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Unité de Somnologie et Fonction Respiratoire, Hôpital Saint-Antoine, Paris, FranceSorbonne Universités, UPMC Université Paris 06, INSERM UMR_S 1158, Neurophysiologie Respiratoire Expérimentale et Clinique, Paris, France
The use custom-made devices is recommended for mandibular advancement therapy of OSA.
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Custom-made devices are expensive and a delay is required to manufacture the device.
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A titrable thermoplastic device was effective in reducing OSA severity and symptoms.
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6-month adherence was high despite more dental discomfort than with a custom-made device.
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A trial with a titrable thermoplastic device could be of interest prior to custome-made device.
Abstract
Backgound and objectives
The disadvantages of custom-made mandibular advancement devices (MAD) for obstructive sleep apnoea (OSA) therapy are the cost and delay required to manufacture the device. This study aimed to evaluate the efficacy of a titrable, thermoplastic MAD compared to a custom-made MAD for OSA therapy.
Methods
In this prospective nonrandomized study, 158 patients with OSA from two French sleep centers were treated for 6 months with a titrable thermoplastic MAD (n = 86) or a custom-made MAD (n = 72). The primary outcome was the change in sleep-disordered breathing (SDB) severity.
Results
After adjustment for baseline values, age, body mass index and study site, no significant intergroup differences were observed between thermoplastic and custom-made MAD for the outcome of apnoea, hypopnoea and oxygen desaturation indices. No between treatment differences were observed for the outcome of subjective sleepiness, symptoms of snoring and fatigue, depressive symptoms, and quality of life. Thermoplastic MAD therapy was associated with higher side effects scores for tooth pain (p < 0.0001) and self-reported occlusal changes (p = 0.0069). Mean (SD) reported compliance was lower in the thermoplastic MAD group than in the custom-made MAD group (6.4 [0.2] vs 7.1 [0.1] h/night; p = 0.035).
Conclusions
This study demonstrates the efficacy of a titrable thermoplastic MAD in reducing SDB and related symptoms in patients with mild to severe OSA. Reported compliance at 6 months was high despite more dental discomfort than with custom-made MAD.
] characterized by recurrent episodes of partial or complete obstruction of the upper airway during sleep. Continuous positive airway pressure (CPAP), being the first line therapy for moderate to severe OSA, improves daytime alertness, health-related quality of life (HRQL) and reduces blood pressure [
Continuous positive airway pressure devices for the treatment of obstructive sleep apnoea-hypopnoea syndrome: a systematic review and economic analysis.
Health Technol. Assess. winch. Engl.2009; 13 (iii–iv, xi–xiv, 1–119): 143-274
]. Observational prospective cohort studies indicate that regular CPAP therapy is also associated with a lower risk of driving-related accidents and cardiovascular events [
]. However, among OSA patients in whom CPAP is recommended, approximately 40% are at risk of non-adherence especially if they have mild to moderate OSA [
IRSR sleep cohort group, Influence of marital status and employment status on long-term adherence with continuous positive airway pressure in sleep apnea patients.
]. Mandibular advancement devices (MAD) have emerged as the main therapeutic alternative for OSA. Despite the superior efficacy of CPAP in reducing sleep-disordered breathing (SDB), most randomized trials comparing MAD and CPAP in OSA have reported similar heath outcomes in terms of sleepiness, neurobehavioral functioning, quality of life and blood pressure [
Comparison of the effects of continuous positive airway pressure and mandibular advancement devices on sleepiness in patients with obstructive sleep apnoea: a network meta-analysis.
Meta-analysis of randomised controlled trials of oral mandibular advancement devices and continuous positive airway pressure for obstructive sleep apnoea-hypopnoea.
]. When MAD therapy is prescribed, practice guidelines also suggest with a low quality of evidence to use a custom, titratable MAD over non-custom devices [
]. However, potential disadvantages of these custom-made MAD are the cost and delay required to manufacture the device. In addition, not all patients benefit from MAD, and presently no method exists to predict the outcome prior to fabrication of the device [
]. Thus, a trial with an inexpensive thermoplastic titrable MAD would be of great interest. A previous randomized cross-over trial found that a monobloc nonadjustable thermoplastic MAD with insufficient overnight retention was less effective that a custom-made MAD [
IRSR sleep cohort group, Influence of marital status and employment status on long-term adherence with continuous positive airway pressure in sleep apnea patients.
]. Approval was obtained from the University of Angers ethics committee and the “Comité Consultative sur le Traitement de l’Information en matière de Recherche dans le domaine de la Santé [C.C.T.I.R.S.] (07.207bis)”. The database is anonymous and complies with the restrictive requirements of the “Commission Nationale Informatique et Liberté [C.N.I.L.]”, the French information technology, and personal data protection authority. All patients included in the IRSR sleep cohort have given their written informed consent.
2.1 Study population
According to French clinical guidelines, MAD therapy is recommended as an appropriate first-line treatment option for mild to moderate OSA in patients without severe cardiovascular comorbidity or as a second line option in patients intolerant to CPAP [
]. Between Jun 01, 2015 and January 25, 2017, consecutive OSA patients in whom MAD therapy was considered in two French sleep centers (University Hospital of Angers and Saint-Antoine Hospital of Paris, France) participating to the IRSR sleep cohort were offered the choice of being treated immediately with a custom-made MAD or starting with a trial of thermoplastic MAD.
A flow diagram is presented in Fig. 1. Two hundred and twenty patients in whom MAD had been prescribed for at least 6 months were eligible for the study. None of these patients were on CPAP therapy during the study period. One hundred and twenty five patients had been treated with thermoplastic MAD and 95 had been treated by custome-made MAD. One hundred and fifty-eight patients were included in the analysis, 86 in the thermoplastic MAD group and 72 in the custom-made MAD group. The baseline characteristics of study participants are summarized in Table 1. Significant intergroup differences were observed for age, body mass index (BMI) and OSA severity. Patients treated with thermoplastic MAD were younger (p = 0.0039), had lower BMI (p = 0.0079) and had less severe OSA (p = 0.0022 for AHI and 0.0445 for sleep time with SaO2 <90%).
Data are expressed as mean (standard deviation) or percentages.
Abbreviations: MAD, mandibular advancement device, BMI, body mass index; VAS, 0–10 visual analog scale; BP, blood pressure; ODI, oxygen desaturation index; T90, time spent with SaO2 <90%; OSA, obstructive sleep apnoea.
] were used in the study: 63 patients were treated with the AMO® device (SomnoMed, France) and 9 with the Somnodent® device (SomnoMed, France) (see Fig. 2B and C). All patients were fitted with the chosen MAD by a qualified dentist. The same MAD titration procedure was used for thermoplastic and custom-made MADs. As previously described, once fitted with the device, patients underwent an acclimatization period during which the mandible was incrementally advanced by 1-mm steps every 1 or 2 weeks until symptom relief or the maximum comfortable limit of advancement was achieved [
All outcomes were assessed at baseline and after 6 months of MAD therapy. Outcome assessors were unaware of the device assignment. The primary outcome was the change in SDB severity as assessed by the apnoea-hypopnoea index (AHI), the apnoea index (AI), the 3% oxygen desaturation index (ODI) and the sleep time with SaO2 <90% (T90) between baseline and after 6 months of thermoplastic or custom-made MAD. Secondary outcome measures included changes in daytime sleepiness, depressive symptoms, HRQL, clinical symptoms of OSA, treatment side effects and compliance. Daytime sleepiness was evaluated by the Epworth Sleepiness Scale (ESS) [
]. Outcome of OSA symptoms, global treatment satisfaction, and reported side effects were assessed at 6-month follow-up using previously described specific questionnaires [
]. Reported compliance was assessed through a diary during the 6 months of treatment with thermoplastic or custom-made MAD. Each night, patients recorded the number of hours that the device was used. A mean reported daily use over the study period was then calculated.
2.4 Sleep recordings
At baseline all patients underwent type III overnight respiratory recordings (CID 102 LX, Cidelec, Sainte-Gemmes sur Loire, France) with continuous recording of arterial oxygen saturation, nasal-oral airflow, chest and abdominal wall motion, and body position [
American academy of sleep medicine, rules for scoring respiratory events in sleep: update of the 2007 AASM manual for the scoring of sleep and associated events. Deliberations of the sleep apnea definitions task force of the american academy of sleep medicine.
]. At 6 months, SDB severity was evaluated under thermoplastic or custom-made MAD with either type III overnight respiratory recording (n = 120) or overnight pulse oximetry (n = 38) using Nonin 8500 M (Nonin Medical Inc. Plymouth, MN, USA) with calculation of the ODI and T90 [
Continuous variables were described as mean (standard deviation [SD]) or mean (95% confidence interval, [CI]) for variables with a normal distribution and as median (interquartile range [IQR]) for variables with a non-normal distribution. Normality of distribution was assessed using the Kolmogorov–Smirnov test. Normal variables were analyzed using an unpaired t-test for intergroup difference and a paired t-test for intragroup difference. Linear regression analysis was used to adjust for baseline values and potential covariates. Non-normal variables were analyzed using the Mann-Whitney test for intergroup difference and the rank-signed Wilcoxon test for intragroup difference. The Chi-square test and Fisher's exact test were used for categorical variables, as appropriate. All reported p-values were two-sided. A p-value less than or equal to 0.05 was considered to indicate statistical significance. All statistical analyses were performed with SAS software (SAS/STAT Package 2002–2003 by SAS Institute Inc. Cary, NC, USA).
3. Results
3.1 Primary outcome
A significant decrease in AHI, AI and ODI was observed with both thermoplastic and custom-made MAD therapies. No significant change was observed in the 2 groups for T90. After adjustment for baseline values, age, BMI and study site, no significant intergroup differences were observed between thermoplastic and custom-made MAD therapies regarding the outcomes of AHI, AI, ODI and T90 (Table 2). No significant adjusted intergroup differences were observed between the 2 devices when changes in AHI were expressed as Δ outcome values as defined as [(baseline value - 6-months follow-up value)/baseline value] * 100 (Table 2). Treatment responses according to AHI reduction under thermoplastic and custom-made MAD are presented in Fig. 3. A complete treatment response (AHI reduced by = 50% to less than 5) was obtained in 34.6% of patients treated with thermoplastic MAD versus 26.2% in the custom-made MAD group (p = 0.32). The rate of partial response (AHI reduced by = 50% to but ≥ 5) was 34.6% in the thermoplastic MAD group versus 35.4% the in the custom-made MAD group (p = 0.92). A treatment failure (AHI reduced by <50%) occurred in 30.8% of patients treated with thermoplastic MAD versus 38.4% in the custom-made MAD group (p = 0.39).
Table 2Effects of thermoplastic mandibular advancement device (MAD) vs custom-made MAD device on sleep-disordered breathing severity.
Data from 120 patients with type III overnight respiratory recording at 6 months (55 in the thermoplastic MAD group and 65 in the custom-made MAD group).
Data from 120 patients with type III overnight respiratory recording at 6 months (55 in the thermoplastic MAD group and 65 in the custom-made MAD group).
Data from 120 patients with type III overnight respiratory recording at 6 months (55 in the thermoplastic MAD group and 65 in the custom-made MAD group).
Data are expressed as mean (standard deviation), or mean (95% confidence interval [CI]).
Abbreviations: AHI, apnoea-hypopnoea index; AI, apnoea index; ODI, 3% oxygen desaturation index; T90; time spent with SaO2 <90%,%.
a Adjusted for baseline value, age and body mass index and study site.
b p < 0.001 versus baseline.
c Data from 120 patients with type III overnight respiratory recording at 6 months (55 in the thermoplastic MAD group and 65 in the custom-made MAD group).
d p < 0.05 versus baseline.
e Changes in AHI are presented as Δ outcome values as defined by [(baseline value - 6-months follow-up value)/baseline value] * 100.
Fig. 3Treatment response for thermoplastic (n = 55) and custom-made mandibular advancement device (MAD) (n = 65) where complete response equals apnea-hypopnea index (AHI) reduced by = 50% to less than 5, partial response equals AHI reduced by = 50% but still ≥5, and failure equals AHI reduced by <50%.
As shown in Table 3, the ESS improved significantly after both thermoplastic and custom-made MAD. A significant improvement of the QD2A depression score was also observed in the thermoplastic MAD group. After adjustment for baseline values, baseline AHI, age, BMI and study site, there was no between treatment difference for the outcome of sleepiness, depressive symptoms, the overall mental and physical component scores and most subscale measures of HRQL. No significant correlations were observed between changes in AHI and changes in SF36 Physical Component Summary (p = 0.5) or Mental Component Summary (p = 0.5). As shown in Table 4, thermoplastic and custom-made MAD therapies for six months were associated with a similar improvements in snoring, fatigue and sleepiness complaints. The global treatment satisfaction was also similar in the 2 groups. However, thermoplastic MAD therapy was associated with significantly higher side effects scores for tooth pain (p < 0.0001) and self-reported occlusal changes (p = 0.0069). Reported daily use of the device was also significantly lower in the thermoplastic MAD group than in the custom-made MAD group (p = 0.035).
Table 3Effects of thermoplastic mandibular advancement device (MAD) vs custom-made MAD device on daytime sleepiness, depressive symptoms and health-related quality of life (HRQL) questionnaires.
Table 4Symptoms of obstructive sleep apnoea (OSA), global treatment satisfaction, perceived side effects and self reported compliance after 6 months of treatment with thermoplastic mandibular advancement device (MAD) vs custom-made MAD.
Patients were asked to give a score from 0 to 3 (0, absent; 1, mild; 2, moderate; 3, severe) for each side-effect of oral appliance therapy. A global side-effects score from 0 to 18 was then calculated.
Data are expressed as percentages, mean (standard deviation) or median [interquartile range].
a Patients were asked to give a score from 0 to 3 (0, absent; 1, mild; 2, moderate; 3, severe) for each side-effect of oral appliance therapy. A global side-effects score from 0 to 18 was then calculated.
b Global treatment satisfaction was assessed using a 0–10 visual analog scale.
This study showed no significant difference in treatment efficacy between thermoplastic and custom-made MADs, whether in terms of reduction of SDB severity or symptom relief. Self-reported treatment compliance was high and only slightly lower with the thermoplastic MAD group. Although global treatment satisfaction was not statistically different, global side-effects score were higher in patients treated with a thermoplastic MAD, mainly because of tooth pain and self-reported occlusal changes.
Numerous prefabricated MADs are currently commercialized, ranging from ready-to-use non-customizable, non-adjustable devices to more sophisticated, thermoplastic, partially customized (the so called “boil and bite” appliances) devices. However, practice guidelines to date still strongly recommend the use of a custom-made MAD over non-custom devices [
]. Among thermoplastic devices evaluated in the literature, those without chairside impressions and/or customized design were found to be poorly effective and uncomfortable, leading to poor compliance and treatment discontinuation [
]. The thermoplastic MAD evaluated in our study was partly customized and was fitted by a qualified dentist, following careful examination to assess contra-indications. Chairside impressions of the thermoplastic material resulted in a customization of a pre-fabricated device, which was immediately available to the patient, in contrast with custom-made devices, which often take several weeks to be manufactured. Titration and follow-up evaluations were conducted along the same guidelines for the thermoplastic MAD and the custom-made device. Clearly, this adds to the process length but ensures suitable fitting and retention, and consequently proper tolerance and efficacy of the appliance, as already shown with other devices [
Discrepant findings were obtained in previous studies evaluating the impact of ready-made or partially customized MADs on SDB and related symptoms. The TOMADO randomized trial compared non-adjustable “boil and bite” thermoplastic appliances with a custom-made MAD for the treatment of mild OSA [
]. All devices reduced AHI compared with no treatment but compliance was lower with the self-moulded device, which was the least preferred treatment at trial exit. Friedman et al. [
] found that a custom-made device achieved higher rates of objective improvement and cure of OSA than a thermoplastic MAD. Self-reported adherence was present in 54% of patients on thermoplastic MAD versus 65% on custom-made MAD. At 6 months, only one third of patients on thermoplastic MAD were still considered adherent, compared to 51% in the other group. Using the same thermoplastic device Vanderveken et al. [
] found that thermoplastic MAD was completely or partially effective in 31% of patients versus 60% for the custom-made MAD. In a recent randomized study, Johal et al. [
] reported a response rate of only 24% with a thermoplastic MAD versus 64% in the custom-made arm. While these studies are difficult to compare due to marked differences in devices and study designs, titration of mandibular advancement appears to be an important factor of treatment success [
Common side effects of MAD therapy include mucosal dryness, hyper salivation, tooth discomfort, temporal mandibular joint and muscle pain, tooth movement and self-reported occlusal changes [
]. Our study showed higher side effect scores with the thermoplastic MAD than in the custom-made group although global satisfaction was not different between the 2 groups. One can hypothesize that the high retention properties of the BluePro® thermoplastic MAD [
] contributed to its therapeutic efficacy but also resulted to greater tooth discomfort and a slightly lower reported compliance.
We acknowledge a number of limitations of the present study. While outcome assessors were unaware of the device assignment, this was not a randomized trial. Patients treated with the thermoplastic MAD presented several baseline characteristics that have been associated with better treatment outcomes on MAD therapy including younger age, lower BMI and less severe OSA [
]. However, no intergroup differences were observed between thermoplastic and custom-made MAD for SDB reduction and symptom relief after adjustment for these confounding factors. Among 158 included patients, only 120 had available AHI data obtained by type III overnight respiratory recording at 6 months. However, all patients had available data on nocturnal hypoxemia which have been found to be more strongly correlated to heath ouctomes than the AHI [
European Sleep Apnoea Database study collaborators, Nocturnal intermittent hypoxia predicts prevalent hypertension in the European Sleep Apnoea Database cohort study.
]. Another potential limitation of the present study is that the comparison between thermoplastic and custom-made devices was mainly based on questionnaires with no cardiovascular outcomes. Symptoms and quality of life are major therapeutic targets in OSA patients. Excessive daytime sleepiness, depressive symptoms and quality of life were evaluated by validated and widely used questionnaires [
]. However, as thermoplastic MAD therapy was associated with significantly higher side effects scores for tooth pain and self-reported occlusal changes, temporomandibular disorders and craniofacial changes related to thermoplastic versus custom-made devices therapy should be objectively measured in future comparative studies [
]. We acknowledge that cardiovascular outcomes have emerged as a therapeutic objective in patients with OSA. A recent review and meta-analysis concluded that both CPAP and MAD therapies were associated with reductions in blood pressure with no statistically significant difference between these therapies regarding blood pressure outcomes [
]. However, lowering blood pressure was not a major therapeutic objective in our population since only 17.5% of patients were hypertensive at inclusion. Whether OSA therapies have the power to reduce the incidence of late cardiovascular events has not been demonstrated yet [
]. However, being uncontrolled with no sham device group, these studies were not accounting for the influence of confounders like lifestyle and dietary modifications on endothelial function [
]. Conversely, a recent multicenter randomized controlled trial showed that treating severe OSA with MAD for 2 months reduces SDB and related symptoms, but has no impact on peripheral endothelial function [
]. Further studies are required to determine whether MAD therapy of OSA may improve cardiovascular outcomes. We also acknowledge the lack of objective measurement of treatment compliance in the present study. However, several studies demonstrated a high agreement between self reported and objectively measured compliance on effective MAD therapy [
]. Finally, the relatively short duration of follow-up in the present study does not allow drawing any conclusion regarding long-term treatment efficacy and side effects of the two types of MAD. However, this drawback is irrelevant if the use of thermoplastic MAD is considered for a short duration trial prior to the fabrication of a custom-made device. Furthermore, recent meta-analyses addressing the impact of MAD therapy on SDB and related symptoms reported significant changes for studies duration from to 2–12 weeks [
Comparison of the effects of continuous positive airway pressure and mandibular advancement devices on sleepiness in patients with obstructive sleep apnoea: a network meta-analysis.
Meta-analysis of randomised controlled trials of oral mandibular advancement devices and continuous positive airway pressure for obstructive sleep apnoea-hypopnoea.
This study demonstrates the efficacy of a titrable thermoplastic MAD in reducing SDB and related symptoms in patients with mild to severe OSA. Reported compliance at 6 months was high despite more dental discomfort than with custom-made MAD.
Financial support
This work was funded by the Institut de Recherche en Santé Respiratoire (IRSR) des Pays de la Loire (9 rue du landreau - BP 77132 - 49071 Beaucouzé cedex, France). The content of this manuscript is solely the responsibility of the authors.
Acknowledgements
Author contributions: F.G., M.L.V. and S.L. conceived the study, analyzed the data and drafted the manuscript; X.L.N., P.P., N.M., A.E., J.D.K.D., C.F., B.V., M.L.,W.T. contributed to the acquisition of data, revised the manuscript critically for important intellectual content, and approved the final version to be submitted.
The authors thank Wissam Boucenna, Sandra Girard and Christelle Gosselin for their help with trial administration, monitoring, and coordination, as well as data management.
BlueSom, France, provided the thermoplastic appliances free of charge but had no involvement in the design of the study, the analysis of data or drafting of the manuscript.
Conflict of interest
This was not an industry-supported study. The authors have indicated no financial conflicts of interest.
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Increased prevalence of sleep-disordered breathing in adults.
Continuous positive airway pressure devices for the treatment of obstructive sleep apnoea-hypopnoea syndrome: a systematic review and economic analysis.
Health Technol. Assess. winch. Engl.2009; 13 (iii–iv, xi–xiv, 1–119): 143-274
IRSR sleep cohort group, Influence of marital status and employment status on long-term adherence with continuous positive airway pressure in sleep apnea patients.
Comparison of the effects of continuous positive airway pressure and mandibular advancement devices on sleepiness in patients with obstructive sleep apnoea: a network meta-analysis.
Meta-analysis of randomised controlled trials of oral mandibular advancement devices and continuous positive airway pressure for obstructive sleep apnoea-hypopnoea.
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