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.

[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.

[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.

[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.

[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.

[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.