Peter A. Cistulli

Health Outcomes of Continuous Positive Airway Pressure versus Oral Appliance Treatment for Obstructive Sleep Apnea A Randomized Controlled Trial

RATIONALE Continuous positive airway pressure (CPAP) and mandibular advancement device (MAD) therapy are commonly used to treat obstructive sleep apnea (OSA). Differences in efficacy and compliance of these treatments are likely to influence improvements in health outcomes. OBJECTIVES To compare health effects after 1 month of optimal CPAP and MAD therapy in OSA. METHODS In this randomized crossover trial, we compared the effects of 1 month each of CPAP and MAD treatment on cardiovascular and neurobehavioral outcomes. MEASUREMENTS AND MAIN RESULTS Cardiovascular (24-h blood pressure, arterial stiffness), neurobehavioral (subjective sleepiness, driving simulator performance), and quality of life (Functional Outcomes of Sleep Questionnaire, Short Form-36) were compared between treatments. Our primary outcome was 24-hour mean arterial pressure. A total of 126 patients with moderate-severe OSA (apnea hypopnea index [AHI], 25.6 [SD 12.3]) were randomly assigned to a treatment order and 108 completed the trial with both devices. CPAP was more efficacious than MAD in reducing AHI (CPAP AHI, 4.5 ± 6.6/h; MAD AHI, 11.1 ± 12.1/h; P < 0.01) but reported compliance was higher on MAD (MAD, 6.50 ± 1.3 h per night vs. CPAP, 5.20 ± 2 h per night; P < 0.00001). The 24-hour mean arterial pressure was not inferior on treatment with MAD compared with CPAP (CPAP-MAD difference, 0.2 mm Hg [95% confidence interval, -0.7 to 1.1]); however, overall, neither treatment improved blood pressure. In contrast, sleepiness, driving simulator performance, and disease-specific quality of life improved on both treatments by similar amounts, although MAD was superior to CPAP for improving four general quality-of-life domains. CONCLUSIONS Important health outcomes were similar after 1 month of optimal MAD and CPAP treatment in patients with moderate-severe OSA. The results may be explained by greater efficacy of CPAP being offset by inferior compliance relative to MAD, resulting in similar effectiveness. Clinical trial registered with https://www.anzctr.org.au (ACTRN 12607000289415).

Effect of short-term hormone replacement in the treatment of obstructive sleep apnoea in postmenopausal women.

BACKGROUND--Women appear to be increasingly susceptible to snoring and sleep disordered breathing after the menopause. This observation, coupled with the considerable sex difference in sleep apnoea, may be explained on the basis of a protective effect of female hormones. This study was carried out to determine whether hormone replacement therapy has a role in the management of obstructive sleep apnoea in postmenopausal women. METHODS--The effect of short-term (mean (SE) 50 (3) days) hormone replacement therapy with either oestrogen alone or in combination with progesterone on sleep disordered breathing was investigated in 15 postmenopausal women with moderate obstructive sleep apnoea. The effect of treatment on the ventilatory response to hypoxia and hypercapnia was assessed in 10 patients. RESULTS--There was no reduction in the clinical severity of obstructive sleep apnoea after hormone treatment despite an increase in the serum oestrogen level from 172 (23) to 322 (33) pmol/l. There was a small but clinically insignificant reduction in the apnoea/hypopnoea index during REM sleep from 58 (6) to 47 (7). There was no difference in response between the oestrogen only group and the oestrogen plus progesterone group. Hypercapnic ventilatory responsiveness did not change with hormone treatment, but an change with hormone treatment, but an increase in hypoxic ventilatory responsiveness was observed. CONCLUSIONS--These data indicate that short-term hormone replacement is unlikely to have an effective role in the clinical management of postmenopausal women with obstructive sleep apnoea. The observed reduction in the apnoea/hypopnoea index during REM sleep, however, suggests that longer term treatment, or the use of higher doses, may have an effect.

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.

Neurobehavioral functioning in obstructive sleep apnea: differential effects of sleep quality, hypoxemia and subjective sleepiness

This study evaluated the relationship between neuropsychological and affective functioning, subjective sleepiness and sleep-disordered breathing in 100 patients with obstructive sleep apnea (OSA). Using principal components analysis, three indices of sleep-disordered breathing were identified from polysomnography: sleep disturbance, extent of nocturnal hypoxemia, and sleep quality. Poorer sleep quality was related to slower processing speed, somatic symptomatology and tension-anxiety levels. Nocturnal hypoxemia was related to visuconstructional abilities, processing speed and mental flexibility. Patients who had high levels of subjective sleepiness had poorer performances on a complex task of executive functioning and higher levels of tension-anxiety. These results imply a differential effect of sleep-disordered breathing on domains of neuropsychological functioning. Additionally, they suggest that a patient’s subjective level of sleepiness is a good predictor of certain aspects of neurobehavioral functioning.

Craniofacial abnormalities in obstructive sleep apnoea: Implications for treatment

Abstract Obstructive sleep apnoea (OSA) is a common disorder, and is characterized by repetitive closure of the upper airway during sleep. Upper airway narrowing and sleep‐induced loss of muscle tone are important factors in the development of OSA. Over the last decade there has been a growing recognition that craniofacial abnormalities occur commonly in OSA patients. The more commonly identified abnormalities include mandibular deficiency, an inferiorly placed hyoid bone relative to the mandibular plane, a narrowed posterior air space, a greater flexion of the cranial base, and elongation of the soft palate. It is thought that these abnormalities result. in upper airway narrowing, thereby predisposing to OSA. When the well established role of obesity in the development of OSA is taken into account, a model of OSA emerges in which the degree of craniofacial abnormalities determines the extent of obesity required to produce OSA in a given individual. The recognition of the role of craniofacial abnormalities in the development of OSA has led to a number of treatment strategies aimed at correcting or improving craniofacial structure, thereby preventing upper airway collapse during sleep. These treatments include dental appliances, and various maxillofacial surgical procedures. An improved understanding of the evolution of OSA from childhood to adulthood, in relation to facial development, may lead to a preventative strategy for this disorder.

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.

Nasopharyngoscopic evaluation of oral appliance therapy for obstructive sleep apnoea

This study aimed to explore the effect of mandibular advancement splints (MAS) on upper airway anatomy during wakefulness in obstructive sleep apnoea (OSA). Patients commencing treatment for OSA with MAS were recruited. Response to treatment was defined by a ≥50% reduction in the apnoea/hypopnoea index. Nasopharyngoscopy was performed in the supine position. Nasopharyngoscopy was performed in 18 responders and 17 nonresponders. Mandibular advancement caused an increase in the calibre of the velopharynx (mean±sem +40±10%), with relatively minor changes occurring in the oropharynx and hypopharynx. An increase in cross-sectional area of the velopharynx with mandibular advancement occurred to a greater extent in responders than nonresponders (+56±16% versus +22±13%; p<0.05). Upper airway collapse during the Müller manoeuvre, relative to the baseline cross-sectional area, was greater in nonresponders than responders in the velopharynx (-94±4% versus -69±9%; p<0.01) and oropharynx (-37±6% versus -16±3%; p<0.01). When the Müller manoeuvre was performed with mandibular advancement, airway collapse was greater in nonresponders than responders in the velopharynx (-80±11% versus +9±37%; p<0.001), oropharynx (-36±6% versus -20±5%; p<0.05) and hypopharynx (-64±6% versus -42±6%; p<0.05). These results indicate that velopharyngeal calibre is modified by MAS treatment and this may be useful for predicting treatment response.

The Effect of Treatment of Obstructive Sleep Apnea on Glycemic Control in Type 2 Diabetes

RATIONALE There is uncertainty about the effects of treating obstructive sleep apnea on glycemic control in patients with type 2 diabetes. OBJECTIVES To determine whether treatment of obstructive sleep apnea in patients with type 2 diabetes improves glycemic control. METHODS In this trial, we randomized patients with type 2 diabetes and no previous diagnosis of obstructive sleep apnea, with a glycated hemoglobin level of 6.5-8.5%, and an oxygen desaturation index of 15 or more events per hour to positive airway pressure therapy or to usual care. MEASUREMENTS AND MAIN RESULTS A total of 416 patients met the entry criteria as determined by each site and were randomized. Of the 298 participants who met centrally adjudicated entry criteria, no differences between the study groups were seen for change in glycated hemoglobin. Furthermore, there were no between-group differences when analyses were restricted to those with poorer baseline glycemic control, those with more severe sleep apnea, or those who were adherent to therapy. A greater fall in diastolic blood pressure occurred in the positive airway pressure group than in the usual care group (-3.5 mm Hg vs. -1.5 mm Hg; P = 0.07). This difference was significant in those who were adherent to positive airway pressure therapy (-4.4 mm Hg vs. -1.6 mm Hg; P = 0.02). There was a significant reduction in sleepiness in the positive airway pressure therapy group (P < 0.0001). Quality of life assessment revealed improvements in vitality, mental health, and mental component summary scores in the positive airway pressure therapy group. CONCLUSIONS This trial showed no effect of positive airway pressure therapy on glycemic control in patients with relatively well-controlled type 2 diabetes and obstructive sleep apnea. Clinical trial registered with www.clinicaltrials.gov (NCT00509223).