HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy.

Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1(∗)01:02-DQB1(∗)06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known triggering factor for narcolepsy is pandemic 2009 influenza H1N1, suggesting autoimmunity triggered by upper-airway infections. Additional effects of other HLA-DQ alleles have been reported consistently across multiple ethnic groups. Using over 3,000 case and 10,000 control individuals of European and Chinese background, we examined the effects of other HLA loci. After careful matching of HLA-DR and HLA-DQ in case and control individuals, we found strong protective effects of HLA-DPA1(∗)01:03-DPB1(∗)04:02 (DP0402; odds ratio [OR] = 0.51 [0.38-0.67], p = 1.01 × 10(-6)) and HLA-DPA1(∗)01:03-DPB1(∗)04:01 (DP0401; OR = 0.61 [0.47-0.80], p = 2.07 × 10(-4)) and predisposing effects of HLA-DPB1(∗)05:01 in Asians (OR = 1.76 [1.34-2.31], p = 4.71 × 10(-05)). Similar effects were found by conditional analysis controlling for HLA-DR and HLA-DQ with DP0402 (OR = 0.45 [0.38-0.55] p = 8.99 × 10(-17)) and DP0501 (OR = 1.38 [1.18-1.61], p = 7.11 × 10(-5)). HLA-class-II-independent associations with HLA-A(∗)11:01 (OR = 1.32 [1.13-1.54], p = 4.92 × 10(-4)), HLA-B(∗)35:03 (OR = 1.96 [1.41-2.70], p = 5.14 × 10(-5)), and HLA-B(∗)51:01 (OR = 1.49 [1.25-1.78], p = 1.09 × 10(-5)) were also seen across ethnic groups in the HLA class I region. These effects might reflect modulation of autoimmunity or indirect effects of HLA class I and HLA-DP alleles on response to viral infections such as that of influenza.

Genome wide analysis of narcolepsy in China implicates novel immune loci and reveals changes in association prior to versus after the 2009 H1N1 influenza pandemic.

Previous studies in narcolepsy, an autoimmune disorder affecting hypocretin (orexin) neurons and recently associated with H1N1 influenza, have demonstrated significant associations with five loci. Using a well-characterized Chinese cohort, we refined known associations in TRA@ and P2RY11-DNMT1 and identified new associations in the TCR beta (TRB@; rs9648789 max P = 3.7 × 10(-9) OR 0.77), ZNF365 (rs10995245 max P = 1.2 × 10(-11) OR 1.23), and IL10RB-IFNAR1 loci (rs2252931 max P = 2.2 × 10(-9) OR 0.75). Variants in the Human Leukocyte Antigen (HLA)- DQ region were associated with age of onset (rs7744020 P = 7.9×10(-9) beta -1.9 years) and varied significantly among cases with onset after the 2009 H1N1 influenza pandemic compared to previous years (rs9271117 P = 7.8 × 10(-10) OR 0.57). These reflected an association of DQB1*03:01 with earlier onset and decreased DQB1*06:02 homozygosity following 2009. Our results illustrate how genetic association can change in the presence of new environmental challenges and suggest that the monitoring of genetic architecture over time may help reveal the appearance of novel triggers for autoimmune diseases.

[Effects of wearing dentures on sleep breathing among edentulous people: a preliminary study].

OBJECTIVE: To investigate the effects of wearing dentures on sleep breathing among edentulous people. METHODS: Nine edentulous people were recruited to participate in this selfcontrolled case series clinical study. Polysomnogram (PSG) was carried out on two consecutive nights, on one night the patients slept wearing dentures, and on the other without dentures. The indexes such as apnea and hypopnea index (AHI), L-SpO2, and morning blood pressure etc. were compared. RESULTS: Among the nine edentulous people, eight showed a higher AHI when they slept with dentures, and only one showed a lower AHI. The average AHI of the nine edentulous people was 8.82 without dentures and 11.72 with dentures, which meant that AHI was significantly higher when the edentulous people slept with dentures in their mouths (P<0.05). While no significant differences were found in the score of L-SpO2 and morning blood pressures (P>0.05). CONCLUSION: Wearing dentures might lead to an increase of AHI during sleep among edentulous people.

[Utility of portable monitoring device with airflow, oxygen saturation and respiratory effort in the diagnosis of sleep apnea hypopnea syndrome].

OBJECTIVE: To validate the values of monitoring airflow, oxygen saturation and respiratory effort in the diagnosis of sleep apnea-hypopnea syndrome (SAHS). METHODS: A total of 70 subjects with suspected SAHS underwent the tests of polysomnography (PSG) and portable monitoring device (PMD) separately at our sleep lab. The portable monitoring device recorded nasal airflow, oxygen saturation and respiratory effort. Apnea-hypopnea index (AHI) or respiratory disturbed index (RDI), lowest oxygen saturation (LSaO2), oxygen desaturation index (ODI4) and percentage of different types of sleep breathing events (central/obstructive/mixed hypopnea) accounting for the total numbers of sleep disordered breathing were also analyzed. The data of AHI and ODI4 showed skew distribution undergoing log transformation to approximate to normal distribution. Pair t test was used for the comparisons of different parameters. The agreement between two methods was analyzed by Bland-Altman plot. RESULTS: Fifty-eight subjects were diagnosed as SAHS with an AHI (RDI) over 5 on PSG. The sensitivity and specificity of portable monitoring device were 94.8% and 75.0% respectively. The mean AHI derived from PSG and RDI derived from PMD were (27 ± 25) and (29 ± 27) times per hour respectively and those after log transformation were (1.2 ± 0.5) and (1. 2 ± 0.5) times per hour (P = 0.411). The mean ODI4 derived from PSG and PMD were (23 ± 25) and (21 ± 24) and those after log transformation (0.9 ± 0.7) and (1.1 ± 0.5) times per hour respectively (P = 0.042). The mean values of LSaO2 were 79% ± 13% and 79% ± 12% respectively (P = 0.550). No significant differences existed between AHI derived from PSG and RDI derived from PMD. Bland-Altman plot also showed a high agreement between AHI derived from PSG and RDI derived from PMD. PMD could also identify major part of different events so as to aid clinical decision-making. CONCLUSION: Portable monitoring device recording airflow, oxygen saturation and respiratory effort shows a great agreement with PSG with regards to AHI (RDI) and the identification of different types of respiratory events.

[Value of cerebral spinal fluid measurement of hypocretin-1 in the diagnosis of Chinese patients with narcolepsy].

OBJECTIVE: To evaluate the diagnostic value of cerebral spinal fluid (CSF) measurement of hypocretin-1 (hcrt-1) in Chinese patients with narcolepsy. METHODS: A total of 139 narcoleptic patients, including 111 narcolepsy with typical cataplexy (NC) and 28 narcolepsy without cataplexy (NWC), were diagnosed at the sleep centre of Peking University People's Hospital from April 2003 to March 2012. And 64 non-narcoleptic controls were recruited. CSF hcrt-1 levels were measured in all subjects.Receiver operating characteristic curve (ROC) was applied to determine the cutoff value of hcrt-1 for Chinese narcoleptic patients. The diagnostic utility of hcrt-1 ≤ 110.0 ng/L and hcrt-1 ≤ 30% of mean normal level defined by International Classification of Sleep Disorders-II and the new Chinese cutoff value were evaluated respectively. RESULTS: The level of hcrt-1 in narcolepsy patients was significantly lower than that of normal controls and the NC group was even lower than NWC group (20 (13, 36) vs 319 (244, 379) and 36 (15, 114) ng/L) (all P < 0.01).Using the international criteria of CSF hcrt-1 ≤ 110.0 ng/L or a level of 1/3 of mean normal control values, a specificity of 100% and sensitivity of 90.6% were generated.ROC curve indicated that CSF hcrt-1 level of 138.0 ng/L was the best cutoff value for the diagnosis of narcolepsy in Chinese narcoleptic patients. There were a specificity of 100%, a sensitivity of 92.8% and the area under the ROC curve of 0.98. CONCLUSIONS: CSF hcrt-1 measurement with high specificity and sensitivity is a useful diagnostic tool for Chinese narcoleptics. And the level of 138.0 ng/L may be the optimal cutoff for the diagnosis of narcolepsy in this group of patients.

[Daytime hypercapnia in patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVES: To evaluate the incidence and factors related to daytime CO2 retention (PaCO2 ≥ 45 mm Hg, 1 mm Hg = 0.133 kPa) in Chinese patients with obstructive sleep apnea hypopnea syndrome. METHODS: 1441 patients with OSAHS had daytime arterial blood gas analysis were recruited from 2007 to 2009 in Peking University People's Hospital. 145 patients underwent pulmonary function test and had FEV1/FVC ratio over 70% were under further analysis. Sex, age, BMI, pulmonary function, polysomnography (PSG) and blood gas analysis results were recorded. Linear regression analysis was used to evaluate the relationship between PaCO2 levels and related parameters. Comparison was done between hypercanpnic and eucapnic patients. RESULTS: Daytime hypercapnia occurred in 25.2% of the 1441 patients with OSAHS, and 26.9% in the 145 OSAHS patients who had lung function test and with FEV1/FVC ratio over 70%. PaCO2 was correlated with BMI, PaO2 and the severity of nocturnal hypoxemia as reflected by the mean SpO2 and SIT90. This was also confirmed by the comparison between the hypercapnic and eucapnic patients. CONCLUSIONS: Hypercapnia occurs in a large part of patients with OSAHS and normal FEV1/FVC. BMI, nocturnal hypoxemia and daytime PaO2 level are all contributed to the development of daytime CO2 retention in OSAHS.

[A study on the differential diagnosis of ciliated epithelial cells from Lophomonas blattarum in bronchoalveolar lavage fluid].

OBJECTIVE: To validate the authenticity of the cases diagnosed as pulmonary Lophomonas blattarum infection in literatures and Lophomonas blattarum as a kind of pathogen resulting in pulmonary infection. METHODS: From June 2012 to May 2013, mobile cells with cilia at the anterior end of the cells were observed in BALF from 6 patients with pulmonary disease in our hospital. Morphological feature and ultrastructure of the cells were further investigated by optical microscope and electron microscope to determine the type of the cells referring to literature-published photos of Lophomonas blattarum. Literatures about Lophomonas blattarum infection were searched with keyword Lophomonas blattarum from Wanfang Data, China National Knowledge Infrastructure (CNKI) and PubMed. Diagnostic methods and figures provided by the literature were carefully reviewed, and the accuracy of diagnosis of pulmonary Lophomonas blattarum was identified. RESULTS: Mobile cells found in BALF from the 6 patients in our hospital had the morphological features of bronchial ciliate epithelial cells. A nucleus far from the cilia was observed in the middle or at the bottom of the cytoplasm, and these cells did not display the characteristic cytological structures of Lophomonas blattarum: calyx, perinuclear tubules and axial filament. Diagnosis of pulmonary Lophomonas blattarum reported in literatures so far were all based on the morphological features of mobile cells with a cluster of flagellate at anterior end of the cell by optical microscopy. None of the authors did further exploration on the ultrastructure of such a kind of cells and compared with features of Lophomonas blattarum described in the literature. All the active cells reported in literatures had the identical morphological features to those found in our investigation. CONCLUSION: In the past 20 years, all the diagnosed cases as pulmonary Lophomonas blattarum infection reported in our country were misdiagnosed. Currently, there is no evidence to show Lophomonas blattarum as a pathogen resulting in pulmonary infection.

Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy.

Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.

[Clinical features of respiratory failure and heart failure in patients with sleep disordered breathing].

OBJECTIVE: To assess the clinical characteristics of heart failure and respiratory failure in patients with sleep disordered breathing (SDB). METHODS: Symptoms, signs, laboratory tests, clinical courses, blood gases responses to voluntary hyperventilation test and non-invasive ventilation treatment were analyzed in 29 patients with SDB. All patients were diagnosed as right and left heart failure and respiratory failure from 1994 to 2009 in Peking University People's Hospital. RESULTS: Among the 29 patients recruited, 13 were male and 16 female. The mean age was 62 ± 13 yrs, and BMI was (34 ± 4) kg/m(2). Fourteen (48.3%) were diagnosed as obstructive sleep apnea syndrome at first visit. Chief complains includes dyspnea, edema, cough, snoring, hypersomnolence, oliguria, and altered mental status. Common signs include obesity, narrow upper airway, cyanosis, moist rales at the base of lungs, enlarged border of cardiac dullness, edema. Polycythemia was seen in 13 patients (44.80%), among the 26 patients who had underwent pulmonary function tests, 14 had FEV(1)/FVC ≥ 70%, the others were FEV(1)/FVC < 70%, with 6 patients had 50% predict value ≤ FEV(1) < 80% predict value and 6 patients had 30% predict value ≤ FEV(1) < 50% predict value. After positive airway pressure (BiPAP and CPAP) treatment, symptoms and arterial blood gases test results improved. Chest X-ray, CT scan and UCG show pulmonary vascular congestion and edema with cardiomegaly and possible pleural effusion, pulmonary hypertension, left ventricular diastolic dysfunction. Five patients underwent 24 h blood pressure monitoring showed non-dipping pattern or morning risen pattern of BP. In 11 patients who undertaken the test, voluntary hyperventilation induced significant improvement of SpO(2), PaCO(2) and PaO(2), and most of the parameters returned from type II respiratory failure to normal level. CONCLUSION: The morbidity of SDB remained to be recognized. This cases report indicated that obese patients complaining of severe dyspnea and edema may have respiratory failure and bilateral heart failure secondary to SDB. The respiratory failure can be completely reversed by voluntary hyperventilation, and noninvasive treatments only could achieve good outcomes in most of the patients.

Comparison of Ring Pulse Oximetry Using Reflective Photoplethysmography and PSG in the Detection of OSA in Chinese Adults: A Pilot Study.

Objective: A novel ring-worn oximeter (Circul) uses reflective photoplethysmography and automated signal processing to calculate oxygen desaturations. We evaluated the ability of Circul to detect obstructive sleep apnea in Chinese adults. Methods: We recruited 207 Chinese Han subjects: 70% males, mean age 48.2±14.7 years, mean BMI 27.6±4.8 kg/m2 and mean AHI 28.6±25.2 events/h. All participants underwent simultaneous polysomnography (PSG) and Circul testing in a sleep laboratory. Oxygen desaturation index (ODI), mean oxygen saturation (MSpO2), cumulative time at SpO2<90% (CT90), cumulative percentage of sleep time spent with SpO2<90% (CT90/TST) were derived and compared for the Circul and the PSG. Results: The ODI was 25.3±24.5 events/h using PSG and 22.2±24.5 events/h using Circul (P<0.0001), with an intraclass correlation coefficient (ICC) of 0.884. CT90 and CT90/TST between the two methods were not different; the MSpO2 level calculated by PSG was slightly lower than Circul, 95.0% (93.0-96.0%) vs 95.3% (93.9-96.6%), P<0.0001. Circul-ODI had a good correlation (r=0.91, p<0.0001) and close agreement with PSG-AHI (Bland-Altman analysis: Mean Difference 6.4, 95% CI -14.8 to 27.5 events/h). Using a threshold of AHI ≥5 events/h, the Circul had 87% sensitivity, 83% specificity, 5.09 positive likelihood ratio (LR+), 86% accuracy, and 0.929 area under the curve (AUC). Conclusion: Circul ring pulse oximetry can detect OSA with reasonable reliability. The Circul system is a reliable and comfortable choice for OSA assessment.

Screening for obstructive sleep apnea using a contact-free system compared with polysomnography.

STUDY OBJECTIVES: To evaluate the utility of a contact-free device in screening for obstructive sleep apnea. METHODS: Three hundred fifty-nine participants (mean age 46 ± 13 years, body mass index 26.1 ± 4.2 kg/m², 67.7% male) underwent overnight monitoring using a contact-free device, the OrbSense, and polysomnography (PSG) in the sleep laboratory simultaneously. The OrbSense recordings were analyzed automatically, and PSG was scored based on recommended guidelines. RESULTS: The respiratory event index from the OrbSense was lower than the apnea-hypopnea index (AHI) from PSG (25.5 ± 20.7 vs 27.0 ± 25.2 events/h; P = .007) and was significantly correlated with AHI (Pearson coefficient, 0.92; P < .0001). Bland-Altman analysis showed a mean difference of 1.5 events/h, and the limit of agreement was -18.6 to 21.5 events/h. Use of the OrbSense resulted in larger underestimates of AHI and lower negative predictive values at higher AHI values (especially when AHI ≥ 30 events/h). When we used a PSG diagnostic criterion of AHI > 5 events/h, the optimal diagnostic cutoff value from the OrbSense was 8 events/h, with a sensitivity of 90.4%, a specificity of 77.6%, a 94.6% positive predictive value, and a 65% negative predictive value. For patients with moderate to severe obstructive sleep apnea whose AHI was > 15 events/h, the OrbSense cutoff was 16.6 events/h, with a sensitivity of 87.1% and a specificity of 89.7%. Among the 359 participants, 250 patients (69.6%) had the same obstructive sleep apnea severity division classified by both PSG and the OrbSense. CONCLUSIONS: The contact-free device OrbSense can detect respiratory events during sleep and has close agreement with in-laboratory PSG in screening for obstructive sleep apnea. Further studies are warranted to test its utility in community-based settings and at home.

Treatment Effects of Short-Term Continuous Positive Airway Pressure on Blood Glucose Control in Type 2 Diabetic Patients with Obstructive Sleep Apnea Syndrome.

PURPOSE: The study aimed at assessing glucose control measured with a continuous glucose monitoring system (CGMS) before and after short-term continuous positive airway pressure (CPAP). MATERIALS AND METHODS: Twenty-four type 2 diabetic patients (T2DM) with Obstructive sleep apnea syndrome (OSAS) (mean age 55.0 ± 9.0 years; BMI 29.5 ± 5.2 kg/m2) were admitted and kept under diet control for 2 days, then underwent 2 overnight polysomnographies: a diagnostic study and one with CPAP titration. Then they were treated by CPAP during sleep for the following three nights. Participants were divided into subgroup D (only diet control) and subgroup M (with DM medication). CGMS was utilized over the last five days. Glucose control was also assessed with plasma insulin and a clinical measure of insulin resistance (HOMA-IR) index. RESULTS: The mean (±SD) apnea-hypopnea index (AHI) at diagnostic polysomnography was 51.2 ± 22.4 (range 10-88) events/h. CPAP treatment in the subjects with OSAS resulted in the index of oxygenation desaturations being reduced from 33.3 ± 20.1 to 1.1 ± 1.6 (P =0.00). CGMS showed mean 24-hours glucose values significantly lower after CPAP treatment than at baseline in both subgroups (7.97±1.31 vs 7.52±0.94, P=0.033 in subgroup D; and 7.72±1.51 vs 7.17±1.21, P=0.05 in subgroup M), as the fasting plasma insulin levels and HOMA-IR were also decreased significantly after CPAP treatment (13.0 ± 7.5µU/mL vs 10.8 ± 5.4µU/mL, P=0.044; and 4.2 ± 2.2 vs 3.1±1.7, P=0.003, respectively). Standard deviation (SD) and mean amplitude of glucose excursions (MAGE) were also decreased in the subgroup D (1.91 ± 1.10 vs 1.61 ± 1.20, P=0.014; 1.26 ± 1.13 vs 1.01 ± 0.98, P=0.008, respectively) only. CONCLUSION: Short-term CPAP treatment in OSAS with type 2 diabetic patients is accompanied by a decrease in blood glucose level and improved insulin sensitivity. Glucose variability was reduced but only in the patients with diet control.

[Effect of continuous positive airway pressure upon 24 h changes of blood glucose level in patients with obstructive sleep apnea hypopnea syndrome and type 2 diabetes].

OBJECTIVE: To assess the effect of short-term continuous positive airway pressure (CPAP) upon 24 h glucose control via a continuous glucose monitoring system (CGMS) in patients with obstructive sleep apnea hypopnea syndrome and type 2 diabetes (OWD). METHODS: Eleven cases of hospitalized OWD with age 43 - 70 (56 +/- 10) years old, body mass index 22.3 - 38.3 (28.5 +/- 5.5) kg/m(2) and apnea hypopnea index (AHI) 12 - 68 (45 +/- 23) times/h was recruited. CGMS was applied 2 days before and 4 days during CPAP treatment. The 24 h, treatment hours (6 h, 0:00-6:00) and non- treatment hours (18 h) glucose level and glucose variability were analyzed. Insulin resistance was assessed with fasting plasma blood glucose (FBG), plasma insulin (FINS) and homeostatic model assessment of insulin resistance index (HOMA-IR). RESULTS: Short-term CPAP treatment corrected sleep disordered breathing, and induced significant decreases of 24 h and treatment hours blood glucose level [(7.97 +/- 1.31) vs (7.52 +/- 0.94) mmol/L, (7.24 +/- 1.51) vs (6.77 +/- 1.65) mmol/L, both P < 0.05). Glucose variability of 24 h and treatment hours and non-treatment hours significantly decreased after CPAP treatment (1.22 +/- 0.34 vs 0.89 +/- 0.28, 0.43 +/- 0.24 vs 0.31 +/- 0.18, 1.23 +/- 0.89 vs 0.49 +/- 0.26, all P < 0.05). Short-term treatment also induced increase of insulin sensitivity, as indicated by a significant decrease of HOMA-IR (3.65 +/- 1.93 vs 2.79 +/- 1.68, P < 0.05). CONCLUSION: Short-term CPAP treatment in OWD may have an improving effect not only upon insulin resistance but also upon whole-day blood glucose and glucose variability.

[Effect of acute hypoxia and hypercapnia on arterial stiffness and blood pressure in patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To investigate the effect of acute hypoxia and/or hypercapnia on cardio-ankle vascular index (CAVI) and blood pressure (BP) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHOD: CAVI and blood pressure were measured before and after isocapnic hypoxic, hyperoxia hypercapnic, and hypoxic and hypercapnic challenge in 28 non-hypertensive patients with OSAHS (AHI > 10/h) and 26 healthy controls (AHI < 5/h), respectively. They were matched for age and sex. Hypoxia and hypercapnia were induced by re-breathing technique. RESULTS: The 2 groups had no differences in regard to systolic (SBP) and diastolic BP(DBP) and CAVI. After hypercapnic challenge, SBP increased significantly in both groups. CAVI decreased significantly in controls, but not in OSAHS. Hypoxia induced significant increase of CAVI, but not in OSAHS. SBP and DBP maintained to the pre-challenge levels in both group. Hypercapnia and hypoxia together caused increase of SBP in both groups, and CAVI increased significantly in controls, but not in OSAHS. CONCLUSIONS: Acute hypoxia and hypercapnia exposure caused change of arterial stiffness and BP in both control and patients with sleep apnea hypopnea syndrome. However, CAVI responses to hypoxic and/or hypercapnic challenge were blunted in patients with OSAHS.

[Effects of short-term continuous positive airway pressure treatment on arterial stiffness in patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To investigate the effect of short-term continuous positive airway pressure (CPAP) treatment on the arterial stiffness in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Cardio ankle vascular index (CAVI) and blood pressure (BP) were measured before and after sleep in 60 non-hypertensive patients with OSAHS and gender and 60 age-matched healthy controls. CPAP was administrated in 22 of the 60 OSAHS patients. And on the first and third days of the CPAP treatment CAVI and BP were measured in the morning, i. e., after sleep. RESULTS: In the morning, the CAVI of the OSAHS patients was 8.0 +/- 1.2 m/s, significantly higher than that before sleep (7.3 +/- 1.0, P = 0.000), the diastolic BP (DBP) was (86 +/- 12) mm Hg, significantly higher than that before sleep (83 +/- 13 mmHg, P = 0.001), and the mean BP (MBP) was (101 +/- 12) mm Hg, significantly higher than that before sleep (98 +/- 14, P = 0.00116). However, there were no significant differences in these parameters among the controls The systolic BP (SBP) of the OSAHS patients did not changed significantly after sleep, however, there was a tendency to decrease in the controls [(123 +/- 14) vs (121 +/- 13) mm Hg, P = 0.074). After the first night treatment, the CAVI, SBP, DBP, and mean BP of the 22 severe OSAHS patients decreased significantly (all P < 0.05), and after three nights treatment, only the CAVI showed further significant decrease (P < 0.05). CONCLUSION: Sleep induces increase of artery stiffness in OSAHS patients, but not in the normal controls. Short-term CPAP may decrease CAVI without affecting the blood pressures. Early atherosclerosis in the patients with OSAHS may be reversed by CPAP therapy.

Gut microbiota controls the development of chronic pancreatitis: A critical role of short-chain fatty acids-producing Gram-positive bacteria

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G+) or Gram-negative bacteria (G-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G+ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G+ bacteria. Additionally, depletion of SCFAs-producing G+ bacteria rather than G- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G+ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G+ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

[Changes of sleep architecture in patients with narcolepsy].

OBJECTIVE: To investigate the sleep architectures of patients with narcolepsy. METHODS: 38 drug-naive narcoleptic patients, 25 males and 13 females, aged 21 +/- 6.5, and 44 age-, sex ratio-, and BMI-matched normal persons underwent polysomnography (PSG) and multiple sleep latency test (MSLT) during one night sleep. Conventional visual scoring of the polysomnograms was performed according to the international. RESULTS: The sleep latency of the patients was 5.6 min, however, 30 patients (79%) complained of fragmented nocturnal sleep and difficulty to fall asleep again. The sleep efficiency of the narcoleptics was 81.7% +/- 12.5%, significantly lower than that of the normal persons (87.1% +/- 7.9%, P = 0.029). The non-rapid eye movement (NREM) I sleep accounted for (21.5 +/- 12.2)% in the patients, a proportion significantly higher than that of the normal persons [(10.3 +/- 6.3)%, P = 0.000]). The AHI of the patients was 0.6 +/- 1.3 times/h, not significantly different from that of the normal persons (0.5 +/- 1.1 times/h). Although the rapid eye movement (REM) period and eye movement density of the narcoleptics were significantly increased, their REM period duration was not significantly different from that of the normal subjects (17.7% +/- 6.9% vs 18.9% +/- 5.5%, P = 0.23), probably due to the interruption of REM sleep by more frequent arousals in narcoleptics. PSG did not show significant periodic leg movements in these 2 groups. CONCLUSION: One of the important symptoms of narcolepsy, night sleep disturbance may contribute to the pathological sleepiness of narcolepsy during daytime.

[Effect of noninvasive ventilation on chemoresponsiveness in patients with sleep apnea and chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the effect of noninvasive ventilation on respiratory control in patients with chronic obstructive pulmonary disease (COPD) combined with sleep a apnea-hypopnea syndrome (SAHS)-overlap syndrome (OS). METHODS: Ten body mass index, apnea-hypopnea index, and age-matched OSAHS patients, 5 being hypercapnic (PaCO(2) > 45 mm Hg) OSAHS patients with normal FEV(1)/FVC, and 5 being OSAHS patients with COPD and the mean FEV(1)/FVC of 59% +/- 6% underwent bi-level positive airway pressure (BiPAP) treatment. Hypoxic responses, including the ratio of the change in minute ventilation (DeltaVE) to the change in arterial oxygen saturation (DeltaSaO(2)), and hypercapnic responses (DeltaVE/DeltaPaCO(2) ratio) were tested during wakefulness before treatment and 6 weeks after the treatment. RESULTS: Before treatment, the DeltaVE/DeltaSaO(2) ratios of the OS and OSAHS patients were (-0.023 +/- 0.049) L.min(-1).%(-1) and (-0.16 +/- 0.06) L.min(-1).%(-1) respectively, both lower than the laboratory normal value [(-0.35 +/- 0.21) L.min(-1).%(-1)]. The DeltaVE/DeltaPaCO(2) ratio of the OS patients was (0.54 +/- 0.16) L.mm Hg(-1), significantly lower than the normal value [(1.26 +/- 0.54) L.mm.Hg(-1), P < 0.05]. After receiving 6 weeks of noninvasive ventilation treatment, the hypoxic response of OSAHS patients were (-0.16 +/- 0.06) L.min(-1).%(-1), significantly higher than that before treatment [(-0.36 +/- 0.14) L.min(-1).%(-1)], and hypercapnic response of the OSAHS patients was (1.30 +/- 0.62) L.min(-1).mm Hg(-1), significantly lower than that before treatment [(1.78 +/- 0.93) L.min(-1).mm Hg(-1)], both bring within the normal ranges. In the patients with OS, the hypercapnic response was unchanged [(0.54 +/- 0.16) vs (0.51 +/- 0.23) L.min(-1).mm Hg(-1)], and the hypoxic responses increased significantly but still remained at a very low level [(-0.023 +/- 0.049) vs (-0.09 +/- 0.007) L.min(-1).%(-1)] after treatment. CONCLUSION: Hypercapnic and hypoxic responses in patients with OS and in patients with OSAHS respond differently after pressure support ventilation. This indicates that depressed chemoresponsiveness in patients with OS may not be only a response to sleep-disordered breathing.

[Respiration control dysfunction and the relationship to sleep-disordered breathing in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To analyze the polysomnographic (PSG) features of sleep apnea hypopnea syndrome (SAHS) in patients with chronic obstructive pulmonary disease (COPD), and to define the association between SAHS and respiratory control disorder. METHODS: Three hundred patients with stable COPD were screened for SAHS using questionnaire, Epworth sleep scale (ESS) and home pulse oximeter testing. Those with ESS > or = 10 or oxygen desaturation over 3% more than 5 times per hour sleep were under further PSG testing. The PSG features were compared between COPD patients with apnea hypopnea index (AHI) > 10 and 118 SAHS patients with normal lung function. The two groups were matched for age, body mass index (BMI) and AHI. Among them 22 with COPD and AHI > or = 10 were tested for the chemo-responsiveness to isocapnic hypoxia and hypercapnia. RESULTS: Among the 300 patients with stable COPD, 79 had AHI over 10, meeting the diagnostic criteria of overlap syndrome (OS). Analysis of the polysomnography found that 32 cases (40%) with OS had more hypoventilation lasting over 1 min during sleep. Compared to patients with SAHS only, OS patients had higher percentage of hypopnea index over AHI [(69 +/- 30)% vs (52 +/- 31)%] and a higher percentage of total hypopnea time over total time of sleep apnea and hypopnea [(15 +/- 12)% vs (12 +/- 10)%]. OS patients also had lower hypoxic [(-0.11 +/- 0.05) vs (-0.35 +/- 0.24) L.min(-1).%(-1)] and hypercapnic responses [(1.1 +/- 0.8) vs (1.6 +/- 0.8) L.min(-1).mm Hg(-1) (1 mm Hg = 0.133 kPa)]. CONCLUSION: Patients with both COPD and SAHS had more episodes of hypopnea and hypoventilation during sleep, and had depressed chemo-responsiveness to hypoxia during wakefulness.