Chapter 16

Oral appliances
J.A. Fleetham* and F.R. Almeida#

Summary
Oral appliances are commonly used for the treatment of snoring and obstructive sleep apnoeahypopnoea (OSAH). Oral appliances increase the size of the upper airway. Mandibular advancement splints (MAS) are the most widely used type of oral appliance. There is increasing evidence that MAS improve sleepiness, blood pressure and indices of sleep-disordered breathing. Continuous positive airway pressure (CPAP) is more effective than MAS in improving sleepiness, health status and indices of sleep-disordered breathing. CPAP remains the primary treatment for severe OSAH. Current guidelines recommend oral appliances as a primary treatment for patients with mild-to-moderate OSAH. Oral appliances are the best alternative treatment for patients with OSAH who are unwilling or unable to comply with CPAP therapy. Oral appliance therapy may also be indicated as an adjuvant to CPAP when the patient is away from home or electrical power. Oral appliance therapy should be supervised by both medical and dental specialists. MAS should not be recommended for patients with major periodontal disease. Follow-up sleep monitoring is needed to verify the efficacy of oral appliance therapy. Patients treated with oral appliances require long-term medical and dental follow-up care. Keywords: Mandibular advancement device, mandibular advancement splint, obstructive sleep apnoea-hypopneoa, oral appliance, tongue retaining device, snoring
*Dept of Medicine, Faculty of Medicine and # Oral health Sciences, Faculty of Dentistry, UBC, Vancouver, BC, Canada. Correspondence: J.A. Fleetham, The Lung Centre, 7th Floor, 2775 Laurel Street, Vancouver, BC V5Z 1M9, Canada, Email John.Fleetham@vch.ca

Eur Respir Mon 2010. 50, 267285. Printed in UK all rights reserved. Copyright ERS 2010. European Respiratory Monograph; ISSN: 1025-448x. DOI: 10.1183/1025448x.00025209

bstructive sleep apnoeahypopnoea (OSAH) is a common syndrome that is characterised by recurrent episodes of partial or complete upper airway obstruction during sleep. Currently, the primary treatment for OSAH is nasal continuous positive airway pressure (CPAP). However, some patients are unable to tolerate and comply with CPAP on a long-term basis. Oral appliances are now widely used for the treatment of snoring and mild-to-moderate OSAH, both as primary therapy and as an alternative for patients who are unwilling or unable to tolerate CPAP. Oral appliances are a simple, reversible, quiet, and cost-effective therapy for selected patients with OSAH. However, oral appliances as therapy for OSAH remain underutilised. There are a variety of synonyms for oral appliances. In addition to oral, they may be called intraoral, dental or mandibular; instead of appliance, they may be called a device, splint or prosthesis. Oral appliances can be divided into two major types: 1) those that reposition the mandible and the attached tongue, the mandibular advancement splints (MAS) or mandibular advancement device (MAD),

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and 2) those that hold the tongue forward, the tongue retaining devices (TRD). Prior to treatment with any oral appliance, a complete assessment by an experienced physician, within the field, is important. Having concluded that treatment with an oral appliance is indicated, the physician provides the dentist, who should be knowledgeable in sleep medicine and have skills and experience in oral appliance therapy, with a written referral and a copy of the sleep diagnostic report. Oral appliances improve OSAH because of an increase in upper airway size, the provision of a stable anterior position of the mandible, advancement of the tongue or soft palate, and possibly by a change in genioglossus muscle activity. Oral appliance therapy for OSAH is a long-term commitment, so it is important that the appliance must be comfortable for the patient. Finally, as is the case with CPAP, oral appliances can only be used to treat OSAH in cooperative patients who are motivated to wear the oral appliance during sleep on a regular and consistent basis every night. This chapter provides an update to previous recent reviews [13] and summarises the recent recommendations from both the Cochrane Collaboration [4] and the American Academy of Sleep Medicine [5]. It provides an overview of the effectiveness of treatment, the predictors of treatment success, adherence and the potential adverse effects associated with this treatment. It also outlines a detailed clinical protocol and titration sequence for MAS, since this clinical procedure is often not well understood by practitioners new to the field. This chapter only focuses on the use of oral appliances in the adult population. Little is known about the efficacy and side-effects of oral appliances for children without craniofacial abnormalities [6, 7]. Orthodontic treatment for children with OSAH and craniofacial anomalies has been shown to be effective not only for the dentition, but also in decreasing respiratory disturbances in children [8, 9].

Appliance
ORAL APPLIANCES

Types of appliances
A large number of different oral appliances are currently available for the treatment of OSAH. Oral appliances increase the size of the upper airway by either advancing the mandible or the tongue. There are other minor design differences in currently available oral appliances that may also impact on their success and treatment adherence. MAS are most widely used and utilise traditional dental techniques to attach the appliance to both dental arches and maintain the mandible in a forward position.

Figure 1 illustrates some common appliances used for the treatment of sleep apnoea: 1) tongue stabilising device Aveo-TSD1 (Innovative Health Technologies, Christchurch, New Zealand), SomnoDent1 MAS (SomnoMed, Denton, TX, USA), PM Positioner1 (Great Lakes Orthodontics University, Ltd, Tonawanda, NY, USA), Monoblock appliance (courtesy of M. Marklund, Umea Sweden), HerbstTM (Great Lakes Orthodontics Ltd), MDSA1 (Medical Dental Sleep Appliance; R.J. and V.K. Bird Pty Ltd, Melbourne, VIC, Australia) and KlearwayTM (Great Lakes Orthodontics Ltd). Construction usually requires dental impressions, bite registration and fabrication by a dental laboratory.
Some MAS are available in a prefabricated form and are sometimes referred to as boil and bite [10], but have limited efficacy [11]. These can either be fitted by the patient, themselves, or moulded to the patients teeth in an office setting. Some MAS restrict mouth opening by means of screw mechanisms, whereas others allow relatively unhindered movement. There have been two significant advances in the MAS design over the past 15 yrs. Adjustable appliances that allow the progressive advancement of the mandible, and the use of materials and designs that improve intraoral retention, are major improvements. Determining the optimal degree of mandibular advancement is the most important step when using MAS therapy successfully. The amount of anteroposterior mandibular movement, similar to the amount of CPAP and the speed with which this can be changed, varies considerably between patients. MAS have been developed with an adjustable hinge that allows progressive advancement of the mandible, after initial construction, until the optimal mandibular position is achieved. Singlepiece or nonadjustable appliances often need to be remade if the initial jaw advancement proves to

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be insufficient. MAS sometimes include anterior tubes or openings that allow for oral breathing or pressure relief. Some oral appliances feature a posterior extension of the maxillary component to modify the position of the soft palate or tongue, but this type of appliance has not been widely studied. A subgroup of patients, particularly those who suffer from sleep bruxism [12], seem to experience jaw discomfort in the morning after wearing a rigid, hard acrylic, single-jaw positioned MAS. MAS have been further developed to allow lateral jaw movement, as well as some degree of vertical jaw opening. There have been major advances made in dental materials, which have lead to improved flexibility and strength of thermosensitive acrylic resin materials. MAS made of temperature-sensitive material, which the patient can heat in hot water prior to insertion and that cool and harden intraorally, provide considerably more retention than traditionally designed coldcure acrylic MAS. The combination of adjustability, lateral and vertical jaw movement, increased retention and better defined titration protocols, have significantly improved the effectiveness of MAS over the last decade.

a)

b)

c)

d)

e)

f)

g)

h)
J.A. FLEETHAM AND F.R. ALMEIDA

Figure 1. Different types of oral appliances used for the treatment

of obstructive sleep apnoeahypopnoea. a) Aveo-TSD1 (Innovative Health Technologies, Christchurch, New Zealand). b) SomnoDent1 MAS (SomnoMed, Denton, TX, USA). c) PM positioner1 (Great Lakes Orthodontics Ltd, Tonawanda, NY, USA). d) Monoblock appliance (courtesy of M. Marklund, Umea University, Sweden). e) HerbstTM (Great Lakes Orthodontics Ltd). f) MDSA1 (Medical Dental Sleep Appliance; R.J. and V.K. Bird Pty Ltd, Melbourne, VIC, Australia). g) KlearwayTM (Great Lakes Orthodontics Ltd), lateral view. h) KlearwayTM, hinge view.

The other major type of oral appliance available is the TRD or tongue stabiliser device (TSD), which keeps the tongue in an anterior position during sleep by means of negative pressure in a soft plastic bulb. It fits over both the mandibular and maxillary arches and has a flange that is placed between the lips and teeth, keeping the appliance stable in the mouth. This appliance was one of the first to be developed and is available in both a fabricated and prefabricated form [1315]. It has recently been evaluated for dentate patients [16]. It is mainly used in edentulous patients and is the oral appliance of choice for patients with no teeth, limited anterior-posterior mandibular movement or a very large tongue.

Mechanisms of action
The majority of oral appliances are designed to maintain the mandible and/or tongue in a protruded posture, thereby preventing upper airway obstruction during sleep. Proposed mechanisms of action

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for oral appliances include increased upper airway size, decreased upper airway collapsibility, activation of upper airway dilator muscles, and stabilisation of mandibular posture. Several different upper airway-imaging techniques have been used to assess changes in upper airway size and function with oral appliances in patients with OSAH. These imaging techniques include cephalometry, computed tomography (CT), magnetic resonance imaging (MRI) and videoendoscopy [17]. Voluntary mandibular and tongue protrusion have been shown to increase upper airway size and alter upper airway shape, particularly in the velopharynx, in subjects with and without OSAH [18]. Several studies have demonstrated an increase in the anteroposterior diameter of the upper airway following MAS insertion [1921], an example is shown in figure 2. This increase was predominantly in the oropharynx and hypopharynx, but some studies have also suggested an effect on the velopharynx [22]. Nonadjustable MAS constructed in the most advanced position without causing discomfort or at 75% of mandibular advancement, have shown an increase in the total volume of the upper airway and cross-sectional areas of the retropalatal and retroglossal regions using CT [23, 24]. Two studies, which used MRI, showed that with mandibular advancement the velopharynx cross-sectional area and volume increases, and that this change was predominantly attributed to an increase in the lateral dimensions [25, 26]. These upper airway changes were associated with an increase in lower anterior facial height, higher position of the hyoid, lateral displacement of the parapharyngeal fat pads away from the airway and anterior positioning of the base of tongue muscles [26].
a)

ORAL APPLIANCES

Almost all of these upper-airway imaging studies have been performed during wakefulness and it is unknown whether the same changes occur during sleep. MAS have also been shown to increase upper airway muscle tone, which may also contribute to an increased upper airway patency [27].

Contradictions
MAS normally requires at least eight teeth in each of the maxillary and mandibular arches to support the appliance in the absence of advanced periodontal disease. Furthermore, the patient should be able to advance their mandible by at least 5 mm without discomfort. Temporomandibular joint disease is common in patients with OSAH [28] and should not be considered as a contraindication. The concern about MAS treatment in patients with temporomandibular joint disease was raised because of mild initial and transitory side-effects of MAS wear, such as pain in the temporomandibular joint and masticatory muscles. It is important to determine, during the clinical exam, whether there is any noise and/or pain in the temporomandibular joint, the degree of mandibular movement and any masticatory muscle tenderness. When temporomandibular joint disease was assessed with MRI, MAS appeared not to cause or increase temporomandibular joint disease over a 1-yr treatment period [29]. Furthermore, if MAS are used in combination with mandibular physiotherapy, patients with previous

b)

Figure 2. Lateral cephalometry of a male patient a) without and b) with a mandibular advancement oral appliance. Note the advancement of the mandible and an increase in the size of the velopharynx with the mandibular advancement oral appliance (b).

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Cross-sectional area of velopharynx mm2

temporomandibular disease are able to use MAS [30]. Therefore, the presence of temporomandibular disease is not currently a contraindication for MAS treatment. Sleep bruxism has been reported to be more prevalent in patients with OSAH [12, 31], and MAS treatment can be used in patients with bruxism. The MAS can help prevent tooth wear and has been associated with a remarkable reduction in sleep bruxism motor activity in patients with OSAH [32]. Finally, bruxism occlusal splints have been shown to exacerbate OSAH [33].

300

250 200 150 100 50 0

#

Treatment optimisation

The optimisation of MAS treatment is quite different from CPAP treatment, which can either be performed Figure 3. Increase in cross-sectional area of the velopharynx after the insertion of a during polysomnography (PSG) or with an automatic mandibular advancement splint (MAS). CPAP machine. Patients may not be able to initially # : median values. n515 and p,0.005. tolerate the degree of mandibular advancement Reproduced from [19] with permission from required to completely relieve the OSAH. There are a the publisher. variety of studies that show how the decrease in apnoea/hypopnoea index (AHI) is dependent upon the amount of mandibular advancement (figs 3 and 4) [19, 3437]. MAS cannot easily be tried for a single night to predict treatment success and patient adherence, and may require up to 6 months of progressive mandibular advancement. One study has used a prefabricated boil and bite mandibular advancement appliance as a screening tool for MAS therapy [11]. This randomised controlled cross-over study found that a prefabricated appliance had a 31% compliance failure, whereas a custom-made appliance showed only a 6% compliance failure. The prefabricated appliance showed an exceptionally high total failure rate of 69%, while the failure rate of the custom-made appliance was 40%. The study concluded that prefabricated boil and bite appliances cannot be recommended as a therapeutic option, nor can they be used as a tool to identify good candidates for MAS therapy. Several studies have evaluated whether titration of mandibular advancement during PSG could be used to optimise MAS treatment, similar to CPAP titration [3842]. The first study of overnight titration used MAS that was removed from the patients mouth and adjusted manually [38]. Other titration studies have used a temporary appliance that can be adjusted by either waking or not waking the patient [39, 40]. The MAS was advanced either manually, after the removal of the temporary appliance [41], by using either a hydraulic system [39], or by remote control of a motorised system [40]. These studies had mixed results in predicting the amount of mandibular advancement needed for successful MAS therapy. Overnight titration of MAS remains an experimental approach and the technology for remote controlled advancement is not yet widely available. The efficacy of titration and timing for repeat-sleep monitoring concerning MAS titrations requires further study. KRISHNAN et al. [42] have shown that although 55% of patients achieve successful self-titration at home, another 32% can reach success with further PSG-guided titration. ALMEIDA et al. [43] showed that titration at night can improve the results, after the usual clinical advancement of the MAS, by up to 35%. The protocol is simple to implement in the sleep laboratory, with the technologist asking the patient to advance the appliance in 1-mm increments if the patient continues to snore or have persistent apnoea, hypopnoea or arterial oxygen desaturation episodes. However, the patients should not be woken more than three times per night in order to achieve an adequate total sleep time.
J.A. FLEETHAM AND F.R. ALMEIDA

Pre Post Insertion of MAS

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a)

100

Effectiveness

The treatment of OSAH should always be individualised for each 50 patient and the future goal is to develop customised treatment, based on each patients phenotype. 0 The patients age, occupation, severity of symptoms, body mass index, comorbid disease, lifestyle -50 and treatment-outcome expectations, may all influence the OSAH b) 200 treatment decision taken. Approxi mately 50% of patients achieve a 150 AHI f10 events?h-1 with MAS treatment [1], and it is often the 100 patients preferred choice of treat ment over CPAP. Although not as 50 efficacious as CPAP, oral appli ances should be considered first 0 line treatment in patients with mild-to-moderate OSAH and who -50 -10 0 10 20 30 40 prefer oral appliances to CPAP, are not appropriate candidates for AHI CPAP, or fail treatment attempts with CPAP or treatment with beFigure 4. Relationship between the change in apnoea/hypopnoea index (DAHI) and a) the absolute (r50.64, p50.01) and b) the havioural measures. Patients with proportional (r50.64, p50.01) change in cross-sectional area severe OSAH should always have an (DCSA) of the velopharynx, following the insertion of a mandibular initial trial of nasal CPAP because advancement splint. Reproduced from [19] with permission from the greater effectiveness has been shown publisher. with this treatment than with oral appliances [5]. Despite MAS therapy being less effective in severe OSAH, HENKE et al. [44] suggested that severity of OSAH and the site of airway closure should not be used to exclude patients from MAS treatment. In the first practice parameters paper by the American Sleep Disorder Association,on the efficacy of oral appliance treatment for OSAH, published in 1995 [45], the majority of the data were from uncontrolled case series studies, which were subject to study design issues such as regression to the mean, and selection and reporting bias. The second practice parameters paper by the American Academy of Sleep Medicine was published in 2006 [5], and included six randomised, controlled trials comparing MAS with an inactive control [4, 4649]. Furthermore, there are approximately ten randomised controlled trials comparing MAS with CPAP, and 12 studies comparing different types of oral appliances.
CSA % CSA mm2

ORAL APPLIANCES

MAS versus placebo

There are six randomised controlled trials on 375 patients comparing active MAS with control oral appliances [4651], and there are two randomised controlled trials on 39 patients comparing TRD with placebo [52, 53]. MAS has been shown to significantly improve objective sleep measurements, such as AHI, arousal index, snoring and in some but not all studies, arterial oxygen desaturation. MAS have also been shown to improve objective measurements for sleepiness when examined using the multiple sleep latency test [47], but not the multiple vigilance test [50]. MAS improved subjective measurements of sleepiness (Epworth Sleepiness Scale) in all but one study [51].

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Neurobehavioral and cognitive function have only been evaluated in a few studies, which demonstrated that MAS can improve cognitive function, tension-anxiety, vigor activity, fatigueinertia, reaction time and quality of life when compared with placebo [49, 50]. MAS therapy was well accepted and o68% of patients report MAS adherence for most nights and for 67 hours per night. MAS has also been shown to significantly reduce systolic (mean 3.03 mmHg), diastolic (mean 3.4 mmHg) and mean (mean 3.6 mmHg) blood pressure measurements when compared with placebo [48]. Finally, with MAS treatment of OSAH, a significant proportion of nondipper subjects regained their normal nocturnal dip in blood pressure when compared with placebo [50]. Table 1 summarises the randomised controlled trials comparing MAS with placebo.

MAS versus CPAP

There are at least 10 randomised controlled trials, with seven crossover studies, which have compared the efficacy of MAS with CPAP [4, 50, 5461, 62]. Although both CPAP and MAS led to improvements in objective sleep measurements, such as AHI, arousal index and minimum arterial oxygen saturation, the magnitude of improvement in AHI was significantly greater with CPAP. Subjectively and objectively, MAS decrease sleepiness to the same degree as CPAP. MAS decrease subjective and objective measurements of snoring in the majority of the patients. MAS and CPAP are effective treatments compared with placebo in improving quality of life and symptoms, and some studies have shown MAS to be superior to CPAP. BARNES et al. [50] showed that CPAP improved vigilance, complex cognitive function, and several mood subscales, whereas MAS improved the complex cognitive function task. These results are controversial and additional studies are needed to establish any differences between MAS and CPAP therapy for OSAH on neurobehavioral outcomes [63]. Table 2 summarises the randomised controlled trials comparing MAS with CPAP. OSAH is considered a potential risk factor for cardiovascular disease and recent studies have demonstrated a significant increased risk of fatal cardiovascular events in untreated sleep apnoea patients [64]. There are limited randomised trial data comparing cardiovascular health outcomes with MAS and CPAP. In a crossover study, no change in blood pressure was observed with the use of CPAP, but MAS decreased nocturnal diastolic blood pressure and significantly increased the proportion of subjects with a normal night-time dip in blood pressure [50]. In a parallel design study, there were no echocardiogram changes with either CPAP or MAS treatment; MAS but not CPAP treatment did decrease brain natriuretic peptide in this study [62]. At present, all of the randomised controlled trials have been short-term studies over 36 months. There are only nonrandomised studies establishing long-term efficacy over 45 yrs [65, 66], confirming high acceptance of MAS treatment. MAS therapy may also be indicated as an adjuvant to nasal CPAP when the patient is away from home or electrical power [67], or in conjunction with CPAP, in an effort to decrease CPAP pressure and therefore increase CPAP adherence [68].
J.A. FLEETHAM AND F.R. ALMEIDA

Comparisons of different oral appliances

Oral appliance design has been proposed as an important determinant regarding treatment compliance and success; there have been at least ten prospective comparative studies evaluating different oral appliance designs [4, 69, 70]. There have been varying degrees of improvement in the indices of sleep-disordered breathing and side-effects with different MAS. These differences may be related to the degree of vertical opening and mandibular advancement achieved with each MAS. In an evaluation of different custom-made, titratable mandibular advancement appliances, with similar vertical opening and similar advancement, the design does not appear to play a major role in the different efficacy between the various oral appliances [6974]. Therefore, there are no preferred MAS, as long they are properly adjusted and patient comfort is achieved. Despite the similarities in efficacy, there are differences in patient preference and side-effects, which emphasises the importance of a dentist with experience in this field being involved. Only one

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ORAL APPLIANCES

Table 1. Summary of the findings in randomised controlled trials comparing mamdibular advancement splints (MAS) with placebo Device SomnoDent1 MAS PSG Measurements Significant improvements compared with placebo

First author [Ref.] Year of study 28

Patients n

M EHTA [46]

2001

J OHNSTON [51]

2002

20

Monoblock appliance

ESS Snoring Sleep quality Compliance Acceptance PSG ESS Snoring

G OTSOPOULOS [47]

2002

73

SomnoDent1 MAS

Compliance PSG

ESS MSLT Subjective Acceptance 67 SomnoDent1 MAS PSG 24 h BP

G OTSOPOULOS [48]

2004

B ARNES [50]

2004

114

MDSA1

Compliance PSG

Significant improvements: AHI 53%, arousal index 34%, snoring frequency 47%, no significant change in Sa,O2 10.1 to 3.9 Total or partial improvement in 70% Improved in 96% 87.5% reported nightly use 96% wanted to continue treatment Reduction in AHI and oxygen desaturation index No difference 53% MAS versus 29% placebo reported subjective reduction 68% used almost all or all nights 52% reduction in AHI, higher minimum Sa,O2, improvements in snoring measurements (frequency and intensity), arousal index and sleep quality Significantly decreased ESS with MAS Significantly increased MSLT Reduced reported apnoea, more mild side-effects than placebo 99% wanted to continue treatment and used average 6.7 h per night 50% reduction of AHI, significant improvement in minimum Sa,O2 and arousal index Reduced 24 h systolic bp reduced by 3.03 mmHg; diastolic BP reduced by 3.4 mmHg and mean BP reduced by 3.6 mmHg 6.8 h per night Improvement in AHI, oxygen desaturation index, decreased stage 1 sleep and increased slow wave sleep

Significant improvements compared with placebo

PSG: polysomnography; AHI: apnoea/hypopnoea index; Sa,O2: arterial oxygen saturation; ESS: Epworth Sleepiness Scale; MSLT: multiple sleep latency test; BP: blood pressure; MWT: maintenance of wakefulness test; VAS: visual analogue scale; FOSQ: function outcome sleep questionnaire; SF36: Short Form 36 Health Survey. SomnoDent1 MAS (SomnoMed, Denton, TX, USA); Monoblock appliance (M. Marklund, UMEA University, Sweden); MDSA1 (Medical Dental Sleep Appliance; R.J. and V.K. Bird Pty Ltd, Melbourne, VIC, Australia).

Improved Improved night diastolic blood pressure, significant proportion of nondipper patients regained normal dip No change No change Improved Change in tension-anxiety domain only Improved mean score and social outcome domain Improved overall score 55% reduction in AHI, minimum Sa,O2 and arousal index improved Improved Improved vigour-activity and fatigue-inertia scales Improved 6.7 h per night

randomised crossover study has examined the impact of vertical opening and efficacy of MAS [75], and it demonstrated a tendency for MAS with less vertical opening to be more effective, and the less vertical opening resulted in better patient acceptance. There are also studies that have examined other oral appliances, such as soft palate lift, TRD and prefabricated devices. In a small crossover design study comparing MAS, soft palate lift appliance and TRD, the MAS was found to be an effective and welltolerated oral appliance, while the soft palate lift was neither effective in reducing AHI or accepted by patients, and the TRD though well accepted showed limited efficacy in the treatment of severe OSAH [76]. A randomised crossover trial of a new design of TRD, called a TSD, showed that the MAS and TSD had similar efficacy in the reduction of AHI and improvement on oxygen saturation. However, the MAS was found to be overwhelmingly better accepted than the tongue stabilising device [16].

ESS Profile mood state Choice reaction time Compliance

ESS 24 h BP MWT, vigilance VAS for alertness Executive cognition Profile mood state FOSQ SF36

Measurements

PSG

Patients n

Comparison of oral appliance with surgery

There is one longitudinal parallel group study [77], which compared the effectiveness of MAS with uvulopalatopharygoplasty (UPPP), in patients with mildto-moderate OSAH over a 4-yr period, with subsequent reports on the same patient pool [37, 78, 79]. This randomised parallel study, assessed 45 patients treated with a MAS and 43 with UPPP. At the 1-yr follow-up, MAS showed a higher success rate in controlling the AHI when compared with UPPP (78 versus 51%). A total of 32 MAS and 40 UPPP patients completed the

First author [Ref.] Year of study

Table 1. Continued

N AISMITH [49]

2005

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73

SomnoDent1 MAS

Device

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ORAL APPLIANCES

Table 2. Summary of randomised controlled trials comparing mandibular advancement splints (MAS) with continuous positive airway pressure (CPAP) Device PSG MAS and CPAP AI, AHI, minimum Sa,O2 CPAP5MAS AHI decreased in CPAP Measurements Significant changes Significant changes compared with baseline compared with CPAP Treatment preference 19 patients MAS, 1 patient CPAP, 1 patient not using CPAP or MAS

First author [Ref.]

Year of Patients n study

C LARK [58]

1996

23

HerbstTM

SSQ

F ERGUSON [54]

1996

25

Snore-guard

PSG

CPAP and MAS both showed significant improvement MAS and CPAP improved AHI and AI CPAP decreased AHI 62% and MAS 48%, only CPAP increased Sa,O2

23 patients MAS, 2 patients CPAP

Questionnaire

F ERGUSON [55] Questionnaire

1997

20

Silencer

PSG

CPAP lower AHI, only CPAP increased Sa,O2

Greater satisfaction with MAS

R ANDERATH [59]

2002

20

HerbstTM PSG

CPAP decreased AHI and improved sleep architecture AHI CPAP.MAS

MAS easier and preferred over CPAP No preference

E NGLEMAN [57] PSG

2002

48

Monoblock appliance

Snoring, unrefreshed sleep, sleepiness and fatigue MAS and CPAP improved AHI and AI Snoring, unrefreshed sleep, sleepiness and fatigue MAS and CPAP improved AHI and arousals N/A

T AN [56]

2002

24

Monoblock appliance and modified silencer ESS

ESS FOSQ MWT Cognitive PSG

MAS and CPAP improved AHI, arousals MAS and CPAP improved

CPAP.MAS MAS.CPAP MAS5CPAP MAS5CPAP Only CPAP increased Sa,O2, CPAP5MAS in AHI and arousal index MAS5CPAP

17 out of 21 patients preferred MAS

Table 2. Continued Device MDSA1 PSG Measurements Significant changes Significant changes compared with baseline compared with CPAP Treatment preference 36% patients MAS

First author [Ref.]

Year of Patients n study

B ARNES [50]

2004

114

44% patients CPAP

H OEKEMA [61] H OEKEMA [60]

2007 2007

48 20

TAP1 TAP1

N/A parallel study N/A parallel study

H OEKEMA [62]

2008

28

TAP1

MAS and CPAP improved CPAP.MAS AHI and Sa,O2, decreased stage 1 sleep and increased slow wave sleep ESS Improved CPAP5MAS MWT Improved CPAP5MAS FOSQ Improved FOSQ only MAS better than placebo PVT lapses MAS decreased diastolic CPAP.MAS BP BP MAS.CPAP, only with MAS a significant proportion of nondipper subjects regained nocturnal dip Sexual function No improvement MAS5CPAP PSG MAS and CPAP improved MAS5CPAP AHI, min Sa,O2 ESS CPAP and MAS both MAS5CPAP decreased Driving CPAP and MAS both MAS5CPAP performance improved NT-pro-BNP MAS showed improvement Only MAS improved NT-pro-BNP

N/A parallel study

PSG polysomnography; AI: apnoea index; AHI: apnoea/hypopnoea index; Sa,O2,: arterial oxygen saturation; SSQ: sleep symptoms questionnaire;ESS: Epworth sleepiness scale; FOSQ: function outcome sleep questionnaire; MWT: maintenance of wakefulness test; PVT: psychomotor vigilance task; BP: blood pressure; NA: nonapplicable; NTpro-BNP: amino-terminal fragment of pro-brain natriuretic peptide. HerbstTM (Great Lakes Orthodontics Ltd, Tonawanda, NY, USA).

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4-yr follow-up [65]. According to predetermined criteria for OSAH (apnoea index (AI) o5 or AHIo10 events?h-1), 63% of the patients in the MAS group attained normalisation after 4 yrs, a proportion that was significantly higher than the 33% among the patients in the UPPP group. This study suggests that MAS was more effective than UPPP in improving indices of sleep-disordered breathing. However, the significance of this finding is questionable, as there is no definitive evidence of the effectiveness of this type of corrective upper airway surgery. MAS have also been used as combination therapy in patients who have had an unsuccessful response to UPPP [80].

Cardiovascular health
There are two randomised controlled trials with intention-to-treat analysis [48, 50] and three nonrandomised prospective studies [8183] in which MAS treatment of OSAH has been shown to reduce blood pressure measurements. These changes are primarily in diastolic blood pressure and re-establishing the nocturnal dip. One study found a correlation between the improvement in AHI and a decrease in blood pressure after MAS treatment [81]. Another study, found that there was no change in blood pressure with CPAP, whereas MAS significantly improved the nocturnal diastolic blood pressure and increased the proportion of subjects with a normal night-time dip in blood pressure [50]. In the evaluation of biomarkers for oxidative stress and inflammation, one study has shown that treatment with MAS improves cardiovascular pathophysiologic factors, such as endothelial function after 3 months and 1 yr of MAS treatment [84]. The endothelial function in the MAS group was not different from a reference non-OSA group. A year of treatment resulted in a normalisation of malondialdehyde levels and a decrease in thiobarbituric acid-reactive substance levels, despite residual sleep-disordered breathing (average AHI of 19 events?h-1). In a parallel study, comparing MAS with CPAP, MAS improved amino-terminal fragment of pro-brain natriuretic peptide [64].
ORAL APPLIANCES

Partner health status

Partners of patients with OSAH have impaired health status, probably due to sleep fragmentation related to the patients loud snoring and restless sleep pattern. Treatment of patients with snoring and OSAH might be beneficial, not only for the patient, but for the bed partner and the couple relationship. MCARDLE et al. [85] reported significant impairment in sleep quality of OSAH bed partners without improvement in objective sleep quality after treatment with CPAP. In contrast, DOHERTY et al. [86], showed significant improvements in bed partner health status following CPAP. In one study sleep changed to better or much better in 64.1% of the bed partners following MAS treatment for OSAH [87] in another report, an improvement in intimate relationships and sexual activity following MAS treatment for OSAH was seen [71].

Treatment
Predictors of treatment success
A variety of clinical, physiological and PSG variables have been identified as possible predictors of MAS treatment success [8891]. It has been suggested that, a younger patient [92, 93] with a lower AHI [46, 88, 93], a smaller neck circumference [50], a lower body mass index [91] and positional OSAH [86, 92, 94] would be more likely to achieve treatment success with MAS. Patients who achieve a greater degree of mandibular advancement have the highest decrease in AHI [35, 95], and females have higher success rates than males. Treatment success may be inversely related to pre-treatment severity, but this relationship may just be a function of the definition of treatment success, although one study has shown that the higher the AHI pre-treatment, the greater the decrease in AHI that could be achieved [44]. Several upper airway skeletal and soft tissue measurements made from pre-treatment lateral cephalometry have been shown to be associated with treatment success. These include a more

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micrognathic or retrognathic mandible, small soft palate and tongue and larger retropalatal area [19, 50, 96, 97]. Upper airway fluoroscopy has also been proposed as a technique to guide successful MAS therapy. A hypopharyngeal site of obstruction may be associated with a better ller manoeuvre, together with treatment outcome. A study of upper airway MRI during a Mu mandibular advancement, has shown that improvement in upper airway patency correlates with treatment success [98]. However, there is considerable overlap between good and poor treatment response in these studies. More recently, physiological assessments of nasal resistance and pulmonary function have shown to be of some predictive value [99, 100]. The utility of any treatment recommendation for MAS based on clinical features, OSAH severity or upper airway anatomy is still questionable and requires prospective validation.

Treatment adherance
The treatment adherence and side-effects of oralappliance treatment differ depending on the type of the appliance, disease severity and patient supervision [101, 102]. Adherence is usually measured subjectively, with the exception of one study in which a compliance monitor indicated that the MAS was worn for a mean of 6.8 h per night [103]. Self-reported treatment adherence has been reported as high as 96% for patients using MAS .75% of the nights and 80% of patients using MAS .75% of each night [54]. Treatment adherence varies between each oral appliance type and appears better with mandibular advancement rather than tongue retaining appliance or boil and bite type appliances. 40% of nonadherence occurs within the first 6 months [104]. The most common reasons to stop using the appliance are discomfort and/or because the patient finds it cumbersome (46%) and it has no or little effect (36%).
J.A. FLEETHAM AND F.R. ALMEIDA

Adherence rates vary widely between studies with a minimum of 4% to a maximum of 82% of adherence after 1 yr of treatment [78]. Adherence rates appear to decrease with the duration of use. In a study of 630 patients, MARKLUND et al. [88] described an adherence of 75% of the patients after 12 months of treatment. After a 25-yr follow-up period, studies have revealed adherence rates from 48% up to 90% [105107], and this has been reported as 60% at 1 yr and 48% at 2 yrs. Previous experience with nasal CPAP suggests that self-reported treatment adherence tends to overestimate actual use. Studies with CPAP have identified that subjective adherence is often higher than objective adherence. Therefore, until there is an adherence monitor available for oral appliance therapy, caution should be taken in the reporting of subjective oral appliance adherence. Table 3 provides a summary of studies evaluating oral appliance adherence rates after a minimum of 1-yr treatment plan.

Side-effects
The main reasons for discontinuing treatment have been reported to be insufficient reduction of snoring and the presence of side-effects [95]. Most side-effects caused by MAS are usually described as mild and transient, most frequently reported as dry mouth, excessive salivation, mouth or teeth discomfort, muscle tenderness and jaw stiffness. Significant and persistent temporomandibular joint (TMJ) problems are rare [1]. One study evaluated the TMJ of seven patients, using MRI, over a mean period of 11 months and concluded that MAS, in the titrated position, appeared to be innocuous to the TMJ in OSA patients [95]. Excessive salivation, mouth dryness, morning-after occlusal changes and discomfort in the gums, teeth or jaw are common side-effects in the first weeks of MAS therapy, but usually resolve with time [104, 109]. More persistent and severe side-effects, which include TMJ dysfunction and dental crown damage, appear uncommon [108]. MAS adjustment can decrease side-effects by reducing pressure on the anterior teeth and excessive mandibular advancement. Side-effects vary between the types of oral appliance used, with tongue pain occurring in tongue retention appliances and gagging associated with appliances that have a maxillary component to modify soft palate position. Long-term sideeffects are more recently described evaluating oral appliance side-effects over a period of more

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Table 3. Adherence rates of mandibular advancement splints in selected studies that evaluated adherence after a minimum of 1 year First author [Ref.] M CG OWN [101] D ORT [102] M ARKLUND [88] DE A LMEIDA [104] M ARKLUND [108] G INDRE [34] Year of study 2001 2004 2004 2005 2006 2008 Interval months 22 22 12 68 60 17 Patients n 166 110 630 544 450 66 Comliance rate WCS/BCS 42/56 40/57 75/76 30/64 56/56 82/82

WCS: worst case scenario, which relates to an analysis interpretation of patients who did not return the questionnaires as compliance failures. BCS: best case scenario, which relates only to the percentage of patients who responded to the questionnaire.

than 5 yrs. ALMEIDA and co-workers [109, 110], using a titratable MAS, demonstrated that MAS used for a mean period of 7.3 yrs have a significant impact on occlusal and dental structures. Changes observed in craniofacial structures were mainly related to significant tooth movements. MARKLUND [109] observed that the frequent use of a single piece MAS with full occlusal coverage for 5 yrs resulted in median reductions in overjet and overbite of 0.6 mm in patients with either snoring or OSAH. Table 4 summarises the long-term side-effects of MAS on occlusal measurements [111114].

Cost
ORAL APPLIANCES

The cost of oral-appliance therapy varies depending on the types of oral appliances used and the extent and expertise of the dental supervision. Consensus opinion indicates that a prefabricated oral appliance can range from J35 to J75 and custom made oral appliances range from J75 to over J700 [1]. Oral appliances usually remain effective for 25 yrs, but they can break and require either repair or replacement. Dental service fees vary greatly between J1501,800, depending on the time spent caring for the patient and geographical economical factors. Costs can equal or exceed those associated with nasal CPAP therapy. There is increasing evidence that both oral appliances and nasal CPAP are cost-effective treatments for OSAH [115, 116].

Treatment recommendations
A Cochrane systematic review performed a variety of meta-analyses on data from 16 randomised controlled trials involving 745 patients available up to 2005, and concluded that there was
Table 4. Long-term side-effects of mandibular advancement stent on occlusal measurements First author [Ref.] M ARKLUND [66] R OBERTSON [111] R OSE [112] G HAZAL [113] A LMEIDA [109, 110] M ARKLUND [108] H AMMOND [114] Year of study 2001 2001 2002 2008 2006 2006 2007 Patients n 75 100 34 24 70 450 64 Interval years 2.5 2.5 2.5 2.5 7.6 5.4 2.1 Change in OB mm -0.5 -1.02 -1.1 3.2 -1.9/-2.8 -0.6 -0.3 Change in OJ mm -0.6 -1.06 -1.3 2.5 -1.2/-2.6 -0.6 -0.2

OB: overbite, vertical overlapping of upper teeth over lower teeth. OJ: overjet, horizontal projection of upper teeth beyond the lower teeth.

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increasing evidence that oral appliances improve subjective sleepiness and sleep-disordered breathing compared with control appliances [4]. However, it recommended that until there was more definitive evidence on the effectiveness of oral appliance compared with CPAP, oral appliance therapy should be restricted to patients with mild, symptomatic OSAH and those patients who are unwilling or unable to comply with CPAP therapy. The American Academy of Sleep Medicine [5] reviewed similar data to the Cochrane Collaboration and recommended that oral appliances were indicated for use in patients with mildmoderate OSAH who prefer them to CPAP, or who do not respond to, are not appropriate candidates for, or who fail treatment with CPAP. They recommended CPAP therapy whenever possible for patients with severe OSAH. These practice parameters emphasise the importance of a combined medical and dental approach to oral appliance treatment. MAS therapies should not be used in patients who have major periodontal disease. Follow-up sleep monitoring is needed to verify the efficacy of oral appliance therapy. OSAH is a chronic disease and therefore patients treated with oral appliances require lifelong follow-up to monitor patient adherence, long-term dental follow-up, evaluations of the oral appliance deterioration or maladjustment, and evaluation of the health of the oral structures and integrity of the occlusion.

Statement of Interest
None declared.

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