy.Inaddition,morecomprehensive,comparativestudies
ofotherlessinvasivetreatmentssuchasavoidanceofthesupinesleepingposition,(61)
oropharyngealexercises,(62),andmyofunctionaltherapywouldbeasignificantadditiontosleep
research.NewstudiesrevealnovelassociationsbetweenOSAandenhancedbonedensity,(63)
reducedmortalityincertaincases,(64)andreducedcardiovascularinjury.Furtherresearchneeds
toexplorehowOSAmayhavedevelopedasaprotectivemechanismincertainstagesortypesof
disease.Comparingothertreatmentsthatcomplementthetheoreticallyprotectivehypoxicroleof
OSAcouldenhancenaturalprocessesofrespirationandmetabolicbalanceforlongtermhealth.
18
References
1. Young,Terry,LaurelFinn,PaulEPeppard,MarianaSzkloCoxe,DianeAustin,FJavier
Nieto,RobinStubbs,andKMaeHla.2008.“SleepDisorderedBreathingandMortality:
EighteenYearFollowupoftheWisconsinSleepCohort.”Sleep31(8):1071–78.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2542952&tool=pmcentrez&ren
dertype=abstract.
2. Punjabi,NareshM.2012.“TheEpidemiologyofAdultObstructiveSleepApnea.”American
ThoracicSociety.http://www.atsjournals.org/doi/full/10.1513/pats.200709155MG#.VHJ
8TDTFDl.
3. Qureshi,Waqas,JosephYeboah,AlainBertoni,GregoryBurke,DavidHerrington,CapriFoy,
andSusanRedline.2014.“AbstractP102:RiskofIncidentHypertensionandDiabetes
MellitusinHabitualSnorersandSleepApneicIndividualsTheMultiethnicStudyof
Atherosclerosis.”Circulation129(Suppl_1):AP102–.
http://circ.ahajournals.org/content/129/Suppl_1/AP102.short.
4. MartinezGarcia,MiguelAngel,FranciscoCamposRodriguez,JoaquinDuranCantolla,
MonicaGonzalez,MonicadelaPena,MariaJoseMasdeu,FelixdelCampo,etal.2012.
“AssociationbetweenSleepApnoeaandCancerMortality.LongitudinalMuticenterStudy
in5,467PatientsfromtheSpanishCohort.”Eur.Respir.J.40(Suppl_56):P3865–.
http://erj.ersjournals.com/content/40/Suppl_56/P3865.short.
5. Bertisch,DanielGottlieb,StewartQuan,NareshPunjabi,SusanRedline.2014.Obstructive
SleepApneaAndIncidentStroke:SleepHeartHealth14YearFollowUpStudy(ATS
Journals).”2014.AccessedNovember17.
http://www.atsjournals.org/doi/abs/10.1164/ajrccmconference.
2014.189.1_MeetingAbstracts.A6361.
19
6. Yaffe,Kristine,AlisonMLaffan,StephanieLitwackHarrison,SusanRedline,AdamPSpira,
KristineEEnsrud,SoniaAncoliIsrael,andKatieLStone.2011.“SleepDisordered
Breathing,Hypoxia,andRiskofMildCognitiveImpairmentandDementiainOlder
Women.”JAMA306(6).AmericanMedicalAssociation:613–19.
doi:10.1001/jama.2011.1115.
7. Chen,YiHua,JiunnHorngKang,ChingChunLin,ITeWang,JosephJKeller,and
HerngChingLin.2012.“ObstructiveSleepApneaandtheRiskofAdversePregnancy
Outcomes.”AmericanJournalofObstetricsandGynecology206(2):136.e1–5.
doi:10.1016/j.ajog.2011.09.006.
8. Su,VincentYiFong,ChiaJenLiu,HsinKaiWang,LiAnWu,ShiChuanChang,
DiahnWarngPerng,WeiJuinSu,etal.2014.“SleepApneaandRiskofPneumonia:A
NationwidePopulationBasedStudy.”CMAJ
:CanadianMedicalAssociationJournal=
Journaldel’AssociationMedicaleCanadienne186(6):415–21.doi:10.1503/cmaj.131547.
9. Kang,JiunnHorng,andHerngChingLin.2012.“ObstructiveSleepApneaandtheRiskof
AutoimmuneDiseases:ALongitudinalPopulationBasedStudy.”SleepMedicine13(6):
583–88.doi:10.1016/j.sleep.2012.03.002.
10. Mokhlesi,Babak,LaurelAFinn,ErikaWHagen,TerryYoung,KhinMaeHla,EveVan
Cauter,andPaulEPeppard.2014.“ObstructiveSleepApneaduringREMSleepand
Hypertension.ResultsoftheWisconsinSleepCohort.”AmericanJournalofRespiratory
andCriticalCareMedicine190(10).AmericanThoracicSociety:1158–67.
doi:10.1164/rccm.2014061136OC.
11. Sedky,Karim,DavidSBennett,andKarenSCarvalho.2014.“AttentionDeficit
HyperactivityDisorderandSleepDisorderedBreathinginPediatricPopulations:A
MetaAnalysis.”SleepMedicineReviews18(4):349–56.doi:10.1016/j.smrv.2013.12.003.
20
12. Punjabi,NareshM.2008.“TheEpidemiologyofAdultObstructiveSleepApnea.”
ProceedingsoftheAmericanThoracicSociety5(2):136–43.
doi:10.1513/pats.200709155MG.
13. Kaw,Roop,VinayPasupuleti,EstebanWalker,AnuradhaRamaswamy,andNancy
FoldvarySchafer.2012.“PostoperativeComplicationsinPatientswithObstructiveSleep
Apnea.”Chest141(2).AmericanCollegeofChestPhysicians:436–41.
doi:10.1378/chest.110283.
14. CorderoGuevara,Jose,JoaquinTeranSantos,MariaLuzAlonsoAlvarez,Javier
CastrodezaSanz,EstrellaOrdaxCarbajo,andFernandoMasaJimenez.2014.
“EffectivenessofNasalContinuousPositiveAirwayPressure(CPAP)Therapyon
CardiovascularOutcomesinObstructiveSleepApneaHypopneaSyndrome(OSAHS).”
BenthamSciencePublishers.AccessedNovember12.
http://www.ingentaconnect.com/content/ben/crmr/2011/00000007/00000002/art00009.
15. Tregear,Stephen,JamesReston,KarenSchoelles,andBarbaraPhillips.2010.“Continuous
PositiveAirwayPressureReducesRiskofMotorVehicleCrashamongDriverswith
ObstructiveSleepApnea:SystematicReviewandMetaAnalysis.”Sleep33(10):1373–80.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2941424&tool=pmcentrez&ren
dertype=abstract.
16. CamposRodriguez,Francisco,MiguelAMartinezGarcia,NuriaReyesNuñez,Isabel
CaballeroMartinez,PabloCatalanSerra,andCarmenVAlmeidaGonzalez.2014.“Roleof
SleepApneaandContinuousPositiveAirwayPressureTherapyintheIncidenceofStroke
orCoronaryHeartDiseaseinWomen.”AmericanJournalofRespiratoryandCriticalCare
Medicine189(12).AmericanThoracicSociety:1544–50.
doi:10.1164/rccm.2013112012OC.
21

17.Marin,JoséM,AlvarAgusti,IsabelVillar,MartaForner,DavidNieto,SantiagoJCarrizo,
FerranBarbé,etal.2012.“AssociationbetweenTreatedandUntreatedObstructiveSleep
ApneaandRiskofHypertension.”JAMA307(20).AmericanMedicalAssociation:
2169–76.doi:10.1001/jama.2012.3418.

18.Mendelson,Monique,IsabelleVivodtzev,RenaudTamisier,DavidLaplaud,Sonia
DiasDomingos,JeanPhilippeBaguet,LaurentMoreau,etal.2014.“CPAPTreatment
SupportedbyTelemedicineDoesNotImproveBloodPressureinHighCardiovascularRisk
OSAPatients:ARandomized,ControlledTrial.”SLEEP37(11):1863–70.
doi:10.5665/sleep.4186.

19.AlAhmari,Mohammed,ChristineMikelsons,RaymondSapsford,JadwigaWedzicha,and
JohnHurst.2013.“NasalInflammationandSleepQualitywithContinuousPositiveAirway
Pressure(CPAP)TherapyinObstructiveSleepApnoea.”Eur.Respir.J.42(Suppl_57):
P2578–.http://erj.ersjournals.com/content/42/Suppl_57/P2578.

20.Comondore,VikramR,RupiCheema,JoelFox,ArsalanButt,GBJohnMancini,JohnA
Fleetham,CFrankRyan,SammyChan,andNajibTAyas.2014.“TheImpactofCPAPon
CardiovascularBiomarkersinMinimallySymptomaticPatientswithObstructiveSleep
Apnea:APilotFeasibilityRandomizedCrossoverTrial.”Lung187(1):17–22.Accessed
November24.doi:10.1007/s0040800891155.

21.JullianDesayes,Ingrid,MarieJoyeuxFaure,RenaudTamisier,SandrineLaunois,
AnneLaureBorel,PatrickLevy,andJeanLouisPepin.2014.“ImpactofObstructiveSleep
ApneaTreatmentbyContinuousPositiveAirwayPressureonCardiometabolicBiomarkers:
ASystematicReviewfromShamCPAPRandomizedControlledTrials.”SleepMedicine
Reviews,July.doi:10.1016/j.smrv.2014.07.004.
22
22.Jennum,Poul,andJakobKjellberg.2011.“Health,SocialandEconomicalConsequencesof
SleepDisorderedBreathing:AControlledNationalStudy.”Thorax66(7):560–66.
doi:10.1136/thx.2010.143958.

23.Behrouz,VahidMohsenin.2014.“IndividualVariabilityInEndothelialDependent
VasodilationInResponseToObstructiveSleepApneaAndHypoxia:ImplicationsFor
CardiovascularRiskStratification(ATSJournals).”2014.AccessedNovember24.

24.“IntermittentHypoxiaAugmentsMelanomaTumorMetastasesInAMouseModelOf
SleepApnea(ATSJournals).”2014.AccessedNovember25.
http://www.atsjournals.org/doi/abs/10.1164/ajrccmconference.2013.187.1_MeetingAbstrac
ts.A2302.

25.Hagen,E.,P.Peppard,J.Barnet,T.Young,L.Finn,andM.Teodorescu.2013.“Asthma
Predicts8YearIncidenceofObstructiveSleepApneaintheWisconsinSleepCohort.”
SleepMedicine14(December):e26.doi:10.1016/j.sleep.2013.11.024.

26.Pite,H.,J.Marques,M.J.Paes,C.C.Martinho,A.R.Dias,A.M.Silva,C.Leitao,etal.2012.
“AllergicRhinitis’ImpactonObstructiveSleepApnoea(OSA).”Eur.Respir.J.40
(Suppl_56):P3830–.http://erj.ersjournals.com/content/40/Suppl_56/P3830.short.

27.Bennett,WilliamD,KirbyLZeman,andAnnieMJarabek.2003.“NasalContributionto
BreathingwithExercise:EffectofRaceandGender.”JournalofAppliedPhysiology
(Bethesda,Md.
:1985)95(2):497–503.doi:10.1152/japplphysiol.00718.2002.

28.Guilleminault,Christian,andShannonSSullivan.2014.“TowardsRestorationof
ContinuousNasalBreathingastheUltimateTreatmentGoalinPediatricObstructiveSleep
Apnea”1(1):1–5.

23
29.Camacho,Macario,VictorCertal,JoseAbdullatif,SoroushZaghi,ChadMRuoff,Robson
Capasso,andCleteAKushida.2014.“MyofunctionalTherapytoTreatObstructiveSleep
Apnea:ASystematicReviewandMetaAnalysis.”Sleep,October.
http://europepmc.org/abstract/med/25348130.

30.Yuksel,M,HKOkur,ZPelin,AVOgunc,andLOzturk.2014.“ArginaseActivityandNitric
OxideLevelsinPatientswithObstructiveSleepApneaSyndrome.”Clinics69(4).
FaculdadedeMedicina/USP:247–52.doi:10.6061/clinics/2014(04)05.

31.Chua,AiPing,LoutfiSAboussouan,OmarAMinai,KellyPaschke,DanielLaskowski,and
RaedADweik.2013.“LongTermContinuousPositiveAirwayPressureTherapy
NormalizesHighExhaledNitricOxideLevelsinObstructiveSleepApnea.”Journalof
ClinicalSleepMedicine
:JCSM
:OfficialPublicationoftheAmericanAcademyofSleep
Medicine9(6):529–35.doi:10.5664/jcsm.2740.

32.Liu,S.Li,Y.Song,C.Bai.2013.“AssessmentOfAirwayAndAlveolarExhaledNitric
OxideInObstructiveSleepApneaHypoapneaSyndrome,”5683.

33.Bruno,RosaM,LeonardoRossi,MonicaFabbrini,EmilianoDuranti,ElisaDiCoscio,
MichelangeloMaestri,PatriziaGuidi,etal.2013.“RenalVasodilatingCapacityand
EndothelialFunctionAreImpairedinPatientswithObstructiveSleepApneaSyndromeand
NoTraditionalCardiovascularRiskFactors.”JournalofHypertension31(7):1456–64
discussion1464.doi:10.1097/HJH.0b013e328360f773.

34.Chatsuriyawong,Siriporn,DavidGozal,LeilaKheirandishGozal,RakeshBhattacharjee,
AhamedAKhalyfa,YangWang,WasanaSukhumsirichart,andAbdelnabyKhalyfa.2013.
“PolymorphismsinNitricOxideSynthaseandEndothelinGenesamongChildrenwith
ObstructiveSleepApnea.”BMCMedicalGenomics6(January):29.
doi:10.1186/17558794629.
24

35.DeMarco,KatiaCristina,LusaniaMariaGreggiAntunes,JoseEduardoTanusSantos,and
FernandoBarbosa.2012.“Intron4PolymorphismoftheEndothelialNitricOxideSynthase
(eNOS)GeneIsAssociatedwithDecreasedNOProductioninaMercuryExposed
Population.”TheScienceoftheTotalEnvironment414(January):708–12.
doi:10.1016/j.scitotenv.2011.11.010.

36.Bruton,Anne,andMikeThomas.2011.“TheRoleofBreathingTraininginAsthma
Management.”CurrentOpinioninAllergyandClinicalImmunology11(1):53–57.
doi:10.1097/ACI.0b013e3283423085.

37.Mendonca,Karla,DianaFreitas,ElizabethHolloway,GabrielaChaves,SelmaBruno,Thalita
Macedo,andGuilhermeFregonezi.2013.“TheEffectsofBreathingExercisesinAdults
withAsthma:ASystematicReview.”Eur.Respir.J.42(Suppl_57):P1309–.
http://erj.ersjournals.com/content/42/Suppl_57/P1309.short.

38.Vranish,JR,andEFBailey.“BreathingTrainingImprovesSleepAndCardiovascular
HealthInObstructiveSleepApnea,”2139.

39.NavarreteOpazo,Angela,andGordonSMitchell.2014.“TherapeuticPotentialof
IntermittentHypoxia:AMatterofDose.”AmericanJournalofPhysiology.Regulatory,
IntegrativeandComparativePhysiology307(10):R1181–97.
doi:10.1152/ajpregu.00208.2014.

40.Sengul,YesimSalik,SevgiOzalevli,IbrahimOztura,OyaItil,andBarisBaklan.2011.“The
EffectofExerciseonObstructiveSleepApnea:ARandomizedandControlledTrial.”Sleep
&Breathing=Schlaf&Atmung15(1):49–56.doi:10.1007/s1132500903111.
25
41.Gerst,DavidG,SanarSYokhana,LauraMCarney,DorothySLee,MSafwanBadr,
TabarakQureshi,MagalieNAnthouard,andJasonHMateika.2011.“TheHypoxic
VentilatoryResponseandVentilatoryLongTermFacilitationAreAlteredbyTimeofDay
andRepeatedDailyExposuretoIntermittentHypoxia.”JournalofAppliedPhysiology
(Bethesda,Md.
:1985)110(1):15–28.doi:10.1152/japplphysiol.00524.2010.

42.Mateika,JasonH,andZiauddinSyed.2013.“IntermittentHypoxia,RespiratoryPlasticity
andSleepApneainHumans:PresentKnowledgeandFutureInvestigations.”Respiratory
Physiology&Neurobiology188(3):289–300.doi:10.1016/j.resp.2013.04.010.

43.Birch,Mary.August,2004.”SleepApnoeaandBreathingRetraining.”AustraliaNursing
Journal.http://www.buteyko.info/pdf/OSA_clinical_update.pdf.

44.“Birch,Mary.2004.”SleepApnoeaandBreathingRetraining.”ButeykoInstituteof
BreathingandHealth.
http://www.buteyko.info/pdf/Sleep_Apnoea_and_Breathing_Retraining_Report_
May_2012.pdf.

45.Kimberly,B,BNejadnik,GDGiraud,andWEHolden.1996.“NasalContributionto
 ExhaledNitricOxideatRestandduringBreathholdinginHumans.”AmericanJournalof 
 RespiratoryandCriticalCareMedicine153(2):829–36.doi:10.1164/ajrccm.153.2.8564
 139.

46.Schmid,Thomas,AloisWastlhuber,OliverGohl,DraganStojanovic,andKonradSchultz.
2012.“ButeykoTechnique(BT)asanAdjunctinPulmonaryRehabilitation(PR)inPatients
withAsthmaandDysfunctionalBreathingFirstResultsofanOngoingProspective
ControlledStudy.”Eur.Respir.J.40(Suppl_56):P3527–.
http://erj.ersjournals.com/content/40/Suppl_56/P3527.short.

26
47.Wellek,Stefan,andMariaBlettner.2012.“OntheProperUseoftheCrossoverDesignin
ClinicalTrials:Part18ofaSeriesonEvaluationofScientificPublications.”Deutsches
ÄrzteblattInternational109(15):276–81.doi:10.3238/arztebl.2012.0276.

48.Young,LauraR,ZacharyHTaxin,RobertGNorman,JoyceAWalsleben,DavidM
Rapoport,andInduAyappa.2013.“ResponsetoCPAPWithdrawalinPatientswithMild
versusSevereObstructiveSleepApnea/hypopneaSyndrome.”Sleep36(3):405–12.
doi:10.5665/sleep.2460.

49.Bernardi,L,aSchneider,LPomidori,EPaolucci,andaCogo.2006.“HypoxicVentilatory
ResponseinSuccessfulExtremeAltitudeClimbers.”TheEuropeanRespiratoryJournal27
(1):165–71.doi:10.1183/09031936.06.00015805.

50.Uçar,Erdem,NecdetSüt,TevfiGülyaşar,İlhanUmut,andLeventÖztürk.2011.“Can
ObstructiveApneaandHypopneaduringSleepBeDiffErentiatedbyUsing
ElectroencephalographicFrequencyBands?StatisticalAnalysisofReceiverOperator
Curve”41(4):571–80.doi:10.3906/sag1007967.

51.Lai,TimothyYY,TszKinNg,PancyOSTam,GaryHFYam,JasmineWSNgai,
WaiManChan,DavidTLLiu,DennisSCLam,andChiPuiPang.2007.“Genotype
PhenotypeAnalysisofBietti’sCrystallineDystrophyinPatientswithCYP4V2Mutations.”
InvestigativeOphthalmology&VisualScience48(11).AssociationforResearchinVision
andOphthalmology:5212–20.doi:10.1167/iovs.070660.

52.Léger,Damien.2005.“HorlogeBiologiqueetRythmeVeille/sommeil.”CahiersdeNutrition
etdeDiététique40(3).ÉditionsMasson:133–36.doi:10.1016/S00079960(05)804778.

27
53.Shokrollahi,Mehrnaz,StudentMember,SridharKrishnan,andSeniorMember.“ChinEMG
AnalysisforREMSleepBehaviorDisorders,”no.613.

54.BaHammam,Ahmed.2004.“ComparisonofNasalProngPressureandThermistor
MeasurementsforDetectingRespiratoryEventsduringSleep.”RespirationInternational
ReviewofThoracicDiseases71(4).KargerPublishers:385–90.doi:10.1159/000079644.

55.Reinhart,Konrad,HansJörgKuhn,ChristianeHartog,andDonaldLBredle.2004.
“ContinuousCentralVenousandPulmonaryArteryOxygenSaturationMonitoringinthe
CriticallyIll.”IntensiveCareMedicine30(8):1572–78.doi:10.1007/s001340042337y.

56.Kodali,BhavaniShankar,andRichardDUrman.2014.“Capnographyduring
CardiopulmonaryResuscitation:CurrentEvidenceandFutureDirections.”Journalof
Emergencies,Trauma,andShock7(4).MedknowPublicationsandMediaPvt.Ltd.:
332–40.doi:10.4103/09742700.142778.

57.Zaiontz,Charles.RealStatisticsUsingExcel,2014,
http://www.realstatistics.com/nonparametrictests/wilcoxonranksumtest/.
58.Röhrig,Bernd,JeanBaptistduPrel,DanielWachtlin,RobertKwiecien,andMariaBlettner.
2010.“SampleSizeCalculationinClinicalTrials:Part13ofaSeriesonEvaluationof
ScientificPublications.”DeutschesÄrzteblattInternational107(3132):552–56.
doi:10.3238/arztebl.2010.0552.

59.Phillips,CraigL,RonaldRGrunstein,MAliDarendeliler,AnastasiaSMihailidou,Vasantha
KSrinivasan,BrendonJYee,GuyBMarks,andPeterACistulli.2013.“HealthOutcomes
ofContinuousPositiveAirwayPressureversusOralApplianceTreatmentforObstructive
SleepApnea:ARandomizedControlledTrial.”AmericanJournalofRespiratoryand
CriticalCareMedicine187(8):879–87.doi:10.1164/rccm.2012122223OC.
28

60.Vonesh,EdwardF.Chinchilli,VernonG.(1997)."CrossoverExperiments".Linearand
NonlinearModelsfortheAnalysisofRepeatedMeasurements.London:ChapmanandHall.
pp.111–202.

61.Oksenberg,Arie,andNatanGadoth.2014.“AreWeMissingaSimpleTreatmentforMost
AdultSleepApneaPatients?TheAvoidanceoftheSupineSleepPosition.”JournalofSleep
Research23(2):204–10.doi:10.1111/jsr.12097.

62.Guimarães,KátiaC,LucianoFDrager,PedroRGenta,BiancaFMarcondes,andGeraldo
LorenziFilho.2009.“EffectsofOropharyngealExercisesonPatientswithModerate
ObstructiveSleepApneaSyndrome.”AmericanJournalofRespiratoryandCriticalCare
Medicine179(10).AmericanThoracicSociety:962–66.doi:10.1164/rccm.200806981OC.

63.Sforza,Emilia,ThierryThomas,JeanClaudeBarthélémy,PhilippeCollet,andFrédéric
Roche.2013.“ObstructiveSleepApneaIsAssociatedwithPreservedBoneMineralDensity
inHealthyElderlySubjects.”Sleep36(10):1509–15.doi:10.5665/sleep.3046.
64.Bolona,Enrique,PeterY.Hahn,andBekeleAfessa.2014.“IntensiveCareUnitandHospital
MortalityinPatientswithObstructiveSleepApnea.”JournalofCriticalCare,October.
Elsevier.doi:10.1016/j.jcrc.2014.10.001.
29
BackgroundonButeykobreathingmethodswassupportedbyJanLeuken,certifiedButeyko
trainerinCulverCity,CA.ProfessorBehrouzJafari,MDandDirectoroftheVALongBeach
HealthcareSystemSleepCenter,providedtipsonthehypothesisandrelevantbiomarkers. 


StacywasresponsiblefortheHypothesisandStudyDesign,StatisticalMethods,andthe
LimitationsandAlternateApproachessections.JohnwasresponsiblefortheStudy
PopulationandProposedMeasuressectionsaswellasorganizingthereferences.Shari
wasresponsibleforBackgroundandRationaleandStudyDesignsections,project
guidance,andcorrespondencewithprofessionaladvisors.

ResearchGate has not been able to resolve any citations for this publication.
Conference Paper
Full-text available
Obstructive sleep apnea (OSA) is a disease defined by airflow limitations (hypopneas) and/or complete obstructions (apneas) throughout the night, and severity is indicated by the number of events per hour of sleep or apnea hypopnea index (AHI). OSA patients experience disrupted sleep and are at greater risk for hypertension, cardiovascular disease, and stroke. Unfortunately, the gold-standard of treatment for OSA, continuous positive airway pressure (CPAP), has discouraging compliance rates. Here, we report on inspiratory muscle strength training (IMST) as a potential new treatment for OSA. Mild-moderate sleep apnea patients underwent six-weeks of IMST. Training consisted of 30 breaths daily, for 6 weeks, using a take-home inspiratory resistance device (POWERbreathe® K3 series). Subjects were randomly assigned to a treatment group: training (75% of maximal inspiratory pressure (PI)) or placebo (15% of PI). max max Pre-and post-assessment measures included: overnight polysomnography (PSG), Pittsburgh sleep quality index (PSQI), spirometry, blood pressure, and PI. We find individuals in the max training group exhibit reductions in PSQI scores (11.0±0.9 vs. 6.0±1.4, pre-post) relative to placebo (10.0±1.1 vs. 9.9±0.7, pre-post). Additionally, individuals in the training group exhibit pre-post reductions in systolic and diastolic blood pressures (131.5±3.1/83.5±2.7 vs. 121.6±2.5/77.4±1.3) relative to placebo (129.8±4.8/80.6±3.1 vs. 131.9±5.0/84.6±2.7). We saw no change in AHI, however PSG results show reductions in periodic limb movement indices in training subjects (32.4 vs. 15.6, pre-post) relative to placebo (11.7 vs. 13.8, pre-post). Individuals in the training group also show improvements in the proportion of time spent in non-REM sleep (70.7% vs. 77.2%, pre-post) relative to placebo (72.0% vs. 74.6%, pre-post). In summary, individuals undertaking 6 weeks of IMST show improvements in: perceived sleep quality, proportion of consolidated sleep time, periodic limb movements, and systolic and diastolic blood pressures when compared to individuals in a placebo group. These results support IMST as a treatment that can improve the cardiovascular and sleep quality parameters in individuals with mild-moderate OSA.
Article
Aim: To investigate whether electroencephalographic (EEG) frequency bands are applicable in distinguishing abnormal respiratory events such as obstructive apnea and hypopnea in patients with sleep apnea. Materials and methods: Th e polysomnographic recordings of 20 patients were examined retrospectively. EEG record segments were taken from C4-A1 and C3-A2 channels and were analyzed with soft ware that uses digital signal processing methods, developed by the study team. Percentage values of delta, theta, alpha, and beta frequency bands were evaluated through discriminant and receiver-operator curve (ROC) analysis to distinguish between apneas and hypopneas. Results: For the C4-A1 channel, delta (%) provided the highest discriminative value (AUC = 0.563; P < 0.001); on the other hand, alpha (%) gave the lowest discriminative value (AUC = 0.519; P = 0.041). Likewise, whereas for the C3-A2 channel delta (%) gave the highest discriminative value (AUC = 0.565; P < 0.001), alpha produced the lowest discriminative value (AUC = 0.501; P = 0.943). Conclusion: As a result of discriminant analysis, the accurate classifi cation rate of hypopneas was 44.8% and the accurate classifi cation of obstructive apneas was 63.5%. Of the 4 frequency bands, the most signifi cant was delta. Th e predictive values were not at signifi cance level.
Article
Introduction Cross-sectionally, obstructive sleep apnea (OSA) is more common among asthmatics, but whether asthma promotes development of OSA in adulthood remains unknown. We investigated whether the presence or development of asthma is associated with risk of new-onset OSA in Wisconsin Sleep Cohort Study (WSCS) participants. Materials and methods At four-year intervals, WSCS participants (ages 30–60 years in 1988) completed in-laboratory polysomnography, clinical assessments, and health history questionnaires. We used logistic regression to model the association of presence of asthma and odds of incident 8-year OSA (apnea–hypopnea index (AHI) ⩾ 5 or OSA treatment initiation) among participants free of OSA (apnea–hypopnea index < 5 events/h and not treated) at baseline. First, asthma was assessed regardless of age of onset (“asthma at any age”); then, categorized by the age of onset as childhood (age < 18 years) or adult (age ⩾ 18 years). The first set of analyses adjusted for baseline variables (age, sex, BMI, smoking, alcoholic drinks/week, and nasal congestion); the second set of models also included new asthma cases and change in BMI. Results Of 1545 WSCS participants with baseline studies, 773 had no OSA at baseline and an 8-year follow-up study. Of these 773 participants, 201 had asthma (61 childhood-onset, 140 adult-onset). Relative to those without asthma, those with asthma at any age had 1.70 times (95% CI = 1.15–2.51) greater odds of new-onset OSA. Each increment in asthma duration of 5 years was associated with 10% higher odds (1.01–1.19) of new-onset OSA at 8-year follow-up. Relative to no asthma, childhood-onset asthma was associated with 2.34 times (1.25–4.37) and adult-onset asthma with 1.48 times (0.92–2.36) greater odds of new-onset OSA. There were 45 subjects who developed asthma during follow-up. New-onset asthma was unassociated with new-onset OSA, both in the model that included asthma with onset at any age (which remained significantly associated 1.67 times (1.12–2.50) and when stratified by age of onset (childhood- onset 2.28 [1.24–4.20] and adult-onset asthma 1.44 [0.88–2.35]). Conclusion In adults, presence of asthma, particularly childhood-onset asthma, predicted 8-year risk of developing OSA. Incremental asthma duration by 5 years was associated with 10% higher odds for OSA 8 years later. Whether and how intrinsic disease characteristics or associated features starting early in life affect upper airway patency during sleep remains unknown. Acknowledgements This work was supported by the National Heart, Lung, and Blood Institute (R01HL62252) and the National Center for Research Resources (1UL1RR025011) at the National Institutes of Health.
Article
Obstructive sleep apnea (OSA) is a common disorder affecting between 5% and 24% of men and women. The prevalence of OSA in the intensive care unit (ICU) population is unknown. This study was undertaken to determine the prevalence of OSA in patients admitted to the ICU and to determine if OSA is an independent predictor of mortality. This is a retrospective study using an Acute Physiology and Chronic Health Evaluation III database cross-referenced to a comprehensive clinical database to identify patients with and without OSA admitted to medical, surgical, and mixed ICUs at a large academic medical center. Between January 2003 and December 2005, 15077 patients were admitted to the ICUs; and of these, 1183 (7.8%) had a physician-documented diagnosis of OSA. Eight hundred thirty-five (71%) patients had polysomnographic testing at our institution with a documented apnea-hypopnea index more than 5 per hour. Patients with OSA were younger (59.1 ± 14.0 vs 62.3 ± 18.0), male (58.9% vs 53.7%), and had lower Acute Physiology and Chronic Health Evaluation III scores (45.3 ± 24.1 vs 54.9 ± 27.7). Predicted mortality (10.3% ± 16.4% vs16.3 ± 21.7), median ICU length of stay (1.13 vs 1.50 days), ICU mortality (2.4% vs 6.2%), and hospital mortality (3.9% vs 11.4%) were all reduced in patients with OSA, P values < .001. When adjusted for the severity of illness, OSA was independently associated with decreased hospital mortality, (0.408; 95% confidence interval, 0.298-0.557). Obstructive sleep apnea is common in patients admitted to the ICU. Obstructive sleep apnea was associated with a reduction in both ICU and hospital mortality. Copyright © 2014 Elsevier Inc. All rights reserved.
Article
Capnography continues to be an important tool in measuring expired carbon dioxide (CO2). Most recent Advanced Cardiac Life Support (ACLS) guidelines now recommend using capnography to ascertain the effectiveness of chest compressions and duration of cardiopulmonary resuscitation (CPR). Based on an extensive review of available published literature, we selected all available peer-reviewed research investigations and case reports. Available evidence suggests that there is significant correlation between partial pressure of end-tidal CO2 (PETCO2) and cardiac output that can indicate the return of spontaneous circulation (ROSC). Additional evidence favoring the use of capnography during CPR includes definitive proof of correct placement of the endotracheal tube and possible prediction of patient survival following cardiac arrest, although the latter will require further investigations. There is emerging evidence that PETCO2 values can guide the initiation of extracorporeal life support (ECLS) in refractory cardiac arrest (RCA). There is also increasing recognition of the value of capnography in intensive care settings in intubated patients. Future directions include determining the outcomes based on capnography waveforms PETCO2 values and determining a reasonable duration of CPR. In the future, given increasing use of capnography during CPR large databases can be analyzed to predict outcomes.
Article
Objective To systematically review the literature for articles evaluating myofunctional therapy (MT) as treatment for obstructive sleep apnea (OSA) in children and adults and to perform a meta-analysis on the polysomnographic, snoring, and sleepiness data. Data Sources Web of Science, Scopus, MEDLINE, and The Cochrane Library. Review Methods The searches were performed through June 18, 2014. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was followed. Results Nine adult studies (120 patients) reported polysomnography, snoring, and/or sleepiness outcomes. The pre- and post-MT apnea-hypopnea indices (AHI) decreased from a mean ± standard deviation (M ± SD) of 24.5 ± 14.3/h to 12.3 ± 11.8/h, mean difference (MD) -14.26 [95% confidence interval (CI) -20.98, -7.54], P < 0.0001. Lowest oxygen saturations improved from 83.9 ± 6.0% to 86.6 ± 7.3%, MD 4.19 (95% CI 1.85, 6.54), P =0.0005. Polysomnography snoring decreased from 14.05 ± 4.89% to 3.87 ± 4.12% of total sleep time, P < 0.001, and snoring decreased in all three studies reporting subjective outcomes. Epworth Sleepiness Scale decreased from 14.8 ± 3.5 to 8.2 ± 4.1. Two pediatric studies (25 patients) reported outcomes. In the first study of 14 children, the AHI decreased from 4.87 ± 3.0/h to 1.84 ± 3.2/h, P = 0.004. The second study evaluated children who were cured of OSA after adenotonsillectomy and palatal expansion, and found that 11 patients who continued MT remained cured (AHI 0.5 ± 0.4/h), whereas 13 controls had recurrent OSA (AHI 5.3 ± 1.5/h) after 4 y. Conclusion Current literature demonstrates that myofunctional therapy decreases AHI by approximately 50% in adults and 62% in children. Lowest oxygen saturations, snoring, and sleepiness outcomes improve in adults. Myofunctional therapy could serve as an adjunct to other OSA treatments.