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.

Clinical, polysomnographic, and cephalometric features of obstructive sleep apnea with AHI over 100.

PURPOSE: Obstructive sleep apnea (OSA) is induced by a sleep-related collapse of the upper airway in association with multiple factors. The severity of OSA is determined by the apnea-hypopnea index (AHI). Although obesity and sex differences are common factors in OSA, the level of the AHI varies to the same degree according to the age and sex and degree of obesity. However, only a few studies have evaluated AHI over 100/h, those reports did not describe why they set the AHI cutoff at 100/h. The purpose of this study was to elucidate the pathogenesis of "very" severe OSA, defined as having an AHI > 100/h. METHODS: AHI > 100/h was set as very severe OSA (VS-OSA) in this study. As controls, moderate to severe OSA patients, matched with VS-OSA for age, sex, and body mass index (BMI), were enrolled. The findings of polysomnography and cephalography between VS-OSA and controls were compared. RESULTS: Eleven patients in the VS-OSA group (mean AHI 110.2/h) and 22 patients in the control group (mean AHI 41.6/h) were compared (mean age 50.2 vs 50.6, male:female 5:6 vs 10:12, mean BMI 35.4 kg/m2 vs 34.5 kg/m2). There were no significant differences in the clinical characteristics. In the polysomnographic parameters, the VS-OSA group showed apnea predominance, the mean percutaneous oxygen saturation (SO2) was significantly lower in all sleep stages, and the minimum SO2 was significantly lower (49.0% vs 77.5%, p = 0.002). A similar apnea duration and rather shorter hypopnea duration were shown. The time of apnea-to-arousal was significantly earlier (- 0.1 s vs 0.9 s, p = 0.003). Lung-to-finger circulation time showed no differences. The cephalometric findings showed no significant differences. CONCLUSIONS: VS-OSA patients were more likely to have apnea predominance, desaturation when sleeping despite a similar apnea duration, and rather shorter hypopnea duration, and arousals were evoked significantly earlier.

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 ).

Usual Interstitial Pneumonia Pattern in the Lower Lung Lobes as a Prognostic Factor in Idiopathic Pleuroparenchymal Fibroelastosis.

BACKGROUND: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare interstitial pneumonia that is characterized by stiffness in both the upper lobes and pleura, which is evident on high resolution computed tomography (HRCT) of the chest. However, prognostic factors for IPPFE have not been identified yet. OBJECTIVE: We aimed to investigate the clinical prognostic factors affecting survival in patients with IPPFE. METHODS: Between April 2009 and September 2017, we enrolled 36 patients who were clinically diagnosed with IPPFE, using HRCT. These patients were classified as either short survival (dead within 12 months from the diagnosis of IPPFE) or long survival (survived for greater than 12 months) groups. We retrospectively analyzed the clinical characteristics, serum markers, pulmonary function test results, and HRCT findings. RESULTS: Twelve patients were classified into the short survival and 24 were categorized into long survival categories. At the time of diagnosis, the incidence of coexistence of a usual interstitial pneumonia (UIP) pattern in the lower lobes on HRCT in the short survival was significantly higher than that in the long survival. Multivariate analysis revealed that a UIP pattern in the lower lobes on HRCT was the only independent variable for poor prognosis. The median survival time from diagnosis in patients with IPPFE was 24 months. Of these patients with IPPFE, the survival time with a UIP pattern was significantly shorter than in those without a UIP pattern. CONCLUSION: Our findings suggest that a UIP pattern in the lower lobes at the time of diagnosis was an independent prognostic factor for IPPFE.

Polysomnographic features of low arousal threshold in overlap syndrome involving obstructive sleep apnea and chronic obstructive pulmonary disease.

PURPOSE: In patients with overlap syndrome (OVS), the pathophysiologies of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease can interact with one another. Focusing on low arousal threshold, the authors evaluated polysomnographic features of OVS patients. METHODS: This retrospective, multicenter study was conducted at three hospitals in Japan. Patients aged ≥ 60 years who underwent polysomnography and pulmonary function testing were reviewed. Severity of airflow limitation (AFL) was classified according to the Global Initiative for Chronic Obstructive Lung Disease criteria. Low arousal threshold was predicted based on the following polysomnography features: lower apnea-hypopnea index (AHI); higher nadir oxygen saturation, and larger hypopnea fraction of total respiratory events. These features were compared among patients with only OSA (n = 126), OVS with mild AFL (n = 16), and OVS with moderate/severe AFL (n = 22). RESULTS: A low arousal threshold was more frequently exhibited by OVS patients with moderate/severe AFL than by those with OSA only (p = 0.016) and OVS with mild AFL (p = 0.026). As forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) decreased in OVS patients, the mean length of apnea decreased (r = 0.388, p = 0.016), hypopnea fractions increased (r = - 0.337, p = 0.039), and AHI decreased (r = 0.424, p = 0.008). FEV1/FVC contributed to low arousal threshold independent of age, sex, smoking history, hospital, or body mass index in all subjects (OR 0.946 [95% CI 0.909-0.984]) and in OVS patients (OR 0.799 [95% CI 0.679-0.940]). CONCLUSIONS: This study first described peculiar polysomnographic features in OVS patients with moderate/severe AFL, suggesting a high prevalence of low arousal threshold.

Practical surrogate marker of pulmonary dysanapsis by simple spirometry: an observational case-control study in primary care.

BACKGROUND: We see patients who present with spirometry airflow limitation despite their forced expiratory volume in one second (FEV1) as well as forced vital capacity (FVC) to be supernormal (FEV1/FVC < 70%, both the %FEV1 and the %FVC ≧ 100%) in asymptomatic healthy non-smokers. Based on previous studies, we hypothesized these spirometry conditions (results measured with spirometry) could be suitably used as a practical surrogate marker of pulmonary dysanapsis: the condition of disproportionate but physiologically normal growth between airways and lung parenchyma. METHODS: We compared the conventional surrogate marker of dysanapsis, maximum mid-expiratory flow to FVC (MMF/FVC), in SUBJECTS (FEV1/FVC < 70%, both the %FEV1 and the %FVC ≧ 100% in healthy non-smokers) (n = 25), in EMPHYSEMA (CT confirmed pulmonary emphysema, same spirometry results with SUBJECTS) (n = 55), and in CONTROLS (age- and height- matched, normal spirometry results) (n = 25). Next we added imaging analysis to evaluate the relationship between the cross sectional airway luminal area (X-Ai) and the lung volume results among the three groups. RESULTS: The MMF/FVC was significantly lower in SUBJECTS and in EMPHYSEMA compared to CONTROLS. However, percent predicted peak expiratory flow (%PEFR) was significantly lower only in SUBJECTS and not in EMPHYSEMA compared to CONTROLS. The ratio of the X-Ai of the trachea and right apical bronchus to lung volume was significantly lower in SUBJECTS compared to CONTROLS. CONCLUSION: The simple spirometry conditions in SUBJECTS are highly suggestive of practical surrogate marker of pulmonary dysanapsis. Awareness of this concept would help to attenuate the risk of overdiagnosis of obstructive pulmonary disease.

Effect of continuous positive airway pressure on regional cerebral blood flow during wakefulness in obstructive sleep apnea.

BACKGROUND: The alteration of regional cerebral blood flow (rCBF) during wakefulness after the treatment for obstructive sleep apnea syndrome (OSA) using continuous positive airway pressure (CPAP) has not been elucidated. The aim of this study was to investigate rCBF characteristics and the effects of nasal CPAP in OSA patients. METHODS: Fifteen severe OSA patients (apnea-hypopnea index, 62.7 ± 22.4/h), when awake, underwent Technetium-99m ethyl cysteinate dimer single photon emission computed tomography before and after CPAP treatment, and the findings were compared to those of nine healthy controls matched for age and sex. RESULTS: Compared to controls, patients with OSA before CPAP treatment showed a significantly lower rCBF in the frontal lobe. After the treatment, no difference in rCBF was observed between the good CPAP compliance group and the controls. In the former group, there was a positive correlation between the 3% oxygen desaturation index on diagnostic polysomnogram and the increase of rCBF after CPAP treatment in the frontal lobe. CONCLUSIONS: When awake, patients with severe OSA were shown to have reversible decreases in rCBF, especially in the frontal lobe, and an appropriate CPAP treatment was thought to improve rCBF in this area. Our results support the importance of appropriate CPAP treatment for severe OSA patients.

A case of middle-aged central sleep apnea due to Joubert syndrome with different treatment effects of oxygen and acetazolamide.

We report a case of severe central sleep apnea incidentally diagnosed during polysomnography for suspected obstructive sleep apnea. Characteristic clinical features included episodic hyperventilation followed by apnea from hypocapnia, which did not follow a Cheyne-Stokes pattern. Combined with the identification of cerebellar and brainstem malformations known as the "molar tooth sign" on a brain MRI, developmental delay, and motor coordination problems, Joubert syndrome (a congenital disease) was first diagnosed at the age of 50 years. Central apneas were also observed during wakefulness, although not continuously. During sleep, continuous positive airway pressure and adaptive servo-ventilation were ineffective at the referring clinic and at our hospital. Supplemental oxygen decreased the frequency of central apneas and significantly shortened the duration of each central sleep apnea compared with room air. In contrast, the opposite response was observed with acetazolamide administration.

Effect of Japanese Cedar Pollen Sublingual Immunotherapy on Asthma Patients with Seasonal Allergic Rhinitis Caused by Japanese Cedar Pollen.

Allergen immunotherapy is a promising treatment for allergic diseases that induce immune tolerance through the administration of specific allergens. In this study, we investigate the efficacy of sublingual immunotherapy (SLIT) in asthmatic patients with SAR-JCP and the dynamics of the parameters before and after treatment in a real-world setting. This was a prospective single-center observational study. Patients with asthma and SAR-JCP (n = 24) were recruited for this study and assessed using symptom questionnaires before SLIT and a year after the SLIT. In addition, a respiratory function test, forced oscillation technique, and blood sampling test were performed during the off-season before and after SLIT. The one-year SLIT for asthma patients with SAR-JCP significantly improved not only allergic rhinitis symptoms, but also asthma symptoms during the JCP dispersal season, and significantly improved airway resistance during the off-season. The change in the asthma control test and the visual analog scale score during the season before and after SLIT was negatively and positively correlated with the change in peripheral blood γδ T cells off-season before and after SLIT, respectively. It was suggested that improvement in asthma symptoms during the JCP dispersal season after SLIT was associated with reduced peripheral blood γδ T cells.

Sleep-related breathing disorders associated with the characteristics of underlying congenital rare diseases of Moebius syndrome and Poland syndrome.

A 24-year-old woman was referred to us with daytime sleepiness. She has two congenital intractable and rare diseases, namely, Moebius syndrome and Poland syndrome. Physiological examinations and a detailed usage analysis under a ventilation device helped to conclude that hypoglossal nerve paralysis and thoracic deformity from her two underlying diseases were associated closely with her final diagnosis of obstructive sleep apnoea and sleep-related hypoventilation due to medical disorders. Bilevel positive pressure ventilation with auto-titrating expiratory positive airway pressure was effective. This is the first report that describes in detail the causal interactions between underlying two intractable and rare diseases and sleep-related breathing disorders.

Difference in upper airway collapsibility during wakefulness between men and women in response to lower-body positive pressure.

Fluid shift from the legs to the neck induced by LBPP (lower-body positive pressure) increases UA (upper airway) collapsibility in healthy men. Rostral fluid displacement during recumbency may therefore contribute to the pathogenesis of OSA (obstructive sleep apnoea). There is a higher prevalence of OSA in men than in women. We therefore hypothesized that UA collapsibility increases more in men in response to rostral fluid displacement than in women. UA collapsibility was assessed in healthy, non-obese men and women while awake by determining UA Pcrit (critical closing pressure) during application of different suction pressures to the UA. Subjects were randomized to 5 min control or LBPP arms after which they crossed-over into the other arm following a 30 min washout. LBPP was applied by inflating anti-shock trousers wrapped around both legs to 40 mmHg. Pcrit, leg fluid volume and neck circumference were measured at baseline and after 5 min of both control and LBPP periods. LBPP caused a decrease in leg fluid volume and an increase in neck circumference that did not differ between men and women. However, compared with the control period, LBPP induced a much greater increase in Pcrit in men than in women (7.2+/-1.8 compared with 2.0+/-1.5 cm H2O, P=0.035). We conclude that rostral fluid displacement by LBPP increases UA collapsibility more in healthy, non-obese men than in women. This may be one mechanism contributing to the higher prevalence of OSA in men than in women.

Borderline pulmonary hypertension associated with chronic hypercapnia in chronic pulmonary disease.

Pulmonary hypertension (PH) due to lung diseases is classified as group 3 by the Dana Point classification. Given the basic pathophysiological conditions of group 3 lung diseases and the previously well-known concept of hypercapnic pulmonary vasoconstriction, chronic hypercapnia besides alveolar hypoxia might be another causative factor to increase mean pulmonary arterial pressure (PAm). Two hundred twenty-five subjects with chronic pulmonary diseases were assessed by a right heart catheterization and blood gas parameters. The subjects were classified into the following 4 groups: Hypercapnic Hypoxia (HCHX), Hypercapnic Normoxia (HCnx), Normocapnic Hypoxia (ncHX), and Normocapnic Normoxia (ncnx). Compared with ncnx, the HCHX, HCnx and ncHX groups all showed significantly higher PAm and met the criteria of borderline PH. Multiple regression analysis showed that PaCO2, as well as SaO2, was an independent variable for PAm. Given the poor prognosis with borderline PH, the elimination of excess pulmonary carbon dioxide in hypercapnia could be a considerable treatment strategy in chronic pulmonary disease.

Lower body positive pressure increases upper airway collapsibility in healthy subjects.

We previously showed that rostral fluid displacement by lower body positive pressure (LBPP) narrows the upper airway (UA) and increases UA resistance, but effects on UA collapsibility remained unknown. To test if LBPP increases UA collapsibility, 13 healthy men were randomized into a control or LBPP arm then crossed over into the other arm with a 30-min washout in between. LBPP was applied by inflating anti-shock trousers wrapped around both legs to 40 mmHg. UA collapsibility was assessed by determining UA critical closing pressure (P crit) during application of different negative airway pressures. P crit and leg fluid volume were measured at baseline and after 5 min during both periods. LBPP caused a significant increase in P crit associated with a reduction in leg fluid volume. We conclude that rostral fluid displacement by LBPP increases UA collapsibility in healthy men, suggesting that fluid shift into the neck could increase UA collapsibility during sleep and thereby predispose patients with fluid overload states to obstructive sleep apnea.

Chronic intermittent hypoxia-mediated renal sympathetic nerve activation in hypertension and cardiovascular disease.

In sleep apnea syndrome (SAS), chronic intermittent hypoxia (CIH) is believed to activate the sympathetic nerve system, and is thus involved in cardiovascular diseases (CVD). However, since patients with SAS are often already obese, and have diabetes and/or hypertension (HT), the effects of CIH alone on sympathetic nerve activation and its impacts on CVD are largely unknown. We, therefore, examined the effects of CIH on sympathetic nerve activation in non-obese mice to determine whether renal sympathetic nerve denervation (RD) could ameliorate CIH-mediated cardiovascular effects. Male C57BL/6 (WT) mice were exposed to normal (FiO2 21%) or CIH (10% O2, 12 times/h, 8 h/day) conditions for 4 weeks with or without RD treatment. Increased urinary norepinephrine (NE), 8-OHdG, and angiotensinogen levels and elevated serum asymmetric dimethyl arginine levels were observed in the CIH model. Concomitant with these changes, blood pressure levels were significantly elevated by CIH treatment. However, these deleterious effects by CIH were completely blocked by RD treatment. The present study demonstrated that CIH-mediated renal sympathetic nerve activation is involved in increased systemic oxidative stress, endothelial dysfunction, and renin-angiotensin system activation, thereby contributing to the development of HT and CVD, thus could be an important therapeutic target in patients with SAS.

Pulmonary Intravascular Large B-cell Lymphoma (IVLBCL) Disguised as an Asthma Exacerbation in a Patient with Asthma.

A 62-year-old man with asthma presented with a 1-month history of wheezing and exertional dyspnea. Although the wheezing symptoms disappeared after systemic corticosteroid therapy, the exertional dyspnea and hypoxemia did not improve. A diagnosis of intravascular large B-cell lymphoma (IVLBCL) with pulmonary involvement was suspected because of the increased serum lactic dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL-2R) level, increased alveolar-arterial oxygen difference (AaDO2), decreased pulmonary diffusing capacity for carbon monoxide (DLCO) and scintigraphic, computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT findings. The patient was diagnosed as having IVLBCL with pulmonary involvement based on a pathological analysis of a random skin biopsy and a transbronchial lung biopsy. IVLBCL should be considered in patients with symptoms of asthma that are refractory to corticosteroid treatment.

Protein-losing Enteropathy Caused by Intestinal or Colonic Lymphangiectasia Complicated by Sporadic Lymphangioleiomyomatosis: A Report of Two Cases.

This report describes two patients with sporadic lymphangioleiomyomatosis complicated by protein-losing enteropathy (PLE). Imaging studies indicated retroperitoneal lymphangioleiomyomas and abnormalities of the adjacent digestive tract. Endoscopic mucosal biopsy revealed colonic lymphangiectasia in one patient; whereas the site in the other patient was intestinal. Treatment with sirolimus led to the complete resolution of PLE within several months; additionally, marked shrinkage was observed in the lymphangioleiomyomas of both cases. These findings suggest that colonic or intestinal lymphatic congestion due to neighboring lymphangioleiomyomas was the mechanism for the development of PLE. At the time of writing this report, the beneficial effect of sirolimus has lasted for more than 3 years.

Effects of transdermal tulobuterol on dyspnea and respiratory function during exercise in patients with chronic obstructive pulmonary disease.

BACKGROUND: Poor exercise tolerability is a major barrier to improving the quality of life of patients with chronic obstructive pulmonary disease (COPD). Although COPD is often treated with long-acting ß2 adrenergic agonists, few studies have examined their effects on exercise tolerability. METHODS: In this study, Japanese COPD patients were treated with 2 mg transdermal tulobuterol, a long-acting ß2 agonist, once daily for 4 weeks. Spirometry and exercise tests were conducted at baseline and at the end of treatment. The patients conducted constant load (30 W for 5 min) and incremental load (starting at 10 W and increasing by 10 W every 1 min for 5 min to a maximum load of 50 W) exercise tests on a cycle ergometer. RESULTS: Thirteen patients with stable COPD participated in this study (mean age ± standard deviation (SD), 69.5±9.7 years; smoking history 55.9±27.8 pack-years). Resting spirometric parameters were unchanged at the end of treatment. The maximum Borg scale for dyspnea and the Borg scale slope (BSS) decreased significantly from baseline to the end of treatment. The threshold load of dyspnea (TLD) increased slightly, although not significantly, in the constant load test but not in the incremental load test. There were no changes in respiratory parameters during exercise after treatment. CONCLUSIONS: In conclusion, we found that treatment with transdermal tulobuterol for 4 weeks improved self-assessed dyspnea in Japanese COPD patients during constant and incremental exercise tests. This improvement in dyspnea may encourage patients to perform daily life activities or regular physical activity.

Hypoxia and hypercapnia affect contractile and histological properties of rat diaphragm and hind limb muscles.

The effects of hypoxia and hypercapnia on contractile and histological properties of the diaphragm and skeletal muscles of the hind limb were examined. Eight-week-old male Sprague-Dawley rats ( [Formula: see text] ) were kept in hypobaric hypoxic ( [Formula: see text] ) or hypercapnic ( [Formula: see text] ) chambers for 6 weeks, and compared with the control rats (room air, [Formula: see text] ). Contractile properties were evaluated with twitch kinetics, force-frequency curve and fatigue tolerance. After the experiments on contractile activities, muscles were fixed for histological examination with ATPase staining. It was demonstrated that peak twitch tension of diaphragm decreased with no significant histological changes under hypoxic conditions while significant contractile and histological changes were observed under hypercapnic conditions. Skeletal muscles of the hind limbs were affected also under hypoxic and hypercapnic conditions but the profiles of the changes in contraction and histology were different from those of the diaphragm. These results suggest that hypoxia and hypercapnia affect differently on contractile and histological properties of respiratory and hind limb muscles. Furthermore, when we consider the conditions involved in chronic obstructive respiratory disease (COPD; both hypoxia and hypercapnia are deeply involved), our results indicate that COPD should be regarded as a systemic disorder rather than a respiratory disease.

Chronic intermittent hypoxia/reoxygenation facilitate amyloid-ß generation in mice.

Previous studies have shown a high prevalence of obstructive sleep apnea (OSA) among patients with Alzheimer's disease (AD). However, it is poorly assessed whether chronic intermittent hypoxia (CIH), which is a characteristic of OSA, affects the pathophysiology of AD. We aimed to investigate the direct effect of intermittent hypoxia (IH) in pathophysiology of AD in vivo and in vitro. In vivo, 15 male triple transgenic AD mice were exposed to either CIH or normoxia (5% O2 and 21% O2 every 10 min, 8 h/day for 4 weeks). Amyloid-ß (Aß) profile, cognitive brain function, and brain pathology were evaluated. In vitro, human neuroblastoma SH-SY5Y cells stably expressing wild-type amyloid-ß protein precursor were exposed to either IH (8 cycles of 1% O2 for 10 min followed by 21% O2 for 20 min) or normoxia. The Aß profile in the conditioned medium was analyzed. CIH significantly increased levels of Aß42 but not Aß40 in the brains of mice without the increase in hypoxia-inducible factor 1, alpha subunit (HIF-1α) expression. Furthermore, CIH significantly increased intracellular Aß in the brain cortex. There were no significant changes in cognitive function. IH significantly increased levels of Aß42 in the medium of SH-SY5Y cells without the increase in the HIF-1α expression. CIH directly and selectively increased levels of Aß42 in the AD model. Our results suggest that OSA would aggravate AD. Early detection and intervention of OSA in AD may help to alleviate the progression of the disease.

Benign giant mediastinal schwannoma presenting as cardiac tamponade in a woman: a case report.

INTRODUCTION: Mediastinal schwannomas are typically benign and asymptomatic, and generally present no immediate risks. We encountered a rare case of a giant benign posterior mediastinal schwannoma, complicated by life-threatening cardiac tamponade. CASE PRESENTATION: We report the case of a 72-year-old Japanese woman, who presented with cardiogenic shock. Computed tomography of the chest revealed a posterior mediastinal mass 150 cm in diameter, with pericardial effusion. The cardiac tamponade was treated with prompt pericardial fluid drainage. A biopsy was taken from the mass, and after histological examination, it was diagnosed as a benign schwannoma, a well-encapsulated non-infiltrating tumor, originating from the intrathoracic vagus nerve. It was successfully excised, restoring normal cardiac function. CONCLUSION: Our case suggests that giant mediastinal schwannomas, although generally benign and asymptomatic, should be excised upon discovery to prevent the development of life-threatening cardiopulmonary complications.