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[Angiotensin-converting enzyme gene polymorphism in patients with obstructive sleep apnea].

UNLABELLED: Obstructive sleep apnea (OSA) is often accompanied by cardiovascular and metabolic disorders. The renin-angiotensin system plays an important role of the cardiovascular regulation. The activity of the angiotensin converting enzyme is genetically determined. The aim of the study was to estimate the relation between angiotensin converting gene polymorphism and cardiovascular diseases or familial history in patients with obstructive sleep apnea. 63 patients with OSA were enrolled to the study. Arterial hypertension was diagnosed in 30 cases, ischaemic heart disease in 5 cases and 10 patients suffered from both mentioned diseases. RESULT: The observed ACE genotype frequencies in the study group were II: ID: DD: 23.81: 47.62: 28.57%, in the hypertension subgroup II: ID: DD--30.0: 46.6: 23.3%. No differences in the study group were observed in relation to familial history :DI:II--30.43: 43.48: 26.09% vs 25.64: 48.72: 25.4%. CONCLUSIONS: 1. In the study group there was no association between ACE polymorphism and OSA. 2. There were also no association between the polymorphism of ACE and cardiac diseases or familial history of cardiac diseases in OSA group. 3. The polymorphism of ACE is not a risk factor for OSA.

Adult↗

A model to facilitate outcome assessment of obstructive sleep apnea.

OBJECTIVES: Obstructive sleep apnea is a common disorder with significant morbidity and effects on quality of life. Management can include a range of mechanical, behavioral, and surgical approaches. This paper aims to devise a model of management options to assist in initial cost-effectiveness investigations. METHODS: In the absence of practice pattern data and widely accepted guidelines, we reviewed published literature and devised a model of treatment options to facilitate initial studies of outcomes, costs, and cost-effectiveness. RESULTS: Obstructive sleep apnea is rarely addressed by conservative behavioral-based strategies because these options, while inexpensive, have only limited effectiveness. Effective treatment most often relies on nasal continuous positive airway pressure, but poor tolerance or compliance sometimes leads to treatment with oral appliances or surgery. Patients treated by one modality may try another if the initial strategy is ineffective. Laboratory evidence that sleep apnea is effectively treated, and long-term follow-up, are necessary regardless of the treatment modality chosen. CONCLUSIONS: Each patient's treatment plan must be individually tailored, but the management model proposed here reflects available evidence-based literature and the authors' impression of current practice patterns. This model should be useful for initial cost-effectiveness investigations.

Cost-Benefit Analysis↗

Objective measurement of patterns of nasal CPAP use by patients with obstructive sleep apnea.

Obstruction of the upper airway during sleep (OSAS) is widely treated by having patients self-administer nasal continuous positive airway pressure (CPAP). To obtain objective evidence of the patterns of CPAP use, information was gathered from two urban sites on 35 OSAS patients who were prescribed CPAP for a total of 3,743 days. Patients were given CPAP machines that contained a microprocessor and monitor that measured actual pressure at the mask for every minute of each 24-h day for an average of 106 days per patient. They were not aware of the monitor inside the CPAP machines. Monitor output was compared with patients' diagnostic status, pretreatment clinical and demographic characteristics, and follow-up self-reports of CPAP use, problems, side effects, and aspects of daytime fatigue and sleepiness. Patients attempted to use CPAP an average of 66 +/- 37% of the days monitored. When CPAP was used, the mean duration of use was 4.88 +/- 1.97 h. However, patients' reports of the duration of CPAP use overestimated actual use by 69 +/- 110 min (p < 0.002). Both frequency and duration of CPAP use in the first month reliably predicted use in the third month (p < 0.0001). Although the majority (60%) of patients claimed to use CPAP nightly, only 16 of 35 (46%) met criteria for regular use, defined by at least 4 h of CPAP administered on 70% of the days monitored. Relative to less regular users, these 16 patients had more years of education (p = 0.05), and were more likely to work in professional occupations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Videonasopharyngoscopy is useful for identifying children with Pierre Robin sequence and severe obstructive sleep apnea.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) commonly appears in patients with Pierre Robin sequence (PR). Polysomnography (PS) is the gold standard for the diagnosis of OSAS. Videonasopharyngoscopy (VNP) is the best diagnostic tool for visualizing the vocal tract and detecting structural abnormalities which can be associated with OSAS. OBJECTIVE: The purpose of this paper is to study whether VNP can be useful for identifying severe OSAS in a population of children with PR. MATERIALS AND METHODS: Fifty-two children with PR who were present with sleep-disordered breathing were studied. All the parents completed a questionnaire concerning the children's sleeping habits and sleep complaints before consultation. Each child underwent a general pediatric examination and an evaluation of craniofacial features and upper airway permeability. In all children, a PS was performed. Also, all children underwent a VNP. RESULTS: The diagnosis of OSAS was confirmed by PS in 31 patients. VNP showed 87% sensitivity and 100% specificity for the detection of OSAS. VNP findings showed a significant correlation with apnea-hypopnea index, arousal index, snoring time, percentage of sleep time spent at saturation of oxygen <90% and a significant inverse correlation with total sleep time, sleep efficiency and the mean saturation of oxygen during sleep. CONCLUSION: This study shows that in children with PR, airway obstruction as detected by VNP seems to be a risk factor for OSAS. VNP appears to be a safe and reliable tool for the evaluation of sleep-disordered breathing in children with PR.

Child, Preschool↗

Evidence of a sleep-specific blunted cortical response to inspiratory occlusions in mild obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) patients have elevated non-rapid eye movement (REM) sleep arousal thresholds to inspiratory loading. To test the hypothesis that this is due to sleep-specific dampening of cortical responses to inspiratory effort, respiratory-related evoked potentials (RREPs) were evaluated in six mild OSAS patients and six age- and body mass index-matched controls during wakefulness and Stage 2 non-REM sleep. Electroencephalogram was recorded from six scalp sites (Fz, FCz, Cz, CPz, Pz, and O(2)). Electrooculogram, electromyogram, and mask pressure signals were also recorded. During sleep, pharyngeal pressure was recorded using a Millar pressure catheter placed 2 cm below the glottis. The RREP waveform was broadly similar in the two groups during wakefulness, but was markedly different during Stage 2 non-REM sleep. During wakefulness, only the N1 component showed reduced amplitude in the OSAS group. During sleep, the occlusion stimulus elicited fewer K-complexes in the OSAS patients. In addition, the N550 component in the average of K-complex responses was smaller in amplitude in the OSAS group. The data suggest that patients with mild OSAS have a "blunted" response to the respiratory occlusion stimulus. This appears not to be related to compromised mechanoreceptor function, as the RREP was normal in the patients when they were awake.

Adult↗

[Epidemiological definition of obstructive sleep apnea syndrome].

Obstructive sleep apnea syndrome (OSAS) is currently a clinically defined syndrome associating somnolence and on or two of the following symptoms: severe snoring, nocturnal respiratory arrest, repeated nocturnal awakening, non-recuperative sleep, diurnal fatigue, and altered concentration. The polysomnographic criterion is a more than 5 apnea-hypopnea episodes plus micro-awakenings related to respiratory efforts per hour of sleep. The epidemiological definition of OSAS is different because the prevalence of OSAS is estimated from the prevalence of the apnea-hyponea index (AHI) per hour of sleep and the prevalence of somnolence in the population. Epidemiological studies have produced different estimates of the prevalence of OSAS. The differences are less pronounced but still persist when comparing studies with a similar methodology, an identical sample, and sleep laboratory polysomnography recordings. These differences are related to the populations studied and also to the recording methods with different sensitivity and specificity. The difference between the prevalence P, which is the ratio between the number of patients in the study population, and the number Q, which is the ratio of the number of positive tests in the population, depends on the sensitivity and the specificity of the test used. The prevalence is also equal to the number of positive tests only if the sensitivity and specificity are both 1. The most widely used method, the thermistance method, has poor sensitivity and specificity. Prevalence is probably underestimated with this test. A rigorous consensual definition of this OSAS and abnormal ventilatory events as well as standardized diagnostic tests adapted for epidemiology studies are indispensable.

Adult↗

Long-term effects of nasal continuous positive airway pressure on vasodilatory endothelial function in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is associated with a dysfunction of vascular endothelial cells. The aim of this study was to investigate long-term improvement of endothelial dysfunction in OSAS with nasal continuous positive airway pressure (nCPAP) treatment. We investigated endothelium-dependent and endothelium-independent vasodilatory function in patients with OSAS using the hand vein compliance technique. Dose-response curves to endothelium-dependent vasodilator bradykinin were obtained in 16 subjects with OSAS before and after 6 months of nCPAP therapy and in 12 control subjects without OSAS. Maximum dilation (Emax) to bradykinin, being impaired in all OSAS patients, was completely restored with nCPAP. Mean Emax to bradykinin rose from 54.9+/-18.5 to 108.2+/-28.7% with 164.4+/-90.0 nights of nCPAP therapy (p<0.0001; Emax healthy controls, 94.8+/-9.5%). At treatment follow-up, endothelium-dependent vasodilatory capacity was not significantly different in nCPAP-treated OSAS patients vs healthy controls. Mean vasodilation with endothelium independently acting nitroglycerin was not altered initially and did not change with nCPAP therapy indicating that nCPAP restored endothelial cell function and not unspecific, endothelium-independent factors. These results suggest that regular nocturnal nCPAP treatment leads to a sustained restoration of OSAS-induced impaired endothelium-dependent nitric oxide-mediated vasodilation, suggesting an improvement of systemic endothelial dysfunction in patients studied.

Anthropometry↗

Plasma adrenomedullin and obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with hypertension. The vasorelaxing peptide adrenomedullin (ADM) may counteract effects of OSA-induced release of vasopressor substances. METHODS: Plasma ADM levels were measured at 9:30 PM, 2:00 AM (after 4 to 5 h of untreated OSA), and 6:00 AM (after 4 h of continuous positive airway pressure treatment) in 15 OSA patients and in 10 controls. RESULTS: Baseline ADM levels were similar in the OSA and control groups (28.7 +/- 6.7 v 27.7 +/- 6.4 pg/mL, respectively), did not change overnight in either group, and were not affected by continuous positive airway pressure. CONCLUSIONS: OSA does not exert any significant acute or chronic effects on plasma ADM levels.

Adrenomedullin↗

The roles of depression and anxiety in the understanding and treatment of Obstructive Sleep Apnea Syndrome.

Obstructive Sleep Apnea Syndrome (OSAS) is a debilitating condition stemming from disruption to the respiratory system during sleep. At present, the nature of the relationship between OSAS and mood, specifically depression and anxiety, is still unclear. The purpose of this paper is to shed some light on this relationship. PsycINFO was used to locate relevant papers on this topic. This literature search formed the basis of our investigation. Results showed that the anxiety and depression methodology is weak. It is now clear that there is an urgent need to better understand the roles of anxiety and depression in OSAS. For example, the research literature suggests that depression and anxiety covary with OSAS. However, because of methodological issues, such as difficulties involved in diagnosis and the use of inappropriate instruments, this conclusion remains tenuous. Future directions are discussed.

Anxiety↗

Airway inflammation in patients affected by obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) has been shown to be associated to upper airway inflammation. The object of the present study was to establish the presence of bronchial inflammation in OSAS subjects. In 16 subjects affected by OSAS, and in 14 healthy volunteers, airway inflammation was detected by the cellular analysis of the induced sputum. OSAS patients, as compared to control subjects, showed a higher percentage of neutrophils (66.7+/-18.9 vs. 25.8+/-15.6) (P<0.001) and a lower percentage of macrophages (29.4+/-18.4 vs. 70.8+/-15.3) (P<0.001). The percentage of eosinophils and lymphocytes were not significantly different in the two groups. OSAS subjects show bronchial inflammation characterized by a significant increase in neutrophils.

Aged↗

[Evolution study in children with suspected obstructive sleep apnea].

INTRODUCTION: Obstructive sleep apnea syndrome is a common disorder in childhood with an uncertain evolution. OBJECTIVES: Study of children's clinical evolution with suspected diagnosis of OSAS, which was carried out after two years of an overnight polisomnogram. PATIENTS AND METHODS: 73 children were studied. We evaluated if they had been operated and what type of surgery was performed, Brouillete Scale and subjective impressions. We have correlated: age, clinical evolution and surgery. RESULTS: Age was inversely correlated with changes in Brouillete (r=-0.39, p=0.002), standing out that children that underwent surgery were younger (4.1 vs. 7.0 years, Student t: -4.22, p=0.00009). Without the influence of age, the difference between evolution in operated and not operated ones was not significative, statistically speaking, but it was if we analysed the different types of surgery by themselves (Snedecor F: 3.9, p=0.007), tonsillectomy was the larger. CONCLUSION: The middle-term evolution in children with OSAS is good if we use the correct treatment.

Adenoidectomy↗

[Obstructive sleep apnea syndrome].

Obstructive sleep apnea syndrome is characterized by recurrent total or partial upper airway collapse during sleep. Although this disease affects more than 5% of general population, it remains largely undiagnosed. It is associated with an increase in cardiovascular risk and with a decrease in sustained attention that may cause automobile accidents or occupational injuries. Several simplified diagnostic tools (polysomnography) now allow easier diagnosis in a sleep laboratory or on an outpatient basis. Nasal continuous positive airway pressure remains the reference treatment, acting as a pneumatic splint that maintains airway patency. CPAP is effective in reducing daytime somnolence and controlling cardiovascular risk. Prosthetic management is an alternative to CPAP in cases of moderate sleep apnea with or without retrognathism in normal-weight patients. The effectiveness of surgery has not been proven, and it is indicated only in exceptional cases.

Humans↗

Changes in brain morphology associated with obstructive sleep apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) causes hypoxemia and fragmented sleep, which lead to neurocognitive deficits. We hypothesised that focal loss of cortical gray matter generally within areas associated with memory processing and learning and specifically within the hippocampus would occur in OSA. METHODS: Voxel-based morphometry, an automated processing technique for magnetic resonance images, was used to characterise structural changes in gray matter in seven right handed, male patients with newly diagnosed OSA and seven non-apneic, male controls matched for handedness and age. RESULTS: The analysis revealed a significantly lower gray matter concentration within the left hippocampus (p=0.004) in the apneic patients. No further significant focal gray matter differences were seen in the right hippocampus and in other brain regions. There was no difference in total gray matter volume between apneics and controls. CONCLUSION: This preliminary report indicates changes in brain morphology in OSA, in the hippocampus, a key area for cognitive processing.

Brain↗

Effects of gender on upper airway collapsibility and severity of obstructive sleep apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) is far more common in males than females. The discrepancy between the lower prevalence of OSA, the greater frequency of obesity and the smaller airway size in women compared to men suggests that a gender difference underlies this condition. We hypothesized that due to differences in tissue linkage women have more stable and less mobile upper airway structures than men, providing protection against severe forms of OSA. METHODS: Seventy-one consecutive patients with OSA, defined as having apnea-hypopnea index > or =5 events per hour, were enrolled into the study. The median (range) apnea-hypopnea index was 20 (5-132) events/h. In addition, measurements of upper airway dimensions were made, using an acoustic reflectance method, while the lower jaw was in the resting position and during retrusive posture. Measurements of upper airway dimensions were used during wakefulness to examine whether changes in pharyngeal dimensions, resulting from retrusive movement of the mandible commonly occurring during sleep, would explain the gender differences in the characteristics of OSA. RESULTS: OSA was much more positional and severe in men than women as indicated by the higher apnea-hypopnea index in supine position compared with sleeping on the side (difference between supine and side apnea-hypopnea index: 43.7+/-5.2 (SEM) events/h in men versus 10.7+/-7.6 events/h in women, P=0.0015). The position dependency of OSA was most pronounced in those patients who demonstrated the largest decrease in pharyngeal cross-sectional area with retrusive movement of the mandible. There was no significant change in pharyngeal cross-sectional area as a result of retrusive movement of the mandible in women. CONCLUSIONS: Men tend to have a larger but more collapsible airway during mandibular movement than women and this, in part, may play a role in the positional dependency and severity of OSA in men.

Adult↗

Improvement in neuropsychological performance following surgical treatment for obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is characterized by snoring and apnea during sleep leading to decreased oxygen saturation and disturbed sleep, excessive daytime sleepiness and neuropsychological disturbances. This study investigates cognitive neuropsychological abilities in a group of 53 OSAS patients before and after treatment with uvulopalatopharyngoplasty. General intellectual ability, verbal learning and memory as well as executive functioning were measured at baseline and 6 months postoperatively. After surgery there were significant improvements in verbal learning and memory (mean change -39, SD 57.3, p < 0.001), recall (mean change -24.3, SD 39.3, p < 0.001) and executive functioning (as assessed by percentage of errors on the Wisconsin Card Sorting Test; mean change -9.1, SD 15.7, p < 0.001). These improvements were in accordance with improvements in the degree of sleep apnea, the oxygen desaturation index (mean change -9.7, SD 15.9, p < 0.001) and arterial minimum oxygen saturation (mean change 4.5%, SD 10.2%, p < 0.01). Surgical treatment seems to improve verbal learning, memory and recall and executive functions in parallel with better oxygenation in OSAS.

Humans↗

Clinical effects of locally delivered nicotine in obstructive sleep apnea syndrome.

Obstructive sleep apnea (OSA) is a common disorder characterized by disordered breathing and associated with increased mortality and cardiovascular morbidity. A factor in the pathogenesis of OSA is hypotonia of the upper airway muscles during sleep, resulting in occlusion of the upper airway. Nicotine may be a suitable drug because it is a stimulant of breathing and activity of oropharyngeal muscles. A novel delivery system, a nicotine tooth patch (NTP) that releases nicotine continuously, has been developed by Perio Products (Jerusalem, Israel). A 2-mg NTP achieved low plasma levels of nicotine with high saliva levels (62 microg/mL), presumably resulting in high nicotine levels in the oropharynx. The aim of this study was to evaluate the effect of two doses of NTP, 2 mg and 4 mg, on the clinical features in OSA. Ten subjects with OSA were admitted overnight and monitored by polysomnography at baseline and during two treatments. The treatments were blind and in a randomized order. After a 4.3-mg NTP, T(max) was 40 +/- 16 minutes, C(max) was 123 +/- 43 microg/mL, and terminal T(1/2) was 29 +/- 11 minutes in saliva. Substantial nicotine levels persisted in saliva for approximately 4 hours. There was no effect of nicotine on the apnea-hypopnea index, even during the first 4 hours when there were high levels of nicotine in saliva (26.4 +/- 11.6, 26.8 +/- 19.5, and 26.8 +/- 23), or on sleep stages. Eppworth Sleepiness Scale scores were lower with a 4.3-mg NTP (9.1 +/- 4.5, 9.1 +/- 7.7, and 5.9 +/- 6.5). Locally delivered nicotine at the doses used had no significant effect on OSA.

Administration, Cutaneous↗

Elevated C-reactive protein in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) has been increasingly linked to cardiovascular and cerebrovascular disease. Inflammatory processes associated with OSA may contribute to cardiovascular morbidity in these patients. We tested the hypothesis that OSA patients have increased plasma C-reactive protein (CRP). METHODS AND RESULTS: We studied 22 patients (18 males and 4 females) with newly diagnosed OSA, who were free of other diseases, had never been treated for OSA, and were taking no medications. We compared CRP measurements in these patients to measurements obtained in 20 control subjects (15 males and 5 females) who were matched for age and body mass index, and in whom occult OSA was excluded. Plasma CRP levels were significantly higher in patients with OSA than in controls (median [range] 0.33 [0.09 to 2.73] versus 0.09 [0.02 to 0.9] mg/dL, P<0.0003). In multivariate analysis, CRP levels were independently associated with OSA severity (F=6.8, P=0.032). CONCLUSIONS: OSA is associated with elevated levels of CRP, a marker of inflammation and of cardiovascular risk. The severity of OSA is proportional to the CRP level.

Adult↗

Association of atrial fibrillation and obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with recurrent atrial fibrillation (AF) after electrocardioversion. OSA is highly prevalent in patients who are male, obese, and/or hypertensive, but its prevalence in patients with AF is unknown. METHODS AND RESULTS: We prospectively studied consecutive patients undergoing electrocardioversion for AF (n=151) and consecutive patients without past or current AF referred to a general cardiology practice (n=312). OSA was diagnosed with the Berlin questionnaire, which is validated to identify patients with OSA. We also assessed its accuracy compared with polysomnography in a sample of the study population. Groups were compared with the 2-tailed t, Wilcoxon, and chi2 tests. Logistic regression modeled the association of AF and OSA after adjustment for relevant covariates. Patients in each group had similar age, gender, body mass index, and rates of diabetes, hypertension, and congestive heart failure. The questionnaire performed with 0.86 sensitivity, 0.89 specificity, and 0.97 positive predictive value in our sample. The proportion of patients with OSA was significantly higher in the AF group than in the general cardiology group (49% versus 32%, P=0.0004). The adjusted odds ratio for the association between AF and OSA was 2.19 (95% CI 1.40 to 3.42, P=0.0006). CONCLUSIONS: The novel finding of this study is that a strong association exists between OSA and AF, such that OSA is strikingly more prevalent in patients with AF than in high-risk patients with multiple other cardiovascular diseases. The coinciding epidemics of obesity and AF underscore the clinical importance of these results.

Aged↗