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1 Centre for Sleep Health and Research, Department of Respiratory Medicine, Royal North Shore Hospital, St. Leonards; and Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia
Correspondence and requests for reprints should be addressed to Peter Cistulli, M.D., Ph.D., Centre for Sleep Health and Research, Department of Respiratory Medicine, Royal North Shore Hospital, St. Leonards, NSW, 2065 Australia. E-mail: cistullip{at}med.usyd.edu.au
ABSTRACT
Although positive airway pressure is the most efficacious treatment for obstructive sleep apnea (OSA), its clinical effectiveness is limited by its obtrusive interface. Two alternative treatment modalities used in clinical practice are mandibular advancement devices (MADs) and positional therapy. The goals in treatment of OSA are to prevent obstructive apneas and hypopneas, to improve symptoms, and to modify the increased cardiovascular risk. MADs achieve this by mechanically protruding the mandible, thereby increasing the dimensions of the upper airway and reducing its collapsibility. By avoiding supine sleep, positional therapy improves the patency of the upper airway in those with positional OSA. There is now a relatively strong evidence base to support the use of MADs in clinical practice, with research studies assessing the impact of treatment on a range of health outcomes. The revised clinical practice parameters of the American Academy of Sleep Medicine recommend their use for mild to moderate OSA; or for patients with severe OSA who are unable to tolerate or refuse treatment with positive airway pressure. The evidence base for positional therapy is emerging, but is less well developed. A better understanding of the range of OSA phenotypes and predictors of response to different treatment modalities is required to allow physicians to tailor the choice of treatment to the individual patient.
Key Words: obstructive sleep apnea • oral appliances • mandibular advancement • positional therapy
The treatment of obstructive sleep apnea (OSA) is aimed at overcoming the imbalance of forces acting on the upper airway so as to reduce the vulnerability to collapse during sleep. By far the most successful approach to date is positive airway pressure (PAP), which acts by pneumatically splinting the airway. It is highly efficacious because it "treats" the entire upper airway, regardless of regional pathophysiology. Nevertheless, its clinical effectiveness is limited by its obtrusive nature, and hence alternative approaches to treatment have received increasing attention in the research and clinical arenas. With the recognition of the enormous health and economic burden associated with OSA, the need for simple and effective treatment approaches is self-evident. The greatest burden in prevalence terms is at the mild end of the OSA spectrum (1), and it is in this group in particular that the potential benefits of PAP may be outweighed by its obtrusive nature. Hence, there is an undoubted need for alternative treatment modalities for OSA. Moreover, there is growing appreciation of the heterogeneous phenotypes among patients with OSA (2), and that a greater understanding of such phenotypes may be a guide to tailoring the most appropriate treatment modality for the individual patient. This review focuses on two such modalities, namely mandibular advancement devices and positional therapy.
MANDIBULAR ADVANCEMENT DEVICES
Mandibular advancement devices (MADs) are the most common class of oral appliance used for the treatment of snoring and OSA. They mechanically protrude the mandible with the aim of improving the patency of the upper airway and thereby prevent the occurrence of snoring, and obstructive apneas and hypopneas during sleep (3) (Figure 1). These devices are variably referred to 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, protrude the tongue by suction pressure (4). Most research studies of oral appliance treatment for OSA have focused on the use of MADs in adult patients, and this is the focus of this review.
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Mechanism of Action
It has been traditionally believed that the primary mechanism of action of MADs is to cause mechanical advancement of the mandible and thereby increase the anteroposterior dimensions of the oropharynx. However, this notion has been challenged by upper airway imaging studies, which have demonstrated that mandibular advancement improves the patency of the velopharyngeal segment of the upper airway, with the improvement occurring predominantly in the lateral dimension (6, 7). The precise reason for this effect on velopharyngeal patency is unclear. However, soft tissue connections exist between the mandible, tongue, lateral pharyngeal walls, and soft palate, within the palatoglossal and palatopharyngeal arches. It has been proposed that such soft tissue connections may be stretched by mandibular advancement (8). These structural changes are associated with a reduction in the collapsibility of the upper airway, as measured by a reduction of the upper airway closing pressure during sleep (9). Although research studies have shown that MADs stimulate genioglossus muscle activity, the clinical importance of upper airway neuromuscular reflexes in the mechanism of action of MADs remains uncertain. Research studies have shown that using oral appliances that do not provide mandibular advancement have no significant clinical benefit for the treatment of OSA, suggesting that such a mechanism plays a minor role (10, 11).
Clinical Efficacy
The goals of treatment with an MAD apply to all treatment modalities for OSA. These are to prevent obstructive apneas and hypopneas during sleep, 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 has been a significant expansion of the evidence base to support the use of MADs, evaluating their effect on a broad range of polysomnographic and health outcomes.
Polysomnographic indices.
Using rigorous definitions of treatment outcome, randomized controlled studies using an inactive acrylic dental plate as a placebo have confirmed the efficacy of MADs for improving the polysomnographic indices of OSA (10, 11). The success rate depends on the criteria used. Overall, approximately 65% of patients achieve a 50% or greater reduction in apnea–hypopnea index (AHI) with MAD. Approximately 35 to 40% of patients achieve a complete response (reduction of AHI to fewer than 5 events/h). Treatment with an 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 (4).
Snoring.
There is both subjective and objective improvement in snoring after treatment with an MAD. Compared with an inactive acrylic dental plate as a placebo, there is a significant reduction of snoring frequency and intensity (10, 11). MADs may also be used for the treatment of habitual snoring, in patients without OSA, as recommended by the practice parameters of the American Academy of Sleep Medicine (12).
Excessive daytime sleepiness.
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 (10, 11, 13). Improvements in simulated driving performance have also been demonstrated, similar to that achieved with PAP (14). However, there have been no published studies of the effect of treatment with an MAD on motor vehicle accident risk or workplace safety.
Neuropsychological function and quality of life.
Small improvements in aspects of neuropsychological functioning after treatment with an MAD have been found in studies using inactive oral devices, placebo tablets, and PAP as comparisons (15, 16). When measured using validated questionnaires, quality of life is also improved when treatment with an MAD is compared with a placebo tablet (15).
Cardiovascular risk.
As OSA is strongly associated with vascular morbidity and mortality, the modification of this risk is an important health outcome. Two randomized placebo-controlled studies, using intention-to-treat analyses, have reported a modest reduction in blood pressure (2 to 4 mm Hg) after treatment with an MAD for periods of 1 and 3 months (15, 17). Uncontrolled studies have shown similar effects (18, 19). The impact of treatment on other cardiovascular end points, such as cardiovascular events and mortality, remains unresolved. Early indications are that treatment of OSA with an MAD may have a positive impact, with improvement of intermediate end points such as oxidative stress and endothelial function (20).
Comparison with PAP.
Treatment with MAD is less efficacious than treatment with PAP for improving the polysomnographic indices of OSA. In crossover trials comparing treatment with an MAD versus PAP, a greater degree of improvement of the apnea–hypopnea index and oxyhemoglobin saturation has been consistently achieved with PAP treatment (15, 21–26).
A randomized study compared the effect of treatment with MAD, PAP, and conservative measures on a range of health outcomes. This study confirmed that PAP was the most efficacious treatment for improving the polysomnographic indices of OSA. Treatment with PAP also resulted in slightly greater degrees of improvement in excessive daytime sleepiness and health-related quality of life. Both PAP and MAD lowered the morning diastolic blood pressure compared with baseline values; however, there were no significant differences in the reduction in blood pressure produced by these two treatments (27).
These findings suggest that treatment of OSA with MAD could provide an equivalent health benefit (e.g., improvement in blood pressure), despite not achieving a complete normalization of polysomnographic indices. It seems likely that this relates to differences in adherence profiles between the two modalities. However, these studies are not conclusive. For instance, comparisons of the effect of MAD and PAP on neuropsychological functioning and quality of life are conflicting (15, 22). In addition, it is possible that studies comparing PAP and MAD were limited by small sample sizes, resulting in failure to detect differences between these treatments.
Prediction of Treatment Outcome
Not all patients are able to achieve a successful outcome when treated with an MAD (4). Although there are anthropomorphic, physiological, and polysomnographic parameters that have been associated with a better treatment outcome (11, 28–30), it is not currently possible to identify with certainty which patients will respond to treatment in clinical practice and this appears to be a barrier to their widespread acceptance by clinicians.
Anthropomorphic, physiological, and polysomnographic 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 (11, 28–30). Flow–volume curves during wakefulness have been shown to provide some predictive utility (31). There are no prospective studies demonstrating the ability to predict the outcome of oral appliance treatment using these parameters, either singly or in combination.
Upper airway imaging may be useful for predicting 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 SNB (sella–nasion–B point) angle, and wider SNA (sella–nasion–A point) angle (11, 32, 33). Upper airway imaging during dynamic maneuvers has provided insight into the relationship between the functional properties of the upper airway and the treatment response. A study using magnetic resonance imaging of the upper airway during the Müller maneuver found that an improvement of upper airway patency after mandibular advancement was associated with a successful treatment outcome (50% or greater reduction in AHI, to fewer than 10 events/h), whereas persistence of upper airway collapse after mandibular advancement was associated with treatment failure (34). Similarly, a study selecting patients for treatment with MAD based on an improvement in upper airway patency with mandibular advancement during a drug-induced sleep nasopharyngoscopy found that 74% in a series of 19 patients achieved an AHI of fewer than 10 events/hour (35). There are preliminary data to suggest that nasopharyngoscopy performed during wakefulness may also be useful for distinguishing responders from nonresponders (36).
One development has been the use of single-night titration of mandibular advancement during sleep to determine polysomnographic response and the amount of mandibular advancement required to achieve a response (37, 38). Further studies are needed to assess its utility in clinical practice.
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.
It is common to experience some adverse effects during the initial acclimatization period; however, these are usually minor and self-limiting. Commonly reported symptoms include excessive salivation, mouth dryness, tooth pain, gum irritation, headaches, and temporomandibular joint discomfort. The reported frequencies of these adverse effects vary widely, ranging from 6 to 86% of patients (4). 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 an MAD had dental changes when assessed by a cephalometric X-ray. There was a reduction in overjet by 1 to 3 mm; however, more than half of these patients were not aware of these changes (39). Earlier studies suggested that these dental changes tended to stabilize after the first 2 years of treatment (40); however, more recent studies have found that the duration of oral appliance use correlated with the extent of changes in the bite relationship and mandibular posture (41, 42). An increase in the facial height, an increase in the degree of mouth opening, and changes in the inclination of the incisors have also been reported (39, 40, 43). Another study monitoring patients for a mean of 5.4 years suggested that the likelihood of long-term occlusal changes could be predicted by the 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 (44). A small proportion of patients will develop clinically important dental changes that will require use of an alternative treatment for OSA (3).
Compliance
Objective adherence data for oral appliances are limited. On the basis of self-reported compliance data, a pooled compliance rate of 77% at 1 year was found (4). Use of a novel intraoral monitoring device to assess objective compliance demonstrated an average nightly use of 6.8 hours (45), similar to the self-reported compliance in other studies (10, 25). In contrast, 46% of patients used PAP for at least 4 hours per night for more than 70% of nights (46).
Studies comparing treatment with an MAD with PAP indicate that, in general, patients find an MAD to be a more acceptable treatment (15, 21–26). This has the potential to influence compliance and clinical effectiveness.
Clinical Practice Guideline
The American Academy of Sleep Medicine (Westchester, IL) has revised its clinical practice parameters for the treatment of snoring and OSA with oral appliances. The practice parameters now state that oral appliances are indicated for the treatment of mild to moderate OSA in patients who prefer oral appliances to PAP, who do not respond to PAP, who are not suitable for treatment with PAP, or for whom treatment attempts with PAP are unsuccessful. As PAP is a more efficacious treatment, it is recommended that PAP be considered before oral appliances for patients with severe OSA (12) and when urgent treatment is indicated to control severe symptoms (e.g., sleepiness while driving) or comorbidities. 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.
POSITIONAL THERAPY
Positional therapy refers to the use of sleep-related postural changes to positively impact on breathing during sleep. This usually involves avoidance of sleep in the supine position, and can be achieved through a variety of means including body belts and specially designed pillows.
Prevalence of Positional OSA
Positional OSA has generally been defined as a supine AHI of at least twice that in the lateral position, and has a prevalence of approximately 50–60% (47–49) (Figure 2). This prevalence remains high at 35%, even if only patients with a normal AHI (fewer than 5 events/h) in the nonsupine position are considered (50). Factors that seem to predispose to this positional dependency include younger age, and lesser degrees of obesity and OSA severity (47–49). In addition to more frequent respiratory events in the supine position, patients with positional OSA also have longer respiratory events, greater oxygen desaturation, louder snoring, and longer and more frequent arousals in the supine position (51). No studies have specifically examined the prevalence of cervical posture–dependent OSA.
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Efficacy and Effectiveness
Reports from the early 1980s suggested the potential use and efficacy of positional therapy for OSA (61, 62). However, treatments directed at altering patient posture during sleep have generally received limited attention in clinical practice. This is largely related to the lack of a standardized clinical approach, absence of large long-term randomized trials, as well as limited examination of key outcome measurements such as cardiovascular benefits, in addition to symptoms and polysomnographic parameters. Despite these limitations, a number of small studies examining the effectiveness of lateral positional treatment, elevated head posture, and specially designed pillows for positional OSA have been published.
An inexpensive and simple method to achieve nonsupine positioning is use of the "tennis ball technique" (TBT), whereby a body belt with a pocket to fit a firm ball posteriorly is worn during the night (63, 64). In a randomized crossover study between the TBT and PAP in 13 subjects with mild to moderate positional OSA, TBT was highly effective in reducing time spent supine, but the total AHI was improved by only 8 events/hour compared with baseline (from 17.9 to 9.5 events/h) (63). PAP was more effective at normalizing the AHI and improving oxygen saturation in this study. However, there were no significant differences between the two treatments in terms of symptomatic improvement, maintenance of wakefulness testing, psychometric test performance, or quality of life measures. Other nonsupine positioning techniques have been used including alarm training and positioning vests (65, 66). Similarly, these techniques significantly, but only partially, improved the AHI. Factors that might be associated with treatment success are uncertain, but lateral posture OSA severity, weight and motivation of the patients appear to influence treatment outcome (65). Combining positional treatment with other therapies such as the use of nasal decongestants or a tongue-retaining device may yield further improvement in the AHI (65, 67). Data on the role of positional therapy as adjuvant to other treatments are limited. Improvement in other health outcomes with supine sleep avoidance will need further investigation, although improvement in 24-hour blood pressure was demonstrated in an uncontrolled study (68).
Effectiveness of a shoulder–head pillow to achieve a partially elevated posture has been assessed in a randomized crossover trial with PAP in subjects with a range of OSA severity (69). Treatment success, defined by a reduction of AHI to 10 events/hour or fewer, was achieved by only 4 of 14 subjects. The likelihood of response to this treatment did not seem to relate to baseline positional dependency, suggesting there might be other patient factors influencing treatment outcome. Sleepiness appeared to be reduced by the postural treatment compared with baseline, but no difference was seen compared with PAP. Improvement in snoring was not assessed.
Specially designed pillows to improve cervical position have also been examined (70–72). One used a pillow that facilitated positioning of the arm under the head while sleeping on the side (72). There was a significant reduction in the mean AHI to fewer than 5 events/hour, as well as improvement in oxygen saturation. Snoring was reported to be reduced or eliminated when using this pillow. Another pillow that promotes solely head extension was investigated, showing marginal improvement in AHI only in mild OSA but not in those with more severe disease (70, 73). No benefit was found with a cervicomandibular support collar that was designed to prevent neck flexion during sleep (71). Overall, although some of these studies did show benefit, response is probably at best suboptimal and complete treatment success occurs only in selected patients. These studies were also limited by small sample sizes and the lack of focus on clinically relevant outcomes. At present, factors associated with successful treatment outcome are unknown and will need further investigation to guide clinical practice.
Compliance
Data on compliance with positional therapies are limited. Most studies did not report compliance during the treatment period, although one suggested that self-reported compliance with a cervical pillow was significantly higher than with PAP (69). However, patient preference for positional therapy may be lower compared with PAP (63). Longer term compliance data in a group of 78 patients who were treated with the TBT appear suboptimal (64). During a 6-month period, only 38% of the patients were still using the treatment and 24% had stopped using the treatment but were still avoiding supine sleep. The remainder had stopped using the treatment, with the main reason being treatment discomfort.
CONCLUSIONS
The quantity and quality of research addressing non–positive airway pressure modalities have steadily increased over the years, and such endeavors need to be encouraged to develop a range of treatment approaches across the full spectrum of OSA. The evidence base supporting the use of MADs in the clinical management of snoring and OSA is now relatively strong, although ongoing research is essential to address a number of unresolved issues, including the prediction of treatment outcome, simplification of titration procedures, and long-term effectiveness and adverse effects. The evidence base for positional therapy is less well developed, and further work is required to develop more rigorous and clinically relevant definitions of positional OSA, and standardized approaches to treatment. A key challenge for the field is to develop a customized approach to patient care, in which the treatment modality is tailored to the patient's disease phenotype.
FOOTNOTES
Supported by the National Health and Medical Research Council of Australia (project grants 300525 and 457557; and medical postgraduate scholarship grants 457155 and 457163).
Conflict of Interest Statement: A.S.L.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. R.W.W.L. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. P.A.C. contributed to the development of an oral appliance that is being commercialized by SomnoMed Ltd. He has previously acted as a consultant/medical advisory board member for SomnoMed Ltd. (2004–2006), and has a pecuniary interest in the company. His department is engaged in a multicenter clinical trial sponsored by ResMed, Inc. His department is engaged in a government-funded clinical trial comparing CPAP and oral appliance treatment, in which support in kind (equipment) is being provided by ResMed Inc. and SomnoMed Ltd. He is a board member of the ResMed Foundation, a nonprofit charitable organization.
(Received in original form July 23, 2007; accepted in final form September 14, 2007)
REFERENCES
This article has been cited by other articles:
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