Epithelial Na+/K+ Imbalance and Impaired Na+/K+-ATPase Activity as Surface Markers of Airway Remodelling in Obstructive Sleep Apnea.

First, to compare the upper airway's anatomic and aerodynamic characteristics of the edentulous older adults who experience mild, moderate, and severe obstructive sleep apnea (OSA). Second, to examine the correlation between the severity of OSA and the anatomic and aerodynamic characteristic(s) of the upper airway in these edentulous individuals. NewTom5G cone beam computed tomography scans of 58 edentulous individuals with mild, moderate, and severe OSA were included in this analysis. 1) Computational models of the upper airway were reconstructed based on cone beam computed tomography images and the anatomical and aerodynamic characteristics of the upper airway were examined by an observer blind to OSA severity. 2) Pearson correlation analysis was used to determine the correlation between apnea-hypopnea index and the anatomic and aerodynamic characteristics of the upper airway. Compared with edentulous patients with mild and moderate OSA, those with severe OSA have a more hourglass-shaped upper airway. The severity of OSA, namely, apnea-hypopnea index, was significantly correlated with the length, shape, and minimum cross-sectional area of the upper airway. During inspiration, the mean velocity of the airflow within the upper airway of the edentulous patients with severe OSA was higher than that of patients with mild and moderate OSA. During both inspiration and expiration, apnea-hypopnea index was found to be significantly correlated with maximum velocity (P = .05) and airway resistance (P = .024, 0.038). The edentulous patients with severe OSA have a more hourglass-shaped upper airway. The findings also suggest that, during inspiration, the airflow travels faster in edentulous patients with severe OSA than in those with mild or moderate OSA. Registry: ClinicalTrials.gov; Name: The Effect of Nocturnal Wear of Dentures on Sleep and Oral Health Related Quality of Life; URL: https://clinicaltrials.gov/ct2/show/NCT01868295; Identifier: NCT01868295. Chen H, Elham E, Li Y, etal. Comparison of anatomic and aerodynamic characteristics of the upper airway among edentulous mild, moderate, and severe obstructive sleep apnea in older adults. J Clin Sleep Med. 2022;18(3):759-768.

The purpose of this study is to conduct a systematic review and meta-analysis evaluating the effects of respiratory muscle therapy (ie, oropharyngeal exercises, speech therapy, breathing exercises, wind musical instruments) compared with control therapy or no treatment in improving apnea-hypopnea index ([AHI] primary outcome), sleepiness, and other polysomnographic outcomes for patients diagnosed with obstructive sleep apnea (OSA). Only randomized controlled trials with a placebo therapy or no treatment searched using PubMed, EMBASE, Cochrane, and Web of Science up to November 2018 were included, and assessment of risk of bias was completed using the Cochrane Handbook. Nine studies with 394 adults and children diagnosed with mild to severe OSA were included, all assessed at high risk of bias. Eight of the 9 studies measured AHI and showed a weighted average overall AHI improvement of 39.5% versus baselines after respiratory muscle therapy. Based on our meta-analyses in adult studies, respiratory muscle therapy yielded an improvement in AHI of -7.6 events/h (95% confidence interval [CI] = -11.7 to -3.5; P ≤ .001), apnea index of -4.2 events/h (95% CI = -7.7 to -0.8; P ≤ .016), Epworth Sleepiness Scale of -2.5 of 24 (95% CI= -5.1 to -0.1; P ≤ .066), Pittsburgh Sleep Quality Index of -1.3 of 21 (95% CI= -2.4 to -0.2; P ≤ .026), snoring frequency (P = .044) in intervention groups compared with controls. This systematic review highlights respiratory muscle therapy as an adjunct management for OSA but further studies are needed due to limitations including the nature and small number of studies, heterogeneity of the interventions, and high risk of bias with low quality of evidence.

I read with interest the recent article by Dr. Michael Levitzky on using the pathophysiology of obstructive sleep apnea (OSA) to teach cardiopulmonary integration ([2][1]). With 10 years of experience of teaching courses in both respiratory physiology and sleep at the University of Toronto, I also

studies addressing the mechanisms underlying upper airway collapsibility during sleep are significant given the prevalence of obstructive sleep apnea (OSA) in the general population ([27][1]) and the serious public health impact of this disorder ([14][2]). A variety of factors predispose to OSA

The Pharyngeal Critical Pressure: The Whys and Hows of Using Nasal Continuous Positive Airway Pressure Diagnostically

This systematic review provides supporting evidence for the accompanying clinical practice guideline on the referral of adults with obstructive sleep apnea (OSA) for surgical consultation. The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of upper airway sleep apnea surgery or bariatric surgery to no treatment as well as studies that reported on patient-important and physiologic outcomes pre- and postoperatively. Statistical analyses were performed to determine the clinical significance of using surgery to treat obstructive sleep apnea in adults. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to assess the evidence for making recommendations. The literature search resulted in 274 studies that provided data suitable for statistical analyses. The analyses demonstrated that surgery as a rescue therapy results in a clinically significant reduction in excessive sleepiness, snoring, blood pressure (BP), apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxygen desaturation index (ODI); an increase in lowest oxygen saturation (LSAT) and sleep quality; and an improvement in quality of life in adults with OSA who are intolerant or unaccepting of positive airway pressure (PAP) therapy. The analyses demonstrated that surgery as an adjunctive therapy results in a clinically significant reduction in optimal PAP pressure and improvement in PAP adherence in adults with OSA who are intolerant or unaccepting of PAP due to side effects associated with high pressure requirements. The analyses also demonstrated that surgery as an initial treatment results in a clinically significant reduction in AHI/RDI, sleepiness, snoring, BP, and ODI and an increase in LSAT in adults with OSA and major anatomical obstruction. Analysis of bariatric surgery data showed a clinically significant reduction in BP, AHI/RDI, sleepiness, snoring, optimal PAP level, BMI, and ODI and an increase in LSAT in adults with OSA and obesity. Analyses of very limited evidence suggested that upper airway surgery does not result in a clinically significant increase in risk of serious persistent adverse events and suggested that bariatric surgery may result in a clinically significant risk of iron malabsorption that may be managed with iron supplements. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. Kent D, Stanley J, Aurora RN, etal. Referral of adults with obstructive sleep apnea for surgical consultation: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2021;17(12):2507-2531.

Freire C, Sennes LU, Polotsky VY. Opioids and obstructive sleep apnea. J Clin Sleep Med. 2022;18(2):647-652.

Insomnia and snoring are common sleep disorders. The aim was to investigate the association of having a combination of insomnia symptoms and snoring with comorbidity and daytime sleepiness. The study population comprised 25,901 participants (16-75 years, 54.4% women) from 4 Swedish cities, who answered a postal questionnaire that contained questions on snoring, insomnia symptoms (difficulties initiating and/or maintaining sleep and/or early morning awakening), smoking, educational level, and respiratory and nonrespiratory disorders. Snoring was reported by 4,221 (16.2%), while 9,872 (38.1%) reported ≥ 1 insomnia symptom. A total of 2,150 (8.3%) participants reported both insomnia symptoms and snoring. The association with hypertension (adjusted odds ratio [OR], 1.4; 95% confidence interval [CI], 1.2-1.6), chronic obstructive pulmonary disease (adjusted OR, 1.8; 95% CI, 1.3-2.4), asthma (adjusted OR, 1.9; 95% CI, 1.6-2.3), daytime sleepiness (adjusted OR, 7.9; 95% CI, 7.1-8.8), and the use of hypnotics (adjusted OR, 7.5; 95% CI, 6.1-9.1) was highest for the group with both insomnia symptoms and snoring. Participants with both snoring and insomnia run an increased risk of hypertension, chronic obstructive pulmonary disease, asthma, daytime sleepiness, and use of hypnotics. It is important to consider snoring in patients seeking medical assistance for insomnia and, vice versa, in patients with snoring inquiring about insomnia. Hägg SA, Ilieva E, Ljunggren M, etal. The negative health effects of having a combination of snoring and insomnia. J Clin Sleep Med. 2022;18(4):973-981.

There is evidence of an important mutual interaction between sleep disorders and cardiovascular problems. Patients with cardiovascular diseases often complain of several sleep disturbances such as sleep fragmentation, insomnia and breathing disorders during sleep. On the contrary, patients with sleep disorders are more frequently affected by cardiovascular problems. Such a reciprocal interaction makes it often difficult to determine which is the cause and which is the effect between these conditions. Sleep-related breathing disorders, particularly obstructive sleep apnoea syndrome (OSAS), formerly named Pickwickian syndrome, are highly prevalent in the general population, OSAS affecting at least 4% of middle-aged men and 2% of middle-aged women in the developed world, with its prevalence increasing in parallel with the growing prevalence of obesity. Individuals with OSAS are also characterized by a worsened quality of life and by excessive daytime somnolence, and are at an increased risk of road traffic and workplace accidents when compared with nonapnoeic individuals [1–3]. From a public health viewpoint, also the reported increased risk of cardiovascular morbidity and mortality associated with a diagnosis of obstructive sleep apnoea (OSA) is of particular importance [4,5]. OSA is associated with a higher prevalence of hypertension, in particular resistant hypertension, myocardial infarction, cardiac arrhythmias, congestive heart failure and stroke. Indeed, untreated severe OSA confers a three-fold increased risk of death from cardiovascular causes [1,2,6]. Prevalence of hypertension in OSA patients ranges from 35 to 80% and appears to be influenced by OSA severity. In fact, more than 60% of individuals with respiratory disturbance index greater than 30 were found to be hypertensive. Conversely, approximately 40% of hypertensive patients are diagnosed with OSA. Finally, when focussing on patients with resistant hypertension, OSA prevalence is significantly higher, reaching 83% [7]. Given this background, and the relevant interaction between OSA and cardiovascular disorders, it is evident that strategies for OSA treatment also play a key role in cardiovascular diseases prevention. The most widely used treatment for OSA is nasal continuous positive airway pressure (CPAP) application, which is reported to be able to reduce blood pressure (BP) values in particular in patients characterized by severe OSA, good compliance to CPAP therapy and hypertension at baseline [1,2]. However, such a support to ventilation is sometimes not well accepted by patients, in particular when they are of young age, affected by milder OSA and not complaining of excessive daytime somnolence. Moreover, its impact on BP reduction, at least based on available meta-analyses, has been reported to be, overall, only of mild entity [1,2]. Other treatment strategies have therefore been proposed, including positional therapies aimed at forcing OSA individuals to sleep on their side, weight loss, use of oral devices, surgery and electrical stimulation of the hypoglossus nerve, all interventions aimed at preventing night-time upper airways occlusion [3,8,9]. All currently available treatment strategies for OSA have been developed based on progress in understanding of OSA pathophysiology, and until now, they have mostly focused on solutions aimed at mechanically or functionally widening upper airways space. More recently, evidence has been provided that nocturnal upper airways occlusion may also be facilitated by fluid accumulation in upper airways walls, either because of increased water and sodium retention at the kidneys levels, owing to an increased aldosterone production and stimulation of mineralcorticoid receptors [10], and/or because of a nocturnal rostral shift of body fluids from peripheral vessels and interstitial spaces of lower limbs [11]. These reports have suggested novel treatment strategies, aimed at antagonizing mineral corticosteroid receptors, for example through spironolactone administration [12]. Also, the possibility to reduce peripheral leg fluid volume, aimed at preventing night-time fluid displacement from the lower extremities to the upper body during sleep and thus at reducing the resulting increased degree of nocturnal upper airways obstruction and the consequent severity of sleep apnoea, could be considered, although no evidence in this regard has been provided yet. The present article by Kasai et al.[13] in this issue of the Journal of Hypertension reports on the results of an experimental approach aimed at exploring the importance of reducing fluid shift from lower extremities to the upper body in determining OSA severity. In particular, this article was aimed at testing the hypothesis that intensified diuretic therapy (metolazone 2.5 mg and spironolactone 25 mg daily for 7 days after which the daily dose was doubled for 7 additional days) can reduce the apnoea-hypopnoea index and BP of uncontrolled hypertensive patients with OSA. This study thus specifically focused on the hypothesis that the ‘fluid shift theory’ could affect the pathogenesis of OSA in uncontrolled hypertensive patients and might thus open the way to a new treatment strategy. The theory of ‘fluid shift’ was one of the proposed mechanisms to explain pathophysiology of sleep-related breathing disorders (SRBDs) in particular in heart failure patients. The theory is based on the hypothesis that during the day, fluid is accumulated by gravity in the feet and legs of upright patients. When patients shift to the recumbent position for sleep, leg oedema is reabsorbed into circulating blood volume and contributes to worsen oedema in the lungs, leading to the central sleep apnoeas, but also in the upper airways, increasing the possibility of their collapse at night and thus leading to OSA [14]. The study by Kasai et al.[13] included 16 (11 men and five women) individuals with uncontrolled hypertension and moderate-to severe OSA [defined as an apnoea/hypopnoea index (AHI) ≥20 /h of sleep, of which ≥50% of events were obstructive]. No patient had been previously diagnosed with OSA or treated with CPAP. All patients underwent full polysomnography combined with noninvasive ‘beat-to-beat’ BP measurement during the night (Portapres device; Finapres Medical Systems Inc, Amsterdam, The Netherlands) before and after intensified diuretic treatment. BP evaluations additionally included baseline 24-h ambulatory BP monitoring; clinic BP and pulse rate measured twice after 5 min of rest in seated position at night before polysomnography; and home BP monitoring performed daily twice in the morning (0600–0800 h) and twice in the evening (2100–2300 h). Moreover, body weight, total body fluid, leg fluid volume, neck circumference and calf circumference were measured just before instrumentation for polysomnography, and after awakening the next morning. Finally, plasma levels of aldosterone and renin, serum sodium, potassium and creatinine were obtained in the early morning following polysomnography, both before and after intensified diuretic treatment. The study by Kasai et al.'s [13] demonstrates that in patients with uncontrolled hypertension and moderate-to severe OSA, a 2-week course of diuretic treatment reduced the volume of fluid accumulating in the legs during the day and also reduced its redistribution to the upper body, including the neck, during sleep. These effects were accompanied by a decrease in total AHI, in particular during non-rapid eye movement sleep. Finally, changes in overnight fluid distribution were significantly correlated to the fall in BP values in the morning. The study by Kasai et al. [13] represents the first experimental assessment of the hypothesis that reducing body fluids, and thus their rostral nocturnal shift, might reduce severity of OSA and the related BP increase. In spite of the interest of such a topic, however, also a few limitations of this work need to be mentioned. A first important limitation is the lack of a control group (including patients with OSA followed up without intensive diuretic treatment), which underlines the need of additional investigations in this field. A second limitation, also acknowledged by the authors, is the small improvement in OSA severity resulting from the intensified diuretic therapy, whose actual clinical relevance still needs to be clearly understood. Indeed, the difference between AHI values measured before and after treatment was statistically significant but of small size (AHI being reduced from 57.7 ± 33.0 to 48.5 ± 28.2 events per hour). Moreover, oxygen saturation during the night was not different before and after treatment. This may suggest that the contribution of fluid shift to severity of OSA is of modest entity only. Finally, this study included only a small number of individuals (n = 16), which may limit the generalizability of its findings. In conclusion, the results of this study, although of theoretical interest, should be considered as pilot observations, and additional investigations of larger size and with appropriate experimental design are needed to further explore this intriguing issue. These studies should in particular focus on the effects of an intensified diuretic treatment on 24-h and night-time ambulatory BP values of OSA patients, which may more faithfully reflect the effects of rostral fluid volume shift during sleep. ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.

Update on Obstructive Sleep Apnea: Implications for Neuropsychiatry.

Obstructive sleep apnea (OSA) is a widely prevalent problem, affecting almost 1 billion people worldwide.1 It is an established risk factor for perioperative cardiorespiratory complications and death.2–4 Much has been written about identifying the problem preoperatively, but inadequate thought has been given to perioperative treatment where significant OSA has been recognized. The accepted standard treatment for moderate to severe OSA is continuous positive airway pressure therapy delivered by nose or facemask. However, while it is highly beneficial to individual patients in controlling obstructive events, its overall population effectiveness is discounted by often inadequate compliance with it, both at home and when used in the hospital. Many patients have difficulty complying with it even when there are persuasive reasons for doing so. Hence, while it should always be considered where OSA is proving difficult to control, other approaches are required. In some cases this is to obviate the need for continuous positive airway pressure and in others as a substitute for it if the patient refuses to use it or cannot do so, for example because of facial injury. These issues provide the rationale for a study reported in this issue of Anesthesiology that considers an alternative approach to continuous positive airway pressure therapy to treat sleep disordered breathing postoperatively.5In this study, Sakaguchi et al. examine the value of combined therapy with high-flow nasal oxygen (20 l.min-1 40% oxygen concentration) and 30-degree head-of-bed elevation to treat this problem.5 Besides the obvious effect of oxygen therapy in enhancing oxygenation, the authors demonstrate that application of either of the therapy components results in a small reduction in the number of partial or complete obstructive events recorded, with these effects additive when they are combined. While the strategy provides incomplete control of OSA, these findings certainly make a case for considering it where continuous positive airway pressure therapy is unsuitable or refused by the patient.The effects described by Sakaguchi et al. have a biologically plausible basis and have been previously investigated in other contexts. Apart from augmenting oxygenation, high-flow oxygen therapy generates up to several cm H2O of positive airway pressure within the upper airway, helping pneumatically splint it.6 Upper-body elevation increases dimensions of the upper airway and decreases its collapsibility through alleviation of gravitational effects on its structures, reduction in the rostral fluid shifts that occur with recumbency, and an increase in functional residual capacity with associated caudal displacement of the diaphragm, which helps increase longitudinal traction on the upper airway.7 While these effects have been previously described, the combined use of high-flow oxygen and upper-body elevation in the perioperative setting has not. Sakaguchi et al. address this knowledge gap adroitly, and in so doing help draw attention both to these therapeutic options and, more generally, to the case for non–continuous positive airway pressure alternatives for postoperative OSA management.5Apart from the approaches described by Sakaguchi et al., these other non–continuous positive airway pressure options deserve exploration for perioperative use. They include other forms of positional therapy besides upper body elevation; oral appliances to produce mandibular advancement (jaw thrust); oropharyngeal and nasopharyngeal airway devices; and, in very limited circumstances, such as with some forms of major upper airway surgery, temporary tracheostomy. Drug considerations are also important, including care with use of drugs with sedative potential in these patients. As yet, specific drug treatments for OSA remain a distant prospect, as do other easy ways of activating dilatory upper airway musculature noninvasively.Besides upper body elevation, other positional strategies for OSA treatment include lateral positioning of the patient, rather than supine. OSA severity is reduced by at least 50% in the lateral relative to the supine posture in approximately 60% of OSA patients. Indeed, in 20% of OSA patients, it is present only when sleeping supine.8 Neck position is another positional influence on OSA severity, with neck flexion increasing propensity to obstruction and extension reducing it.9Oral appliances that are designed to advance the mandible—produce jaw thrust—are in widespread use for OSA treatment, and many consider them first-line treatment for snoring and milder forms of OSA.10 The most effective of these are made-to-measure, adjustable appliances where construction is individualized based on dental impressions taken from the patient, followed by careful titration of the degree of mandibular advancement to effect. However, the perioperative setting is not the place for slowly implemented therapies, and there are an increasing number of off-the-shelf alternatives available for home use that may prove useful perioperatively, even in patients previously naïve to them. This is a proposition that deserves further investigation.Oropharyngeal and nasopharyngeal airway devices are time-honored methods of controlling upper airway obstruction. However, they are likely to have limited applicability in the perioperative management of upper airway obstruction beyond the postanesthetic care unit because of discomfort with their use and, in the case of oropharyngeal devices, easy displacement. Nevertheless, they may be useful at least as a stopgap measure while other OSA treatment strategies are implemented, such as withdrawal of sedatives where these are in use. Furthermore, nasopharyngeal stenting devices have been used, with some success, to address sleep-related velopharyngeal obstruction, the primary site of obstruction in the majority of OSA cases.11 Again, this is another continuous positive airway pressure alternative that deserves further consideration.Tracheostomy is a drastic measure to treat OSA that, while highly effective, has very rarely been used for this application since the advent of continuous positive airway pressure therapy. However, there remain limited indications for its (usually temporary) use, such as in cases of severe postoperative edema or other airway obstruction after major upper airway surgery.Caution with use of opioid, hypnotic, and sedating drugs is an important OSA management principle. These drugs are commonly used perioperatively, and OSA management guidelines recommend minimizing this, asking that thought be given to analgesic alternatives such as multimodal analgesic therapy or, where applicable, regional analgesic techniques, together with use of readily reversible anesthetic techniques.12 It follows that where these drugs are in use perioperatively and OSA-related problems develop, their withdrawal should be considered along with alternative ways to address analgesic requirements.Specific drug therapy for OSA remains a distant prospect. The notion of a drug that activates upper airway muscles in a sleeping individual to a similar degree to that observed during wakefulness is attractive, but to date, efforts to achieve this have been unrewarding. Other ways of activating upper airway dilator muscles during sleep, such as with an implanted hypoglossal nerve stimulator, have a place in OSA treatment,13 and it is possible that transcutaneous stimulatory techniques may evolve to a point where they become a readily applicable way of achieving this in the perioperative setting.As Sakaguchi et al. imply, in all of this, it must be remembered that continuous positive airway pressure and other positive airway pressure therapies, such as bilevel ventilatory support where there is concurrent hypoventilation, remain an accepted standard in terms of capacity to control OSA and should always be considered where difficult-to-control OSA is evident. They can be made to work consistently in closely supervised circumstances, such as high-dependency units, if attending staff are well trained in their application and motivated to apply them.The author is not supported by, nor maintains any financial interest in, any commercial activity that may be associated with the topic of this article.

IN THIS ISSUE OF SLEEP, THERE IS AN INTERESTING CASE CONTROL STUDY FROM THE LABORATORY OF CISTULLI AND COLLEAGUES1 DEMONSTRATING A number of craniofacial differences between subjects with and without obstructive sleep apnea (OSA), based on a quantitative photographic analysis technique involving measurements from digital photographs. A total of 71 craniofacial measurements were computed using this novel photogrammetry technique on 114 OSA patients (defined as having apnea-hypopnea index [AHI] ≥ 10/hr on polysomnography) versus 66 sleep clinic controls with AHI < 10/hr, all of Caucasian ethnicity. Photographic differences were noted across all the craniofacial regions, with larger measurements of face width, mandible width, intercanthal width, and nose width in the OSA subjects than controls in the primary analysis. Following body mass index (BMI) and sex-matched subgroup analysis involving 51 patients with OSA versus 51 controls, the study revealed that subjects with OSA have a shorter and retruded jaw, smaller enclosed area within the mandible, wider and flatter mid and lower face, and more soft tissues or fat deposition on the anterior neck, without the influence of obesity.1 In a related prospective cohort study of 180 subjects referred for the initial investigation of OSA, the same group of investigators demonstrated that anatomical data useful in the prediction of OSA could be obtained from craniofacial photographic analysis, providing correct subject classification in about 76%.2 OSA syndrome is equally common among middle-aged male Caucasian and Asian populations, with prevalence rates of at least 4%.3–5 Most OSA patients have an anatomically small upper airway with augmented pharyngeal dilator muscle activation maintaining airway patency awake but not asleep.6 OSA is likely caused by a combination of multiple anatomical and pathophysiological factors. Obesity, sleep-induced loss of muscle tone, craniofacial abnormalities, and upper airway collapsibility probably all contribute to varying degrees in individual cases. Enlargement of the oropharyngeal soft tissue structures, especially the lateral pharyngeal walls (LPW),7 and a more collapsible velopharynx8 are some of the other important factors that may contribute to upper airway obstruction. Obesity is the most important risk factor in the pathogenesis of OSA in middle-aged adults.9 Neck circumference, a surrogate measure of neck fat, seems to be a better predictor of the presence of OSA than overall obesity.10 However, neck circumference is a gross measurement of a combination of structures including subcutaneous fat, neck muscle, parapharyngeal fat, and parapharyngeal wall muscle. It remains uncertain which structures in the neck are more important in the pathogenesis of OSA. It has been suggested that fat deposits, particularly at the lateral parapharyngeal space, might play a key role in the pathogenesis of OSA, whereas other studies have suggested that increased parapharyngeal wall thickness is a major cause of OSA.11,12 Enlargement of soft tissue structures, particularly the LPW, is associated with an increased likelihood of OSA among patients presenting to sleep disorders centers.7 Sonographic measurement of LPW thickness has been reported as a novel and reliable technique and has good correlations with measurement by magnetic resonance imaging (MRI) and the severity of OSA.13 Although the studies by Lee et al.1,2 dealt exclusively with Caucasians, craniofacial abnormality appears to play a particularly important role in OSA in Asian populations. While Asian patients with OSA are generally less obese than the Caucasian counterparts, despite having similar prevalence rates of OSA,3–5 craniofacial abnormalities such as a low hyoid bone and retroposition of the maxilla or mandible are common predisposing factors for OSA in the Asian populations.14,15 Nevertheless, previous studies with lateral cephalometric radiographs and other imaging techniques have revealed rather inconsistent and conflicting findings when comparing the craniofacial structures between Caucasian and Asian subjects with OSA. A study of a mixed group of Asians (consisting of Chinese, Japanese, and Korean) with OSA has shown that they had maxillo-mandibular protrusion, narrower cranial base angle, larger posterior airway space, and a more superiorly positioned hyoid bone as compared with Caucasians.16 In contrast, Liu et al.17 found no significant differences between Caucasians and Chinese, matched for age and BMI, with reference to the position of hyoid bone or maxilla. They did note, however, a smaller midface with a smaller and more posteriorly positioned mandible in the Chinese group. A study of OSA patients in Hong Kong and in Vancouver has shown that a crowded posterior oropharynx and a steep thyromental plane predicted OSA across two different ethnic groups and varying degrees of obesity.18 After removal of prior differences in BMI and neck circumference, Asians differed from Caucasians in Mallampati score (MS), thyromental distance (TMD), and thyromental angle (TMA). In order of importance, Asians had higher MS, smaller TMD, and larger TMA than Caucasian subjects.18 Upper airway imaging is a useful research tool that has improved our understanding of the biomechanics, pathophysiology, and treatment of OSA. A number of different imaging modalities have been used to evaluate the upper airway and surrounding structures including acoustic reflection, fluoroscopy, nasopharyngoscopy, cephalometry, computed tomography, MRI, and sonographic measurement of the LPW thickness.13,19 The novel craniofacial photogrammetry technique described by Cistulli and colleagues1,2 has several advantages over some of these imaging methods, including being widely available, safe without radiation, inexpensive, portable, and quick image acquisition. In conclusion, the craniofacial photographic analysis described by Lee et al.1,2 can detect phenotypic differences in OSA subjects versus sleep clinic controls, and provide detailed anatomical data useful in the prediction of OSA. The novel photographic analysis technique may have great potential as a clinical and research tool in the field of OSA. Further studies are needed with this technique to examine if there are any differences in craniofacial anatomy between different ethnic groups, and between OSA subjects and controls preferably recruited from a non-clinical population, in addition to testing its role in OSA risk stratification and management algorithm.

It is generally considered that patients with obstructive sleep apnea syndrome (OSAS) at increased perioperative risk should be placed in nonsupine positions throughout the recovery process; however, not all patients with OSAS show positional dependence. The authors hypothesized that morphological differences exist in three-dimensional (3D) soft tissue and craniofacial structures of the pharyngeal airway between positional and nonpositional OSAS. The subjects of the study were body mass index-matched, age-matched, and apnea hypopnea index-matched positional (n = 10) and nonpositional (n = 10) Japanese OSAS patients and body mass index-matched Japanese control subjects (n = 10). Pharyngeal magnetic resonance imaging and cephalometric radiography were performed during wakefulness. The patients with positional OSAS had a smaller volume of the pharyngeal lateral wall soft tissues, larger maxilla-nasion-mandible angle, and smaller lower facial height than the nonpositional OSAS and the control subjects. The patients with positional OSAS showed a significantly steeper sella-nasion-mandible angle and smaller craniofacial volume than the control subjects. There were no significant differences in tongue volume and 3D pharyngeal anatomical balance between positional and nonpositional OSAS. Multivariate stepwise regression for positional dependence showed that the dominant determinant was the volume of the lateral pharyngeal wall, followed by lower facial height and maxilla-nasion-mandible angle. Patients with positional OSAS have wider airways in the lateral parts, lower facial height, and more backward position of the lower jaw, which may explain differences in the maintenance of pharyngeal airway patency in the lateral sleep position.

Recent animal and human physiology studies indicate that noradrenergic and muscarinic processes are key mechanisms that mediate pharyngeal muscle control during sleep. The noradrenergic agent reboxetine combined with the anti-muscarinic hyoscine butylbromide has recently been shown to improve upper airway function during sleep in healthy individuals. However, whether these findings translate to the clinically relevant patient population of people with obstructive sleep apnoea (OSA), and the effects of the agents on OSA severity, are unknown. We found that reboxetine plus hyoscine butylbromide reduced OSA severity, including overnight hypoxaemia, via increases in pharyngeal muscle responsiveness, improvements in respiratory control and airway collapsibility without changing the respiratory arousal threshold. These findings provide mechanistic insight into the role of noradrenergic and anti-muscarinic agents on upper airway stability and breathing during sleep and are important for pharmacotherapy development for OSA. The noradrenergic agent reboxetine combined with the anti-muscarinic hyoscine butylbromide has recently been shown to improve upper airway function during sleep in healthy individuals. However, the effects of this drug combination on obstructive sleep apnoea (OSA) severity are unknown. Accordingly, this study aimed to determine if reboxetine plus hyoscine butylbromide reduces OSA severity. Secondary aims were to investigate the effects on key upper airway physiology and endotypic traits. Twelve people with OSA aged 52±13years, BMI=30±5kg/m2 , completed a double-blind, randomised, placebo-controlled, crossover trial (ACTRN12617001326381). Two in-laboratory sleep studies with nasal mask, pneumotachograph, epiglottic pressure sensor and bipolar fine-wire electrodes into genioglossus and tensor palatini muscles were performed separated by approximately 1week. Each participant received either reboxetine (4mg) plus hyoscine butylbromide (20mg), or placebo immediately prior to sleep. Polysomnography, upper airway physiology and endotypic estimates of OSA were compared between conditions. Reboxetine plus hyoscine butylbromide reduced the apnoea/hypopnoea index by (mean±SD) 17±17events/h from 51±30 to 33±22events/h (P=0.005) and nadir oxygen saturation increased by 6±5% from 82±5 to 88±2% (P=0.002). The drug combination increased tonic genioglossus muscle responsiveness during non-REM sleep (median [25th, 75th centiles]: -0.007 [-0.0004, -0.07] vs. -0.12 [-0.02, -0.40] %maxEMG/cmH2 O, P=0.02), lowered loop gain (0.43±0.06 vs. 0.39±0.07, P=0.01), and improved airway collapsibility (90 [69, 95] vs. 93 [88, 96] %eupnoea, P=0.02), without changing the arousal threshold (P=0.39). These findings highlight the important role that noradrenergic and muscarinic processes have on upper airway function during sleep and the potential for pharmacotherapy to target these mechanisms to treat OSA.

Chiari malformation Type I (CM-I) has been associated with sleep disordered breathing (SDB). The aim of this study was to evaluate the prevalence of SDB in CM-I and its clinical correlates in a population of children and adolescents. Fifty-three consecutive children and adolescents affected by CM-I were enrolled (27 girls and 26 boys, mean age 10.3 ± 4.3, range: 3-18 years). All patients underwent neurological examination, MRI, and polysomnography (PSG). Otorhinolaryngologic clinical evaluation was performed in patients with polysomnographic evidence of sleep-related upper airway obstruction. Mean size of the herniation was 9.5 ± 5.4 mm. Fourteen patients had syringomyelia, 5 had hydrocephalus, 31 presented neurological signs, 14 had epileptic seizures, and 7 reported poor sleep. PSG revealed SDB in 13 subjects. Patients with SDB, compared to those without SDB, had a higher prevalence hydrocephalus (p = 0.002), syringomyelia (p = 0.001), and neurological symptoms (p = 0.028). No significant difference was observed in age, gender, prevalence of epilepsy, and size of the herniation. Obstructive SDB was associated with syringomyelia (p = 0.004), whereas central SDB was associated with hydrocephalus (p = 0.034). In our population of CM-I patients the prevalence of SDB was 24%, lower than that reported in literature. Moreover, our findings suggest that abnormalities in cerebrospinal fluid dynamics in CM-I, particularly syringomyelia and hydro-cephalus, are associated with SDB.