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PubMed2002

The length-force relationship of the human genioglossus in patients with obstructive sleep apnea.

During sleep, patients with obstructive sleep apnea (OSA) have repetitive episodes of upper airway collapse, which are terminated by increased activity of upper airway dilator muscles. The repetitive activation of the genioglossus (GG) may result in muscle remodeling. We hypothesized that OSA patients have an altered length-force relationship, increased force generation and/or decreased force maintenance as compared with control subjects. The GG length-force relationship was determined in 12 patients with OSA and 12 normal control subjects. The optimum length of the GG (LO) was at a longer muscle length in OSA patients than in control subjects. At longer muscle lengths, OSA patients produced greater percentages of their maximum protrusion force than control subjects. Force maintenance was not significantly different between the two groups. We conclude that in OSA patients relative to normal controls, the length-force relationship of the GG is altered, specifically at longer muscle lengths. We speculate that the GG is remodeled in OSA patients and that this facilitates airway re-opening to terminate obstructive events.

Adult↗

PubMed2003

Obstructive sleep apnea syndrome due to adenotonsillar hypertrophy in infants.

OBJECTIVE: Adenotonsillar hypertrophy (ATH) is the leading cause for obstructive sleep apnea syndrome (OSAS) in children. The peak age for adenoid and tonsillar hypertrophy and related OSAS is 3-6 years. It has been suggested that OSAS due to ATH is extremely rare in infants. The purpose of the present study was to delineate OSAS due to ATH in infants. METHODS: Twenty-nine consecutive infants <18 months of age who underwent polysomnography (PSG) and were diagnosed with OSAS due to ATH were studied. A pediatric sleep questionnaire was completed by parents of all infants. Information regarding demographic variables, referring physician specialty, assessment of infant's development and recurrence of symptoms post treatment was collected. Pre and post surgery body weight and developmental assessment by parents were evaluated. RESULTS: The mean age of adenotonsillectomy was 12.3+/-3.9 months with the mean duration of symptoms ranging 6.2+/-3.0 months. 24% of the infants were born preterm. Snoring was the most common finding and appeared in all infants. Other symptoms were sleep apnea (72%), frequent movements during sleep (69%), mouth breathing (62%) and recurrent awakenings (38%). During the preoperative period, mean body weight decreased from the 67th+/-25 percentile to the 42nd+/-32 percentile (P<0.00001). 14/29 (48%) of the infants dropped two or more major percentiles before treatment. A significant weight gain to the 59th+/-31 percentile was observed post surgery (P<0.0001). 5/29 (17%) infants were considered by their parents as having a developmental delay preoperatively, which resolved in 3/5 (60%) post treatment. Clinical symptoms resolved or improved significantly after surgery. Recurrence of symptoms was documented in 6/23 (26%) of infants. CONCLUSIONS: Infantile OSAS due to hypertrophic adenoids and tonsils does occur in infants. Unique characteristics for this age group include: male predominance, high incidence of preterm infants, failure to gain weight and high recurrence rate after surgery. Otolaryngologists and pediatricians should be aware to the existence of the "early OSAS" in small infants.

Adenoidectomy↗

PubMed2003

Behavioral and pharmacologic therapy of obstructive sleep apnea.

Previous attempts at using pharmacologic agents in the treatment of OSA have been disappointing. Medroxyprogesterone has not been found to be useful in the treatment of OSA. Use of protriptyline is limited by frequent side effects, but its role in mild and REM-related OSA must be clarified. SSRIs seem to be ineffective in treatment of severe OSA. Further studies are needed to determine their effect in persons with mild disease. This is important because patients with mild OSA (AHI < 15 hours) are most likely to be noncompliant with CPAP therapy [91]. A recent systematic review of drug treatments for OSA concluded that the current data do not support the use of any drug as an alternative to CPAP [92]. Of 56 studies identified, only 9 studies met methodologic criteria. Clearly, basic research and adequately powered clinical trials are needed to identify an effective medication for OSA.

Behavior Control↗

PubMed1993

Genioglossus muscle activity and inspiratory timing in obstructive sleep apnea.

Atypical tongue muscle activity during sleep may contribute to the development of obstructive sleep apnea (OSA). Inspiratory genioglossus (GG) muscle activity was investigated in 10 OSA adults and 4 symptom-free controls. On the basis of overnight monitoring during nonREM sleep, the duration of the inspiratory GG activity and the total GG activity cycle is shorter in patients with OSA. The duration of inspiration and the duration of one total respiratory cycle is also shorter in patients with OSA. The commencement time lag between inspiratory GG activity and the onset of inspiration is shorter in patients with OSA during nonapneic breathing which indicates that inspiratory GG activity is activated relatively later in these patients. Furthermore, the inspiratory GG activity occurs after inspiration during an apnea, but the timing of GG activity onset progressively advances during the apnea. Earlier GG reactivation occurs before inspiration during the first nonoccluded breath at the end of an apnea. During subsequent tidal breathing, the timing of the GG onset progressively decreases after the onset of inspiration until the next obstructive apnea occurs. This observation suggests that the timing relationship between GG inspiratory activity and inspiratory effort is of physiologic importance in the pathogenesis of OSA. Furthermore, it may explain why dental appliances, such as the tongue retaining device, are highly effective in the resolution of OSA in selected patients.

Adult↗

PubMed2001

Hemodynamic responses to obstructive respiratory events during sleep are augmented in women with preeclampsia.

Preeclampsia is the most common disease of pregnancy, occurring in up to 10% of the pregnant population. The cause of the disease is as yet undetermined; however, most of the clinical effects are commonly attributed to damage to the endothelial layer, leading to increased pressor activity of all the maternal blood vessels. Therefore, we suspected that if obstructive sleep apnea (OSA) coexisted with preeclampsia in pregnancy, the hemodynamic effects of the OSA would be markedly potentiated. To test this hypothesis, we performed full sleep studies and overnight beat-to-beat blood pressure (BP) monitoring. The control patient group included 10 pregnant women with OSA and no evidence of hypertensive disease either before or during their current pregnancy. The test group included 10 women with preeclampsia and coexisting OSA. The pressor responses to obstructive respiratory events during sleep were enhanced in preeclamptic patients compared with control OSA patients (21+/-2/12+/-1 mm Hg and 38+/-5/25+/-4 mm Hg above baseline in control OSA and preeclamptic OSA patients, respectively, P = .005/.005). In contrast, there was no difference in heart rate responses between the two groups of subjects (34+/-5 beats/min and 49+/-13 beats/min above baseline in control and preeclamptic patient groups, respectively, P = .326). We suggest that the augmented pressor responses in preeclamptic women occur as a result of maternal endothelial damage induced by the preeclampsia disease process. These findings may have important implications in the management of preeclamptic patients.

Adult↗

PubMed2002

Effect of continuous positive airway pressure therapy on 24-hour blood pressure in patients with obstructive sleep apnea syndrome.

BACKGROUND: Patients with obstructive sleep apnea syndrome (OSAS) are subject to an increased cardiovascular morbidity including systemic hypertension. Little is known about the effects of treatment with nasal continuous positive airway pressure (CPAP) on systemic hypertension. METHODS: Automated ambulatory 24-h blood pressure (BP) monitoring was performed in 88 consecutive patients who were referred for evaluation of snoring or suspected OSAS. In addition, the long-term effects of CPAP therapy on 24-h BP were assessed. RESULTS: A total of 62 patients had OSAS and 26 habitual snoring. Patients with OSAS had significantly higher mean arterial BP values than snorers (102.7 +/- 10.7 v 94.0 +/- 10.2 mm Hg; P < .01). Multiple stepwise linear regression analysis disclosed that the degree of systemic hypertension was independently associated with the severity of OSAS as determined by the apnea/hypopnea index (R = 0.43; P < .001), but not with age, body mass index, or smoking habits. Of the 62 patients with OSAS, 52 were treated with CPAP and reevaluated after 9 months. The CPAP resulted in a significant decrease in mean arterial BP (from 103.7 +/- 10.4 to 99.1 +/- 10.8 mm Hg; P < .05). For those patients with systemic hypertension whose BP improved with CPAP therapy, 24-h mean pulse pressure at baseline (r = -0.36; P < .05) as well as average heart rate during the day (r = -0.35; P < .05) turned out as predictors. CONCLUSIONS: Obstructive sleep apnea syndrome contributes, at least in part, to the development of systemic hypertension, and CPAP may improve BP values in treated OSAS patients. Predictors of a beneficial CPAP effect on BP are a high heart rate and a high pulse pressure before treatment.

Blood Pressure↗

PubMed2003

Diastolic blood pressure is the first to rise in association with early subclinical obstructive sleep apnea: lessons from periodic examination screening.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with long-term cardiovascular morbidity. Little is known about these relations at early stages. We conducted a case-control study in which we analyzed the clinical characteristics of young adults who underwent a periodic health examination and were screened for, and eventually found to experience, OSAS. METHODS: We identified 121 subjects newly diagnosed in a sleep study as having OSAS, and 229 matched control subjects in which screening for OSAS was negative. All had a medical interview, physical examination, and routine laboratory tests. RESULTS: Subjects who had OSAS had a higher, body mass index (3-kg/m(2) difference) and a higher diastolic blood pressure (4-mm Hg difference) value, without elevation in systolic blood pressure. There was no metabolic difference (lipids profile and fasting glucose levels) between groups. CONCLUSIONS: Diastolic blood pressure is higher early in the course of OSAS. Long term follow-up may determine effects of prevention and early intervention in OSAS and associated hypertension.

Adult↗

PubMed1998

Diagnostic approach to obstructive sleep apnea in children.

Obstructive sleep apnea syndrome (OSAS) in childhood is a disorder of breathing during sleep characterized by prolonged partial upper airway obstruction and/or intermittent complete obstruction that disrupts normal ventilation during sleep and normal sleep patterns. A spectrum of severity related to the degree of upper airway resistance, to the duration of the disease, to the presence or absence of hypoxemia episodes, and to certain clinical features can be described. Symptomatic children may not fit the criteria for diagnosis established for OSAS in adults; age-specific standards are needed. Both anatomical factors that increase upper airway resistance, e.g. adenotonsillar hypertrophy, and functional processes that decrease upper airway tone, e.g. REM sleep, contribute to the pathogenesis of pediatric OSAS. Sequelae of OSAS in children include neurobehavioural abnormalities, stunting of growth, and cor pulmonale. Both the history and physical examination should target the sleeping child; parents often report loud snoring, difficulty breathing, and obstructive apneas. The gold standard investigation to establish the diagnosis and to quantitate disease severity is overnight polysomnography. Home cardiopulmonary sleep studies have been shown to be an accurate and practical alternative to overnight laboratory polysomnography for routine evaluation of non-complex children with adenotonsillar hypertrophy. Children with documented severe OSAS are at increased post-operative risk for airway compromise and should be observed and monitored carefully. Adenotonsiliectomy is the most common therapy for OSAS in children; as a second-line treatment, the use of nasal CPAP in children with OSAS has been very successful in experienced hands.

Journal Article↗

PubMed2003

Genomic approaches to understanding obstructive sleep apnea.

Obstructive sleep apnea (OSA) is an increasingly recognized, common chronic disease in the developed nations and is a complex disease that has high social and economic costs. OSA and its associated 'intermediate' phenotypes-craniofacial structure, body fat distribution and metabolism, and neurological control of the upper airway muscles and of sleep and circadian rhythm-are under a substantial degree of genetic control. Investigating the genetic aetiology of OSA offers a means of better understanding its pathogenesis, with the goal of improving preventive strategies, diagnostic tools and therapies. Molecular studies of OSA itself are in their infancy, but considerable effort and expense has already been expended in attempts to detect genetic loci contributing to OSA-associated intermediate phenotypes, such as obesity. However, many of the fundamental questions relating to the genetic epidemiology of OSA and associated factors remain unanswered. This chapter reviews the current state of knowledge of the genetics of OSA, with a focus on genomic approaches to understanding sleep disorders.

Animals↗

PubMed2003

Sleepiness and residual sleepiness in adults with obstructive sleep apnea.

Sleepiness is a common, but not necessary symptom of the obstructive sleep apnea syndrome (OSA) and is a frequent chief complaint of patients with OSA who seek medical attention. While sleepiness may seem simple in nature, the underlying mechanisms producing daytime sleepiness in OSA are complex and poorly characterized. Moreover, the meaningful assessment of pathological sleepiness is frequently far from straightforward. Effective treatment of OSA is generally expected to resolve or ameliorate daytime sleepiness. An unknown percentage of treated OSA patients, however, remain sleepy during waking hours. The assessment and treatment of residual sleepiness in treated OSA can range from simple to difficult, depending on the nature and causes of the continued sleepiness. Recently, however, data from clinical trials have been generated which provide direction in the evaluation and management of the OSA patient suffering residual daytime sleepiness.

Evaluation Studies as Topic↗

PubMed1997

Cephalometric and demographic characteristics of obstructive sleep apnea: an evaluation with partial least squares analysis.

Obstructive sleep apnea (OSA) is caused by repeated obstruction of the upper airway during sleep. The purpose of this study was to test the relative contributions of specific demographic and cephalometric measurements to OSA severity. Demographic, cephalometric, and overnight polysomnographic records of 291 male OSA patients and 49 male nonapneic snorers were evaluated. A partial least squares (PLS) analysis was used for statistical evaluation. The results revealed that the predictive powers of obesity and neck size variables for OSA severity were higher than the cephalometric variables used in this study. Compared with other cephalometric characteristics, an extended and forward natural head posture, lower hyoid bone position, increased soft palate and tongue dimensions, and decreased nasopharyngeal and velopharyngeal airway dimensions had relatively higher associations with OSA severity. The respiratory disturbance index (RDI) was the OSA outcome variable that was best explained by the demographic and cephalometric predictor variables. We conclude that the PLS analysis can successfully summarize the correlations between a large number of variables, and that obesity, neck size, and certain cephalometric measurements may be used together to evaluate OSA severity.

Adolescent↗

PubMed2002

Relationship between cephalometric characteristics and obstructive sites in obstructive sleep apnea syndrome.

Patients with obstructive sleep apnea syndrome (OSAS) have characteristic dentofacial features, but the sites of obstruction differ greatly. The purpose of this study was to investigate the dentofacial characteristics of patients with OSAS with respect to the obstructive sites. The subjects consisted of 30 Japanese men with OSAS divided into 3 groups of 10 patients each. One group had obstruction at the retropalatal and retroglossal region (Rp + Rg group), a second group had obstruction at the retropalatal region (Rp group), and a third group had obstruction due to tonsillar hypertrophy (tonsillar hypertrophy group). To identify the Rp + Rg and Rp groups, dynamic magnetic resonance imaging (MRI) was used. To identify the tonsillar hypertrophy group, Mackenzie's classification, axial MRI, and the weight of the tonsils were used. A control group was composed of 10 Japanese men showing no symptoms suggestive of OSAS. Lateral cephalometric radiographs were obtained for all of the subjects, and analysis of variance was performed for the 46 cephalometric parameters. Among the many dentofacial characteristics of OSAS patients, the tendencies for retrognathia, micrognathia, and skeletal Class II were strongest in the Rp + Rg group and somewhat strong in the Rp group. The presence of a long soft palate was dominant in the Rp group, whereas the tendency for a long face was dominant in the tonsillar hypertrophy group. All of the groups shared the characteristic of having an inferior position of the hyoid bone. Based on the results of the current study, we conclude that many features of OSAS are specifically related to each obstructive type of OSAS.

Adult↗

PubMed2004

Maxillary morphology in obstructive sleep apnea: a cephalometric and model study.

The relationship between maxillary constriction and the etiology of obstructive sleep apnea (OSA) is not clear. This prospective case-control study compared maxillary morphology in 94 dentate subjects (47 OSA and 47 control subjects), using upright lateral cephalograms and study models. Each subject had height, weight, and neck circumference measurements recorded and underwent an orthodontic examination. An upright lateral cephalogram and dental impressions were obtained. All data were analyzed using the SPSS statistical package applying nonparametric tests at the 5% level of significance. Male and female subjects were examined separately, and statistically significant differences were found between the cephalometric measurements for OSA and the control subjects. The palatal angle was more obtuse in male OSA subjects (P < .05). The PNS-posterior pharyngeal wall was shorter (P < .05) and the soft palate longer in female OSA subjects (P < .05). Minimum palatal airway widths were significantly reduced in both male (P < .01) and female (P < .001) subjects. In the comparison of study model measurements, palatal heights in OSA subjects were greater (P < .05). Thus, maxillary morphological differences do exist between OSA and control subjects, supporting their role as a etiological factor.

Adult↗

PubMed1997

Visceral fat accumulation as an important risk factor for obstructive sleep apnoea syndrome in obese subjects.

OBJECTIVES: It is well known that obstructive sleep apnoea-(OSA) is frequently associated with obesity. In the current study, we investigated the correlation between abdominal visceral fat accumulation and the presence of OSA in obese subjects. SUBJECTS: A consecutive series of 37 patients (17 men and 20 women) with primary obesity who were admitted to the Second Department of Internal Medicine. Osaka University Hospital, were investigated Patients with OSA were designated as those whose apnoea index (number of apnoea h-1 of sleep) was more than 5. MAIN OUTCOME MEASURES: The distribution of body fat was determined using computed tomographic sections. The upper airway dimensions were evaluated with indices obtained by cephalometry in both inspiratory and expiratory phases. RESULTS: Visceral adipose tissue (AT) area which was measured at the level of the umbilicus, and its ratio to total AT area were both significantly greater in OSA patients as compared with those in non-OSA patients. All subjects whose visceral AT area measured more than 220 cm2 manifested OSA. These two parameters also closely correlated with an increase in apnoea index. A multiple linear regression analysis revealed that the visceral AT area significantly correlated to apnoea index when age, AT mass and lean body mass were taken into account. The fluctuations of the upper airway were significantly greater in the large visceral fat group than in the small visceral fat group. CONCLUSIONS: These results suggest that visceral fat accumulation is an important risk indicator for OSA in obese subjects.

Adipose Tissue↗

PubMed2000

Differential diagnosis of obstructive sleep apnea syndrome patients and snorers using cephalograms.

Severe snoring is thought by many to be an early stage of obstructive sleep apnea syndrome (OSAS), but the anatomical relation between snoring and OSAS, if any, has remained unclear. To compare the morphology of the airway between snorers and OSAS patients for possible similarities, we conducted a cephalometric analysis of Japanese OSAS patients (n=10), habitual snorers (n=10), and non-snoring controls (n=50). There was no significant difference in SNB (the angle formed by the sella, nasion and point B) between OSAS patients and the control subjects. Obstructive sleep apnea syndrome patients tended to have an anteriorly positioned maxilla, and an anteroposterior misalignment between the maxilla and mandible. There was also a tendency toward skeletal openbite. Both OSAS patients and snorers had large tongues and large soft palates, thus causing constriction of the airway with resultant smaller airway diameter and smaller airway surface area. Significant differences between OSAS patients and snorers were found in thickness and length of soft palate surface area, and thickness, length, and position of the hyoid bone. These results suggest that cephalographic measurements may be of considerable use in determining the seriousness of a patient's condition.

Adult↗

PubMed2003

Relationship among the severity of sleep apnea syndrome, cardiac arrhythmias, and autonomic imbalance.

The relationship between obstructive sleep apnea syndrome (OSAS), cardiac arrhythmias, and conduction disturbances in adults remains controversial. Early studies showed a higher prevalence than more recent and designed epidemiological studies. To clarify the actual prevalence of cardiac arrhythmias and conduction disturbances in patients referred for assessment of OSAS, a prospective cohort study was conducted: 147 consecutive patients (103 men; mean age of 54.5 +/- 10.7 years) underwent time-synchronized polysomnography and ECG Holter monitoring. OSAS was diagnosed in 66 (44.9%) of them based on an apnea hypopnea index (AHI) > or = 10. Prevalence of heart failure, of prior myocardial infarction, of hypertension, and of ventricular arrhythmias were similar in patients with or without OSAS. Nocturnal paroxysmal asystole was significantly more prevalent in OSAS patients (10.6 vs 1.2%; P < 0.02) and the number of episodes of bradycardia and pauses increased with the severity of the syndrome. Almost all bradycardic events occurred in patients with severe OSAS (AHI > 30), prolonged periods of arterial oxyhemoglobin desaturation, and low diurnal awake PaO2. Moreover, using heart rate variability analysis, nocturnal sinusal dysfunction contrasted with a blunted diurnal parasympathetic modulation of the sinus node. Frequent nocturnal nonsustained supraventricular tachycardias were predominantly found in patients with severe sleep related breathing disorders; however, an increased risk of ventricular arrhythmias was not found. Under continuous positive airway pressure treatment, the 1-year follow-up of OSAS patients with nocturnal pauses did not reveal any arrhythmic event justifying a specific intervention.

Arrhythmias, Cardiac↗

PubMed2003

Alteration of QT rate dependence reflects cardiac autonomic imbalance in patients with obstructive sleep apnea syndrome.

QT rate dependence is one of the major properties of ventricular repolarization with its circadian and autonomic modulations. The authors postulated that dynamic alterations in QT interval adaptation could help characterize patients with cardiac autonomic alterations, like those with obstructive sleep apnea syndrome (OSAS). To assess ventricular repolarization features in patients with OSAS, QT parameters and their dynamicity along RR intervals were compared from 24-hour ECG data of patients with and without this syndrome, assessing cardiac autonomic nervous system equilibrium by means of time-domain and frequency-domain analyses of heart rate variability (HRV). The study group consisted of 74 consecutive patients referred to the Sleep Laboratory for clinically suspected OSAS. The syndrome was confirmed in 30 (40.5%) patients according to standard polysomnographic criteria. QT length related to heart rate (HR) was found significantly shorter for HR < 70 beats/min in patients with OSAS(-1.32 +/- 0.35)compared with patients without OSAS(-1.99 +/- 0.40; P < 0.01). This flattened relationship was correlated with the severity of the sleep related disorder. Using multiple linear regression analysis, the apnea/hypopnea index and nocturnal normalized high frequencies (HFnu) were the most significant predictors of the QT/RR slope(R = 0.61; P < 0.0001). OSAS is significantly associated with a flattened relationship between QT duration and RR interval at low HRs. The alteration of cardiac parasympathetic tone occurring in severe OSAS patients may explain this altered rate dependent adaptation of myocardial repolarization.

Autonomic Nervous System↗

PubMed2003

Treatment of obstructive sleep apnea in children: do we really know how?

Obstructive sleep apnea syndrome (OSAS) is a frequent, albeit underdiagnosed problem in children. If left untreated, OSAS may lead to substantial morbidities affecting multiple target organs and systems. The immediate consequences of OSAS in children include behavioral disturbance and learning deficits, pulmonary hypertension, as well as compromised somatic growth. However, if not treated promptly and early in the course of the disease, OSAS may also impose long-term adverse effects on neurocognitive and cardiovascular function, thereby providing a strong rationale for effective treatment of this condition. This review provides a detailed description of the current treatment modalities for pediatric OSAS, and uncovers the potential limitations of the available data on these issues. Furthermore, we postulate that OSAS will persist relatively often after tonsillectomy and adenoidectomy, and that critical studies need to be conducted to identify such patients and refine the clinical management algorithm for pediatric OSAS.

Anti-Inflammatory Agents↗