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Volume 12 No. 08
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Scientific Investigations

Effectiveness of Oral Appliances in Obstructive Sleep Apnea with Respiratory Arousals

Pia Nerfeldt, MD, PhD; Danielle Friberg, MD, PhD
Karolinska Institute Department of Clinical Science, Intervention and Technology, Division of Ear, Nose and Throat Diseases, Stockholm, Sweden

ABSTRACT

Study Objectives:

To compare adherence and treatment effects with an oral appliance (OA) in patients with different types of obstructive sleep apnea (OSA): those with mainly respiratory arousals (“arousers”), and those with oxygen desaturations (“desaturaters”) at polysomnography (PSG).

Methods:

A prospective intervention study on 72 “tired snorers” with “normal” home sleep study (HSS), but later diagnosed as OSA with PSG, who accepted OA treatment. They were offered evaluation with a follow-up PSG and questionnaires, including the Epworth Sleepiness Scale (ESS), general health (GH), satisfaction, and side effects.

Results:

Sixty-six patients, 33 arousers and 33 desaturaters, were adapted to OA. The 1-year adherence rate was significantly higher among arousers (85%) than desaturaters (55%) (p = 0.034). Thirty-six of 66 patients underwent follow-up PSG; the apnea-hypopnea index was significantly reduced in 22 arousers from a median of 14 to 3 (p < 0.001), and in 14 desaturaters from 18 to 7 (p = 0.002; no significant group difference). ESS and GH showed no significant improvements in either group, although sleepy “arousers” (ESS ≥ 10) significantly improved their ESS. In total, 77% reported side effects, while 63% were still satisfied with the OA treatment. Gender analysis showed a significant dominance of females classified as “arousers” (p = 0.025).

Conclusions:

OSA patients with mainly arousals at PSG showed higher adherence to OA treatment, compared to patients with desaturations. Both groups responded similarly to treatment: improved nocturnal respiration, but only a small reduction of symptoms. We suggest that “tired snorers” with “normal HSS” should be offered PSG, and if OSA, also OA treatment.

Citation:

Nerfeldt P, Friberg D. Effectiveness of oral appliances in obstructive sleep apnea with respiratory arousals. J Clin Sleep Med 2016;12(8):1159–1165.


INTRODUCTION

Sleep-disordered breathing (SDB) is a common disorder including snoring, upper airway resistance syndrome (UARS), and obstructive sleep apnea (OSA). The symptoms for OSA include witnessed apneas and daytime sleepiness, and an association with increased morbidity and mortality has been documented.1,2 UARS is a milder form of OSA according to pathology seen during polysomnography (PSG). It is characterized by repetitive minor increases in resistance to airflow in the upper airway during sleep, leading to arousals without desaturations—so-called respiratory effort-related arousals (RERAs).35 UARS has also been shown to cause morbidity comprising daytime fatigue, hypertension, and depressive mood.35 Therefore, diagnosis and effective therapy are essential goals.

Diagnostic criteria for OSA in adults have changed over time; for example, the definition of hypopnea according to the American Academy of Sleep Medicine (AASM) has changed significantly. In 2007 the AASM published a new manual with two different definitions: (1) the “recommended” definition stipulates that hypopnea scoring requires ≥ 30% reduction in nasal pressure, associated with ≥ 4% desaturation; and (2) the “alternative” definition requires ≥ 50% reduction in nasal pressure, associated with ≥ 3% desaturation or an arousal.6 With these new scoring rules, the definition of hypopnea has been widened, with the added inclusion of arousals. Therefore, more events (previously classified as RERAs), are now defined as hypopneas, leading to a diagnosis of OSA rather than UARS. However, these new scoring rules are only applicable to “gold standard” PSG. In Sweden and other Nordic countries, the overnight respiratory recording, i.e., home sleep study (HSS), is widely used as a diagnostic method for OSA, since resources for PSG are limited. Furthermore, the scoring of the oxygen desaturation index (ODI) differs between HSS and PSG: HSS has a 4% desaturation limit, while PSG has a 3% limit.

BRIEF SUMMARY

Current Knowledge/Study Rationale: Polysomnography (PSG) rather than of home sleep study, could be justified by diagnosing obstructive sleep apnea (OSA) in patients with mainly respiratory arousals and evaluating their treatment outcome. This clinical study aimed to compare treatment adherence and success with an oral appliance (OA) between patients with mostly arousals and patients also with oxygen desaturations. If so, this would justify the costs of PSG and OA.

Study Impact: High OA treatment adherence and success in patients with mainly arousals strengthens the motivation for use of PSG and OA treatment in this subgroup of OSA patients.

In addition to diagnostic criteria, the AASM has also issued therapeutic practice guidelines. Oral appliance (OA) therapy is recommended for simple snoring and mild OSA, as well as for moderate to severe OSA if continuous positive airway pressure (CPAP) is not accepted, or if surgery is not appropriate.7 In Nordic countries, OA is widely used and well accepted by patients, as has been reported in many studies.8 However, in many regions, the government-financed therapeutic possibilities are limited for mild OSA and UARS. In Stockholm County, Sweden, where this study was performed, OA is not financed when the AHI is below 10. The cost for an OA is approximately 800 euros, which many patients with UARS do not want to pay. The new AASM rules from 2007 made it possible to improve the diagnostics for these patients with PSG and offer some of them government-financed OA treatment. We have earlier reported that in a selected population with “normal” HSS, but still elevated ratings of daytime sleepiness and snoring (UARS symptoms), the PSG results, based on the new diagnostic criteria since 2007, showed OSA in as many as 90%.9 The clinical question in the present study is if the treatment success (adherence, subjective outcomes, and AHI reduction) with an OA is as good in these patients with arousals without desaturations as in typical OSA patients with oxygen desaturations. If so, this would justify the excessive costs of PSG and OA. The worry of the caregiver is that patients with arousals caused by a minor respiratory restriction may have sleep so easily disturbed that they will not tolerate treatment with an OA. However, if an OA is accepted, its dilating/activating effect on the upper airway should be similar, regardless of whether the patient responds to the airway restriction with arousal or with arousal plus oxygen desaturation.

In this study patients with a “normal” HSS, but diagnosed as having OSA with PSG according to AASM rules from 2007, were offered and treated with an OA. Our aims were, firstly, to determine if patients with respiratory arousals and without oxygen desaturations (arousers) adhere to an OA in a manner similar to that of patients with oxygen desaturations (desatu-raters), and secondly, if treatment success with an OA is different among arousers compared to desaturaters in nocturnal respiration and subjective outcomes.

METHODS

The first aim of this prospective intervention cohort study was to investigate whether OSA patients with an oxygen desatu-ration index (ODI) < 6 (arousers) have a different adherence rate to OA than patients with ODI ≥ 6 (desaturaters). The second aim was to investigate whether arousers and desaturaters responded to OA with similar changes in nocturnal respiration and subjective outcomes. We also wanted to perform a subgroup analysis of sleepy patients (ESS ≥ 10) on treatment-induced changes in ESS.

The inclusion criteria were: (1) HSS result of AHI rating < 5; (2) questionnaire with responses for snoring as “often” or “always” rated on a 4-point Likert scale (“never,” “sometimes,” “often,” or “always”); (3) questionnaires for sleepiness using the Epworth Sleepiness Scale (ESS) ≥ 8 and/or tiredness, either in the morning or during the day, rated as “often” or “always”; (4) PSG performed between May 2008 and November 2009, median 7 (range 2–21) months after HSS; (5) PSG should fulfill the 2007 diagnostic criteria for OSA, with AHI or RDI ≥ 5; (6) suitable dental status for OA according to the dentist; (7) acceptance, defined as accepting OA as therapy.

For responding to the secondary aims, additional criteria should be fulfilled: (8) adaptation, defined as having an OA fitted, and adherent, defined as using the OA for at least 3 months; (9) having follow-up PSG with OA, median 13 (6–29) months after baseline PSG; (10) evaluating subjective outcomes of OA treatment with questionnaires, median 12 (range 5–24) months after adapted OA.

The number of patients who were offered and accepted OA as therapy at the visit to the ENT department was 72. Of these, 38 had ODI < 6 at the baseline PSG (referred to here as arousers) and 34 had ODI ≥ 6 (referred to as desaturaters). See Figure 1 for flow scheme. Baseline characteristics are shown in Table 1.

Flow scheme of inclusion and follow-up.

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Figure 1

Flow scheme of inclusion and follow-up.

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Baseline characteristics and results from home sleep study (HSS) and polysomnography (PSG) for 72 patients.

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Table 1

Baseline characteristics and results from home sleep study (HSS) and polysomnography (PSG) for 72 patients.

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The patients who were adherent to OA were offered a follow-up PSG with OA. Treatment success criteria were set to AHI reduction ≥ 50% and AHI < 10. The patients who had undergone a follow-up PSG were also mailed questionnaires.

Questionnaires for Subjective Evaluation

  1. Epworth Sleepiness Scale (ESS)10: 8 questions, 4-point Likert scale, range: 0–24.

  2. Hospital anxiety and depression (HAD) scale11: 7 questions measuring depression and 7 measuring anxiety, 4-point Likert scale, range 0–21 for anxiety and depression, respectively. Patients with 0–7 points are considered normal, those with 8–10 points are borderline, and those with ≥ 11 points have signs of depression or anxiety.

  3. The validated question concerning self-rated general health (GH) on a 5-point Likert scale,12 range 1–5.

  4. A local questionnaire on adherence, satisfaction, side effects of OA therapy, and also with questions regarding the impact of the OA treatment on improved sleep, improved daytime sleepiness, improved general health, and improved quality of life.

Oral Appliance Therapy

The OA has been suggested to act by maintaining the activity of the muscles, protracting the tongue, and holding the mandible in an increased vertical and protrusive position, thereby reducing the airflow resistance in the upper airway.13 The OA in this study is a mandibular repositioning appliance, custom-made at two specialized dental centers by, in total, 4 dentists. The models used include hard monobloc (58%), soft monobloc (8%) and split (34%) devices, with the same purpose: to advance the mandible approximately 75% of maximal protrusion. They are all titratable; the monobloc by cutting it into two halves and then glued together in a more protruded position. The choice of model depends on patient and dentist preference. All patients were seen at least once by the dentist after OA adaptation, and offered further consultation if needed for adjustment or motivation. The protrusion grade was increased when the PSG showed residual OSA.

Sleep Apnea Recordings

The home sleep study (HSS) was done using ambulant Embletta technology and was manually scored. The following parameters were recorded: oronasal flowmetry, SpO2, respiratory movements (abdomen and thorax), snoring, ECG, plethysmography, and position.

Polysomnography (PSG) was done in-lab, full-night, using the Embla technology, and manually scored. A total of 16 parameters were recorded EEG (C3-A2, O1-A2, O2-A1, C4-A1), EOG (right and left), EMG (chin and tibialis), oronasal flowmetry, SpO2, respiratory movements (abdomen and thorax), snoring, ECG, plethysmography, and position.

Statistics

Results are presented as the median (range) and nonparametric statistical analyses were used, as the material was non-normally distributed. Spearman rank correlation (SRC), Mann-Whitney U (MWU), and Wilcoxon matched pair (WMP) tests were used. All statistical calculations were done in Statistica.

Ethics

The study was approved by the Swedish National Ethics Committee at Karolinska University Hospital, Huddinge, Stockholm (number 2009/1076-32). Informed consent was obtained from all individual participants included in the study.

RESULTS

In total, 72 patients met the inclusion criteria and were offered and accepted an OA. Four patients were denied financial support for the OA from the County Council, 2 were lost to follow-up due to moving away (dropout rate, 8.3%), and the remaining 66 were adapted with an OA (33 arousers and 33 desaturaters). Twenty stopped OA treatment because of side effects (17 patients) or no subjective therapeutic effect (3 patients)—all together 5 arousers and 15 desaturaters. Among these 20 non-adherent, 9 dropped out during the preparation period at the dentist, while 7 patients were adapted with a hard monobloc, 2 with a soft monobloc, and 2 with a split device. The median 12-month adherence rate was significantly higher (28/33 = 85%) among arouser than among desaturaters (18/33 = 55%) (p = 0.034, MWU). Gender analyses showed that the females were classified as “arousers” in 24 of 35 (69%) cases, while the males only were arousers in 14 of 37 (38%) cases, a significant group difference (p = 0.025, MWU). At baseline the desaturaters had significantly higher body mass index (BMI) than arousers (p = 0.002, MWU), Table 1.

Of the 36 patients who underwent a follow-up PSG and filled out questionnaires, 22 were arousers and 14 desaturaters. Baseline and 6-month follow-up PSG results are presented in Table 2, showing significant improvements in nocturnal respiration (AHI, AHI supine, and RDI) in both arousers and desaturaters, with no group differences. No gender differences in outcomes were demonstrated. The reduction of AHI, measured as the ratio of the mean (ROM), was 74% for arousers and 68% for desaturaters. Altogether, 27 of 36 patients (75%) were successfully treated with OA according to the success criteria of AHI reduction ≥ 50% and AHI < 10. Nine patients were not successfully treated according to the AHI criteria, only one of whom had stopped using the OA; 3 of the 27 successfully treated had stopped.

Results from polysomnography and questionnaires at baseline and with oral appliance (OA) for each group.

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Table 2

Results from polysomnography and questionnaires at baseline and with oral appliance (OA) for each group.

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Of the 36 patients who completed the follow-up PSG with the OA, 26 to 33 patients filled out the various questionnaires (dropout rate, 8% to 28%) after a median of 12 months (range 5–24). Among the sleepy arousers with ESS ≥ 10, there was a significant improvement of ESS, Table 2. Otherwise, there were no significant improvements in the outcomes from questionnaires, and no significant differences between the groups (arousers/desaturaters) or gender, Table 2. Among adherent patients, 84% reported use of OA at least 5 nights per week.

Twenty-seven of the 36 patients answered general questions regarding the impact of the OA treatment; 16 patients (59%) reported that the OA had improved their sleep, 14 (52%) reported improved daytime sleepiness, 9 (33%) improved general health, and 11 (41%) an improved quality of life with the OA. The analysis showed no group (arousers/desaturaters) or gender differences.

Thirty of the 36 patients answered questions regarding side effects of the OA. Seven of 30 (23%) reported no side effects, but the rest reported the following problems: 16 with sore teeth, 14 with sore muscles, 9 with mouth dryness, 8 with movement of the teeth, and 1 with bad fitting of the device. There were no group (arousers/desaturaters) or gender differences.

In total, 20 of 32 (63%) reported that they were satisfied with the OA treatment, without group (arousers/desaturaters) or gender differences.

There was a positive correlation between improvements in AHI and improvement in the depression-rating on the HAD scale (r = 0.44, p < 0.05 SRC). There were no other correlations between changes in respiratory parameters (AHI or RDI) compared to changes in subjective parameters (ESS, GH, or HAD).

DISCUSSION

This clinical study on OA treatment for patients with “normal” HSS, but who were diagnosed as having OSA after PSG, compared the objective and subjective outcomes in 38 arousers and 34 destauraters. There was a significant difference in the OA adherence rate between arousers (85%) and desaturaters (55%). Further analyses of the 36 patients who had both baseline and 6-month follow-up-PSG showed a rather high treatment success (75%), with a significant AHI reduction in both arousers (median from 14 to 3) and desaturaters (from 18 to 7). There were no group differences in the reduction of nocturnal respiratory parameters between the arousers and the desaturaters. After a median of 12 months, the outcomes from questionnaires ESS, HAD, and General Health ratings showed no significant improvement in either group, but 63% reported that they were satisfied with the OA treatment.

The fact that the adherence rate was significantly higher among arousers than among desaturaters was a surprising finding. We had speculated that the arousers, who are easily aroused from sleep by even a minor respiratory restriction, would also be more sensitive to the side effects of OA, and therefore would not adhere to this treatment. This speculation could not be confirmed, which is a positive and clinically important finding. A possible explanation to the difference in adherence rate could be that among the sleepy arousers with ESS ≥ 10, there was a significant improvement of ESS, not seen among the sleepy desaturators. On the other hand, there was no significant change in ESS among arousers. This could be explained by the fact that we included excessively tired patients, but we also included some patients with low ESS scores, since it is known that ESS has a low predictive value for OSA diagnosis.14 Another explanation of adherence differences could be that the total arousal index at baseline did not differ between groups, meaning that both groups had equal sleep fragmentation. The finding that desaturaters had a significantly higher BMI than arousers could indicate desaturations due to excessive weight.

Another important result is that the AHI reduction by the OA was equally significant in both groups. Our results give substance to the argument for further investigation with PSG when the HSS is “normal.” Not only is pathologic nocturnal respiration often detected, as shown in our previous study (90%),9 but treatment is also well adhered to and successful when analyzing the patient group with OA. The gender aspect—women are more numerous in the OSA population with mainly arousals (35/72 = 49%) compared to the general OSA population, where the female proportion is estimated to be 33%,15,16—is noteworthy and clinically important. The female OSA phenotype is likely dominated more by arousals and thereby more difficult to diagnose in screening with simple HSS. Furthermore, symptoms in women have been thought to be less specific, often leading to delay in diagnosis,5,17 thus requiring awareness on the part of physicians. The positive correlation between improvements in the AHI and improvement in the HAD-depression rating is considered to be of minor importance since the HAD itself did not improve; this was the only correlation between subjective and objective treatment results.

Our results can be compared to those of other OA studies. In a review, Hoffstein estimated that, after 30 months, 56% to 68% of patients continue to use an OA.18 Long-term adherence has been evaluated by Marklund, who showed a 5.2-year adherence of 58% (19/33)8 and showed that patients with mild OSA were more likely to continue treatment than patients with more severe OSA.19 These adherence figures are consistent with ours. Trying to compare with other studies on patients with OSA mainly due to arousals is more difficult. These patients are sometimes defined as UARS patients, depending on sleep registration methods and hypopnea criteria, and therapeutic studies of UARS are few in number.20 However, Yoshida et al. were able to demonstrate effects of an OA on the treatment of 32 UARS patients screened to have an AHI < 5 but an arousal index > 10. After only 14 to 60 days, they found effects on both subjective (ESS) and objective (MSLT) sleepiness parameters. Furthermore, the arousal index was reduced as much as from a mean of 35.5 ± 8.8 to 8.9 ± 4.1 with OA.21 The effects seem much more pronounced in this study than in ours; however, their effects were very short-termed (14 to 60 days). Furthermore, the screened study population was found to have an AHI < 5 but an arousal index > 10, which is a very specific population, probably not only with RERAs as the cause of arousal, and since the definition of hypopnea in this study was the wider Chicago criteria from 1999,22 the population differs from ours.

Is OA the most likely treatment to be successful in this phenotype of OSA patients? CPAP is a highly effective treatment, but it also has a limited adherence of 50% to 80% in long term, and patients with mild symptoms have been found to be most likely to discontinue treatment.23 The treatment of the SDB subgroup UARS is not well documented. CPAP was used in the initial report by Guilleminault et al.4 and showed short-term upper airway widening during sleep, but long-term prescription had variable success.24 A crossover study between OA and CPAP reported that OA is effective for OSA, especially for mild to moderate cases, and that they are associated with fewer side effects and greater patient satisfaction than CPAP.23 Another similar crossover study reported higher compliance with an OA, and thereby a greater reduction of oxidative stress and diastolic blood pressure, compared to CPAP.25 The Cochrane Review concludes that responders to both CPAP and an OA expressed a strong preference for the OA.26

Our studies indicate that the wider definition of hypopnea from 2007 is relevant and important; sleepy snorers screened and diagnosed with OSA do have a therapeutic gain. In 2012 the AASM published an updated version of their scoring manual27 in which the definition of hypopnea is even wider28: ≥ 30% reduction in nasal pressure, associated with ≥ 3% desaturation or arousal. This leads to an increased number of patients diagnosed with OSA who were previously probably missed.

The major weaknesses in this study are the rather small study population and the loss to follow-up. Secondly, as the dentists and the patients chose between three different types of OA, and not by randomization, it is not possible to analyze which OA type had the best adherence. Furthermore, the OA had no equipment to measure adherence objectively, but such equipment was not available at study start. The major strength is the focus on OA treatment adherence and success in a seldom investigated study population.

The rather high OA treatment adherence and success in this subgroup of OSA patients, diagnosed only with PSG, and having mainly respiratory arousals, strengthens the motivation for the use of diagnostic PSG and an OA treatment. We recommend further research in these patients to find possible treatment modifications to improve acceptance, adherence, and successful treatment.

DISCLOSURE STATEMENT

This work was supported in part by research grants received from the funding agencies ACTA Oto-Laryngologica, Swedish Association for Sleep Medicine and Sleep Research, and from the Stockholm County Council (ALF project). The authors have indicated no financial conflicts of interest.

ABBREVIATIONS

AHI

apnea-hypopnea index

CPAP

continuous positive airway pressure

ESS

Epworth Sleepiness Scale

GH

general health

HAD

hospital anxiety and depression scale

HSS

home sleep study

MWU

Mann-Whitney U

OA

oral appliance

ODI

oxygen desaturation index

OSA

obstructive sleep apnea

PSG

polysomnography

SDB

sleep-disordered breathing

SRC

Spearman rank correlation

WMP

Wilcoxon matched pair

UARS

upper airway resistance syndrome

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