Original Article 3, Issue 8.1

Polysomnographic Pilot Study of a New Mandibular Oral Device for Mild to Moderate Obstructive Sleep Apnea

http://dx.doi.org/10.15331/jdsm.7174

Giacomo Chiaro, MD¹; Ninfa Amato, PhD¹; Francesco Fanfulla, MD²; Massimo Ciocco, DMD³; Damiano Frigerio, DMT³; Alessia Sada, DMD⁴; Renato Piantanida, MD⁵; Marco Pons, MD⁶; Mauro Manconi, MD, PhD^1,7,8
 
1Sleep Medicine Unit, Neurocenter of Southern Switzerland, Ospedale Regionale, Lugano, Switzerland; ²Respiratory Function and Sleep Medicine Unit, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy; ³Private Practice, Lugano, Switzerland; ⁴Private Practice, Verbania, Italy; ⁵Department of Otorhinolaryngology, Civic Hospital of Lugano, Lugano, Switzerland; ⁶Department of Pulmonology, Civic Hospital of Lugano, Lugano, Switzerland; ⁷Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano; ⁸Bern University, Bern, Switzerland

ABSTRACT

Study Objectives:

The mandibular advancement device (MAD) in study, the velolingual bite (VLB), was a custom-made, monobloc device including a tongue retention and suction cavity and a direct anchorage onto the mandibular bone and not onto the teeth. The main objective of the study was to evaluate the efficacy of the MAD in reducing pathologic sleep-related breathing events and in improving overall sleep quality. The study also sought to evaluate tolerability of and compliance to the MAD therapy.

Methods:

This was a monocentric, prospective, open-label, interventional, polysomnographic pilot study. The main study outcome was the reduction in pathologic sleep-related breathing events. Treatment response was defined as a decrease of ≥50% in apnea-hypopnea index (AHI) and respiratory disturbance index (RDI). Treatment success was defined as the normalization of the AHI (< 5 events per hour). Secondary outcomes included improvement of video-polysomnographic parameters and subjective sleep quality and daytime somnolence. Side effects, tolerability, and compliance to treatment were adjunctive secondary outcomes, measured subjectively by means of a semi-structured self-administered questionnaire. 

Results:

Twenty patients (3 females) were enrolled, of whom 19 completed the study. Complete treatment success (AHI <5 events per hour) was met in 11 cases. Treatment response (decrease of ≥50% in AHI and RDI) was reached in 13 and 14 patients, respectively. The MAD was well tolerated and no major side effects were reported.

Conclusions:

The VLB was effective in reducing pathologic sleep-related breathing events. Treatment response and treatment success were both met in a large proportion of subjects. The MAD was well tolerated, with mild side effects that were mostly confined to salivation issues and initial and transient toothache and temporomandibular joint discomfort.

Keywords:

mandibular advancement device; custom-made; velolingual bite; sleep apnea; polysomnography

Citation:

Chiaro G, Amato N, Fanfulla F, et al. Polysomnographic pilot study of a new mandibular oral device for mild to moderate obstructive sleep apnea. J Dent Sleep Med. 2021;8(1)

INTRODUCTION

Mandibular advancement devices (MAD) are a valid alternative to continuous positive airway pressure (CPAP) ventilation during sleep in the treatment of snoring and mild to moderate obstructive sleep apnea syndrome (SAS).¹ MADs may also be considered in patients with se­vere SAS who do not tolerate CPAP treatment or in combi­nation with it.² Worn intraorally during sleep, they are usu­ally anchored onto the dental arches and induce mandibular advancement (i.e., protrusion), resulting in several benefi­cial anatomic changes, including anteroposterior and lat­eral retrolingual and pharyngeal space enlargement, result­ing in increased oropharyngeal cross-sectional areas and upper airway volume. The reduction in pathologic respira­tory events during sleep seems to correlate with the previ­ously mentioned modifications in upper airway dimensions induced by MADs.³

A wide variety of MADs are available on the market, covering a range of sophistication and cost. They slightly differ from one another in the following aspects: configu­ration (i.e., one or two pieces); size; material; degree of at­tachment to patient's dentition; coupling mechanism (i.e., the method by which the two upper and lower pieces con­nect); occlusal coverage (i.e., coverage of the surfaces of the teeth that touch each other when the mouth is closed); ability to titrate the mandibular protrusion (so far, only two-piece devices are available for custom titration); propulsive mechanism, and oral respiration. Custom-fitted and titrata­ble MADs are preferrable to self-administered and non-ti­tratable, over-the-counter varieties (i.e., boil and bite), since they appear to be more effective, comfortable, and more likely to be retained by both dental arches, ensuring that the lower jaw does not fall out of the appliance during sleep.^4-6 There has been a proliferation of various designs since the first commercially available oral appliances were introduced in the 1980s.⁷ In March 2013, the American Academy of Dental Sleep Medicine (AADSM) published a definition of an effective MAD, focusing on custom-ti­tratable MADs.⁸

The MAD in the study, the velolingual bite (VLB), consists in a custom-made monobloc device including a tongue retention and suction cavity to push the tongue down and forward onto the mouth floor, thus preventing its lifting towards the hard palate.  Its design requires the pres­ence of only four occlusal points, allowing for a non-inva­sive frontal push onto the vestibular face of the mandibular bone, thus reducing the risk for occlusal changes, tooth loosening, and the development of an anterior crossbite, which represent the major long-term adverse effects of oral appliances. Currently, the VLB represents the first mon­obloc device that can be titrated. It holds a Swiss patent and trademark. European equivalents are underway. All VLB components are CE marked and have a 5-year warranty. The possibility of printing further duplicates with three-di­mensional machinery is currently under development (Ap­pendix A, supplemental materials).

STUDY OBJECTIVES

The main objective of this study consisted in explor­ing the efficacy of the VLB in reducing pathologic sleep-related breathing events and improving overall sleep qual­ity. The study also sought to evaluate the tolerability of and compliance to MAD therapy.

METHODS

Trial Design

This was a monocentric, prospective, open-label, in­terventional, polysomnographic pilot study.

Inclusion and Exclusion Criteria

Eligible study subjects had to be consecutive female and male patients aged 18 to 65 years referred to the sleep center for suspected SAS, and who underwent video-poly­somnography (VPSG) within the past 3 months from study beginning date. Patients had to have mild to moderate SAS (AHI ≥ 5 events per hour and < 30 events per hour). The presence of at least four teeth both in the posterior lower and upper arches and the ability to protrude the mandible for at least 6 mm were a requirement.

Any one of the following criteria led to the exclusion of the participant: other significant neurologic conditions; major ear, nose, and throat surgery modifying the anatomy of the upper airways (i.e., uvulopalatopharyngoplasty; pa­latoschisis; neoplastic lesions); limited mental capacity; treatment with drugs affecting sleep (i.e.: hypnotics, anti­depressants, neuroleptics, antiepileptics); trigeminal neu­ralgia and/or myofacial pain dysfunction; sleep-related central breathing disorders; obesity with a body mass index (BMI) ≥ 30 kg/m². Prior to inclusion, significant oropha­ryngeal disease (especially adenotonsillar  and/or tonsillar hyper­trophy) had to be ruled out by means of fibro- endoscopic evaluation, performed by a trained ear, nose, and throat (ENT) specialist (RP). Patients who concomitantly used CPAP or positional therapy were excluded from the study. All patients gave their written consent for the study, which was approved by the local ethics committee.

Design of the Study

The study consisted of seven visits (Figure 1). At visit 1, inclusion and exclusion criteria were checked and eligi­ble subjects were included in the study. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were administered.

At visit 2, subjects underwent an odontologic evalua­tion. Thereafter, the MAD was produced and, at visit 3, it was administered at 50% of each subject’s mandibular ad­vancement, as previously assessed on calculations of the subject’s maximal mandibular protrusion. Immediate toler­ability and side effects (myofacial pain, temporomandibu­lar tension) were checked at study visits 3 and 7 by means of a semi-structured self-administered questionnaire (Ap­pendix B, supplemental materials). If the subject experi­enced important side effects at this stage, the study would be discontinued.

At visits 4 and 5, further mandibular advancements – to 60% and 70% respectively – of the calculated maximal mandibular protrusion were performed by the dentist.

At visit 6, the subject underwent a second VPSG while wearing the MAD. If, at any point from MAD administra­tion (visit 3) to the achievement of a 70% mandibular pro­trusion (visit 5), any serious side effect occurred, the dentist would stop the mandibular advancement process and return to the previous level of mandibular protrusion, at which no side effects were experienced. The subject would then pro­ceed directly to VPSG and leave the study thereafter.

At the final evaluation (visit 7), the subject met with the investigators again. PSQI and ESS were administered. The custom-made MAD was left with the subject free of charge.

VPSG Methods

Each subject underwent two full-night VPSG record­ings, carried out following standard American Academy of Sleep Medicine procedures,⁹ described in detail in a previ­ous study.¹⁰ All recordings were scored by a single physi­cian expert in sleep medicine (GC) and the final diagnosis of SAS was confirmed by the senior author (MM). Those patients who had a supine AHI at least double the non­supine AHI during basal PSG were defined as positional.

Outcome Measures and Assessments

The main study outcome was the reduction in patho­logic sleep-related breathing events. Related primary out­come measures were the AHI, RDI, and supine AHI. Treat­ment success per each patient was defined as the normali­zation of the AHI (< 5 events per hour). Positive treatment response was defined as a decrease of ≥50% in AHI and RDI.

Secondary outcomes included improvement of sleep efficiency, sleep quality, and daytime somnolence. The im­provement of sleep quality and daytime somnolence were measured subjectively with the PSQI and ESS. Related sec­ondary outcome measures were polysomnographic param­eters such as sleep efficiency, sleep latency, and wake after sleep onset, a measure of infrasleep awakenings.

Side effects, tolerability, and compliance to treatment were monitored and measured subjectively by means of a semi-structured self-administered questionnaire (Appendix B, supplemental materials) covering the following aspects: usage (nights/week; hours/night); side effects, reasons for interrupting usage; Visual Analog Scale for Pain (VAS Pain)¹¹; Visual Analog Scale for Satisfaction (VAS Satis­faction). The number of dropouts and the percentage of in­complete mandibular advancements were other outcome measures.

Statistical Analysis

Values are presented as mean ± standard deviation. Data were first checked for normality and homogeneity of variance using the Shapiro-Wilk test and the Levene test, respectively. Within subjects, comparisons were then per­formed using the Wilcoxon rank-sum test. The Holm cor­rection was applied to deal with multiple testing, and dif­ferences were considered significant at a value of P < 0.05 after correction. All statistical analyses were performed us­ing SPSS® Version 25 (IBM, Armonk, NY).

The power calculation estimated at least 15 subjects, evaluated with two polysomnograms (PSGs) each (one ba­sal and one on-treatment), as the number of subjects to al­low the rejection of the null hypothesis with a power of 0.8 and type I error probability of 0.01.

Figure 1 Study design. (more ...)

RESULTS

Demographics

A total of 20 subjects (3 females) were enrolled, with an age range between 25 and 59 years (49.3 ± 9.2). Base­line BMI was 25.3 ± 2.4 and 25.2 ± 2.2 at the time of the second VPSG recording. One subject decided to discon­tinue the study before the MAD was produced. The remain­ing 19 patients completed the study, with 18 of them having proceeded to a mandibular advancement equal to 70% and one to 60% of their calculated total jaw excursion.

Polysomnographic Results

Polysomnographic data are summarized in Table 1. Overall, statistically significant reductions in AHI, supine AHI, RDI,  and oxygen desaturation index 3% were found between PSGs before and during treatment. Complete treatment success (AHI <5 events per hour), which repre­sented the main study outcome, was met in 11 cases. Treat­ment response (decrease of ≥50% in AHI or RDI) was reached in 13 and 14 cases, respectively (Figure 2). The arousal respiratory index significantly decreased (9.9 ± 4.8 vs. 3.5 ± 2.7, P = 0.009). Supine AHI as well non-rapid eye move­ment AHI were strongly suppressed by treatment, whereas the effect on rapid eye movement (REM) AHI was less ev­ident. Twelve of 19 patients were affected by positional ob­structive sleep apnea, as defined in the Methods section.

Age, BMI, RDI, AHI, supine AHI, and REM AHI were not predictors of either complete or partial response, when compared between responders (14 subjects, RDI cut­off value 50%) and non –responders (5 subjects). The same was true for those 11 subjects meeting treatment success (AHI >5 events per hour). These results should be taken into account carefully, given the low number of subjects.

Questionnaires

Eleven and 17 subjects out of 19 returned the semi-s­tructured self-administered questionnaire regarding MAD tolerability and safety at study visit 3 and at the final eval­uation, respectively. Results are summarized in Table 2. Overall, 70% of subjects reported using the device for 7 nights a week and 78% all night long. No subjects reported a score higher than 4 on the VAS Pain at 50% advancement and no subjects reported a score higher than 5 on the VAS Pain at final evaluation (only mean results are shown in the table). Regarding device satisfaction, all subjects reported a score higher than 5 on the VAS Satisfaction at 50% ad­vancement, as well as a score higher than 7 at final evalua­tion.

All patients returned both sleep questionnaires (PSQI and ESS) at both study times. There was a significant re­duction in the PSQI total score (6.6 ± 24 vs. 4.9 ± 2.6, P = 0.006), as well as in the ESS scores (7.0 ± 4.7 vs 5.0 ± 3.6, p = 0.02), although both scores (before and after treatment) were not pathologic.
 

Figure 2 Changes in AHI between VPSG 1 and 2. (more ...)

 

Table 1 Polysomnographic parameters. (more ...)

 

Table 2 Usage, tolerability and side effects. (more ...)

DISCUSSION

This study documented a significant efficacy of the new VLB device in reducing pathologic sleep-related breathing events, as measured by the reduction in AHI, in the supine position, as well as in non-REM sleep. A signif­icant reduction was also detected for the RDI before and after intervention. Both treatment success and response were met in most of the subjects. Although RDI improved in all subjects, treatment response was not achieved in 4 of 19 subjects. A specific risk factor involved in such reduced efficacy for this minority of patients was not identified.

A significant improvement in sleep efficiency was not detected, nor was a reduction in both sleep latency and wake after sleep onset between the two PSGs, which is in line with previous findings and might depend on having normal values at baseline.⁴ Conversely, it was noted that the subjective perception of overall sleep quality, assessed through the PSQI, improved with treatment. Although the mean ESS score was normal at baseline, but close to the pathologic threshold, a significant improvement after treat­ment was observed.

Overall, the MAD was well tolerated, with mild side effects, mostly confined to salivation issues and initial and transient toothache and temporomandibular joint discom­fort. New-onset symptoms provoked by VLB use were very mild and limited to transient muscle rigidity, pain dur­ing yawning, and temporary bite modifications. Compli­ance with the device was satisfactory, with more than 70% of the subjects using it every night of the week and 80% of them all night long. The short duration and the lack of com­parison with another effective MAD are the two main lim­itations of the study.

The efficacy results of this study are in line with data existing in the previous literature, in particular, the latest meta-analysis by Sharples and colleagues,¹² which recapit­ulated findings from three previous main meta-analyses.^13-15 All these works stated, in summary, that MADs were ef­fective in reducing AHI, ESS score, and other measures of sleep-disordered breathing compared with conservative management, but less than CPAP. Moreover, the VLB seemed to fulfill the characteristics proposed by Ramar et al. in their clinical practice guidelines for the treatment of SAS with MAD.⁴ Additionally, the VLB could sustain an effective protrusion level in all study subjects.¹⁶

Side effects causing patients to discontinue use of their oral appliance are less common than side effects causing adult patients with obstructive sleep apnea to dis­continue the use of CPAP and include dry mouth, excessive salivation, tooth discomfort, muscle tenderness, and jaw stiffness.¹⁷ Problems such as pain and occlusal changes have been related to discontinuation of MAD use in 7.5% to 25% of cases. A much higher percentage of tooth move­ment and occlusal change have been documented in longer follow-up periods (1 to 4 years).^{18, 19}

The new VLB is a custom-made, titratable oral device made out of biocompatible materials. In comparison with other MADs already available on the market, it features some novelties. Although it is one single piece, it allows the opening of the mouth and oral respiration through frontal holes. Its design requires the presence of only four occlusal points, allowing for a direct push onto the mandib­ular bone (no surgery required), thus reducing the risk for occlusal changes, tooth loosening, and the development of an anterior crossbite, which seem to represent the major long-term adverse effects of oral appliances.²⁰ In addition, the VLB can be applied to patients with a reduced number of teeth. The presence of the winglet vault, which acts as a tongue retainer, might have a double benefit. On one side, it creates a suction cavity that pulls the tongue forward. On the other side, it acts as a tongue retainer, preventing pres­sure of the tongue on the hard palate, which is a defensive mechanism spontaneously occurring during obstructive sleep apneas. Such vertical pressure is accompanied by the lingual vertical muscle contraction against the hard palate, which, in turn, produces an increase of the tongue volume toward its posterior portion, favoring a retrolingual occlu­sion. Currently, the VLB represents the first monobloc de­vice that can be titrated.

In conclusion, the new MAD was well tolerated and effective in mild-to-moderate obstructive sleep apnea on all sleep-related PSG breathing parameters. Longer and com­parative studies are needed to test the long-term tolerability of this MAD and its superiority in comparison with other MADs.

ABBREVIATIONS 

AHI = apnea/hypopnea index
BMI = body mass index
CPAP = continuous positive airway pressure
ESS = Epworth Sleepiness Scale
PSQI = Pittsburgh Sleep Quality Index
RDI = respiratory distress index
REM = rapid eye movement
SAS = sleep apnea syndrome
VAS = visual analog scale
VLB = velolingual bite
VPSG = video-polysomnography

ACKNOWLEDGMENTS

The authors thank Dr. Gennaro Lucera for his essen­tial contribution in creating the prototype of the tested de­vice (VLB). The patent of the VLB belongs to Lucera In­vestments AGL. The study was partially supported by an unrestricted grant provided by Lucera Investments Sagl (Via Curti 5, 6900 Lugano, Switzerland).

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SUBMISSION & CORRESPONDENCE INFORMATION

Submitted for publication March 24, 2020
Submitted in final revised form June 30, 2020
Accepted for publication August 1, 2020
 
Address correspondence to: Mauro Manconi, MD, PhD, Sleep and Epilepsy Center, Neurocenter of Southern Switzerland,  Civic Hospital of Lugano, Via Tesserete, 48 CH-6900 Lugano, Switzerland

DISCLOSURE STATEMENT

The authors have no conflicts of interest to disclose.

APPENDICES

Appendix A (more ...)

 

Appendix B (more ...)

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