Andrew L. Chan

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±0.7u2005cm3 vs 18.1±0.8u2005cm3; p<0.01) that occurred predominantly because of an increase in the volume of the velopharynx (5.7±0.3u2005cm3 vs 6.5±0.3u2005cm3; p<0.001). This increase in airway calibre was associated with an increase in the lower anterior facial height (6.8±0.1u2005cm vs 7.5±0.1u2005cm; p<0.001), reduction in the distance between the hyoid and posterior nasal spine (7.4±0.1u2005cm vs 7.2±0.1u2005cm; p<0.001), lateral displacement of the parapharyngeal fat pads away from the airway (right parapharyngeal fat pad 0.17±0.02u2005cm; left parapharyngeal fat pad 0.22±0.02u2005cm) and anterior movement of the tongue base muscles (0.33±0.03u2005cm). 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.

A review of current and novel therapies for idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressively fibrotic interstitial lung disease that is associated with a median survival of 2-3 years from initial diagnosis. To date, there is no treatment approved for IPF in the United States, and only one pharmacological agent has been approved outside of the United States. Nevertheless, research over the past 10 years has provided us with a wealth of information on its histopathology, diagnostic work-up, and a greater understanding of its pathophysiology. Specifically, IPF is no longer thought to be a predominantly pro-inflammatory disorder. Rather, the fibrosis in IPF is increasingly understood to be the result of a fibroproliferative and aberrant wound healing cascade. The development of therapeutic targets has shifted in accord with this paradigm change. This review highlights the current understanding of IPF, and the recent as well as novel therapeutics being explored in clinical trials for the treatment of this devastating disease.

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.

Obstructive sleep apnoea - an update

Obstructive sleep apnoea (OSA) is a common disorder characterized by the repetitive complete or partial collapse of the upper airway during sleep. It results in intermittent hypoxaemia and hypercapnia, cortical arousals and surges of sympathetic activity. The occurrence of OSA has also been linked to serious long‐term adverse health consequences; such as hypertension, metabolic dysfunction, cardiovascular disease, neurocognitive deficits and motor vehicle accidents. There have been several advances in the field of particular clinical importance: (i) the development of portable monitoring as part of a simplified clinical algorithm for the diagnosis of OSA in selected patients; (ii) growing awareness of the cardio‐metabolic health consequences of OSA and (iii) emerging evidence to support a range of non‐continuous positive airway pressure (CPAP) treatment modalities, such as oral appliances.

Australian and New Zealand Pulmonary Rehabilitation Guidelines

The aim of the Pulmonary Rehabilitation Guidelines (Guidelines) is to provide evidence‐based recommendations for the practice of pulmonary rehabilitation (PR) specific to Australian and New Zealand healthcare contexts.

Acute exacerbation of idiopathic pulmonary fibrosis-a review of current and novel pharmacotherapies.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive form of lung disease of unknown etiology for which a paucity of therapies suggest benefit, and for which none have demonstrated improved survival. Acute exacerbation of IPF (AE-IPF) is defined as a sudden acceleration of the disease or an idiopathic acute injury superimposed on diseased lung that leads to a significant decline in lung function. An AE-IPF is associated with a mortality rate as high as 85% with mean survival periods of between 3 to 13 days. Under these circumstances, mechanical ventilation (MV) is controversial, unless used a as a bridge to lung transplantation. Judicious fluid management may be helpful. Pharmaceutical treatment regimens for AE-IPF include the use of high dose corticosteroids with or without immunosuppressive agents such as cyclosporine A (CsA), and broad spectrum antibiotics, despite the lack of convincing evidence demonstrating benefit. Newer research focuses on abnormal wound healing as a cause of fibrosis and preventing fibrosis itself through blocking growth factors and their downstream intra-cellular signaling pathways. Several novel pharmaceutical approaches are discussed.

Use of flow-volume curves to predict oral appliance treatment outcome in obstructive sleep apnea: a prospective validation study

PurposeFlow–volume curves have been shown to relate to upper airway physiology during sleep and may be useful for predicting the response to treatment of obstructive sleep apnea (OSA) with mandibular advancement splints (MAS). The aim of this study was to prospectively assess the potential clinical utility of a previously derived prediction method using flow–volume curves performed during wakefulness.MethodsPatients with newly diagnosed OSA interested in undertaking treatment with a custom-made MAS were approached to participate in the study. Response to treatment was defined by a 50% or greater reduction in the apnea–hypopnea index. Flow–volume curves were performed in the erect position prior to construction of the MAS.ResultsFlow–volume curves were performed in 35 patients. Of these, 25 patients were responders, and 10 patients were non-responders. A combined cut-off of an inspiratory flow rate at 50% of vital capacity (MIF50) less than 6.0xa0L/s and a ratio of the expiratory flow rate at 50% of vital capacity to MIF50 of greater than 0.7 correctly classified 48.6% of the patients. It had a sensitivity of 36.0%, specificity of 80.0%, positive predictive value of 81.8%, and negative predictive value of 33.3%.ConclusionsThese results suggest that the previously derived prediction model, using flow–volume curves performed during wakefulness, was not sufficient to reliably predict the response to treatment of OSA with MAS. A combination of a functional assessment using flow–volume curves and a structural evaluation of the upper airway with imaging modalities may result in a prediction model with better performance characteristics.

New combination treatments in the management of asthma: Focus on fluticasone/vilanterol

Despite the 2007 National Asthma Education and Prevention Program Expert Panel 3 guidelines for the treatment of uncontrolled asthma, many patients with poorly controlled asthma still continue to tax the health care system. Controlling asthma symptoms and preventing acute exacerbations have been the foundation of care. Using long-term controller treatments such as inhaled corticosteroids (ICS) and inhaled long-acting beta2-agonists (LABAs) is a common approach. While patient responses to recommended pharmacotherapy may vary, poor adherence to therapy also contributes to poor asthma control. A once-daily combination inhaler, such as fluticasone furoate, an ICS, in combination with vilanterol, a LABA, offers increased convenience and potential improved adherence, which should result in enhanced clinical outcomes and reduced exacerbations. The ICS/LABA combination inhaler of fluticasone furoate and vilanterol is currently approved in the United States for use in the maintenance of chronic obstructive pulmonary disease and to reduce exacerbations. This paper reviews the expanding literature on the efficacy of fluticasone furoate and vilanterol in treating asthma.

Three-dimensional assessment of anatomical balance and oral appliance treatment outcome in obstructive sleep apnoea.

PurposeMandibular advancement splints (MAS) are an effective treatment for obstructive sleep apnoea (OSA). However, MAS are not equally efficacious across all patients and the reasons are not well understood. Craniofacial and upper airway structure individually influence MAS response. We aimed to assess anatomical balance, defined as the ratio of upper airway soft tissue (ST) volume to maxillomandibular enclosure volume, between MAS treatment responders and non-responders.MethodsOSA patients (apnoea-hypopnea index (AHI) >10xa0h−1) were recruited for MAS treatment. Magnetic resonance imaging of the upper airway was performed during wakefulness without and with MAS in situ. Images were processed for volumetric analysis of upper airway soft tissues (tongue, soft palate, paraphayrngeal fat pads and lateral pharyngeal walls) and three-dimensional cephalometry to acquire intra-mandibular space area (IMA) and total maxillomandibular (Mm) volume. Anatomical balance ratios were compared between MAS treatment responders (AHI <10xa0h−1u2009+u200950xa0% reduction) and non-responders.ResultsImage analysis was completed in 69 patients (68xa0% male, age 50.5u2009±u200910.1xa0years, BMI 29.6u2009±u20095.0xa0kgm2, AHI 27.0u2009±u200914.7xa0h−1) including 36 responders. Soft tissue volumes did not differ between MAS responders and non-responders. Non-responders had increased ST/IMA compared to responders (4.9u2009±u20090.6 vs. 4.6u2009±u20090.6, pu2009=u20090.031). In multivariate logistic regression with AHI and BMI, ST/IMA was the only predictive variable (pu2009=u20090.036, ROC AUC 0.7). However, changes in ST/Mm did not directly relate to treatment response.ConclusionsAnatomical imbalance assessed by intra-mandibular space area was associated with poor MAS treatment response. However, changes in anatomical balance with mandibular advancement did not reflect treatment outcome as static imaging may not adequately capture improvements in upper airway function.