Characteristics of clinical descriptive variables and polysomnographic findings of catathrenia.

STUDY OBJECTIVES: Catathrenia has been classified as a sleep-related breathing disorder variant in the third edition of the International Classification of Sleep Disorders, but its validity remains unverified. We analyzed the clinical descriptive variables and polysomnographic findings of catathrenia and discussed the similarities and differences to those of obstructive sleep apnea (OSA), non-REM parasomnias, and sleep bruxism (SB). METHODS: A retrospective analysis was conducted on 47 patients diagnosed with nocturnal groaning through polysomnography. We examined sex, body mass index, age at symptom onset, weekly symptom frequency, and presence/absence of comorbidities, including OSA, periodic limb movement disorder, non-REM parasomnia, and SB. The groaning event (GE) index was calculated according to sleep position and sleep stage. RESULTS: The distribution of patients with catathrenia did not show sex difference (male/female = 20:27), body mass index was 20.6 ± 3.0 kg/m2, and age of onset was 18.2 ± 7.4 years. The GE index was higher in stages N1 and R than in stage N3 and in the supine position than in the lateral position. There were no cases complicated with non-REM parasomnia, but the complication of SB was observed in 30% of the participants, and SB events appeared immediately before or during the interictal period of the GE episodes in these cases. CONCLUSIONS: Given the clinical background, posture- and sleep stage-dependent appearance of GEs, and the relatively high complication rate of SB, catathrenia pathogenesis may be heterogeneous or comprise elements of different sleep disorders.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 ).

A case of imatinib-related obstructive bronchiolitis followed long term.

Obstructive bronchiolitis (OB) is an intractable disease causing stenosis in the surrounding bronchiolar region and bronchiolar lumen obstruction. Causes of OB are lung and hematopoietic stem-cell transplantation, collagen diseases, infections, and foods, but there are very few reports of drug-induced OB [1]. Imatinib is a drug used for the treatment of leukemia, gastrointestinal stromal tumors, etc. Although there are some reports of imatinib-induced lung injury as a complication (Ohnishi et al., 2006; Ma et al., 2003; Yamasawa et al., 2008; Koide et al., 2011) [[2], [3], [4], [5]], OB has not been reported. We have encountered a patient with OB related to imatinib administered for chronic myelogenous leukemia, who we have followed for 10 years. Drug-induced OB is very rare, but our case demonstrates the importance of considering the possibility of airway lesions by evaluating pulmonary function and expiratory computed tomography in patients with respiratory symptoms despite no shading on imaging.

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.

Chylothorax after spinal fusion surgery: A case report and literature review.

Chylothorax is reported as a postoperative complication, mainly in the field of thoracic surgery, but there are only 14 reports in the field of spinal surgery. A 64-year-old woman underwent spinal fusion surgery by the anterior and posterior approach for her scoliosis. She developed leg edema and right pleural effusion 2 months after the surgery. Laboratory findings showed decreased total protein and albumin levels in serum. The color of the thoracentesis sample was pinkish white, and the Triglyceride level in the pleural effusion was high. So, her leg edema was found to be associated with malnutrition and the pleural effusion was caused by chylothorax. The point of leakage from the lymph duct was confirmed in the right thoracic cavity of the slice that corresponded to that with the screw at Th11 by lymphatic scintigraphy. Her symptoms did not improve by diet restriction and lipidol lymphography, but her pleural effusion and albumin levels improved by the administration of octreotide. In the clinical course, serum albumin levels appeared to show an inverse correlation with the amount of pleural effusion, so it was thought that her serum albumin level decreased owing to leakage of protein, including albumin, into the thoracic cavity via the injured thoracic duct. We concluded that the chylothorax was owing to complications of the surgery. Although reports of chylothorax occurring as a complication of spinal fusion surgery are rare, when prolonged hypoalbuminemia or unilateral pleural effusion is observed, chylothorax should be considered as a differential diagnosis.

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.

Breathing Irregularity Is Independently Associated With the Severity of Obstructive Sleep Apnea in Patients With Multiple System Atrophy.

STUDY OBJECTIVES: Multiple system atrophy (MSA) is a neurodegenerative disease characterized by the combination of cerebellar ataxia, parkinsonism, and autonomic disturbance. Patients with MSA frequently have sleep-disordered breathing. In some patients with MSA, central sleep apnea manifests during the disease's natural course or as a treatment effect. Breathing instability may be involved in the development of obstructive sleep apnea (OSA); therefore, we investigated whether breathing instability affects the severity of OSA in patients with MSA. METHODS: Patients with MSA and a control group of individuals who were matched for age, body mass index (BMI), and supine apnea-hypopnea index (AHI) were recruited. Breathing instability was evaluated by using polysomnography to determine the irregular pattern with approximate entropy (ApEn) of chest respiratory movements during wakefulness before sleep onset. The ApEn values were compared between the groups. The severity of OSA was evaluated with background parameters and ApEn values by regression analysis. RESULTS: Twenty patients with MSA (9 men; mean age, 61 years; BMI, 24.1 kg/m2; supine AHI, 37.9 events/h) were compared to the control group. The ApEn values were higher in the patients with MSA than those in the control group (1.28 versus 1.11; P < .05). Multiple regression analysis showed that supine AHI was associated with ApEn values but not with BMI in patients with MSA and associated with BMI but not with ApEn values in the individuals in the control group. CONCLUSIONS: Patients with MSA had more breathing irregularity. In patients with MSA, breathing instability may be a more influential factor for OSA than BMI. COMMENTARY: A commentary on this article appears in this issue on page 1641.

Ochratoxin A, citrinin and deoxynivalenol decrease claudin-2 expression in mouse rectum CMT93-II cells.

Intestinal epithelial cells are the first targets of ingested mycotoxins, such as ochratoxin A, citrinin and deoxynivalenol. It has been reported that paracellular permeability regulated by tight junctions is modulated by several mycotoxins by reducing the expression of specific claudins and integral membrane proteins in cell-cell contacts, accompanied by increase in phosphorylation of mitogen-activated protein kinases, including extracellular signal-related kinase (ERK) 1/2, p38 and c-Jun NH2-terminal protein kinase. Claudin-2 is expressed in the deep crypt cells, but not in the villus/surface cells in vivo. While Caco-2, T84 and IPEC-J2 cells, which are widely used intestinal epithelial cell lines to assess the influence of mycotoxins, do not express claudin-2, CMT93-II cells express claudin-2. We previously reported that inhibition of the ERK pathway reduced claudin-2 levels in cell-cell contacts in CMT93-II cells. In this study, we examined whether ochratoxin A, citrinin and deoxynivalenol affect claudin-2 expression and ERK1/2 phosphorylation in CMT93-II cells. We found that all mycotoxins reduced claudin-2 expression in cell-cell contacts, with reduction (by citrinin and deoxynivalenol) or no change (by ochratoxin A) in phosphorylated ERK1/2. All mycotoxins increased transepithelial electrical resistance, but did not affect flux of fluorescein. While ochratoxin A and citrinin are known to be nephrotoxic, only deoxynivalenol reduced claudin-2 expression in MDCK II cells derived from the renal tubule. These results suggest that claudin-2 expression is regulated not only by the ERK pathway, but also by other pathways in an organ-specific manner.

Natural course and potential prognostic factors for sleep-disordered breathing in multiple system atrophy.

OBJECTIVE/BACKGROUND: Multiple system atrophy (MSA) frequently results in the development of sleep-disordered breathing (SDB). Few reports have described the natural course of this phenomenon. The aim of the present study was to determine the natural course of SDB and prognostic factors associated with such conditions in MSA. PATIENTS/METHODS: Twenty-four consecutive patients were recruited with probable MSA, who had not been treated with continuous positive airway pressure (CPAP) and had undergone overnight polysomnography (PSG) more than once following the development of snoring or stridor. Based on changes in the apnea-hypopnea index (AHI) over the course of the disease, patients were divided into two groups (AHI-maintained and AHI-deteriorated) and the clinical findings were compared. RESULTS: Mean duration between the first and last PSG was 2.4 ± 1.5 years, and patients underwent PSG assessment an average of 2.5 ± 0.6 times during this period. During this interval, AHI increased from 19.4 ± 22.8/hour to 34.4 ± 30.1/hour (p = 0.006), although spontaneous improvement was observed in 29% of patients. Following the first PSG, all patients were diagnosed with obstructive sleep apnea; however, the SDB type changed from obstructive sleep apnea to central sleep apnea in 3 of the 24 (13%) patients during the period between the first and last PSG. CONCLUSIONS: Although SDB associated with MSA exacerbates with disease progression, spontaneous improvement in AHI may occur in some patients. Earlier development of snoring or stridor may predict rapid progression of SDB in MSA.