Richard W. W. Lee

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.

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.

Levosimendan for the treatment of acute severe heart failure: A meta-analysis of randomised controlled trials

BACKGROUND The objective of this study was to critically review the literature to evaluate whether levosimendan compared to standard therapy, in patients with acute severe heart failure, is associated with improved clinical outcomes. METHODS Medline, EMBASE, and the Cochrane central register of clinical trials were searched. We also searched clinical trials registries, bibliographies of included studies and review articles and contacted the manufacturers of levosimendan to identify unpublished studies. Randomised clinical trials comparing levosimendan to standard therapy or placebo, in adult patients with acute severe heart failure, reporting at least one outcome of interest were included. Data were extracted regarding the characteristics, methodological quality and clinical outcomes, and combined using a fixed-effect meta-analysis. RESULTS We identified 19 RCTs enrolling 3650 patients, only two studies fulfilled all of the validity criteria. There was a non-significant reduction in mortality with levosimendan compared with placebo (OR 0.83, 95%CI, 0.62-1.10, p=0.20). Levosimendan was associated with reduced mortality compared to dobutamine (OR 0.75, 95%CI, 0.61-0.92, p=0.005). Levosimendan was associated with improvements in haemodynamic parameters when compared to either placebo or dobutamine. CONCLUSIONS Levosimendan improved haemodynamic parameters when compared with placebo, without showing evidence of survival benefit. Levosimendan improved both haemodynamics and survival when compared with dobutamine.

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.

Non-positive airway pressure modalities: mandibular advancement devices/positional therapy.

Although positive airway pressure is the most efficacious treatment for obstructive sleep apnea (OSA), its clinical effectiveness is limited by its obtrusive interface. Two alternative treatment modalities used in clinical practice are mandibular advancement devices (MADs) and positional therapy. The goals in treatment of OSA are to prevent obstructive apneas and hypopneas, to improve symptoms, and to modify the increased cardiovascular risk. MADs achieve this by mechanically protruding the mandible, thereby increasing the dimensions of the upper airway and reducing its collapsibility. By avoiding supine sleep, positional therapy improves the patency of the upper airway in those with positional OSA. There is now a relatively strong evidence base to support the use of MADs in clinical practice, with research studies assessing the impact of treatment on a range of health outcomes. The revised clinical practice parameters of the American Academy of Sleep Medicine recommend their use for mild to moderate OSA; or for patients with severe OSA who are unable to tolerate or refuse treatment with positive airway pressure. The evidence base for positional therapy is emerging, but is less well developed. A better understanding of the range of OSA phenotypes and predictors of response to different treatment modalities is required to allow physicians to tailor the choice of treatment to the individual patient.

A teaching hospital's experience applying the Pneumonia Severity Index and antibiotic guidelines in the management of community‐acquired pneumonia

Background and objectives:  The Pneumonia Severity Index (PSI) was developed to predict mortality in community‐acquired pneumonia (CAP). It has been prospectively validated to identify patients who are at low risk of death and thereby aid in the selection of patients for outpatient management. This study assessed the compliance of medical staff at a university teaching hospital with the use of the PSI and the PSI‐based local antibiotic guidelines in admitted patients.

Early switch to oral antibiotics and early discharge guidelines in the management of community-acquired pneumonia.

Background and objective:  The major cost of managing community‐acquired pneumonia (CAP) relates to the duration i.v. antibiotic use and length of hospital stay (LOS). Guidelines on early switch to oral antibiotics and early discharge from hospital may help to achieve a unified approach to managing CAP. The aim of this study was to assess the benefits and safety of these guidelines in an Australian respiratory medicine unit.

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.

Craniofacial phenotyping for prediction of obstructive sleep apnoea in a Chinese population

Craniofacial morphology is a risk factor for obstructive sleep apnoea (OSA). Facial photography has previously shown utility in predicting OSA in a Caucasian sleep clinic. However, ethnic differences in OSA risk factors may influence these facial predictors. Our aim was to assess phenotypical facial measurements for OSA prediction in a Chinese population.