RESUMO
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 ).
Assuntos
Doença de Depósito de Glicogênio Tipo II/diagnóstico , Programas de Rastreamento , Síndromes da Apneia do Sono/epidemiologia , Idade de Início , Diagnóstico Precoce , Doença de Depósito de Glicogênio Tipo II/epidemiologia , Humanos , Japão/epidemiologia , Polissonografia , Estudos Prospectivos , Projetos de PesquisaRESUMO
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.
Assuntos
Nível de Alerta , Síndrome de Sobreposição da Doença Pulmonar Obstrutiva Crônica e Asma/diagnóstico , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Idoso , Nível de Alerta/fisiologia , Síndrome de Sobreposição da Doença Pulmonar Obstrutiva Crônica e Asma/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Estudos Retrospectivos , Limiar Sensorial/fisiologia , Apneia Obstrutiva do Sono/fisiopatologia , EspirometriaRESUMO
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.
Assuntos
Asma/complicações , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/patologia , Humanos , Lactato Desidrogenases/sangue , Pulmão/patologia , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Receptores de Interleucina-2/sangue , Tomografia Computadorizada por Raios XRESUMO
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.
Assuntos
Enteropatias/complicações , Linfangiectasia/complicações , Linfangioleiomiomatose/complicações , Enteropatias Perdedoras de Proteínas/etiologia , Adulto , Doenças do Colo/complicações , Dietoterapia/métodos , Dieta com Restrição de Gorduras , Feminino , Humanos , Imunossupressores/uso terapêutico , Enteropatias Perdedoras de Proteínas/terapia , Sirolimo/uso terapêutico , Resultado do TratamentoAssuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Receptores ErbB/genética , Cloridrato de Erlotinib/administração & dosagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Meníngeas/tratamento farmacológico , Mutação , Feminino , Humanos , Neoplasias Meníngeas/secundário , Pessoa de Meia-IdadeRESUMO
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.
RESUMO
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.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Lobo Frontal/irrigação sanguínea , Apneia Obstrutiva do Sono/fisiopatologia , Vigília/fisiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Valores de Referência , Fluxo Sanguíneo Regional/fisiologia , Apneia Obstrutiva do Sono/terapia , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
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.
Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Oxigenoterapia Hiperbárica , Hipóxia/metabolismo , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Ácido Aspártico Endopeptidases/metabolismo , Linhagem Celular Tumoral , Transtornos Cognitivos/etiologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neuroblastoma/patologiaRESUMO
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.
RESUMO
The patient was an 84-year-old man patient diagnosed as malignant pleurisy associated with lung cancer. After drainage of the right pleural effusion, pleurodesis with distilled water was performed. Despite the enlargement of the primary lesion of the lung cancer during the follow-up period, the amount of pleural effusion did not increase for more than one year. No adverse effects associated with pleurodesis were noted. Pleurodesis with distilled water should be considered as one of the choices for treatment in the management of malignant pleurisy especially in elderly.
Assuntos
Neoplasias Pulmonares/complicações , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/terapia , Pleurisia/etiologia , Pleurisia/terapia , Pleurodese/métodos , Idoso de 80 Anos ou mais , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Derrame Pleural Maligno/diagnóstico por imagem , Pleurisia/diagnóstico por imagem , Pleurodese/efeitos adversos , Radiografia Torácica , Tomografia Computadorizada por Raios X , Água/administração & dosagemRESUMO
BACKGROUND: The impulse oscillation system (IOS) measures respiratory impedance (Zrs) in terms of resistance (Rrs) and reactance (Xrs) at multiples of 5 Hz. These measurements can be used clinically to help diagnose and monitor respiratory disorders, independent of effort. METHODOLOGY: The predictive equation for resistance at 5 and 20 Hz and impedance at 5 Hz (R5, R20, X5), for the first time, in 299 Japanese adult subjects was determined. In addition, the within single day variation and between day variation were determined. RESULTS: The predictive equation for R5, R20 and X5 revealed a clear difference with respect to the subject's smoking history (lifelong non-smoker, n = 166, adjusted r = 0.55, 0.46 and 0.57, respectively, vs. smoker, n = 133, adjusted r = 0.47, 0.42 and 0.47, respectively). This difference was less obvious with respect to gender (female, n = 120, adjusted r = 0.42, 0.20 and 0.47, respectively, vs. male, n = 179, adjusted r = 0.46, 0.37 and 0.47, respectively). The predictive equations were dependent on the log of height (H) for both R5 and R20, and on age and log of height for X5. The equations were: R5 (KPa/L/s) = -3.841167 x logH + 8.671580; R20 (KPa/L/s) = -2.546561 x logH + 5.841867; and X5 (KPa/L/s) = -0.000097 x Age + 1.018597 x logH - 2.343672. For these parameters there were no statistically significant differences for within day repeatability or between day variations (P > 0.05), suggesting a high degree of reproducibility for IOS measurements. CONCLUSION: It was possible to determine a predictive equation and confirm a high degree of reliability of IOS parameters in Japanese adult subjects.