Multimodal Telemonitoring for Weight Reduction in Patients With Sleep Apnea: A Randomized Controlled Trial.

BACKGROUND: Telemonitoring the use of CPAP devices and remote feedback on device data effectively optimizes CPAP adherence in patients with OSA. RESEARCH QUESTION: Can expanding the scope of telemonitoring and remote feedback to body weight (BW), BP, and physical activity enhance efforts for BW reduction in Patients with OSA receiving CPAP? STUDY DESIGN AND METHODS: Participants were recruited from patients at 16 sleep centers in Japan with OSA and obesity who were receiving CPAP therapy. Obesity was defined as a BMI of ≥ 25 kg/m2, based on Japanese obesity guidelines. Implementation of CPAP telemonitoring was enhanced with electronic scales, BP monitors, and pedometers that could transmit data from devices wirelessly. Participants were randomized to the multimodal telemonitoring group or the usual CPAP telemonitoring group and were followed up for 6 months. Attending physicians provided monthly telephone feedback calls to the usual CPAP telemonitoring group on CPAP data obtained remotely. In the multimodal telemonitoring group, physicians additionally encouraged participants to reduce their BW, after sharing the remotely obtained data on BW, BP, and step count. The primary outcome was set as ≥ 3% BW reduction from baseline. RESULTS: One hundred sixty-eight participants (BMI, 31.7 ± 4.9 kg/m2) completed the study, and ≥ 3% BW reduction occurred in 33 of 84 participants (39.3%) and 21 of 84 participants (25.0%) in the multimodal telemonitoring and usual CPAP telemonitoring groups, respectively (P = .047). Whereas no significant differences were found between the two groups in the change in office and home BP, daily step counts during the study period were significantly higher in the multimodal telemonitoring group than in the usual CPAP telemonitoring group (4,767 steps/d [interquartile range (IQR), 2,864-6,617 steps/d] vs 3,592 steps/d [IQR, 2,117-5,383 steps/d]; P = .02) INTERPRETATION: Multimodal telemonitoring may enhance BW reduction efforts in patients with OSA and obesity. TRIAL REGISTRY: UMIN Clinical Trials Registry; No.: UMIN000033607; URL: www.umin.ac.jp/ctr/index.htm.

Sleep Apnea Syndrome (SAS) Clinical Practice Guidelines 2020.

The prevalence of sleep disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously believed, with patients having moderate-to-severe OSA accounting for approximately 20% of adult males and 10% of postmenopausal women not only in Western countries but also in Eastern countries, including Japan. Since 1998, when health insurance coverage became available, the number of patients using continuous positive airway pressure (CPAP) therapy for sleep apnea has increased sharply, with the number of patients about to exceed 500,000 in Japan. Although the "Guidelines for Diagnosis and Treatment of Sleep Apnea Syndrome (SAS) in Adults" was published in 2005, a new guideline was prepared in order to indicate the standard medical care based on the latest trends, as supervised by and in cooperation with the Japanese Respiratory Society and the "Survey and Research on Refractory Respiratory Diseases and Pulmonary Hypertension" Group, of Ministry of Health, Labor and Welfare and other related academic societies, including the Japanese Society of Sleep Research, in addition to referring to the previous guidelines. Because sleep apnea is an interdisciplinary field covering many areas, this guideline was prepared including 36 clinical questions (CQs). In the English version, therapies and managements for SAS, which were written from CQ16 to 36, were shown. The Japanese version was published in July 2020 and permitted as well as published as one of the Medical Information Network Distribution Service (Minds) clinical practice guidelines in Japan in July 2021.

Three cases of parasomnias similar to sleep terrors occurring during sleep-wake transitions from REM sleep.

Sleep terrors are a non-rapid eye movement (NREM) sleep-related parasomnia characterized by abrupt terror with a frightening scream. However, it remains unknown whether sleep terrors occur only from NREM sleep. We evaluated 3 cases of a sleep terrors-like parasomnia that occurred exclusively during arousals from rapid eye movement (REM) sleep. These parasomnia events occurred at REM sleep-wake transitions, manifesting with screaming or crying, similar to sleep terrors, without alertness or clear orientation. The patients were all young-adult females without notable medical conditions. REM sleep behavior disorder and nocturnal frontal lobe epilepsy were not detected based on their video-polysomnographic findings. These 3 cases should be provisionally diagnosed as "Parasomnia, Unspecified" according to the International Classification of Sleep Disorders, third edition; however, the phenomenological diagnosis is proposed to be "Disorders of Arousal from REM Sleep." Our reported cases indicate that sleep terrors may also arise from REM sleep. CITATION: Futenma K, Inoue Y, Saso A, Takaesu Y, Yamashiro Y, Matsuura M. Three cases of parasomnias similar to sleep terrors occurring during sleep-wake transitions from REM sleep. J Clin Sleep Med. 2022;18(2):669-675.

Sleep Apnea Syndrome (SAS) Clinical Practice Guidelines 2020.

The prevalence of sleep-disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously believed, with patients having moderate-to-severe OSA accounting for approximately 20% of adult males and 10% of postmenopausal women not only in Western countries but also in Eastern countries, including Japan. Since 1998, when health insurance coverage became available, the number of patients using continuous positive airway pressure (CPAP) therapy for sleep apnea has increased sharply, with the number of patients about to exceed 500,000 in Japan. Although the "Guidelines for Diagnosis and Treatment of Sleep Apnea Syndrome (SAS) in Adults" was published in 2005, a new guideline was prepared to indicate the standard medical care based on the latest trends, as supervised by and in cooperation with the Japanese Respiratory Society and the "Survey and Research on Refractory Respiratory Diseases and Pulmonary Hypertension" Group, of Ministry of Health, Labor and Welfare and other related academic societies, including the Japanese Society of Sleep Research, in addition to referring to the previous guidelines. Since sleep apnea is an interdisciplinary field covering many areas, this guideline was prepared including 36 clinical questions (CQs). In the English version, therapies and managements for SAS, which were written from CQ16 to 36, were shown. The Japanese version was published in July 2020 and permitted as well as published as one of the Medical Information Network Distribution Service (Minds) clinical practice guidelines in Japan in July 2021.

Very early-onset of RBD with ADHD: a case report study.

We experienced a case of very early-onset REM sleep behavior disorder (RBD) with ADHD. This case showed typical RBD symptoms with REM sleep without atonia on polysomnography. Methylphenidate, which enhances the dopamine system, attenuated his ADHD symptoms but not RBD symptoms. We speculate that the dysfunction of the laterodorsal tegmental nucleus in the pontine was responsible for the symptoms of RBD and ADHD in this case. Very early-onset RBD is rare, and its profile is not well known. ADHD with dysfunction in the laterodorsal tegmental nucleus may form asubtype of ADHD that is commonly comorbid with very early-onset RBD.

A Randomized Controlled Trial of Telemedicine for Long-Term Sleep Apnea Continuous Positive Airway Pressure Management.

Rationale: The effects of telemedicine on adherence in patients with obstructive sleep apnea with long-term continuous positive airway pressure (CPAP) use have never been investigated.Objectives: To examine effects of a telemedicine intervention on adherence in long-term CPAP users.Methods: In a prospective, randomized, multicenter noninferiority trial conducted in 17 sleep centers across Japan, patients who had used CPAP for >3 months and were receiving face-to-face follow-up by physicians every 1 or 2 months were randomized by a coordinating center in a blind manner to the following three groups: 1) follow-up every 3 months accompanied by a monthly telemedicine intervention (telemedicine group: TM-group), 2) follow-up every 3 months (3-month group: 3M-group), or 3) monthly follow-up (1-month group: 1M-group). Each group was followed up for 6 months. The change in percentage of days with ≥4 h/night of CPAP use from baseline to the end of the study period was evaluated. A decline of ≥5% from baseline was considered deterioration of adherence. Noninferiority of TM- and 3M-groups compared with the 1M-group according to the number of patients with deterioration of adherence was evaluated with the Farrington and Manning test (noninferiority margin 15%).Results: A total of 483 patients were analyzed (median duration of CPAP use, 29 [interquartile range, 12-71] mo), and deterioration of adherence was found in 41 of 161 (25.5%), 55 of 166 (33.1%), and 35 of 156 (22.4%) patients in the TM-, 3M-, and 1M-groups, respectively. The noninferiority of the TM-group compared with the 1M-group was verified (difference in percentage of patients with adherence deterioration, 3.0%; 95% confidence interval [CI], -4.8% to 10.9%; P < 0.01). Conversely, the 3M-group did not show noninferiority to the 1M-group (percentage difference, 10.7%; 95% CI, 2.6% to 18.8%; P = 0.19). In the stratified analysis, adherence in TM- and 1M-group patients with poor adherence at baseline improved (TM: 45.8% ± 18.2% to 57.3% ± 24.4%; P < 0.01; 1M: 43.1% ± 18.5% to 53.6% ± 24.3%; P < 0.01), whereas that of the 3M-group did not (39.3% ± 20.8% to 39.8% ± 24.8%; P = 0.84).Conclusions: Intensive telemedicine support could help to optimize CPAP adherence even after long-term CPAP use.Clinical trial registered with www.umin.ac.jp/ctr/index.htm (trial number: UMIN000023118).

Decrease of Plasma Soluble (Pro)renin Receptor by Bariatric Surgery in Patients with Obstructive Sleep Apnea and Morbid Obesity.

BACKGROUND: Plasma concentrations of soluble (pro)renin receptor [s(P)RR], which are elevated in patients with obstructive sleep apnea (OSA), have not been studied in morbid obesity. The aim of this study is to clarify effects of bariatric surgery on plasma s(P)RR concentrations and identify associated factors for their changes in OSA patients with morbid obesity. METHODS: Twenty-three patients with OSA complicated by morbid obesity (10 men and 13 women; body mass index, 40.7 ± 6.16 kg/m2) without chronic kidney disease were followed up after bariatric surgery. Overnight polysomnography (PSG) was performed before surgery, and 4 and 24 weeks after surgery. Plasma s(P)RR concentrations were measured each morning after PSG. RESULTS: Preoperative plasma s(P)RR concentrations showed significant positive correlations with serum creatinine (P < 0.05), arousal index (P < 0.01), apnea-hypopnea index (AHI) (P < 0.05), apnea index (P < 0.005), and desaturation index (P < 0.05), and a significant inverse correlation with an estimated glomerular filtration rate (P < 0.05). With the improvement of these PSG parameters, plasma s(P)RR concentrations significantly decreased from 15.3 ± 3.6 to 12.5 ± 2.7 ng/mL 4 weeks after surgery, which further decreased to 11.4 ± 2.4 ng/mL 24 weeks after surgery. The association observed before surgery between plasma s(P)RR concentrations and the PSG parameters was not seen after surgery. CONCLUSIONS: Bariatric surgery in patients with OSA complicated by morbid obesity decreased plasma s(P)RR concentrations. The most associated factors for their changes were arousal index, AHI, apnea index, and desaturation index.

Prevalence of sleep-disordered breathing in Japanese medical students based on type-3 out-of-center sleep test.

BACKGROUND: Sleep-disordered breathing (SDB), especially obstructive sleep apnea disorder (OSA), is thought to mainly affect men over the age of 40. Following findings that Asian people are more likely to experience severe OSA, regardless of obesity, we investigated the prevalence of SDB and OSA in a larger sample and in more younger age groups than those described in previous reports. METHODS: Between 2011 and 2016, 487 medical students (358 males, mean age 24.8 ± 1.9 years; 129 females: mean age 23.8 ± 1.6 years) underwent an out-of-center sleep test using a type-3 portable monitor. The results were analyzed visually. RESULTS: The mean ± standard deviation of the respiratory event index (REI: events/hour of monitoring) was 5.4 ± 6.7 (6.7 ± 7.5 in male participants, 2.6 ± 2.1 in female participants). There were 170 participants (36.6%) with an REI≥5, including 158 male participants (46.9%) and 12 female participants (9.1%). SDB or undefined OSA with low REI (15 > REI≥5) was observed in 141 participants (30.4%), defined OSA with moderate REI (30 > REI≥15) in 19 participants (4.1%), and defined OSA with high REI (REI≥30) in 10 participants (2.2%). Among the male students, 129 had low REI (38.3%), 19 had moderate REI (5.6%), and 10 had high REI (3.0%). All female participants with OSA events (9.4%) had a low REI. CONCLUSIONS: The prevalence of OSA in Japanese young adults, especially males under 30 years old, is similar or even higher than that in older age groups described previously. Thus, an aggressive sleep study for SDB might be necessary for the younger generation in the Asian population.

Elevated Plasma Levels of Soluble (Pro)Renin Receptor in Patients with Obstructive Sleep Apnea Syndrome in Parallel with the Disease Severity.

(Pro)renin receptor ((P)RR), a receptor for renin and prorenin, is implicated in the pathophysiology of diabetes mellitus, hypertension and their complications. Soluble (P)RR (s(P)RR) is composed of extracellular domain of (P)RR and thus exists in blood. We have reported that plasma concentrations of s(P)RR were elevated in male patients with obstructive sleep apnea syndrome (OSAS). The aim of the present study was to clarify the difference in plasma s(P)RR concentrations between male and female OSAS patients. Plasma s(P)RR concentrations were studied in 289 subjects (206 males and 83 females) consisting of 259 OSAS patients and 30 non-OSAS control subjects. The 259 OSAS patients were classified into mild (5 ≤ apnea hypopnea index (AHI) < 15 events/h), moderate (15 ≤ AHI < 30), and severe OSAS (AHI ≥ 30). Plasma s(P)RR levels were significantly elevated in all three OSAS groups compared to non-OSAS control subjects (AHI < 5) in the entire cohort and male subjects, whereas in female subjects, the significant elevation was found only in severe OSAS. Plasma s(P)RR levels were significantly correlated with AHI in both sexes, with a higher r value found in male subjects (male r = 0.413, p < 0.0001; female r = 0.263, p < 0.05). Importantly, when OSAS patients (26 males and 15 females) with AHI ≥ 20 underwent continuous positive airway pressure treatment, plasma s(P)RR levels were significantly decreased. In conclusion, plasma s(P)RR levels are elevated in both male and female OSAS patients in parallel with the disease severity.

Efficacy and safety of adjunctive modafinil treatment on residual excessive daytime sleepiness among nasal continuous positive airway pressure-treated japanese patients with obstructive sleep apnea syndrome: a double-blind placebo-controlled study.

STUDY OBJECTIVES: This double-blind study evaluated the efficacy and safety of modafinil for treating excessive daytime sleepiness in Japanese patients with obstructive sleep apnea syndrome (OSAS). METHODS: Patients with residual excessive sleepiness (Epworth Sleepiness Scale [ESS] ≥ 11) on optimal nasal continuous positive airway pressure (nCPAP) therapy (apnea-hypopnea index ≤ 10) were randomized to either 200 mg modafinil (n = 52) or placebo (n = 62) once daily for 4 weeks. Outcomes included baseline-week 4 changes in ESS total score, sleep latency on maintenance of wakefulness test (SL-MWT), nocturnal polysomnography, Pittsburgh Sleep Quality Index (PSQI), and safety. RESULTS: All 114 randomized patients completed the study. Mean change in ESS total score (-6.6 vs -2.4, p < 0.001) and SL-MWT (+2.8 vs -0.4 minutes, p = 0.009) were significantly greater with modafinil than with placebo. ESS total score decreased from > 11 to < 11 at the final assessment in 69.2% of modafinil-treated patients and 30.6% of placebo-treated patients (p < 0.001). Corresponding rates at week 1 were 57.7% and 33.9% (p = 0.014). Changes in nocturnal polysomnography, PSQI, and apnea-hypopnea index from baseline to the final assessment were similar in both groups. Adverse drug reactions occurred in 36.5% and 22.6% of patients in the modafinil and placebo groups, respectively (p = 0.146). CONCLUSIONS: Once-daily modafinil was effective and well tolerated for managing residual daytime sleepiness in Japanese OSAS patients with residual excessive daytime sleepiness on optimal nCPAP therapy.

Cephalometric assessment of craniofacial morphology in Japanese male patients with obstructive sleep apnea-hypopnea syndrome.

CRANIOFACIAL MORPHOLOGICAL ANOMALIES CAN BE DIVIDED INTO TWO PRINCIPAL CATEGORIES: skeletal anomalies and soft tissue anomalies. This study examined the hypothesis that the assessment of indices representing both skeletal and soft tissue can be used to appropriately identify the risk factor of obstructive sleep apnea-hypopnea syndrome (OSAHS). 232 suspected OSAHS male patients were examined with polysomnography and divided into two groups (202 males with OSAHS and 30 male controls without OSAHS). Cephalometric analysis was performed on all patients to evaluate craniofacial morphological anomalies. The measurement sites were as follows: skeletal morphology; soft tissue morphology; mixed morphology including mandibular plane to hyoid bone (MP-H); and jaw soft tissue (JS) ratio; a novel ratio we defined, between the area of jaw and area of tongue with soft palate. JS ratio increased with AHI as well as MP-H. MP-H and JS ratio showed significant but weak correlation with apnea-hypopnea index. JS ratio was significantly associated with an increased risk for severe OSAHS, even after adjusting age and BMI, its odds ratio was the greatest among these variables. These results showed that mixed craniofacial, skeletal and soft tissue morphology are correlated with AHI, and JS ratio may be a useful parameters to explain the characteristics of OSAHS in male patients.

Is laryngeal descent associated with increased risk for obstructive sleep apnea?

BACKGROUND: A lower (more caudal) position of the larynx may result in a longer collapsible segment of the upper airway. One could thus hypothesize that the lower the larynx the greater the risk for obstructive sleep apnea (OSA). To test this hypothesis, we measured the upper airway length to the level of the vocal cord and the horizontal and vertical segments of the supralaryngeal vocal cord tract (SVT) using multislice CT scan in Japanese patients with OSA. METHODS: We recruited 249 consecutive patients who had polysomnography for suspected OSA (age, 47.8 ± 14.8 years; BMI, 24.8 ± 4.3 kg/m(2)). Using CT images, we measured airway length (AL), airway length to vocal cord (ALVC), ALVC-AL, horizontal segment of SVT (SVTH), and vertical segment of SVT (SVTV). The ratio SVTR (SVTH to SVTV) was calculated. The correlation between these measurements and age, BMI, and AHI were evaluated. RESULTS: Men had a longer ALVC than women. AL, ALVC, and SVTR were significantly correlated with age and AHI in all patients. Logistic regression analysis showed that ALVC > 0.24 (OR, 4.2; CI, 2.3-7.6) and BMI > 25 (OR, 4.8; CI, 2.7-8.5) were significant variables predicting AHI > 30. Even after controlling for BMI, the effect of ALVC was still significant. CONCLUSIONS: The laryngeal position is lower in men than women. Aging is associated with a lower laryngeal position, and a longer ALVC is independently associated with OSA severity in Japanese patients. We conclude that both laryngeal descent and BMI may be risk factors for OSA.

Evaluation of sympathetic activity by 123I-metaiodobenzylguanidine myocardial scintigraphy in dilated cardiomyopathy patients with sleep breathing disorder.

BACKGROUND: Because increased sympathetic nervous activity (SNA) in patients with dilated cardiomyopathy (DCM) associated with sleep breathing disorder (SBD) is known to deteriorate the prognosis of cardiac failure, (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was used as the investigative tool in the present study. METHODS AND RESULTS: The study group comprised 53 patients (47 men, 6 women; mean age 56+/-3 years) with chronic stable DCM. Patients were divided into SBD(+) or SBD(-) group according to 24-h pulse oximetry results. SBD(+) was defined when the 3% oxygen desaturation index was more than 15/h during sleep. In total, 32 patients were SBD(-) and 21 were SBD(+). In both groups, pulse oximetry were performed during sleep and awakening pulse rate, and measurement of the blood levels of catecholamines and B-type natriuretic peptide was performed. MIBG myocardial scintigraphy and echocardiography were performed at the same time. No significant difference was found between the 2 groups in catecholamine levels or left ventricular ejection fraction. However, MIBG had a significantly increased washout rate and a significantly decreased delayed heart to mediastinum ratio in the SBD(+) group compared with the SBD(-) group. CONCLUSIONS: SNA is increased in DCM patients when associated with SBD. MIBG myocardial scintigraphy may be a sensitive method of detecting increased SNA.

Anatomical balance of the upper airway and obstructive sleep apnea.

BACKGROUND: Obesity and craniofacial abnormalities such as small maxilla and mandible are common features of patients with obstructive sleep apnea (OSA). The authors hypothesized that anatomical imbalance between the upper airway soft-tissue volume and the craniofacial size (rather than each alone) may result in pharyngeal airway obstruction during sleep, and therefore development of OSA. METHODS: Blind measurements of tongue cross-sectional area and craniofacial dimensions were performed through lateral cephalograms in 50 adult male patients with OSA and 55 adult male non-OSA subjects with various craniofacial dimensions. RESULTS: Maxillomandibular dimensions were matched between OSA and non-OSA groups. While the tongue was significantly larger in subjects with larger maxillomandible dimensions, OSA patients had a significantly larger tongue for a given maxillomandible size than non-OSA subjects. The hypothesis was also supported in subgroups matched for both body mass index and maxillomandible dimensions. CONCLUSIONS: Upper airway anatomical imbalance is involved in the pathogenesis of OSA.

Sepsis caused by food-borne infection with Escherichia coli.

We report a case of sepsis caused by Escherichia coli (E. coli) of serotype O-143. A 78-year-old man developed symptoms of gastroenteritis after ingesting raw meat on noodles. He rapidly developed respiratory failure. Blood culture grew E. coli. The sepsis seemed to have directly spread from a food-borne infection. The development of primary sepsis after ingesting E. coli is very rare. We suspect that bacterial translocation played a major role. Serotype O-143 is recognized in enteroinvasive E. coli (EIEC) as well as in Shigella dysenteriae. The pathogen in the present case is suspected of being EIEC although the isolated E. coli strain was negative for the inv and ipa genes.

[Adverse effects and adherence to nasal continuous positive airway pressure in patients with obstructive sleep apnea hypopnea syndrome].

The adverse effects of and adherence of a treatment with nasal continuous positive airway pressure (nCPAP) for obstructive sleep apnea and hypopnea syndrome (OSAHS) were examined. The subjects comprised 321 patients with OSAHS. An all-night polysomnography was performed for all subjects. Titration of CPAP was performed manually. Regarding the adverse effects of nCPAP therapy, the subjects most frequently complained of nasal symptoms, air-leaks and any trouble with the mask. Complaints heard less frequently were sleep disturbances, dry pharyngeal and oral cavities, noises, and pronounced pressure sensations due to CPAP. No adverse effects were noted in 13% of the subjects. The adherence was as high as 73.0% in 122 patients in whom time spent for nCPAP treatment could be analyzed. The mean treatment time was 4.7 +/- 1.8 hours. We found no significant correlation between mean treatment time and age, BMI, ESS, CPAP, AHI, Ar-I, ODI, lowest SpO 2, or %TST with SpO 2 < 90%. Multivariate analysis revealed no factor significantly correlated with treatment time. These results showed that detailed instructions for the prevention of adverse effects may improve the adherence of CPAP.