Telemedicine management of obstructive sleep apnea disorder in China: a randomized, controlled, non-inferiority trial.

PURPOSE: Previous studies assessed different components of telemedicine management pathway for OSA instead of the whole pathway. This randomized, controlled, and non-inferiority trial aimed to assess whether telemedicine management is clinically inferior to in-person care in China. METHODS: Adults suspected of OSA were randomized to telemedicine (web-based questionnaires, self-administered home sleep apnea test [HSAT], automatically adjusting positive airway pressure [APAP], and video-conference visits) or in-person management (paper questionnaires, in-person HSAT set-up, APAP, and face-to-face visits). Participants with an apnea-hypopnea index (AHI) ≥ 15 events/hour received APAP for 3 months. The non-inferiority analysis was based on the change in Functional Outcomes of Sleep Questionnaire (FOSQ) score and APAP adherence. Cost-effectiveness analysis was performed. RESULTS: In the modified intent-to-treat analysis set (n = 111 telemedicine, 111 in-person), FOSQ scores improved 1.73 (95% confidence interval [CI], 1.31-2.14) points with telemedicine and 2.05 (1.64-2.46) points with in-person care. The lower bound of the one-sided 95% non-inferiority CI for the difference in change between groups of - 0.812 was larger than the non-inferiority threshold of - 1. APAP adherence at 3 months was 243.3 (223.1-263.5) minutes/night for telemedicine and 241.6 (221.3-261.8) minutes/night for in-person care. The lower bound of the one-sided 95% non-inferiority CI of - 22.2 min/night was higher than the non-inferiority delta of - 45 min/night. Telemedicine had lower total costs than in-person management (CNY 1482.7 ± 377.2 vs. 1912.6 ± 681.3; p < 0.0001), driven by patient costs, but no significant difference in QALYs. CONCLUSIONS: Functional outcomes and adherence were not clinically inferior in patients managed by a comprehensive telemedicine approach compared to those receiving in-person care in China. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn , Registration number ChiCTR2000030546. Retrospectively registered on March 06, 2020.

Diurnal changes in blood pressure and heart rate in children with narcolepsy with cataplexy.

The hypocretin neurons in the lateral hypothalamus are connected not only to brain alertness systems but also to brainstem nuclei that regulate blood pressure and heart rate. The premise is that regulation of blood pressure and heart rate is altered and affected by methylphenidate, a stimulant drug in children with narcolepsy with cataplexy. The changes in 24-hr ambulatory systolic and diastolic blood pressure and heart rate were compared among pre-treated narcolepsy with cataplexy patients (40 males, 10 females), with mean age 10.4 ± 3.5 years (M ±â€…SD, range 5-17 years) with values from 100 archival age-sex-body mass index matched controls. Patients had a lower diurnal systolic blood pressure (-6.5 mmHg; p = 0.000) but higher heart rate (+11.0 bpm; p = 0.000), particularly evident in the waketime, while diastolic blood pressure was comparable. With methylphenidate (18 mg sustained release at 08:00 hours), patients with narcolepsy with cataplexy had higher systolic blood pressure (+4.6 mmHg, p = 0.015), diastolic blood pressure (+3.3 mmHg, p = 0.005) and heart rate (+7.1 bpm, p = 0.028) during wake time, but nighttime cardiovascular values were unchanged from pre-treated values; amplitude variation in cardiovascular values was unchanged over 24 hr. In conclusion, children with narcolepsy with cataplexy had downregulation blood pressure profile but a higher heart rate, and lesser non-dipping profiles. Daytime methylphenidate treatment increases only waketime blood pressure and further elevated heart rate values.

Study on adherence to positive airway pressure treatment for patients with obstructive sleep apnea using real-world big data in a telemedicine management system.

Obstructive Sleep Apnea (OSA) is a disorder that is characterized by obstructive apneas and hypopneas/respiratory effort-related arousals caused by upper airway collapse during sleep. Positive Airway Pressure (PAP) is the first-line treatment for moderate to severe OSA. However, the effectiveness of PAP therapies is contingent on treatment adherence. With the implementation of the wireless transmission for PAP treatment, it is possible to evaluate the objective adherence to PAP use. The purpose of this study is to assess the adherence to PAP therapy of Chinese OSA patients in a telemedicine management system which could fulfill automatic transmission of PAP treatment data. First, we use the telemedicine management system to extract PAP adherence information of OSA adult patients in one week, one month, three months, six months and 12 months. Second, we describe the general profile of PAP therapy adherence. Third, the latent class growth modeling and growth mixture modeling was conducted using Mplus 8.0 to identify the trajectories of adherence over time. Of all the 662 patients involved in our study, PAP adherence declined over time. After one year, the proportion of days compliant was 53.7%, the proportion of good compliance was 45.2%, the daily usage (all days) was 3.9 h/night, slightly lower than subjective adherence reported in the previous literatures. In addition, we identified three patterns of adherence over time: great users (39.9%; high mean value and level, negative slope, slow decline), good users (34.8%; moderate mean value and level, negative slope, rapid decline) and low users (25.3%; low mean value and level, negative slope, rapid decline). In brief, telemedicine management system provides a convenient platform for monitoring the treatment compliance of OSA patients powerfully and accurately. To improve the low PAP adherence in China, we should make good use of the PAP therapy telemedicine management platform to detect patients with poor adherence and provide timely intervention. Besides, our research provides a foundation for future studies to explore the determinants of observed trajectories of PAP adherence based on the telemedicine platforms.

The Impact of Symptom Severity on Health-Related Quality of Life in People with Narcolepsy Type 1.

OBJECTIVE: To assess the impact of symptom severity on health-related quality of life (HRQoL) in people with narcolepsy type 1 (NT1). METHODS: A total of 174 people with NT1 were enrolled. They completed the Narcolepsy Severity Scale (NSS) and EQ-5D-3L consisting of five dimensions (EQ-5D utility values) and a visual analog scale (EQ-5D VAS). The relationship between severity of symptoms and HRQoL dimensions was evaluated by Pearson correlation analyses. Logistic regression was used to identify significant predictors of HRQoL. Nomogram was established based on results of independent predictors of factors on logistic regression analyses. RESULTS: The mean score for NSS, EQ-5D utility values, and EQ-5D VAS were 29.8 (10.08), 0.78 (0.09), and 64.30 (19.84) in people with NT1, respectively. NSS score showed a significant correlation with self-care (r = 0.157, p < .05), usual activities (r = 0.236, p < .01), pain/discomfort (r = 0.174, p < .05), anxiety/depression (r = 0.2, p < .01), and EQ-5D utility values (r = -.261, p < .01). EDS (excessive daytime sleep), cataplexy, hallucinations, paralysis, and disrupted nocturnal sleep (DNS) were significantly associated to EQ-5D VAS (r ranged from -0.154 to -0.354, p < .05). EDS (OR = -0.297) and DNS (OR = -0.16) were predictors of HRQoL. NSS score (OR = -0.360) and treatment (OR = 0.215) were predictors of the metrics of HRQoL. The C-indices of the nomogram were 0.726. CONCLUSION: The severity of symptoms could disrupt self-care and usual activities, and increase pain/discomfort and anxiety/depression. HRQoL might be improved by alleviating symptom severity.

Combination mode of physiological signals for diagnosis of OSAS using portable monitor.

PURPOSE: Portable respiratory monitor (PRM) has been proposed for pre-diagnosis of obstructive sleep apnea syndrome (OSAS). However, discrepant physiological signal combinations were rarely studied for diagnostic assessment of OSAS. This study was designed to evaluate combination modes of key physiological signals collected by portable sensor modules for OSAS screening in comparison with polysomnography (PSG). METHODS: People with suspected OSAS were submitted to PRM at a sleep laboratory monitoring concurrently with PSG. The diagnostic accuracy was assessed by sensitivity, specificity, Pearson correlation coefficients, kappa statistic, and Bland-Altman plot. Four combination modes of PRM, including mode 1 with single nasal airflow, mode 2 with airflow plus body activity, mode 3 with airflow plus SpO2, tri-combination mode 4 with airflow plus SpO2 plus activity were studied. RESULTS: Thirty-five subjects (69% men, mean age ± SD, 49 ± 12 years) with averaged apnea-hypopnea index (AHI) of 36 ± 29 events/h were tested. Excluding incomplete recordings, 33 valid samples were analyzed. All PRM modes demonstrated good concordances with PSG in diagnostic outcomes. Tri-combination mode had optimum with sensitivity of 96.5%, specificity of 100%, +LR of 4, -LR of 0.03, and kappa coefficient of 0.85 for screening OSAS holding AHI ≥5. Its Bland-Altman plots also showed the smallest dispersion. CONCLUSIONS: This study used clinical comparison to demonstrate diagnostic accuracy of PRM with different physiological signal combination. The combination of respiratory airflow, oxygen saturation, and body activity provided sufficiently high accuracy for diagnosing OSAS. Single respiratory airflow sensor as the simplest PRM was also feasible for pre-screening OSAS.

Process and outcome for international reliability in sleep scoring.

OBJECTIVES: The aim was to evaluate the inter-rater reliability in scoring sleep stages in two sleep labs in Berlin Germany and Beijing China. METHODS: The subjects consist of polysomnography (PSGs) from 15 subjects in a German sleep laboratory, with 7 mild to moderate sleep apnea hypopnea syndrome (SAHS) patients and 8 healthy controls, and PSGs from 15 narcolepsy patients in a Chinese sleep laboratory. Five experienced technologists including two Chinese and three Germans without common training scored the PSGs following the 2007 AASM manual except the EEG signals included only two EEG leads (C3/A2 and C4/A1). Differences in inter-scorer agreement were analyzed based on epoch-by-epoch comparison by means of Cohen's κ, and quantitative sleep parameters by means of intra-class correlation coefficients. RESULTS: Inter-laboratory epoch-by-epoch agreement comparison between scorers from the two countries yielded a moderate agreement with a mean κ value of 0.57 for controls, 0.58 for SAHS, and 0.54 for narcolepsy. When compared with controls, the inter-scoring agreement is higher for wake and N3 stage scoring in SAHS and N1 and N3 scoring in narcolepsy (p < 0.05). The only sleep stage with lower scoring agreement in both SAHS (κ 0.69 vs. 0.79, p = 0.034) and narcolepsy (0.66 vs 0.79, p = 0.022) was stage REM. Inter-laboratory comparisons showed that the most common combinations of deviating scorings were N1 and N2, N2 and N3, and N1 and wake. A 6.5 % deviating scoring rate of wake and REM and a 13.4 % deviating scoring rate of N1 and REM indicated that inter-laboratory scoring in narcolepsy was about twice as in SAHS and controls confused. This was further confirmed by agreement analysis of quantitative parameters using intra-class correlation coefficients ICC(2,1) indicating REM sleep scoring agreement was lower in narcolepsy than in controls (p < 0.05). CONCLUSION: Low REM stage scoring agreement exists for narcoleptics and SAHS, indicating the necessity to study sleep stage scoring agreement for a specific sleep disorder. Intensive training is needed for the scoring of sleep in international multiple center studies to improve the scoring agreement.

[Value of actigraphy and oximetry for diagnosing sleep apnea-hypopnea syndrome].

OBJECTIVE: To explore the value of actigraphy and oximetry for diagnosing sleep apnea-hypopnea syndrome (SAHS). METHODS: Suspected SAHS subjects were enrolled from sleep center of Peking University People's Hospital between December 2013 and September 2014. Light-out and light-on were simultaneously recorded for polysomnography (PSG), actigraphy and oximetry. Actigraphy was used to correct total sleep time (TST) for oximetry. Oxygen desaturation index (ODI4), namely the times of pulse oxygen saturation (SpO2) drop≥4% per hour, was detected by oximetry. ODIA was used instead of ODI4 with TST corrected by actigraphy. Receiver operating characteristic (ROC) curve was used for evaluating the value of ODI4 and ODIA for diagnosing SAHS and cut-off value was calculated. Paired t-test or signed rank t-test was used for data acquired using actigraphy or oximetry compared with data acquired by PSG. Sensitivity and specificity were calculated using fourfold table. Disease severity of SAHS was classified by apnea-hypopnea index (AHI) detected by PSG. If AHI<5/h, SAHS was not considered. 5-<15/h was classified as mild, 15-<30/h was classified as moderate and AHI≥30/h was classified as severe. RESULTS: Among 213 SAHS subjects, 38 of them were normal, 34 of them were mild, 51 were moderate and 90 were severe. Compared with PSG, actigraphy can correctly estimate TST in non-SAHS (P=0.408) and mild SAHS groups (P=0.949); while in moderate and severe SAHS groups, TSTs detected by actigraphy were shorter than TSTs acquired by PSG ((405±51) vs (419±40) min and (399 ± 62) vs (422 ± 60) min) (both P<0.05). Area under ROC curve (AUC) of ODI4 for diagnosing SAHS was 0.956 using a cut-off value of 5; the AUC of ODIA for diagnosing SAHS was 0.951 with a cut-off value of 5 as well. The sensitivity of ODI4 for mild, moderate and severe SAHS was 80.6%, 66.7% and 58.9% respectively, all with a specificity of 100%. After adjusting TST with actigraphy, the sensitivity of ODIA for mild, moderate and severe SAHS was 84.0%, 73.8 % and 68.9%, with specificity of 94.7%, 100% and 99.2% respectively. CONCLUSIONS: Actigraphy can correctly estimate TST in non-SAHS and mild SAHS groups. ODI4 can be used for diagnosing SAHS. After correcting TST by actigraphy, the sensitivity of ODIA is higher.

[Validation of the advanced event detection in patients with sleep apnea hypopnea syndrome using auto-CPAP treatment].

OBJECTIVE: To validate the use of the event detection capabilities in an auto-CPAP system used by patients with sleep apnea hypopnea syndrome (SAHS). METHODS: A total of 28 subjects with SAHS were recruited in the study. All the underwent tests of polysomnography (PSG) before and during treatment by an-auto-CPAP system with advanced event detection (AED) in the sleep lab. Apnea-hypopnea index (AHI), apnea index (AI) and hypopnea index (HI) by PSG and PAP machine were compared. RESULTS: The mean AHI derived from PSG and AED was (6.1 ± 5.6) and (7.1 ± 5.3) times/h (P>0.05), AI was (5.4 ± 5.4) and (4.6 ± 4.2) times/h (P>0.05), HI was (0.77 ± 1.07) and (2.54 ± 1.98) times/h (P<0.05). The Spearman correlation coefficient of AHI was 0.698 (P<0.05), AI was 0.767 (P<0.05), HI was 0.141 (P>0.05). Bland-Altman plot also showed a high agreement between AHI derived from PSG and AHI derived from AED. CONCLUSION: AED showed a high agreement with PSG in the detection of AHI and AI, but not in HI. This technique may be helpful to monitor the efficacy of PAP treatment at home for long-term follow-up.

[The clinical-radiologic-pathologic features of imported pulmonary histoplasmosis].

OBJECTIVE: To describe the clinical features and treatment of imported pulmonary histoplasmosis and therefore to improve the recognition and differential diagnosis of this disease. METHODS: The clinical data of 3 patients with imported pulmonary histoplasmosis in our hospital were collected and analyzed. Literatures published since 1989 were retrieved with 'pulmonary histoplasmosis' from PubMed, China National Knowledge Infrastructure (CNKI), Wanfang Data and VIP data, of which all the literatures about imported pulmonary histoplasmosis were reviewed. The clinical manifestations, diagnostic methods and treatment were summarized. RESULTS: All the 3 cases of imported pulmonary histoplasmosis were immunocompetent hosts, all were males, age were from 44-67 years, and had a history of exploring the cave or tunnel inhabited by bats in the epidemic areas. All of them developed influenza-like symptoms varying in severity after the onset of the disease. Pulmonary multiple nodules and mediastinal lymphadenopathy were found on chest images. One patient underwent percutaneous lung biopsy and the other two received video-assisted thoracoscopic lung biopsy. All the 3 patients showed consistent histopathological findings, such as granulomatous inflammation with necrosis. Pathogen culture with lung biopsy in the first case was identified as histoplasma. All the 3 cases were treated with itraconazole, and recovered with good prognosis. Thirteen literatures in English were obtained, which reported 60 cases with imported pulmonary histoplasmosis. Forty-two of them were males, 16 were females and 2 undefined. The range of their age was from 17-64 years. No imported pulmonary histoplasmosis was reported so far in Chinese literature. Common features of imported pulmonary histoplasmosis were consistent with our patients, including epidemiology, influenza-like symptoms and bilateral pulmonary nodules, recovery with or without antifungal therapy. CONCLUSION: The epidemiologic history, influenza-like symptoms and bilateral pulmonary nodules provide valuable diagnostic clues for imported histoplasmosis. Clinical features with pathologic findings and good response to antifungal therapy could make the diagnosis even without pathogen detection if other etiology is unlikely.

[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.

[Decreased hypoxic ventilatory chemoresponsiveness and clinical features in patients with narcolepsy cataplexy].

OBJECTIVE: To explore the relationship between hypoxic responsiveness of the patients with narcolepsy-cataplexy and their clinical features. METHODS: A total of 113 patients with narcolepsy-cataplexy (narcolepsy group) at Peking University People's Hospital from June 2007 to May 2008 and 128 gender-age matched volunteers (control group) were recruited. And their status of human leukocyte antigen (HLA)-DQB1*0602 was examined to differentiate hypercapnic and hypoxic responsiveness. Among them, 93 patients with severe hypersomnolence had hypercapnic and hypoxic responsiveness tested before and after the treatment of methylphenidate and another 20 with severe cataplexy did the same before and after the treatment of chlorimiopramine. RESULTS: Compared with the control group, the narcolepsy group had depressed hypoxic responsiveness ((-0.135 ± 0.105) vs (-0.223 ± 0.136) L×min⁻¹ × %SpO2⁻¹, P < 0.001). After the treatment of methylphenidate, sleepiness improved significantly in all 93 patients, but their low hypoxic responsiveness did not change ((-0.151 ± 0.111) vs (-0.149 ± 0.105) L×min⁻¹× % SpO2⁻¹, P = 0.780). After the treatment of chlorimiopramine, cataplexy also improved in 20 patients.However their low hypoxic responsiveness had no change ((-0.114 ± 0.054) vs (-0.115 ± 0.065) L×min⁻¹ × %SpO2⁻¹, P = 0.949). CONCLUSION: Lower hypoxic responsiveness in narcolepsy group is not related with the clinical features of disease.

[Value of transcutaneous monitoring of CO2 pressure in the diagnosis and treatment of sleep and breathing disorders].

OBJECTIVE: To evaluate the clinical value of transcutaneous carbon dioxide (TcPCO2) measurement during sleep respiratory monitoring. METHODS: A total of 29 patients were prospectively recruited. Their age range was (49.5 ± 12.9) years and body mass index (BMI) (28.2 ± 3.6) kg/m(2). All of them underwent polysomnography (PSG) at Sleep Center, Peking University People's Hospital during the period of January-August 2013. TcPCO2 signal was entered into PSG systems and TcPCO2 (TCM4, Radiometer,Demark) measured simultaneously. Arterial blood gas (ABG) analysis for arterial pressure of CO2 (PaCO2) was undertaken to validate TcPCO2 measurement. The data were statistically analyzed by Pearson's product-moment correlation. Dynamic change of TcPCO2 was monitored during rapid eye movement (REM) and non-rapid eye movement (NREM) sleep stages. The effect of noninvasive positive airway pressure ventilation (NPPV) treatment on TcPCO2 during sleep was also observed. RESULTS: TcPCO2 (44.2 ± 4.0) mmHg (1 mmHg = 0.133 kPa) was highly correlated with PaCO2 (43.2 ± 4.7) mmHg (Pearson's correlation, r = 0.896, P = 0.000), TcPCO2 (45.8 ± 5.4) mmHg level during wakefulness correlated significantly with that during N1, N2, N3 and REM sleep stages (r = 0.658, 0.871, 0.898,0.775; P = 0.009, 0.000, 0.003, 0.000). TcPCO2 levels during different sleep stages were all higher than that of wakefulness.However, TcPCO2 levels did not differ between two sleep stages. During both NREM and REM, elevated TcPCO2 returned to the level during wakefulness on NPPV treatment. CONCLUSIONS: Continuous monitoring of PCO2 is well-tolerated during PSG testing. And the signal is stable. During whole night sleep, TcPCO2 monitoring provides more accurate and clinically acceptable estimation of PaCO2 so that it helps to titrate the NPPV pressure levels.

[Chemo-responsiveness in patients with obesity hypoventilation syndrome and respiratory failure].

OBJECTIVE: To the evaluate chemo-responsiveness in patients with obesity hypoventilation syndrome (OHS) and respiratory failure (RF). METHODS: A total of 14 OHS and RF patients with a mean body mass index (BMI) of (34.3 ± 2.68) kg/m(2) hospitalized between January 2009 to December 2011 were recruited. Lung function test (LFT), polysomnograghy (PSG), arterial blood gases (ABG) before and after voluntary hyperventilation maneuver and respiratory responses to hypoxia (ΔVE/ΔSpO(2)) and hypercapnia (ΔVE/ΔPaCO(2)) were measured. Ten of them received bi-level positive airway pressure (BiPAP) for 1 week and pre and post-treatment ABG were compared. RESULTS: All of them fulfilled the criteria of type II respiratory failure. PSG sleep study indicated a mean sleep apnea hypopnea index of (66.6 ± 30.1) times/h and LFT revealed a predicted FEV(1)/FVC% over 70%, excluding chronic obstruction pulmonary disease. Voluntary hyperventilation maneuver induced significant improvements in PaO(2) (52.5 ± 7.6 vs 81.3 ± 11.1 mmHg (1 mmHg = 0.133 kPa, P = 0.001) and PaCO(2) (50.4 ± 5.3 vs 43.2 ± 1.9 mmHg, P = 0.001). RF was reversed in all patients. As compared with normal controls, all patients had decreased ΔVE/ΔSpO(2) ((-0.11 ± 0.08) vs (-0.38 ± 0.04) L×min(-1)×%SpO(2)(-1), P < 0.001) and ΔVE/ΔPaCO(2) (0.31(0.18, 0.66) vs 1.20 (0.82, 1.50) L×min(-1)×mmHg(-1), P < 0.001). One-week BiPAP therapy induced significant improvement of sleep disordered breathing and daytime ABGs without any change of BMI in 10 patients. And PaCO(2) was normalized in 8/10 patients. CONCLUSIONS: OHS patients have sleep disordered breathing and depressed chemo-responsiveness. Voluntary hyperventilation maneuver may reverse the "unwilling breathing" type of RF. Non-invasive ventilation treatment may improve nocturnal sleep apnea and daytime ABG abnormality.

[Positivity analysis of human leukocyte histocompatibility antigen-DQB1*0602 allele in Chinese patients with narcolepsy].

OBJECTIVE: To explore the association of narcolepsy with human leukocyte histocompatibility antigen (HLA)-DQB1*0602 allele in Chinese narcoleptic patients and examine its relationship with different phenotypes. METHODS: A total of 1 223 narcoleptic patients (NC, narcolepsy with typical cataplexy, n = 1 132; NWC, narcolepsy without cataplexy, n = 91) diagnosed at Sleep Center of Peking University People's Hospital from August 1998 to July 2011 were recruited into this retrospective study. According to the onset age, they were divided into early-onset group (onset age ≤ 15 y, n = 1 037) and late-onset group (onset age >15 y, n = 181). All of them underwent a polymerase chain reaction with specific sequence primer (PCR-SSP) HLA-DQB1*0602 typing. And the cerebrospinal fluid levels of hypocretin-1 (hcrt-1) were measured in 156 narcoleptic patients and they were divided into hcrt deficiency group (hcrt-1<138 ng/L, n = 115) and hcrt normal group (hcrt-1 ≥ 138 ng/L, n = 41). And 728 healthy volunteers were selected as control group. The expression positivity of HLA-DQB1*0602 gene was analyzed for each group. RESULTS: There were 1 223 narcoleptic patients including 825 males (67.5%) and 398 females (32.5%) with an average age of (16.6 ± 12.6) years on visiting. There were 728 normal controls including 443 males (60.9%) and 285 females (39.1%) with an average age of (26.6 ± 11.4) years on blood sampling. The positive rate of HLA-DQB1*0602 in narcoleptic, NC and NWC groups was 94.7% (1 158/1 223), 97.0% (1 098/1 132) and 65.9% (60/91) respectively.NC group had a higher rate of HLA-DQB1*0602 positivity (χ² = 155.4, P = 0.000). Both groups were higher than that in control group of 19.5% (142/728). The positive rate of HLA-DQB1*0602 in early-onset group was 95.5% (990/1 037) versus 90.1% (163/181) in late-onset group (χ² = 9.25, P = 0.010). Among those with hcrt-1 measurement, 98.3% (113/115) were HLA-DQB1*0602 positive in hcrt deficiency narcolepsy group versus 25.6% (11/43) in hcrt non-deficiency group (χ² = 94.6, P = 0.001). CONCLUSIONS: HLA-DQB1* 0602 is an important marker in this large sample of Chinese patients with narcolepsy.Its frequency is much higher in patients with cataplexy, early-onset age and hcrt-1 deficiency.

Clinical features, polysomnography, and genetics association study of restless legs syndrome in clinic based Chinese patients: A multicenter observational study.

STUDY OBJECTIVES: To systemically describe the clinical features, polysomnography (PSG) finding, laboratory tests and single-nucleotide polymorphisms (SNPs) in a clinic based Chinese primary restless legs syndrome (RLS) population. METHODS: This observational study, conducted from January 2020 to October 2021 across 22 sleep labs in China, recruited 771 patients diagnosed with RLS following the 2014 RLSSG criteria. Clinical data, PSG testing, and laboratory examination and SNPs of patients with RLS were collected. A total of 32 SNPs in 24 loci were replicated using the Asian Screening Array chip, employing data from the Han Chinese Genomes Initiative as controls. RESULTS: In this study with 771 RLS patients, 645 had primary RLS, and 617 has DNA available for SNP study. Among the 645 primary RLS, 59.7% were women. 33% had a family history of RLS, with stronger familial influence in early-onset cases. Clinical evaluations showed 10.4% had discomfort in body parts other than legs. PSG showed that 57.1% of RLS patients had periodic leg movement index (PLMI) of >5/h and 39.1% had PLMI >15/h, respectively; 73.8% of RLS patients had an Apnea-Hypopnea Index (AHI) > 5/h, and 45.3% had an AHI >15/h. The laboratory examinations revealed serum ferritin levels <75 ng/ml in 31.6%, and transferrin saturation (TSAT) of <45% in 88.7% of RLS patients. Seven new SNPs in 5 genes showed a significant allelic association with Chinese primary RLS, with one previously reported (BTBD9) and four new findings (TOX3, PRMT6, DCDC2C, NOS1). CONCLUSIONS: Chinese RLS patients has specific characters in many aspects. A high family history with RLS not only indicates strong genetic influence, but also reminds us to consider the familial effect in the epidemiological study. Newly developed sequencing technique with large samples remains to be done.

[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.