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PubMed2004

Mood improvement after surgery for obstructive sleep apnea.

OBJECTIVE: Patients with obstructive sleep apnea (OSA) may experience unfavorable psychologic symptoms such as depression and anxiety. The aim of this study was to confirm this hypothesis and to investigate whether the psychologic symptoms among OSA patients can be relieved by surgical intervention. STUDY DESIGN: Prospective, longitudinal intervention study. METHODS: The 5-Item Mental Health scale (MH-5) was used to evaluate the postoperative changes of mood after extended uvulopalatal flap (EUPF) surgery on 84 Taiwanese patients with OSA. The preoperative and postoperative MH-5 data obtained from these patients were compared with a Taiwanese population norm. RESULTS: Before surgery, the MH-5 scores of the OSA patients were significantly worse than the Taiwanese population norm of 72.8 (P <.0001). Postoperatively, mean MH-5 scores significantly increased from 61.8 +/- 16.0 to 70.0 +/- 15.8 (P =.0006). The effect size of this score change was 0.51, indicating a moderate degree of mood improvement. However, this score was still inferior to that of the population norm (P =.0045). The mood improvement was not significantly associated with the changes in either sleep apnea events or the level of sleepiness. Neither the changes in respiratory disturbance index (P =.4382), maximum arterial oxygen saturation (P =.4866), nor the change in Epworth Sleepiness Scale scores (P =.4951) were predictive of the MH-5 score improvement (R = 0.07). CONCLUSIONS: This study demonstrated that patients with OSA had a higher level of anxiety, depression, and probable behavior or personality changes than the population norm. EUPF surgery could significantly improve the mood status among OSA patients; the effect of surgery was mild but clinically relevant. However, the extent of mood improvement experienced by OSA patients receiving operations may not simply be attributable to the changes in sleep apnea events or a reduced level of sleepiness.

Adult↗

PubMed2005

Association of serotonin transporter gene polymorphism with obstructive sleep apnea syndrome.

BACKGROUND AND OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) is a common condition characterized by repetitive pharyngeal collapse during sleep and daytime sleepiness. There is genetic predisposition to sleep disorders. Serotonin is involved in the regulation of sleep. The synaptic 5-hydroxytryptamine (HT) is inactivated by presynaptic reuptake, which is mediated by the serotonin transporter. Blockage of the serotonin transporter leads to increased extracellular 5-HT. Polymorphism of the serotonin transporter gene (STG) leads to alterations in serotonin level and may be important in OSAS. In this study, we aimed to assess the role of STG polymorphism in OSAS. METHODS: Twenty-seven OSAS patients and 162 healthy volunteers were involved in the study. STG polymorphism was investigated using leukocytes obtained from peripheral blood. RESULTS: There was no difference between the genotypes and allele frequencies of the patients and controls regarding VNTR and HTTLPR polymorphisms (P > .05). The VNTR and HTTLPR variants and the frequencies of 12/12, 12/10, L, and S alleles were not significantly different between male and female control subjects (P > .05). The 12/12 and SS genotypes were over-represented in the female patients, whereas 12/10 and LL genotypes were over-represented in the male patients (P < .05). The genotypes 12 to 12 were over-represented in the male controls, whereas the genotypes 12 to 10 and L/S were over-represented in the male patients (P < .05). The alleles 10 and L were more frequent in the male patients than male controls (P < .05). The genotypes of female patients and female controls were not significantly different (P > .05). The allele 10 and L were less frequent in the female patients than female controls with Fisher's exact testing (P < .05). There was no relation between genotypes and clinical data of the patients (P > .05). CONCLUSION: STG polymorphism appears to be associated with the occurrence of OSAS, especially in male patients. Absence of association of between genetic variants and polysomnography findings may suggest that some mechanisms other than STG polymorphism are involved in OSAS pathophysiology. Our results need confirmation in a larger group of patients with OSAS.

DNA Primers↗

PubMed2004

Obese patients with obstructive sleep apnoea syndrome show a peculiar alteration of the corticotroph but not of the thyrotroph and lactotroph function.

OBJECTIVE: Obstructive sleep apnoea syndrome (OSAS) is strongly associated with obesity (OB) and is characterized by several changes in endocrine functions, e.g. GH/IGF-I axis, adrenal and thyroid activity. It is still unclear whether these alterations simply reflect overweight or include peculiar hypoxia-induced hormonal alterations. Hormonal evaluations have been generally performed in basal conditions but we have recently reported that OSAS is characterized by a more severe reduction of the GH releasable pool in comparison to simple obesity. We aimed to extend our evaluation of anterior pituitary function to corticotroph, thyrotroph and lactotroph secretion under dynamic testing in OSAS in comparison with simply obese and normal subjects. SUBJECTS AND METHODS: In 15 male patients with OSAS [age, mean +/- SEM 43.5 +/- 1.6 years; body mass index (BMI) 39.2 +/- 3.1 kg/m2; apnoea/hypopnoea index, (AHI) 53.4 +/- 8.7], 15 male patients with simple obesity (OB, age 39.7 +/- 1.2 years; BMI 41.2 +/- 2.0 kg/m2; AHI 3.1 +/- 1.2 events/h of sleep) and in 15 normal lean male subjects (NS, age 38.2 +/- 1.4 years; BMI 21.2 +/- 0.8 kg/m2; AHI 1.9 +/- 0.8 events/h of sleep) we evaluated: (a) the ACTH and cortisol responses to CRH [2 microg/kg intravenously (i.v.)] and basal 24 h UFC levels; (b) the TSH and PRL responses to TRH (5 microg/kg iv) as well as FT3 and FT4 levels. RESULTS: Twenty-four-hour UFC levels in OSAS and OB were similar and within the normal range. Basal ACTH and cortisol levels were similar in all groups. However, the ACTH response to CRH in OSAS (Deltapeak: 30.3 +/- 3.8 pmol/l; DeltaAUC: 682.8 +/- 128.4 pmol*h/l) was markedly higher (P < 0.001) than in OB (Deltapeak: 9.3 +/- 1.4 pmol/l; DeltaAUC 471.5 +/- 97.3 pmol*h/l), which, in turn, was higher (P < 0.05) than in NS (Deltapeak: 3.3 +/- 0.9 pmol/l; DeltaAUC 94.7 +/- 76.7 pmol*h/l). On the other hand, the cortisol response to CRH was not significantly different in the three groups. Basal FT3 and FT4 levels as well as the TSH response to TRH were similar in all groups. Similarly, both basal PRL levels and the PRL response to TRH were similar in the three groups. CONCLUSIONS: With respect to patients with simple abdominal obesity, obese patients with OSAS show a more remarkable enhancement of the ACTH response to CRH but a preserved TSH and PRL responsiveness to TRH. These findings indicate the existence of a peculiarly exaggerated ACTH hyper-responsiveness to CRH that would reflect hypoxia- and/or sleep-induced alterations of the neural control of corticotroph function; this further alteration is coupled to the previously described, peculiar reduction of somatotroph function.

Adrenocorticotropic Hormone↗

PubMed2005

Sleep apnea-related cognitive deficits and intelligence: an implication of cognitive reserve theory.

Cognitive deficits in patients with obstructive sleep apnea syndrome (OSAS) are well demonstrated, but the pathophysiology of these deficits is still controversial, as the relationship between OSA severity and cognitive deficits is usually weak. Our study considers the possible relationship between OSA-related cognitive deficits and the overall intellectual function of OSA patients. Forty-seven OSA patients and 36 normal individuals underwent a neuropsychological battery test assessing attention and alertness. According to the resulting IQ score, patients and controls were divided into a high-intelligence group (IQ > or = 90th percentile) and a normal-intelligence group (50 < or = IQ < 90%ile). Between the two patient groups there were no significant differences noticed, regarding OSA severity or sleepiness. High-intelligence patients showed the same attention/alertness performance compared with the high-intelligence controls. On the contrary, patients with normal-intelligence showed attention/alertness decline compared with the normal-intelligence control group. The two patient groups were re-examined with the same battery test after at least 1 year of CPAP treatment. At re-examination neither patient group showed any differences regarding attention and alertness compared with the control groups. We assume that high-intelligence may have a protective effect against OSA-related cognitive decline, perhaps due to increased cognitive reserve.

Adolescent↗

PubMed2006

Dry mouth upon awakening in obstructive sleep apnea.

The aim was to assess the significance of dry mouth upon awakening as a symptom of obstructive sleep apnea (OSA). The participants were 668 consecutive adults referred for polysomnographic evaluation (PSG) because of snoring and suspected OSA, and 582 adults who were attending a general health check-up. Data were obtained from self-administered questionnaires and PSG evaluation. The participants were asked to answer the following question: 'During the last month, did you experience waking up in the morning with a dry mouth?'. The response scale consisted of five categories: 'never', 'rarely', 'sometimes', often', or 'almost always'. We classified patients as having dry mouth upon awakening complaint only if they reported experiencing the symptom 'almost always'. The prevalence of dry mouth upon awakening was twofold higher in patients with OSA (31.4%) than in primary snorers (16.4%, P < 0.001), and increased linearly from 22.4%, to 34.5%, and 40.7% in mild, moderate, and severe OSA respectively (P < 0.001). The prevalence of dry mouth upon awakening in the control group was 3.2%. Logistic regression results indicated that this symptom significantly differentiated OSA patients from primary snorers after adjusting for age, BMI, gender, hypertension, and other classical OSA symptoms (OR 2.33, 95% CI 1.34-4.07). Dry mouth upon awakening appears as a significant symptom of OSA. We suggest that increased sleep time spent with an open mouth is a likely explanation for these findings.

Adult↗

PubMed2006

N-terminal pro-brain natriuretic peptide for detection of cardiovascular stress in patients with obstructive sleep apnea syndrome.

Patients with obstructive sleep apnea syndrome (OSAS) have an elevated incidence of cardiovascular events that may be related to an increased ventricular load and hypoxemia caused by apneas and hypopneas. N-terminal pro-brain natriuretic peptide (NTproBNP) appears to be an excellent marker of myocardial stretch and could serve as an indicator of subclinical cardiac stress, thereby identifying a patient population at risk for cardiac effects from OSAS. Adult patients presenting with suspected OSAS and scheduled for nocturnal polysomnography were recruited. Patients with heart or renal failure or severe lung disease were excluded. NTproBNP was measured the evening before and the morning after sleep. Blood pressure (BP) was monitored intermittently throughout the night. Fifteen male and 15 female subjects with a mean +/- SD body mass index of 38.2 +/- 9.8 were studied. Mean Apnea-Hypopnea Index (AHI) was 38.4 +/- 26, with 17 subjects having severe OSAS (AHI > 30). No subject had a significant rise in BP. NTproBNP values overnight decreased in 19 patients and rose in 11 (mean change 3.8 +/- 33 pg mL(-1)), but only one patient had an abnormal morning value. Three patients had an abnormal NTproBNP value prior to sleep, but their levels decreased with sleep. No correlations were detected between the evening baseline or postsleep NTproBNP levels and OSAS. Monitoring pre- and postsleep NTproBNP levels revealed no association with the occurrence or degree of OSAS, making it unlikely that NTproBNP could serve as a marker of cardiac stress in OSAS patients with stable BP and without overt heart failure.

Adult↗

PubMed1995

Obstructive sleep apnoea presenting as failure to thrive in infancy.

OBJECTIVE: To study the postoperative outcome of infants under the age of 18 months in whom an adenotonsillectomy had been performed, with particular emphasis on the pre- and postoperative weight gain and linear growth velocities, and the resolution of symptoms of obstructive sleep apnoea (OSA). METHODOLOGY: A retrospective study of all infants in whom an adenotonsillectomy had been performed during the 5 year period to January 1990. Details of pre- and postoperative outcome variables were obtained by review of hospital and office records and by telephone calls to the parents. RESULTS: Complete data were available for 29 (76%) of the 38 infants in whom an adenotonsillectomy had been performed. The data from these infants are reported. Pre-operatively, all infants had clinical symptoms of OSA, and 52% of infants also presented with failure to thrive (FTT). Seven infants were dysmorphic: three had Down syndrome, three had a craniofacial anomaly and one infant had Mobius syndrome. Following adenotonsillectomy, 23 infants (79%) had complete resolution of their OSA symptoms. Two infants with Down syndrome required a tracheostomy to relieve persistent upper airway obstruction. Eighty-seven per cent of the infants with pre-operative FTT had a significant increase in weight gain velocity postoperatively (mean 195.1 +/- 80.8 s.d. vs 509.8 +/- 249.1 g/month; P < 0.001), including the infants with mild persistent symptoms of OSA. The weight gain velocity of infants who were not failing to thrive pre-operatively did not change significantly following adenotonsillectomy (328.1 +/- 106.9 vs 333.2 +/- 146.4 g/month; P = 0.82). The linear growth velocity of all infants did not change significantly postoperatively. CONCLUSIONS: OSA should be considered in infants with FTT, as adenotonsillectomy is an effective treatment for OSA in infancy, and the weight gain velocity of these infants may increase significantly postoperatively. Overnight oximetry or other physiological studies may be required if the clinical signs and symptoms of OSA are equivocal.

Adenoidectomy↗

PubMed1998

New insights into the therapy and pathophysiology of patients with obstructive sleep apnoea syndrome.

The objective of this study was to investigate the effects of obstructive sleep apnoea on: (i) PaCO2 levels; (ii) coagulation systems (plasma fibrinogen levels and whole blood viscosity); and (iii) heat shock proteins (HSPs) levels, which are also called stress proteins, in patients with obstructive sleep apnoea syndrome (OSAS). Patients treated with or without nasal continuous positive airway pressure (NCPAP) had arterial blood gases, plasma fibrinogen, haematocrit, serum total protein and changes in PaCO2 (estimated by transcutaneous PaCO2) measured before and after polysomnography. Heat shock protein 72 levels in peripheral blood mononuclear cells were also measured during sleep with and without NCPAP. OSAS patients with hypercapnia demonstrated significant increases in PaCO2 in the morning compared with the previous night. In such OSAS patients, treatment with NCPAP resulted in a normalization of the 20 mg/dL increase in fibrinogen levels which had been seen previously in the morning after sleep. Basal HSP 72 levels (08.00 pm before sleep) were high in OSAS patients compared to normal subjects and progressively decreased during sleep in the absence of NCPAP therapy. NCPAP relieved disabling day-to-day symptoms in addition to improving cardiovascular morbidity in patients with OSAS. Therefore it is important to understand the effects of OSAS on various organ systems as the prevalence of patients with OSAS is high.

Blood Viscosity↗

PubMed2006

Obesity-related cardiovascular disease: implications of obstructive sleep apnea.

Obesity and obstructive sleep apnea (OSA) often coexist. OSA has been linked to cardiovascular disease. Thus, OSA may contribute to the cardiovascular consequences of obesity. In this review, we explore clinical and pathophysiological interactions between obesity, cardiovascular disease and OSA. We discuss the mechanisms whereby OSA may contribute to hypertension, atherosclerosis, insulin resistance and atrial fibrillation associated with obesity, and emphasize the potential implications for understanding why only a subgroup of obese patients develop cardiovascular disease. Identification of the OSA-dependent and OSA-independent pathways in the cardiovascular pathophysiology of obesity may hold clinical and therapeutic promise.

Atherosclerosis↗

PubMed2006

Hypertension research in sleep apnea.

Obstructive sleep apnea (OSA) is characterized by repetitive partial and total collapse of the upper airway that induces stressful arousals throughout sleep to reestablish breathing. Although estimates vary, prevalence has been reported as high as 20% in the adult population. OSA is common in several chronic diseases, the most common of which is obesity. Evidence is strong that OSA increases the risk of hypertension and both fatal and nonfatal cardiovascular events. Several mechanisms linking OSA to hypertension have been proposed, with increased sympathetic activation implicated as the prime mediator. This review summarizes recent data on the influence of OSA on blood pressure, the effect of standard OSA therapy on improving blood pressure, and the potential of lifestyle modification for further decreasing hypertension risk. Challenges confronting the investigation of blood pressure outcomes in response to treatment in OSA patients are discussed.

Blood Pressure↗

PubMed2006

Clinical characteristics of obstructive sleep apnea in community-dwelling older adults.

OBJECTIVES: To examine whether traditional risk factors are common in older adults with obstructive sleep apnea (OSA). DESIGN: Cross-sectional study. SETTING: Atlanta, Georgia. PARTICIPANTS: A convenience sample of 94 community-dwelling adults aged 62 to 91. MEASUREMENTS: Demographic, medical, and sleep-related information obtained using questionnaires. Epworth Sleepiness Scale (ESS) and 72-hour voiding diary were used to determine daytime sleepiness and nocturia frequency, respectively. Overnight ambulatory sleep recording device was used to screen for OSA. RESULTS: Fifteen female and 15 male subjects had an apnea-hypopnea index (AHI) of 15 or more per hour of sleep (moderate to severe OSA). Traditional risk factors such as snoring, body mass index, and neck circumference were not significantly associated with OSA. An AHI of 15 or more per hour was independently associated with not feeling well rested in the morning, higher ESS score, and greater frequency of nocturia. CONCLUSION: Traditional risk factors for OSA were not common presenting symptoms and signs in study subjects with an AHI of 15 or more per hour of sleep; this may contribute to underdiagnosis of OSA in this population. Subjects with an AHI of 15 or more per hour had more sleep-related complaints and excessive daytime sleepiness. Although occult, this suggests that OSA may contribute to disease burden in this group of people.

Aged↗

PubMed2006

Sexual function status in women with obstructive sleep apnea syndrome.

INTRODUCTION: Several co-morbid diseases have been shown to affect sexual functions in both genders. In the literature, sexual function status in men with obstructive sleep apnea syndrome (OSAS) has been studied; however, sexual functions in women with OSAS have not yet been studied. AIMS: In this prospective study, we aimed to determine sexual function status in women with OSAS and its relationship with the disease parameters of OSAS. METHODS: Women, who were diagnosed with OSAS with polysomnography performed in the sleep center of our university hospital, formed the study population. Women with any genital deformity, postmenopausal women, and women without a regular partner were excluded from the study. General demographic properties, medical histories, polysomnography parameters, and frequency of intercourse per month were noted for each patient. Patients completed the Sexual Function Questionnaire Version 2 (SFQ-V2) and Epworth Sleepiness Scale. The patients were grouped as mild, moderate, and severe OSAS according to the level of respiratory disturbance index (RDI). MAIN OUTCOME MEASURES: Scores of sexual function domains were determined from SFQ, and their relationships with parameters of polysomnography and demographics were studied. RESULTS: Twenty-five patients were included in the study. Mean age was 48.1 +/- 2.7 years. All were married with a mean marriage duration of 25.6 +/- 3.3 years. Mean frequency of intercourse per month was 3.3 +/- 1.8. All domains of sexual functions except pain and enjoyment significantly decreased with increasing severity of OSAS. When we controlled for factors of age and co-morbid diseases, correlation analyses showed significant negative correlation between levels of RDI and all domains of sexual functions except pain and enjoyment (P < 0.05). CONCLUSIONS: Obstructive sleep apnea syndrome negatively impacts sexual function in women independent of age and associated co-morbid diseases.

Adult↗

PubMed2001

Relationship between obstructive sleep apnoea, driving simulator performance, and risk of road traffic accidents.

BACKGROUND: Obstructive sleep apnoea (OSA) has been shown to be associated with an increased risk of road traffic accidents (RTAs). Predicting the driving ability and risk of RTAs in an individual with OSA is difficult. On-road testing is the gold standard, but this is time consuming, expensive, and potentially dangerous. Simple computer based driving simulators have been developed to help determine driving ability. Although patients with OSA have been shown to perform poorly compared with matched controls, it is not known whether these simulators can predict those at most risk of accidents. In this study we evaluated whether data derived from a simple driving simulator provided information over and above that obtained from the history and a sleep study that might be useful for advising patients about driving. METHODS: We examined 150 patients admitted for routine sleep studies for investigation of OSA and snoring. Each patient performed a 20 minute driving simulation and completed a questionnaire regarding their driving history and experience. RESULTS: Logistic regression analysis was used to investigate factors associated with patients' performance on the simulator. It was found that patient characteristics, older age (OR 1.05, 95% CI 1.01 to 1.09, p<0.01), female sex (OR 9.32, 95% CI 1.09 to 79.4, p<0.04), and self-reported alcohol consumption (OR 1.04, 95% CI 1.01 to 1.07, p<0.01) had the greatest influence; however, the number of self-reported near miss accidents was independently associated with a poor performance (OR 2.62, 95% CI 1.00 to 6.88, p<0.05). A further logistic regression was used to investigate whether clinical history, sleep study results, and data from the driving simulator were useful in classifying patients with OSA as having had an RTA. The number of off-road events per hour on the simulator was independently associated with a history of previous RTA (OR 1.004, 95% CI 1.0004 to 1.008, p<0.03). The Epworth score was independently associated with episodes of falling asleep at the wheel (OR 1.21, 95% CI 1.12 to 1.31, p<0.00001) and near miss accidents (OR 1.15, 95% CI 1.07 to 1.23, p<0.0001). Using this model, 100% of patients who did not have an accident could be identified, but only 10% of those who did. CONCLUSIONS: Although factors not directly related to OSA influence performance on a driving simulator, there is an independent relationship between driving ability in patients with OSA and performance on a simple computer based simulator. When combined with clinical history, it is those not reporting hypersomnolence and not having off-road events on the simulator who appear to be at least risk of adverse driving events. Poor performance on the simulator, however, relates poorly to accident history. These data require confirmation in future studies before simple computer simulators can be used in clinical practice to advise whether an individual is safe to drive.

Accidents, Traffic↗

PubMed2005

Craniofacial profile in Asian and white subjects with obstructive sleep apnoea.

BACKGROUND: Clinical detection of structural narrowing of the upper airway may facilitate early recognition of obstructive sleep apnoea (OSA). To determine whether the craniofacial profile predicts the presence of OSA, the upper airway and craniofacial structure of 239 consecutive patients (164 Asian and 75 white subjects) referred to two sleep centres (Hong Kong and Vancouver) were prospectively examined for suspected sleep disordered breathing. METHODS: All subjects underwent a history and physical examination with measurements of anthropometric parameters and craniofacial structure including neck circumference, thyromental distance, thyromental angle, and Mallampati oropharyngeal score. OSA was defined as an apnoea-hypopnoea index (AHI) of > or = 5/hour on full overnight polysomnography. RESULTS: Discriminant function analysis indicated that the Mallampati score (F = 0.70), thyromental angle (F = 0.60), neck circumference (F = 0.54), body mass index (F = 0.53), and age (F = 0.53) were the best predictors of OSA. After controlling for ethnicity, body mass index and neck circumference, patients with OSA were older, had larger thyromental angles, and higher Mallampati scores than non-apnoeic subjects. These variables remained significantly different between OSA patients and controls across a range of cut-off values of AHI from 5 to 30/hour. CONCLUSIONS: A crowded posterior oropharynx and a steep thyromental plane predict OSA across two different ethnic groups and varying degrees of obesity.

Analysis of Variance↗

PubMed1993

Effects of posture on carbon dioxide responsiveness in patients with obstructive sleep apnoea.

BACKGROUND: It is well known that upper airway resistance increases with postural change from a sitting to supine position in patients with obstructive sleep apnoea (OSA). It is not known, however, how the postural change affects the ventilatory and occlusion pressure response to hypercapnia in patients with OSA when awake. METHODS: The responses of minute ventilation (VE) and mouth pressure 0.1 seconds after the onset of occluded inspiration (P0.1) to progressive hypercapnia (delta VE/delta PCO2, delta P0.1/delta PCO2) both in sitting and supine positions were measured in 20 patients with OSA. The ratio of the two (delta VE/delta P0.1) was obtained as an index of breathing efficiency. The postural changes in response to carbon dioxide (CO2) after uvulopalatopharyngoplasty (UPPP) were also compared in seven patients with OSA. RESULTS: There were no significant changes in the resting values of end tidal PCO2, P0.1, or VE between the two positions. During CO2 rebreathing, delta VE/delta PCO2 did not differ between the two positions, but delta P0.1/delta PCO2 was significantly higher in the supine than in the sitting position (supine, mean 0.67 (SE 0.09) cm H2O/mm Hg; sitting, mean 0.57 (SE 0.08) cm H2O/mm Hg), and delta VE/delta P0.1 decreased significantly from the sitting to the supine position (sitting, 4.6 (0.4) l/min/cm H2O; supine, 3.9 (0.4) l/min/cm H2O). In seven patients with OSA who underwent UPPP, delta VE/delta P0.1 improved significantly in the supine position and postural change in delta VE/delta P0.1 was eliminated. CONCLUSIONS: These results suggest that in patients with OSA the inspiratory drive in the supine position increases to maintain the same level of ventilation as in the sitting position, and that the postural change from sitting to supine reduces breathing efficiency. Load compensation mechanisms of patients with OSA appear to be intact while awake in response to the rise in upper airway resistance.

Female↗

PubMed2000

Increases in leptin levels, sympathetic drive, and weight gain in obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) are frequently obese and are predisposed to weight gain. They also have heightened sympathetic drive. We reasoned that noradrenergic activation of beta(3)-receptors on adipocytes would inhibit leptin production, predisposing to obesity in sleep apnea. We therefore tested the hypothesis that obesity and predisposition to weight gain in OSA are associated with low levels of plasma leptin. We prospectively studied 32 male patients (43 +/- 2 yr) with OSA who were newly diagnosed and never treated and who were free of any other diseases. Control measurements were obtained from 32 similarly obese closely matched male subjects (38 +/- 2 yr). Leptin levels were 13.7 +/- 1.3 and 9.2 +/- 1.2 ng/ml in patients with OSA and controls, respectively (P = 0.02). Weight gain over the year before diagnosis was 5.2 +/- 1.7 and 0.5 +/- 0.9 kg in sleep apnea patients and similarly obese control subjects, respectively (P = 0.04). Muscle sympathetic activity was 46 +/- 4 and 30 +/- 4 bursts/min in patients with OSA (n = 16) and control subjects (n = 18), respectively (P = 0.01). Plasma leptin levels are elevated in newly diagnosed otherwise healthy patients with untreated sleep apnea beyond the levels seen in similarly obese control subjects without sleep apnea. Higher leptin levels in OSA, independent of body fat content, suggest that OSA is associated with resistance to the weight-reducing effects of leptin.

Adult↗

PubMed1995

Ventilatory response to consecutive short hypercapnic challenges in children with obstructive sleep apnea.

In healthy adults, a ventilatory pattern characterized by progressively increased tidal volume (VT), and decreased respiratory rate (RR) accompany repeated short hypercapnic ventilatory challenges, while minute ventilation (VE) remains constant. We hypothesized that the peculiar ventilatory pattern seen in adults would be blunted in children with obstructive sleep apnea syndrome (OSAS) who undergo comparable intermittent or chronic alveolar PCO2 elevation. We measured ventilatory responses to five challenges of 2-min duration (C1-C5) with 5% CO2 in O2, separated by 5-min room-air breathing intervals (R1-R4), in nine children with OSAS and in eight age-, sex-, and body mass index-matched controls. In all children, CO2 significantly increased VE when compared with baseline conditions (22.3 +/- 2.2 vs. 9.5 +/- 0.9 (SE) l/min; P < 0.001). In control subjects, progressive VT increases from 0.67 +/- 0.10 liter in C1 to 0.92 +/- 0.13 liter in C5 occurred (P < 0.01), whereas RR decreased from 33.9 +/- 5.1 breaths/min in C1 to 27.8 +/- 3.7 breaths/min in C5 (P < 0.02), resulting in VE increases across CO2 challenges (22.3 +/- 4.9 l/min in C1 vs. 25.1 +/- 5.0 l/min in C5; P < 0.005). The RR decrease was primarily related to progressive prolongation of expiratory time (TE) (1.1 +/- 0.1 s in C1 to 1.5 +/- 0.2 s in C5; P < 0.002). In contrast, VT, RR, and TE did not change in a consistent fashion in OSAS patients with repeated CO2 challenges (OSAS vs. control: P < 0.0001). Furthermore, in OSAS, VE was similar with repeated challenges (22.4 +/- 2.2 1/min in C1 vs. 23.9 +/- 1.9 l/min; P = not significant), such that changes in VE over time significantly differed in OSAS and controls (P < 0.001). We conclude that healthy children modify their ventilatory strategy to repeated hypercapnia. We speculate that in OSAS these mechanisms are already fully implemented because of recurrent alveolar hypoventilation accompanying increased upper airway resistance, leading to blunted temporal trends of ventilatory response.

Adolescent↗

PubMed1999

Increased levels of circulating ICAM-1, VCAM-1, and L-selectin in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) may be one of the most important risk factors of cardiovascular disorders, although the exact mechanism remains to be elucidated. In the present study, we hypothesized that OSAS-induced hypoxic stress might be involved in the etiology of cardiovascular disorders by activating adhesion molecules, including intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and L-selectin. To examine this hypothesis, we measured circulating ICAM-1, VCAM-1, and L-selectin levels before and after sleep in OSAS patients and age-matched controls. The circulating ICAM-1, VCAM-1, and L-selectin levels increased in the OSAS patients before sleep compared with the normal subjects (ICAM-1: 392.9 +/- 48.5 vs. 201.2 +/- 55.0 ng/ml, P < 0.05; VCAM-1: 811.0 +/- 87.8 vs. 574.2 +/- 42.7 ng/ml, P < 0.05; L-selectin: 1,386.6 +/- 77.9 vs. 1,038.8 +/- 78.6 ng/ml, P < 0.01, respectively). After sleep, significantly greater levels of ICAM-1 and L-selectin, but not VCAM-1, were observed in the OSAS group. These observations suggest that OSAS-induced hypoxia activates adhesion molecules, resulting in the important risk factor of cardiovascular disorders. Treatment of OSAS can be, therefore, a potential approach to prevention of cardiovascular events.

Adult↗