Associations of self-efficacy and outcome expectancy with adherence to continuous positive airway pressure therapy in Japanese patients with obstructive sleep apnea.

Objective: To examine the associations of self-efficacy and outcome expectancy with adherence to continuous positive airway pressure (CPAP) therapy among Japanese men with obstructive sleep apnea (OSA) using objective adherence data for CPAP therapy. Methods: We conducted a retrospective study of 497 Japanese men with OSA who were receiving CPAP therapy. Good adherence was defined as CPAP use of ≥4 hours per night for ≥70% of nights. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of good adherence to CPAP therapy with self-efficacy and outcome expectancy (measured with the CPAP Self-Efficacy Questionnaire for Sleep Apnea in Japanese). The models were adjusted for age, duration of CPAP therapy, body mass index, apnea-hypopnea index, Epworth Sleepiness Scale score, and comorbidities (diabetes mellitus and hypertension). Results: In total, 53.5% of participants had good adherence to CPAP therapy. The mean CPAP use was 5.18±1.53 hours/night. After adjusting for related factors, we found significant associations of good adherence to CPAP therapy with self-efficacy scores (OR, 1.10; 95% CI, 1.05-1.13; p<0.001) and outcome expectancy scores (OR, 1.10; 95% CI, 1.02-1.15; p=0.007). Conclusions: Our results indicate that self-efficacy and outcome expectancy are associated with good adherence to CPAP therapy among Japanese men with OSA.

Associations of diabetes mellitus and hypertension with adherence to continuous positive airway pressure therapy in male patients with obstructive sleep apnea.

Methods: We conducted a retrospective study among 497 male patients with OSA on CPAP therapy. Participants with pretreatment Apnea-Hypopnea Index (AHI) data based on overnight polysomnographic recordings completed a questionnaire. Adherence data for CPAP therapy were collected using a smart card system. We classified CPAP use of ≥4 hours per night and ≥70% of nights as good adherence; other CPAP use was categorized as poor adherence. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for poor adherence to CPAP therapy in the hypertension and diabetes mellitus groups, compared with the no comorbidity group, adjusting for body mass index, duration of CPAP therapy, AHI, and Epworth Sleepiness Scale score. Results: In the no comorbidity, hypertension, and diabetes mellitus groups, 43.4%, 44.7%, and 56.0%, respectively, had poor adherence to CPAP therapy. Being in the diabetes mellitus group was significantly associated with poor adherence to CPAP therapy (OR=1.86, 95% CI: 1.18-2.92, p=0.007); there was no association for the hypertension group. Conclusion: Our results indicate that comorbidity of diabetes mellitus is associated with poor adherence to CPAP therapy in male patients with OSA.

Asthma exacerbations in patients with asthma and rhinitis: Factors associated with asthma exacerbation and its effect on QOL in patients with asthma and rhinitis.

BACKGROUND: The comorbidity of asthma and allergic rhinitis is remarkably high, but not much is known about the effects of this combined condition on the quality of life. We aimed to evaluate the factors associated with asthma exacerbations and the effect of the exacerbations on the quality of life (QOL) through a one-year, large-scale, observational study in Japanese patients with asthma and rhinitis. METHODS: A case survey by attending physicians and a patient survey was conducted at each assessment timepoint over a period of one year. Patients were divided into two groups according to the presence or absence of asthmatic attacks after enrollment and were matched using propensity scores to evaluate the factors associated with asthma exacerbations and the effect of the exacerbation on QOL. RESULTS: Potential factors associated with asthma exacerbations included high body mass index value, low forced expiratory flow 75% of forced vital capacity (FEF75%), severe rhinitis as determined based on ARIA (Allergic Rhinitis and its Impact on Asthma). Although patients with asthma exacerbations had significantly impaired quality of life at baseline as evidenced by the economic aspects, in addition to physical, mental, and social activities, no further reduction with the attacks was observed. CONCLUSIONS: This study suggested that higher body mass index (BMI) and severe asthma as well as severe rhinitis were factors associated with asthma exacerbations. Although patients with asthma exacerbations had impaired QOL, attacks caused no further reduction.

Gender Differences in the Clinical Features of Sleep Apnea Syndrome.

Objective Sleep apnea syndrome is more prevalent among men than women and is frequently accompanied by metabolic syndrome (MetS). However, gender differences in the effect of sleep-disordered breathing (SDB) leading to the risk of MetS remain unclear. The aim of our study was to investigate the clinical characteristics of SDB in women and the differential influence of SDB on MetS between genders. Methods In a single-center retrospective study, we compared the data of 1,809 consecutive SDB patients by gender to clarify the characteristics of sleep disorders in women. We also compared the prevalence of MetS and its related abnormalities by gender. A logistic regression analysis was used to determine the contributory factors for MetS. Results The mean age and proportion of patients over 50 years of age were higher in women than in men. SDB was milder in women than in men according to polysomnography findings. Elevated Hemoglobin A1c levels and hyperlipidemia were less frequent in women than in men. The MetS prevalence was similar in women and men (30.0% vs. 35.2%). A logistic regression analysis showed that the apnea-hypopnea index (AHI) was an independent risk factor for MetS in both genders, but that female gender was independently associated with a decreased prevalence of MetS and its related abnormalities. Conclusion Female SDB patients tend to be older with milder apnea and sleepiness than male SDB patients. A higher AHI is a significant risk factor for MetS in both genders, although female gender is an independent inhibitory factor for developing MetS in SDB patients.

Development and evaluation of a self-efficacy instrument for Japanese sleep apnea patients receiving continuous positive airway pressure treatment.

The purpose of this study was to develop and evaluate a self-efficacy instrument for Japanese obstructive sleep apnea (OSA) patients treated with continuous positive airway pressure (CPAP). Analyzed subjects were 653 Japanese OSA patients (619 males and 34 females) treated with CPAP at a sleep laboratory in a respiratory clinic in a Japanese city. Based on Bandura's social cognitive theory, the CPAP Self-Efficacy Questionnaire for Sleep Apnea in Japanese (CSESA-J) was developed by a focus group of experts, using a group interview of OSA patients for the items of two previous self-efficacy scales for Western sleep apnea patients receiving CPAP treatment. CSESA-J has two subscales, one for self-efficacy and the other for outcome expectancy, and consists of a total of 15 items. Content validity was confirmed by the focus group. Confirmatory factor analysis showed that the factor loadings of self-efficacy and outcome expectancy were 0.47-0.76 and 0.41-0.92, respectively, for the corresponding items. CSESA-J had a significant but weak positive association with the General Self-Efficacy Scale, and a strong positive association with "Self-efficacy scale on health behavior in patients with chronic disease." Cronbach's alpha coefficient was 0.85 for the self-efficacy subscale and 0.89 for the outcome expectancy subscale. The intraclass correlation coefficient using data from the first and second measurements with CSESA-J for a subset of 130 subjects was 0.93 for the self-efficacy and outcome expectancy subscales. These results support CSESA-J as a reliable and valid instrument for measuring the self-efficacy of Japanese OSA patients treated with CPAP. Further studies are warranted to confirm validity for female OSA patients and generalizability.

Central sleep apnoea and inflammation are independently associated with arrhythmia in patients with heart failure.

AIMS: We examined whether the severity of central sleep apnoea (CSA) and the level of C-reactive protein are associated with the prevalence and complexity of arrhythmias, and whether these factors contribute to increased risk of nocturnal sudden death. METHODS AND RESULTS: We prospectively examined 178 patients (age 70 ± 1 years) who were admitted to our hospital due to worsening heart failure. We recorded a simultaneous overnight cardiorespiratory polygraph and Holter ECG. Obstructive sleep apnoea was excluded and patients were dichotomized based on the median value of the central apnoea index (CAI) of 7.5/h. The prevalence and complexity of arrhythmias were compared between daytime (06:00 h to 15:00 h) and night-time (21:00 h to 06:00 h). A multivariate logistic regression analysis revealed that the CAI was associated with prevalence of atrial fibrillation (AF) [odds ratio 1.03, 95% confidence interval (CI) 1.02-2.51)] and sinus pause during the night-time period (1.12, 95% CI 1.08-1.35). The CAI and C-reactive protein were independently associated with non-sustained ventricular tachycardia during both daytime (1.22, 95% CI 1.00-6.92; and 5.82, 2.58-56.1, respectively) and night-time periods (3.57, 95% CI 1.06-13.1; and 10.7, 3.30-44.4, respectively). During a mean follow-up period of 22 months, 30 (17%) patients had cardiovascular deaths and the CSA was an independent predictor (hazard ratio 1.29, 95% CI 1.16-2.32); only 5 (2.8%) of them died due to ventricular tachyarrhythmia, occurring during wakefulness. CONCLUSIONS: We demonstrated that the severity of CSA and C-reactive protein levels are independently associated with the prevalence and complexity of arrhythmias. CSA was associated with increased mortality risk, but it was not related directly to nocturnal death due to ventricular tachyarrhythmia.

Classification of chronic cough by systematic treatment cascade trial starting with beta agonist.

BACKGROUND: Chronic cough is one of the most challenging symptoms to diagnose and treat, not only because of the variety of underlying disorders but also its varying susceptibility to treatments. Etiological studies of chronic cough vary depending on the clinical settings and the particular interests of investigators. OBJECTIVES: The purposes of this study were first to categorize the etiology of chronic cough by its response to systematic diagnostic treatments starting from the ß2 agonist and second to sub-categorize ß2 agonist responsive cough (BRC) by the airway hyperresponsiveness. METHODS: One hundred and eighty-four never-smokers received the maximal dose of procaterol to diagnose BRC. BRC was sub-categorized into two groups with or without airway hyperresponsiveness measured by the methacholine challenge test. Sinobronchial syndrome (SBS) was diagnosed by postnasal drip symptoms and by the response to clarythromycin and carbocysteine. Atopic cough (AC) was diagnosed by the evidence of atopy and the response to cetirizine hydrochloride. Gastroesophageal reflux disease (GERD) was diagnosed by the response to rabeprazole sodium. Since we did not investigate eosinophil counts in the tissue or in the induced sputum, no diagnosis of eosinophilic bronchitis was made. RESULTS: One hundred and nine patients had BRC. Twenty-three of them had bronchial asthma (BA), 53 had cough variant asthma (CVA) and 33 had non-hyperresponsive BRC (NHBRC). Thirty-one patients had GERD, 27 had AC and 14 had SBS. Twenty-five patients had more than one diagnosis in combination, while 6 had other miscellaneous diseases. Twelve patients were undiagnosed and 11 dropped out of the study. CONCLUSIONS: The majority of chronic cough was BRC. NHBRC was a new chronic cough entity. GERD is a common cause of chronic cough in Japan, as in Western countries. AC and SBS are also causes of chronic cough in Japan. TRIAL REGISTRATION: University hospital medical information network (UMIN 000007483).

Validity of sheet-type portable monitoring device for screening obstructive sleep apnea syndrome.

PURPOSE: The SD-101 is a non-restrictive sheet-like medical device that measures sleep-disordered breathing using pressure sensors that can detect the gravitational alterations in the body that accompany respiratory movement. One report has described that the screening specificity of the SD-101 for mild to moderate obstructive sleep apnea syndrome (OSAS) is relatively low. The present study examines whether the accuracy of the SD-101 for OSAS screening is improved by simultaneously measuring percutaneous oxygen saturation (SpO2). METHODS: Sixty consecutive individuals with suspected OSAS consented to undergo overnight polysomnography (PSG) together with simultaneous measurements of SD-101 and SpO2 at our laboratory. RESULTS: The apnea-hypopnea index (AHI) determined from PSG and the respiratory disturbance index determined from SD-101 measurements significantly correlated (SD-101 alone: r = 0.871, p < 0.0001; SD-101 with SpO2: r = 0.965, p < 0.0001). Bland-Altman plots showed a smaller dispersion for the SD-101 with SpO2 than for the SD-101 alone. The SD-101 with SpO2 detected an AHI of >15 on PSG with a sensitivity and specificity of 96.9 and 90.5 % compared with 87.5 and of 85.7 %, respectively, of the SD-101 alone. CONCLUSIONS: Simultaneously measuring SpO2 improved the accuracy of the SD-101 for OSAS screening. Furthermore, this modality appears to offer high sensitivity and specificity for detecting even moderately severe OSAS.

Accuracy of ECG-based screening for sleep-disordered breathing: a survey of all male workers in a transport company.

PURPOSE: Sleep-disordered breathing (SDB) is associated with increased risk for cardiovascular morbidity and mortality and for sleepiness-related accidents, but >75 % of the patients remain undiagnosed. We sought to determine the diagnostic accuracy of ECG-based detection of SDB when used for population-based screening. METHODS: All male workers, mostly truck drivers, of a transport company (n = 165; age, 43 ± 12 years) underwent standard attended overnight polysomnography. Cyclic variation of heart rate (CVHR), a characteristic pattern of heart rate associated with SDB, was detected from single-lead ECG signals during the polysomnography by a newly developed automated algorithm of autocorrelated wave detection with adaptive threshold (ACAT). RESULTS: Among 165 subjects, the apnea-hypopnea index (AHI) was ≥5 in 62 (38 %), ≥15 in 26 (16 %), and ≥30 in 16 (10 %). The number of CVHR per hour (CVHR index) closely correlated with AHI [r = 0.868 (95 % CI, 0.825-0.901)]. The areas under the receiver operating characteristic curves for detecting subjects with AHI ≥5, ≥15, and ≥30 were 0.796 (95 % CI, 0.727-0.855), 0.974 (0.937-0.993), and 0.997 (0.971-0.999), respectively. With a predetermined criterion of CVHR index ≥15, subjects with AHI ≥15 were identified with 88 % sensitivity and 97 % specificity (likelihood ratios for positive and negative test, 30.7 and 0.12). The classification performance was retained in subgroups of subjects with obesity, hypertension, diabetes mellitus, dyslipidemia, and decreased autonomic function. CONCLUSIONS: The CVHR obtained by the ACAT algorithm may provide a useful marker for screening for moderate-to-severe SDB among apparently healthy male workers.

Screening for obstructive sleep apnea by cyclic variation of heart rate.

BACKGROUND: Despite the adverse cardiovascular consequences of obstructive sleep apnea, the majority of patients remain undiagnosed. To explore an efficient ECG-based screening tool for obstructive sleep apnea, we examined the usefulness of automated detection of cyclic variation of heart rate (CVHR) in a large-scale controlled clinical setting. METHODS AND RESULTS: We developed an algorithm of autocorrelated wave detection with adaptive threshold (ACAT). The algorithm was optimized with 63 sleep studies in a training cohort, and its performance was confirmed with 70 sleep studies of the Physionet Apnea-ECG database. We then applied the algorithm to ECGs extracted from all-night polysomnograms in 862 consecutive subjects referred for diagnostic sleep study. The number of CVHR per hour (the CVHR index) closely correlated (r=0.84) with the apnea-hypopnea index, although the absolute agreement with the apnea-hypopnea index was modest (the upper and lower limits of agreement, 21 per hour and -19 per hour) with periodic leg movement causing most of the disagreement (P<0.001). The CVHR index showed a good performance in identifying the patients with an apnea-hypopnea index ≥15 per hour (area under the receiver-operating characteristic curve, 0.913; 83% sensitivity and 88% specificity, with the predetermined cutoff threshold of CVHR index ≥15 per hour). The classification performance was unaffected by older age (≥65 years) or cardiac autonomic dysfunction (SD of normal-to-normal R-R intervals over the entire length of recording <65 ms; area under the receiver-operating characteristic curve, 0.915 and 0.911, respectively). CONCLUSIONS: The automated detection of CVHR with the ACAT algorithm provides a powerful ECG-based screening tool for moderate-to-severe obstructive sleep apnea, even in older subjects and in those with cardiac autonomic dysfunction.

Diagnosis of sleep apnea by the analysis of heart rate variation: a mini review.

Cyclic variation of heart rate (CVHR) associated with sleep apnea/hypopnea episodes has been suggested as a marker of sleep disordered breathing (SDB). This study examined the utility of ECG-based CVHR detection for diagnosing SDB using simultaneous polysomnography as the reference standard. We used a previously developed automated CVHR detection algorithm (autocorrelated wave detection with adaptive threshold, ACAT) that provides the number of CVHR per hour (CVHR index). The ACAT was refined using a polysomnographic database of 194 subjects with various severities of SDB and then, applied to a single channel ECG obtained during standard overnight polysomnography in 862 consecutive subjects referred for SDB diagnosis. Using multiple thresholds of CVHR index ≥ 38 and <27, positive and negative predictive values of 95.6% and 95.1%, respectively, were achieved for detecting and excluding subjects with apnea-hypopnea index (AHI) ≥ 30, leaving 58 (6.7%) unclassified subjects. Positive and negative likelihood ratios (LRs) were 97.3 and 0.23, respectively. Also, thresholds of CVHR index ≥ 29 and <7 provided 96.1% and 95.1% of positive and negative predictive values, respectively, for subjects with AHI ≥ 15 (LRs, 50.6 and 0.11), leaving 426 (49.4%) unclassified subjects. The CVHR correlated with the AHI (r = 0.86) and showed the limits of agreement with the AHI of 19.6 and -18.6. Automated detection of CVHR by the ACAT algorithm provides useful screening tool for both increasing and decreasing probability of moderate and sever SDB with adequate thresholds.

Risk factors for obstructive sleep apnea syndrome screening in mood disorder patients.

AIMS: Previous studies have reported that the incidence of obstructive sleep apnea syndrome (OSAS) in patients with depression is higher than in the general population. We examined the risk factors to predict OSAS in mood disorder patients with depressive symptoms. METHOD: We conducted polysomnography for patients who satisfied the following criteria: (i) diagnosis of major depressive disorder or bipolar disorder according to the Mini-International Neuropsychiatric Interview (MINI); (ii) a score of > or =10 on the Hamilton Rating Scale for Depression (HAM-D); (iii) fulfillment of either (a) or (b) below: (a) at least one of the following: severe snoring, witnessed apnea during sleep, excessive daytime sleepiness; (b) at least one of the following plus an oxygen desaturation index of 4% > or =5 times/h by pulse oximeter: mild snoring, sleep disturbance, headache, high blood pressure. The patients with apnea hypopnea index > or =5 were diagnosed with OSAS. RESULTS: Of the 32 mood disorder patients who met the subject conditions, 59.4% had OSAS. The diagnosis rate with our criteria was significantly higher than the previously reported incidence of OSAS in patients with depression. There was no significant difference among diagnosis rates as to individual risk factors or the number of risk factors. A multiple regression test showed no significant association between apnea-hypopnea index and other clinical factors including depression severity. CONCLUSION: The present results showed that OSAS can be detected at a remarkably higher rate by considering appropriate OSAS risk factors in mood disorder patients, and suggested that there is a high rate of undetected and therefore untreated OSAS among mood disorder patients.

[The relationships between initial clinical features and prognosis in 14 cases of diffuse alveolar hemorrhage syndrome].

Diffuse pulmonary alveolar hemorrhage (DAH) is caused by various disorders and is a medical emergency that often results in acute respiratory failure requiring prompt diagnosis and aggressive treatment. However, the relationships between the prognosis and the initial clinical feature in DAH remain unclear. We investigated the relationships between initial clinical features and prognosis in 14 cases of DAH. We examined 14 patients with DAH about laboratory data, CT scan findings, treatment and outcome. Three of 14 patients died of acute respiratory failure due to DAH. In the laboratory data on admission, the patients with over 230 IU/L of serum LDH levels had a poor outcome. In pulmonary function data on admission, the patients with under 300 of P/F ratio had poor outcome. On CT scan findings on admission, the patients with consolidation shadows had a poor outcome compared to the patients with ground-glass shadows. In our data, serum LDH concentration, P/F ratio and CT scan findings on admission are important factors in the prognosis of DAH.

A phase II study of S-1 monotherapy as second-line treatment for advanced non-small cell lung cancer.

PURPOSE: To assess the efficacy and toxicity of an oral anticancer fluoropyrimidine derivative, S-1, for previously treated patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced (clinical stage IIIB-IV) NSCLC who had previously received one platinum-based chemotherapy were enrolled. S-1 was administered orally at the dosage decided by using the nomogram based on patient BSA b.i.d. for 28 consecutive days, repeated every 6 weeks. RESULTS: Between August 2005 and July 2007, 50 patients were entered into this study. Six patients achieved partial response (PR), and the overall response rate of eligible patients was 12.5% (6/48) (95% confidence interval (95%CI), 3.1-21.9%). Disease control rate was 39.6% (19/48) (95%CI, 25.7-53.4%). Median progression-free survival was 2.5 months. Median survival time was 8.2 months, and 1-year survival rate was 29.6%. No grade 4 toxicities were encountered. Grade 3 hematological toxicities comprised neutropenia in one patient (2.1%) and anemia in one patient (2.1%). Grade 3 non-hematological toxicities were observed in only five patients (10.4%). Treatment-related death did not occur. CONCLUSION: S-1 is an active and well-tolerated monotherapy for second-line treatment of advanced NSCLC.

[A case of advanced small cell lung cancer complicated by chronic renal failure treated with amrubicin].

A 64-year old man first visited our clinic approximately 10 years ago because of diabetic nephropathy that had developed into chronic renal failure. He was hospitalized to examine a left S10 tumor shadow. Based on the results of these examinations, a primary left S10 T2N0M1, ED small cell lung cancer, was diagnosed. During his outpatient visits nephropathy was found. Following admission, he began dialysis (HD). During the detailed examinations, chemotherapy with amrubicin (AMR)was performed and the blood concentration of the drug was measured. The results showed no significant variations in blood concentration before and after the dialysis. While PR was achieved in this patient, a reduction in grade 4 eosinophils was observed as an adverse reaction.

[Clinical usefulness and health-economic benefits of a new sheet-like medical device (SD-101) for the diagnosis of sleep apnea syndrome].

The SD-101 (Kenzmedico co. Ltd., Saitama, Japan), a non-invasive medical device capable of measuring respiratory parameters during sleep, has recently been developed. It operates while placed under the body like a bed pad equipped with 162 pressure sensors, with the patient in bed. To evaluate the efficacy and safety of the SD-101 for the diagnosis of sleep apnea syndrome (SAS), we enrolled 52 patients with suspected SAS (45 men and 7 women; mean age, 45.6 +/- 10.9 years) in this study. Each subject underwent measurement using the SD-101 and a polysomnograph simultaneously, and we analyzed and compared them. In addition, health-economic benefits of the SD-101 were estimated based on the results. A significantly strong correlation was obtained between the apnea hypopnea index of PSG and its of SD-101 (r = 0.86, p < 0.0001). No adverse event due to the SD-101 occurred, while use of the SD-101 greatly reduced "feeling of being constrained" and discomfort during examination (Wilcoxon test: p < 0.0001). These findings could indicate that the SD-101 is clinically useful and will make a contribution to health-economic benefits for SAS in Japan.

Incidence of chronic obstructive pulmonary disease, and the relationship between age and smoking in a Japanese population.

BACKGROUND: Accurately evaluating a risk of chronic obstructive pulmonary disease (COPD) requires a large-scale longitudinal study using a standard criterion for diagnosing COPD. There have been only a few such follow-up studies in Europe and no reports in Asia. We estimated the incidence rate and incidence rate ratio (IRR) of age and smoking for COPD in a Japanese population using the diagnosis criterion of the Global Initiative for Chronic Obstructive Lung Disease guidelines. METHODS: Subjects were 17,106 participants aged 25-74 years during health check-ups including spirometry from April 1997 through March 2005 in Japan. Total follow-up of participants were 47,652 person-years in males and 25,224 person-years in females. The IRR of age and smoking was estimated using Cox proportional hazard models with both variables. RESULTS: We identified 466 incidence cases of COPD. The incidence rate per 100 person-years was 0.81 (95% confidence interval [CI], 0.73-0.89) in males and 0.31 (0.24-0.38) in females, and significantly increased with age in both sexes. The incidence rate for current smokers was significantly higher than that for male non-smokers but not significantly for females. Among males, the IRR for current smokers with Brinkman Index < 400, 400-799, and 800+ was 1.2 (0.8-1.9), 2.7 (1.9-3.8), and 4.6 (3.3-6.5), respectively. CONCLUSION: These results indicated that the COPD risk gradually increased with aging, and that there was a dose-response relationship between smoking and COPD risk.

Treatment for Churg-Strauss syndrome: induction of remission and efficacy of intravenous immunoglobulin therapy.

Churg-Strauss syndrome (CSS) is characterized by the presence of asthma, eosinophilia, and small-vessel vasculitis with granuloma. It is a distinct entity, as determined from all classifications of systemic vasculitis. The poor prognostic factors in CSS are renal insufficiency, cardiomyopathy, severe gastrointestinal (GI) tract, and central nervous systems (CNS) involvement. The initial management of CSS should include a high dose of a corticosteroid: prednisone at 1 mg/kg/day or its equivalent for methylprednisolone with tapering over 6 months. In patients with severe or rapidly progressing CSS, the administration of methylprednisolone pulse at 1 g/body/day for 3 days is recommended. When corticosteroid therapy does not induce remission, or when patients have poor prognostic factors, immunosuppressive cytotoxic therapy is indicated. However, some patients with severe CSS often show resistance to conventional treatment. We think that IVIG therapy is a hopeful candidate for second-line treatment for CSS patients, particularly in the case of neuropathy and/or cardiomyopathy, which are resistant to conventional therapy. However, there is not much evidence supporting the effectiveness of IVIG in CSS, and the mechanisms underlying the action of IVIG remain unclear. Now we are performing clinical trials of IVIG therapy for CSS patients who are resistant to conventional treatment, through a nationwide double-blinded placebo-controlled study in Japan.