The role of long-term continuous positive airway pressure in the progression of obstructive sleep apnoea: A longitudinal cohort study.

Recent evidence suggests that short-term obstructive sleep apnea (OSA) treatment could affect OSA pathogenesis such as ventilatory control. The aim of our present study was to identify the impact of long-term treatment on the change in pathogenesis and natural progression of OSA. In a longitudinal analysis of a non-obese cohort study, patients with OSA treated with either continuous positive airway pressure (CPAP) or an oral appliance (OA), interrupted their treatment for 1 week and underwent a polysomnography (PSG) off treatment that was compared with their initial PSG taken 5 years before treatment initiation. In all, 154 consecutive patients with OSA who were treated by CPAP using an auto-titrating continuous positive airway pressure device (CPAP-APAP) (n = 112), or by OA (n = 27) or were untreated (n = 15), PSG was performed twice with a median (range) follow-up of 93 (60-176) months. Multivariate logistic regression showed that reduction of body mass index (BMI) and good treatment adherence to be significant predictors of favourable OSA progression, as represented by an improved or unchanged apnea-hypopnea index (AHI) (odds ratios were 5.14 and 2.89, respectively). Amongst the patients with an unchanged BMI and good CPAP-APAP adherence (n = 55), the improvement in AHI was significantly associated with the decrease in supine non-rapid eye movement-AHI and mixed apnoea index/apnoea index, which are generally recognised to be determinants of ventilator instability. These findings suggest that not only weight but also treatment adherence are determinants in the natural progression of OSA severity.

Machine learning for image-based detection of patients with obstructive sleep apnea: an exploratory study.

PURPOSE: In 2-dimensional lateral cephalometric radiographs, patients with severe obstructive sleep apnea (OSA) exhibit a more crowded oropharynx in comparison with non-OSA. We tested the hypothesis that machine learning, an application of artificial intelligence (AI), could be used to detect patients with severe OSA based on 2-dimensional images. METHODS: A deep convolutional neural network was developed (n = 1258; 90%) and tested (n = 131; 10%) using data from 1389 (100%) lateral cephalometric radiographs obtained from individuals diagnosed with severe OSA (n = 867; apnea hypopnea index > 30 events/h sleep) or non-OSA (n = 522; apnea hypopnea index < 5 events/h sleep) at a single center for sleep disorders. Three kinds of data sets were prepared by changing the area of interest using a single image: the original image without any modification (full image), an image containing a facial profile, upper airway, and craniofacial soft/hard tissues (main region), and an image containing part of the occipital region (head only). A radiologist also performed a conventional manual cephalometric analysis of the full image for comparison. RESULTS: The sensitivity/specificity was 0.87/0.82 for full image, 0.88/0.75 for main region, 0.71/0.63 for head only, and 0.54/0.80 for the manual analysis. The area under the receiver-operating characteristic curve was the highest for main region 0.92, for full image 0.89, for head only 0.70, and for manual cephalometric analysis 0.75. CONCLUSIONS: A deep convolutional neural network identified individuals with severe OSA with high accuracy. Future research on this concept using AI and images can be further encouraged when discussing triage of OSA.

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 ).

Heated Tobacco Product Smokers in Japan Identified by a Population-Based Survey.

BACKGROUND: In this study, we aim to estimate the prevalence of heated tobacco product (HTP) smokers 3 years after the launch of HTPs in Japan. METHODS: Our study, performed in February 2018 in Japan, had a cross-sectional population-based design. A total of 4,628 adult participants (2,121 men and 2,507 women) were randomly sampled from all regions of Japan. The response rate was 57.9%. Interviews were conducted by trained investigators who visited participants' homes. A survey on current (past 30 days) and lifetime tobacco use (including e-cigarettes and HTPs), as well as numerous sociodemographic factors, was conducted. RESULTS: The age-adjusted rates and estimated number of lifetime-HTP smokers were 14.1% (95% confidence interval [CI], 12.5-15.6%; 7.11 million men) and 3.7% (95% CI, 2.9-4.4%; 1.99 million women). The age-adjusted rates for current HTP smokers were 8.3% (95% CI, 7.1-9.6%; 4.21 million men) and 1.9% (95% CI, 1.3-2.4%; 1.02 million women). Multiple variables were found to be associated with a higher prevalence of current HTP use, including being male, aged 20-39 years, a current Internet user, a risky drinker, or a heavy episodic drinker. HTP use was also higher among men with 10 years or more of education, women with 15 years or less of education, and men with middle- or high-level household incomes. CONCLUSION: We concluded that HTP use has increased substantially in Japan. However, regulations for HTPs are weaker than those for combustible cigarettes in Japan. Thus, HTPs should be subjected to the same regulations as combustible tobacco products.

Obstructive sleep apnea phenotypes in men based on characteristics of respiratory events during polysomnography.

PURPOSE: The upper airway (UA) anatomical collapsibility, UA muscle responsiveness, breathing control, and/or arousability are important contributing factors for obstructive sleep apnea (OSA). Differences in clinical manifestations of OSA are believed to reflect interactions among these factors. We aimed to classify OSA patients into subgroups based on polysomnographic (PSG) variables using cluster analysis and assess each subgroup's characteristics. METHODS: Men with moderate or severe OSA and without any concomitant heart or psychosomatic disease were recruited. A hierarchical cluster analysis was performed using variables including fraction of apnea, respiratory event duration, minimum oxygen saturation, arousal rate before termination, and frequency of respiratory events in the supine position. The impact of sleep stages or body position on PSG variables was also evaluated in each cluster. RESULTS: A total of 210 men (mean age, 50.0 years, mean body mass index, 27.4 kg/m2) were studied. The three subgroups that emerged from the analysis were defined as follows: cluster 1 (high fraction of apnea and severe desaturation (20%)), cluster 2 (high fraction of apnea and long event duration (31%)), and cluster 3 (low fraction of apnea (49%)). There were differences in the body mass index and apnea type between the three clusters. Sleep stages and/or body position affected PSG variables in each cluster. CONCLUSIONS: Patients with OSA could be divided into three distinct subgroups based on PSG variables. This clustering may be used for assessing the pathophysiology of OSA to tailor individual treatment other than continuous positive airway pressure therapy.

Progression of obstructive sleep apnoea syndrome in Japanese patients.

PURPOSE: The aggravation of obstructive sleep apnoea syndrome (OSAS) is reportedly associated with weight gain. The present study investigated the factors associated with worsening of respiratory functional parameters in Japanese OSAS patients who showed no body weight change during the follow-up period. METHODS: A follow-up polysomnography (PSG) was performed in 82 patients with a mean of 7.5 years after the diagnostic PSG, and the apnoea-hypopnoea index (AHI), respiratory event duration, minimum percutaneous oxygen saturation (SpO2), baseline SpO2, and 3 % oxygen desaturation index (ODI) during sleep were compared between the two PSGs. Furthermore, factors associated with worsened AHI, respiratory event duration, and minimum SpO2 were investigated using logistic regression analysis. RESULTS: No significant differences were observed in AHI, baseline SpO2, and 3 % ODI between the two PSGs. However, there was a significantly increased respiratory event duration and decreased minimum SpO2 observed. In addition, 17 patients had a ≥25 % AHI increase, and the age of 40-60 years and initial OSAS severity (mild and moderate) were the significantly associated factors. Age of ≥60 years and a baseline body mass index (BMI) of ≥25 kg/m(2) were significantly associated with prolonged respiratory event duration. The age of 40-60 years was significantly associated with decreased minimum SpO2. CONCLUSIONS: Untreated middle-aged patients may be at a high risk for worsened AHI and SpO2 even without weight gain.

Esophageal Involvement in Multiple System Atrophy.

The prevalence of esophageal involvement and its impact on clinical manifestations in patients with multiple system atrophy (MSA) remains unknown. We recruited 16 consecutive patients with dysphagia associated with MSA (MSA group) and 16 consecutive patients with dysphagia associated with amyotrophic lateral sclerosis (ALS group). We assessed the presence or absence of food stagnation within the esophagus using videofluorography. Food stagnation within the esophagus was observed in 16 patients (100 %; 7 severe, 9 mild) in the MSA group and in 4 patients (25 %; 4 mild) in the ALS group (P < 0.001). Follow-up videofluorography revealed that food stagnation in patients with MSA could exacerbate during the disease course. Patients with MSA and severe food stagnation showed a wide range of intraesophageal stasis by videofluorography. Among the 16 patients in the MSA group, 4 developed aspiration pneumonia and 1 died of suffocation associated with food regurgitation during continuous positive airway pressure therapy. In conclusion, food stagnation within the esophagus occurs more frequently in MSA patients with dysphagia than in ALS patients with dysphagia. Because food stagnation can cause serious complications such as aspiration pneumonia and suffocation, patients with MSA should be evaluated by videofluorography, especially those with stagnation in the esophageal phase.

Obstructive sleep apnea syndrome attenuated high-density lipoprotein function.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. High-density lipoproteins (HDLs) exert anti-atherogenic effects, even on cholesterol efflux capacity (CEC). The HDL proteome is reportedly altered in patients with coronary artery disease. OBJECTIVE: We hypothesized that OSA attenuates HDL function through an altered HDL proteome, which could be alleviated by continuous positive airway pressure (CPAP) therapy. METHODS: Patients aged ≥20 years (n = 115) with suspected OSA were enrolled in this cross-sectional study, with 34 patients diagnosed with moderate and severe OSA included in the interventional study and treated with CPAP therapy for 12 weeks. To further investigate the HDL proteome in OSA, we conducted a discovery study by analyzing HDL proteomes in 10 patients. RESULTS: In this study, CEC was significantly lower in the sleep apnea syndrome (SAS) group (apnea-hypopnea index [AHI] ≥5) than in the non-SAS group (AHI <5; 0.96 ± 0.14 vs. 1.06 ± 0.15, p = 0.01). Multiple regression analysis revealed that minimal pulse oxygen saturation (MinSpO2) was positively correlated with CEC. In the interventional study, a 12-week CPAP therapy did not affect CEC. We identified orosomucoid 1 (ORM1), an acute-phase inflammatory molecule, as a candidate protein for OSA-induced HDL dysfunction. Further validation study revealed that serum ORM1 levels were inversely associated with CEC, independent of HDL-cholesterol and high-sensitivity C-reactive protein. CONCLUSIONS: HDL function was impaired in patients with OSA and a reduced CEC. However, CPAP therapy did not affect CEC. An altered HDL proteome, particularly with increased ORM1 levels, may be associated with impaired HDL function. TRIAL REGISTRATION: This clinical study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000025335 and UMIN000025341).

Low fat intake is associated with pathological manifestations and poor recovery in patients with hepatocellular carcinoma.

BACKGROUND: This study aimed to clarify whether dietary deviation is associated with pathological manifestations in hepatocellular carcinoma (HCC) patients. METHODS: Dietary intake was estimated in 35 HCC cases before and after hospitalization by referencing digital camera images of each meal. Pathological conditions were evaluated in nitrogen balance, non-protein respiratory quotient (npRQ), neuropsychiatric testing and recovery speed from HCC treatment. RESULTS: On admission, nitrogen balance and npRQ were negative and less than 0.85, respectively. Five patients were judged to have suffered from minimal hepatic encephalopathy that tended to be associated with a lowered value of npRQ (p = 0.082). The energy from fat intake showed a tendency of positive correlation with npRQ (p = 0.11), and the patients with minimal hepatic encephalopathy took significantly fewer energy from fat (p = 0.024). The energy difference from fat between diets at home versus those in the hospital showed a significant positive correlation with npRQ change after admission (p = 0.014). The recovery speed from invasive treatments for HCC showed a significant negative correlation with npRQ alteration after admission (p = 0.0002, r = -0.73). CONCLUSIONS: These results suggest the lower fat intake leads to deterioration of energy state in HCC patients, which associates with poor recovery from invasive treatments and various pathological manifestations.

[Sleep-disordered breathing].

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction resulting in apneas, hypopneas, oxygen desaturation, and arousal from sleep. Obesity is one of the most significant risk factors for OSA. Although continuous positive airway pressure is considered the first choice of treatment of OSA, weight reduction is another important measure in obese OSA patients. Conversely, a couple of studies showed that OSA itself might lead to increase weight gain by the reduction in sleep and/or the daytime sleepiness. And obesity hypoventilation syndrome (OHS) is defined as chronic daytime hypercapnia in combination with obesity and OSA. OHS patients are more likely to suffer from congestive heart failure, pulmonary hypertension and have worse prognosis than obese eucapnic OSA patients.

Reliability and validity of the Japanese version of the Ullanlinna Narcolepsy Scale and Swiss Narcolepsy Scale for screening Japanese individuals with narcolepsy type 1.

OBJECTIVE: To validate the Japanese versions of the Ullanlinna Narcolepsy Scale (J-UNS) and Swiss Narcolepsy Scale (J-SNS) for screening narcolepsy in the Japanese population and to discuss strategies for their use in hypersomniac individuals. METHODS: We selected 451 outpatients with excessive daytime sleepiness (EDS) already diagnosed according to the International Classification of Sleep Disorders third edition. They responded to both scales twice at 1-month intervals. After eliminating individuals who met the exclusion criteria, validity and reliability analyses were performed on 408 and 381 participants, respectively. RESULTS: Patients with narcolepsy type 1 (NT1) displayed higher J-UNS and lower J-SNS scores than those with NT2 and other sleep disorders. The intraclass correlation coefficients and weighted κ coefficient for scale scores in the total participants and patients with NT1 were ≥0.70 and ≥ 0.40, respectively, indicating high reliability. Furthermore, both the sensitivity and specificity of these scales upon using the original cut-off scores (14 for UNS and 0 for SNS) for detecting NT1 were 0.70 or ≥0.70, suggesting high validity. Additionally, the receiver operating characteristic curve analysis revealed that the best cut-off score did not change for the J-SNS but that for the J-UNS, it increased to 18. In our study, the scale's sensitivity and specificity changed from 96% to 82% and 58%-78%, respectively. CONCLUSIONS: Both scales revealed satisfactory screening abilities for NT1 in the Japanese population. However, it may be better to use J-UNS cut-off scores of 18 for a population with EDS.

Variation of respiratory and pulse events in multiple system atrophy.

INTRODUCTION: A study is eagerly awaited that will reveal the unknown mechanisms of multiple system atrophy (MSA), in which the risk of sudden death is the greatest during sleep. The blunted pulse response to nocturnal respiratory events suggests an abnormal cardiac response to a sleep-related breathing disorder. Patients with MSA have a lower pulse event index (PEI), despite a greater hypoxic burden and a similar frequency of respiratory events. However, the evidence is speculative and not directly proven, and many limitations require further study. METHODS: We conducted a retrospective analysis of 26 patients with MSA who had undergone overnight oximetry between April 2016 and December 2022. RESULTS: The median 4% oxyhemoglobin desaturation index (ODI) was 11.6/h, the 6-bpm PEI was 8.9/h, and the PEI/ODI ratio was as low as 0.91. There were three patients with suspected sudden death; all had low PEI/ODI ratios. The PEI/ODI ratio was followed over time in seven patients, all of whom had a decrease in the ratio. However, the PEI was higher than the ODI in 12/26 (46%) of the patients. CONCLUSION: A low PEI/ODI ratio, reflecting a blunted pulse response to nocturnal respiratory events in patients with MSA, may indicate a worse prognosis. This finding and the significance of the longitudinal decrease in the PEI/ODI ratio will require a prospective study.

Continuous positive airway pressure treatment reduces renal tubular damage in patients with obstructive sleep apnea: A retrospective single-center cohort study.

BACKGROUND: Chronic intermittent hypoxia (IH) plays a significant role in the pathogenesis of obstructive sleep apnea (OSA) comorbidities. The prevalence of chronic kidney disease is higher in patients with OSA than the general population, and renal function decline is well correlated with renal tubular injury. However, little is known about the impact of OSA-induced chronic IH on the renal tubules. METHODS: We conducted a retrospective survey of clinical records performing multiple regression analysis and cluster analysis with particular attention to the 3% oxygen desaturation index (ODI) and urinary N-acetyl-ß-d-glucosaminidase (NAG). RESULTS: In patients with suspicion of OSA, urinary NAG creatinine ratio (UNCR) was elevated as their 3% ODI increased (n = 197, p < 0.001), and the elevated UNCR decreased following CPAP treatment in patients with OSA (n = 46, p = 0.014). Multiple regression analysis showed that 3% ODI was associated with UNCR. Cluster analysis identified three clusters of patients with OSA, including two younger age clusters, one of which was characterized by high BMI, high 3% ODI, and high prevalence of major comorbidities. In a comparative analysis of younger age cases (age ≤ 55, n = 82), the UNCR level was higher in patients with severe 3% ODI (3% ODI > 40 events/h, n = 24) (p = 0.014). CONCLUSIONS: Our results indicate that even at younger ages, OSA patients with severe chronic IH and major comorbidities are susceptible to renal tubular damage. Early treatment with CPAP may attenuate renal tubular injury and progression toward end-stage renal disease.

Significance and usefulness of heart rate variability in patients with multiple system atrophy.

BACKGROUND: The purpose of this study was to investigate whether heart rate variability parameters can be useful for evaluating cardiac autonomic dysfunction in multiple system atrophy patients. METHODS: Both the time and frequency domains of heart rate variability were investigated among 17 multiple system atrophy patients and 27 normal control subjects. RESULTS: All time- and frequency-domain measures, except the low- to high-frequency ratio, were significantly lower in multiple system atrophy patients than in controls. In multiple system atrophy patients, there were significant inverse correlations between heart rate variability parameters and disease duration, as well as disease severity, but heart rate variability parameters were not affected by other autonomic dysfunctions. CONCLUSIONS: The cardiac autonomic state of multiple system atrophy was characterized by decreases in both sympathetic and parasympathetic tones. Because heart rate variability parameters were not affected by other autonomic dysfunctions, this may be a useful method for evaluating cardiac autonomic dysfunction in multiple system atrophy.

Daytime sleepiness in Japanese patients with multiple system atrophy: prevalence and determinants.

BACKGROUND: The recent SLEEMSA study that evaluated excessive daytime sleepiness (EDS) in Caucasian patients with multiple system atrophy (MSA) demonstrated that EDS was more frequent in patients (28%) than in healthy subjects (2%). However, the prevalence and determinants of EDS in other ethnic populations have not been reported to date. METHODS: We performed a single-hospital prospective study on patients with probable MSA. To ascertain the prevalence and determinants of EDS in Japanese MSA patients, we assessed the patients' degree of daytime sleepiness by using the Japanese version of the Epworth Sleepiness Scale (ESS). In addition, we investigated the effects of sleep-disordered breathing (SDB) and abnormal periodic leg movements in sleep (PLMS), which were measured by polysomnography, on the patients' ESS scores. RESULTS: A total of 25 patients with probable MSA (21 patients with cerebellar MSA and 4 patients with parkinsonian MSA) were included in this study. All patients underwent standard polysomnography. The mean ESS score was 6.2 ± 0.9, and EDS was identified in 24% of the patients. SDB and abnormal PLMS were identified in 24 (96%) and 11 (44%) patients, respectively. The prevalences of EDS in patients with SDB and abnormal PLMS were 25% and 18%, respectively. No correlations were observed between ESS scores and the parameters of SDB or abnormal PLMS. CONCLUSIONS: The frequency of EDS in Japanese patients with MSA was similar to that in Caucasian MSA patients. SDB and abnormal PLMS were frequently observed in MSA patients, although the severities of these factors were not correlated with EDS. Further investigations using objective sleep tests need to be performed.

Fraction of apnea is associated with the required continuous positive airway pressure level and reflects upper airway collapsibility in patients with obstructive sleep apnea.

STUDY OBJECTIVES: We aimed to determine whether the fraction of apnea (Fapnea) could be used as an alternative index to reflect upper airway collapsibility. METHODS: We retrospectively recruited 161 patients (16 women, mean age 47.8 years, body mass index [BMI] 28.0 kg/m2, and apnea-hypopnea index 46.4 events/h) with moderate to severe obstructive sleep apnea who had undergone nasal continuous positive airway pressure (CPAP) titration. Fapnea is defined as the percentage of apneic events relative to the total number of apneic and hypopneic events during sleep in a supine position on diagnostic polysomnography. We randomly split the data (70/30) into the development and validation datasets. In the development dataset, we conducted a multiple regression analysis to assess the association of variables, including age, sex, BMI, supine rapid eye movement (REM) sleep apnea-hypopnea index, and apnea with a CPAP level during supine REM sleep (REM_CPAP). Moreover, we developed an equation for predicting the CPAP level. Thereafter, we evaluated the correlation between the actual CPAP level and the value calculated using the model. RESULTS: BMI and Fapnea were the only significant factors that predicted the REM_CPAP level (adjusted r = .60, P < .001) in the development dataset. The validation data revealed a significant correlation between the actual and predicted CPAP levels (r = .69, P < .0001). We observed similar associations during supine non-REM sleep. CONCLUSIONS: Fapnea could significantly predict the CPAP levels during both REM and non-REM sleep, which likely reflects the upper airway collapsibility, independent of the BMI. CITATION: Nakayama H, Takei Y, Kobayashi M, Yanagihara M, Inoue Y. Fraction of apnea is associated with the required continuous positive airway pressure level and reflects upper airway collapsibility in patients with obstructive sleep apnea. J Clin Sleep Med. 2022;18(5):1243-1249.

[Effects of anticoagulant therapy for rapidly progressive interstitial pneumonias].

To clarify the effects of anticoagulant therapy, we investigated patients with rapidly progressive interstitial pneumonias, retrospectively. We defined rapidly progressive pneumonia as idiopathic or secondary interstitial pneumonia with acute exacerbation of respiratory symptoms within 2 months, without infection or heart failure. A total of 20 cases admitted to our hospital between April 1999 and January 2010 met our criteria. Of those 20 cases, 6 were non-idiopathic pulmonary fibrosis (non-IPF), 3 were IPF, 6 were amyopathic dermatomyositis (ADM), 2 were DM, 2 were rheumatoid arthritis, and 1 was mixed connective-tissue disease. We divided the 20 cases into two groups according to whether they were treated with anticoagulant therapy (dalteparin and/or warfarin) (group A, n = 11) or not (group B, n = 9), and compared their outcomes. They were all given standard therapy. There was significantly better survival time in group A than in group B by the Kaplan-Meier survival curve (p = 0.0389). Anticoagulant therapy may improve the survival of patients with rapidly progressive interstitial pneumonias.

Prevalence, clinical symptoms and polysomnographic findings of REM-related sleep disordered breathing in Japanese population.

BACKGROUND: Rapid eye movement sleep -predominant sleep-disordered breathing (REM-SDB) is a condition in which sleep apneas or hypopneas predominantly occur during REM sleep. This study aimed to investigate the prevalence, clinical findings including daytime sleepiness or comorbid cardio-metabolic diseases, and detailed polysomnographic features of REM-SDB in Japanese population. METHODS: Total of 1458 patients diagnosed as SDB were selected for this study. Prevalence of REM-SDB was estimated in the groups of mild, moderate and severe SDB. Polysomnographic findings, daytime sleepiness self-measured with Epworth Sleepiness Scale (ESS) and history of comorbid cardio-metabolic diseases were obtained and compared between the groups with REM-SDB and non-stage specific SDB. RESULTS: Prevalence of REM-SDB according to the criteria #2 was 22.1% in total SDB subjects, 46,1% in mild SDB and 18.9% in moderate SDB. None was found in severe SDB. Patients with REM-SDB showed milder SDB, higher BMI and higher female predominance than those with non-stage specific SDB. They also showed lower arousal index, respiratory arousal index per total AHI, percentage of N1 sleep, total AHI, ODI, and higher sleep efficiency. Meanwhile, maximum event durations of obstructive apnea and hypopnea were significantly longer, and the nadir SpO2 was lower in REM-SDB. The ESS score and percentages of comorbid cardio-metabolic diseases were roughly equivalent between REM-SDB and non-stage specific SDB. CONCLUSION: REM-SDB was associated with high obesity, female gender, and mild severity of SDB. They showed daytime sleepiness and comorbid cardio-metabolic diseases quite equally to patients with non-stage specific SDB in spite of their lower AHI and better sleep quality.

Gradual reduction in the STOP score in patients with obstructive sleep apnea undergoing oral appliance therapy.

Purpose In the treatment of obstructive sleep apnea (OSA), there is not yet a convenient tool for deciding whether a mandibular advancement oral appliance (OA) is adequately adjusted or when to perform post-treatment sleep-testing. We hypothesized that a gradual reduction in the STOP (snoring, tiredness during daytime, observed apnea, high blood pressure) score, i.e., fewer Yes responses in the STOP questionnaire, in patients undergoing OA treatment could be an indicator of better OA adjustment and, thus, the best timing for follow-up polysomnography.Methods The STOP score was recorded at every patient visit when the OA was adjusted ventrally as necessary (i.e., STOP group). We considered that the appropriate timing for follow-up polysomnography was when the STOP score stopped decreasing. A historical control group was established from consecutive patients without a STOP score.Results In the STOP group (n=57), the median (interquartile range) of STOP scores gradually decreased with OA treatment, from 3 (2-3) to 0 (0-1) (p<0.05). While the apnea hypopnea index (AHI) was improved in both the STOP group (19±10 to 5±4 /hr, p<0.01) and the control group (n=61; 19±7 to 8±7 /hr, p<0.01), there was a significant difference in follow-up AHI between the two groups (p<0.05) after controlling for gender (male), age, body mass index, and baseline AHI: a superior treatment outcome in the STOP group.Conclusions The appropriate timing for follow-up sleep-testing in OSA patients undergoing OA therapy is when the STOP score stopped decreasing. This evaluation using the STOP score partly resolves the current "trial-and-error nature" of OA adjustment and facilitates proper post-treatment sleep-testing.

Serum Neutrophil Gelatinase-associated Lipocalin (NGAL) Is Elevated in Patients with Asthma and Airway Obstruction.

Neutrophilic airway inflammation is one of the features of severe asthma. Neutrophil gelatinase-associated lipocalin (NGAL), or lipocalin-2, is a glycoprotein associated with neutrophilic inflammation and can be detected in blood. Recently, blood NGAL levels have been reported to be elevated in chronic obstructive pulmonary disease. However, the clinical significance of serum NGAL levels in patients with asthma has not been elucidated. The aim of this study was to explore the association between serum NGAL level and clinical parameters in patients with asthma. Sixty-one non-smoking people with stable asthma were enrolled in this study. All patients underwent blood collection and pulmonary function tests. The associations between serum NGAL levels and clinical parameters were analyzed retrospectively. Serum NGAL levels in patients with asthma and obstructive ventilatory defect were higher than those in patients with asthma without obstructive ventilatory defect (76.4±51.4 ng/mL vs. 39.3±27.4 ng/mL, P=0.0019). Serum NGAL levels were correlated with forced expired flow at 50% of vital capacity %predicted and forced expired flow at 75% of vital capacity %predicted (r=-0.3373, P=0.0078 and r=-0.2900, P=0.0234, respectively). Results of a multiple regression analysis demonstrated that serum NGAL level was independently associated with obstructive ventilatory defect. Serum NGAL levels were elevated in patients with asthma and obstructive ventilatory defect. NGAL may be involved in airway remodeling possibly mediated by neutrophilic inflammation in asthma.