Oral appliance treatment of obstructive sleep apnea: an update Andrew S.L. Chan a,b and Peter A. Cistulli a,b

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1 Oral appliance treatment of obstructive sleep apnea: an update Andrew S.L. Chan a,b and Peter A. Cistulli a,b a Centre for Sleep Health and Research, Department of Respiratory Medicine, Royal North Shore Hospital, St Leonards and b Woolcock Institute of Medical Research, University of Sydney, New South Wales, Australia Correspondence to Professor Peter Cistulli, MD, PhD, Centre for Sleep Health and Research, Department of Respiratory Medicine, Royal North Shore Hospital, St Leonards, NSW 2065, Australia Tel: ; fax: ; cistullip@med.usyd.edu.au Current Opinion in Pulmonary Medicine 2009, 15: Purpose of review Oral appliances are an alternative to continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnea (OSA). Although CPAP is a highly efficacious treatment, there is a need for other treatment options because the clinical effectiveness of CPAP is often limited by poor patient acceptance and tolerance, and suboptimal compliance. Recent findings There has been an expansion of the research evidence to support the use of oral appliances in clinical practice. Recent work has focused on the following clinically relevant areas: the effect of device design on efficacy and patient compliance, the role of different modalities for assessing the upper airway in the prediction of treatment outcome, the assessment of the impact of treatment on a range of health outcomes and the evaluation of long-term adverse effects. Summary There is robust evidence of the efficacy of oral appliances for improving polysomnographic indices and modifying the health risk associated with OSA. The current evidence suggests a similar impact on health outcomes as CPAP. However, further research is required to address a number of unresolved issues, including the influence of device design, titration procedures, prediction of treatment outcome and the clinical effectiveness of oral appliances for modifying the adverse health consequences of OSA. Keywords mandibular advancement splints, obstructive sleep apnea, oral appliances Curr Opin Pulm Med 15: ß 2009 Wolters Kluwer Health Lippincott Williams & Wilkins Introduction Oral appliances are an alternative to continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnea (OSA) [1]. Although CPAP is a highly efficacious treatment, there is a need for other treatment options because the clinical effectiveness of CPAP is often limited by poor patient acceptance and tolerance, and suboptimal compliance [2 4]. With increasing recognition of the role of craniofacial factors in the pathogenesis of OSA, there has been an expansion of the research evidence to support the use of oral appliances in clinical practice [5]. Mandibular advancement devices (MADs) are the most common class of oral appliance used for the treatment of OSA. They mechanically protrude the mandible with the aim of preventing collapse of the upper airway [1]. These devices are also known as mandibular advancement appliances, mandibular repositioning appliances or mandibular advancement splints. Tongue-retaining devices, the other main class of oral appliance used for the treatment of OSA, use a suction pressure to maintain the tongue in a protruded position during sleep [5]. Most research studies of oral appliance treatment for OSA have focused on the use of MADs in adult patients, and this will be the focus of this review. Clinical guidelines and clinical efficacy In 2006, the American Academy of Sleep Medicine (AASM) updated its practice parameters for the treatment of OSA with oral appliances. In this update, the AASM stated that oral appliances are indicated for use in patients with mild-to-moderate OSA who prefer oral appliances to CPAP, who do not respond to CPAP, are not appropriate candidates for CPAP, or who fail treatment attempts with CPAP or treatment with behavioral measures such as weight loss or sleep position change. As CPAP is a more efficacious treatment, it is recommended that CPAP should be considered before oral appliances for patients with severe OSA [6], and in patients in whom urgent treatment is indicated to control severe symptoms (e.g. sleepiness while driving) or medical comorbidities. The accompanying evidence-based review of the literature [5] provided the basis of this revised recommendation, with randomized controlled studies, using an inactive acrylic dental plate as a placebo, confirming ß 2009 Wolters Kluwer Health Lippincott Williams & Wilkins DOI: /MCP.0b013e b12

2 592 Sleep and respiratory neurobiology the efficacy of MADs for improving the polysomnographic indices of OSA [7,8]. The success rate depends on the criteria used. Overall, approximately 65% of patients achieve a 50% or greater reduction in the apnea hypopnea index (AHI) with MAD treatment. Approximately 35 40% of patients achieve a complete response (reduction of AHI to less than five events per hour). Treatment with a MAD also improves oxyhemoglobin saturation, but rarely to normal levels. Improvements in sleep architecture and reduction of arousal indices have also been shown in some studies [5]. Multidisciplinary approach and device titration Treatment of OSA with an oral appliance requires a multidisciplinary approach, involving a sleep physician and a dental practitioner with expertise in the management of sleep disorders. An initial medical assessment is needed to confirm the diagnosis of OSA, determine its severity and to decide whether oral appliance treatment is appropriate. As part of this evaluation, objective overnight monitoring should be performed. This is followed by a dental assessment and selection and fitting of a device [6]. Patients considered for treatment with MADs require sufficient teeth to retain the device. Caution is needed for those with periodontal disease or temporomandibular joint problems. Little is known about the optimal method for titrating mandibular advancement; however, the degree of mandibular advancement appears to have an important influence on treatment efficacy [9] and titration of mandibular advancement to the maximum comfortable limit is thought to be superior to titration on the basis of subjective reports of symptom resolution. A recent randomized study [10 ] compared CPAP and MADs after one-night polysomnographic titration of both treatments, with the aim of titration of mandibular advancement being to optimize MAD efficacy. In this study [10 ], successfully titrated MADs resulted in a relatively high response rate, and produced similar improvements in subjective and objective measures of sleepiness, cognitive function tests and health-related quality of life. After a period of acclimatization, a medical review and another objective overnight assessment are required to determine the effectiveness of treatment. Regular review of the patient by a sleep physician and dental practitioner is required to monitor the treatment response, adverse effects and compliance. Should symptoms of OSA recur or if there is significant weight gain, the efficacy of treatment should be re-evaluated. Device design Despite the diverse assortment of MAD designs that have been used in clinical practice and research studies, little is known about the impact of these variations on clinical outcome. In general, MADs have either a onepiece (monobloc) or two-piece (duobloc) configuration. There are also differences in construction material, size, coupling mechanism and the degree to which these devices are customized to the patient s dentition. It is important to consider these design features when choosing a device, as they may influence the retention of the oral appliance within the oral cavity during sleep, the degree of advancement of the mandible and the range of movement of the mandible that is permitted. In turn, such variations may affect clinical efficacy, patient compliance and adverse effects [11,12]. Customized devices are generally thought to have better retention within the oral cavity and provide higher levels of comfort and efficacy. A recent comparison between a custom-made and thermoplastic oral appliance in a randomized controlled crossover trial showed that a custom-made device resulted in significantly higher levels of treatment efficacy. Compliance with the custom-made device was also higher, mainly because of better overnight retention, and a higher proportion of patients preferred this device. Furthermore, it was found that there was no role for thermoplastic devices in screening candidates for treatment with a custom-made MAD [13 ]. The vertical dimension of mouth opening may be another important influence on tolerance and efficacy [14]. Prediction of treatment outcome As not all patients are able to achieve a successful outcome when treated with a MAD [5], the development of methods to assist the selection of patients who will respond to treatment would be of significant clinical importance. Previous studies [8,15 17] had identified a range of anthropomorphic, physiologic and polysomnographic parameters associated with a better treatment outcome. Such predictors of successful oral appliance treatment outcome include female sex, lower age, lower body mass index, smaller neck circumference, lower baseline AHI, supine-dependent OSA and primary oropharyngeal collapse of the upper airway during sleep [8,15 17]. However, there have been no published prospective studies demonstrating the ability to predict the outcome of oral appliance treatment using any parameter, either singly or in combination. Recent developments include the use of flow volume curves and the measurement of nasal resistance to assess aspects of upper airway function during wakefulness. These studies suggest that such measurements may have some predictive utility. Significant differences in measurements of inspiratory flow rate at 50% of vital capacity (MIF 50 ) and the ratio of expiratory flow rate at 50% of vital capacity (MEF 50 ) to MIF 50 on flow volume curves were observed between responders and nonresponders,

3 Oral appliance treatment of OSA Chan and Cistulli 593 with responders having lower values of MIF 50 and higher MEF 50 : MIF 50 ratios. A combined cutoff of MIF 50 less than 6.0 l/s and a MEF 50 : MIF 50 ratio greater than 0.7 had positive and negative predictive values for treatment success of 89 and 76%, respectively [18]. However, validation is required in a further prospective cohort to verify the clinical utility of these findings. Nonresponders have also been shown to have higher baseline nasal resistance in the sitting position and an increase in nasal resistance when using a MAD in the supine position. However, there was significant interindividual variability, and the sensitivity and specificity of these observations were thought to be inadequate for use in the clinical setting [19 ]. The use of upper airway imaging has been another approach to the development of a method to predict treatment outcome. Cephalometric predictors of successful oral appliance treatment outcome include a shorter soft palate, larger retropalatal airway space, decreased distance between the hyoid and mandibular plane, narrow sella nasion B point angle and wider sella nasion A point angle [8,20,21]. When magnetic resonance imaging of the upper airway during the Müller maneuver was performed, an improvement of upper airway patency following mandibular advancement was found to be associated with a successful treatment outcome (50% or greater reduction in AHI to less than 10 events per hour), whereas persistence of upper airway collapse following mandibular advancement was associated with treatment failure [22]. A study [23] selecting patients for treatment with MADs based on an improvement in upper airway patency with mandibular advancement during drug-induced sleep nasopharyngoscopy found that 74% in a series of 19 patients achieved an AHI of less than 10 events per hour. Preliminary evidence suggests that nasopharyngoscopy performed during wakefulness may be useful in the clinical prediction of treatment response [24]. In a recent proof of concept study, a model of the upper airway using computed tomography of the upper airway suggested that an assessment of upper airway volume and resistance with computational fluid dynamics may also have some clinical utility [25]. The use of one-night titration of mandibular advancement during sleep to determine polysomnographic response and the amount of mandibular advancement required to achieve a response may be another method for predicting treatment outcome [26,27]. Further studies are needed to assess its feasibility in clinical practice. Health outcomes As for other treatment modalities for OSA, the goals of treatment with a MAD are not only to prevent obstructive apneas and hypopneas, and associated oxyhemoglobin desaturation during sleep, but also to improve the symptoms of OSA (such as snoring, excessive daytime sleepiness and neurocognitive impairment) and to modify the increased cardiovascular risk associated with OSA. There is both subjective and objective improvement in snoring following treatment with a MAD. Compared with an inactive acrylic dental plate as a placebo, there is a significant reduction of snoring frequency and intensity [7,8]. Treatment of OSA with MADs improves both subjective and objective measures of excessive daytime sleepiness, although part of the subjective improvement may be attributable to a placebo effect [7,8,28]. Improvements in simulated driving performance have also been demonstrated, similar to that achieved with CPAP [29]. Small improvements in aspects of neuropsychological functioning following treatment with a MAD have been found in studies using inactive oral devices, placebo tablets and CPAP as comparisons [30,31]. When measured using validated questionnaires, quality of life is also improved when treatment with a MAD is compared with a placebo tablet [30]. Two randomized placebo-controlled studies [30,32], using intention-to-treat analyses, have reported a modest reduction in blood pressure (BP; 2 4 mmhg) following treatment with a MAD for periods of 1 and 3 months. Uncontrolled studies have shown similar effects [33,34]. The impact of treatment on other cardiovascular endpoints, such as cardiovascular events and mortality, remains unresolved. Early indications are that treatment of OSA with a MAD may have a positive impact, with improvement of intermediate endpoints such as oxidative stress and endothelial function [35]. Treatment with MADs is less efficacious than treatment with CPAP for improving the polysomnographic indices of OSA. In crossover trials [30,36 41] comparing treatment with a MAD versus CPAP, a greater degree of improvement of the AHI and oxyhemoglobin saturation has been consistently achieved with CPAP treatment. However, there is preliminary evidence to suggest that the effectiveness of MADs in achieving health outcomes (such as improvement in BP) may not be inferior to CPAP in clinical practice, despite not achieving a complete normalization of polysomnographic indices. A randomized study [42] comparing the effect of treatment with MADs, CPAP and conservative measures (lifestyle advice about sleep hygiene and weight loss) on a range of health outcomes confirmed that CPAP was the most efficacious treatment for improving the polysomnographic indices of OSA. Treatment with CPAP also resulted in slightly greater degrees of improvement in excessive daytime sleepiness and health-related quality of life. However, there were no significant differences in the reduction in BP produced by these two treatments,

4 594 Sleep and respiratory neurobiology Figure 1 A conceptualized comparison of treatment performance of continuous positive airway pressure and mandibular advancement devices across various domains Convenience Affordability Patient and partner acceptance Polysomnographic efficacy Tolerance Symptom control Adherence Health benefits Current evidence suggests that, despite the superior efficacy of CPAP, both treatments produce similar subjective and objective health benefits. The superior self-reported tolerance and compliance associated with MAD treatment is a likely explanation. Data comparing the costs of each treatment are scant. CPAP, continuous positive airway pressure; MAD, mandibular advancement devices , CPAP;, MAD. with both treatments lowering the morning diastolic BP compared with baseline values [42]. These findings suggest that treatment of OSA with MADs could provide an equivalent health benefit despite not achieving a complete normalization of polysomnographic indices, and this is likely to be related to differences in adherence profiles. However, this concept (illustrated in Fig. 1) is not conclusive and further studies are needed to compare the effectiveness and cost-effectiveness of different treatment modalities in clinical practice for modifying the adverse health consequences of OSA. Adverse effects MADs exert reciprocal forces on the teeth and jaw, and may apply pressure on the gums and oral mucosa, depending on their design. These mechanical effects can result in acute symptoms, as well as long-term dental and skeletal changes. Minor and transient adverse effects are often experienced during the initial acclimatization period, including excessive salivation, mouth dryness, tooth pain, gum irritation, headaches and temporomandibular joint discomfort. The reported frequencies of these adverse effects vary widely, ranging from six to 86% of patients [5]. This is probably due to differences in the device design, the degree of mandibular advancement, the expertise of the dentist and the frequency and duration of follow-up. As acute adverse effects may influence the patient s acceptance of treatment, early recognition and attention to these symptoms are important. Longitudinal studies have shown that dental and skeletal changes occur with long-term use of MADs, with data extending up to 7 years. After a 5-year period, 14% of patients using a MAD had dental changes when assessed by a cephalometric radiograph. There was a reduction in overjet by 1 3 mm, but more than half of these patients were not aware of these changes [43]. An earlier study [44] had suggested that these dental changes tended to stabilize after the first 2 years of treatment. However, more recent studies have found changes in occlusal contact area with long-term use [45], with the duration of oral appliance use correlating with the extent of changes in the bite relationship and mandibular posture [46,47]. An increase in facial height, an increase in the degree of mouth opening and changes in the inclination of the incisors have also been reported [43,44,48,49]. It has been suggested that the likelihood of long-term occlusal changes can be predicted by pretreatment dental characteristics. A smaller change in overjet (less than 1 mm) at follow-up was more common in those who had a baseline overbite of more than 3 mm, an overjet of less than 3 mm or in those who had used a soft elastomeric device rather than a hard acrylic device [50]. A small proportion of patients will develop clinically important dental changes that will require use of an alternative treatment for OSA [1]. Conclusion The practice parameters of the AASM recommend the use of oral appliances for mild-to-moderate OSA, or for patients with severe OSA who are unable to tolerate CPAP or refuse treatment with CPAP. There is robust evidence of the efficacy of oral appliances for improving polysomnographic indices and modifying the health risk associated with OSA. Although not as efficacious as CPAP, oral appliances are often considered by patients to be a more acceptable treatment. This has the potential to translate to better treatment compliance and may provide a similar level of effectiveness in clinical practice. Further research is required to address a number of unresolved issues, including the influence of device design, titration procedures, prediction of treatment outcome, the clinical effectiveness of oral appliances for modifying the adverse health consequences of OSA and long-term adverse effects. Acknowledgements This manuscript was supported by National Health and Medical Research Council of Australia (Project Grants No and ; and Medical Postgraduate Scholarship Grant No ).

5 Oral appliance treatment of OSA Chan and Cistulli 595 References and recommended reading Papers of particular interest, published within the annual period of review, have been highlighted as: of special interest of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (pp ). 1 Cistulli PA, Gotsopoulos H, Marklund M, Lowe AA. Treatment of snoring and obstructive sleep apnea with mandibular repositioning appliances. Sleep Med Rev 2004; 8: McArdle N, Devereux G, Heidarnejad H, et al. Long-term use of CPAP therapy for sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med 1999; 159: Weaver TE, Kribbs NB, Pack AI, et al. Night-to-night variability in CPAP use over the first three months of treatment. Sleep 1997; 20: Kribbs NB, Pack AI, Kline LR, et al. Objective measurement of patterns of nasal CPAP use by patients with obstructive sleep apnea. 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Eur Respir J 2009 [Epub ahead of print]. This randomized study compared CPAP and MAD after one night polysomnographic titration of both treatments. Successfully titrated MAD resulted in a relatively high response rate, and produced similar improvements in subjective and objective measures of sleepiness, cognitive function tests and health-related quality of life. 11 Gauthier L, Laberge L, Beaudry M, et al. Efficacy of two mandibular advancement appliances in the management of snoring and mild-moderate sleep apnea: a cross-over randomized study. Sleep Med 2009; 10: Ghazal A, Sorichter S, Jonas I, Rose EC. A randomized prospective long-term study of two oral appliances for sleep apnoea treatment. J Sleep Res 2009; 18: Vanderveken OM, Devolder A, Marklund M, et al. Comparison of a custommade and a thermoplastic oral appliance for the treatment of mild sleep apnea. 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