Treatment-emergent central sleep apnea: a unique sleep-disordered breathing / 中华医学杂志(英文版)

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.

Hippocampal impairments are associated with intermittent hypoxia of obstructive sleep apnea / 中华医学杂志(英文版)

Obstructive sleep apnea (OSA), which is the most common sleep-related breathing disorder, is characterized as frequent upper airway collapse and obstruction. It is a treatable disorder but if left untreated is associated with complications in several organ systems. The health risk to OSA patients shows a strong association with acute cardiovascular events, and with chronic conditions. To the central nervous system, OSA causes behavioral and neuropsychologic deficits including daytime sleepiness, depression, impaired memory, mood disorders, cognition deficiencies, language comprehension and expression deficiencies, all of which are compatible with impaired hippocampal function. Furthermore, there exists a significant correlation between disease severity and cognitive deficits in OSA. Children with severe OSA have significantly lower intelligence quotient (IQ) and executive control functions compared to normal children matched for age, gender and ethnicity. This corroborates the findings of several pediatric studies of cognition in childhood OSA, where deficits are reported in general intelligence and some measures of executive function. In studies of OSA, it is difficult to differentiate the effects of its two main pathologic traits, intermittent hypoxia (IH) and sleep fragmentation. Many OSA studies, utilize IH as the only exposure factor in OSA studies. These approaches simplify research process and attain most of the academic goals. IH, continuous hypoxia and intermittent continuous hypoxia can all result in decreases in arterial O2. There are striking differences to them in the response of physiological systems. There are multiple studies showing that IH treatment in a rodent model of OSA can impair performance of standard water maze tests associated with deficits in spatial learning and memory which most likely are hippocampal-dependent. Cellular damage to the hippocampal cornuammonis 1 (CA1) region likely contributes to neuropsychological impairment among OSA patients, since neural circuits in the hippocampus are important in learning and memory. In this article, studies of hippocampal impairments from IH are reviewed for elucidating the mechanisms and relationships between hippocampal impairments and IH of OSA.

Elevated nocturnal and morning blood pressure in patients with obstructive sleep apnea syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The nocturnal nondipping and elevated morning blood pressure (BP) in patients with obstructive sleep apnea syndrome (OSAS) have not yet been well investigated in Chinese patients. This study aimed to describe the BP profile, and to elucidate the relationships between daytime BP and nighttime BP, and between evening BP and morning BP in patients with OSAS.</p><p><b>METHODS</b>Twenty teaching hospital sleep centers in China were organized by the Chinese Medical Association to participate in this study and 2297 patients were recruited between January 2004 and April 2006. BP assessments were made at four time points (daytime, evening, nighttime and morning) and polysomnography (PSG) was performed and subjects were classified into four groups by their apnea-hypopnea index (AHI): control, n = 213 with AHI < 5; mild, n = 420 with AHI ≥ 5 and < 15; moderate, n = 460 with AHI ≥ 15 and < 30; and severe, n = 1204 with AHI ≥ 30. SPSS 11.5 software package was used for statistical analysis and figure drawing.</p><p><b>RESULTS</b>All the average daytime, nighttime, evening and morning BPs were positively correlated with AHI and negatively correlated with nadir nocturnal oxygen saturation. The ratios of nighttime/daytime and morning/evening average BP were positively correlated with AHI. The ratio of nighttime/daytime systolic BP became a "reversed BP dipping" pattern until the classification reached severe, while the ratio of nighttime/daytime diastolic BP became reversed at moderate. Similarly, the ratio of morning/evening diastolic BP becomes reversed even at mild.</p><p><b>CONCLUSIONS</b>OSAS may result in higher BP levels at all four time points. The ratios of nighttime/daytime and morning/evening BP increase with increased AHI. The increasing of diastolic BP, which is inclined to rise more quickly, is not parallel with increasing systolic BP.</p>

Influence of different degrees of chronic intermittent hypoxia on c-fos protein and apoptosis in rats / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To establish different degrees and duration of animal hypoxia model of sleep apnea hypopnea syndrome according to the mechanism of intermittent hypoxia, to observe the effect of c-fos protein and apoptosis, and to explore the mechanism of nervous system injury.</p><p><b>METHODS</b>By using the model of chronic intermittent hypoxia in rats, male Wistar rats (n = 72) were randomly divided into three groups: 5% of chronic intermittent hypoxia group (the fraction of oxygen volume reduced to 5% under hypoxia), 10% of chronic intermittent hypoxia group (the fraction of oxygen volume reduced to 5% under hypoxia) and control group. The levels of on c-fos protein and apoptosis of hippocampal cell in three groups were detected at the 2nd, 4th, 6th and 8th week respectively. The expression of c-fos protein in hippocampal cell was detected by immunohistochemical method and the apoptosis of hippocampal cell was detected by TUNEL.</p><p><b>RESULTS</b>The relative quantity of c-fos protein and apoptotic index in CIH groups were significantly higher than that of the control group on the 2nd, 4th, 6th and 8th weeks (F were 44.52, 57.56, 24.20 and 13.18, P < 0.05), and these were higher obviously in 5% CIH group than that in 10% CIH group (P < 0.05). The expression of c-fos protein and apoptotic index in two CIH groups was different depending upon the different degree and duration of chronic intermittent hypoxia. With increased exposure time, the expression of c-fos protein and apoptotic index was high generally at first, peaked at 6th week, then down at 8th week (P < 0.05). While it in UC group was invariability in different time (P > 0.05). The correlation between the relative quantity of c-fos protein and apoptotic index in two CIH groups was positive (r were 0.816 and 0.701, P < 0.01).</p><p><b>CONCLUSION</b>Moderate and severe intermittent hypoxia induced the excessive expression of c-fos protein in hippocampus, caused nerve cell apoptosis, and may play an important role in the mechanism of early brain injury of intermittent hypoxia.</p>

Sleep-related hypoxemia aggravates systematic inflammation in emphysematous rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Sleep disturbance is common in patients with emphysema. This study aimed to develop a novel model of sleep-related hypoxemia (SRH) in emphysema (SRHIE) with rats, and to explore the inflammatory status of SRHIE in lung, liver, pancreas, carotid artery and whole blood.</p><p><b>METHODS</b>Seventy-five male Wistar rats were assigned to 5 groups with 15 per group according to the exposure conditions. The protocols varied with the degree of hypoxia exposure and severity of pre-existing emphysema caused by cigarette smoke exposure: (1) SRH control (SRHCtrl) group, sham smoke exposure (smoke exposure, exposed to smoke of 15 cigarettes twice everyday, 16 weeks) and SRH exposure (12.5% O2, 3 hours, SRH exposure, divide total hypoxia time (1.5 hours or 3 hours) into 4 periods evenly (22.5 minutes or 45 minutes) and distribute these hypoxia periods evenly into physiological sleep time of rats identified by electroencephalogram, week 9 to week 16); (2) Emphysema control (ECtrl) group, smoke exposure and sham SRH exposure (21% O2, 3 hours); (3) Short SRH in emphysema (SRHShort) group, smoke exposure and short SRH exposure (12.5% O2, 1.5 hours); (4) Mild SRH in emphysema (SRHMild) group, smoke exposure and mild SRH exposure (15% O2, 3 hours); (5) Standard SRH in emphysema (SRHStand) group, smoke exposure and SRH exposure (12.5% O2, 3 hours). ECtrl, SRHShort, SRHMild and SRHStand groups were groups with emphysematous rats. Two days before the end of exposure, 5 rats in each group were randomly selected for arterial blood gas analysis. In the rest 10 rats in each group, we obtained blood samples and bronchoalveolar lavage fluid (BALF) for routine tests. We also obtained tissue blocks of lung, liver, pancreas, and right carotid artery for pathologic scoring and measurements of liver oxidative stress (measuring hepatic oxidative stress enzymes, superoxide dismutase (SOD) activity, catalase (CAT) activity and malondialdehyde (MDA) concentration).</p><p><b>RESULTS</b>Emphysematous groups had higher mean linear intercept (MLI) and mean alveolar number (MAN) values than SRHCtrl group. MLI values in SRHStand group were the highest (all P < 0.05). O2Sat in SRHStand rats when SRH exposure was (83.45 ± 1.76)%. Histological scores of lung, liver, pancreas and right carotid artery were higher in emphysematous groups than SRHCtrl group, and SRHStand group were the highest (all P < 0.05) (SOD and CAT values were lower and MDA values were higher in groups with emphysema than without and in SRHStand group than in ECtrl group (all P < 0.05)). MDA values were the highest in SRHStand group (all P < 0.05). Total cellular score in BALF and White blood cell (WBC) in whole blood were the highest in SRHStand group (all P < 0.05). Lymphocyte ratios were the highest in SRHStand group both in BALF and blood (all P < 0.05). Red blood cell (RBC) and hemoglobin in emphysematous groups were higher than that in SRHCtrl group, and SRHStand group were higher than ECtrl group (all P < 0.05).</p><p><b>CONCLUSIONS</b>With a proper novo model of SRHIE with Wistar rats, we have demonstrated SRH may aggravate the degree of emphysematous changes, polycythemia, oxidative stress and systematic inflammation. SRH and emphysema may have a synergistic action in causing systematic damages, and lymphocyte may be playing a central role in this process. Longer duration and more severe extent of SRHIE exposure also seem to result in more serious systematic damages. The mechanisms of all these concerned processes remain to be studied.</p>

Effect of different intermittent hypoxia patterns on interleukin-6 and interleukin-8 levels of human umbilical vein endothelial cells / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of different patterns of intermittent hypoxia on the levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) of vascular endothelial cell.</p><p><b>METHODS</b>The human umbilical vein endothelial cells of the line ECV304 were used to set up the cells model. The experiment cell strains contained one control group and eight experimental groups, 1 constance normoxia group (control group), 3 different intermittent hypoxia (IH) degree groups (10% O₂ group, 1.5% O₂ group, 0.5% O₂ group with 12 times/h), 4 different IH frequency groups (40 times/h, 20 times/h, 12 times/h, 9 times/h and 6 times/h with 0.5%O2). The specimen were put into a program-controlled gas delivery system with different level and frequency of IH respectively. Then enzyme linked immunosorbent assay (ELISA) was used to examine the levels of IL-6 and IL-8.</p><p><b>RESULTS</b>Higher level of IL-6 and IL-8 were found in 3 different IH degree groups than in control group (F were 1961.100 and 103.855 respectively, P all < 0.001). The level of IL-6 and IL-8 was gradually increased with the decreasing of IH degree. The difference of IL-6 and IL-8 levels between each two different groups in IH degree was significant (P all < 0.05). The level of IL-6 and IL-8 groups was significantly different in severe IH exposure (F were 544.396 and 149.328 respectively, P all < 0.001 in both groups). There was a trend as the IH frequency decreased, the level of IL-6 and IL-8 was tenderly increased in 20/hour group (P < 0.05), highest in 12/hour group (P < 0.05), decreased in 9/hour group (P < 0.05), and decreased further in 6/hour group (P < 0.05) in severe IH expose. There was statistical significance between each two different frequency IH groups (P < 0.05).</p><p><b>CONCLUSIONS</b>Intermittent hypoxia caused significant inflammatory reaction in vascular endothelial cells. The secreted level of IL-6 and IL-8 depended on the degree of hypoxia. There was a trend as the level of IH frequency decreased, the level of IL-6 and IL-8 gradually increased at first, and then decreased in the same way.</p>

Sleep apnea hypopnea syndrome and liver injury / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>A general review was made of studies involving: (1) the relationship between sleep apnea hypopnea syndrome/sleep apnea style intermittent hypoxia and liver injury and (2) the mechanism that causes the liver injury.</p><p><b>DATA SOURCES</b>The data used in this review were mainly from Medline and PubMed published in English from 1993 to February 2009. The search term was "sleep apnea hypopnea syndrome".</p><p><b>STUDY SELECTION</b>(1) Clinical and laboratory evidence that sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia leads to liver injury; (2) the mechanism that causes the liver injury.</p><p><b>RESULTS</b>The effect of sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia on the liver function is characterized by serum aminotransferase elevation. The liver histological injury includes hepatic steatosis, hepatocyte ballooning, lobular inflammation, lobular necrosis, and liver fibrosis. Sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia can cause insulin resistance and oxidative stress.</p><p><b>CONCLUSIONS</b>Sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia can lead to chronic liver injury, which, in most cases, is shown as nonalcoholic fatty liver disease. Insulin resistance and oxidative stress caused by sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia play an important role in the mechanism of chronic liver disease development.</p>

Relationship of daytime blood pressure and severity of obstructive sleep apnea among Chinese: a multi-center investigation in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Epidemiologic studies have shown an independent and definite association between obstructive sleep apnea (OSA) and hypertension. This study aimed to define the association between daytime blood pressure and severity of OSA in Chinese population in mainland of China.</p><p><b>METHODS</b>Twenty university hospital sleep centers in mainland of China were invited by the Chinese Medical Association (CMA) to participate in this epidemiologic study and 2297 consecutive patients (aged 18 - 85 years; 1981 males and 316 females) referred to these twenty sleep centers for evaluation of OSA between January 2004 and April 2006 were prospectively enrolled. Nocturnal polysomnography was performed in each patient, and disease severity was assessed based on the apneahypopnea index (AHI). These patients were classfied into four groups: nonapneic control (control, n = 257) with AHI < or = 5 episodes/hour; mild sleep apnea (mild, n = 402) with AHI > 5 and < or = 15 episodes/hour; moderate sleep apnea (moderate, n = 460) with AHI > 15 and < or = 30 episodes/hour and severe sleep apnea (severe, n = 1178) with AHI > 30 episodes/hour. Daytime blood pressure measurements were performed under standardized conditions in each patient at 10 a.m. in office on the day of referring to sleep centers for getting average value. All the patients were requested to quit medications related to blood pressure for three days before the day of assessing.</p><p><b>RESULTS</b>Both daytime systolic blood pressure and diastolic blood pressure values were significantly related to AHI positively (r = 0.201 and 0.276, respectively; both P values < 0.001) and to nadir nocturnal oxygen saturation negatively (r = -0.215 and -0.277, respectively; both P values < 0.001), which were the parameters of OSA severity. In two special designed mean plots, means of daytime systolic and diastolic blood pressure increased gradually with increasing AHI. Beyond AHI of 61 - 65, this increasing trend reached a plateau.</p><p><b>CONCLUSIONS</b>The results showed that OSA severity was associated with daytime blood pressure until AHI of 61 - 65, providing evidence for early OSA management, especially in OSA patients with concomitant hypertension.</p>

Asymptomatic patients of chronic obstructive pulmonary disease in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chronic obstructive pulmonary disease (COPD) has a variable natural history and not all individuals follow the same course. This study aimed to identify the prevalence and characteristics of asymptomatic COPD patients from a population-based survey in China.</p><p><b>METHODS</b>A multistage cluster sampling strategy was used in a population from seven different provinces/cities. All residents (over 40 years old) were interviewed with a standardized questionnaire and spirometry. Post-bronchodilator forced expiratory volume in 1 second (FEV(1))/forced vital capacity (FVC) of less than 70% was defined as the diagnostic criterion of COPD. All COPD patients screened were divided into symptomatic group and asymptomatic group according to the presence or absence of chronic respiratory symptoms. Socio-demographic, personal and exposure variables were collected and analyzed.</p><p><b>RESULTS</b>Among the 1668 patients who were diagnosed with COPD from the 25 627 sampling subjects, 589 (35.3%) were asymptomatic. The age, sex, body mass index (BMI), rural and urban distributions, smoking habit and education levels were similar in the two groups. A total of 64.7% of the asymptomatic patients had no comorbidities. Cardiovascular diseases and lung cancer were more common among symptomatic COPD patients than asymptomatic group. Asymptomatic COPD group were less likely to present with poor ventilation in the kitchen, a family history of respiratory disease and recurrent childhood cough. Asymptomatic COPD patients had significantly higher FEV(1) (73.1% vs. 61.0%), FVC (91.9% vs. 82.0%), and a higher ratio of FEV(1)/FVC (62.9% vs. 58.7%) (all P < 0.001) than symptomatic group. More asymptomatic patients were underdiagnosed (91.9% vs. 54.3%, P < 0.001) than symptomatic patients.</p><p><b>CONCLUSIONS</b>This large population-based survey confirmed a high prevalence of asymptomatic COPD patients in China. More use of spirometry screening test may be important to the early detection of COPD.</p>

An epidemiological study on chronic obstructive pulmonary disease in a rural area of Tianjin / 中华全科医师杂志

Objective To understand epidemiological characteristics of chronic obstructive pulmonary disease(COPD)in people aged over 40 years in a rural area of Tianjin.Methods Using cluster sampling,1 508 subjects over 40 years old at five villages in Xinkaikou Township,Baodi District,Tianjin were investigated with respiratory questionnaire,lung function test and physical examination.Confirmed patients with COPD were examined by chest roentgenography and electrocardiography.Results One hundred and forty-two subjects in that area suffered from COPD,with prevalence of 9.4%,24 of them (16.9%)were diagnosed as cor pulmonale.Prevalence of COPD increased with age,higher in men (13.5%)than that in women(6.2%),higher in smokers(12.2%)than that in non-smokers(7.2%), higher in those with family history(21.4%)than that in those without it(8.45%),and higher in those with coughing history during their childhood(75.0%)than that in those without it(9.2%),all with a P-value of less than 0.01.Univariate analysis showed that out-door air pollution,cooking,time length of burning firewood during cooking,smoking,coughing history during childhood,gender,age,family history all were predisposing factors for COPD.Multivariate analysis with logistic regression model showed that gender,age, family history were independently predisposing factors for COPD.Quality of life was better in non-COPD subjects than in those with COPD,with statistically significant difference.Conclusions Prevalence of COPD was relatively higher in people of rural Tianjin,with gender,age,family history and outdoor air pollution as main risk factors.

A study on the respiratory mechanics and inflammatory status in elderly patients with stable chronic obstructive pulmonary diseases / 中华老年医学杂志

Objective To evaluate the respiratory mechanics and inflammatory status in elderly patients with stable chronic obstructive pulmonary diseases (COPD).Methods The arterial blood gases (ABGs),respiratory drive and its derivatives,mechanics of respiratory muscles,resistance and compliance of airway,interleukin-8 (IL-8)and interferon-?(IFN-?)were measured in 42 cases withstable COPD and 40 subjects of normal control.Results The elderly patients with stable COPD had great changes in the following parameters while compared with the control group:peak inspiratory pressure(PIMAX) [(4.48?2.11)vs(6.10?2.91)kPa],maximum expiratory pressure (PEMAX)[(6.30?3.20)vs(9.15?93.30)kPa],0.1s mouth occlusion pressure(P_(0.1)) with its correction index,airway resistance,compliance,ABGs,the levels of IL-8[(218.46?91.14) vs (161.84?14.40)ng/L]and IFN-?[(2435.82?639.92)vs(1652.40?95.08)ng/L],which might aggravate the progress of COPD consistently.Conclusions The elderly patiends with stable COPD has marked changes in respiratory drive,airway resistance,and airway compliance,respiratory mechanic and inflammatory status.The intervention should be performed in the elderly stable COPD patients.