Hideaki Nakayama

Background Pompe disease is an autosomal recessive disorder caused by a deficiency of acid α-glucosidase (GAA) enzyme. This deficiency induces progressive glycogen accumulation, leading to weakness of the respiratory muscle, including the diaphragm. As established enzyme replacement therapy is available for Pompe disease, earlier detection of potential Late-Onset Pompe Disease (LOPD) and subsequent intervention would have a significant clinical impact. Purpose Our hypothesis was that sleep problems, including sleep-disordered breathing (SDB) and clinical symptoms, may indicate an early stage of LOPD, since decreased respiratory muscle activity often presents initially during sleep. The primary aim of the PSSAP-J study was to demonstrate a higher prevalence of LOPD in a sleep-laboratory-based population. Secondary aims included identifying predictive factors for LOPD from diagnostic polysomnography (PSG) findings and clinical symptoms. Methods This prospective multicenter observational cohort study enrolled consecutive patients presenting to sleep laboratories for overnight PSG due to suspected SDB. All patients underwent a Dried Blood Spot (DBS) screening for GAA activity. Genetic analysis of the GAA gene was performed for confirmatory testing when indicated. Result A total of 724 participants were analyzed, although the COVID-19 pandemic prevented reaching the target sample size (n = 1,500). No definitive LOPD cases were confirmed among those who completed the confirmatory testing (prevalence 0%; 95% confidence interval [CI], 0.00%–0.51%). However, seven screen-positive patients declined confirmatory testing and were classified as indeterminate cases. Consequently, we could not definitively establish a higher prevalence or identify predictive factors for LOPD in this population. Conclusion Although the primary study aims could not be confirmed due to the sample size shortfall and the presence of indeterminate cases, our findings highlight the importance for sleep physicians to maintain a high index of suspicion for underlying myopathies, such as LOPD, in clinical practice. Clinical trial registration UMIN000039191, UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr).

Background: REM sleep behavior disorder (RBD) is a parasomnia characterized by recurrent dream-enactment behaviors and REM sleep without atonia (RWA). Obstructive sleep apnea (OSA) frequently coexists with RBD, particularly in older men. Previous studies suggest that OSA in RBD is often mild with less prominent REM-related events. However, the longitudinal interaction between aging, changes in RWA, and development of OSA in RBD remains unclear. Methods: We retrospectively analyzed 60 patients with polysomnography (PSG)-confirmed RBD (mean age 65.9 ± 7.2 years) and AHI <20 events/h who underwent at least two nocturnal video-PSGs separated by ≥1 year (median interval 5.4 years). Changes in OSA severity, total, NREM-, and REM-AHI were compared between baseline and follow-up. RWA including phasic activity was quantified using AASM criteria. Multivariable linear regression analyses were performed with covariates including changes in age, body mass index, and RWA, as well as sex, to identify factors associated with longitudinal changes in AHI. Results: Mean AHI increased from 4.8 ± 4.3 to 8.6 ± 9.7 events/h (p < 0.001). OSA newly developed in 33% without baseline OSA, and severity worsened in 38%. Changes in age were independently associated with increases in total AHI and NREM-AHI. In contrast, changes in REM-AHI were not associated with aging but were inversely associated with changes in phasic RWA. Conclusions: In patients with RBD, sleep-disordered breathing commonly develops or worsens over time. Increased phasic RWA may attenuate the progression of REM-related OSA, suggesting a protective effect on upper airway stability. Periodic reassessment for OSA should be considered in patients with RBD.

This study investigated factors associated with possible consultation behavior (PCB) for obstructive sleep apnea (OSA; together, PCB-OSA) among male Japanese workers to promote early intervention and treatment. Data from 20,063 male employees were retrospectively analyzed. PCB-OSA was identified by the presence of at least one of the following medical procedure codes in the medical claim records from April 1, 2018, to March 31, 2019: polysomnography, home sleep apnea test, or percutaneous arterial blood oxygen saturation with an OSA diagnosis. Binomial logistic regression was used to assess factors related to PCB-OSA and the initiation of continuous positive airway pressure treatment in both the overall cohort and the OSA risk groups, defined by our objective measure-based OSA risk scale. Age (odds ratio [OR] = 1.01, 95% confidence interval [CI] [1.00, 1.02]), hypertension (OR = 1.38, 95% CI [1.10, 1.74]), heart disease (OR = 2.17, 95% CI [1.31, 3.58]), subjective sleepiness (OR = 1.49, 95% CI [1.16, 1.92]), habitual snoring (OR = 1.41, 95% CI [1.12, 1.77]), and witnessed apnea (OR = 2.13, 95% CI [1.63, 2.80]) were significantly and positively associated with PCB-OSA. Meanwhile, blue-collar workers (OR = 0.65, 95% CI [0.51, 0.82]) were significantly and negatively associated with the behavior. In the OSA high-risk group, working 6 or more days per week (OR = 0.62, 95% CI [0.40, 0.96]) was significantly and negatively associated with PCB-OSA. The study population showed a low rate of PCB-OSA. Obesity was not associated with PCB-OSA, and blue-collar workers exhibited a negative association, highlighting the need for disease education in this population. The online version contains supplementary material available at 10.1007/s41105-026-00647-7.

Purpose: To investigate the real-world status of continuous positive airway pressure (CPAP) persistence in patients with sleep apnea syndrome (SAS) using administrative claims data in Japan. Methods: We designed a retrospective longitudinal study using administrative claims and medical check-up data collected from April 2014 to February 2022. We identified patients newly starting CPAP therapy as their first-line SAS treatment, and assessed patient characteristics, CPAP persistence rates, predictors of CPAP discontinuation, and second-line therapy options. Results: The analysis population ( n = 13,007) was 76.2% male, and the mean age (± standard deviation) was 64.0 ± 15.0 years. CPAP persistence rates were 90.1% at 90 days, 77.1% at one year, 70.3% at two years, and 66.5% at three years. More discontinuation was noted in patients aged 18 to 44 (adjusted hazard ratio [95% confidence interval]: 1.27 [1.13–1.42]) and ≥ 65 (65–74 years, 1.18 [1.07–1.30]; ≥75 years, 1.59 [1.43–1.76]) than in those aged 45 to 64. Comorbidities of dementia (1.47 [1.25–1.73]), insomnia (1.26 [1.16–1.36]), and restless legs syndrome (RLS, 1.60 [1.16–2.23]) were also associated with more discontinuation. Testing with a Type 3 portable monitor (1.31 [1.21–1.42]), or no record of sleep testing before therapy (1.21 [1.09–1.36]), tended to be associated with more discontinuation than polysomnography. CPAP therapy starting in 2020 (0.72 [0.63–0.82]) and 2021 (0.63 [0.46–0.85]) resulted in better persistence than that starting in 2016. Only 6.1% of patients received second-line therapy after CPAP discontinuation. Conclusions: CPAP therapy was continued for at least a year by about 80% of patients. Because second-line therapies are rarely implemented, efforts are needed to ensure CPAP persistence by considering the factors that influence it. It is also crucial to raise awareness of alternative therapies. Registration number: NA.

Study Objectives:We aimed to determine whether the fraction of apnea (Fapnea) could be used as an alternative index to reflect upper airway (UA) collapsibility. Methods:We retrospectively recruited...

Background Pompe disease is an autosomal recessive disorder caused by deficiency of the acid α-glucosidase (GAA) enzyme. GAA deficiency induces progressive glycogen accumulation which leads to weakness of the respiratory muscle including the diaphragm. Pompe disease is one of the few myopathies, for which an established therapy is available. Thus, earlier detection of potential late-onset Pompe disease (LOPD) and earlier intervention would have a significant clinical impact. Purpose Our hypothesis is that sleep problems including sleep disordered breathing (SDB) and clinical symptoms may indicate an early stage of LOPD since decreased respiratory muscle activity generally first presents during sleep. Thus, the aims of this prospective, multicenter observational cohort study in Japan (PSSAP-J) are to demonstrate a higher prevalence of LOPD in a sleep lab–based population (primary outcome), and to identify predictive factors for LOPD from findings in diagnostic polysomnography (PSG) and clinical symptoms (secondary outcomes). Methods The study design is a prospective multicenter observational cohort study. Consecutive patients who present to sleep labs due to suspected SDB for an overnight PSG will be enrolled. All patients will be measured for creatine kinase, GAA activity, and if necessary, genetic analysis of GAA. Furthermore, chest X-ray, pulmonary function test, and arterial blood gas analysis will be collected. Then, prevalence and specific findings of LOPD will be assessed. Result Congenital myopathy shows a shift from slow-deep to rapid-shallow breathing during transition from wakefulness to sleep accompanying a symptom of waking with gasping (actual further results are pending). Discussion The distribution in respiratory physiology between during wakefulness and sleep specific to LOPD may provide insights into early-stage detection. Clinical trial registration number UMIN000039191, UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr).