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Drug-induced Sleep Endoscopy: Are there Predictors for Failure of Oral Appliance Treatment?

Abstract

Introduction

In the literature, evidence is lacking on the predictive value of druginduced sleep endoscopy (DISE) for oral appliance treatment (OAT).

Objectives

The aim of the present study is to evaluate whether DISE with concomitant mandibular advancement maneuver can predict failure of OAT.

Methods

An observational retrospective study including patients diagnosed with obstructive sleep apnea (OSA) who previously received OAT. Results of DISE were analyzed in a group with documented OAT failure (apnea-hypopnea index [AHI] >10 events/hour or < 50% reduction) and a group with OAT benefit (AHI <10 events/hour or >50% reduction). The upper airway was assessed using the velum, oropharynx, tongue base, epiglottis (VOTE) classification. Additionally, a mandibular advancement maneuver, manually protruding the mandible by performing a jaw thrust, was performed to mimic the effect of OAT.

Results

The present study included 50 patients with OAT failure and 20 patients with OAT benefit. A subgroup analysis of patients with OAT failure and an AHI <30events/hour included 26 patients. In the OAT failure group, 74% had a negative jaw thrust maneuver. In the subgroup with an AHI <30 events/hour, 76.9% had a negative jaw thrust maneuver. In the OAT benefit group, 25% had a negative jaw thrust maneuver (p< 0.001).

Conclusions

A negative jaw thrust maneuver during DISE can be a valuable predictor for OAT failure, independent of AHI. Drug-induced sleep endoscopy should be considered as a diagnostic evaluation tool before starting OAT.

Keywords
obstructive sleep apnea; drug-induced sleep endoscopy; oral appliance treatment; mandibular advancement device; treatment outcome prediction

Introduction

Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterized by repetitive partial or complete upper airway obstruction that often results in decreased arterial oxygen saturation and arousal from sleep.11 American Academy of Sleep Medicine Task Force. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 1999;22(05):667–689, 22 Vonk PE, Beelen AMEH, de Vries N. Towards aprediction model for drug-induced sleep endoscopy as selection tool for oral appliance treatment and positional therapy in obstructive sleep apnea. Sleep Breath 2018;22(04):901–907, 33 Vroegop AVMT, Vanderveken OM, Dieltjens M, et al. Sleep endoscopy with simulation bite for prediction of oral appliance treatment outcome. J Sleep Res 2013;22(03):348–355, 44 Aktas O, Erdur O, Cirik AA, Kayhan FT. The role of drug-induced sleep endoscopy in surgical planning for obstructive sleep apnea syndrome. Eur Arch Otorhinolaryngol 2015;272(08): 2039–2043 The currentgold standard treatmentof moderatetosevere OSA is continuous positive airway pressure (CPAP).55 Sullivan CE, Issa FG, Berthon-Jones M, Eves L. Reversal of obstructive sleep apnoea by continuous positive airway pressure applied through the nares. Lancet 1981;1(8225): 862–865,66 Vanderveken OM, Vroegop AV, van de Heyning PH, Braem MJ. Drug-induced sleep endoscopy completed with a simulation bite approach for the prediction of the outcome of treatment of obstructive sleep apnea with mandibular repositioning appliances. Oper Tech Otolaryngol–Head Neck Surg 2011;22(02): 175–182 However, compliance and long-term use of CPAP is rather low.77 Lindberg E, Berne C, Elmasry A, Hedner J, Janson C. CPAP treatment of a population-based sample–what are the benefits and the treatment compliance? Sleep Med 2006;7(07): 553–560 In patients with mild to moderate OSA or in cases of CPAP intolerance, other treatment options include oral appliance treatment (OAT), a noninvasive alternative to CPAP.22 Vonk PE, Beelen AMEH, de Vries N. Towards aprediction model for drug-induced sleep endoscopy as selection tool for oral appliance treatment and positional therapy in obstructive sleep apnea. Sleep Breath 2018;22(04):901–907,33 Vroegop AVMT, Vanderveken OM, Dieltjens M, et al. Sleep endoscopy with simulation bite for prediction of oral appliance treatment outcome. J Sleep Res 2013;22(03):348–355,66 Vanderveken OM, Vroegop AV, van de Heyning PH, Braem MJ. Drug-induced sleep endoscopy completed with a simulation bite approach for the prediction of the outcome of treatment of obstructive sleep apnea with mandibular repositioning appliances. Oper Tech Otolaryngol–Head Neck Surg 2011;22(02): 175–182 Mandibular advancement devices (MADs), which are used intraorally at night to advance the mandible, are the most common class of oral appliances.66 Vanderveken OM, Vroegop AV, van de Heyning PH, Braem MJ. Drug-induced sleep endoscopy completed with a simulation bite approach for the prediction of the outcome of treatment of obstructive sleep apnea with mandibular repositioning appliances. Oper Tech Otolaryngol–Head Neck Surg 2011;22(02): 175–182 Oral appliance treatment appears to have higher compliance rate and a higher patient preference, with fewer side effects and greater satisfaction when compared with CPAP therapy.88 Ferguson KA, Cartwright R, Rogers R, Schmidt-Nowara W. Oral appliances for snoring and obstructive sleep apnea: a review. Sleep 2006;29(02):244–262 However, OAT is not always as effective in treating OSA. In a recent review article, approximately one-third of patients did not experience a therapeutic benefit.99 Sutherland K, Vanderveken OM, Tsuda H, et al. Oral appliance treatment for obstructive sleep apnea: an update. JClin Sleep Med 2014;10(02):215–227 Finding predictors to select suitable patients that may benefit from OAT is therefore of great importance. Various anthropometric and polysomnographic predictors for OAT have been described in the literature, including lower apnea-hypopnea index (AHI), lower body-mass index (BMI), lower age, female gender, and supine-dependent OSA.1010 Marklund M, Stenlund H, Franklin KA. Mandibular advancement devices in 630 men and women with obstructivesleep apnea and snoring: tolerability and predictors of treatment success. Chest 2004;125(04):1270–1278 However, no diagnostic prediction tool for the effectiveness of OAT has been identified so far.

Drug-induced sleep endoscopy (DISE), first described in 1991 by Croft et al., is a diagnostic evaluation tool for the degree, level(s), and pattern of upper airway obstruction in OSA patients.22 Vonk PE, Beelen AMEH, de Vries N. Towards aprediction model for drug-induced sleep endoscopy as selection tool for oral appliance treatment and positional therapy in obstructive sleep apnea. Sleep Breath 2018;22(04):901–907,1111 Croft CB, Pringle M. Sleep nasendoscopy: a technique of assessment in snoring and obstructive sleep apnoea. Clin Otolaryngol Allied Sci 1991;16(05):504–509 During DISE, a mandibular advancement maneuver is performed as a prediction tool for the effectiveness of OAT. However, opinions concerning the performance of a mandibular advancement maneuver during DISE vary among studies, and evidence on the positive and negative predictive values are limited so far.33 Vroegop AVMT, Vanderveken OM, Dieltjens M, et al. Sleep endoscopy with simulation bite for prediction of oral appliance treatment outcome. J Sleep Res 2013;22(03):348–355,66 Vanderveken OM, Vroegop AV, van de Heyning PH, Braem MJ. Drug-induced sleep endoscopy completed with a simulation bite approach for the prediction of the outcome of treatment of obstructive sleep apnea with mandibular repositioning appliances. Oper Tech Otolaryngol–Head Neck Surg 2011;22(02): 175–182,1212 Battagel JM, Johal A, Kotecha BT. Sleep nasendoscopy as a predictor of treatment success in snorers using mandibular advancement splints. J Laryngol Otol 2005;119 (02):106–112, 1313 Eichler C, Sommer JU, Stuck BA, Hörmann K, Maurer JT. Does drug-induced sleep endoscopy change the treatment concept of patients with snoring and obstructive sleep apnea? Sleep Breath 2013;17(01):63–68, 1414 Johal A, Battagel JM, Kotecha BT. Sleep nasendoscopy: a diagnostic tool for predicting treatment success with mandibular advancement splints in obstructive sleep apnoea. Eur J Orthod 2005;27 (06):607–614, 1515 De Corso E, Bastanza G, Della Marca GC, Rizotto G, Marchese MR, Fiorita A, Sergi B, Meucci D, Di Nardo W, Paludetti G, Scarano E. Drug-induced sleep endoscopy as a selection tool for mandibular advancement therapy by oral device. Acta Otorhinolaryngol Ital 2015;35:426–432, 1616 Huntley C, Cooper J, Stiles M, Grewal R, Boon M. Predicting success of oralappliancetherapyintreating obstructive sleep apnea using drug-induced sleep endoscopy. J Clin Sleep Med 2018;14(08): 1333–1337, 1717 Kent DT, Rogers R Sr, Soose RJ. Drug-Induced Sedation Endoscopy in the Evaluation of OSA Patients with Incomplete Oral Appliance Therapy Response. Otolaryngol Head Neck Surg 2015;153(02): 302–307, 1818 Lechner M, Wilkins D, Kotecha B. A review on drug-induced sedation endoscopy – Technique, grading systems and controversies. Vol. 41;Sleep Medicine Reviews. W.B. Saunders Ltd; 2018: 141–148 Presently, patients are often prescribed OAT without evaluation of the upper airway through DISE. In case of ineffectiveness of OAT, there is a large delay in the appropriate treatment of the disorder and a waste of healthcare supplies.

In the present retrospective study, the DISE results from patients with documented OAT benefit and OAT failure will be analyzed, and individual predictors for OAT failure will be identified. To the best of our knowledge, this is the first study to compare DISE results both of patients with OAT failure and with OAT benefit.

Materials and Methods

Study Design and Patient Population

Data from 201 patients who were referred to this tertiary referral sleep center in the Netherlands between January 2017 and June 2019 were retrospectively analyzed. Patients referred to this center have repeatedly failed different therapies, and often present with CPAP- and OAT- failure or intolerance. Drug-induced sleep endoscopy is performed in all patients in order to consider other treatment options, such as surgical procedures and upper airway stimulation. The inclusion criteria were patients >18 years old, previous treatment with OAT (specifically MAD) and DISE with concomitant mandibular advancement maneuver performed in this hospital. A recent apnea-hypopnea index (AHI) measured by polysomnography (PSG) or respiratory polygraphy (PG or home sleep apnea test) had to be available. The exclusion criteria were patients with no history of OAT treatment, or OAT treatment different from a MAD, missing apnea-hypopnea index (AHI), or technically inadequate P(S) G, and if DISE was not performed in this hospital, or if a mandibular advancement maneuver was not performed. In the outpatient clinic, routine ear, nose, and throat (ENT) examination was performed. The following clinical parameters were collected for all patients: gender, age, height, weight, BMI, tonsil size (0–4), and Mallampati score.11 American Academy of Sleep Medicine Task Force. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 1999;22(05):667–689, 22 Vonk PE, Beelen AMEH, de Vries N. Towards aprediction model for drug-induced sleep endoscopy as selection tool for oral appliance treatment and positional therapy in obstructive sleep apnea. Sleep Breath 2018;22(04):901–907, 33 Vroegop AVMT, Vanderveken OM, Dieltjens M, et al. Sleep endoscopy with simulation bite for prediction of oral appliance treatment outcome. J Sleep Res 2013;22(03):348–355, 44 Aktas O, Erdur O, Cirik AA, Kayhan FT. The role of drug-induced sleep endoscopy in surgical planning for obstructive sleep apnea syndrome. Eur Arch Otorhinolaryngol 2015;272(08): 2039–2043

Pretreatment Sleep Study

All patients were diagnosed with OSA, which was either confirmed by PSG or respiratory PG. The variables collected were AHI, oxygen desaturation index ≥3%, and oxygen desaturation index ≥4%, if available. Apnea was defined as a decrease of at least 90% of airflow from baseline for > 10 seconds. Hypopnea was defined as a decrease of at least 30% of airflow from baseline for > 10 seconds, associated with either an arousal or with ≥ 3% arterial oxygen saturation decrease. The mean number of apneas and hypopneas per hour of sleep (AHI) was calculated. The ODI ≥ 3% was defined as the mean number of arterial oxygen desaturations ≥ 3%. The ODI ≥ 4% was defined as the mean number of arterial oxygen desaturations ≥ 4%. The variables from the most recent sleep study were used in the analysis. If surgery was performed (for example, upper airway stimulation, pharyngoplasty), the last sleep study before surgery was used.

Drug-induced Sleep Endoscopy

Drug-induced sleep endoscopy was performed in a quiet operating room with dimmed lights. All procedures were performed by the same experienced ENT-surgeon (Copper, MP) with an anesthesiologist to manage sedation. Sleep was induced by an initial bolus of 1mg/kg propofol, followed by a titration of propofol. The optimal depth of sedation was reached when the patient began to snore and/or hypores-ponsiveness to vocal and tactile stimuli was achieved (Ramsay sedation level 5). Once a proper level of sedation was achieved, the upper airway was thoroughly observed by flexible fiberoptic laryngoscopy. The upper airway was assessed in the supine position using the velum, oropharynx, tongue base, epiglottis (VOTE) classification system as described by Kezirian et al. in 2011.1919 Kezirian EJ, Hohenhorst W, de Vries N. Drug-induced sleep endoscopy: the VOTE classification. Eur Arch Otorhinolaryngol 2011;268(08):1233–1236 Upper airway collapse was evaluated on four different levels and structures, namely the velum (V), the oropharynx (O), the tongue base (T), and the epiglottis (E). The degree of obstruction was defined as 0: no obstruction (collapse < 50%); 1: partial collapse (between 50% and 75%, typically with vibration); or 2: complete collapse (> 75%). The configuration of obstruction can be classified as anteroposterior (AP), lateral (La) or concentric (Co).22 Vonk PE, Beelen AMEH, de Vries N. Towards aprediction model for drug-induced sleep endoscopy as selection tool for oral appliance treatment and positional therapy in obstructive sleep apnea. Sleep Breath 2018;22(04):901–907,1919 Kezirian EJ, Hohenhorst W, de Vries N. Drug-induced sleep endoscopy: the VOTE classification. Eur Arch Otorhinolaryngol 2011;268(08):1233–1236 After the first assessment of the upper airway using the VOTE classification system, a mandibular advancement maneuver, manually protruding the mandible by performing a jaw thrust, was performed to mimic the effect of OAT. The hands of the practitioner were placed behind the angles of the mandible and thrust forward. The jaw thrust maneuver was performed without extensive force, bringing the lower incisors past the upper incisors by a couple of millimeters, producing a mild anterior protrusion of the mandible of ~ 75% of the maximal protrural range. The jaw thrust maneuver was called positive if the obstruction was discontinued on all levels. The jaw thrust maneuver was called negative if the obstruction was still present on one or more levels.

Data Analysis

Our primary analysis describes the patient group with documented OAT failure. Oral appliance treatment failure was defined as an insignificant decrease in AHI on a follow-up sleep study (AHI>10 events/hour or<50% reduction from thebaseline AHI). Oral appliancetreatment intolerance, like temporomandibular dysfunction, dental pain or hyper-salivation, was not counted as OAT failure. The secondary analysis describes the patient group with documented OAT benefit. Oral appliance treatment benefit was defined as a significant decrease in AHI on a follow-up sleep study (AHI <10events/hour or >50% reduction from baseline AHI). One subgroup analysis was performed in the patient group with OAT failure. This subgroup analysis describes the patient group with documented OAT failure and an AHI<30 events/hour. This cutoff point was used to obtain comparable baseline characteristics. Furthermore, the Dutch guideline regarding OSA treatment states that OAT is not the first treatment choice in patients with an AHI> 30 events/h.

Statistical Analysis

The statistical analysis was performed by using IBM SPSS Statistics for Windows version 24 (IBM Corp., Armonk, NY, USA). Continuous data are presented as means with standard deviations (SDs). Categorical variables are presented as frequencies with percentages. Comparisons between groups were performed using chi-squared tests for categorical variables and the unpaired Student t test for continuous variables. The predictive performance of the jaw thrust maneuver for OAT failurewas estimatedfrom thearea under the curve(AUC) obtained by receiver operator characteristic (ROC) curves. Additionally, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using four-grid contingency tables. All estimates are reported with their respective 95% confidence interval (CI). The association between various individual demographic data and clinical variables obtained from the sleep study test and DISE and the presence of OAT failure was established by using a multi-variate logistic regression model (backward stepwise selection, p < 0.05). All variables that were associated with OAT failure (p < 0.20) were entered into the regression model. Additionally, a multivariate logistic regression analysis adjusted for confounding factors was used to assess the relation between OAT failure and the jaw thrust maneuver. A two-tailed p-value < 0.05 was considered statistically significant.

Results

Baseline Characteristics

Seventy patients met our inclusion criteria. The patients were subdivided in an OAT failure and an OAT benefit group; 50 patients with OAT failure were included in the primary analysis and 20 patients with OAT benefit were included in the secondary analysis. The subgroup analysis of patients with OAT failure and an AHI < 30 events/hour included 26 patients (►Fig. 1).

Fig. 1
Flowchart of patient inclusion. AHI = apnea-hypopnea index. DISE = drug-induced sleep endoscopy. JM =jaw thrust maneuver. OAT = oral appliance treatment. OSA = obstructive sleep apnea.

Primary Analysis - OAT Failure (n = 50)

Baseline characteristics are shown in ►Table 1. Sleep study data was obtained by PSG in 68% (34/50) of the patients and by PG in 32% (16/50) of the patients. A total of 84% (42/50) of the patients with OAT failure were male. The mean age was 57.2 ± 10.8 years old, with a mean BMI of 28.0 ± 2.8 kg/m2, and a mean AHI of 31.1 ±17.1 events/hour. The mean ODI ≥ 3% was 30.6 ± 16.8 events/hour, and the mean ODI ≥ 4% was 20.0 ±15.2 events/hour. Previous tonsillectomy was performed in 36% (18/50) of the patients. The distribution of the levels and the pattern of upper airway collapse during DISE is shown in ►Table 2. A total of 74% (37/50) of the patients with OAT failure had a negative jaw thrust maneuver (Tab. 1, ►Fig. 2a).

Table 1
Baseline characteristics
Table 2
Overview of the distribution of the levels and pattern of upper airway collapse during DISE according to the VOTE classification

Fig. 2
Outcome of the jaw thrust maneuver in all the patients with OAT failure (A), in patients with OAT benefit (B) and in patients with OAT failure and AHI <30 (C).

Secondary Analysis - OAT Benefit (n = 20)

Baseline characteristics are shown in ►Table 1. Sleep study data was obtained by PSG in 90% (18/20) of the patients and by PG in 10% (2/20) of the patients. A total of 70% (14/20) of the patients with OAT benefit was male. The mean age was 55.6 ± 7.6 years old, with a mean BMI of 26.8 ± 2.9 kg/m2, and a mean AHI of 22.8 ± 10.4 events/hour. The mean ODI ≥ 3% was 18.7 ±1 0.2 events/hour, and the mean ODI ≥ 4% was 12.1 ± 8.8 events/hour. Previous tonsillectomy was performed in 70% (14/20) of the patients. The distribution of the levels and the pattern of upper airway collapse during DISE is shown in ►Table 2. A total of 25% (5/20) of the patients with OAT benefit had a negative jaw thrust maneuver (Tab. 1, ►Fig. 2b).

Sleep study data was obtained by PSG in 90% of the patients with OAT benefit and in 68% of the patients with OAT failure. This difference was statistically significant (p = 0.01). The group with OAT benefit contained fewer male patients and had a lower average BMI than the group with OAT failure; however, these differences were not significant (p = 0.202; p = 0.103, respectively). The AHI, ODI > 3% and ODI > 4% were significantly lower in the group with OAT benefit (p = 0.017; p = 0.006; p = 0.048, respectively). Additionally, the tonsil size was significantly lower in the group with OAT benefit (p = 0.003). The percentage of negative jaw thrust maneuver in the OAT benefit group was significantly lower than in the OAT failure group (p < 0.001).

Subgroup Analysis - OAT Failure (AHI <30) (n = 26)

Baseline characteristics are shown in ►Table 1. A total of 84.6% (22/26) of the patients with OAT failure and AHI < 30 events/hour were male. The mean age was 54.6 ± 11.1 years old, with a mean BMI of 27.6 ± 2.8 kg/m2, and a mean AHI of 18.2 ± 6.4 events/hour. The mean ODI ≥ 3% was 20.8 ± 9.0 events/hour, and the mean ODI ≥ 4% was 13.2 ± 7.8 events/hour. The distribution of the levels and the pattern of upper airway collapse during DISE is shown in ►Table 2. A total of 76.9% (20/26) of the patients with OAT failure and AHI < 30 had a negative jaw thrust maneuver (Tab. 1, >►Fig. 2c).

The group with OAT failure and an AHI < 30 events/hour and the group with OAT benefit presented no significant differences in the baseline characteristics. The AHI in the OAT failure (AHI < 30) group was lower than the AHI in the OAT benefit group; however, this difference was not significant (p = 0.069). The percentage of negative jaw thrust maneuver in the OAT failure (AHI < 30) group was significantly higher than in the OAT benefit group (p < 0.001) (Tab. 1).

Prediction of Treatment Outcome

In the present patient cohort, the percentage of patients with a negative jaw thrust maneuver was significantly higher in the OAT failure group (p < 0.001). The AHI, ODI ≥ 3%, ODI ≥ 4% and tonsil size were also significantly higher in the OAT failure group (p = 0.017; p = 0.006; p = 0.048; p = 0.003, respectively). Multivariate logistic regression analyses were performed to establish the association between individual demographic and clinical variables and the effectiveness of OAT. Adjusting for confounding factors like previous tonsillectomy, a negative jaw thrust maneuver and a higher ODI ≥ 3% proved to be the strongest predictors in the OAT failure group (p = 0.003; p = 0.029, respectively). Tonsil size did not prove to be a strong individual predictor in this group (p = 0.364). In the subgroup analysis of patients with OAT failure and AHI < 30 events/hour, only negative jaw thrust maneuver proved to be a strong predictor (p = 0.001). The ROC curve in ►Fig. 3a shows the discrimination of the jaw thrust maneuver between OAT failure and OAT benefit and has an AUC of 0.754 (95%CI: 0.614-0.876). The test sensitivity of the jaw thrust maneuver is 0.75 (95%CI: 0.53-0.89), and the test specificity is 0.74 (95%CI: 0.60-0.84). The PPV is 0.54 (95%CI: 0.36-0.70), and the NPV is 0.88 (95%CI: 0.75-0.95). The ROC curve in ►Fig. 3b shows the discrimination of the jaw thrust maneuver between OAT failure (AHI < 30 events/hour) and OAT benefit, and has an AUC of 0.760 (95%CI: 0.614-0.905) (►Fig. 3). The test sensitivity of the jaw thrust maneuver is 0.75 (95%CI: 0.53-0.89), and the test specificity is 0.77 (95%CI: 0.58-0.89). The PPV is 0.71 (95%CI: 0.5-0.86), and the NPV is 0.80 (95%CI: 0.61-0.91).

Fig. 3
Receiver operating characteristic (ROC) curve. A. OAT failure versus OAT benefit. The AUC is 0.754 (95%CI: 0.614–0.876). B. OAT failure (AHI <30) versus OAT benefit. The AUC is 0.760 (95%CI: 0.614–0.905).

Discussion

The percentage of patients with a negative jaw thrust maneuver was significantly higher in the group with OAT failure in comparison with the group with OAT benefit. The AHI, ODI ≥ 3%, ODI ≥ 4% and tonsil size were also significantly higher in the patient group with OAT failure. In a recent study by Marklund et al, it was already described that a lower AHI is a predictor for benefit from OAT.1010 Marklund M, Stenlund H, Franklin KA. Mandibular advancement devices in 630 men and women with obstructivesleep apnea and snoring: tolerability and predictors of treatment success. Chest 2004;125(04):1270–1278 It could be argued that the results that we found are due to differences in AHI in the baseline characteristics of both patient groups, rather than to differences in outcome of the jaw thrust maneuver. To rule out this possible confounding bias in the analysis, a subgroup analysis was performed in patients with OAT failure and an AHI < 30 events/hour. In this subgroup analysis, there were no significant differences in the baseline characteristics. The percentage of patients with a negative jaw thrust maneuver was found to be significantly higher in the patients with OAT failure (AHI < 30 events/hour). Additionally, multivariate logistic regression analyses adjusted for confounding factors were performed to assess the relation between OAT failure and the jaw thrust maneuver. The jaw thrust maneuver proved to be the strongest predictor for OAT failure.

It must be acknowledged that 25% of the patients with OAT benefit had a negative jaw thrust maneuver. When only using the results of the jaw thrust maneuver to predict OAT failure, certain patients would not receive OAT although they would benefit from the therapy. The patients with OAT benefit and a negative jaw thrust maneuver had a lower BMI and a lower AHI in comparison with the patients with OAT benefit and a positive jaw thrust maneuver. However, these differences were not significant. These results are in line with those of previous studies, indicating that lower AHI and lower BMI are also important predictors for the success of OAT.1010 Marklund M, Stenlund H, Franklin KA. Mandibular advancement devices in 630 men and women with obstructivesleep apnea and snoring: tolerability and predictors of treatment success. Chest 2004;125(04):1270–1278

A total of 26% (13/50) of the patients with OAT failure had a positive jaw thrust maneuver. These patients were older and had a higher AHI in comparison with the patients with a negative jaw thrust maneuver. Again, these differences were not significant. Previously, Marklund et al. already described a higher AHI and older age to be predictors for OAT failure.1010 Marklund M, Stenlund H, Franklin KA. Mandibular advancement devices in 630 men and women with obstructivesleep apnea and snoring: tolerability and predictors of treatment success. Chest 2004;125(04):1270–1278 These results suggest that DISE with concomitant jaw thrust maneuver should be used together with anthropometric and polysomnographic predictors to accurately predict the success of OAT. Further prospective research needs to be done to develop a screening instrument for the effectiveness of OAT.

Seventy percent of the patients in the OAT benefit group had undergone a previous tonsillectomy, in contrast with 36% in the OAT failure group (p = 40.003; ►Table 1). In ►Table 2, it is shown that, in the OAT failure group, lateral collapse at the oropharyngeal level (28%) was more common than in the OAT benefit group (10%). These results might indicate that previous tonsillectomy is a predictor for the success of OAT. This is in line with a previous study by Op de Beeck et al., who found that a complete lateral collapse at the oropharyngeal level is related to OAT failure.2020 Op de Beeck S, Dieltjens M, Verbruggen AE, et al. Phenotypic labelling using drug-induced sleep endoscopy improves patient selection for mandibular advancement device outcome: A prospective study. J Clin Sleep Med 2019;15(08): 1089–1099 However, a logistic regression analysis was performed, and tonsil size did not prove to be a strong individual predictor in this patient cohort. Adjusting for previous tonsillectomy, the jaw thrust maneuver proved to be a significant independent predictor.

Sleep study data was obtained by PSG from 68% of the patients with OAT failure and from 90% of the patients with OAT benefit. This difference was statistically significant (p = 0.01). Previous studies have shown that the AHI is underestimated in PG.2121 Tan HL, Gozal D, Ramirez HM, Bandla HPR, Kheirandish-Gozal L. Overnight polysomnography versus respiratory polygraphy in the diagnosis of pediatric obstructive sleep apnea. Sleep (Basel)2014; 37(02):255–260,2222 Kirsch DB. PRO: sliding into home: portable sleep testing is effective for diagnosis of obstructive sleep apnea. J Clin Sleep Med 2013;9(01):5–7 If we take this into account, the mean AHI in the OAT failure group might be higher than the AHI that is presented, potentially influencing the outcome of patients with OAT failure. A logistic regression analysis was performed, and AHI did not prove to be a strong individual predictor inthis patientcohort. Adjusting for the AHI,thejaw thrust maneuver proved to be a significant independent predictor.

Previously, other authors have tried to find a correlation between DISE results and OAT effectiveness. Battagel et al. and De Corso et al. have suggested that the effect of a mandibular protrusion < 5 mm is predictive of OAT benefit.1212 Battagel JM, Johal A, Kotecha BT. Sleep nasendoscopy as a predictor of treatment success in snorers using mandibular advancement splints. J Laryngol Otol 2005;119 (02):106–112,1515 De Corso E, Bastanza G, Della Marca GC, Rizotto G, Marchese MR, Fiorita A, Sergi B, Meucci D, Di Nardo W, Paludetti G, Scarano E. Drug-induced sleep endoscopy as a selection tool for mandibular advancement therapy by oral device. Acta Otorhinolaryngol Ital 2015;35:426–432 Vanderveken et al. and Vroegop et al. have supported the concept of DISE with the addition of a simulation bite.33 Vroegop AVMT, Vanderveken OM, Dieltjens M, et al. Sleep endoscopy with simulation bite for prediction of oral appliance treatment outcome. J Sleep Res 2013;22(03):348–355,66 Vanderveken OM, Vroegop AV, van de Heyning PH, Braem MJ. Drug-induced sleep endoscopy completed with a simulation bite approach for the prediction of the outcome of treatment of obstructive sleep apnea with mandibular repositioning appliances. Oper Tech Otolaryngol–Head Neck Surg 2011;22(02): 175–182,2323 De Vito A, Carrasco Llatas M, Ravesloot MJ, et al. European position paper on drug-induced sleep endoscopy: 2017 Update. Clin Otolaryngol 2018;43(06):1541–1552 Vonk et al. demonstrated that a manual jaw thrust during DISE protruding the mandible at roughly between 50 and 75% of protrusion leads to an overestimation of the effect of OAT.22 Vonk PE, Beelen AMEH, de Vries N. Towards aprediction model for drug-induced sleep endoscopy as selection tool for oral appliance treatment and positional therapy in obstructive sleep apnea. Sleep Breath 2018;22(04):901–907 It is possible that this overestimation of the effect of OAT is present in the current study. Overestimation could account for the 13 patients in the OAT failure group with a positive jaw thrust maneuver. In a recent study by Huntley et al., the results of patients who underwent DISE and received OAT based on the recommendations during DISE were compared with a patient group who received OAT without prior selection by DISE. They found a significantly lower AHI and an increased number of patients reaching an AHI<5with OATinthe DISEgroup.1616 Huntley C, Cooper J, Stiles M, Grewal R, Boon M. Predicting success of oralappliancetherapyintreating obstructive sleep apnea using drug-induced sleep endoscopy. J Clin Sleep Med 2018;14(08): 1333–1337 These results are in line with the results of our study.

Clinical Relevance

To thebestofour knowledge, the presentstudy thefirststudy to compare the results of DISE in patients with OAT failure and OAT benefit. Additionally, the present study is the first study to analyze the predictive value of the jaw thrust maneuver for the effectiveness of OAT. Without suitable predictors for failure of OAT, there is an average to large percentage of patients that is inadequately treated for a short to longer period. The findings of the present study are, therefore, of great importance for the prediction of the effectiveness of OAT. Furthermore, finding suitable predictors for selecting patients that will benefit from OAT will potentially have a beneficial effect on the cost reduction in OSA treatment. Additionally, it is expected that decreasing the group of inadequately-treated OSA patients will have a favorable effect on cost reduction in OSA healthcare in general.

Limitations and Strengths

The present study has several limitations. In the present study, the mandibular advancement maneuver was performed by manually performing a jaw thrust maneuver. Previous authors have criticized this technique, since it is nonreproducible and nontitratable and it does not account for vertical opening while closing the mouth, and state that the simulation bite is more accurate to predict the response to OAT.33 Vroegop AVMT, Vanderveken OM, Dieltjens M, et al. Sleep endoscopy with simulation bite for prediction of oral appliance treatment outcome. J Sleep Res 2013;22(03):348–355,66 Vanderveken OM, Vroegop AV, van de Heyning PH, Braem MJ. Drug-induced sleep endoscopy completed with a simulation bite approach for the prediction of the outcome of treatment of obstructive sleep apnea with mandibular repositioning appliances. Oper Tech Otolaryngol–Head Neck Surg 2011;22(02): 175–182,2323 De Vito A, Carrasco Llatas M, Ravesloot MJ, et al. European position paper on drug-induced sleep endoscopy: 2017 Update. Clin Otolaryngol 2018;43(06):1541–1552 However, in daily practice, the simulation bite technique might prove to be time-consuming and costly, potentially delaying and raising the cost of adequate OSA treatment, whereas performing a jaw thrust maneuver can easily and routinely be augmented to DISE. Additionally, it has been argued that the relaxation implied by the pharmacology necessary for DISE can possibly influence the tolerability for the jaw thrust maneuver, possibly leading to an overestimation of the OAT effect. Overestimation could possibly explain the patients in the OAT failure group with a positive jaw thrust maneuver. The assessment of the upper airway during DISE and the concomitant jaw thrust maneuver are based on subjectivefindings and, therefore, are prone to experience bias. Prior studies have shown DISE to be reliable and its interobserver reliability to be moderate to substantial, especially in experienced ENT surgeons.2424 Carrasco-Llatas M, Zerpa-Zerpa V, Dalmau-Galofre J. Reliability of drug-induced sedation endoscopy: interobserver agreement. Sleep Breath 2017;21(01):173–179, 2525 Vroegop AVMT, Vanderveken OM, Wouters K, et al. Observer variation in drug-induced sleep endoscopy: experienced versus nonexperienced ear, nose, and throat surgeons. Sleep (Basel) 2013;36(06):947–953, 2626 Kezirian EJ, White DP, Malhotra A, Ma W, McCulloch CE, Goldberg AN. Interrater reliability of drug-induced sleep endoscopy. Arch Otolaryngol Head Neck Surg 2010;136(04):393–397 In the present study, the jaw thrust maneuver was executed by one single surgeon and was identically performed in every individual according to the description in the method section. Thus, it can be expected that the jaw thrust maneuver was very similar in each individual. With the method description, it can easily be reproduced in daily practice in other healthcare institutions. However, the fact that the jaw thrust maneuver does not exactly simulate the effect of the OAT, the difficulty of reproduction and the lack of a better system to control the sedation does affect the internal and external validity of the study. Undoubtedly, the retrospective nature of the present study is a limiting factor. The present retrospective analysis was performed in a larger research design, and currently, prospective studies are being conducted to validate the observed retrospective correlations. The present study also has several important strengths; DISE was executed by one single surgeon and the jaw thrust maneuver was performed identically in every individual. Furthermore, this is the first study to analyze the predictive value of the jaw thrust maneuver for the effectiveness of OAT.

Conclusion

According to the present retrospective analysis, a negative jaw thrust maneuver can be a valuable independent predictor for OAT failure. Therefore, we suggest that DISE should be considered as a diagnostic evaluation tool to accurately predict the success of OAT. Based on the findings of the present retrospective study, we are currently prospectively evaluating the predictive value of the jaw thrust maneuver for the effectiveness of OAT.

List of abbreviations

AHI Apnea-hypopnea index
AP Anteroposterior
AUC Area under the curve
BMI Body mass index
CPAP Continuous positive airway pressure
Co Concentric
DISE Drug-induced sleep endoscopy
ENT Ear, nose, throat
JM Jaw thrust maneuver
La Lateral
MAD Mandibular advancement device
MAM Mandibular advancement maneuver
NPV Negative predictive value
OAT Oral appliance treatment
ODI Oxygen desaturation index
OSA Obstructive sleep apnea
PG Respiratory polygraphy
PPV Positive predictive value
PSG Polysomnography
ROC Receiver operating characteristic
VOTE Velum, oropharynx, tongue base, epiglottis

Acknowledgments

We want to thank the study participants. We thank E. Tromp for her assistance with the data analysis. J.A. Hardeman is acknowledged for critically proofreading the manuscript.

  • Ethical Approval
    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Data on study subjects was collected and stored anonymously to protect personal information.
  • Manuscript Approval
    All authors declare that they have read and approved the final version of the manuscript.
  • Availability of Data and Materials
    The dataset is available on request from: c.veugen@anto-niusziekenhuis.nl
  • Funding
    No financial support received for the present research.

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Publication Dates

  • Publication in this collection
    04 Nov 2022
  • Date of issue
    Jul-Sep 2022

History

  • Received
    12 July 2020
  • Accepted
    19 Mar 2021
  • Published
    26 Oct 2021
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