Updates in oral appliance therapy for snoring and ... · Updates in oral appliance therapy for...
Transcript of Updates in oral appliance therapy for snoring and ... · Updates in oral appliance therapy for...
REVIEW
Updates in oral appliance therapy for snoringand obstructive sleep apnea
Hui Chen & Alan A. Lowe
Received: 27 January 2012 /Revised: 27 January 2012 /Accepted: 16 April 2012# Springer-Verlag 2012
AbstractBackground Obstructive sleep apnea (OSA) is increasinglybeing recognized by the public due to its life-threateningand low curability rate nature. Oral appliances (OAs) wereintroduced as a treatment option for both non-apneic snoringand OSA to maintain the patency of the upper airway duringsleep by repositioning the mandible, tongue, and soft palate.Results Over the past decade, OAs are enthusiastically stud-ied and concluded as a simple, silent, bed partner-friendly,less invasive, tolerable, and efficacious choice for mild-to-moderate OSA. In the meantime, some challenges remainuncertain such as titration management, 3D image diagnos-tic tools reliability, and long-term adherence for adultpatients. Improvement of temporomandibular joint (TMJ)monitoring and management is recommended, althoughthere is no scientific evidence suggesting consistent unde-sirable long-term effects of OA on the TMJ. Now thatpediatric OSA is being diagnosed more frequently, OAtherapy is becoming a promising option for children as well.Conclusion Consistent follow-up and management areneeded to increase clinical success rates in OA therapy forOSA. Further educational preparation and support is re-quired for dental and medical professionals to recognizeOSA and ensure the best possible patient care.
Keywords Obstructivesleepapnea .Oralappliance therapy .
Mandibular advancement . Snoring . Titration . Side effects .
Compliance . Adherence . Efficacy
Introduction
Obstructive sleep apnea (OSA) is characterized by repeti-tive episodes of upper airway obstruction that occur duringsleep, usually associated with a reduction in blood oxygensaturation, loud snoring, witnessed breathing interruptions,and/or arousal due to gasping or choking in the presence ofobstructive respiratory events [1]. OSA is associated withsignificant co-morbidities such as cardiovascular, metabol-ic/neurocognitive complications, motor vehicle crashes,and occupational accidents. In population-based epidemi-ology studies, the prevalence of OSA is different depend-ing upon the age, gender, obesity, ethnicity, severity, andinvestigation methodology [2]. The American NationalSleep Foundation 2005 poll based on Berlin questionnairescores indicated the prevalence of OSA ranged from 16%to 37% in the 18–65+ age groups with the 50–64-year-oldgroup having the greatest chance of being diagnosed withthe disease in both gender groups (37% in males and 29%in females) [3].
Currently, the in-laboratory polysomnography (PSG) isused as a standard to diagnose OSA [4]. The severity ofOSA is differentiated based on Apnea Hypopnea Index(AHI), which is the average number of apneas and hypo-pneas per hour of sleep. Since each apnea event differs induration (some last for 10 s while others a minute long), thenumber of events may not be better than the total time of airblockage hourly in order to demonstrate the true severity ofOSA.
Behavioral modifications for OSA treatment includeweight loss, alcohol avoidance, and changes in sleepingposition. If these conservative management practices donot solve the problem, then therapeutic interventions suchas continuous positive airway pressure (CPAP), oral appli-ances (OAs), and/or a range of surgical procedures can be
H. Chen (*) :A. A. LoweDivision of Orthodontics, Department of Oral Health Sciences,Faculty of Dentistry, The University of British Columbia,2199 Wesbrook Mall,Vancouver, BC, Canada V6T 1Z3e-mail: [email protected]
Sleep BreathDOI 10.1007/s11325-012-0712-4
used. In a recent practice parameters article published by theAmerican Academy of Sleep Medicine (AASM), OAs areindicated for snorers, for mild to moderate OSA subjects, forsevere OSA subjects who have not responded to CPAP, whoare not appropriate candidates for CPAP, or whose previousattempts to use CPAP failed [5].
This review will summarize the current understandingand controversy of OA therapy for the treatment of OSAand/or non-apneic snoring from publications collected overthe past 10 years (2001–2011). Searches were limited toarticles in English, clinical trials, meta-analyses, practiceguidelines, randomized controlled trials, and reviews.The detailed literature search criteria are described inFig. 1. The updated studies on pediatric OSA, three-dimensional (3D) imaging analysis on upper airwaystructure, titration strategies, and side-effects manage-ment will be integrated to address further research chal-lenges in the field.
OA therapy in general
Types and action mechanisms
There are over 100 OA designs available on the marketwhich differ in the fabrication material, location of thecoupling mechanism, titration capability, degree of custom-ization, amount of vertical opening, and lateral jaw move-ment. Most of OAs cover the upper and lower teeth and holdthe mandible in an advanced position with respect to theresting position [1]. These appliances are further dividedinto titratable and non-titratable OAs based on the capabilityof the “dose-dependent” effect of mandibular protrusion.The tongue retaining devices (TRDs) and tongue stabilizingdevices (TSDs) may be an alternative for edentulouspatients or patients with inadequate healthy teeth and aredesigned to hold the tongue in a forward position withrespect to the resting position. Boil-and-bite appliancesmay be used for patients while repairs to their regular OAsare being made.
It has been agreed that the rationale for OA therapy isto advance the mandible and tongue in order to positivelyimpact upper airway caliber and function [6, 7]. Theupper airway behind the base of the tongue and the softpalate is vulnerable due to a lack of rigid skeletal support.Airway patency is determined by a balance of forces asestablished by the interplay of anatomical factors anddilator muscle activation. Dilator muscle activation isdirectly related to airway narrowing and reduces resis-tance across patients with OSA [8]. OAs may improveupper airway patency during sleep by decreasing upperairway collapsibility and improving upper airway muscletone [9].
Mechanisms supported by images
Upper airway 3D imaging is an ideal modality to exam-ine the anatomy of the pharynx and surrounding cranio-facial and soft-tissue structures. Both static and dynamicupper airway imaging techniques have been used tosignificantly verify the understanding of the pathogene-sis of OSA and the therapeutic bio-mechanisms duringwakefulness and sleep. In a MRI study on upper airwaystructure, both mandibular repositioners and TSDsaltered upper airway geometry associated with move-ment of the parapharyngeal fat pads away from theairway. TSD increased velopharyngeal lateral diameterto a greater extent and also increased antero-posteriordiameter with anterior displacement of the tongue [7].Awake videoendoscopy suggests that mandibular ad-vancement enlarges the upper airway and may reduceupper airway dilator muscle activity during inspiration[10]. With sleep videofluoroscopy, Lee and colleagues[11] found that the length of the soft palate and theangle of mouth opening increased while the retropalatalspace and retrolingual space became narrower duringsleep events. The OA had marked effects in wideningthe retropalatal and retrolingual space and decreasing thelength of the soft palate with the mouth closed. The OAappears to enlarge the pharynx to a greater degree in thelateral than in the sagittal plane at the retropalatal andretroglossal levels of the pharynx based on CT findings[12]. Recently, patient-specific modeling created from3D reconstruction of airway and related anatomy tovisualize the different obstruction sites has been usedto choose treatment alternatives [13, 14].
Inadequate knowledge of OSA in dental professionals
Dentists often refer and treat OSA with OAs sinceanatomical structures such as the tongue, soft palate,tonsil tissues, and tori are routinely checked in regulardental exams. In a retrospective analysis of 175 maleand 156 female patients who received dental care, 67%of the men and 28% of the women were identified asbeing at risk of at least mild OSA. Over 33% of themen and 6% of the women surveyed were predicted tohave moderate or severe OSA [15]. However, a survey[16] showed that 58% of dentists in a group of 192 USpractitioners could not identify common signs andsymptoms of OSA; 40% knew little or nothing aboutOA therapy for OSA while 30% learned about it duringpostgraduate training. Some 54% have never consultedwith a physician for a suspected OSA patient in theirpractice; 75% of dentists have never had patientsreferred to them by a physician. This under-preparedsituation demands that basic education and training
Sleep Breath
regarding OSA and OAs be provided in dental schoolsand continuing education programs. In addition,
improved co-operation between dentists and physiciansis required for better overall patient care.
Fig. 1 Flow diagram of the citation selection process
Sleep Breath
Efficacy of OA therapy
Indicators for OA candidates
OA patients must have a complete medical review by a sleepspecialist and a PSG examination if required before theinitiation of treatment. Candidates for a mandibular reposi-tioner require ample healthy teeth upon which to seat theappliance, the absence of significant temporomandibulardisorder (TMD), an adequate range of jaw motion, andsufficient manual dexterity and motivation to insert andremove the OA, as determined by a qualified dental profes-sional [1]. Certain baseline variables such as a younger age[5, 17–21], smaller neck circumference [22], supine-dependent OSA [21, 23], and sufficient amount of mandib-ular protrusion [24–28] are related to better treatmentresponses. In a 10-year OA follow-up study, lower bodymass index (BMI) did not seem to be related to long-termsuccess [29] which did not agree with other studies [5,19–21, 28]. Baseline AHI also played a controversial rolein predicating the OA efficacy; some report that lower AHIscores were related to a greater improvement in OSA [5, 17,19–21] while others demonstrate reasonably good successrates in patients with more severe OSA [18, 22, 28, 30–32].This controversy may be explained by different inclusioncriteria, treatment success definitions, OA design character-istics (titratable versus non-titratable), and/or different treat-ment protocols.
Based on a nasopharyngoscopic evaluation, mandibularadvancement was associated with enlargement of the velo-pharynx, with relatively minor changes occurring in theoropharynx and hypopharynx for OA responders [33]. ACT scan study did not find any significant correlationbetween upper airway variables and baseline/follow-upAHI, nor between the changes with OA therapy. Therewas no significant difference between good and moderateresponders in cross-sectional areas at the velopharynx andhypopharynx levels, hypopharynx to velopharynx ratio, andtotal upper airway volume before and during OA use [34].Since adults had larger, more elliptical, less uniform, andless compact airways than children based on CT data, the3D size and morphological changes in the upper airwayrelated to age may serve as a basis for evaluating patientswith OSA and may help to predict and evaluate treatmentoutcomes [35].
Comparison of efficacy
There are many studies which have attempted to comparethe overall treatment efficacy between different interven-tions for OSA. The focus has mainly been on the compar-ison of OA versus CPAP [36–39], active OA therapy versuscontrols [40–42], different types of OA therapy [27, 32,
43–45], or upper airway/maxillomandibular advancement(MMA) surgery [46, 47].
To date, there have been no published or well-acceptedindications or contraindications for each treatment modality,but practice parameter guidelines and standards are avail-able [5, 48, 49]. CPAP is more effective than OA in reduc-ing the AHI [17, 36, 37, 39, 50] since OA simply dilates theairway and does not provide air under pressure directly tothe lungs. Other articles did not find clinically relevantdifference between OA and CPAP in the treatment ofmild/moderate OSA when both treatment modalities aretitrated objectively [51, 52]. There was no significant dif-ference in baseline AHI between patients who preferred OAover CPAP [37]. With respect to improvements in symp-toms, quality of life, Epworth Sleepiness Scale (ESS), andcompliance, OA is similar to that of CPAP [39]. An OA isusually preferred in effective cases over CPAP due to its lessinvasive characteristics [52].
Based on the fact that definition of success/failure criteriain different studies was not uniform, the rates of reportedefficacy may be biased and varies from study to study [53].Some evidences showed that there was no one mandibularadvancement design that most effectively improves poly-somnographic indices [53, 54]. Others announced the effi-cacy depends on severity of OSA, materials and method offabrication, type of device (mono-block vs. twin block), andthe degree of protrusion (sagittal and vertical) [27, 43, 45,55, 56]. In a retrospective review, the titratable OAs werefound to be more superior to fixed (non-titratable) OAs intheir ability to reduce the AHI among a cohort of 805patients with a wide range of OSA severity although thefixed OAs were frequently successful in mild cases [19].Some researchers advised that pre-fabricated, over-the-counter appliances are less effective, less accepted, and notqualified as a screening tool to predict OA responders [45].
An OA or CPAP cannot be compared with surgicalprocedures in crossover studies due to the irreversible natureof the surgeries. In 2010, Sleep Medicine Reviews publisheda clinical review [57] of 53 reports (627 adults with OSA)showing that the mean AHI decreased from 63.9/h to9.5/h (p<0.001) following MMA surgery. This meta-analysis showed that a younger age, lower preoperativeweight and AHI, and greater degree of maxillary advance-ment were predictive of increased surgical success.Hoekema and co-workers [46] suggested that OA therapymight be a good predictor for the success of MMA surgeryin OSA management.
It is often difficult to decide which modality is superiorbecause patients vary in terms of initial perception, behav-ioral motivation, adherence, and facility accessibility. In thiscomplicated situation, who (i.e., a certain patient) is consid-ered prior to which (i.e., a certain therapy) when determin-ing what is the best choice. Table 1 lists the randomized
Sleep Breath
Tab
le1
Rando
mized
controlledtrialsstud
iesregardingOA
advancem
ent,efficacy,side
effects,andcompliance
Reference
Study
design
OA/com
parator
Com
pleted
numbers
OA
titratio
n/advancem
ent
amount
Efficacy
Sideeffects
Com
pliance
Barnes
(2004)
[36]
RCT3-way
crossover
CPA
Pvs.OAvs.
placebotablet
114OSAS
(baselineAHI
21.3±1.3)
Mandibularadvancem
entwith
theOAwas
10.3±0.3mm
and
ranged
between1and13
mm.
77%
ofsubjectsachieved
atleast70
%of
maxim
umpossible
protrusion
Bothactiv
etreatm
entsim
proved
sleepoutcom
esbutCPA
Phadagreatereffect.Subjective
outcom
esim
proved
toasimilardegree
with
both
treatm
ents.Mostneuropsychologic
improvem
entswerenotbetterthan
the
placeboeffect
N/A
CPA
P:91.8
%;with
average
use4.2±0.3nights/week,
3.6±0.3h/night
3monthsper
period
CPA
P=97
OA:85.9
%;with
average
use5.3±0.3nights/week,
5.5±0.3h/night
2weeks
washout
OA=99
Placebo:91.8
%
Placebo
=98
Blanco
(2005)
[40]
Prospectiv
eRCT
parallel
3months
Softelastic
silicone
positio
ner(O
A)
vs.nonadvanced
mandiblemodel
(MND)
15/24OSAS
(13M
,2F
)OA:single
initial
advancem
ent
to75
%of
themaxim
umforced
advancewith
a5-mm
opening
AHIdecreased:
OA
(p<0.01);MND
(p<0.05);
ESS,snoring,
andfunctio
naloutcom
esof
sleepquestio
nnaire
significantly
decreased
only
intheOA
group
Excessive
saliv
ationnotcausing
abandonm
ent:OA=2
OA:7.7±0.5h/night
OA=8(baseline
AHI33.8±14.7)
5with
drew
dueto:
MND:6.5±1.4h/night
MND=7(baseline
AHI24.0±12.2)
Nausea:
OA=1;
MND=1
Appliancedisplacement:
OA=2;
MND=1
Deane
(2009)
[44]
RCT crossover
OAvs.tongue
stabilizing
device
(TSD)
27OSA
patients
(20M
,7F
)(baselineAHI
29.96±17.17)
OA:77
±8%
(2–10
mm)of
the
maxim
aljaw
protrusion
AHIandarousalindexweresignificantly
reduced
with
OA
andTSD.68
%of
patientsachieved
aresponse
with
OA
comparedto
45%
with
TSD
OA:jaw
discom
fort(59.1%)
anddrymouth
(50%)
Subjectivecompliancewas
betterforOA
(≥6h/night)
reported
by81.8
%of
patientscomparedwith
27.3
%forTSD
1weekper
period
TSD:non-adjustable,with
the
patient
controlling
theam
ount
oftongue
protrusion
andsuction
TSD:excess
saliv
ation(86.4%),
drymouth
(59.1%),and
soft-tissueirritatio
n(50%)
1week
washout
Dort
(2008)
[100
]
RCT crossover
TRD
with
activ
esuctionvs.non-
suctiondevice
(control)
32/38OSA
patients(22M
,10F)(baseline
RDI15.5±17.6)
N/A
TRD:RDIandsnoringindexsignificantly
reduced
Excessive
saliv
a,tender
oral
mucosaandtongue
were
resolved
spontaneously
54%
ofsubjectswishedto
continue
theTRD
1weekper
period
Control:no
significantchangesfound
1week
washout
Gotsopoulos
(2004)
[101
]
RCT crossover
OAvs.control
oral
appliance
61/74OSAS
(baselineAHI
27±15)
Meanadvancem
entof
mandible
with
theOA:7±2mm
Com
paredwith
control,OA
resultedin
50%
reductionin
meanAHI,im
proved
MinSaO
2and
arousalindex(p<0.05),andsignificantly
reduced
24-h
diastolic
BP(p=0.001)
butnot24-h
systolic
BP.
OA
significantly
reducedboth
awakediastolic
BP(p<0.0001)andsystolic
BP(p=0.003)
N/A
OA:6.8±0.1h/night
4weeks
per
period
OA
1st=
32Control:6.9±0.1h/night
1week
washout
Control
1st=
29Both:
97±1%
nightsduring
4weeks
Hoekema
(2007)
[38]
RCTparallel
OAvs.CPA
P47/48maleOSAHS
Initial
setting
at50
%of
the
maxim
umadvancem
ent.2-week
adaptatio
n.1–2increm
ents
(0.2–0.4mm)pernightfor
6-weekperiod
oruntil
symptom
sabated
orfurtheradvancem
ent
caused
discom
fort.The
mean
advancem
entwas
81±20
%of
themaxim
umadvancem
ent
Bothgroups
show
edsignificantim
provem
entsin
the
ESS,AHIandlowestoxyhem
oglobinsaturatio
nduring
sleep.
Neither
groupshow
edsignificant
improvem
entsin
sexual
functio
ning
N/A
Nosignificantdifferences
betweenthetwogroups.
OA
groupreported
using
treatm
entsignificantly
morehourspernight
(7.1±1.1)
whencompared
with
theCPA
Pgroup
(6.3±1.3)
2–3months
OA=20
(baseline
AHI9.5–
31.1)
CPA
P=27
(baseline
AHI10.0–64.6)
Lam (2
007)
[39]
RCTparallel
Non-adjustableOA
vs.CPA
Pvs.
91/101
OSAS
(baselineAHI
21.4±1.1)
OA
single
advancem
entat
the
mostadvanced
positio
nwith
out
AHIreduced:
OA
(p<0.05);CPA
P(p<0.001);
CM
(NS).SAQLIandmorning
diastolic
blood
CPA
P:drynessof
thenose,
mouth,or
throat
(47%);
feelingof
pressure
(32%);
CPA
P:4.4±0.1nights/week;
4.2±0.1h/night
Sleep Breath
Tab
le1
(con
tinued)
Reference
Study
design
OA/com
parator
Com
pleted
numbers
OA
titratio
n/advancem
ent
amount
Efficacy
Sideeffects
Com
pliance
conservativ
emeasures(CM)
causingdiscom
fortwith
some
vertical
opening
pressure:significantly
improved
inboth
OA
and
CPA
Pwith
nodifference
betweenthetwogroups
noisefrom
machine
(24%);
facial
skin
abrasion
(21%)
10weeks
OA=30
OA:excessivesaliv
ation(56%);
TMJdiscom
fort(38%);
drynessof
thethroat
(33%);
toothdiscom
fort(33%)
OA:5.2±0.3nights/week;
6.4±0.2h/night
CM=28
1/34
CPA
Pwith
drew
dueto
intolerance
CPA
P=32
4/34
OAwith
drew
dueto
gum
problems
Naism
ith(2005)
[102
]
RCT crossover
OAvs.inactiveoral
device
(control)
73/86OSA
Given
acclim
atizationphaseof
8.3±4.1weeks,themandible
was
increm
entally
advanced
tothemaxim
umcomfortable
limitof
advancem
ent
OA:55
%reductionin
AHIcomparedwith
control,
OA
improved
AHI,AHI–REM,AHI–NREM,
minSaO
2,arousalindex,
ESS,fatig
ue–inertia
(p<0.01);andvigor–activ
ity,somatic
items(p<0.05)
N/A
N/A
4weeks
per
period
OA
1st=
36(baseline
AHI27.9±17.5)
1week
washout
Control
1st=
37(baselineAHI
25.9±13.2)
Petri (2008)
[103
]
RCTparallel
OAvs.mandibular
non-advancem
ent
appliance(M
NA)
vs.no
interventio
n(N
I)
81/93OSAS
OA
single
advancem
ent:mean
protrusion
74%
(64–85
%)
ofthedifference
betweenthe
retrusivepositio
nandthe
maxim
alprotrusion
OA:reducedAHI(p<0.001),reducedESS
(p<0.001),im
proved
vitality(p<0.001),im
proved
MCS(p<0.05),andim
proved
mental/g
eneral
health
(p<0.05).MNA:no
placeboeffect
FourOA
patients(14.8%)and
twoMNA
patients(8
%)
discontin
uedinterventio
nsbecauseof
adverseeffects:
87%
ofpatientscompleted
thetrail
4weeks
OA=27
(baseline
AHI39.1±23.8)
Not
tolerate
theappliance:
OA=2,
MNA=1
MNA=25
(baseline
AHI32.6±22.0)
Loosening
oftheteeth:
OA=1,
MNA=1
NI=
29(baseline
AHI34.3±26.3)
TMJpain:OA=1
Vanderveken
(2008)
[45]
RCT crossover
Mono-bloc
thermoplastic
OA
(MADtp)vs.
custom
-madeOA
(MADcm)
35OSA
patients
(baselineAHI
13±11)
(29M
,6F
)
N/A
AHIsignificantly
reducedwith
MADcm.NoAHI
effect
with
MADtp
Sideeffectscausing
discontin
uatio
n:Com
pliancerate:MADtp:
69%,notrecommendedas
therapeutic
optio
nMADcm:94
%4monthsper
period
TMJor
toothpain:MADcm=2;
MADtp=1
1month
washout
Lackof
retention:
MADtp=8
Sleepingproblem
ordiscom
fort
atnight:MADtp=2
Walker-
Engstrom
(2002)
[47]
RCTparallel
OAvs.UPPP
72/95maleOSA
The
meanmaxim
umprotrusive
capacity
was
thesame,9.7mm,
atthe4-year
follo
w-upas
before
treatm
ent.Nopatient
changed
theirprotrusive
capacity
>2mm
63%
oftheOA
groupattained
norm
alization(A
I<5
orAHI<10),while
thenorm
alizationrate
forthe
UPPPgroupwas
33%
Success
(≥50
%reduction
inAI)rate
was
significanthigher
intheOA
group(81%)than
theUPPPgroup(53%)
OA:few
adverseeffectson
the
stom
atognathic
system
with
amoderatenumberof
adjustments
andrepairsover
time
Com
pliancerate
forOAwas
62%.75
%of
theUPPP
groupcontinuedwith
out
complem
entary
treatm
ent;
25%
startedto
usethe
dental
applianceas
complem
entary
treatm
ent
afterthe1-year
follo
w-up
4years
OA=32
(baseline
AHI17.9)
UPPP:complaintsof
nasopharyngeal
regurgitatio
nof
fluid(8
%)anddifficulty
with
swallowing(10%)
UPPP=40
(baseline
AHI19.9)
Sleep Breath
controlled trials (RCT) that compared individual therapy regard-ing OA advancement, efficacy, side effects, and compliance.
Titration protocol
Since the titratability and the degree of protrusion are con-sidered to be related to the efficacy of an OA, some articlesevaluated titration protocols for specific OAs. Clinically, thetitration starting point and technique vary with the OA typeand the patient’s ability to protrude the mandible [58]. Thesuccess of titration is dependent on the clinician’s experi-ence and determined by subjective feedback from the patientand their family members. The usual advice is to stoptitration when the patient or bed partner reports a cessationof snoring, a resolution of symptoms, or finds furtheradvancement uncomfortable [59]. In fact, the use of onlysymptomatic responses to finalize titration can on occasionleave a patient with residual sleep apnea on a PSG [60].Determining the effective protrusive setting for an OA usuallytakes place over several months and may involve multiplevisits to the dental practitioner’s office [61]. In-laboratoryPSG is still believed to be a good method for optimizing thetitration end point. Some studies [61, 62] used titration toolsduring a PSG in order to provide an optimal advancementmeasurement as a guide for the patients. One-night mandibu-lar advancement was advocated to achieve the best possibletherapeutic dose of advancement more rapidly and has thepotential to predict the response from an individual patient[63, 64]. Ambulatory monitoring devices with limited chan-nels are also suggested in order to detect the titration end point[65, 66]. These issues need to be further studied to quantifytheir therapeutic usefulness.
A follow-up PSG after titration is routinely indicated as aparameter standard by AASM in order to confirm the clin-ical response to OA treatment in patients with moderate tosevere OSA and to ensure therapeutic benefit [4]. In reality,the follow-up PSG is rarely performed due to various rea-sons such as insurance coverage and/or sleep laboratoryavailability. Table 2 summarizes some titration strategiesand evaluates the benefits of each method.
Side effects and managements
The side effects of OA therapy differ depending upon theindicated individual titration amount and patient manage-ment. Although the significance of AHI improvement pro-portionally relies on the amount of mandibular advancement[26], it has been suggested that more titration would lead tomore side effects [65].
Short-term side effects such as hypersalivation, mucosaldryness or irritation, tooth discomfort, morning occlusalchanges, myofascial stiffness, and/or temporomandibular
discomfort are mostly transient or minor and resolutionsare reported within several days to several weeks withcontinued adaption to OAs [45, 65, 67]. More severe andcontinuous side effects in the titration/initial treatmentstage may include tooth movements, occlusal changes,gingival pain, and temporomandibular and/or myofascialdiscomfort. These side effects, if not addressed andcorrected by the dentist, can be one reason for discon-tinuing treatment.
Side effects over a long period of time are common andnon-preventable but are usually mild and well tolerated bymost patients [26, 68]. An evidence-based review [20] sum-marized side effects and complications from 38 publishedstudies (over 1,700 patients evaluated) concluded that minoradverse effects were frequent whereas major adverse effectswere uncommon while using OAs. The topics that are ofgreatest concern to dentists are listed below.
Dental/occlusal/skeletal changes
Robertson and co-workers [69] recorded that changes inface height, the position of the mandible, overjet, and over-bite occurred as early as 6 months, whereas over-eruption ofthe maxillary first premolars and mandibular first molarsand proclination of the mandibular incisors were not evidentfor at least 2 years. Five-year OA therapy may be associatedwith permanent occlusal changes [68, 70, 71]. The patientswith the original greater overjet and/or overbite appears tohave the most favorable occlusion changes after long-termtherapy based on cephalometric and model analysis [68, 71].In other words, dental changes may result in favorablereductions in overjet and/or overbite in Angle Class II,Division 1 (mandibular retrognathism with protrusive max-illary anterior teeth) patients. A prospective and randomizedstudy [72] revealed the overjet, overbite, and mandibularlength in 63% cases who on average had 50% maximal jawadvancement did not show significant changes after 4 yearsof wearing an OA. This agrees with Hammond andco-workers who regard dentofacial changes as negligiblefor long-term users [73]. Monitoring of occlusal changesin 45 patients (≥4 days/week for over 5 years) identified 39patients with changes in occlusion detected by a dentalprescale pressure-sensitive sheet [74]. Even unfavorabledental side effects in terms of jaw position should not beconsidered a contraindication to OA therapy since occlusalchanges are most often adapted to and accepted by patientswhen compared with the consequences of life-threateningOSA [71]. A recent study documented that the use of CPAPmachine for over 2 years may change craniofacial form byreducing maxillary and mandibular prominence and/or byaltering the relationship between the dental arches [75]. Thisis the first study that shows not only OA but also CPAPcould cause subtle dental and skeletal changes since the
Sleep Breath
Tab
le2
OA
titratio
nprotocol
summary
Reference
Study
design
OA
type
Titrationstrategy
Com
ments
Aarab
(2010)
[65]
17OSA
patients(m
eanAHI21.6±11.1)
underw
entfour
PSGswith
theirOA
insitu
at0%
,25%,50%,and75%
ofthe
maxim
umprotrusion
toassess
the
influenceof
four
mandibularprotrusive
positio
nsat
aconstant
vertical
dimension
Mandibular
advancem
ent
device
The
OAwas
setat
aconstant
vertical
openingof
6mm
betweenthefirstincisors
with
theOA
inthemouth.The
patientswereaskedto
undergofour
ambulatory
PSG
recordings
athomewith
theOA
insitu
at0%
,25%,50%,
and75%
ofthemaxim
umprotrusion
inarandom
order.
The
averageinterval
duratio
nof
3weeks
between
subsequent
recordings
was
required
The
meanAHIvalues
differed
significantly
betweenthe
protrusion
positio
ns.T
he25%
protrusion
resultedin
asignificantreductio
nof
theAHIwhilein
the50%
and75%
protrusionseven
lower
AHIvalues
werefound.The
number
ofside
effectswas
greaterstartin
gatthe50%
protrusive
positio
nso
thisam
ount
ofstartin
gprotrusion
was
recommended,beingaweightedcomprom
isebetween
efficacy
andside
effects
Alm
eida
(2009)
[60]
Retrospective
study;
23OSA
subjects
(17M
,6F
)(m
eanAHI36.2±21.7)
AdjustablePM
Positioner™
Initialadvancem
ent:60%
ofmaxim
ummandibular
advancem
ent.Patientsstartedto
advanceon
the2ndweek
with
0.5mm
every3nightsuntil
thesymptom
snorm
alized.
TitrationPSGmonito
redwith
theOAin
place.The
PSG
technician
assisted
patientsobtain
upto
3mm
more
advancem
entifnecessarybasedon
AHI
Success
rate
(AHI≤1
0associated
with
atleasta50%
reductionin
AHI):65.2%.17.4–30.4%
(depending
upon
differentsuccesscriteriachosen)of
patientswere
incompleteresponders
andonly
successfully
treatedafter
titratio
nPSG.The
averagetim
ebetweeninsertionof
the
OA
andthetitratio
nPSG
was
5.8months.Eight
subjects
required
in-lab
advancem
ent(m
ean2.7mm)
Dort
(2006)
[61]
33OSA
patients(RDI26.9±18.3)
underw
entaremotelycontrolled
mandibularpositio
ner(RCMP)test
during
PSG
monito
ring
Mandibular
repositio
ning
appliances
The
mandiblewas
advanced
in1-mm
increm
entsin
stable
stage2sleep.
Ifan
EEG
arousaloccurred,no
further
advancem
entwas
attempted
until
stable
sleepreturned.If
thepatientsaw
okeandwas
unable
tofallasleep
with
in10
min,alladvancem
entwas
reversed
andre-initiated.
Otherwise,theadvancem
entcontinueduntil
elim
inationof
apneas,h
ypopneas,and
nocturnaloxygen
desaturatio
nwas
achieved
The
RCMPtestwas
asuccessin
15subjectsandafailu
rein
18subjects.The
OA
therapywas
successful
attarget
protrusion
in80%
ofsubjectswho
hadasuccessful
RCMP
testandfailedin
78%
ofthosewho
failedtheRCMPtest
Gauthier(2009)
[43]
RCTsingle
blindcrossover;12
weeks
per
period,5females
and11
males
with
OSA
(RDI9.4±1.1)
Silencer
vs.
Klearway™
Silencer:initial
advancem
entof
50%
ofmaxim
alprotrusion;
twoadvancem
entsof
2mm
each
madeby
thedentistat
4and8weeks.Klearway:initial
advancem
entof
75%
ofmaxim
alprotrusion;selfadvancem
entstwiceaweekand
verified
bythedentistevery4weeks
BothOAssignificantly
reducedtheRDI.Subjects’
preferenceswerein
favorof
theKlearway.The
Epw
orth
score,FOSQ,respiratorynoise,andmorning
headaches
werealso
improved
follo
wingtheuseof
both
appliances
Ghazal
(2009)
[80]
103OSA
patientswererandom
ized
and
treatedwith
twotypesof
OA
(baseline
AHI32
±6and37
±8).The
follo
w-up
sleepstudiesin
thesleeplaboratory
were
conductedwith
andwith
outtheappliance
after6months(shortterm
)andover
24months(longterm
)
IST®
(amodified
Herbstappliance)
vs.TA
P™
(Thornton
Anterior
Positioner)
IST®:constructio
nbite
at75%
ofmaxim
umprotrusion
(5±
2mm).TA
P™:increase
theprotrusion
in1–
3-mm
stepsif
patient
was
dissatisfied
with
thetherapyafterthefirst
2months.Protrusionwas
reducedin
stepsof
1–3mm
upto
halfof
width
ofabicuspid
ifdiscom
fortwas
reported
Qualityof
life,sleepquality,sleepiness,symptom
s,andsleep
outcom
esshow
edsignificantimprovem
entintheshort-term
evaluatio
nwith
both
OAs.TA
P™
revealed
asignificantly
greatereffect.T
helong-term
sleepoutcom
esrevealed
anequaleffectw
ithboth
OAs
Gindre
(2008)
[26]
66OSA
patients(m
eanAHI38.6±20.3)
underw
entPSGsat
baselin
eandat
the
finalmandibularadvancem
entandlim
ited
sleeprecordings
during
progressive
mandibularadvancem
enttitratio
n
AMC™
Initial
advancem
ent:80%
ofmaxim
ummandibular
advancem
entadjusted
with
semi-adjustable
articulator
1mm
every2weeks
until
AHI<10
orattainmentof
the
maxim
umcomfortable
limitof
advancem
entwas
achieved
70%
ofpatientsneeded
asingletitrationwith
amarkeddecrease
inmeanAHIfrom
36to10.30%
ofpatientsneeded
multiple
titrations
with
aprogressivereductioninAHI.Im
provem
entin
AHIduring
OAtherapyisdependentupontheam
ountof
mandibularadvancem
ent
Krishnan(2008)
[18]
Retrospective
study;
57OSA
subjects
(meanbaselin
eAHI=
24.8)treated
with
OA
Mandibular
repositio
ning
appliances
Hom
eself-titrationuntil
symptom
resolutio
nor
discom
fort.
Additionaltitratio
n(≤1mm)was
performed
asneeded
dependingon
thefollo
w-uptitratio
nPS
G.T
wentyminutes
ofsleepafteratitratio
nor
sleeppositio
nchange,and
ifnotin
rapideyemovem
entsleep,the
OAwas
advancein
1-mm
increm
entsor
less
ifnottolerated
andPS
Gcontinued.The
optim
almandibularposition
wasdeterm
ined
bythereview
ing
sleepphysicianandsleep-traineddentist
64.9%
ofsubjectsregardless
ofOSA
severity
were
successfully
treated(defined
asAHI<10
anddecreased
≥50%
from
baselin
e)with
OAT.
55%
ofthesubjects
achieved
successful
treatm
entby
self-titrationwith
outthe
need
forfurthertitratio
nduring
follo
w-upPSG.The
majority
ofsubjects,regardless
ofOSA
severity,are
successfully
treatedwith
anOA.M
enandyoungerpatients
werefoundto
bethebestresponders
Sleep Breath
CPAP mask and straps are designed to be tightened on thenose and face region to avoid air leakage.
Temporomandibular joint/jaw muscle complications
Since the patient’s mandible is held in a forward positionduring sleep, it is predictable and has been substantiated bysome studies [39, 44, 76] that OAs may cause jaw discom-fort or pain especially during the early stages of use. TheOA therapy resulted in more pain of the temporomandibularjoint (TMJ) complex compared to CPAP therapy in a paral-lel randomized controlled study [76], but the transient natureof the initial TMJ pain was not considered a reason tocontraindicate an OA in OSA patients. Other researchersreport that the intensity of TMD symptoms decreases sig-nificantly throughout treatment among patients who are ableto continue use of the OA [25, 70, 76, 77]. The improve-ment of TMJ monitoring and management is recommended,although there is no scientific evidence suggesting consis-tent undesirable long-term effects of OA on the TMJ.
A crossover study compared the efficacy of a reinforcedadjustable OA and a mandibular occlusal splint on sleepbruxism found that the OA reduced sleep bruxism episodesto a greater extent than a splint alone. It concluded that thereinforced OA design may be an alternative for patients withconcomitant tooth grinding and snoring or apnea duringsleep [78].
There are very few articles designed to investigate how toease the temporomandibular/myofascial complications. Ifthe problems cannot be solved due to the jaw not settlingback to its regular position throughout the day, someresearchers suggest certain jaw exercises (jig exercise andstretching movements) to relieve the occlusal function im-pairment [79]. Ten patients were recruited to do either of theexercises with 1-month wash-out and found that both exer-cises produced significant increases in occlusal contact areaand bite force in the morning compared with the period ofno exercise. There was no significant difference between thetwo exercises although the jig exercise tended to be moreeffective in the anterior region while the stretching move-ments tended to more effective in the molar region. Thestudy did not answer the question if these exercises enablemore aggressive advancement by counteracting the occlusalside effects. More evidence-based clinical trials with largerpatient pools are required to help more patients to benefitfrom OAs with less discomfort.
Compliance of OA
Long-term compliance is usually determined by follow-upquestionnaire studies. Response rates to the mailed ques-tionnaires were reported of 40–46.1% due to the patientsT
able
2(con
tinued)
Reference
Study
design
OA
type
Titrationstrategy
Com
ments
Kuna
(2006)
[24]
21OSA
patients(m
eanAHI33.5±18.3)
underw
entbaselin
e,titratio
nappliance
(EMA-T),andOA
PSGs
Klearway™
Duringthetitratio
nPSG
with
EMA-T,themandiblewas
advanced
in3-mm
increm
entsuntil
apneas
andhypopneas
wereelim
inated
orthemaxim
umtolerableadvancem
ent
was
reached.
The
participantsthen
used
theOAathome.A
PSG
with
OAwas
performed
once
themandiblewas
advanced
totheam
ount
determ
ined
during
thetitratio
nPSG
Based
ontheposthocmeasurementson
theGalletti
articulator,
maxim
ummandibularadvancem
entachievedwith
the
titratio
nappliancewas
7.8±1.8mm.T
hisam
ount
ofmandibularadvancem
entw
as85.2±25.8%
ofmaxim
alvoluntaryadvancem
ent.9subjectsachieved
anAHI<10
and
≥50%
reductioninAHI.EMA-T
lowered
theAHIacutelybut
nolong-term
predictio
ncouldbe
achieved
Tsuiki(2004)
[59]
20maleOSA
patients(m
eanAHI
31.6±13.0)received
PSG
andsupine
cephalom
etry
before
andaftertitratio
n
Klearway™
Initial
advancem
ent:67%
ofthemaxim
umprotrusion.Once
patientswereaccustom
edto
wearing
theOAwith
outany
discom
fort,they
startedadvancingthemandiblein
gradual
increm
entsof
0.25
or0.5mm
perweekuntil
any
discom
fortoccurred
orpatient/bed
partnerreported
acessationof
snoringandaresolutio
nof
symptom
s
The
meanAHIwas
significantly
decreased(9.8±7.4)
after
titratio
n.Thistitratio
nprotocol
reducedOSA
severity,
enlarged
thevelopharynx,
anddiminishedthecurvatureof
theanterior
velopharyn
geal
wallin
good
responders
Sleep Breath
unwilling to return the questionnaires or not updated theiraddress to their dental provider [29, 68]. Lost contactpatients could be considered non-compliant because theybecome less interested in re-call exams. A survey of 180OSA patients who had been using a OA for 10 yearsreported a 65% compliance rate; 47% wore the device everynight and 18% wore the device up to six nights per week[29]. The titratable adjustable OA made from thermoelasticacrylic was worn for a mean of 6.8 h with a range of 5.6 to7.5 h per night [30]. Lack of compliance may be due to aninsufficient improvement in anticipated subjective symp-toms and/or a recurrence of symptoms over time [80]. Ithas been shown that the initial discomfort of masticatorymuscles or the temporomandibular joint is a possible reasonfor poor compliance or abandonment of OA treatment [25,73, 81, 82]. Some other studies state that transient sideeffects do not require the discontinuation of treatment ifthey are well managed [22, 83].
The OAs that allow lateral jaw movement and verticalopening may reduce the risk of adverse effects and thusenhance patient adherence [84]. The amount of bite openinginduced by OAs does not have a significant impact ontreatment efficacy but does have an impact on patientacceptance, with the larger interincisal opening (14 mmversus 4 mm) significantly decreasing the patient’s prefer-ence [85]. Although there is still uncertainty about theinfluence of OA design on treatment outcomes, adverseeffects, adherence to treatment, and potential long-termcomplications of therapy [6], OA selection needs to be takeninto account when considering the benefit of the AHIreduction versus the subject’s compliance [43].
OA therapy in pediatric OSA
Increasing attention has been paid to children with OSA indentistry [86]. The polysomnographic diagnostic criteria forOSA in children are different than adults: an AHI >1 andoxygen desaturation ≥4% are indicators of mild OSA amongthose under 15 years of age [87]. Pediatric OSA can occur inany age group, including infants, with a peak incidencebetween the age of 2 and 8 years old, which correlates withthe age during which adenotonsillar hypertrophy is mostmarked. Increasing prevalence has also been noted in mid-dle childhood and adolescent age groups due to the risingprevalence of obesity in these age groups in some parts ofthe world [88].
When investigating prevalence, predication, sleep quali-ty/duration, daytime sleepiness, and performance in chil-dren, most articles use unique sleep questionnaires[89–91]. The questionnaires usually were answered by thechild’s parents or school teacher based on judgments andcomparisons with siblings or classmates of the same age. So
the screening examination for the SDB in childhood wasrelatively subjective but the ambulatory monitoring mighthelp to remedy this situation in the future [92].
Due to a lack of standard diagnostic resources and ongo-ing changes in a child’s anatomy and physiology frominfancy to adolescence, therapeutic strategies for childhoodOSA remain challenging. Unlike adult patients who mayundergo uvulopalatopharyngoplasty (UPPP) and MMA sur-geries, surgeries such as adenotonsillectomy or tonsillarpillar manipulation are generally considered to be the stan-dard treatment for childhood sleep apnea to relieve airwayobstruction in the retroglossal region, the nose, and/or theretropalatal area [93, 94].
Children with craniofacial abnormalities resulting inmaxillary or mandibular insufficiency may benefit fromOA or surgery [86, 95]. There is no long-term report onwhether childhood jaw surgeries cause alterations in jawgrowth. Some investigators encourage that if the signs andsymptoms of SDB had been noticed, the young patientshould be referred to a sleep medicine specialist in conjunc-tion with an orthodontist if there are dentoskeletal abnor-malities [92].
Rapid maxillary expansion (RME), as a powerful ortho-pedic OA for maxillary transverse deficiency, was found tobe a useful approach in dealing with abnormal breathingduring sleep in children. Pirelli and co-investigators [96]recruited 31 children with OSA in addition to maxillaryconstriction using RME to expand the maxilla for10–20 days followed by orthodontic treatment for 6 to12 months. They found the mean AHI was decreased from12.2±2.6 to 0.4±1.1 events/hour. The investigators were notsure if the study indicated the RME should be the firsttreatment approach for the children with adenotonsillarenlargement because they only enlisted the subjects withabsence of adenotonsillar hypertrophy. A systematic reviewevaluated 15 articles based on inclusion criteria and con-cluded that RME improved nasal breathing for an average of11 months of stability [97]. The review also indicated thatall the studies selected had methodologic deficiencies suchas less randomization and a lack of double-blindedinvestigation.
An OA is probably more conservative and predictable asit has a similar mechanism as an orthodontic functional fordeveloping children. The treatment procedure also requiresa sleep study in addition to the same baseline records (ceph-alometric and panoramic X-rays, study models, intra-/extra-oral photos) as used in traditional orthodontic patients. Intwo 6-month trials on children OSA patients treated withtwo types of OA [98, 99], both found significant improve-ment on AHI in OSA subjects. The initial problems with useof the OAs were salivation [98, 99] and discomfort onwaking [98] which gradually diminished after a few daysof wear. A pilot study at the University of British Columbia
Sleep Breath
orthodontic program demonstrated that selected Class II,Division 1 pediatric snoring/OSA patients undergoing OAtreatment had a fast adaptation, different titration strategy,accommodated the mixed to permanent dentition transition,rapid tooth movement, and had exhibited both tissue-bornein addition to tooth-borne retention. The outcome of suchtreatment over a long term is under investigation includingits impact on growth development.
Conclusion
In summary, an OA for OSA requires full documentation ina medical/dental history, and a sleep study to be able toselect prospective candidates. OA therapy is not a cure butappears to be an important treatment option for OSApatients who meet indications for this therapy. Further ran-domized controlled trials on OAs for pediatric patients needto be designed and investigated. Dentists who are responsi-ble for treating OSA and/or snoring may need to upgradetheir knowledge in dental sleep medicine. Sleep physiciansalso may need to further develop a working relationshipwith dentists to provide more treatment options for diag-nosed patients. Titration and side-effect management as wellas close follow-up during OA treatment are keys to achievecompliance and treatment success over the long term. Long-term OA outcome investigations require efficient patientinformation update systems and more objective measure-ments should be taken into consideration during assess-ments of covert compliance.
Acknowledgment The authors would like to thank Mrs. Ingrid Ellisfor her editorial assistance in the final preparation of this manuscript.
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