The Effectiveness of Nasal Airway Stent Therapy for the Treatment of Mild-to-Moderate Obstructive Sleep Apnea Syndrome.

BACKGROUND: Patients with obstructive sleep apnea syndrome (OSAS) experience excessive daytime sleepiness and insomnia and they are at risk of developing cardiovascular disease and stroke. Continuous positive airway pressure therapy could improve symptoms and decrease these risks; however, adherence is problematic. Although the oral appliance is another therapeutic option, patient satisfaction is limited and the effect of the nasal airway stent - a new device - remains unclear. OBJECTIVES: The aim of this study was to evaluate the effect of NAS therapy in patients with mild-to-moderate OSAS in a prospective, single-arm, interventional pilot study. METHOD: Patients with mild/moderate sleep apnea (n = 71; Apnea-Hypopnea Index [AHI], 5-20 events/h on polysomnography) were recruited. Sleep-associated events were measured using a portable device (WatchPAT200) pre- and immediately post-treatment and at 1 month follow-up. AHI (including supine and non-supine AHI), Oxygen Desaturation Index (ODI), Respiratory Disturbance Index (RDI), percutaneous oxygen saturation, heart rate, and snore volume were evaluated. Symptoms were assessed using the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and Hospital Anxiety and Depression Scale. RESULTS: NAS use significantly improved AHI, supine AHI, RD, ODI, and snore volume compared to pre-intervention (r = 0.44, 0.48, 0.3, 0.42, and 0.34; p < 0.001, p < 0.001, p = 0.011, p < 0.001, and p = 0.048, respectively). Additionally, 25 and 10% of patients showed complete and partial response for AHI, respectively; these improvements remained significant 1 month later. Pittsburgh Sleep Quality Index scores improved from 6.0 to 5.3 (r = 0.46, p = 0.022). CONCLUSIONS: NAS therapy reduced severity and snoring in patients with mild-to-moderate OSAS. Approximately 30% of patients did not tolerate NAS due to side effects.

Potential patient screening for late-onset Pompe disease in suspected sleep apnea: a rationale and study design for a Prospective Multicenter Observational Cohort Study in Japan (PSSAP-J Study).

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 ).

Factors associated with improvements in subjective symptoms of obstructive sleep apnea syndrome after continuous positive airway pressure therapy.

PURPOSE: Continuous positive airway pressure (CPAP) therapy improves subjective symptoms in obstructive sleep apnea syndrome (OSAS) patients; however, factors predicting symptom improvement post-CPAP therapy and the CPAP duration necessary for improving subjective symptoms are unclear. This study aimed to identify these factors and the appropriate nightly CPAP duration for improving subjective symptoms. METHODS: We recruited 359 subjects who completed both overnight polysomnography and subjective symptom assessments using the Epworth Sleepiness Scale (ESS), Zung Self-Depression Scale (SDS), and Pittsburgh Sleep Quality Index (PSQI). Firstly, we analyzed subject characteristics, and the associations between each assessment score and the Apnea-Hypopnea Index. These assessments were then repeated for 138 subjects who could continue for 3 months after starting CPAP. Secondly, associations between changes in self-reported outcome measures and nightly CPAP duration were analyzed. We identified subjects with abnormal initial ESS, PSQI, and SDS scores and divided them into "improvement" and "non-improvement" groups to examine factors associated with a positive outcome after CPAP therapy. RESULTS: Subjective symptom scores and proportions of subjects exceeding the cutoff values of each symptom score were not significantly related to OSAS severity. ESS, SDS, and PSQI scores improved 3 months after CPAP treatment, and factors involved in each improvement were found. Remarkably, longer CPAP nightly duration resulted in improvements in all subjective symptom scores. Furthermore, minimum durations between 4.75 and 5.40 h were necessary for improvements in subjective symptoms based on ROC curve analysis. CONCLUSIONS: Longer nightly CPAP use significantly improved OSAS subjective symptoms.

The association of coffee consumption and oxygen desaturation index during sleep among Japanese male workers.

BACKGROUND AND OBJECTIVE: Coffee is a major caffeine-containing food source that can be used for treatment of apnea in prematurity. However, few studies have examined the association between coffee consumption and sleep-disordered breathing (SDB). We investigated whether coffee consumption is associated with the oxygen desaturation index (ODI) as a marker of SDB among middle-aged Japanese male workers. METHODS: The subjects were 1126 male local government workers aged 22-59 who participated in SDB screening in 2011-2012. Daily coffee consumption was assessed by a self-administered questionnaire. We measured 3% oxygen desaturation (3%ODI) during a night's sleep using a pulse oximeter. A general linear model was used to calculate the multivariate-adjusted means of 3%ODI per quartile of coffee consumption. We further analyzed the data after stratifying by overweight and current smoking status. RESULTS: A inverse association between coffee consumption and 3%ODI was found. The multivariate-adjusted mean of 3%ODI for the lowest and highest coffee consumption groups were 11.9 times/h and 10.6 times/h (p for trend = 0.06), respectively; 14.6 and 11.5 times/h (p for trend = 0.01) in overweight participants; and 12.7 and 11.0 times/h (p for trend = 0.06) in non-smokers. No associations were found in non-overweight and smoking workers. CONCLUSIONS: Our results suggest that higher coffee consumption was associated with lower 3% ODI as a marker of SDB in overweight and non-smoking workers.

Proteome analysis of bronchoalveolar lavage fluid in chronic hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an immune-mediated lung disease induced by inhalation of numerous antigens. Pathologically, chronic HP tends to show usual interstitial pneumonia (UIP) and fibrotic nonspecific interstitial pneumonia (fNSIP) patterns. Patients with UIP pattern present insidious onset and a risk for acute exacerbations. METHODS: To evaluate the proteomic differences of bronchoalveolar lavage fluid (BALF) between UIP and fNSIP patterns, BALF from seven patients with UIP pattern and four patients with fNSIP pattern was examined using two-dimensional gel electrophoresis and mass spectrometry. RESULTS: By individually comparing each BALF sample, we found that the protein levels of surfactant protein A (SP-A), immunoglobulin heavy chain α, α-2 heat shock glycoprotein, haptoglobin ß, and immunoglobulin J chain were significantly higher in the patients with UIP pattern than those in the patients with fNSIP pattern. In contrast, the protein levels of glutathione s-transferase, vitamin D-binding protein, and ß-actin were significantly higher in the patients with fNSIP pattern than those in the patients with UIP pattern. To confirm the results of SP-A in the BALF proteome, we performed enzyme-linked immunosorbent assay in a larger group. The concentrations of SP-A in BALF from the patients with UIP pattern were significantly higher than those from the patients with fNSIP pattern (2.331 ± 1.656 µg/ml vs. 1.319 ± 1.916 µg/ml, p = 0.034). CONCLUSIONS: We identified several proteins that may play roles in the development of pathological differences between UIP and fNSIP patterns of chronic HP.

Association of sleep-disordered breathing and alcohol consumption with hypertension among Japanese male bus drivers.

There is limited evidence regarding the combined effects of sleep-disordered breathing (SDB) and alcohol consumption on hypertension. The aim of this study was to examine the combined effects of SDB and alcohol consumption on hypertension in Japanese male bus drivers. This cross-sectional study included 2525 Japanese male bus drivers aged 20-65 years. SDB was assessed using a single-channel airflow monitor, which measured the respiratory disturbance index (RDI) during overnight sleep at home. Alcohol consumption (g/day) was assessed by a self-administered questionnaire and calculated per unit of body weight. Hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg and/or use of antihypertensive medications. Multiple logistic regression analyses were performed to examine the association of the combined categories of RDI and alcohol consumption with hypertension. The multivariable-adjusted odds ratio (OR) and 95% confidence interval (95% CI) of hypertension for the alcohol consumption ≥1.0 g/day/kg and RDI ≥ 20 events/h group were 2.41 (1.45-4.00) compared with the alcohol consumption <1.0 g/day/kg and RDI < 10 events/h group. Our results suggest that Japanese male bus drivers with both SDB and excessive alcohol consumption are at higher risk of hypertension than those without SDB and excessive alcohol consumption, highlighting the importance of simultaneous management of SDB and excessive alcohol consumption to prevent the development of hypertension among bus drivers.

Risk of Developing Metabolic Syndrome Is Affected by Length of Daily Siesta: Results from a Prospective Cohort Study.

BACKGROUND: Siesta has been associated with increased incidence of cardiovascular disease but the mechanism remains unclear. New studies into the relationship between siesta and metabolic syndrome have identified siesta length as a crucial differential, suggesting that siesta less than 40 min is associated with decreased risk of metabolic syndrome, while longer siesta is associated with increased risk. We aimed to investigate the effect of siesta duration on development of metabolic syndrome in a Mediterranean population using a prospective cohort study design. METHODS: Our sample consisted of 9161 participants of the SUN cohort without components of metabolic syndrome at baseline. Siesta exposure was assessed at baseline and the development of metabolic syndrome components was assessed after an average 6.8 years of follow-up. We estimated odds ratios and fitted logistic regression models to adjust for potential cofounders including night-time sleep duration and quality, as well as other diet, health, and lifestyle factors. RESULTS: We observed a positive association between average daily siesta >30 min and development of metabolic syndrome (aOR = 1.39 CI: 1.03-1.88). We found no significant difference in risk of developing metabolic syndrome between the group averaging ≤30 min of daily siesta and the group not taking siesta (aOR = 1.07 CI: 0.83-1.37). Further analysis suggested that average daily siesta <15 min may reduce risk of metabolic syndrome. CONCLUSIONS: Our study supports the J-curve model of the association between siesta and risk of metabolic syndrome, but suggests the protective effect is limited to a shorter range of siesta length than previously proposed.

Long-term effect of continuous positive airway pressure therapy on blood pressure in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a common cause of hypertension. Previous studies have demonstrated beneficial short-term effects of continuous positive airway pressure (CPAP) therapy on blood pressure. However, long-term antihypertensive effects of CPAP have not been properly verified. This study examined the longitudinal effect of CPAP therapy adherence on blood pressure among OSA patients. All patients diagnosed with OSA and undergoing subsequent CPAP therapy at a Kanagawa-area sleep clinic were clinically followed for 24 months to examine CPAP adherence, as well as longitudinal changes in blood pressure and body weight because it may become a confound factor for changes in blood pressure. The hours of CPAP usage were collected over the course of 30 nights prior to each follow-up visit (1st, 3rd, 6th, 12th, and 24th month). The relationship between CPAP adherence and blood pressure was analyzed using mixed-effect logistic regression models. A total of 918 OSA patients were enrolled in the study. We found a significant reduction in diastolic blood pressure among patients with good CPAP adherence during the 24-month follow-up period (ß = - 0.13, p = 0.03), when compared to the group with poor CPAP adherence. No significant association was found between CPAP adherence and weight loss (ß = - 0.02, p = 0.59). Long-term, good CPAP therapy adherence was associated with lower diastolic blood pressure without significant weight loss.

Proteome analysis of bronchoalveolar lavage fluid in lung fibrosis associated with systemic sclerosis.

BACKGROUND: Interstitial lung disease (ILD) is the major cause of mortality in collagen vascular diseases. However, its pathogenesis still needs to be elucidated. METHODS: To evaluate the alteration of certain proteins in bronchoalveolar lavage fluid (BALF) and clarify the causative role in the processes of ILD in systemic sclerosis (SSc), we compared a BALF protein profile between 5 patients with systemic sclerosis with pulmonary fibrosis (SSc-fib+) and 4 patients with systemic sclerosis without pulmonary fibrosis (SSc-fib-) using two-dimensional gel electrophoresis (2-DE), and matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). RESULTS: We analyzed spots over the range of 10.1kDa to 207.4kDa. SSc-fib+ patients showed increased 3 proteins compared to SSc-fib- including α2-macroglobulin, α1-antitrypsin, and pulmonary surfactant protein A and decreased 2 proteins including α2 heat shock protein (HSP) and glutathione S-transferase (GST) compared to SSc-fib- patients. CONCLUSIONS: In conclusion, we identified several interesting proteins that might have roles in ILD of SSc patients. Further studies are warranted to clarify the role of these proteins in the processes of pulmonary fibrosis in SSc.

[Sleep-disordered breathing in occupational places: from screening to Health and Productivity Management].

BACKGROUND: Sleep-disordered breathing (SDB), represented by sleep apnea, is highly prevalent in the general population and is associated with alcohol intake and obesity. Since SDB is further associated with hypertension, diabetes, and future cardiovascular diseases, as well as accidents and injuries in workplaces, there is a need for complete SDB assessment in workers, including screening and the application of diagnostic and therapeutic approaches. RESULTS: Currently, it appears that SDB assessment is not sufficiently conducted, even among commercial motor vehicle (CMV) drivers, despite CMV drivers with SDB being at a high risk of serious traffic accidents. Based on a discussion conducted in The Study Group for Sleep Disordered Breathing in Work Places, we summarized the current situation in Japan and tried to elucidate the bottleneck of these approaches. Then, the situation in Japan was compared with that in South Korea; Professor Chol Shin substantiated that the situation in South Korea was similar to that in Japan. However, recently published data on CMV drivers in the United States showed that appropriate treatment of SDB reduced the risk of traffic accidents among CMV drivers. This will encourage the implementation of the required processes, from screening to maintenance of treatment. CONCLUSION: We propose a new approach based on "harmonizing work with treatment and prevention" and "Health and Productivity Management (HPM)" as a solution for implementing SDB programs.

Harmonizing work with the treatment and prevention of sleep disordered breathing in commercial motor vehicle drivers: implications for health and productivity management.

The desastrous traffic accidents to date have provided the relevance for promotion of harmonization of work with treatment and prevention of sleep disordered breathing (SDB) in transport sectors. SDB is highly prevalent in commercial motor vehicle (CMV) drivers and is one cause of cognitive impairment and consequent traffic accidents, potentially costing billions and leading to many deaths. Various screening, diagnostic, and therapeutic approaches, some well established, are explored in this paper. Although drivers with SDB need to be appropriately diagnosed and treated, some are reluctant to continue their treatment or never submit to screening because of a lack of information. Thus, CMV drivers need to be well informed and screened, in addition to being encouraged to continue the treatment. The harmonization of work with treatment and prevention aids these objectives, providing benefits not only for individual health but also for transport companies, and further being an essential step towards uptake of "health and productivity management" in the transport sectors.

Impact of sleep disordered breathing on performance in judo players.

OBJECTIVE: Previous studies have suggested that young sports players may suffer from sleep disordered breathing (SDB). It was hypothesised that SDB in heavy-class judo players was far more prevalent than expected and that it could reduce judo performance, which could be improved by appropriate therapies. To address this, the present study estimated the percentage of heavy-class judo players with SDB and investigated the effect of SDB treatment on judo performance. METHODS: We enrolled 19 young judo players from a university judo team with body weight >100 kg and/or body mass index >30 kg/m2. Both excessive daytime sleepiness (EDS) and respiratory disturbance index (RDI) were evaluated using the Epworth Sleepiness Scale (ESS) and an overnight type 3 sleep monitor. RESULTS: The percentages of young heavyweight-class judo players with EDS (ESS ≥11) and those with SDB (RDI ≥5) were both 63%, which was unexpectedly high for the age class. Seven of the participants underwent continuous positive airway pressure therapy, which improved both RDI and ESS scores (p<0.05 for each) and subsequently the sleep quality and judo performance of the participants. CONCLUSIONS: Our study indicates that young judo players might silently suffer from SDB, leading to poorer judo performance and to future cardiovascular diseases. Clinicians should be aware of the possible presence of SDB in young sports players and consider the application of diagnostic and therapeutic remedies.

Nocturnal enuresis and sleep disordered breathing in primary school children: Potential implications.

INTRODUCTION: The association between nocturnal enuresis (NE) and sleep disordered breathing (SDB) has been repeatedly reported, but has primarily been focused on clinical cohorts. The purpose of this study, was to assess whether SDB-related symptoms such as snoring and unrefreshing sleep in the morning are associated with NE in a large-scale community school-based survey. METHODS: A cross-sectional assessment using a standard questionnaire was conducted on nearly 20 000 primary school children (5-12 years old) in Matsuyama, Japan. Associations between NE and the frequencies of snoring and unrefreshing sleep were evaluated using multivariate logistic and regression analyses. RESULTS: Multivariate adjusted odds ratios (95% confidence intervals) for enuresis were 1.21 (1.04 to 1.40) and 1.36 (1.07 to 1.73) in boys who snored 1 or 2 nights per week and ≥3 nights per week, respectively (P for trend <0.0001). Those for enuresis were 1.67 (1.41 to 1.99) and 1.96 (1.63 to 2.36) in boys who showed unrefreshing sleep 1 or 2 nights per week and ≥3 nights per week, respectively (P for trend <0.0001). Significant associations between NE and snoring frequency emerged among children who did not report unrefreshing sleep (P-trend for boys and girls were <0.0001 and <0.01, respectively), while significant associations between NE and frequency of unrefreshing sleep were detected among children who snored ≥1 nights per week (P for trend >0.1). CONCLUSIONS: The pathogenic mechanisms linking snoring and unrefreshing sleep to increased risk of NE are unknown. However, snoring, a surrogate reporter of SDB, is associated with increased urine production, while unrefreshing sleep may result from disrupted sleep facilitating increased sleep pressure and elevated arousal thresholds. Thus, both SDB and unrefreshing sleep are potential independent risk factors of NE in school age children.

Association Between Heart Rate Variability and Home Blood Pressure: The Toon Health Study.

BACKGROUND: Although blood pressure (BP) is regulated by the autonomic nervous system, it is not fully understood how autonomic activity affects BP at home in the general population. METHODS: Subjects were enrolled from 2009 to 2012 and included 1,888 men and women aged 30-79 years. We measured casual BP in the morning during health checkups and asked participants to monitor BP at home twice in the morning and evening for 1 week. The mean of the two measurements of mean arterial pressure (MAP) was calculated. Five-minute recordings of the pulse wave from a fingertip sensor were used to determine the following indices of heart rate variability (HRV): standard deviation of normal-to-normal RR intervals (SDNN), root mean square of successive differences in RR intervals (RMSSD), high frequency (HF) power, low frequency (LF) power, and LF/HF. RESULTS: Sex- and age-adjusted means of casual MAP, and morning and evening MAP at home were significantly different among quartiles of SDNN, RMSSD, and HF. When further adjusted for smoking, alcohol drinking, medication for hypertension, diabetes, sleeping hours, snoring, and mental health status, the associations were somewhat attenuated. Inverse relationships were found between the means of morning home MAP, and RMSSD (P = 0.02) and HF (P = 0.051) after adjustment for confounders. The association between MAP and RMSSD, or MAP and HF was evident in individuals <65 years old. CONCLUSION: Low HF and RMSSD, which reflect impaired parasympathetic nervous system activity, were associated with increased home MAP in the morning rather than in the evening.

Obstructive sleep apnea syndrome should be considered as a cause of nocturia in younger patients without other voiding symptoms.

INTRODUCTION: This study aimed to evaluate urination frequency among patients with obstructive sleep apnea syndrome (OSAS) and the effect of continuous positive airway pressure (CPAP) treatment. METHODS: We evaluated 138 men with moderate-to-severe OSAS by using polysomnography. Urination status was assessed at baseline and three months using the International Prostate Symptom Score and Overactive Bladder Symptom Score. Nocturia was defined as ≥2 nighttime urinations and patients were classified into Group A (<50 years old with nocturia), Group B (≥50 years old with nocturia), and Group C (patients without nocturia). OSAS severity and other urinary symptoms were also evaluated. RESULTS: Patients with nocturia exhibited more severe OSAS, compared to patients without nocturia (apnea-hypopnea index [AHI]: 52.0 vs. 44.7; p=0.021). Group A had the worst AHI, but did not have additional voiding symptoms, compared to Group B (p<0.001). The number of urinations was significantly correlated with OSAS severity in <50-year-old patients (p=0.013). CPAP reduced the number of urinations in Group A (75% of patients) and Group B (90% of patients). Patients with and without improved nocturia exhibited significant differences in their baseline OSAS severity (AHI: 53.7 vs. 37.3; p=0.042). CONCLUSIONS: OSAS severity was associated with the number of urinations in <50-year-old patients. CPAP decreased the nocturia frequency in 85% of patients with nocturia and was most effective in patients with severe AHI. However, additional studies should evaluate voiding volume in order to elucidate the mechanism of nocturia in patients with OSAS.