A predictive model for optimal continuous positive airway pressure in the treatment of pure moderate to severe obstructive sleep apnea in China.

BACKGROUND: Numerous predictive formulas based on different ethnics have been developed to determine continuous positive airway pressure (CPAP) for patients with obstructive sleep apnea (OSA) without laboratory-based manual titrations. However, few studies have focused on patients with OSA in China. Therefore, this study aimed to develop a predictive equation for determining the optimal value of CPAP for patients with OSA in China. METHODS: 526 pure moderate to severe OSA patients with attended CPAP titrations during overnight polysomnogram were spited into either formula derivation (419 patients) or validation (107 patients) group according to the treatment time. Predictive model was created in the derivation group, and the accuracy of the model was tested in the validation group. RESULTS: Apnea hypopnea index (AHI), body mass index (BMI), longest apnea time (LAT), and minimum percutaneous oxygen saturation (minSpO2) were considered as independent predictors of optimal CPAP through correlation analysis and multiple stepwise regression analysis. The best equation to predict the optimal value of CPAP was: CPAPpred = 7.581 + 0.020*AHI + 0.101*BMI + 0.015*LAT-0.028*minSpO2 (R2 = 27.2%, p < 0.05).The correlation between predictive CPAP and laboratory-determined manual optimal CPAP was significant in the validation group (r = 0.706, p = 0.000). And the pressure determined by the predictive formula did not significantly differ from the manually titrated pressure in the validation cohort (10 ± 1 cmH2O vs. 11 ± 3 cmH2O, p = 0.766). CONCLUSIONS: The predictive formula based on AHI, BMI, LAT, and minSpO2 is useful in calculating the effective CPAP for patients with pure moderate to severe OSA in China to some extent.

Obstructive sleep apnea and respiratory center regulation abnormality.

PURPOSE: Obstructive sleep apnea (OSA) is a complex disease in which phenotypic analysis and understanding pathological mechanisms facilitate personalized treatment and outcomes. However, the pathophysiology responsible for this robust observation is incompletely understood. The objective of the present work was to review how respiratory center regulation varies during sleep and wakeness in patients with OSA. DATA SOURCES: We searched for relevant articles up to December 31, 2019 in PubMed database. METHODS: This review examines the current literature on the characteristics of respiratory center regulation during wakefulness and sleep in OSA, detection method, and phenotypic treatment for respiratory center regulation. RESULTS: Mechanisms for ventilatory control system instability leading to OSA include different sleep stages in chemoresponsiveness to hypoxia and hypercapnia and different chemosensitivity at different time. One can potentially stabilize the breathing center in sleep-related breathing disorders by identifying one or more of these pathophysiological mechanisms. CONCLUSIONS: Advancing mechanism research in OSA will guide symptom research and provide alternate and novel opportunities for effective treatment for patients with OSA.

Formoterol as reliever medication in asthma: a post-hoc analysis of the subgroup of the RELIEF study in East Asia.

BACKGROUND: As-needed formoterol can effectively relieve asthma symptoms. Since budesonide/formoterol is available as maintenance and reliever therapy in Asia, formoterol is now being used as-needed, but always with concomitant inhaled corticosteroids. The objective of this analysis was to assess the safety and efficacy of formoterol therapy in patients in East Asia (China, Indonesia, Korea, the Philippines and Singapore) with asthma. METHODS: Post-hoc analyses of data from the East Asian population of the RELIEF (REal LIfe EFfectiveness of Oxis® Turbuhaler® as-needed in asthmatic patients; study identification code: SD-037-0699) study were performed. RESULTS: This sub-group comprised 2834 randomised patients (formoterol n = 1418; salbutamol n = 1416) with mean age 35 years; 50.7% were male. 2678 patients completed the study. There was no significant difference in the total number of adverse events (AEs) reported in the formoterol and salbutamol groups (21.3% vs 20.9% of patients; p = 0.813), nor in the total number of serious AEs and/or discontinuations due to AEs (4.6% vs 5.5%, respectively; p = 0.323). Compared with salbutamol, formoterol was associated with a significantly longer time to first exacerbation (hazard ratio 0.86; p = 0.023) and a 14% reduction in the risk of any exacerbation (p < 0.05). Relative to salbutamol, mean adjusted reliever medication use throughout the study was significantly lower in the formoterol group (p = 0.017) and the risk of increased asthma medication use was 20% lower with formoterol (p = 0.005). CONCLUSIONS: Among patients with asthma in East Asia, as-needed formoterol and salbutamol had similar safety profiles but, compared with salbutamol, formoterol reduced the risk of exacerbations, increased the time to first exacerbation and reduced the need for reliever medication.

The organ specificity in pathological damage of chronic intermittent hypoxia: an experimental study on rat with high-fat diet.

PURPOSE: It is known today that sleep apnea hypopnea syndrome and its characteristic chronic intermittent hypoxia can cause damages to multiple organs, including the cardiovascular system, urinary system, and liver. It is still unclear, however, whether the damage caused by sleep apnea hypopnea syndrome and the severity of the damage are organ-specific. METHODS: This research observed the pathological effects of chronic intermittent hypoxia on rat's thoracic aorta, myocardium, liver, and kidney, under the condition of lipid metabolism disturbance, through establishing the rat model of chronic intermittent hypoxia with high-fat diet by imitating the features of human sleep apnea hypopnea syndrome. In this model, 24 male Wistar rats were randomly divided into three groups: a control group fed by regular diet, a high-fat group fed by high-fat diet, and a high-fat plus intermittent hypoxia group fed by high-fat diet and treated with intermittent hypoxia 7 h a day. At the end of the ninth week, the pathological changes of rat's organs, including the thoracic aorta, myocardium, liver, and kidney are observed (under both optical microscopy and transmission electron microscopy). RESULTS: As the result of the experiment shows, while there was no abnormal effect observed on any organs of the control group, slight pathological changes were found in the organs of the high-fat group. For the high-fat plus intermittent hypoxia group, however, remarkably severer damages were found on all the organs. It also showed that the severity of the damage varies by organ in the high-fat plus intermittent hypoxia group, with the thoracic aorta being the worst, followed by the liver and myocardium, and the kidney being the slightest. CONCLUSIONS: Chronic intermittent hypoxia can lead to multiple-organ damage to rat with high-fat diet. Different organs appear to have different sensitivity to chronic intermittent hypoxia.

Optimized ultrasound-assisted extraction of phenolic compounds from Polygonum cuspidatum.

In this study the phenolic compounds piceid, resveratrol and emodin were extracted from P. cuspidatum roots using ultrasound-assisted extraction. Multiple response surface methodology was used to optimize the extraction conditions of these phenolic compounds. A three-factor and three-level Box-Behnken experimental design was employed to evaluate the effects of the operation parameters, including extraction temperature (30-70 °C), ethanol concentration (40%-80%), and ultrasonic power (90-150 W), on the extraction yields of piceid, resveratrol, and emodin. The statistical models built from multiple response surface methodology were developed for the estimation of the extraction yields of multi-phenolic components. Based on the model, the extraction yields of piceid, resveratrol, and emodin can be improved by controlling the extraction parameters. Under the optimum conditions, the extraction yields of piceid, resveratrol and emodin were 10.77 mg/g, 3.82 mg/g and 11.72 mg/g, respectively.

[The prevalence and risk factors of bronchiectasis in residents aged 40 years old and above in seven cities in China].

OBJECTIVE: To investigate the prevalence and risk factors of bronchiectasis in urban city of China. METHODS: A cross-sectional survey was conducted in 17 urban areas in Beijing, Shanghai, Tianjin, Chongqing cities, and Guangdong, Liaoning, Shanxi provinces. In this study, urban population-based cluster samples were randomly selected from each city/province. In the selected city communities, all residents at least 40 years old were recruited, interviewed with questionnaires and tested with spirometry. Each participant was asked whether he/she was ever diagnosed as bronchiectasis by physician, whether had symptoms of respiratory diseases and possible risk factors, etc. RESULT: Data of 10 811 participants was enrolled for analysis, with a response rate of 75.4% (10 811/14 337). The overall prevalence of physician-diagnosed bronchiectasis was 1.2% (135/10 811), with 1.5% (65/4382) in male and 1.1% (70/6429) in female, without statistical difference in gender (χ² = 3.289, P = 0.070). Prevalence of bronchiectasis increased with age (χ² = 31.029, P < 0.001). There were no statistical significances in crude prevalences of bronchiectasis among cities (χ² = 10.572, P = 0.103), while there was a significant difference among cities after adjustment with confounders (Wald value = 22.116, P = 0.001), by using logistic regression analysis. Logistic regression analysis showed, bronchiectasis was significantly associated with elder ( ≥ 70 years vs 40-49 years; OR = 4.11, 95% CI 2.29-7.36), the family history of respiratory diseases (having two subjects with respiratory diseases in family vs no suffered relatives; OR = 2.04, 95% CI 1.06-3.94), respiratory infection during childhood (suffering two kinds of respiratory diseases vs never; OR = 4.89, 95% CI 2.03-11.81), exposure to coal (OR = 2.30, 95% CI 1.17-4.52), chronic pharyngitis (OR = 3.96, 95% CI 1.38-11.40) and pulmonary tuberculosis (OR = 3.07, 95% CI 1.89-4.98), heart diseases (OR = 1.64, 95% CI 1.11-2.42) and lung cancer(OR = 18.61, 95% CI 7.67-45.18). CONCLUSION: The prevalence of bronchiectasis in population aged 40 years old and above in urban area in China is high and associated with multiple factors such as age, family history of respiratory diseases, respiratory infection during childhood, exposure to coal, chronic pharyngitis, pulmonary tuberculosis, heart diseases, lung cancer and so on.

[Impact of chronic intermittent hypoxia upon rat liver lipid metabolism and interventional effect of Tempol].

OBJECTIVE: To explore the impact of chronic intermittent hypoxia (CIH) upon rat liver lipid metabolism and effect of anti-oxidant Tempol. METHODS: Male Wistar rats (n = 80) were randomly divided into intermittent hypoxia group (10, 20, 30, 40 times/h), intermittent hypoxia Tempol treatment group, intermittent hypoxia normal saline treatment group, intermittent air mimic group (IA) and blank control group (CG). Sections of liver were stained with hematoxylin and eosin. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. Levels of liver homogenate triglyceride (TG), total cholesterol (TC), free fatty acids (FFA) and serum TG, TC, adiponectin (ADP) were measured. RESULTS: Liver histology: IH group exhibited hepatocellular swelling, hyperchromatosis, disrupted hepatocellular membrane. With the increase of frequency, there were local necrosis and infiltration of inflammatory cells. But no steatosis was seen. Tempol early treatment and IA groups exhibited no hepatocellular swelling or inflammatory cell infiltration. The activities of ALT and AST increased along with the increased frequency in IH group (all P < 0.01). The levels of ALT and AST in IH group ((48.6 ± 3.6), (25.4 ± 2.6) U/L) were higher than those in IA group ((20.3 ± 3.1), (18.7 ± 1.3) U/L) and CG group ((17.5 ± 2.4), (18.8 ± 1.3) U/L) (all P < 0.01). It decreased in Tempol treatment group, and more obviously when early intervention was applied (all P < 0.01). Liver homogenate TG, TC and FFA had no difference among IH, IA and CG groups (all P > 0.05), and no difference in different frequencies in IH group (all P > 0.05). The levels of serum TG, TC in IH groups were higher than those in IA and CG groups while ADP was lower (all P < 0.01). It changed more obviously in different frequencies in IH group (all P < 0.01). In Tempol treatment group, serum TG, TC decreased while ADP increased and changed more obviously when early intervention was applied (all P < 0.01). CONCLUSIONS: CIH causes the morphologic changes of liver and the elevations of ALT and AST, but results not in lipid deposition in liver cells. Anti-oxidation of Tempol can block intermittent hypoxia associated with liver injury.

Ultrasonic-assisted extraction of the botanical dietary supplement resveratrol and other constituents of Polygonum cuspidatum.

The roots of Polygonum cuspidatum produce several phenolic compounds, including trans-resveratrol (1), trans-piceid (2), and emodin (3), and are a commercial source of the botanical dietary supplement 1. Ultrasonic-assisted extraction technology and conventional shaking extraction procedures were compared for the extraction of 1-3 from P. cuspidatum roots, using 50% ethanol as a food grade solvent. These compounds were extracted successfully, and their mass transfer coefficients were calculated by fitting the experimental results to a model derived from Fick's second law. The results indicated that ultrasonic-assisted extraction had higher mass transfer efficacies and extraction yields for 1-3 as compared with conventional shaking extraction. Under the extraction conditions used (extraction temperature 50 °C; ultrasonic power 150 W), yields of 3.5, 9.2, and 7.8 mg/g were obtained for 1-3, respectively.

Epworth Sleepiness Scale may be an indicator for blood pressure profile and prevalence of coronary artery disease and cerebrovascular disease in patients with obstructive sleep apnea.

OBJECTIVE: This study seeks to determine whether scores of a short questionnaire assessing subjective daytime sleepiness (Epworth Sleepiness Scale [ESS]) are associated with blood pressure (BP) level, BP profile, and prevalence of related coronary artery disease (CAD) and cerebrovascular disease (CVD) in obstructive sleep apnea (OSA) patients diagnosed by polysomnography (PSG). METHODS: Twenty university hospital sleep centers in China mainland were organized by the Chinese Medical Association to participate in this study. Between January 2004 and April 2006, 2,297 consecutive patients (aged 18-85 years; 1,981 males and 316 females) referred to these centers were recruited. BP assessments were evaluated at four time points (daytime, evening, nighttime, and morning) under standardized conditions. Anthropometric measurements, medical history of hypertension, CAD, and CVD were collected. ESS score was calculated for each participant and at the night of BP assessment, nocturnal PSG was performed and subjects were classified into four groups based on the apnea-hypopnea index (AHI) from PSG as follows: control group (control, n = 213) with AHI < 5; mild sleep apnea (mild, n = 420) with AHI ≥ 5 and <15; moderate sleep apnea (moderate, n = 460) with AHI ≥ 15 and <30; and severe sleep apnea (severe, n = 1,204) with AHI ≥ 30. SPSS 11.5 software package was used for the relationships between ESS and BP profile and prevalence of CAD and CVD. RESULTS: ESS is correlated positively with average daytime, nighttime, evening, and morning BP before and even after controlling for confounding effects of age, sex, BMI, AHI, and nadir nocturnal oxygen saturation (before--r = 0.182, 0.326, 0.245, and 0.329, respectively, all P values < 0.001; after--r = 0.069, 0.212, 0.137, and 0.208, respectively, all P values < 0.001). In the severe group, nighttime, evening, morning average BPs (ABPs), the ratio of nighttime/daytime average BP (ratio of nighttime average BP to daytime average BP), and prevalence of hypertension, drug-resistant hypertension (R-HTN), isolated nighttime hypertension (IN-HTN), CAD, and CVD in excessive daytime sleepiness (EDS, ESS ≥ 11) subjects are higher than those in non-EDS (ESS 0-10; t/χ(2) = -8.388, -6.207, -8.607, -5.901, 12.742, 38.980, 16.343, 59.113, and 67.113, respectively; all P values < 0.05). For EDS subjects in the moderate group but not in the control and mild group, nighttime ABP and the ratio of nighttime/daytime average BP are higher (t = -2.086 and -3.815, respectively, all P values < 0.05). Linear fitting with ESS and the ratio of nighttime/daytime average BP shows a positive correlation (r(2) = 0.049, P < 0.001). CONCLUSIONS: In severe OSA patients with comparable AHI, EDS may identify a subset of individuals with OSA at higher risk of hypertension, R-HTN, IN-HTN, CAD, and CVD. Overall, nighttime ABP seems to be more sensitive to be influenced by EDS than other ABP parameters. Future studies should investigate the potential dose-effect relationship between EDS and hypertension and the possibility that diagnosis and treatment of EDS could aid in BP reduction and ultimately in decreased morbidity and mortality from cardiovascular and cerebrovascular complications (TMUIRB20010002 at www.clinicaltrials.gov ).

[Influence of chronic intermittent hypoxia on sympathetic nerve activity in rats and effect of the antioxidant Tempol].

OBJECTIVE: To study the role of sympathetic nerve activity during the development of hypertension resulting from chronic intermittent hypoxia, and whether or not elevated sympathetic nerve activity is related to oxidative stress, and to investigate the preventive effect and possible mechanism of Tempol. METHODS: Forty-eight male Wistar rats were randomly divided into 6 groups of 8 each, including normoxic control group (NC), intermittent hypoxia group (IH) and 4 treatment groups (IHT1, IHT2, IHN1, IHN2). Among the treatment groups, IHT1, IHT2 groups were treated with 10% Tempol 100 mg × kg(-1)× d(-1) by intraperitoneal injection before exposed to IH and on day 28 after exposed to IH respectively, while IHN1 and IHN2 groups were treated with NS as controls. RESULT: There was no statistic difference in artery systolic blood pressure (SBP) between IH group, IHN1 group [(114 ± 6) mm Hg, 1 mm Hg = 0.133 kPa], and IHN2 group [(128 ± 6) mm Hg, P < 0.05] at the end of 6(th) week. SBP in the all IH groups was significantly elevated compared with NC group (P < 0.05) and the baseline SBP (P < 0.05) except of the group IHT1. SBP in the 2 tempol treatment groups was lower than the NS groups [(138 ± 10) mm Hg, both P < 0.05], while SBP of IHT2 group was higher than the IHT1 group (P < 0.01). No significant changes were found in the NC group. There were no statistic difference of NE and E in plasma and MDA in adrenal gland tissues between IH groups, IHN1 group and IHN2 group. The levels in NE and E and MDA in the 2 tempol treatment groups were lower than the NS groups (P < 0.05 or P < 0.01), but those in the IHT2 group were higher than the NC group (P < 0.05 or P < 0.01) and IHT1 groups (P < 0.05 or P < 0.01). No significant difference were found between IHT1 group and NC group. CONCLUSION: CIH could generate ROS by causing oxidative stress, which results in elevated sympathetic nerve activity. This may be one of the important mechanisms for CIH-induced hypertension. Tempol may be useful for prevention and treatment of OSAS-induced hypertension.

[The effects of chronic intermittent hypoxia on blood pressure and sympathetic nerve activity in rats].

OBJECTIVE: To observe the changes of blood pressure and sympathetic nerve activity under different degrees of chronic intermittent hypoxia (CIH) in rats, and therefore to explore the effects of CIH on blood pressure and sympathetic nerve activity and the correlation between blood pressure and sympathetic nerve activity in the pathogenesis of CIH-induced hypertension. METHODS: Male Wistar rats (n = 168) were randomly divided into untreated group (UD), severe intermittent hypoxia group (IH(1)), moderate intermittent hypoxia group (IH(2)), mild intermittent hypoxia group (IH(3)), continuous hypoxia group (CH), sham control group (SC) and were exposed to different conditions. Rats (n = 8) of the UD group were sacrificed before the experiment, while rats of the other groups were killed in weeks 2, 4, 6, and 8 of the experiment. Anticoagulated venous blood was obtained and plasma was stored at -80°C. Systolic arterial pressure (SBP) was recorded before and after the experiment, while plasma norepinephrine (NE) was measured after the experiment. RESULTS: Before the experiment, the SBP of rats showed no significant differences among groups (F = 0.008, P > 0.05), but the SBP of rats in the intermittent hypoxia groups increased gradually, and higher than the UD group, the SC group and the CH group from the beginning of week 4 (P < 0.05 or P < 0.01). The blood pressure was positively related with the degree of hypoxia (F = 9.844, P < 0.01), and that of the IH(1) group was significantly higher than that of the IH(3) group (P < 0.05), while no significant changes were found in the SC and the CH groups. The plasma NE level of rats in the intermittent hypoxia groups increased gradually with the experiment and significantly higher than that of the UD group, the SC group and the CH group at week 8 (P < 0.05 or P < 0.01), and the level of NE was positively related with the degree of hypoxia (F = 11.537, P < 0.01). The NE level of the IH(1) group was significantly higher than that of the IH(3) group (P < 0.05), but no significant change was found in the SC and the CH groups. The plasma NE levels were positively related with blood pressure (r = 0.530, P < 0.01). CONCLUSIONS: CIH can cause increased blood pressure and sympathetic activity in rats, and the effect was dependent on the degree of hypoxia and the time of exposure. The results suggested that CIH-induced higher blood pressure was associated with increased sympathetic activity.

[A preliminary study on the measurement of (1,3)-ß-D-glucan in bronchoalveolar lavage for the diagnosis of pulmonary fungal infections].

OBJECTIVE: To explore the measurement of (1,3)-ß-D-glucan bronchoalveolar lavage fluid (BALF) for the diagnosis of pulmonary fungal infections. METHODS: A total of 135 patients in the General Hospital of Tianjin Medical University from February 2010 to February 2011 were enrolled. There were 34 cases of confirmed or clinically diagnosed pulmonary fungal infections, 53 cases of bacterial pneumonia, and 48 cases of non-infection diseases. All patients underwent BAL and the BALF samples were obtained. (1,3)-ß-D-glucan content (G test), in BALF and plasma were tested and the data were analyzed statistically by Mann-Whitney while the receiver operating characteristic curve (ROC curve) was established, from which the best threshold of the 2 G tests was derived. RESULTS: The median of BALF G test in the fungal infection group, pneumonia group and non-infection group was 281, 28 and 10 ng/L, respectively; the level in the fungal infection group being significantly higher than those of the other 2 groups (P < 0.001), but no significant difference being observed between the pneumonia group and the non-infection group (P > 0.05). The median of plasma G tests in the fungal infection group, the pneumonia group and the non-infection group was 27, 10, and 5 ng/L, respectively; the level in the fungal infection group being significantly higher than those in the other 2 groups (P < 0.001), but there was no significant difference between the pneumonia group and the non-infection group (P > 0.05). The best threshold of BALF G test was 67 ng/L, while the best threshold of G test of plasma was 17 ng/L. CONCLUSION: As compared to G test of plasma, G test of BALF may be more accurate, and have a higher clinical value for the earlier diagnosis of pulmonary fungal infections.

[The relation of learning deficits with oxidative stress in rats exposed to severe intermittent hypoxia].

OBJECTIVE: To observe the relations between learning memory function and oxidative stress in rats exposed to severe intermittent hypoxia (IH). METHODS: Adult male Wistar rats (n = 48) were randomly assigned to 2 groups: untreated control group (UC) and 5% intermittent hypoxia group (5%IH). At 2, 4, 6 and 8 weeks, the learning and memory ability of the rats in each group were assessed with the Morris water maze (MWM) test. The ultrastructural changes in the hippocampus of the rats were observed with transmission electron microscopy (TEM). The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by colorimetric method. RESULTS: The water maze test showed that the rats in the 5% IH group had prolonged latency in escaping, reduced target quadrant time in crossing and reduced frequency of crossing the platform, as compared to the UC group (P < 0.05). With longer time of hypoxia, the damage became more significant. It was observed that the structure of neuron cell was complete and organelles were abundant in UC groups. With the extension of exposure time, the number of hippocampus neurons and synaptic were decreased in 5%IH groups, nucleus shrank, synaptic frame became indefinite and synaptic cleft widen. Comparing with control group, the level of MDA in the hippocampal region group was significantly higher (P < 0.05) and the activity of SOD significantly was lower (P < 0.05) in 5%IH, along with the time expand, which aggravated. CONCLUSION: Severe intermittent hypoxia that results in learning and memory dysfunction. It is possible that oxidative stress change the quantity and structure of hippocampal neurons and synaptic, which aggravates along with the intermittent low oxygen time expand.

[Hepatic injury in rats exposed to chronic intermittent hypoxia and the effect of tempol].

OBJECTIVE: To investigate the mechanism of liver injury in rats exposed to chronic intermittent hypoxia (CIH) and to investigate the effect of tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl or 4-hydroxy-TEMPO). METHODS: A CIH animal model of rats was established to mimic the intermittent hypoxia/re-oxygenation (IH/ROX) of obstructive sleep apnea syndrome in humans. Thirty-two healthy male Wistar rats were randomly assigned to 4 groups: conventional intermittent hypoxia group (CIH group), intermittent hypoxia Tempol treatment group (CIH + T group), intermittent hypoxia normal saline matched group (CIH + NS group), and normoxic control group (NC group), with 8 rats in each group. The frequency of every CIH group was 30 times/h, and the minimum oxygen concentration was 5%. After the experiment, sections of liver were stained with hematoxylin-eosin (HE) and the levels of nuclear factor-kappaB (NF-κB), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) in rat liver homogenate were measured. RESULTS: Liver histology revealed that the CIH group and the CIH + NS group showed hepatocellular swelling with rarefaction of the cytoplasm, hyperchromatosis and hepatocellular membrane disruption, but the liver histology of the CIH + T group and the NC group was normal. Compared with the NC group, the levels of NF-κB and MDA in the CIH group [(12.4 ± 2.0) ng/g, (101 ± 22) µmol/g] and the CIH + NS group [(12.2 ± 1.9) ng/g, (99 ± 18)µmol/g] were increased (all P < 0.05), but the activities of GSH-PX [(88 ± 17) U/mg, (90 ± 15) U/mg] were decreased (all P < 0.05). Compared with the CIH + NS group and the CIH group, the activity of GSH-PX in the CIH + T group [(181 ± 29) U/mg] was increased (P < 0.05), but the levels of NF-κB [(7.8 ± 1.3) ng/g] and MDA [(59 ± 10) µmol/g] were decreased (all P < 0.05). The levels of GSH-PX and MDA in the CIH + T group were not significantly different compared to the NC group (P were 0.242, 0.177 respectively), but the level of NF-κB in the CIH + T group was higher than that in the NC group (P < 0.05). The levels of NF-κB, GSH-PX, and MDA in the CIH + NS group were not significantly different as compared to those in the CIH group (all P > 0.05). The level of NF-κB was correlated negatively with GSH-PX, but positively with MDA (r = -0.754, 0.689, respectively, all P < 0.01) CONCLUSIONS: CIH could cause rat liver injury through oxidative stress and activating the proinflammatory transcription factors of NF-κB. Tempol could prevent CIH-induced liver injury through scavenging ROS by its anti-oxidative effect.

The level of carbon dioxide is the determinant of successful noninvasive ventilation pressure titration in patients with nonhypercapnic primary central sleep apnea: a case report.

Primary central sleep apnea is classified as nonhypercapnic central sleep apnea. High loop gain, lower CO2 reserves, and other reasons can lead to hypocapnia in patients who develop intermittent hyperventilation during sleep. Therefore, it is necessary to monitor nocturnal CO2 level for these patients. We report a female patient diagnosed with nonhypercapnic primary central sleep apnea who complained of snoring, apnea, and excessive daytime sleepiness. With the monitoring of transcutaneous partial pressure of CO2, manual noninvasive ventilation pressure titration was performed with continuous positive airway pressure, bilevel positive airway pressure in a spontaneous-timed mode, and adaptive servo-ventilation mode for 3 nights, respectively. Only adaptive servo-ventilation mode could stabilize the transcutaneous partial pressure of CO2 above the apneic threshold (approximately 40 mm Hg) with successfully eliminating central apnea events. It is concluded that the level of CO2 is the determinant of successful noninvasive ventilation pressure titration in patients with nonhypercapnic central sleep apnea. CITATION: Han X, Zhao D, Wang J, Wang Y, Dong L, Chen B-y. The level of carbon dioxide is the determinant of successful noninvasive ventilation pressure titration in patients with nonhypercapnic primary central sleep apnea: a case report. J Clin Sleep Med. 2022;18(1):319-324.

An experimental research on chronic intermittent hypoxia leading to liver injury.

PURPOSE: Sleep apnea-hypopnea syndrome and its chronic intermittent hypoxia component may cause multi-system-targeted injury. The latest finding shows that liver is one of the injured organs. The purpose of the study is to observe the dynamic process of the influence that chronic intermittent hypoxia plays on rat liver enzyme, hepatic histology, and ultrastructure based on lipid disorders. METHODS: A total of 72 male Wistar rats were randomly divided into three groups. The control group was fed with a regular chow diet, the high fat group with a high fat diet, and the high fat plus intermittent hypoxia group with a high fat diet with a 7-h/day intermittent hypoxia treatment. Changes were observed in rat liver enzyme, hepatic histology, and ultrastructure of the three groups on the third, sixth, and ninth weeks, respectively. The liver paraffin sections were detected with myeloperoxidase. RESULTS: The liver function and structure of the control group were found to be normal; the liver enzyme level of the high fat group was significantly higher than that of the control group on the sixth and ninth weeks; and the liver enzyme level of the high fat plus intermittent hypoxia group was significantly higher than that of the control group and the high fat group on the third, sixth, and ninth weeks (all P < 0.01). Observed by a light microscope and a transmission electron microscope, the high fat group and the high fat plus intermittent hypoxia group were all characterized by nonalcoholic fatty liver disease: the high fat group was characterized by simple fatty liver on the third and sixth weeks and by steatohepatitis on the ninth week; the damage of the high fat plus intermittent hypoxia group was significantly more severe than that of the high fat group in all the monitoring points, characterized by steatohepatitis on the sixth week and by obvious liver fibrosis on the ninth week; the myeloperoxidase level of the high fat plus intermittent hypoxia group was significantly higher than that of the control group and the high fat group (all P < 0.01). CONCLUSIONS: Under the conditions of high fat and intermittent hypoxia, the injury to the liver function, hepatic histology, and ultrastructure is more severe than that of the high fat group. The injury mainly was characterized by nonalcoholic fatty liver disease and becomes more severe with increased exposure time. Oxidative stress may play an important role in the mechanism.

[The effect of intermittent hypoxia with different degrees and frequencies on levels of superoxide dismutases and malondialdehyde in vascular endothelial cells].

OBJECTIVE: To investigate the effect of degree and frequency of intermittent hypoxia on level of superoxide dismutase (SOD) and malondialdehyde (MDA) in vascular endothelial cell. METHODS: We used umbilical vein endothelial cell ECV304 to set up cell model. The experiment cell strains contained one control group and eight experimental groups. We exposed cells by 3 different degree and 5 different frequency intermittent hypoxia gas separately as experimental groups, and the cells exposed to normal air as a control group. We determined levels of SOD and MDA by the way of ELISA in cytoblastema. RESULTS: The level of MDA of three different degree intermittent hypoxia groups were higher than the level in the control group (P < 0.01). The level of SOD in three different degree hypoxia groups is lower than the level in the group (P < 0.01). The level of SOD was decreased and the level of MDA was increased gradually with the decreasing of hypoxia degree (P < 0.01). There is a trend as the level of MDA and SOD increased and decreased with frequency decreased. The level of MDA was no different between the group of frequency in 40 per hour and 20 per hour (P > 0.05). When hypoxia frequency decreased, the level of MDA increased, and the level of 9.2 per hour exposure group was the lowest, but the level of MDA decreased again when the frequency was reaching 6.3 per hour (P < 0.01). When hypoxia frequency decreased, the level of SOD decreased, and the level of 9.2 per hour group was the highest, but the level of SOD decreased again if the hypoxia frequency was reaching 6.3 per hour (P < 0.01). The level of SOD was negative correlated to that of MDA under different hypoxia degree exposure (r = 0.932, P = 0.000), and the level of SOD was negative correlated to that of MDA under different frequency exposure (r = 0.832, P = 0.000). CONCLUSION: The intermittent hypoxia activates oxidative stress reaction in endothelial cells, and that induces the increasing of reactive oxygen species, and the antioxygen capacity become weaker. The decreasing and increasing of oxidative stress reaction depends on the degree of hypoxia and, is correlated to the frequency of hypoxia. Exposed to intermittent hypoxia, the balance of oxidative stress reaction and antioxygenative system of endothelial cell was disturbed.

[Study on hypoxemia during sleep in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the influence of hypoxemia during sleep on elements of polysomnography (PSG) in patients with chronic obstructive pulmonary disease (COPD) and the correlation of sleep hypoxemia and arterial blood gases, pulmonary function in daytime. METHODS: Two hundred and four moderate to very severe stable COPD patients with an age range of 40-75 years [mean age was (70.41+/-7.84) years ] were admitted. All patients underwent overnight PSG, and percentage of the time with oxygen saturation below 0.90 and total sleep time (T90)>or=5% was taken as nocturnal oxygen desaturation (NOD), and if not, they were non-NOD. Arterial blood gases, lung function and PSG examinations were performed in all patients. RESULTS: Ninety-five patients (46.57%) had NOD were enrolled. Compared with patients of non-NOD, both daytime oxygen saturation (SaO2, 0.90+/-0.04 vs. 0.94+/-0.01) and nocturnal mean SaO2 (MSaO2, 0.83+/-0.08 vs. 0.93+/-0.02) in NOD were lower significantly (both P<0.01). Sleep-related elements such as awake period (minutes: 97.86+/-41.74 vs. 76.13+/-55.15), awake frequency (times: 31.50+/-15.69 vs. 23.23+/-19.81), mean heart rate (beat per min: 80.80+/-12.80 vs. 66.21+/-6.53), sleep components [(S1+S2)%: (74.36+/-16.52)% vs. (67.55+/-12.62)%, (S3+S4)%: (12.99+/-12.18)% vs. (19.35+/-12.71)%] in NOD were significantly different from non-NOD (all P<0.01). The levels of arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of oxygen (PaO2), percentage of forced expiratory volume in one second (FEV1) and anticipate value, percentage of forced vital capacity (FVC) and anticipate value, percentage of FEV1/FVC and anticipate value in daytime were respectively correlated with the T90, MSaO2 and minimum SaO2 (miniSaO2) in sleep. Among these measurements, PaCO2 was best correlated with sleep hypoxemia (r1=0.767, r2=-0.758, r3=-0.689, all P<0.01). CONCLUSION: Sleep hypoxemia existed generally in patients with moderate to very severe stable COPD. There was significant difference in nocturnal SaO2, daytime SaO2 and sleep-related elements between NOD and non-NOD. The measurements in daytime are correlated with sleep hypoxemia, and some of them may predict sleep hypoxemia.

Treatment-emergent central sleep apnea: a unique sleep-disordered breathing.

Treatment-emergent central sleep apnea (TECSA) is a specific form of sleep-disordered breathing, characterized by the emergence or persistence of central apneas during treatment for obstructive sleep apnea. The purpose of this review was to summarize the definition, epidemiology, potential mechanisms, clinical characteristics, and treatment of TECSA. We searched for relevant articles up to January 31, 2020, in the PubMed database. The prevalence of TECSA varied widely in different studies. The potential mechanisms leading to TECSA included ventilatory control instability, low arousal threshold, activation of lung stretch receptors, and prolonged circulation time. TECSA may be a self-limited disorder in some patients and could be resolved spontaneously over time with ongoing treatment of continuous positive airway pressure (CPAP). However, central apneas persist even with the regular CPAP therapy in some patients, and new treatment approaches such as adaptive servo-ventilation may be necessary. We concluded that several questions regarding TECSA remain, despite the findings of many studies, and it is necessary to carry out large surveys with basic scientific design and clinical trials for TECSA to clarify these irregularities. Further, it will be vital to evaluate the baseline demographic and polysomnographic data of TECSA patients more carefully and comprehensively.

Slow-wave sleep is associated with incident hypertension in patients with obstructive sleep apnea: a cross-sectional study.

OBJECTIVE: This study aimed to examine the association between slow-wave sleep ([SWS] N3 stage) and the risk of hypertension in patients with obstructive sleep apnea (OSA) or primary snorers. METHODS: A retrospective cross-sectional study of 1145 participants who were evaluated for suspected OSA at our Sleep Medical Center were included. Among these participants, 1022 had OSA and 123 were primary snorers. Logistic regression modeling was performed to evaluate the association between the prevalence of hypertension and combined OSA and SWS based on polysomnographic measurements. RESULTS: Patients with OSA in the lowest SWS quartile (quartile 1, < 2.0%) showed a two-fold increased risk of hypertension after adjustment for confounding factors compared with primary snorers (odds ratio, 2.13 [95% confidence interval 1.54-2.06]). In logistic analysis stratified according to SWS quartiles, there was no significant difference in the risk of hypertension between patients with OSA and primary snorers in quartile 1. However, in the highest quartile (quartile 4), SWS was significantly associated with incident hypertension in patients with OSA rather than primary snorers. CONCLUSION: SWS is associated with prevalent hypertension in patients with OSA. Notably, a low proportion of SWS confers a stronger association with incident hypertension than OSA.