Diurnal PaCO2 tension in obese women: relationship with sleep disordered breathing

OBJECTIVE: Several obese subjects show a wide array of respiratory disturbances during sleep due to an increased upper-airway resistance. The aim of the present study was to evaluate diurnal PaCO(2) tension in nonsmoking obese women and the possible relationship of this parameter with the presence of sleep disordered breathing (SDB). DESIGN: Cross-sectional study of PaCO(2) tension in obese women. PATIENTS AND METHODS: A total of 91 nonsmoking obese women (BMI > or =30 kg/m(2), aged 42.8+/-15.7 y) were recruited and evaluated for general and anthropometric parameters, respiratory function, sleep-related symptoms, and sleep disorders of breathing. RESULTS: A total of 10 subjects (10.9%) had diurnal hypercapnia (PaCO(2)> or =43 mmHg). Age, BMI, neck circumference, apnoea/hypopnoea index, and nocturnal desaturation (expressed as TST(SaO(2<90%)); TST(SaO(2<90%))=percentage of total sleep time with oxyhaemoglobin saturation <90%) were significantly higher in obese patients with diurnal hypercapnia, compared to normocapnic women. Moreover, hypercapnic patients had reduced forced expiratory volume in 1 s compared to normocapnic individuals. By using multiple regression analysis, the best fitting model (r=0.62, P<0.001) for predicting diurnal PaCO(2) tension in the study population showed that 24.23% of the variance may be explained by TST(SaO(2<90%)), according to the equation: PaCO(2)=0.09 age+0.07 TST(SaO(2<90%))+33.00. CONCLUSIONS: This study suggests that severity of SDB is the most important factor in determining diurnal PaCO(2) tension in apparently healthy nonsmoking obese women.     

The effect of sibutramine-assisted weight loss in men with obstructive sleep apnoea

OBJECTIVE: Obstructive sleep apnoea (OSA) occurs frequently in obese patients and may be reversible with weight loss. Obstructive sleep apnoea and obesity are both independent risk factors for hypertension and increased sympathetic activity. Sibutramine has been increasingly used in the management of obesity, but is relatively contraindicated in patients with hypertension. No studies have investigated the effect of sibutramine on OSA, blood pressure and heart rate. We aimed to assess the changes in OSA and cardiovascular parameters in obese men with OSA enrolled in a sibutramine-assisted weight loss programme (SIB-WL). DESIGN: Open uncontrolled cohort study of obese male subjects with OSA in an SIB-WL. SUBJECTS: Eighty-seven obese (body mass index =34.2+/-2.8 kg/m(2)) middle-aged (46.3+/-9.3 years) male subjects with symptomatic OSA (Epworth score 13.4+/-3.6; respiratory disturbance index (RDI) 46.0+/-23.1 events/h) completed the study. RESULTS: At 6 months, there was significant weight loss (8.3+/-4.7 kg, P<0.0001), as well as a reduction in waist and neck circumference and sagittal height (all P<0.0001). These changes were accompanied by a reduction in OSA severity (RDI fell by 16.3+/-19.4 events/h and Epworth score by 4.5+/-4.6), both P<0.0001). There was no significant change to systolic (P=0.07) or diastolic blood pressure (P=0.87); however, there was a mild rise in resting heart rate (P<0.0001). CONCLUSION: Moderate (approximately 10%) weight loss with SIB-WL results in improvement in OSA severity without increase in blood pressure in closely monitored OSA subjects.     

Role of diffuse airway obstruction in the hypercapnia of obstructive sleep apnea

The mechanisms responsible for the development of chronic hypercapnia in patients with obstructive sleep apnea (OSA) are not well defined. Therefore, we tested the hypothesis that diffuse airway obstruction may be involved by studying 50 patients with a well-documented OSA syndrome. Seven patients had daytime hypercapnia with a mean PaCO2 of 51 +/- 2 (SEM) mm Hg, compared to a PaCO2 of 35 +/- 1 in the other 43 patients. There were no differences between the 2 groups in the number or duration of nocturnal obstructive events. In contrast, the hypercapnic patients were significantly heavier than the normocapnic patients (body weight, 189 +/- 11 versus 148 +/- 6% of ideal; p less than 0.005) and had evidence of diffuse airway obstruction, as indicated by an increased residual volume and a reduction in all expiratory flow rates. When the hypercapnic patients were compared with a weight-matched group of 9 normocapnic patients (body weight, 196 +/- 8% of ideal), there were still no differences in nocturnal obstructive events, but the differences in tests of airway mechanics persisted. Multiple regression analysis of PaCO2 against several anthropometric, respiratory physiologic, and polysomnographic variables revealed that only 2 variables (expiratory reserve volume and FEV1/FVC), both of which are influenced by airway mechanics, were significantly correlated with PaCO2 (multiple r = 0.78; p = 0.0001). The findings suggest that OSA alone does not produce daytime hypercapnia even in obese patients, and that the presence of diffuse airway obstruction is an important predisposing factor to the development of chronic CO2 retention in such patients.     

Effects of octreotide on sleep apnoea and tongue volume (magnetic resonance imaging) in patients with acromegaly

OBJECTIVES: Sleep apnoea has been consistently reported to occur in acromegaly. Both obstructive apnoeas, in which apnoeas are due to intermittent obstruction of the upper airways, as well as central apnoeas are known to occur. Because the relationship between disease activity and severity of sleep apnoea is currently unclear, we have performed a prospective study to address this issue. DESIGN AND METHODS: In 14 newly diagnosed patients with active acromegaly (eight females and six males; mean age 57+/-4 years; IGF-I 583+/-48 microg/l; GH 13.5+/-7.0 microg/l (means+/-s.e.m.)), tongue volume and signal intensity of the tongue were examined by magnetic resonance imaging and sleep apnoea was characterised by polysomnography before and after 6 months of treatment with octreotide acetate (Sandostatin LAR 10-30 mg every 4 weeks i.m.). RESULTS: The initial tongue volume was significantly higher in patients with acromegaly (151+/-9 ml; females 133+/-10 ml; males 172+/-10 ml) in comparison with the body mass index (BMI)- and age-matched healthy control group (97+/-5 ml, P<0.001; females 75+/-1 ml, P<0.001; males 120+/-3 ml, P<0.003). After treatment with octreotide, IGF-I was normalised within the age-adjusted normal range in 50% of the patients. In these patients, tongue volume significantly decreased (120+/-14 ml, P<0.05) in comparison with the persistent uncontrolled group of acromegalics (137+/-10 ml, P=not significant). Overall, tongue volume (128+/-8 ml, P<0.05) and the signal intensity ratio of the tongue decreased significantly after treatment with octreotide acetate (120+/-3 vs 105+/-3, P=0.003). The BMI-adjusted tongue volume correlated with IGF-I levels (r=0.60, P<0.002) and the disease duration (r=0.71, P=0.006). At baseline, 50% had obstructive sleep apnoea with a mean respiratory disturbance index (RDI) of >20/h (range 5.1-91.5) and no patient had central sleep apnoea. After 6 months of octreotide treatment, there was a 28+/-10% decrease in RDI. However, RDI did not correlate with IGF-I or GH levels, but correlated positively with BMI (r=0.58, P=0.001) and age (r=0.46, P=0.02). CONCLUSIONS: Obstructive sleep apnoea but not central sleep apnoea frequently occurs in patients with active acromegaly. Successful treatment with octreotide can decrease tongue volume, which may have benefits for coexisting sleep-disordered breathing.     

Hypoxemia and hypercapnia during exercise and sleep in patients with cystic fibrosis.

BACKGROUND: In patients with cystic fibrosis (CF), it has been proposed that hypoxemia and hypercapnia occur during episodes of stress, such as exercise and sleep, and that respiratory muscle weakness because of malnutrition may be responsible. METHODS: Pulmonary function, respiratory muscle strength, and nutrition were assessed and correlated with the degree of hypoxemia and hypercapnia during exercise and sleep in 14 patients with CF and 8 control subjects. RESULTS: Despite no differences in maximum static inspiratory pressure (PImax) between the two groups, the CF group developed more severe hypoxemia (minimum oxyhemoglobin saturation [SpO2], 89 +/- 5% vs 96 +/- 2%; p < 0.001) and hypercapnia (maximum transcutaneous CO2 tension [PtcCO2], 43 +/- 6 vs 33 +/- 7 mm Hg; p < 0.01) during exercise. Similarly, during sleep, the CF group developed greater hypoxemia (minimum SpO2, 82 +/- 8% vs 91 +/- 2%; p < 0.005), although CO2 levels were not significantly different (maximum PtcCO2, 48 +/- 7 vs 50 +/- 2 mm Hg). Within the CF group, exercise-related hypoxemia and hypercapnia did not correlate with FEV1, residual volume/total lung capacity ratio (RV/TLC), PImax, or body mass index (BMI). Hypoxemia and hypercapnia during sleep correlated with markers of gas trapping (RV vs minimum arterial oxygen saturation [r = -0.654; p < 0.05]), RV vs maximum PtcCO2 (r = 0.878; p < 0.001), and RV/TLC vs maximum PtcCO2 (r = 0.790; p < 0.01) but not with PImax or BMI. CONCLUSION: Patients with moderately severe CF develop hypoxemia and hypercapnia during exercise and sleep to a greater extent than healthy subjects with similar respiratory muscle strength and nutritional status. Neither respiratory muscle weakness nor malnutrition are necessary to develop hypoxemia or hypercapnia during exercise or sleep.     

Long-term follow-up of untreated patients with sleep apnoea syndrome

Obstructive sleep apnoea (OSA) is a common disorder with numerous potential sequelae. Although the majority of these consequences can be reduced with appropriate treatment, only limited data exist regarding the natural progression ofthis disorder in untreated individuals. We hereby report a long-term follow-up of all untreated patients (n = 40) followed-up in the Technion Sleep Clinic, using both subjective and objective measurements. In addition, we report a long-term follow-up of 11 patients who attempted dietary weight loss. The average time interval between the first and second polysomnographies for the untreated group was 5.0 +/- 2.8 yrs, and 2.5 +/- 2.3 yrs for the weight reduction group. There was no significant change in Body Mass Index (BMI) or Respiratory Disturbance Index (RDI) between the two Polysomnographic (PSG) evaluations in the untreated patients. However, eight patients developed hypertension (n=5) or ischaemic heart disease (IHD) (n=3) between the two evaluations. RDI, age and BMI at the time ofthe initial evaluation were not predictive of changes in RDI, snoring intensity or minimal oxygen saturation. However, the patients who developed hypertension/IHD had significantly higher RDI than the patients who did not (46 +/- 27 vs. 23 +/- 17 h(-1), P < 0.005). In the weight-loss group, BMI decreased by a mean of 3.1 kg m(-2), and RDI decreased by 20events h(-1), P<0.05 for both.There was a significant correlation between the weight loss and improvement in RDI (R = 0.75, P = 0.005). We conclude that in untreated obstructive sleep apnoea patients RDI does not necessarily increase over time, but associated hypertension or ischaemic heart disease may develop.When weight loss is successfully achieved, sleep apnoea significantly improves with a high correlation between the extent of weight loss and the improvement in apnoea status.     

Obstructive sleep apnea syndrome in morbid obesity: effects of intragastric balloon

STUDY OBJECTIVES: In obese patients, obstructive sleep apnea syndrome (OSAS) is attributed to a reduction in pharyngeal cross-sectional area due to peripharyngeal fat deposition. The effect of weight loss on the size of the upper airways of obese subjects is still unknown. We analyzed the pharyngeal cross-sectional area before and after weight loss in morbidly obese patients with OSAS. DESIGN, SETTING, AND SUBJECTS: A group of 17 middle-aged, morbidly obese men was evaluated by anthropometry and cardiorespiratory sleep studies before and after weight loss obtained by insertion of an intragastric balloon. The pharyngeal cross-sectional area was measured by acoustic pharyngometry. RESULTS: The mean (+/- SD) body mass index was 55.8 +/- 9.9 kg/m2 at baseline and 48.6 +/- 11.2 kg/m2 at the time of balloon removal (6 months after insertion) [p < 0.001]. At baseline, patients had visceral obesity, large necks, and severe OSAS. Weight loss was associated with a significant mean reduction of waist circumference (156.4 +/- 17.6 vs 136.7 +/- 18.4 cm, respectively; p < 0.001), sagittal abdominal diameter (37.8 +/- 3.0 vs 32.3 +/- 4.0 cm, respectively; p < 0.001), and neck circumference (51.1 +/- 3.7 vs 47.9 +/- 4.3 cm, respectively; p < 0.001). Moreover, weight loss induced a nearly complete resolution of OSAS (apnea-hypopnea index, 52.1 +/- 14.9 vs 14.0 +/- 12.4 events/h, respectively; p < 0.001). At baseline, obese patients had significantly lower pharyngeal cross-sectional areas compared to a group of 20 nonobese male control subjects, both in the upright and supine position, at different levels of the pharynx. In obese patients, the weight loss induced by the positioning of the intragastric balloon was associated with an increase in the size of the upper airway passage. After weight loss, both the mean pharyngeal cross-sectional area and the area at glottis level were still lower in obese subjects than in nonobese subjects; however, the pharyngeal cross-sectional area at the oropharyngeal junction was similar in the two groups. CONCLUSIONS: Morbidly obese men with OSAS have a reduced pharyngeal cross-sectional area. A weight reduction of about 15% of baseline body weight may substantially increase the pharyngeal cross-sectional area and substantially improve the severity of OSAS in morbidly obese subjects with sleep apnea.     

Short-term use of fluoxetine in asymptomatic obese subjects with sleep-related hypoventilation.

Disordered nocturnal breathing with significant arterial oxygen desaturation and sleep apnoea is a feature of extreme obesity which is often difficult to manage in the short term. We have evaluated the effect of fluoxetine, a centrally acting 5-HT re-uptake inhibitor, on sleep-breathing patterns in asymptomatic extremely obese subjects. A double-blind cross-over study was used to compare fluoxetine (60 mg for three days) to placebo. Eleven obese subjects (ten males, one female, mean weight +/- s.d. 131 +/- 2 kg) slept overnight in a sleep laboratory with the polysomnographic study recorded after an initial acclimatization night. The obese subjects had normal respiratory function and normal fully awake arterial oxygen saturation (%SaO2 97 +/- 1). Marked O2 desaturation was seen in all the subjects during sleep but the average asleep %SaO2 did not differ between the two treatment phases (placebo 90 +/- 5; fluoxetine 92 + 2%). However, fluoxetine significantly increased the minimum %SaO2 recorded during the study night either by abolishing or reducing REM sleep (placebo 73 +/- 2%; fluoxetine 81 +/- 8%; P < 0.05, 95% CI -12.3 to -2.03). Frequent hypopnoea was observed in all subjects in both REM and non-REM sleep whereas apnoea was uncommon. The total apnoea/hypopnoea index fell in six subjects during the fluoxetine night, the largest reduction being seen in the most severely affected. In five of the six the improvement was associated with the abolition of REM sleep. Total sleep time did not differ between the placebo and fluoxetine nights nor did a qualitative assessment of sleep using a visual analogue score.(ABSTRACT TRUNCATED AT 250 WORDS)     

The long-term results of gastric bypass on indexes of sleep apnea

STUDY OBJECTIVES: Weight loss improves obstructive sleep apnea (OSA), and clinicians regularly recommend dieting to their patients with OSA; however, many morbidly obese patients may be unable to lose weight without medical or surgical intervention. Gastric bypass surgery (GB) facilitates weight loss for morbidly obese patients. Studies show GB will improve symptoms associated with OSA, but little is known regarding the long-term effects of GB on this population. DESIGN: Historical, retrospective, cohort study. SETTING: Sleep Disorders Center, Sentara Norfolk General Hospital, Norfolk, VA. PARTICIPANTS: A list of subjects who underwent vertical Roux-en-Y GB was cross-referenced with the Sleep Disorders Center at Sentara Norfolk General Hospital to identify patients with a diagnosis of OSA during the preoperative evaluation prior to undergoing GB. INTERVENTIONS: GB. MEASUREMENTS: Our primary end point was the respiratory disturbance index (RDI). Secondary variables were body mass index (BMI), mean oxygen saturation, low oxygen saturation, a standardized depression scale, and the continuous positive airway pressure (CPAP) requirement. RESULTS: Thirty-four subjects with a diagnosis of OSA prior to GB were identified. Of these, 28 subjects were located and offered follow-up polysomnography after GB. Eight subjects returned for repeat polysomnography. The subjects were re-evaluated an average of 28 months after GB. Seven subjects had a lower BMI after GB. Mean BMI was reduced by 31% (p = 0.001). The mean decrease in RDI was 75% (p = 0.01), and five of the eight subjects no longer required nasal CPAP. Mean nocturnal oxygen saturation improved from 95 to 97% (p = 0.04). CONCLUSIONS: Weight reduction following GB is associated with significant improvements in sleep apnea indexes an average of 28 months after GB. Re-evaluation after GB is necessary to identify and treat those patients who, despite subjective improvement, may continue to require CPAP for residual OSA.     

Cardiorespiratory fitness and obstructive sleep apnea syndrome in morbidly obese patients

BACKGROUND: Conflicting data exist regarding the effects of obstructive sleep apnea syndrome (OSAS) on cardiorespiratory fitness in morbidly obese individuals with normal resting left ventricular function. METHODS: Ninety-two morbidly obese subjects without any prior diagnosis of OSAS underwent cardiorespiratory fitness testing, two-dimensional echocardiography, and overnight polysomnography. Using the results of the polysomnogram, comparisons were made between subjects with (n = 42) and without (n = 50) OSAS. RESULTS: Mean body mass index (BMI) for the study population (n = 92) was 48.6 +/- 9.3 kg/m(2) (+/- SD); mean age was 45.5 +/- 9.8 years, and approximately 69% were female. Despite having a higher resting, exercise, and resting mean arterial pressures, the OSAS cohort had a maximum oxygen consumption that was lower than the cohort without OSAS (21.1 mL/kg/min vs 17.6 mL/kg/min; p < 0.001). There was no difference in BMI, age, gender, waist circumference, and neck circumference between those with and without OSAS. Differences were observed between the cohorts in systolic BP, diastolic BP, and heart rate during rest, exercise, and recovery periods. There was no difference in ejection fraction, diastolic dysfunction, and treadmill test duration between cohorts. CONCLUSIONS: Morbidly obese individuals with OSAS demonstrate reduced cardiorespiratory fitness and differing hemodynamic responses to exercise testing as compared with their counterparts without this disorder. These data suggest chronic sympathetic nervous system activation negatively influences aerobic capacity in OSAS.     

Increased central adiposity in morbidly obese patients with obstructive sleep apnoea

Background: With the growing epidemic of obesity, few data are available regarding adipose distribution and the severity of sleep apnoea. Our aim was to measure precisely adipose distribution with dual‐energy X‐ray absorptiometry (DXA) in a morbidly obese population with and without obstructive sleep apnoea (OSA). Methods: Morbidly obese female subjects without a history of OSA underwent overnight polysomnography and DXA analysis. Subject demographics, DXA variables, serum laboratory markers and physical exam characteristics were compared between individuals with and without OSA. Results: For the study population (n= 26), mean body mass index (BMI) was 45.9 ± 7.8 kg/m²; mean age was 47.5 ± 10.2 years and all were female. The central adiposity ratio (CAR) was higher in individuals with OSA (apnoea–hypopnoea index > 5) than those without OSA (1.1 ± 0.05 vs 1.0 ± 0.04; P= 0.004). No difference was observed in Epworth Sleepiness Scale scores, body mass index (BMI) or neck circumference between groups. Conclusions: OSA is associated with increased central adipose deposition in patients with a BMI of >40 kg/m². These data may be helpful in designing future studies regarding the pathophysiology of OSA, and potential treatment options.     

Gender difference in sleep profile of severely obese patients with obstructive sleep apnea (OSA)

OBJECTIVES: Few papers addressed the gender difference in the polisomnographic features of obstructive sleep apnea (OSA). In this paper we investigated the sleep architecture and the nocturnal respiratory pattern in a group of severely obese women with OSA compared with a group of men with OSA matched by age and weight. DESIGN: A cross-sectional study. SETTING: Primary-care setting. SUBJECTS, MAIN OUTCOME MEASURES: Anthropometric parameters, respiratory function data and a full night polisomnography were evaluated in a group of 45 obese subjects, 20 females and 25 males, with a previous diagnosis of OSA. RESULTS: The group of the severely obese women with OSA presented greater disturbances of the sleep architecture than the group of the men does (wake time after sleep onset 92.6+/-52.4 vs 58.2+/-45.2 min, P<0.05; total wake time 104.8+/-51.4 vs 67.8+/-47.4, P<0.05; number of awakenings 15.5+/-3.6 vs 10.2+/-6.215, P<0.001; OSA that occurred almost exclusively during REM sleep (REM OSA) 35% vs 4%, P<0.05) and a reduced sleep efficiency (69.6+/-15.9 vs 80.3+/-14.0%, P<0.05). CONCLUSIONS: Severely obese women with OSA, even with milder OSA, present greater disturbances of the sleep architecture with a more severe sleep disruption and more frequently REM OSA in comparison with men matched by age and weight.     

Frequency and mechanism of daytime pulmonary hypertension in patients with obstructive sleep apnoea syndrome

In order to study the frequency and the mechanisms of daytime pulmonary hypertension (PH) in obstructive sleep apnoea syndrome (OSAS) lung function tests, blood gas analysis and right-heart catheterization were performed in 46 consecutive patients. OSAS was assessed by polysomnography. 9 patients only (20%) had PH (mean pulmonary artery pressure (Ppa) greater than or equal to 20 mmHg). Patients with PH had lower daytime PaO2 (60.8 +/- 7.6 vs. 76.2 +/- 9.4 mmHg; p less than 0.001), higher daytime PaCO2 (44.8 +/- 4.2 vs. 38.0 +/- 4.0 mmHg; p less than 0.001), lower forced vital capacity (FVC) and forced expiratory volume (FEV1) (p less than 0.001), but the severity of OSAS was not different whether PH was present or not (apnoea index: 62 +/- 34 hour in the PH group vs. 65 +/- 40 hour, apnoea + hypopnoea index 102 +/- 33 hour in the PH group vs. 86 +/- 36 hour, lowest sleep SaO2: 59 +/- 21% in the PH group vs. 66 +/- 18%). There were significant correlations between Ppa and: daytime PaO2 (r = -0.61; p less than 0.001), PaCO2 (r = 0.55; p less than 0.001), FEV1 (r = -0.52; p less than 0.001) but not between Ppa and apnoea index, apnoea + hypopnoea index, lowest sleep SaO2. PH and daytime hypoxaemia were associated either with chronic airway obstruction or with severe obesity.     

阻塞性睡眠呼吸暂停综合征的睡眠结构改变

目的研究阻塞性睡眠呼吸暂停综合征（ＯＳＡＳ）病情严重程度及持续气道内正压（ＣＰＡＰ）治疗对睡眠结构的影响。方法通过分析多导睡眠图，分析了３１例非ＯＳＡＳ者和１４７例ＯＳＡＳ患者的睡眠结构及ＣＰＡＰ治疗对１１例ＯＳＡＳ患者睡眠结构的影响。结果与对照组相比ＯＳＡＳ组的睡眠结构存在如下异常：（１）睡眠期转换次数（ＯＳＡＳ组：１２０±７１，对照组：９２±６０，Ｐ＝０．０１０６）、快波睡眠次数（ＯＳＡＳ组：８８±５４，对照组：６５±４５，Ｐ＝０．００７５）、醒觉次数（ＯＳＡＳ组：２７±２８，对照组：１９±１８，Ｐ＝０．０１７）差异有显著性；（２）慢波睡眠次数（ＯＳＡＳ组：５±９，对照组：８±８，Ｐ＝０．００３５）、占总睡眠时间的比例（ＯＳＡＳ组：５％±８％，对照组：８％±９％，Ｐ＝０．００６２）及慢波睡眠的缺乏率（ＯＳＡＳ组：４８％，对照组：２６％，Ｐ＜０．０５）亦明显不同；（３）睡眠呼吸紊乱指数低于２５的ＯＳＡＳ者与对照组比较睡眠各参数相差不大；（４）ＣＰＡＰ治疗能使上述参数得到不同程度的改善。结论ＯＳＡＳ主要引起睡眠的破碎、深睡减少及浅睡增加，且与病情的严重程度有一定关系。ＣＰＡＰ治疗能够改善这些紊乱。     

Depression of peripheral chemosensitivity by a dopaminergic mechanism in patients with obstructive sleep apnoea syndrome.

In the present study, respiratory drives to chemical stimuli and peripheral chemosensitivity were evaluated in patients with obstructive sleep apnoea (OSAS). The effects of oral administration of domperidone, a selective dopamine D2-receptor antagonist, were also examined, to study the respiratory effects of endogenous dopamine on peripheral chemoreceptors. Sixteen patients with OSAS and nine normal control subjects were studied. Respiratory responses to hypercapnia and hypoxia were measured using the rebreathing method and isocapnic progressive hypoxia method, respectively. The hypoxic withdrawal test, which measures the decrease in ventilation caused by two breaths of 100% O2 under mild hypercapnic hypoxic conditions (end-tidal oxygen and carbon dioxide tensions approximately 8.0 kPa and 5.3-6.7 kPa, respectively), was used to evaluate peripheral chemosensitivity. In the patients with OSAS, ventilatory responses to hypercapnia and hypoxia were significantly decreased compared with those of control subjects. Hypoxic withdrawal tests showed that peripheral chemosensitivity was significantly lower in patients with OSAS than in normal subjects. Hypercapnic ventilatory response and peripheral chemosensitivity were enhanced by administration of domperidone in the patients with OSAS, although no changes in either of these were observed in the control subjects. The hypoxic ventilatory response and peripheral chemosensitivity in the patients with OSAS were each significantly correlated with severity of hypoxia during sleep. These findings suggest that peripheral chemosensitivity in patients with obstructive sleep apnoea syndrome may be decreased as a result of abnormality in dopaminergic mechanisms and that the reduced chemosensitivity observed in patients with obstructive sleep apnoea syndrome may affect the severity of hypoxia during sleep.     

Association of subclinical right ventricular dysfunction with obesity.

OBJECTIVES: The purpose of this research was to identify the determinants of right ventricular (RV) dysfunction in overweight and obese subjects. BACKGROUND: Right ventricular dysfunction in obese subjects is usually ascribed to comorbid diseases, especially obstructive sleep apnea. We used tissue Doppler imaging to identify the determinants of RV dysfunction in overweight and obese subjects. METHODS: Standard and tissue Doppler echocardiography was performed in 112 overweight (body mass index [BMI] 25 to 29.9 kg/m2) or obese (BMI >30 kg/m2) subjects and 36 referents (BMI <25 kg/m2), including 22 with obstructive sleep apnea but no obesity. Tissue Doppler was used to measure RV systolic (s(m)) and diastolic (e(m)) velocities and strain indexes. RESULTS: Obese subjects with BMI >35 kg/m2 had reduced RV function compared with referent subjects, evidenced by reduced s(m) (6.5 +/- 2.4 cm/s vs. 10.2 +/- 1.5 cm/s, p < 0.001), peak strain (-21 +/- 4% vs. -28 +/- 4%, p < 0.001), peak strain rate (-1.4 +/- 0.4 s(-1) vs. -2.0 +/- 0.5 s(-1), p < 0.001), and e(m) (-6.8 +/- 2.4 cm/s vs. -10.3 +/- 2.5 cm/s, p < 0.001), irrespective of the presence of sleep apnea. Similar but lesser degrees of reduced systolic function (p < 0.05) were present in overweight (BMI 25 to 29.9 kg/m2) and mildly obese (BMI 30 to 35 kg/m2) groups. Differences in RV e(m), s(m), and strain indexes were demonstrated between the severely versus overweight and mildly obese groups (p < 0.05). Body mass index remained independently related to RV changes after adjusting for age, log insulin, and mean arterial pressures. In obese patients, these changes were associated with reduced exercise capacity but not the duration of obesity and presence of sleep apnea or its severity. CONCLUSIONS: Increasing BMI is associated with increasing severity of RV dysfunction in overweight and obese subjects without overt heart disease, independent of sleep apnea.     

Obstructive sleep apnea with severe chronic airflow limitation. Comparison of hypercapnic and eucapnic patients

The mechanism of sustained awake hypercapnia in the obstructive sleep apnea syndrome (OSA) is unknown. Recent work has implicated coexisting chronic airflow limitation (CAL) as an important contributing factor. We approached this question by studying consecutive patients with both OSA syndrome and severe CAL in detail and comparing those with and without retention of CO2 while awake. Of 28 patients with both severe OSA (mean NREM apnea index = 48 +/- 9, SEM) and severe CAL (mean FEV1 = 1.07 +/- 0.07 L), 14 had persistent awake hypercapnia (mean PaCO2 = 50 +/- 1 mm Hg), and 14 were normocapnic (mean PaCO2 = 40 +/- 1 mm Hg). When separated according to their PaCO2 level, there was no difference in the apnea indices in both non-rapid-eye-movement (NREM) sleep, or rapid-eye-movement (REM) sleep, although the hypercapnic group had lower average levels of oxyhemoglobin saturation in both NREM (SaO2 = 77 +/- 2% versus 85 +/- 3%, p less than 0.05) and REM (SaO2 = 60 +/- 4% versus 82 +/- 3%, p less than 0.001) sleep. The mean values for FEV1, VC, lung volumes, and diffusing capacity for CO measured while awake did not differ. The hypercapnic group had lower awake PaO2 levels (p less than 0.001), were heavier (p less than 0.05), had narrower upper airway size on CT scan measurements (p less than 0.01), and gave a history of much heavier alcohol intake (p less than 0.05). Our results demonstrate that some patients with severe OSA and severe CAL can maintain normal awake arterial CO2 levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cephalometric abnormalities in non-obese and obese patients with obstructive sleep apnoea.

The aim of this work was to comprehensively evaluate the cephalometric features in Japanese patients with obstructive sleep apnoea (OSA) and to elucidate the relationship between cephalometric variables and severity of apnoea. Forty-eight cephalometric variables were measured in 37 healthy males and 114 male OSA patients, who were classed into 54 non-obese (body mass index (BMI) <27 kg x m(-2), apnoea-hypopnoea index (AHI)=25.3+/-16.1 events x h(-1)) and 60 obese (BMI > or = 27 kg x m(-2), AHI=45.6+/-28.0 events h(-1)) groups. Diagnostic polysomnography was carried out in all of the OSA patients and in 19 of the normal controls. The non-obese OSA patients showed several cephalometric defects compared with their BMI-matched normal controls: 1) decreased facial A-P distance at cranial base, maxilla and mandible levels and decreased bony pharynx width; 2) enlarged tongue and inferior shift of the tongue volume; 3) enlarged soft palate; 4) inferiorly positioned hyoid bone; and 5) decreased upper airway width at four different levels. More extensive and severe soft tissue abnormalities with a few defects in craniofacial bony structures were found in the obese OSA group. For the non-obese OSA group, the stepwise regression model on AHI was significant with two bony structure variables as determinants: anterior cranial base length (S-N) and mandibular length (Me-Go). Although the regression model retained only linear distance between anterior vertebra and hyoid bone (H-VL) as an explainable determinant for AHI in the obese OSA group, H-VL was significantly correlated with soft tissue measurements such as overall tongue area (Ton), inferior tongue area (Ton2) and pharyngeal airway length (PNS-V). In conclusion, Japanese obstructive sleep apnoea patients have a series of cephalometric abnormalities similar to those described in Caucasian patients, and that the aetiology of obstructive sleep apnoea in obese patients may be different from that in non-obese patients. In obese patients, upper airway soft tissue enlargement may play a more important role in the development of obstructive sleep apnoea, whereas in non-obese patients, bony structure discrepancies may be the dominant contributing factors for obstructive sleep apnoea.     

Success and failure of mirtazapine as alternative treatment in elderly stroke patients with sleep apnea—a preliminary open trial

More than two thirds of stroke patients suffer from sleep apnea. A recent study showed that mirtazapine reduced the respiratory disturbance index (RDI) of a stroke patient by 80%. These promising results prompted us to offer mirtazapine to non-depressed stroke patients who suffered from sleep apnea and refused treatment with a continuous positive airway pressure (CPAP) device. Polysomnography was performed between 2200 and 0600 hours. We examined ten inpatients [nine male, one female; mean age of 68.7 +/- 1.5 years +/- SE; body mass index of 26.1 +/- 1.2 kg/m(2), basal ganglia bleeding (n = 3), middle cerebral artery ischemia (n = 4), basal ganglia ischemia (n = 1), cerebellar bleeding (n = 2)] in the Neurologic Clinic's sleep laboratory. The mean duration of illness before the first polysomnography was 52.6 +/- 11.4 days. Mirtazapine effectively consolidated sleep in all patients, i.e., sleep efficiency significantly increased from 63.1 +/- 4.8% to 75.7 +/- 5.0%. A moderate increase in RDI (137.4 +/- 15.3% of baseline) occurred during initial mirtazapine administration (intake duration 15.8 +/- 5.5 days). After 51.9 +/- 8.4 days, the RDI was either reduced (51.9% in "responders" who were identified arbitrarily by a reduction in RDI >or= 25% at any time point of the investigation) or increased (154.4% in "non-responders"). Mirtazapine administration was stopped in the four patients with increased RDI. Mirtazapine may be a probably effective treatment in stroke survivors with obstructive sleep apnea who refuse nasal CPAP treatment. As it may worsen central and mixed sleep apnea, patients who receive mirtazapine to alleviate sleep apnea or to control post-stroke depression with sleep disturbances should be monitored for changes in breathing parameters during sleep.