Kate Sutherland

The Effect of mandibular advancement on upper airway structure in obstructive sleep apnoea

Background The mechanisms by which mandibular advancement splints (MAS) improve obstructive sleep apnoea (OSA) are not well understood. This study aimed to evaluate the mechanism of action of MAS by assessing their effect on upper airway structure in patients with OSA. Methods Patients were recruited from a sleep disorders clinic for treatment with a custom-made MAS. MRI of the upper airway was performed during wakefulness in the supine position, with and without the MAS. Results Sixty-nine patients with OSA were recruited. Treatment with the MAS reduced the apnoea–hypopnoea index (AHI) from 27.0±14.7 events/h to 12.2±12.5 events/h (p<0.001). There was an increase in the total airway volume with mandibular advancement (16.5±0.7 cm3 vs 18.1±0.8 cm3; p<0.01) that occurred predominantly because of an increase in the volume of the velopharynx (5.7±0.3 cm3 vs 6.5±0.3 cm3; p<0.001). This increase in airway calibre was associated with an increase in the lower anterior facial height (6.8±0.1 cm vs 7.5±0.1 cm; p<0.001), reduction in the distance between the hyoid and posterior nasal spine (7.4±0.1 cm vs 7.2±0.1 cm; p<0.001), lateral displacement of the parapharyngeal fat pads away from the airway (right parapharyngeal fat pad 0.17±0.02 cm; left parapharyngeal fat pad 0.22±0.02 cm) and anterior movement of the tongue base muscles (0.33±0.03 cm). Subanalyses in responders and non-responders to MAS treatment showed that the increase in upper airway calibre with mandibular advancement occurred only in responders. Conclusion These results suggest that the mechanism of action of MAS is to increase the volume of the upper airway, predominantly by increasing the volume of the velopharynx, and this increased volume is associated with changes in the surrounding bony and soft tissue structures.

Oral Appliance Treatment for Obstructive Sleep Apnea: An Update

Oral appliances (OA) have emerged as an alternative to continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA) treatment. The most commonly used OA reduces upper airway collapse by advancing the mandible (OAm). There is a strong evidence base demonstrating OAm improve OSA in the majority of patients, including some with more severe disease. However OAm are not efficacious for all, with approximately one-third of patients experiencing no therapeutic benefit. OAm are generally well tolerated, although short-term adverse effects during acclimatization are common. Long-term dental changes do occur, but these are for the most part subclinical and do not preclude continued use. Patients often prefer OAm to gold-standard CPAP treatment. Head-to-head trials confirm CPAP is superior in reducing OSA parameters on polysomnography; however, this greater efficacy does not necessarily translate into better health outcomes in clinical practice. Comparable effectiveness of OAm and CPAP has been attributed to higher reported nightly use of OAm, suggesting that inferiority in reducing apneic events may be counteracted by greater treatment adherence. Recently, significant advances in commercially available OAm technologies have been made. Remotely controlled mandibular positioners have the potential to identify treatment responders and the level of therapeutic advancement required in single night titration polysomnography. Objective monitoring of OAm adherence using small embedded temperature sensing data loggers is now available and will enhance clinical practice and research. These technologies will further enhance efficacy and effectiveness of OAm treatment for OSA.

Obesity and craniofacial structure as risk factors for obstructive sleep apnoea: impact of ethnicity.

OSA is the result of structural and functional abnormalities that promote the repetitive collapse of the upper airway during sleep. This common disorder is estimated to occur in approximately 4% of men and 2% of women, with prevalence studies from North America, Australia, Europe and Asia indicating that occurrence is relatively similar across the globe. Anatomical factors, such as obesity and craniofacial morphology, are key determinants of the predisposition to airway collapse; however, their relative importance for OSA risk likely varies between ethnicities. Direct inter‐ethnic studies comparing craniofacial phenotypes in OSA are limited. However, available data suggest that Asian OSA populations primarily display features of craniofacial skeletal restriction, African Americans display more obesity and enlarged upper airway soft tissues, while Caucasians show evidence of both bony and soft tissue abnormalities. Our recent comparison of Chinese and Caucasian OSA patients found for the same degree of OSA severity. Caucasians were more obese, and Chinese had more skeletal restriction. However, the ratio of obesity to craniofacial bony size (or anatomical balance, an important determinant of upper airway volume and OSA risk) was similar between Caucasians and Chinese OSA patients. Ethnicity appears to influence OSA craniofacial phenotype but furthermore the relative contribution of the anatomical factors underlying OSA risk. The skeletal restriction craniofacial phenotype may be particularly vulnerable to increasing obesity rates. Better understanding of craniofacial phenotypes encompassing ethnicity may help improve OSA recognition and treatment; however, further studies are needed to elucidate ethnic differences in OSA anatomical risk factors.

Effect of weight loss on upper airway size and facial fat in men with obstructive sleep apnoea

Background Obstructive sleep apnoea (OSA) is commonly associated with obesity and can be improved by weight loss. Changes in upper airway size related to regional fat loss may mediate the improvement in OSA. This study aimed to assess changes in upper airway size and regional facial and abdominal fat with weight loss and their association with OSA improvement. Methods Middle-aged obese men with moderate-to-severe OSA underwent a 24-week sibutramine-assisted weight loss trial. Polysomnography and CT of the head and neck were performed at baseline and 24 weeks. The upper airway lumen and facial and parapharyngeal fat were measured with image analysis software. Results Post-intervention there was a significant reduction in weight (−7.8±4.2 kg, p<0.001) and apnoea-hypopnoea index (AHI) (−15.9±20.5 events/h, p<0.001). Velopharyngeal airway volume significantly increased from baseline (5.3±0.4 to 6.3±0.3 cm3, p<0.01) and facial and paraphayngeal fat volume significantly reduced. A reduction in upper airway length was associated with improvement in AHI (r=0.385, p=0.005). The variance in AHI improvement was best explained by changes in upper airway length and visceral abdominal fat (R2=0.31, p=0.004). Conclusions Weight loss increases velopharyngeal airway volume, but changes in upper airway length appear to have a greater influence on the reduction in apnoea frequency. Inter-individual variability in the effects of weight loss on OSA severity cannot be explained in terms of changes in upper airway structure and local fat deposition alone.

Computational fluid dynamics for the assessment of upper airway response to oral appliance treatment in obstructive sleep apnea

Mandibular advancement splints (MAS), which protrude the lower jaw during sleep, are recognized as an effective treatment for obstructive sleep apnea (OSA) through their action of enlarging the airway space and preventing upper airway collapse. However a clinical challenge remains in preselecting patients who will respond to this form of therapy. We aimed to use computational fluid dynamics (CFD) in conjunction with patient upper airway scans to understand the upper airway response to treatment. Seven OSA patients were selected based on their varied treatment response (assessed by the apnea-hypopnoea index (AHI) on overnight polysomnography). Anatomically-accurate upper airway computational models were reconstructed from magnetic resonance images with and without MAS. CFD simulations of airflow were performed at the maximum flow rate during inspiration. A physical airway model of one patient was fabricated and the CFD method was validated against the pressure profile on the physical model. The CFD analysis clearly demonstrated effects of MAS treatment on the patients UA airflow patterns. The CFD results indicated the lowest pressure often occurs close to the soft palate and the base of the tongue. Percentage change in the square root of airway pressure gradient with MAS (Δsqrt(ΔP(Max))%) was found to have the strongest relationship with treatment response (ΔAHI%) in correlation analysis (r=0.976, p=0.000167). Changes in upper airway geometry alone did not significantly correlate with treatment response. We provide further support of CFD as a potential tool for prediction of treatment outcome with MAS in OSA patients without requiring patient specific flow rates.

Influence of Oral and Craniofacial Dimensions on Mandibular Advancement Splint Treatment Outcome in Patients With Obstructive Sleep Apnea

BACKGROUND Mandibular advancement splints (MASs) can effectively treat obstructive sleep apnea (OSA); however, no validated and reliable prediction method for treatment outcome currently exists. The efficacy of MAS may relate to anatomic factors, including craniofacial size and upper-airway soft-tissue volume and anatomic balance between them. We aimed to assess whether craniofacial and oral measurements are associated with MAS treatment outcome. METHODS Dental impressions and lateral cephalometric radiographs were obtained from patients with OSA prior to commencing MAS treatment. Intertooth distances and palatal depths were measured on dental casts, and standard cephalometric analysis was performed with the addition of cross-sectional area (CSA) of the tongue and bony oral enclosure. Treatment outcome was determined by polysomnography. RESULTS Of 53 patients, 25 were complete responders (posttreatment apnea-hypopnea index [AHI] < 5/h), 17 were partial responders (≥ 50% AHI reduction), and 11 were nonresponders (< 50% AHI reduction). Cephalometric analyses did not reveal any significant differences between responders and nonresponders. Oral cavity measurements or CSA did not differ with treatment outcome; however, there was a trend toward a larger tongue CSA in complete vs partial and nonresponders (39.5 ± 1.3 cm(2) vs 35.5 ± 0.5 cm(2), P = .09). Tongue/oral enclosure CSA ratio, indicating a larger tongue for a given oral cavity size, was greater in complete responders (P = .012, n = 30). CONCLUSIONS Oral dimensions do not appear to differ between patients who respond and those who do not respond to MAS treatment. However, the larger tongue for a given oral cavity size in responders suggests that MAS may help to correct anatomic imbalance. Further research to assess whether the ratio between tongue and bony oral enclosure size may be useful in selecting patients for MAS treatment is warranted.

Oral Appliance Treatment Response and Polysomnographic Phenotypes of Obstructive Sleep Apnea.

STUDY OBJECTIVES Mandibular advancement splints (MAS) are an effective treatment for obstructive sleep apnea (OSA); however, therapeutic response is variable. Younger age, female gender, less obesity, and milder and supine-dependent OSA have variably been associated with treatment success in relatively small samples. Our objective was to utilize a large cohort of MAS treated patients (1) to compare efficacy across patients with different phenotypes of OSA and (2) to assess demographic, anthropometric, and polysomnography variables as treatment response predictors. METHODS Retrospective analysis of MAS-treated patients participating in clinical trials in sleep centers in Sydney, Australia between years 2000-2013. All studies used equivalent customized two-piece MAS devices and treatment protocols. Treatment response was defined as (1) apnea-hypopnea index (AHI) < 5/h, (2) AHI < 10/h and ≥ 50% reduction, and (3) ≥ 50% AHI reduction. RESULTS A total of 425 patients (109 female) were included (age 51.2 ± 10.9 years, BMI 29.2 ± 5.0 kg/m2). MAS reduced AHI by 50.3% ± 50.7% across the group. Supine-predominant OSA patients had lower treatment response rates than non-positional OSA (e.g., 36% vs. 59% for AHI < 10/h). REM-predominant OSA showed a lower response rate than either NREM or non-stage dependent OSA. In prediction modelling, age, baseline AHI, and anthropometric variables were predictive of MAS treatment outcome but not OSA phenotype. Gender was not associated with treatment outcome. CONCLUSION Lower MAS treatment response rates were observed in supine and REM sleep. In a large sample, we confirm that demographic, anthropometric, and polysomnographic data only weakly inform about MAS efficacy, supporting the need for alternative objective prediction methods to reliably select patients for MAS treatment.

Mandibular advancement splints for the treatment of sleep apnea syndrome.

Oral devices, in particular Mandibular Advancement Splints (MAS), which hold the mandible in a protruded position during sleep, are increasingly used for the treatment of Obstructive Sleep Apnoea (OSA). These devices can be effective in treating OSA across a range of severity. Complete resolution of OSA (Apnoea-Hypopnoea Index [AHI] reduced <5/hr) with use of an MAS occurs in around 40% of patients. Overall two thirds of patients experience some clinical benefit (≥50% AHI reduction AHI) however others will not objectively respond to this form of treatment, despite improvement in symptoms. Although MAS are less efficacious in reducing polysomnographic indices of OSA than the standard treatment, Continuous Positive Airway Pressure (CPAP), improvements in health outcomes appear to be comparable. Therefore, the superiority of CPAP in improving oxygen desaturations and reducing AHI may be extenuated by its low compliance, resulting in both treatments having similar effectiveness in clinical practice. MAS are now recommended as a first line treatment for mild to moderate OSA, as well as in more severe patients who are unable to tolerate or refuse CPAP. Success with MAS treatment has been associated with factors such as female gender, younger age, supine-dependent OSA, lower BMI, smaller neck circumference and craniofacial factors, however a reliable, validated method for prediction in the clinical setting has yet to be established. MAS are well tolerated, however short-term side effects are common although generally minor and transient. Long-term dental changes are for the most part subclinical, but can be problematic for a minority of patients. MAS are a dental-based treatment for a medical sleep disorder and, as such, an interdisciplinary care model is considered important for the attainment of optimal patient outcomes.

Facial phenotyping by quantitative photography reflects craniofacial morphology measured on magnetic resonance imaging in Icelandic sleep apnea patients.

STUDY OBJECTIVES (1) To determine whether facial phenotype, measured by quantitative photography, relates to underlying craniofacial obstructive sleep apnea (OSA) risk factors, measured with magnetic resonance imaging (MRI); (2) To assess whether these associations are independent of body size and obesity. DESIGN Cross-sectional cohort. SETTING Landspitali, The National University Hospital, Iceland. PARTICIPANTS One hundred forty patients (87.1% male) from the Icelandic Sleep Apnea Cohort who had both calibrated frontal and profile craniofacial photographs and upper airway MRI. Mean ± standard deviation age 56.1 ± 10.4 y, body mass index 33.5 ± 5.05 kg/m(2), with on-average severe OSA (apnea-hypopnea index 45.4 ± 19.7 h(-1)). INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Relationships between surface facial dimensions (photos) and facial bony dimensions and upper airway soft-tissue volumes (MRI) was assessed using canonical correlation analysis. Photo and MRI craniofacial datasets related in four significant canonical correlations, primarily driven by measurements of (1) maxillary-mandibular relationship (r = 0.8, P < 0.0001), (2) lower face height (r = 0.76, P < 0.0001), (3) mandibular length (r = 0.67, P < 0.0001), and (4) tongue volume (r = 0.52, P = 0.01). Correlations 1, 2, and 3 were unchanged when controlled for weight and neck and waist circumference. However, tongue volume was no longer significant, suggesting facial dimensions relate to tongue volume as a result of obesity. CONCLUSIONS Significant associations were found between craniofacial variable sets from facial photography and MRI. This study confirms that facial photographic phenotype reflects underlying aspects of craniofacial skeletal abnormalities associated with OSA. Therefore, facial photographic phenotyping may be a useful tool to assess intermediate phenotypes for OSA, particularly in large-scale studies.

CPAP pressure for prediction of oral appliance treatment response in obstructive sleep apnea.

STUDY OBJECTIVES Mandibular advancement splints (MAS) are often preferred to CPAP treatment for OSA but are not always equally efficacious. High therapeutic CPAP pressure has been associated with MAS treatment failure in a Japanese population. We sought to assess the relationship between CPAP pressure and MAS treatment response in an Australian population. METHODS Therapeutic CPAP pressure and MAS treatment response were obtained from a one-month crossover trial of both treatments. Predictive utility of CPAP pressure to identify MAS treatment response was assessed. RESULTS Seventy-eight OSA patients were included (age 49.3 ± 11.1 years, BMI 29.1 ± 5.8 kg/m(2)) with predominantly moderate-severe OSA (AHI 30.0 ± 12.7/h). CPAP pressure was lower in MAS responders (MAS AHI < 10/h) 9.7 ± 1.6 vs. 11.7 ± 2.4 cm H O, p < 0.01, with area under ROC curve of 0.74 (95% CI 0.63-0.86), p < 0.01. The best cutoff value of 10.5 cm H O useful for discriminating MAS responders and non-responders in the previous Japanese population, was inadequate for prediction in the current population (0.47 negative predictive value [NPV]). However a cutoff of 13 cm H O identified MAS non-responders (1.0 NPV). Multivariate regression identified CPAP pressure (odds ratio [95% confidence interval] 0.53 [0.33-0.87], age (0.93 [0.87-0.99]) and AHI (0.92 [0.86-0.97]) as predictors of MAS treatment response (model r(2) = 0.54, p < 0.001). CONCLUSIONS In Australian patients, the majority of whom are Caucasian, a higher therapeutic CPAP pressure requirement in conjunction with age and OSA severity characteristics may be useful to indicate likelihood of success with MAS as an alternative therapy.