Predictive factors of therapeutic response according to craniofacial skeletal biotype in patients with sleep apnea syndrome using mandibular advancement devices: a pilot study

Sleep apnea–hypopnea syndrome (SAHS) is characterized by repeated collapse of the upper airway during sleep, causing intermittent hypoxia and disturbances with interruption of sleep.¹  Nasal continuous positive airway pressure (CPAP) in the upper airway is the gold standard and first choice of treatment in patients with moderate to severe symptomatic SAHS.²  Intraoral mandibular advancement devices (MADs) are indicated in patients with night-time snoring and mild to moderate SAHS. MADs are less effective than CPAP, but patients show more acceptance and compliance in their use at night. However, until now, few studies have analyzed MAD prognostic factors that predict response or failure after their application, and there is a lack of agreement on it.³  A recent study by Sutherland et al.⁴  focused on evaluating the craniofacial influence on the response of MADs in awake patients but had no conclusive results regarding predictive factors in MAD therapy.

It is important to determine facial type because treatment mechanics and the stability of correction will vary accordingly. Ricketts and colleagues⁵  used five parameters describing facial types: facial axis angle, facial angle, mandibular plane angle, lower facial height, and mandibular arc. Mesofacial, brachyfacial, and dolichofacial facial patterns were defined based on these parameters.⁵ 

The efficacy of MADs is uncertain and not predictable, and more studies are needed to determine the best therapy for SAHS patients.^6,7  The objective of this study was to evaluate how facial biotypes can influence the therapeutic effect of MADs according to polysomnographic records of patients diagnosed with mild to moderate SAHS.

This research was performed by the Sleep Unit of the Gómez Ulla Central Defense Military Hospital (HCD), composed of the Departments of Pulmonology, Neurophysiology, Otorhinolaryngology, Radiology and Odontology, and approved by the ethical committee in the same institution (No. 49/18).

All methods used in this study were performed in accordance with the Declaration of Helsinki. Patients gave their written consent to be treated with MADs, knowing their long-term side effects and that their data could be used for future studies.

The sample was made up of patients with the health insurance of the Spanish armed forces (ISFAS). Patients were referred to the Dentistry Department of the HCD for MAD therapy after being diagnosed with mild to moderate SAHS.

A total of 46 patients of both sexes, without age limits, were recruited. They were diagnosed with mild to moderate SAHS by previously conducted polysomnography (PSG). In patients diagnosed with severe SAHS by PSG, a central component of SAHS, comorbidities of cardiovascular diseases, presence of any sign or symptom of temporomandibular joint pathology, active periodontal disease with loss of major bone support in 50% of teeth per hemiarch, absence of more than 50% of teeth per hemiarch, are seen.

Patients participating in the study underwent a lateral X-ray of the skull with the Instrumentarium Orthopantomograph OP300 (Finland) in the natural head position while occluding. The natural position of the head was obtained following the methodology described by Moorees and Kean⁸  in 1958. A cephalometric study was carried out in which the craniofacial structure was examined and patients were classified according to their facial biotype. The cephalometric study was carried out and analyzed by the same person, and the measurements were made using Dolphin Imaging cephalometric diagnostic software (Chatsworth, Calif), through which the cephalometric prescription FACE was used. Jarabak’s spheres of percentage were analyzed, determined by the averages obtained between the anterior facial height (nasion-menton distance) and posterior facial height (sella-gonion distance). Using the classification of the 46 patients according to this methodology, three subgroups were constructed as brachyfacial (n = 16), mesofacial (n = 14), and dolichofacial (n = 16) biotypes.

The brachyfacial pattern shows hypodivergent growth, in which the lower facial height is decreased, being in the 64% to 80% interval (Figure 1). The dolichofacial pattern is characterized by hyperdivergent growth, in which the anterior facial height is increased, being in the 54% to 58% interval (Figure 2). The mesofacial skeletal pattern is accepted as growth within normal limits, being in the 59% to 63% interval (Figure 3). The cephalometric points used in the study are described in Figure 4.

The device in this study was made with two independent splints fused with acrylic and two lateral unidirectional screws that classified this kind of MAD as an adjustable advance type (Figure 5).

This device is dental supported, and the splints were extended 3 to 5 mm beyond the dental equator to avoid dental side effects.⁹  The design of the construction bite to advance the mandible was the same in all groups of patients at 70% of the protrusive maximum. Measurements were carried out using the George gauge.

The patients were instructed on how to place the MAD intraorally and had at least a 3-month trial period to adjust to the MAD before performing the second PSG test. The patients used the device for the recommended time after it was delivered, and they presented good cooperation. Patients with poor cooperation were not included in the study.

All patients had an initial PSG study that diagnosed mild to moderate SAHS. The PSG system used in this study was the Net Beacon.

The MAD therapeutic validation examination was carried out by means of a second nightly polysomnographic examination. Finally, there were two PSG recordings: the first one was the diagnosis, and the second one was to check the therapeutic effect of the MAD. The following PSG parameters were evaluated:

• Respiratory Disturbance Index (RDI) is the number of apneas and hypopneas per hour, along with the respiratory effort associated with micro-awakening. The patient was classified as mild if they had 5 to 14 events per hour, moderate if they had 15 to 30 events per hour, and severe if they had more than 30 events per hour. The MAD treatment success rate was established to achieve a reduction in the RDI to a value <10 and >50% RDI reduction compared with baseline.

• Oxygen Desaturation Index (ODI) is the number of episodes of oxygen desaturation by at least 4%/h.

• Number of arousals or awakenings are brief alerts of the brain that interrupt the structure of dreams without having to wake up the subject. They were detected through the electroencephalogram.

The Shapiro-Wilk test was used to choose parametric or nonparametric tests. The quantitative variables were described by arithmetic mean and standard deviation or the median and interquartile range. Absolute and relative frequencies (%) were used for qualitative variables. The hypothesis tests used were Pearson’s chi-square test, paired-sample Student’s t-test, Wilcoxon test, one-way analysis of variance, Kruskal-Wallis test, and Mann-Whitney U-test. P < .05 was considered statistically significant. Data were analyzed using the Statistical Package for Social Sciences (SPSS), version 25 for Windows (Chicago, Ill). Consecutive nonprobabilistic sampling was chosen.

A total of 46 patients of both sexes, without age limit, were recruited. The mean age in each facial biotype was between 53 and 66 years, with no significant difference among them. This was also true for body mass index, neck circumference, and sex. The distribution of these characteristics was homogeneous among the three groups studied (Table 1).

A reduction in RDI by 15 events/h (P < .001) in the brachyfacial group and by 14 events/h (P < .001) in the mesofacial group were seen. The dolichofacial group did not show a significant reduction in RDI (Table 2).

In the brachyfacial group, ODI was reduced by 45 episodes/h (P = .001) and was reduced in the mesofacial group by 18 episodes/h (P = .001). The dolichofacial group did not show a significant reduction in ODI (Table 2).

The brachyfacial group had a reduction in the number of awakenings by 23 events/h (P = .003). The mesofacial group had a reduction by 37 episodes/h (P = .012). The dolichofacial group did not have a reduction in the number of awakenings during sleep (Table 2).

The reduction obtained in the number of arousals was not significantly different between facial types, but there was a significant reduction in both RDI and ODI for all groups.

The brachyfacial group had a reduction in the RDI of 57% and a reduction in the ODI of 60%. The mesofacial group had the greatest percentage decrease in the RDI of 73% and a reduction in the ODI of 75%. The dolichofacial group obtained the smallest decrease in the polysomnographic variables, with a reduction in the RDI of 22% and a reduction in ODI of 19% (Table 3).

The Kruskal-Wallis test showed that there was significant response difference among skeletal patterns in the RDI and ODI (Table 4). The mesofacial group obtained a greater reduction in the RDI, 16% greater than the brachyfacial group and 51% greater than the dolichofacial group. The brachyfacial group had an improvement in RDI of 35% compared with the dolichofacial group. The mesofacial group had an improvement in ODI 15% greater than brachyfacial patients and 56.8% greater than the dolichofacial group. The brachyfacial group had a reduction in ODI 41.7% greater than the dolichofacial group (Table 5).

A meta-analysis performed by the American Academy of Sleep Medicine included 34 studies with a total of more than 1300 patients.⁶  Most striking was that, in only four studies, MAD therapy reduced the Apnea-Hypopnea Index (AHI) to below 5 events/h.⁶  These results are considered far from reaching the therapeutic range of healing. Compared with CPAP in the study carried out by Gagnadoux et al.¹⁰  MAD therapy reduced the AHI to less than 5 events/h in 42.8% of patients, while CPAP achieved it in 73.2% of patients. Treatment with MAD was shown to be less effective and with less predictable efficacy when compared with CPAP therapy.¹¹ 

Many research papers have urged the importance of increasing studies to find predictive factors to improve efficacy of MAD treatment.¹²  Currently, there is great controversy in the scientific literature about the influence of the craniofacial structure as a predictive factor in the treatment of SAHS with MAD.^13,14 

The results obtained in the current study showed how mesofacial and brachyfacial patients obtained a significant reduction in all polysomnographic parameters. In contrast, subjects with a dolichofacial pattern did not show a significant reduction in all of these polysomnographic variables. This variation in response may have resulted from anatomical differences and muscle physiology.¹⁵  Knowing in advance the small number and the nonhomogeneity of the current sample, in-depth statistical examination was carried out to analyze the reduction percentage of each facial biotype according to the PSG variables. Those who obtained the most significant reduction in the RDI and ODI were the mesofacial and brachyfacial groups.

A study by Guarda-Nardini et al.¹⁶  found results similar to the current study. The most common anatomical characteristics that the authors considered to be responsible for a negative response to MAD were common to the dolichofacial group: high mandibular plane angle and increased anterior facial height. In comparison, for brachyfacial and mesofacial patients, the shorter facial height was considered a good prognostic factor for MAD treatment.^17–19 

In contrast, results contradicting the literature were found on the response in reducing the AHI by using MAD therapy in dolichofacial patients.^20–22  In agreement with the current results, Woods et al.²³  showed that mesofacial and brachyfacial patients had more sagittal projection of the lower jaw than dolichofacial patients did. Dolichofacial patients have the mandible further down and back, increasing airway resistance and resulting in a poor prognosis for MAD treatment and a higher risk for SAHS.^24,25  This may have repercussions for mandibular dynamics. During protrusion, the mandible moves more downward and back, affecting other structures such as the hyoid bone.^26,27  It was observed that dolichofacial SAHS patients have the hyoid bone in a more caudal position, which may be considered a bad prognostic factor.^28,29  When the distance of it to the mandibular plane is reduced, the AHI displays a greater decrease using the MAD.³⁰ 

For patients with any previous signs or symptoms of temporomandibular joint (TMJ) dysfunction, MAD treatment is contraindicated.³¹  Joint pain in the TMJ is a usual side effect that can appear in up to 33% of patients undergoing MAD treatment.^21,32  Dolichofacial patients are more susceptible to TMJ problems due to decreased ramus height, decreased effective mandibular length, and backward rotation of the ramus, which may contribute to TMJ problems.³³  Thus, it would not be highly recommended that they undergo MAD treatment.^27,34  It would be preferable to consider other, alternative therapies that may be more effective, such as CPAP or SAHS orthognathic surgery.³⁵ 

The limitations of the study may be related to the number of patients studied and it not being a multicenter study and finding enough patients treated with MAD belonging to the same skeletal SAHS group to make the sample balanced.

• The craniofacial skeletal pattern in patients with SAHS influences the efficacy of the MAD, being a predictive factor for its efficacy.

• The MAD reduced the number of apneas in SAHS patients with a mesofacial or brachyfacial skeletal structure.

• In contrast, dolichofacial SAHS patients did not respond significantly to treatment with the MAD. Other therapeutic alternatives should be considered for this group of patients.

Thanks to I. Villar Blanco, C. Guiterrez Ortega, L. Callol, J. Jareno Esteban, and Ferhan Elmalı for their knowledge and advice.