Characteristics of the upper airway pressure-flow relationship during sleep

In examining the mechanical properties of the respiratory system during sleep in healthy humans, we observed that the inspiratory pressure-flow relationship of the upper airway was often flow limited and too curvilinear to be predicted by the Rohrer equation. The purposes of this study were 1) to describe a mathematical model that would better define the inspiratory pressure-flow relationship of the upper airway during sleep and 2) to identify the segment of airway responsible for the sleep-related flow limitation. We measured nasal and total supralaryngeal pressure and flow during wakefulness and stage 2 sleep in five healthy male subjects lying supine. A right rectangular hyperbolic equation, V = (alpha P)/(beta + P), where V is flow, P is pressure, alpha is an asymptote for peak flow, and beta is pressure at a flow of alpha/2, was used in its linear form, P/V = (beta/alpha) + (P/alpha). The goodness of fit of the new equation was compared with that for the linearized Rohrer equation P/V = K1 + K2V. During wakefulness the fit of the hyperbolic equation to the actual pressure-flow data was equivalent to or significantly better than that for the Rohrer equation. During sleep the fit of the hyperbolic equation was superior to that for the Rohrer equation. For the whole supralaryngeal airway during sleep, the correlation coefficient for the hyperbolic equation was 0.90 +/- 0.50, and for the Rohrer equation it was 0.49 +/- 0.25. The flow-limiting segment was located within the pharyngeal airway, not in the nose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolic effects of the obstructive sleep apnea syndrome and cardiovascular risk

The obstructive sleep apnea syndrome (OSAS) is characterized by collapse of the upper airway during sleep, recurring apneas, intermittent hypoxemia and daytime somnolence. OSAS is often associated with obesity, and its prevalence is expected to rise due to the obesity epidemics worldwide. OSAS is associated with increased cardiovascular risk which appears to be normalized by treatment with nasal continuous positive airway pressure (nCPAP) during sleep, suggesting an independent role of OSAS in accelerating atherosclerosis. Insulin resistance (IR) and the metabolic syndrome (MetS) are often found in OSAS patients, but the relative role played by OSAS and obesity is still unclear. Both OSAS and MetS may exert negative synergistic effects on the cardiovascular system through multiple mechanisms (hypoxemia, sleep disruption, activation of the sympathetic nervous system, inflammatory activation). Besides nCPAP treatment, pharmacologic interventions to treat obesity and the MetS could improve cardiovascular prevention in OSAS.     

Determinants of heart rate variability in obstructive sleep apnea syndrome during wakefulness and sleep

Heart rate variability (HRV) is mediated by at least three primary mechanisms: 1) vagal feedback from pulmonary stretch receptors (PSR), 2) central medullary coupling between respiratory and cardiovagal neurons (RCC), and 3) arterial baroreflex (ABR)-induced fluctuations. We employed a noninvasive experimental protocol in conjunction with a minimal model to determine how these sources of HRV are altered in obstructive sleep apnea syndrome (OSAS). Respiration, heart rate, and blood pressure were monitored in eight normal subjects and nine untreated OSAS patients in relaxed wakefulness and stage 2 and rapid eye movement sleep. A computer-controlled ventilator delivered inspiratory pressures that varied randomly from breath to breath. Application of the model to the corresponding subject responses allowed the delineation of the three components of HRV. In all states, RCC gain was lower in OSAS patients than in normal subjects (P < 0.04). ABR gain was also reduced in OSAS patients (P < 0.03). RCC and ABR gains increased from wakefulness to sleep (P < 0.04). However, there was no difference in PSR gain between subject groups or across states. The findings of this study suggest that the adverse autonomic effects of OSAS include impairment of baroreflex gain and central respiratory-cardiovascular coupling, but the component of respiratory sinus arrhythmia that is mediated by lung vagal feedback remains intact.     

Response to inspiratory resistive loading during sleep in normal children and children with obstructive apnea.

The response to inspiratory resistance loading (IRL) of the upper airway during sleep in children is not known. We, therefore, evaluated the arousal responses to IRL during sleep in children with the obstructive sleep apnea syndrome (OSAS) compared with controls. Children with OSAS aroused at a higher load than did controls (23 +/- 8 vs. 15 +/- 7 cmH(2)O. l(-1). s; P < 0.05). Patients with OSAS had higher arousal thresholds during rapid eye movement (REM) vs. non-REM sleep (P < 0.001), whereas normal subjects had lower arousal thresholds during REM (P < 0.005). Ventilatory responses to IRL were evaluated in the controls. There was a marked decrease in tidal volume both immediately (56 +/- 17% of baseline at an IRL of 15 cmH(2)O. l(-1). min; P < 0.001) and after 3 min of IRL (67 +/- 23%, P < 0.005). The duty cycle increased. We conclude that children with OSAS have impaired arousal responses to IRL. Despite compensatory changes in respiratory timing, normal children have a decrease in minute ventilation in response to IRL during sleep. However, arousal occurs before gas-exchange abnormalities.     

Increased risk of cerebral white matter lesions in obstructive sleep apnea syndrome

Sleep and Biological Rhythms - The aim of this study was to investigate the relation between obstructive sleep apnea syndrome (OSAS) and cerebral white matter lesions (CWML) on brain magnetic...     

Orthodontic treatment for obstructive sleep apnea syndrome

Sleep and Biological Rhythms - We report a case where obstructive sleep apnea syndrome (OSAS) was improved with orthodontic treatment. The lower dental arch was expanded, the distance between the...     

Computational fluid dynamics modeling of the upper airway of children with obstructive sleep apnea syndrome in steady flow

Computational fluid dynamic (CFD) analysis was used to model the effect of airway geometry on internal pressure in the upper airway of three children with obstructive sleep apnea syndrome (OSAS), and three controls. Model geometry was reconstructed from magnetic resonance images obtained during quiet tidal breathing, meshed with an unstructured grid, and solved at normative peak resting flow. The unsteady Reynolds-averaged Navier-Stokes equations were solved with steady flow boundary conditions in inspiration and expiration, using a two-equation low-Reynolds number turbulence model. Model results were validated using an in-vitro scale model, unsteady flow simulation, and reported nasal resistance measurements in children. Pharynx pressure drop strongly correlated to airway area restriction. Inspiratory pressure drop was primarily proportional to the square of flow, consistent with pressure losses due to convective acceleration caused by area restriction. On inspiration, in OSAS pressure drop occurred primarily between the choanae and the region where the adenoids overlap the tonsils (overlap region) due to airway narrowing, rather than in the nasal passages; in controls the majority of pressure drop was in the nasal passages. On expiration, in OSAS the majority of pressure drop occurred between the oropharynx (posterior to the tongue) and overlap region, and local minimum pressure in the overlap region was near atmospheric due to pressure recovery in the anterior nasopharynx. The results suggest that pharyngeal airway shape in children with OSAS significantly affects internal pressure distribution compared to nasal resistance. The model may also help explain regional dynamic airway narrowing during expiration.     

Technology on sleep surgery

Sleep and Biological Rhythms - Sleep-disordered breating (SDB), including obstructive sleep apnea–hypopnea syndrome (OSAS) is a clinical syndrome mainly characterized by recurrent upper...     

Determinants of the changes in positive airway pressure for the retitration in patients with obstructive sleep apnea syndrome

Sleep and Biological Rhythms - During long-term follow-up of the patients with obstructive sleep apnea syndrome (OSAS) under the positive airway pressure (PAP) therapy, it waits to be explored...     

OSAS对冠心病患者的血糖和血脂水平的影响

目的:探讨阻塞性睡眠呼吸暂停综合征(Obstructive sleep apnea syndrome,OSAS)对冠心病患者血糖和血脂的影响。方法:纳入我科住院的明确诊断冠心病患者共168人,根据呼吸暂停低通气指数(Apnea-hypopnea index,AHI)共分2组:冠心病组133例,冠心病合并OSAS组45例(轻度OSAS组16例;中度OSAS组18例,重度OSAS组12例)。对比分析冠心病组和冠心病合并OSAS组患者血脂及血糖水平及其相关性。结果:BMI、LDL、HDL在四组间差异有统计学意义(P0.05)。冠心病合并OSAS的BMI、LDL、HDL明显高于冠心病组,各组间BMI差异有统计学意义(P0.05)。FPG、HOMA-I、RHb A1、OX-LDL、AHI在冠心病组和冠心病合并轻度OSAS组之间差异无统计学意义(P0.05)。FPG、HOMA-I、RHb A1、OX-LDL、AHI在OSAS轻、中、重各组间差异有统计学意义(P0.05)。冠心病合并OSAS患者AHI和BMI、LDL、FPG、HOMA-I、OX-LDL呈正相关关系(P0.05)。结论:OSAS增加了冠心病患者血脂水平和糖尿病的风险,及机制可能与胰岛素抵抗和OX-LDL水平增高有关。     

Good esthetic results after modified maxillomandibular advancement for obstructive sleep apnea syndrome

Sleep and Biological Rhythms - Recently, obstructive sleep apnea syndrome (OSAS) is commonly treated conservatively, in particular with continuous positive airway pressure and oral appliance....     

阻塞性睡眠呼吸暂停综合征临床监测分析

目的:探讨阻塞性睡眠呼吸暂停综合征患者的临床特征及评价疗效。方法:回顾分析70例阻塞性睡眠呼吸暂停综合征患者PSG监测数据。结果:随着呼吸紊乱指数的增加,年龄、体重指数、最长呼吸暂停时间、最低SaO_2%、平均SaO_2%下降等指标在轻度与中、重度SAS之间差异显著;70例患者中伴有高血压52.9%、糖尿病5.7%、冠心病21.4%。结论:OSAS是一种具有潜在危险的疾痛,对OSAS早期诊断治疗是预防发生严重并发症的关键。     

Sleep apnea: epidemiology, pathophysiology, and relation to cardiovascular risk

Several studies have shown the occurrence of an independent association between obstructive sleep apnea syndrome (OSAS) and cardiovascular disease, including arterial hypertension, ischemic heart disease, and stroke. The pathogenesis of the cardiovascular complications of OSAS is still poorly understood, however. Several mechanisms are likely to be involved, including sympathetic overactivity, selective activation of inflammatory molecular pathways, endothelial dysfunction, abnormality in the process of coagulation, and metabolic dysregulation. The latter may involve insulin resistance and disorders of lipid metabolism. The aim of this review, which reports the data presented at a workshop jointly endorsed by the European Society of Hypertension and by the European Union COST action on OSAS (COST B26), is to critically summarize the evidence available to support an independent association between OSAS and cardiovascular disease.     

悬雍垂腭咽成形术治疗阻塞性睡眠呼吸 暂停综合征46 例疗效分析

目的：通过对睡眠呼吸暂停综合征病人（obstructlve sleep apnea syndrome,OSAS）睡眠呼吸参数的比较,探讨UPPP治疗OSAS的效果。方法：经多导睡眠图（Polysomnography,PSG）确诊为OSAS的病人46例,选择呼吸紊乱指数（apnea and hypopnea index,AHI）、呼吸暂停指数（apnea index,AI）及睡眠中的最低SaO2值作为评价OSAS轻重程度的指标。计算轻中度组、重度组在手术前后的AHI缓解率、最低SaO2缓解率厦显效率,并作为衡量UPPP手术治疗效果的指标。分析患者在手术前后AHI、最低SaO2的相关性;分析轻中度组和重度组的缓解率、最低SaO2缓解率及治愈率的相关性。结果：1利用UPPP手术治疗OSAS,患者手术前后AHI、最低SaO2具有相关性。2在分组资料中,轻中度组和重度组的缓解率、最低SaO2缓解率及显效率都具有显著相关性。结论：（1）UPPP是治疗OSAS的有效方法;（2）轻中度组的治疗效果要好于重度组。     

The relationship between serum cytokine levels with obesity and obstructive sleep apnea syndrome

Inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) may have a direct effect on glucose and lipid metabolism. On the other hand, it is known that IL-6 and TNF-alpha are important pro-inflammatory cytokines in the pathogenesis of atherosclerosis. The goal of present study was to test whether sleep apnea contributes to the previously reported increases of IL-6 and TNF-alpha independent of obesity. Forty-three obese (body mass index, BMI>27 kg/m2) men with newly diagnosed obstructive sleep apnea syndrome (OSAS) (apnea-hypopnea index, AHI> or =5) and age- and BMI-matched 22 obese nonapneic male controls (AHI<5) were enrolled in this study. To confirm the diagnosis, all patients underwent standard polysomnography in the sleep disorders center. Serum samples were taken at 08:00 h in the morning after overnight fasting. Serum IL-6 and TNF-alpha levels were found significantly higher in OSAS patients than in controls (p=0.002, p=0.03). Serum IL-6 and TNF-alpha levels were significantly correlated with AHI in OSAS patients (r=0.03, p=0.046 and r=0.36, p=0.016). There was no significant correlation between serum IL-6, TNF-alpha levels and AHI in controls. Serum IL-6 and TNF-alpha levels were not correlated with BMI both in OSAS patients and controls. In conclusion, circulating IL-6 and TNF-alpha levels in patients with OSAS, as independent of BMI are significantly higher than levels in controls and there is a positive relationship between previously mentioned cytokines' levels and the severity of OSAS. According to these results, the link between cardiovascular morbidity and OSAS may be explained by the coexistence of other cardiovascular risk factors such as circulating IL-6 and TNF-alpha levels.     

Obstructive Sleep Apnea Syndrome (OSAS), Metabolic Syndrome and Mental Health in Small Enterprise Workers. Feasibility of an Action for Health

Objective

To determine the frequency of obstructive sleep apnea syndrome (OSAS), metabolic syndrome and common mental disorders in the working population of 11 small enterprises and the feasibility of a program of action for health.

Method

The clinical risk of OSAS, the prevalence of metabolic syndrome, and the level of psychological disorders were assessed during routine medical examination at the workplace in 2012. The response to medical advice was assessed in 2013.

Results

12.3% of the workers were suspected of being affected by OSAS. One or more components of metabolic syndrome were present in 24.5% of cases. OSAS in “healthy” workers was significantly associated with the presence of one or more components of metabolic syndrome (OR = 3.83; 95%CI 1.45–10.13) and with a psychological disorders score in the highest quartile (OR = 4.67; 95%CI = 1.72–12.64). Workers with suspected OSAS were reluctant to follow advice about undergoing further tests under the NHS. However, in some cases, confirmation of the OSAS diagnosis and subsequent treatment led to an improvement in metabolic condition.

Conclusion

Although participation in treatment was limited, anecdotal cases support the idea that prevention of obstructive sleep apnea in the workplace might be useful for workers’ health.     

Flow and volume dependence of expiratory resistance in anesthetized cats

In five anesthetized paralyzed cats, mechanically ventilated with tidal volumes of 36-48 ml, the isovolume pressure-flow relationships of the lung and respiratory system were studied. The expiratory pressure was altered between 3 and -12 cmH2O for single tidal expirations. Isovolume pressure-flow plots for three lung volumes showed that the resistive pressure-flow relationships were curvilinear in all cases, fitting Rohrer's equation: P = K1V + K2V2, where P is the resistive pressure loss, K1 and K2 are Rohrer's coefficients, and V is flow. Values of K1 and K2 declined with lung inflation, consistent with the volume dependence of pulmonary (RL) and respiratory system resistances (Rrs). During lung deflation against atmospheric pressure, RL and Rrs tended to remain constant through most of expiration, resulting in a nearly linear volume-flow relationship. In the presence of a fixed respiratory system elastance, the shape of the volume-flow profile depended on the balance between the volume and the flow dependence of RL and Rrs. However, the flow dependence of RL and Rrs indicates that their measured values will be affected by all factors that modify expiratory flow, e.g., respiratory system elastance, equipment resistance, and the presence of respiratory muscle activity.     

Dynamic modulation of upper airway function during sleep: a novel single-breath method.

To examine the dynamic modulation of upper airway (UA) function during sleep, we devised a novel approach to measuring the critical pressure (Pcrit) within a single breath in tracheostomized sleep apnea patients. We hypothesized that the UA continuously modulates airflow dynamics during transtracheal insufflation. In this study, we examine tidal pressure-flow relationships throughout the respiratory cycle to compare phasic differences in UA collapsibility between closure and reopening. Five apneic subjects (with tracheostomy) were recruited (2 men, 3 women; 18-50 yr; 20-35 kg/m2; apnea-hypopnea index >20) for this polysomnographic study. Outgoing airflow through the UA (face mask pneumotachograph) and tracheal pressure were recorded during brief transtracheal administration of insufflated airflow via a catheter. Pressure-flow relationships were generated from deflation (approaching Pcrit) and inflation (after Pcrit) of the UA during non-rapid eye movement sleep. During each breath, UA function was described by a pressure-flow relationship that defined the collapsibility (Pcrit) and upstream resistance (Rus). UA characteristics were examined in the presence and absence of complete UA occlusion. We demonstrated that Pcrit and Rus changed dynamically throughout the respiratory cycle. The UA closing pressure (4.4 +/- 2.0 cm H2O) was significantly lower than the opening pressure (10.8 +/- 2.4 cm H2O). Rus was higher for deflation (18.1 +/- 2.4 cm H2O x l(-1) x s) than during inflation (7.5 +/- 1.9 cm H2O x l(-1) x s) of the UA. Preventing occlusion decreases UA pressure-flow loop hysteresis by approximately 4 cm H2O. These findings indicate that UA collapsibility varies dynamically throughout the respiratory cycle and that both local mechanical and neuromuscular factors may be responsible for this dynamic modulation of UA function during sleep.     

Insertion/Deletion Polymorphism and Serum Activity of the Angiotensin-Converting Enzyme in Turkish Patients with Obstructive Sleep Apnea Syndrome

This study determined the allelic frequency and genotypic distribution of an angiotensin-converting enzyme (ACE) polymorphism and serum ACE activity in Turkish patients with obstructive sleep apnea syndrome (OSAS). A colorimetric assay measured serum ACE activity in 73 of 97 subjects. Frequencies for II, ID, and DD genotypes were 19.6, 53.6, and 26.8% in the OSAS group and 15, 38, and 47% in the control group, respectively (P = 0.02). The I allele frequency was higher in the OSAS group than in the healthy control group (P = 0.02). Carrying the I allele (II or ID genotypes) increased OSAS risk 2.41 times in the Turkish population. Mean ACE activity was significantly lower in patients with the II genotype than in the DD genotype (P = 0.011), and ACE activity was significantly lower in patients with severe OSAS than in those with mild OSAS (P = 0.006). Our results suggest that II and ID genotypes of the ACE gene increase the risk of developing OSAS in the Turkish population.     

Obesity-Hypoventilation Syndrome: Increased Risk of Death over Sleep Apnea Syndrome

AimTo study whether mortality and cardiovascular morbidity differ in non-invasive ventilation (NIV)-treated patients with severe obesity-hypoventilation syndrome (OHS) as compared with CPAP-treated patients with obstructive sleep apnea syndrome (OSAS), and to identify independent predictors of mortality in OHS.ResultsThree hundred and thirty subjects (110 patients with OHS and 220 patients with OSAS) were studied. Mean follow-up time was 7±4 years. The five year mortality rates were 15.5% in OHS cohort and 4.5% in OSAS cohort (p< 0.05). Patients with OHS had a 2-fold increase (OR 2; 95% CI: 1.11–3.60) in the risk of mortality and 1.86 fold (OR 1.86; 95% CI: 1.14–3.04) increased risk of having a cardiovascular event. Diabetes, baseline diurnal SaO₂ < 83%, EPAP < 7 cmH2O after titration and adherence to NIV < 4 hours independently predicted mortality in OHS.ConclusionMortality of severe OHS is high and substantially worse than that of OSAS. Severe OHS should be considered a systemic disease that encompasses respiratory, metabolic and cardiovascular components that require a multimodal therapeutic approach.