In-home evaluation of efficacy and titration of a mandibular advancement device for obstructive sleep apnea

There is increasing evidence that mandibular advancement devices (MADs) can be an effective treatment for some patients with obstructive sleep apnea, a highly prevalent chronic disease. In this study, the objectives were to objectively assess the effectiveness of MAD therapy using a limited channel recorder, and to develop a model for identifying patients who may be appropriate for MAD therapy as the initial treatment option. Thirty patients were prospectively recruited and studied at two independent dentist offices and the participants’ homes. Subjects wore the ARES Unicorder for two nights before insertion of the MAD, and again when the dentist determined that the patient had reached the titration endpoint. Self-reported measures of depression, sleepiness, and quality of life were obtained pre- and posttreatment. The reviewer was blinded to the study status while the physiological signals were being visually inspected. Significant reductions in the apnea/hypopnea index (AHI), hypoxemia measures, and snoring level were observed posttreatment. Twenty-seven of the 30 (90%) patients had a posttreatment AHI (using a 4% desaturation for hypopneas) below a clinical cut-off of 10. All but one patient (97%) exhibited at least a 50% decrease in AHI or had a posttreatment AHI ≤ 10. Significant differences in body mass index, weight, and neck circumference in patients with posttreatment AHIs above and below a clinical cut-off of five were identified. The linear regression used to predict the posttreatment AHI using pretreatment data resulted in an R ² of 0.68. The model correctly predicted two patients who were unable to obtain a posttreatment AHI of 10 or less. This study was designed to demonstrate two models of collaboration between a dental sleep medicine specialist and a sleep medicine physician in the monitoring of a patient treated with a MAD. The outcome data suggest that the limited channel recording system can be used as an alternative to laboratory polysomnography to reduce the cost of MAD treatment, and to improve the quality and consistency of posttreatment patient care.     

Plasma homocysteine in obstructive sleep apnoea.

AIMS: Whether increased homocysteine is one mechanism linking obstructive sleep apnoea (OSA) to cardiovascular abnormalities is unclear. We hypothesised that plasma homocysteine would be higher in OSA patients than in control subjects, would increase further during sleep, and decrease after treatment with continuous positive airway pressure (CPAP). METHODS AND RESULTS: For study A, homocysteine was measured in 22 OSA patients and 20 controls first before sleep, then after 5 h of untreated OSA, and then in the morning after CPAP treatment. Homocysteine was similar in the OSA and control subjects at all three time points, and declined overnight in both groups (P=0.0017, P=0.036, respectively). To further assess this diurnal variation, we studied plasma homocysteine under a full-night protocol in 10 OSA patients and 12 controls (study B). Homocysteine was measured before sleep, in the morning after sleep, and at noon. Results in both OSA and control groups showed an overnight decline in homocysteine which was reversed by noon (repeated measures ANOVA: OSA, P=0.04; controls, P=0.02). Study C showed that disturbed sleep did not affect homocysteine levels in normal subjects. CONCLUSION: There is a significant diurnal variation in plasma homocysteine, so that homocysteine is lower in the morning after waking. Neither OSA nor disturbed sleep elicit acute or chronic changes in homocysteine.     

RETRACTED ARTICLE: Management of obstructive sleep apnea in an edentulous patient with a combination of mandibular advancement splint and tongue-retaining device: a clinical report

Background  Treatment of obstructive sleep apnea (OSA) in dentate patients by using mandibular advancement splint (MAS), had been documented in detail. Nevertheless, studies about completely edentulous patients with OSA are sparse. Report  This clinical report describes a clinical and laboratory method for producing a new functional splint combining a MAS and a tongue-retaining device with a custom-made tongue-tip housing and discusses the rationale for using such a device.     

Long-term nasal CPAP does not ameliorate obstructive sleep apnoea

Fifty-seven patients with obstructive sleep apnoea (OSA) were treated for at least six months with nasal continuous positive airway pressure (CPAP). At follow-up, sleep studies were performed in which CPAP was not used for the first half of the night. We compared the severity of OSA at follow-up without CPAP to the severity of OSA during the patient's initial diagnostic study. Apnoea and hypopnoea index (AHI) fell from 41.4 ± 7.5 (mean ±95% CI) to 34.8 ± 7.9 (p= 0.06 by Wilcoxon test) and minimum oxygen saturation rose from 71.6 ± 3.2 to 78.5 ± 2.6 (p<0.001). Some of this change may have been due to reduced REM sleep in the follow-up study (10.5±2.1% Total Sleep Time vs 7.4±2.4% TST, p<0.05). Long-term nasal CPAP was not associated with any reduction of obesity (BMI before CPAP 31.9 ± 1.0, after CPAP 31.7 ± 1.0 (p= 0.39). Systolic arterial pressure fell (before CPAP 143.0 ±4.5 mmHg, after CPAP 136.3 ± 4.6, p < 0.05) but diastolic pressure did not (before CPAP 88.5 ± 3.0 mmHg, after CPAP 85.6 ±2.9 mmHg, p = 0.11). We concluded that the effect of CPAP treatment for six or more months was a small fall in AHI and a small rise in minimum Sa0₂, but that this would be of marginal clinical significance, and may be artefactual. (Aust NZ J Med 1991; 21: 235–238.)     

The effect of oral appliance therapy on blood pressure in patients with obstructive sleep apnea

The objective of the study was to investigate the effects of oral appliance (OA) therapy on ambulatory blood pressure in patients with obstructive sleep apnea (OSA). Eleven OSA patients who received OA therapy were prospectively investigated. Ambulatory blood pressure was measured for 20 h from 4:00 p.m. to 12:00 noon the next day using an ambulatory blood pressure monitor. The Respiratory Disturbance Index (RDI) was measured in the pretreatment and posttitration periods. The OA was titrated to reach a therapeutic jaw position over 2 to 8 months, and posttitration measurements were repeated. At posttitration, the RDI was significantly decreased from a mean (SD) of 24.7 (20.1) to 6.1 (4.5). Significant reductions in diastolic blood pressure (DBP) and mean arterial pressure (MAP) were found for the 20-h periods, and systolic blood pressure (SBP), DBP, and MAP while asleep. The mean values were 79.5 (5.5) to 74.6 (6.0) for DBP and 95.9 (5.4) to 91.2 (5.9) for MAP, for over a 20-h period, and 118.4 (10.0) to 113.7 (9.1) for SBP, 71.6 (8.0) to 67.2 (7.9) for DBP, and 88.4 (8.0) to 83.9 (7.5) for MAP, while asleep. This study suggests that successful OSA treatment with an OA may also be beneficial to lower blood pressure in OSA patients, as previously suggested for nasal continuous positive airway pressure therapy. This study was conducted in the Division of Orthodontics, The University of British Columbia, Canada     

Oxidative stress in obstructive sleep apnoea.

AIMS: Any sustained elevation of oxidative stress in patients with obstructive sleep apnoea (OSA) might help explain their increased risk for cardiovascular diseases. We tested the hypothesis that measures of oxidative stress are increased in otherwise healthy subjects with OSA when compared to closely matched OSA-free control subjects. METHODS AND RESULTS: Plasma indices of oxidative stress and lipid peroxidation [thiobarbituric acid-reactive substances (TBARS), oxidized LDL (oxLDL), isoprostanes] were measured in 41 moderate-severe OSA males without other diseases and in 35 matched controls first before sleep, then after 4 h of untreated OSA, and again in the morning after 4 h of effective treatment with continuous positive airway pressure (CPAP). Plasma levels of oxLDL, TBARS, and isoprostanes in OSA patients (n=34, 26, 17, respectively) were comparable to the controls (n=28, 27, 15 for the three markers, respectively). Neither untreated OSA nor CPAP treatment nor normal sleep affected levels of any of the three measures of oxidative stress. There was no association between the severity of sleep apnoea and any measure of oxidative stress. CONCLUSION: Otherwise healthy OSA patients, without any other co-morbidities, do not manifest evidence for higher oxidative stress and lipid peroxidation. Thus, oxidative stress and lipid peroxidation do not appear to be key mediators of increased cardiovascular disease in OSA patients.     

Functional contribution of mandibular advancement to awake upper airway patency in obstructive sleep apnea

In the narrowed upper airway of patients with obstructive sleep apnea (OSA), a neuromuscular compensatory mechanism augments the activity of the upper airway dilator muscles in defense of upper airway patency, particularly during inspiration. We hypothesized that mechanical enlargement of the upper airway by a mandibular advancement oral appliance would permit a reduction in this neuromuscular compensation during wakefulness. To test this hypothesis, we focused on changes in the cross-sectional (CS) area of the upper airway before and after emplacement of a ventrally titrated oral appliance in 12 awake OSA patients. The CS areas at the end of tidal expiration (CS area-EET) and at the nadir of intraluminal pressure during inspiration (CS area-IN) were obtained using videoendoscopy. The median apnea–hypopnea index decreased with mandibular advancement. Before mandibular advancement, there was no difference between CS area-EET and CS area-IN in the velopharynx, oropharynx, and hypopharynx. This indicates that upper airway dilator muscle activity increased during inspiration to counteract the intraluminal negative pressure of the upper airway. After mandibular advancement, CS area-EET increased in the velopharynx, oropharynx, and hypopharynx, but CS area-IN was unchanged at any level and was less than CS area-EET in the velopharynx and oropharynx. These findings suggest that mandibular advancement enlarges the upper airway and may reduce upper airway dilator muscle activity during inspiration. We conclude that oral appliances act to return the upper airway towards a normal configuration and pattern of muscle function in OSA patients.     

Exhaled breath markers in patients with obstructive sleep apnoea

The objectives of the present study were to assess the level of exhaled breath markers indicating airway inflammation and oxidative stress in patients with obstructive sleep apnoea syndrome (OSAS) in comparison with non-apnoeic (obese and non-obese) subjects and investigate whether therapy with continuous positive airway pressure (CPAP) can modify them. The design was a retrospective observational study, set in Evgeneidio Hospital. Twenty-six OSAS patients and nine obese and 10 non-obese non-apnoeic subjects participated in this study. We measured nasal nitric oxide (nNO), exhaled nitric oxide (eNO), exhaled carbon monoxide (eCO) in exhaled breath, and 8-isoprostane, leukotriene B(4) (LTB(4)), nitrates, hydrogen peroxide (H(2)O(2)), and pH in exhaled breath condensate (EBC) before and after 1 month of CPAP therapy. The levels of eNO and eCO were higher in OSAS patients than in control subjects (p < 0.05). Nasal NO was higher in OSAS patients than in obese controls (p < 0.01). The level of H(2)O(2), 8-isoprostane, LTB(4), and nitrates were elevated in OSAS patients in comparison with obese subjects (p < 0.01). Conversely, pH was lower in OSAS patients than in non-apnoeic controls (p < 0.01). One month of CPAP therapy increased pH (p < 0.05) and reduced eNO (p < 0.001) and nNO (p < 0.05). Apnea/hypopnoea index was positively correlated with 8-isoprostane (r = 0.42; p < 0.05), LTB(4) (r = 0.35; p < 0.05), nitrates (r = 0.54; p < 0.001), and H(2)O(2) (r = 0.42; p < 0.05). Airway inflammation and oxidative stress are present in the airway of OSAS patients in contrast to non-apnoeic subjects. Exhaled breath markers are positively correlated with the severity of OSAS. One-month administration of CPAP improved airway inflammation and oxidative stress.     

Benefits of obstructive sleep apnoea treatment in coronary artery disease: a long-term follow-up study.

AIM: The aim of this long-term prospective study was to evaluate the effect of treating obstructive sleep apnoea (OSA) on the rate of cardiovascular events in coronary artery disease (CAD). METHODS AND RESULTS: We prospectively studied 54 patients (mean age 57.3 +/- 10.1 years) with both CAD (> or = 70% coronary artery stenosis) and OSA (apnoea-hypopnoea index > or = 15). In 25 patients, OSA was treated with continuous positive airway pressure (n=21) or upper airway surgery (n=4); the remaining 29 patients declined treatment for their OSA. The median follow-up was 86.5 +/- 39 months. The two groups were similar at baseline in age, body mass index, smoking history, hypertension, hypercholesterolaemia, diabetes mellitus, number of diseased vessels, left ventricular ejection fraction, and CAD therapy. Treatment of risk factors other than OSA was similar in the two groups. The endpoint (a composite of cardiovascular death, acute coronary syndrome, hospitalisation for heart failure, or need for coronary revascularisation) was reached in 6 (6/25, 24%) and 17 (17/29, 58%) patients with and without OSA treatment, respectively (P<0.01). OSA treatment significantly reduced the risk of occurrence of the composite endpoint (hazard ratio 0.24; 95% confidence interval, 0.09-0.62; p<0.01) and of each of its components. CONCLUSIONS: Our data indicate that the treatment of OSA in CAD patients is associated with a decrease in the occurrence of new cardiovascular events, and an increase in the time to such events.     

Atrial overdrive pacing compared to CPAP in patients with obstructive sleep apnoea syndrome.

AIMS: Obstructive sleep apnoea (OSA) is associated with oxygen desaturation, blood pressure increase, and neurohumoral activation, resulting in possible detrimental effects on the cardiovascular system. Continuous positive airway pressure (CPAP) is the therapy of choice for OSA. In a recent study, nocturnal atrial overdrive pacing (pacing) reduced the severity of sleep apnoea in pacemaker patients. We compared the effects of CPAP with those of pacing in patients with OSA but without pacemaker indication or clinical signs of heart failure. METHODS AND RESULTS: Ten patients with OSA on CPAP therapy were studied for three nights by polysomnography. During the nights that followed a night without any treatment (baseline), the patients were treated with CPAP or pacing in a random order. Pacing was performed with a temporary pacing lead. The pacing frequency was 15 b.p.m. higher than the baseline heart rate. The apnoea-hypopnoea index was 41.0 h(-1) (12.0-66.6) at baseline and was significantly lower during CPAP [2.2 h(-1) (0.3-12.4)] compared with pacing [39.1 h(-1) (8.2-78.5)]. Furthermore, duration and quality of sleep were significantly improved during CPAP when compared with pacing. CONCLUSION: Nocturnal atrial overdrive pacing is no alternative therapeutic strategy to CPAP for the treatment of OSA in patients without clinical signs of heart failure and without conventional indication for anti-bradycardia pacing.     

Screening for atrial fibrillation in patients with obstructive sleep apnoea to reduce ischaemic strokes

Obstructive sleep apnoea is an independent risk factor for stroke. A number of different mechanisms have been identified which link OSA and stroke including hypertension and oxidative stress. Atrial fibrillation (AF) is likely to play a role in the development of stroke in patients with OSA. Indeed, patients with OSA have a higher incidence of AF than the general population. Given the higher constellation of cardiovascular co-morbidities seen in patients with OSA, we believe that a strategy of actively screening for the presence of AF in patients with OSA and initiating oral anticoagulation therapy when appropriate may reduce the burden of stroke in this population. This is a question that needs to be addressed in a clinical trial.     

Prevalence of sleep apnoea in patients undergoing operation

Obstructive sleep apnoea (OSA) is defined as episodes of obstructive apnoeas and hypopnoeas during sleep with daytime somnolence. The gold standard in diagnostic tool patients with these symptoms is polisomnography. The goals of this study were to determine the frequency of OSA symptoms and the prevalence of OSA in patients undergoing operation. Patients were asked questions pertaining to symptoms of sleep apnoea. The patients who had two major symptoms or one major and two minor symptoms were invited to undergo a sleep study. Patients were diagnosed as OSA when they had apnoea–hypopnoea index higher than five. Forty-one patients with two major or one major and two minor symptoms of 433 patients were referred to the sleep laboratory. The most frequent major symptom was snoring, and the most frequent minor symptom was morning tiredness. In this connection, 18 (43.9%) patients accepted to be studied in the sleep laboratory (14 with two major, 4 with one major and two minor symptoms). Obstructive sleep apnoea was finally diagnosed in 14 patients or 3.2% of the initial entire population. Thirteen of them had two major symptoms, and only one of the 14 had one major and two minor symptoms. Six of the OSA patients were women. High percentage of OSA focus attention on anaesthesiology concerns of OSA. The exact management of each sleep apnoea patient with regard to intubation, extubation and pain control requires judgement and is a function of many anaesthesia, medical and surgical considerations. Therefore, we suggest that all patients should be asked for OSA symptoms, and patients with two major OSA symptoms must be evaluated with polisomnography.     

Cardiac pacing in sleep apnoea: diagnostic and therapeutic implications.

The sleep apnoea syndrome is a particularly common health problem associated with increased cardiovascular morbidity and mortality, as well as harmful socioeconomical and familial complications. In this article, the diagnostic and therapeutic role of cardiac pacing in this syndrome is discussed.     

The genetics of obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is a common chronic disease and is associated with high social and economic costs. OSA is heritable, and there is evidence of both direct genetic contributions to OSA susceptibility and indirect contributions via ‘intermediate’ phenotypes such as obesity, craniofacial structure, neurological control of upper airway muscles and of sleep and circadian rhythm. Investigation of the genetics of OSA is an important research area and may lead to improved understanding of disease aetiology, pathogenesis, adverse health consequences and new preventive strategies and treatments. Genetic studies of OSA have lagged behind other chronic diseases; however recent gene discovery efforts have been successful in finding genetic loci contributing to OSA‐associated intermediate phenotypes. Nevertheless, many of the seminal questions relating to the genetic epidemiology of OSA and associated factors remain unanswered. This paper reviews the current state of knowledge of the genetics of OSA, with a focus on genomic approaches to understanding sleep apnoea.     

阻塞性睡眠呼吸暂停综合征不同压力滴定方法及其比较

阻塞性睡眠呼吸暂停综合征(OSAS)是一种常见的睡眠疾病,目前首选治疗方法仍然是经鼻无创持续气道正压通气技术.压力滴定的目的是为气道正压治疗确定最佳治疗压力,是决定治疗效果和治疗依从性的关键.本文就气道正压治疗压力滴定技术与方法进行了系统复习.     

The sympathetic nervous system and catecholamines metabolism in obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is the most common sleep disorder of breathing in middle-aged and overweight subjects. It features recurrent episodes of upper airway total (apnoea) o partial (hypopnea) collapse during sleep, which are associated with a reduction in blood oxygen saturation and with arousal from sleep to re-establish airway patency. An association of OSA with dysregulation of the autonomous nervous system (ANS) and altered catecholamines (CAs) metabolism has been contended for years. However, the pathophysiology mechanisms underlying these alterations remain to be fully clarified. Nonetheless, these alterations are deemed to play a key pathogenic role in the established association of OSA with several conditions besides arterial hypertension (HT), including coronary artery disease, stroke, and, more in general, with increased risk of cardiovascular (CV) events. Hence, in this review we will analyse the relationship between the sleep disturbances associated with OSA and the altered function of the ANS, including CAs metabolism.     

Insulin resistance,glucose intolerance and diabetes mellitus in obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is a highly prevalent disorder, which conveys an increased risk of cardiovascular disease and death. Type 2 diabetes mellitus (T2DM), glucose intolerance and insulin resistance (IR) are common in subjects with OSA, but a shared intimate relationship with obesity makes discerning an independent link challenging. Nonetheless, mechanistic studies suggest that OSA could contribute to impaired glucose metabolism via the effects of sleep fragmentation, sympathetic excitation and intermittent hypoxia (IH) on pancreatic B-cell function, insulin sensitivity, and systemic inflammation. In particular, emerging data suggest that IH may have an important detrimental effect on adipose tissue function and inflammation. Similarly, data from population—and clinic-level studies suggest that OSA is independently related with the prevalence and incidence of T2DM and IR, and may also lead to worse glycaemic control in diabetics. However, the ability of continuous positive airway pressure (CPAP) therapy to make a meaningful impact on T2DM or IR remains uncertain. In this review we explore the available evidence linking OSA with IR, glucose intolerance and T2DM, and discuss potential pathobiological mechanisms by which sleep disordered breathing can affect metabolic health.     

NADPH oxidase p22phox polymorphisms and oxidative stress in patients with obstructive sleep apnoea

Background

Obstructive Sleep Apnoea (OSA) is associated with increased oxidative stress. NADPH oxidases are the main source of Reactive Oxygen Species (ROS) in the vasculature. Several polymorphisms related to NADPH oxidase expression or activity have been identified. We compared the distribution of the allelic frequencies of A-930G and C242T polymorphisms and their possible relationship with the levels of 8-isoprostanes as a marker of oxidative stress in patients with OSA and in a control group without OSA.

Methods

This is a case-control study. We determined the A-930G and C242T p22phox genotypes in 427 patients with OSA and in 139 healthy subjects recruited from the Sleep Unit of Son Dureta University Hospital, (Palma de Mallorca, Spain). 8-Isoprostane was measured as an oxidative stress marker.

Results

The distribution of the p22phox genotypes in OSA and in control subjects was different. The risk of OSA was associated with the presence of the G allele in the A-930G p22phox independently of age, gender, Body Mass Index (BMI), hypertension, dyslipemia and diabetes, but no association was found with the C242T polymorphism. The median level of 8-isoprostane was significantly higher in OSA patients. Synergic effect in 8-Isoprostane levels was observed when these two polymorphisms were analysed together.

Conclusion

the A-930G polymorphism of the p22phox gene may play an important role in genetic susceptibility to OSA. Furthermore, the C242T and A-930G polymorphisms of the p22phox gene have a synergic effect on the 8-isoprostane levels, suggesting that they may be involved in the development of oxidative stress in these patients.     

Sexual function in male patients with obstructive sleep apnoea

Objective: Our objective was to investigate general and functional aspects of sexuality in male patients with a confirmed diagnosis of obstructive sleep apnoea (OSA) and compare the results with normative data. Materials and Methods: We investigated 308 male patients (age 30–69) admitted to a sleep laboratory and receiving a diagnosis of OSA, using questions drawn from two self‐administered questionnaires on sexuality [Fugl‐Meyer Life satisfaction checklist (LiSat) and Brief Sexual Function Inventory (BSFI)]. Results: We found that both general (Fugl‐Meyer LiSat) and functional (BSFI) aspects of sexuality were worse in patients with (untreated) OSA when compared with normative data. Both aspects were dependent on age, obesity, social factors and concomitant medication but not on the severity of OSA as reflected by the apnoea–hypopnoea index or subjective sleepiness. Conclusion: We conclude that although sexual dysfunction is more prevalent in OSA patients than in the general population, it is a complex problem relating more to age, obesity, social factors and comorbidity than to the severity of OSA. Please cite this paper as: Petersen M, Kristensen E, Berg S, Midgren B. Sexual function in male patients with obstructive sleep apnoea. The Clinical Respiratory Journal 2010; 4: 186–191.