Adjustable Thermoplastic Mandibular Advancement Device for Obstructive Sleep Apnea: Outcomes and Practicability

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1 The Laryngoscope VC 2014 The American Laryngological, Rhinological and Otological Society, Inc. Adjustable Thermoplastic Mandibular Advancement Device for Obstructive Sleep Apnea: Outcomes and Practicability Wish Banhiran, MD; Phantipar Kittiphumwong, MD; Paraya Assanasen, MD; Cheerasook Chongkolwatana, MD; Choakchai Metheetrairut, MD Objectives/Hypothesis: To assess outcomes including efficacy, adverse effects, and quality of life (QOL) of an adjustable thermoplastic mandibular advancement device (AT-MAD) fitted by an otolaryngologist for obstructive sleep apnea (OSA) treatment. Study Design: Prospective, nonrandomized, before-after study. Methods: Sixty-four adult patients (40 men and 24 women) were recruited. Inclusion criteria were OSA patients who had failed or refused treatment with continuous positive airway pressure and surgery. Exclusion criteria were insufficient teeth, active intraoral disease, and temporomandibular joint (TMJ) disorders. Outcomes were measured using polysomnography, symptom questionnaires, Epworth Sleepiness Scale (ESS), and Functional Outcomes of Sleep Questionnaire (FOSQ) before treatment and 4 to 6 months thereafter. Results: Mean apnea-hypopnea index (AHI) and ESS scores decreased from to and from to , respectively, after treatment (P <.001). Thirty-nine patients (60.9%) achieved post-treatment AHI of <5, with the highest success rate in those with mild OSA (75%). FOSQ global scores increased from to (P <.05), along with most FOSQ subscale scores. Thirty-four patients (53.1%) regularly used the device for 5 nights per week. Adverse effects include TMJ discomfort, dry mouth, and excessive salivation, which were largely tolerable. Only four patients withdrew from the study because of adverse effects. Conclusions: This is the first study in Asians demonstrating that an AT-MAD, if done properly, is a practical short-term treatment of OSA, with good outcomes including improved QOL. Its advantages are its low cost and ready-to-use nature. However, further randomized controlled trials are required. Key Words: Obstructive sleep apnea, quality of life, thermoplastic, mandibular advancement splint, Somnoguard, oral appliances, Asian, Thai. Level of Evidence: 4 Laryngoscope, 124: , 2014 INTRODUCTION Obstructive sleep apnea (OSA) is an upper airway disorder, which if left untreated can lead to several adverse consequences such as impaired quality of life (QOL), 1,2 hypertension, 3 and cardiovascular disease. 4 Although continuous positive airway pressure (CPAP) is accepted as the first-line treatment of OSA, its clinical effectiveness is often limited by poor patient adherence. 5,6 Oral appliances (OAs), enlarge the pharyngeal airway by advancing the mandible and/or tongue forward, have been increasingly accepted as another effective treatment because they may achieve outcomes comparable to those of CPAP while being smaller and easier to use. 7,8 Current practice guidelines of the American Academy of Sleep From the Department of Otorhinolaryngology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. Editor s Note: This Manuscript was accepted for publication January 21, This work was funded by the Faculty of Medicine, Siriraj Hospital. The authors have no other funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Wish Banhiran, MD, Department of Otorhinolaryngology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand wishbanh@gmail.com DOI: /lary Medicine (AASM) state that OAs are indicated for use in patients with mild to moderate OSA who prefer them to CPAP, and do not respond to, are not appropriate candidates for, or fail treatment attempts with CPAP. 9 Some studies have also recommended OAs in patients with residual OSA after surgery. 10 In general, OAs can be classified into tongueretaining devices (TRDs) and mandibular advancement devices (MADs). TRDs use negative pressure to hold the tongue in a protruded position, whereas MADs use traction on dental arches to protrude the mandible during sleep. 11 Traditionally, custom-made MADs fabricated from a dental laboratory have been recommended for OSA treatment, with success rates of 60% to 70% depending on the designs and outcome criteria chosen. 12 However, most of these have a relatively high cost and require several days for treatment to be initiated; this is not suitable for some patients. Recently, prefabricated biocompatible thermoplastic MADs, also known as boiland-bite OAs, have been reported in the otolaryngology literature. These devices offer several advantages over custom-made MADs including lower cost, simplicity, and ready-to-use nature. 10,13,14 At first, these were made in a mono-bloc and nonadjustable fashion, which may have led to unimpressive outcomes and adverse effects, 2427

2 particularly when compared with custom-made MADs However, adjustable thermoplastic MADs (AT-MADs), which allow physicians to adjust the extent of advancement of the mandible and enlargement of the pharyngeal airway, are now available in the market. 10,16 Friedman et al. reported on patient compliance with AT-MADs and the efficacy of these devices in 2012, and found them to be poorer than custom-made MADs. 16 However, their device was titrated during an overnight sleep study, which required awakening patients several times to remove the device; it is possible that this led to inadequate titration due to poor sleep quality. Because there is currently no best method to predict the success of OAs in an individual patient, 17 a strategy of trial with a cheaper AT-MAD is of significant interest. The objectives of this study were therefore to prospectively assess the efficacy, adverse effects, and practicability of using AT-MADs fitted by an otolaryngologist for the treatment of OSA, and the impact of these devices on the QOL of patients. This is possibly the first report of this device in Asian subjects, results in whom might be different from those seen in Caucasian subjects. MATERIALS AND METHODS This prospective nonrandomized study was conducted at Siriraj Hospital between July 2011 and August 2013 after obtaining approval from the Siriraj institutional review board. The study procedure was explained to all patients before they signed the consent form. Subjects Sixty-four patients aged 18 years or older, were recruited from a sleep clinic at the Department of Otolaryngology, Faculty of Medicine, Siriraj Hospital. Inclusion criteria were patients with OSA who refused or had failed treatment attempts with either CPAP or upper airway surgery. Exclusion criteria were patients who had severe periodontal disease, unstable teeth, active dental caries, disorders of the temporomandibular joint (TMJ), limited lower jaw protrusion (less than 6 mm), insufficient teeth (fewer than three in each quadrant), and those who did not have a bed partner or observer to report results. Device Fitting and Titration The device used in this study was SomnoGuard AP (Tomed Dr. Toussaint GmbH, Bensheim, Germany), 16 which Fig. 2. Adjustable thermoplastic oral appliance (Somnoguard AP) after fitting. [Color figure can be viewed in the online issue, which is available at consists of two separable prefabricated trays filled with a thermoplastic material. Both pieces can be attached together by inserting an adjustable screw of the lower tray into a groove in the upper tray (Fig. 1). All fitting procedures were performed according to the manufacturer s instructions by an otolaryngologist in an outpatient clinic. Briefly, the prefabricated trays were boiled in hot water (>90 C) for at least 3.5 minutes. After allowing the trays to cool for at least 30 seconds, the impressions of both the upper and lower jaw were taken in a preset protruded position. The devices were then put in cold water for hardening. The entire procedure could be finished in 10 to 15 minutes depending on the physician s experience. Remolding for a better fit and trimming of any excessive part could be performed whenever patients desired. The picture of the device after finishing the fitting processes is shown in Figure 2. Initially, the mandibular position of the device was preset at approximately midway between maximal protrusion and the normal bite position of the respective patients. Afterward, its position was advanced by 0.5 to 1 mm every 1 to 2 weeks by adjusting the screw, until patients were either most satisfied with symptom relief or they could not tolerate the increasing discomfort. According to the protocol of this study, all patients were scheduled for a second polysomnography (PSG) with the AT-MAD in place at 4 to 6 months after the first treatment or approximately 3 to 4 months after final position of the device was achieved, depending on the individual. Subjective Measurement All patients were asked to complete questionnaires including sleep-related symptoms, Epworth Sleepiness Scale (ESS), 18 and Functional Outcomes of Sleep Questionnaire (FOSQ) 2 to assess their disease-specific QOL before starting treatment. The visual analog scale (VAS) regarding snoring intensity and frequency were rated by bed partners; a score of 0 indicated no detectable snoring, whereas a score of 10 indicated maximal or intolerable snoring. The VAS, ESS, and adverse effects of the AT- MADs were assessed during each follow-up visit. Patients were asked to complete the FOSQ again after 4 to 6 months of treatment and state whether they preferred using the same device or change over to other treatments, specifically custom-made OAs. Regardless of satisfaction with the device, patients were advised to consult dentists for a regular check-up at least twice a year. Fig. 1. Adjustable thermoplastic oral appliance (Somnoguard AP) before fitting. [Color figure can be viewed in the online issue, which is available at Objective Measurement Objective outcomes were assessed approximately 4 to 6 months after beginning treatment with standard technicianattended PSG (Somte, ProGusion III; Compumedics, Victoria, Australia) with the patient wearing the AT-MAD. Recordings included electroencephalogram, electro-oculogram, electromyogram,

3 Characteristic TABLE I. Baseline Clinical Characteristics of Patients. Data Age (yr) BMI (kg/m 2 ) AHI (events/h) Gender Male 40 (62.5) Female 24 (37.5) Disease severity Mild OSA 36 (56.3) Moderate OSA 20 (31.2) Severe OSA 8 (12.5) Previous upper airway surgery 19 (29.6) Nasal surgery 2 (3.1) Modified UPPP 2 (3.1) Modified UPPP 1 nasal surgery 3 (4.7) Modified UPPP 1 nasal surgery 1 TBS 12 (18.7) The continuous data are presented as mean 6 standard deviation. The categorical data are presented as number of patients (percentages). AHI 5 apnea-hypopnea index; BMI 5 body mass index; ESS 5 Epworth Sleepiness Scale; OSA 5 obstructive sleep apnea; TBS 5 tongue base surgery; UPPP 5 uvulopalatopharyngoplasty. electrocardiogram, nasal airflow from pressure transducer and thermistor, respiratory efforts from thoracic and abdominal movement, body position, and pulse oximetry. All sleep parameters were scored manually by certified technologists and reviewed by a sleep specialist who was blinded to the clinical information of the patients. Apnea-hypopnea index (AHI) was defined as numbers of apnea plus hypopnea events per hour of sleep. Apnea was defined as a reduction of airflow amplitude of 90% for at least 10 seconds, and hypopnea was defined as a reduction of airflow amplitude of 30% to 89% for at least 10 seconds, along with oxygen desaturation of 4% from the pre-event baseline, according to standard criteria recommended by the AASM manual for scoring of the respiratory events (first edition, 2007). 19 Patients were classified by their AHI into: mild OSA (AHI ), moderate OSA (AHI ), and severe OSA (AHI 30). Outcome Definitions Treatment success was defined as post-treatment AHI of <5, a good response was defined as post-treatment AHI of <20 plus a reduction of 50% from baseline, 16 and a partial response was defined as a reduction AHI of >20% that did not meet the aforementioned criteria. Failure was defined as a reduction of AHI of <20% or when the patient discontinued using the device and withdrew from the study without followup PSG. Good adherence to treatment was defined as regular use of the devices for 4 hours per night on 5 days per week, which is comparable to that of CPAP therapy. 6 Adverse effects were classified by self-reported severity into mild (minor or little discomfort that can be ignored), moderate (discomfort that sometimes caused patients to stop using the device), and severe degree (significant discomfort leading to intolerability or possibly of treatment discontinuation). Statistical Analysis Continuous data were presented as mean 6 standard deviation, and categorical data were presented as frequency and percentage. Paired t test or Wilcoxon signed rank test were used to compare differences of continuous data before and after treatment. The predictive analytics software PASW Statistics 18 (IBM SPSS, Armonk, New York) was used for statistical analysis. Significance level was set at P <.05 in two-tailed tests. RESULTS Sixty-four patients (40 men and 24 women), aged between 21 and 66 years, were initially recruited for AT- MAD fitting. There was no immediate complication, but four patients could not tolerate the adverse effects of the device and withdrew from the study 2 to 3 weeks after starting treatment. Therefore, a second PSG with the device in place was available in only 60 patients, with a median follow-up time of 22 weeks (16 25 weeks). Additional details of demographic data are shown in Table I. At last follow-up, their mean body mass index (BMI) ( kg/m 2 ) did not change significantly from baseline values (P 5.295). Subjective Outcomes Snoring loudness and frequency, as reported by observers, decreased significantly after treatment, as did the ESS scores (P <.001). Global FOSQ scores and most of the subscale scores increased after treatment (P <.05), except for general productivity and social outcomes. Additional details are shown in Table II. Objective Outcomes Mean AHI was significantly reduced from to after treatment (P <.001). Other important sleep parameters, including mean, lowest oxygen saturation, and slow wave sleep, were also significantly improved after treatment, as shown in Table III. Intention-to-treat analyses revealed that treatment was successful in 39 of 64 patients (60.9%), whereas a good response was seen in 41 of 64 patients (64.1%); the remaining 13 patients (20.3%) were considered to have had a partial response to treatment according to the criteria of this study. The success rate was highest in patients with mild OSA (75%). Details of the response rates are presented in Table IV. Twelve patients (18.8%) were considered to have failed treatment. There were nine men and three women in this group, with pretreatment mean age, BMI, and AHI of , , and , respectively. Device Adherence Thirty-four patients (53.1%) reported using their device for 4 hours every night on 5 nights a week; this was considered good adherence. Twenty patients (31.3%) even reported that they used the device every night. Thirty-seven patients (57.8%) reported that they did not have any problems with device retention. At the end of the study protocol, 22 patients (34.4%) decided to continue using the device, 17 patients (26.6%) changed their treatment option to a custom-made MAD, four patients (6.3%) changed to CPAP, three patients (4.7%) changed to upper airway surgery, and 18 patients 2429

4 TABLE II. Subjective Outcomes After Treatment With Adjustable Thermoplastic Oral Appliance. Pretreatment Post-treatment Difference P Value VAS snoring loudness <.001* VAS snoring frequency <.001* ESS scores <.001* FOSQ subscales General productivity Social outcome Activity level Vigilance Sexual relationship FOSQ global scores The data are presented as mean 6 standard deviation. *The mean difference is significant at the level of <.001 (two-tailed). The mean difference is significant at the level of <.05 (two-tailed). ESS 5 Epworth Sleepiness Scale; FOSQ 5 Functional Outcomes of Sleep Questionnaire; VAS 5 visual analog scales (1 10). (28.2%) decided to discontinue definitive treatment and changed over to conservative treatments such as weight reduction, positional therapy, and good sleep hygiene. because the device was too bulky and difficult to put into her mouth for adequate bite impressions. Adverse Effects The most common adverse effects found in this study during the acclimatization period were TMJ discomfort (90.6%), dry mouth (81.2%), and excessive salivation (79.7%). Other common adverse effects included occlusion change, halitosis, gingival pain, toothache, and problems with retaining ill-fitting devices, as demonstrated in Table V. However, most adverse effects were mild to moderate in severity and tolerable; they declined over time. Only three patients (4.7%) had severe TMJ discomfort or toothache to the degree that they could not continue using the device. One patient had poor device retention despite repeated remolding and adjustment DISCUSSION The literature on OA for the treatment of OSA has grown dramatically in recent years. 7,8,10 17 However, much of this has focused on custom-made MADs that are relatively expensive and take a lot of time to implement because of the multiple steps involved. Cheaper prefabricated thermoplastic MADs are available, but reports on these are still rare and the results are generally unimpressive. 10,13 16 However, intention-to-treat analysis of the findings of the present study demonstrates that 39 out of 64 OSA patients (60.9%) who had used the AT-MAD achieved a post-treatment AHI of <5, which is considered to be a complete success; the highest success rates (75%) were seen in the mild OSA group. TABLE III. Important Polysomnographic Parameters at Baseline and With Device in Place. Parameters PSG Baseline PSG 1 AT-MAD Difference P Value Total sleep time (min) Sleep efficiency (%) Stage N1 (%) <.001* Stage N2 (%) Stage N3 (%) <.001* Stage R (%) AHI (events/h) <.001* AI (events/h) Mean O 2 (%) <.001* Minimal O 2 (%) Time O 2 >90% (%) The data are presented as mean 6 standard deviation. *The mean difference is significant at the level of <.001 (two-tailed). The mean difference is significant at the level of <.05 (two-tailed). AHI 5 apnea-hypopnea index; AI 5 apnea index; AT-MAD 5 adjustable thermoplastic mandibular advancement device; N 5 non-rapid eye movement sleep; O 2 5 oxygen saturation; PSG 5 polysomnography; R 5 rapid eye movement sleep; Time O 2 >90% 5 percentage of time spent during oxygen saturation >90% 2430

5 TABLE IV. Response Rates of Adjustable Thermoplastic Oral Appliances on Different Criteria. Criteria Overall, N 5 64 Mild OSA, N 5 36 Moderate OSA, N 5 20 Severe OSA, N 5 8 Post-treatment AHI <5 Success 39 (60.9) 27 (75) 10 (50) 2 (25) Partial response 13 (20.3) 2 (5.6) 6 (30) 5 (62.5) Failure 12 (18.8) 7 (19.4) 4 (20) 1 (12.5) Post-treatment AHI <20 plus a reduction of 50% from baseline Good response 41 (64.1) 24 (66.7) 11 (55) 6 (75) Partial response 12 (18.8) 5 (13.9) 6 (30) 1 (12.5) Failure 11 (17.1) 7 (19.4) 3 (15) 1 (12.5) The data are presented as number of patients (percentages). AHI 5 apnea-hypopnea index; OSA 5 obstructive sleep apnea. The success rates of this study are thus comparable to those of several reports of custom-made OAs 11,12,17 but higher than those of nonadjustable devices reported by Vanderveken et al., 14,15 Maurer et al., 13 and Friedman et al. 10 In our opinion, these high success rates were possibly because 1) our devices could be fitted and adjusted by an otolaryngologist to an optimal point before the patients were followed up with a second PSG, which may have yielded a better result than that obtained after adjusting the device during an overnight PSG 16 ; 2) the majority of our patients had less severe OSA and lower BMI compared to participants in other studies 10,13,16 ; and 3) our patients were Asians who may have responded to this treatment differently from Westerners. However, it is currently unclear whether differences of craniofacial profiles between these races influence the response to OA treatment. 11,17 This study showed that mean and minimal oxygen saturation, the amount of slow wave sleep, as well as AHI improved significantly after treatment. These findings are in agreement with statistically significant reductions in the scores of snoring intensity, snoring frequency, and daytime sleepiness as measured by ESS. Furthermore, there was statistically significant improvement in most aspects of disease-specific QOL, as assessed by FOSQ after treatment. It is unclear why the general productivity and social outcomes subscale of FOSQ did not show statistically significant improvement after using the AT-MAD despite a tendency of their improvement in majority of the patients. We hypothesized that our Asian patients might have fewer problems with these subscales at the beginning, particularly for social outcomes as demonstrated by their higher pretreatment scores compared with other subscales (Table II). Whether these differences came from the cultural effects or other causes, such as inadequate sample sizes, subsequent research might better clarify this issue. All of these indicators, however, confirmed that AT-MADs can improve sleep quality, which is in agreement with several other reports on thermoplastic and custom-made MADs. 7,8,11 13,17,20 Our patients themselves reported a good device adherence rate of 53.1%, which is comparable to that of CPAP but lower than that of custom-made MADs. 6,12,17,21,22 More than 80% of our patients also reported that they had only mild or no problems with device retention; this is different from what was found for nonadjustable MADs in a crossover study by Vanderveken et al. 15 However, these data were subjective and short term in nature. Although there were no immediate complications with AT-MADs, there were some adverse effects afterward, the most common of which were TMJ discomfort, dry mouth, excessive salivation, occlusion change, halitosis, gingival pain, toothache, and problems with device retention. However, most of these adverse effects were mild in nature, and they declined over a time frame comparable to that seen with custom-made OAs, 11,12,17 and only four patients (6.2%) dropped out from the study because of adverse effects. The majority of our patients (61%) preferred either the same device or a custom-made OA as their primary treatment at the end of the study. All of the aforementioned data convinced us that an AT-MAD is a practicable treatment option, at least on a short-term basis. Although this prospective study was done with an adequate number of patients and used the gold standard test of PSG for monitoring, there were some limitations. First, it was not a randomized controlled trial (RCT), which could provide the highest level of evidence. However, conducting an RCT with this device was considered unethical in view of the rarity of reports, most of which had unimpressive results anyway. In addition, there was no evidence that it was beneficial in Asian patients. This situation has now been changed by the evidence of acceptable outcomes, safety, and practicability of the device provided by our study, and we propose that RCTs be conducted to provide conclusive proof of the utility of this device. Second, this study had a relatively short follow-up period. Because compliance, efficacy, and several adverse effects have been reported even with the custom-made OA, 12,21 24 it was not our objective to study AT-MADs as long-term treatment options. Instead, the primary objective was to consider them as inexpensive trials of treatment for patients until they could decide which was the most suitable. Finally, we used only a single size of the AT-MAD (Somnoguard AP) for all patients who normally had different oral and dental contours. TABLE V. Side Effects of Adjustable Thermoplastic Oral Appliances. None Mild Moderate Severe TMJ pain or discomfort 6 (9.4) 28 (43.8) 25 (39.0) 5 (7.8) Occlusion change 28 (43.8) 26 (40.6) 6 (9.4) 4 (6.2) Excessive salivation 13 (20.3) 27 (42.2) 21 (32.8) 3 (4.7) Halitosis 20 (31.3) 37 (57.8) 7 (10.9) 0 (0) Dry mouth or dry throat 12 (18.8) 31 (48.4) 20 (31.2) 1 (1.6) Gingival or buccal pain 22 (34.4) 26 (40.6) 16 (25) 0 (0) Toothache 29 (45.3) 22 (34.4) 9 (14.1) 4 (6.2) Problem with device retention 37 (57.8) 18 (28.2) 5 (7.8) 4 (6.2) The data are presented as number of patients (percentages). TMJ 5 temporomandibular joint. 2431

6 Thus, it is not surprising that our devices would not be compatible or well fitted with every patient and may lead to significant adverse effects including poor device retention. However, we believe that the availability of the AT-MAD in various sizes and shapes, with better quality comparable to the custom-made MAD, may resolve these problems in the future. As a practical approach, we suggest that OSA patients should be offered all possible treatment options and informed about potential adverse effects to allow them to make their own informed decisions. Because an AT-MAD, which costs approximately $100 USD, is cheaper than custom-made MADs, which cost $1,000 to $2,000 USD, an empirical trial of AT-MADs by otolaryngologists would be entirely worthwhile, provided there are no contraindications to its use. Nonetheless, there are some potential disadvantages of treatment with the AT-MAD. One concern is that the time for fitting and adjustment of this device may require increased physician time and an overall cost to the system, particularly for some systems where physicians are salaried and when the savings in equipment dollars does not flow back to fund them. However, our experiences revealed that these issues are manageable and improvable. With learning curves, the time for fitting procedures could be reduced to only 10 minutes or less, which is comparable to other routine procedures performed by experienced otolaryngologists. The time per visit of the device adjustment could also be reduced to 5 minutes or less, similar to other routine clinical follow-up, and the final position of the device could be achieved within only 2 to 3 visits after an initial fitting in a majority of patients. Furthermore, the treatment with this inexpensive AT-MAD may expand the role of otolaryngologists in OSA management and decrease the overall cost in the healthcare system by reducing unnecessary use of more expensive treatment modalities. However, cost-effective analyses are required to confirm this hypothesis in the future. In our experience, it was relatively specific that most patients who responded well to AT-MAD treatment had similar or better results with a custom-made MAD. In contrast, the failure of AT-MAD did not always predict the failure of a custom-made OA. Therefore, good collaboration between otolaryngologists and dentists will continue to be vital for optimal treatment outcomes. CONCLUSION This is possibly the first report of AT-MADs fitted by an otolaryngologist in Asian patients. Our results confirm that an AT-MAD, if done properly, is an effective and practical treatment for OSA, as demonstrated by improved outcomes, including patients symptoms, sleeprelated parameters, and QOL, with a good adherence rate. However, we recommend an RCT of this device to compare it with either custom-made MADs or CPAP and confirm its usefulness for OSA management. Acknowledgments The authors gratefully appreciate the kind contributions of their consulting statistician, Mr. Suthipol Udompanturak, as well as those of their research assistants, Mr. Kongsak Suwanarak, Ms. Chopetch Saleesingh, Ms. Nongyaow Nujchanart, and Ms. Jeerapa Kerdnoppakhun. The authors also thank all of the staff members of the Department of Otorhinolaryngology and the Siriraj Sleep Center, as well as all patients who were involved in this project. BIBLIOGRAPHY 1. Baldwin CM, Griffith KA, Nieto FJ, O Connor GT, Walsleben JA, Redline S. 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