Language：English  

DOI： 10.1016/j.sleep.2023.07.005

PubMed

researchmap

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1016/j.parkreldis.2023.105817

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

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-β-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.

DOI： 10.1016/j.sleep.2023.03.028

PubMed

researchmap

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Nasal breathing disorders are associated with obstructive sleep apnea (OSA) syndrome and influence the availability of continuous positive airway pressure (CPAP) therapy. However, information is scarce about the impact of nasal resistance assessed by rhinomanometry on CPAP therapy. This study aimed to examine the relationship between CPAP adherence and nasal resistance evaluated by rhinomanometry, and to identify clinical findings that can affect adherence to CPAP therapy for patients with OSA. This study included 260 patients (199 men, 61 women; age 58 [interquartile ranges (IQR) 50-66] years) with a new diagnosis of OSA who underwent rhinomanometry (before, and 1 and 3 months after CPAP introduction) between January 2011 and December 2018. CPAP use was recorded, and the good and poor CPAP adherence groups at the time of patient registration were compared. Furthermore, those with improved and unimproved pre-CPAP high rhinomanometry values were also compared. Their apnea-hypopnea index (AHI) by polysomnography at diagnosis was 45.6 (IQR 33.7-61.6)/hour, but the residual respiratory event (estimated AHI) at enrollment was 2.5 (IQR 1.4-3.9)/hour and the usage time was 318 (IQR 226-397) minutes, indicating that CPAP was effective and adherence was good. CPAP adherence was negatively correlated with nasal resistance (r = -0.188, p = 0.002). The participants were divided into good (n = 153) and poor (n = 107) CPAP adherence groups. In the poor adherence group, rhinomanometry values before CPAP introduction were worse (inspiration, p = 0.003; expiration, p = 0.006). There was no significant difference in patient background when comparing those with improved (n = 16) and unimproved (n = 12) pre-CPAP high rhinomanometry values. However, CPAP usage time was significantly longer in the improved group 1 month (p = 0.002) and 3 months (p = 0.026) after CPAP introduction. The results suggest that nasal resistance evaluated by rhinomanometry is a useful predictor of CPAP adherence, and that improved rhinomanometry values may contribute to extending the duration of CPAP use.

DOI： 10.1371/journal.pone.0283070

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: This study aimed to examine the factors associated with cytomegalovirus (CMV) antigenemia and the time of onset of CMV antigenemia among patients with rheumatic diseases. METHODS: A single-center, retrospective, observational study was conducted in our institution from January 2009 to December 2017. This study included patients with rheumatic diseases who had at least one CMV antigen measurement. Multivariate analysis and receiver operating characteristic analysis was performed. RESULTS: A total of 249 patients underwent CMV antigenemia assay, and 84 (33.7%) patients tested positive. When the association between CMV antigenemia and possible associated factors was investigated, multivariate analysis showed that daily steroid dose increased the odds of having CMV [odds ratio 16.25, 95% confidence interval (CI), 5.360-49.253]. In this study, the cutoff value of daily steroid dose found in this study (0.45 mg/kg/day) was reasonable in clinical practice, and the area under the curve of the steroid dose was 0.838 [95% CI 0.781-0.882], which was the largest of the known indicators. Moreover, the median time from the start of immunosuppressive therapy to the onset of CMV antigenemia was 30 (interquartile range, 21-44) days, and most of the daily steroid users (85.7%) developed CMV antigenemia within 60 days. CONCLUSIONS: The daily steroid dose is the most important factor associated with CMV antigenemia. Therefore, monitoring and treatment strategies based on the steroid dose, especially in the initial 2 months, are important.

DOI： 10.1016/j.jiac.2022.07.004

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: A recent study demonstrated that continuous positive airway pressure (CPAP) may exacerbate obstructive sleep apnea (OSA) in patients with multiple system atrophy (MSA) and a floppy epiglottis (FE) as the CPAP promotes downward displacement of the epiglottis into the laryngeal inlet. In this case series, we examined the effectiveness of an oral appliance (OA) for treating OSA in three patients with MSA and an FE. METHODS: Patients with MSA were demonstrated to have an FE on fiberoptic laryngoscopy under sedation using intravenous propofol. The therapeutic intervention was fitting an OA. Polysomnography (PSG) was performed subsequently with the OA in place. RESULTS: In three patients with MSA, some parameters used to assess the severity of OSA improved with an OA. Both apnea-hypopnea index (AHI) and arousal index (ArI) decreased while wearing the OA in two cases while in the third case, apnea index (AI) and cumulative time at peripheral oxygen saturation (SpO2) below 90% (CT90) decreased, but AHI and ArI increased. The only side effects were transient TMJ discomfort, masseter muscle pain, and tooth discomfort. CONCLUSION: OA therapy using a two-piece type mandibular advancement device (MAD) may be a useful treatment intervention for patients with OSA who have MSA and FE.

DOI： 10.1007/s11325-022-02607-0

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：AME Publishing Company  

DOI： 10.21037/tlcr-21-838

researchmap

Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00298&link_issn=&doc_id=20211216270004&doc_link_id=10.18907%2Fjjsre.43.6_589&url=https%3A%2F%2Fdoi.org%2F10.18907%2Fjjsre.43.6_589&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s00262-021-03078-0

researchmap

Other Link： https://link.springer.com/article/10.1007/s00262-021-03078-0/fulltext.html

Language：Japanese   Publisher：(NPO)日本肺癌学会  

researchmap

Language：Japanese   Publisher：(NPO)日本肺癌学会  

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

<sec><title>Objectives</title>Although immune checkpoint inhibitors (ICIs) have been shown to improve overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) patients, ICIs sometimes cause various types of immune-related adverse events (irAEs), which lead to the interruption of ICI treatment. This study aims to evaluate the clinical significance of the continuation of ICIs in NSCLC patients with irAEs and to assess the safety and efficacy of the readministration of ICIs after their discontinuation due to irAEs.

</sec><sec><title>Methods</title>We retrospectively identified patients with advanced NSCLC who were treated with first- to third-line anti-programmed cell death-1 (PD-1) therapy from January 2016 through October 2017 at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. Progression-free survival (PFS) and OS from the initiation of ICI treatment were analyzed in patients with and without irAEs, with and without ICI interruption, and with and without ICI readministration. A 6-week landmark analysis of PFS and OS was performed to minimize the lead-time bias associated with time-dependent factors.

</sec><sec><title>Results</title>Of 231 patients who received anti-PD-1 antibodies, 93 patients (40%) developed irAEs. Of 84 eligible patients with irAEs, 32 patients (14%) continued ICIs, and OS was significantly longer in patients who continued ICIs than that in patients who discontinued ICIs [not reached (95% CI: NE-NE) <italic>vs</italic>. not reached (95% CI: 22.4–NE); p = 0.025]. Of 52 patients who discontinued ICIs, 14 patients (6.1%) readministered ICIs, and OS in patients with ICI readministration was significantly longer than that in patients without ICI readministration [not reached (95% CI: NE-NE) <italic>vs</italic>. not reached (95% CI: 8.4–NE); p = 0.031].

</sec><sec><title>Conclusion</title>The current study demonstrated that both the continuation and readministration of ICIs after irAE occurrence improved OS compared to the permanent interruption of ICIs in NSCLC patients with ICI-related irAEs.

</sec>

DOI： 10.3389/fonc.2021.704475

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

There has been a long-standing controversy regarding the physiological role of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) in sleep/wake architecture. Some studies have reported that 5-HT acts as a sleep-promoting agent, but several studies have suggested that DRN 5-HT neurons function predominantly to promote wakefulness and inhibit rapid eye movement (REM) sleep. Furthermore, recent studies have reported that there is a clear neurobiological difference between a waking state that includes alertness and active exploration (i.e., active wakefulness) and a waking state that is devoid of locomotion (i.e., quiet wakefulness). These states have also been shown to differ clinically in terms of memory consolidation. However, the effects of 5-HT neurons on the regulation of these two different waking states have not been fully elucidated. In the present study, we attempted to examine the physiological role of DRN 5-HT neurons in various sleep/wake states using optogenetic methods that allowed manipulation of cell-type specific neuronal activation with high temporal and anatomical precision. We crossed TPH2-tTA and TetO-ChR2(C128S) mice to obtain mice with channelrhodopsin-2 (ChR2) [C128S]-expressing central 5-HT neurons, and we activated DRN-5HT neurons or medullary 5-HT neurons. Optogenetic activation of DRN 5-HT neurons caused rapid transition from non-REM sleep to active wakefulness, not quiet wakefulness, whereas activation of medullary 5-HT neurons did not appear to affect sleep/wake states or locomotor activity. Our results may shed light on the physiological role of DRN 5-HT neurons in sleep/wake architecture and encourage further investigations of the cortical functional connectivity involved in sleep/wake state regulation.

DOI： 10.1016/j.brainresbull.2021.09.019

PubMed

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Background: Although immune checkpoint inhibitors (ICIs) are effective for advanced non-small cell lung cancer (NSCLC), ICIs may cause interstitial lung disease (ILD), which results in treatment discontinuation and is sometimes fatal. Despite the high incidence of ICI-related ILD, there are few cancer treatment options for patients. This study aimed to evaluate the safety and efficacy of subsequent systemic cancer therapy in NSCLC patients with ICI-related ILD. Methods: We retrospectively assessed NSCLC patients who received programmed cell death-1 (PD-1) inhibitors as first- to third-line therapy at participating institutions of the Niigata Lung Cancer Treatment Group from January 2016 to October 2017. Results: This analysis included 231 patients, 32 (14%) of whom developed ICI-related ILD. Of these patients, 16 (7%) received subsequent systemic cancer treatments. The median overall survival (OS) tended to be longer in the systemic cancer therapy group than in the no systemic cancer therapy group [22.2 months (95% CI: 1-NE) vs. 4.5 months (95% CI: 1-NE); P=0.067]. ICI-related ILD recurred in half of the patients who received systemic cancer therapy, and the median OS tended to be shorter in patients with recurrent ICI-related ILD [22.0 months (95% CI: 1-NE) vs. 7.0 months (95% CI: 1-NE); P=0.3154]. Conclusions: According to the current study, systemic cancer treatment is effective in patients with ICI-related ILD; however, its safety is uncertain because of the high risk of ICI-related ILD recurrence and poor survival outcome following ILD recurrence.

DOI： 10.21037/tlcr-21-198

PubMed

researchmap

Language：English  

We herein report the case of a 20 year-old-man who developed bronchiolitis obliterans after living-donor renal transplantation. The patient presented with dyspnea on exertion and wheezing two years after renal transplantation, and spirometry showed an obstructive pattern. Surgical lung biopsy revealed subepithelial fibrosis that constricted and obstructed the intrabronchiolar space. Based on these findings, the patient was diagnosed with bronchiolitis obliterans. He was prescribed bronchodilators and azithromycin, and he achieved stable respiratory function for two years. The differential diagnosis of respiratory symptoms after renal transplantation includes opportunistic infection and drug-induced lung injury; however, bronchiolitis obliterans should also be considered.

DOI： 10.1016/j.resinv.2020.12.003

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Viral pneumonia caused by varicella-zoster virus (VZV) infection is a rare but important complication, especially regarding varicella infections. Although disseminated cutaneous herpes zoster (DCHZ) is often associated with visceral diseases, there have been few reports of DCHZ-related pneumonia. We herein report a rare case of a lethal disseminated VZV infection that caused severe pneumonia in a Japanese patient who had chronic interstitial pneumonia. Physicians should consider the possibility of VZV-related pneumonia, especially in patients with a medical history of hematopoietic stem cell transplantation and immunosuppressive therapy.

DOI： 10.2169/internalmedicine.5396-20

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

A 31-year-old woman who was clinically diagnosed with Silver-Russell syndrome (SRS) in childhood was admitted with complaints of dyspnea. She had hypercapnic respiratory failure accompanied by nocturnal hypoventilation. Computed tomography revealed systemic muscle atrophy and superior mesenteric artery syndrome; however, the bilateral lung fields were normal. She was treated with nocturnal noninvasive positive pressure ventilation and showed improvement of respiratory failure. In this case, loss of methylation on chromosome 11p15 and maternal uniparental disomy of chromosome 7, which are the common causes of SRS, were not detected. This is a rare case of adult SRS manifesting as chronic hypercapnic respiratory failure.

DOI： 10.2169/internalmedicine.5479-20

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Cisplatin, one of the most active anticancer agents, is widely used in standard chemotherapy for various cancers. Cisplatin is more poorly tolerated than other chemotherapeutic drugs, and the main dose-limiting toxicity of cisplatin is its nephrotoxicity, which is dose-dependent. Although less toxic methods of cisplatin administration have been established, cisplatin-induced nephrotoxicity remains an unsolved problem. Megalin is an endocytic receptor expressed at the apical membrane of proximal tubules. We previously demonstrated that nephrotoxic drugs, including cisplatin, are reabsorbed through megalin and cause proximal tubular cell injury. We further found that cilastatin blocked the binding of cisplatin to megalin in vitro. In this study, we investigated whether cilastatin could reduce cisplatin-induced nephrotoxicity without influencing the antitumor effects of cisplatin. Nephrotoxicity was decreased or absent in mice treated with cisplatin and cilastatin, as determined by kidney injury molecule-1 staining and the blood urea nitrogen content. Combined with cilastatin, a twofold dose of cisplatin was used to successfully treat the mice, which enhanced the antitumor effects of cisplatin but reduced its nephrotoxicity. These findings suggest that we can increase the dose of cisplatin when combined with cilastatin and improve the outcome of cancer patients.

DOI： 10.1038/s41598-020-80853-6

PubMed

researchmap

Language：English  

A 70-year-old man, treated for asthma for 2 years and chronic sinusitis for several months, presented with fever, numbness in the lower limbs, heaviness in the head, gross hematuria, and black stools. He also had eosinophilia, elevated serum IgG4 levels, high levels of myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA), and pulmonary infiltrative shadows. Bronchoscopy revealed multiple white flattened lesions (white moss) on the airway mucosa, suggesting mycobacterial infection or malignancy. A biopsy from tracheal mucosa revealed airway inflammation with marked eosinophil infiltration. The patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) and treated with steroids, and all findings improved. However, a year and a half after the initiation of treatment, eosinophils and IgE gradually increased; subjective symptoms, such as asthma symptoms and numbness in the lower limbs, worsened; and ANCA, which had been negative, turned positive. Therefore, we suspected disease relapse and anti-IL-5 antibody (mepolizumab) treatment was initiated. Thereafter, ANCA turned negative again, eosinophils and IgE normalized, and subjective symptoms decreased. The presence of airway mucosal lesions in EGPA is relatively rare, and we report this case as a valuable case owing to the interesting bronchoscopic findings that are worth comprehending as a respiratory physician.

DOI： 10.1016/j.rmcr.2021.101451

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Each of the currently available (1→3)-β-D-glucan (BDG) measurement kits follows a different measurement method and cut-off value. Comparisons of diagnostic performance for invasive fungal infections (IFIs) are desirable. Additionally, ecological considerations are becoming increasingly important in the development of new measurement kits. METHODS: The plasma BDG levels in clinical samples were measured using the following currently available kits: the Fungitec G test MKII, the Fungitec G test ES, Fungitell, the β-Glucan test Wako, and the newly developed Wako kit (Wako-Eu). Wako-Eu uses a pre-treatment solution that conforms to European regulations for the registration, evaluation, authorisation, and restriction of chemicals. The values obtained for the samples using each kit were studied and compared. RESULTS: Of the 165 patients evaluated, 12 had IFIs, including pneumocystis pneumonia, aspergillosis, and candidiasis. BDG values obtained using the kits were moderately correlated with each other. Clinical diagnoses of the evaluated cases indicated that 21 false positives were diagnosed by at least one kit. The sensitivity of the Fungitell kit was relatively low, but those of the other four were over 90%. The specificity was above 90% for all kits. For positive predictive value, the Wako and the Wako-Eu methods were superior to the others owing to fewer false positive results. CONCLUSIONS: The newly developed Wako-Eu method, which considers ecological concerns, shows diagnostic performance equivalent to that of its predecessor. To improve the diagnostic accuracy of IFIs, it is necessary to interpret the results carefully, giving due consideration to the characteristics of each measurement kit.

DOI： 10.1371/journal.pone.0255172

PubMed

researchmap

Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/osi2.1061

researchmap

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/osi2.1061

Language：English   Publishing type：Research paper (scientific journal)  

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 ).

DOI： 10.1007/s11325-020-02170-6

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本内科学会  

researchmap

Language：Japanese   Publisher：(公社)日本矯正歯科学会  

researchmap

Language：Japanese   Publisher：(NPO)日本肺癌学会  

researchmap

Language：Japanese   Publisher：(NPO)日本肺癌学会  

researchmap

Language：Japanese   Publisher：(NPO)日本睡眠歯科学会  

researchmap

Language：Japanese   Publisher：(一社)日本睡眠学会  

researchmap

Language：Japanese   Publisher：(一社)日本アレルギー学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Mycobacterium avium complex lung disease (MAC-LD) can deteriorate rapidly to become fatal. Reported poor prognostic factors include radiographic findings, undernutrition, anemia and high inflammation test values. However, the association of these prognostic factors with the pathophysiology of the disease remains unknown. We aimed to clarify the pathophysiology of MAC-LD and develop a new biomarker that reflects the immune response to the disease. METHODS: We performed the cytokine panel analyses of serum from patients with MAC-LD and compared each cytokine level with clinically negative prognostic factors (radiographic disease type, body mass index, albumin, C-reactive protein and hemoglobin) and high-resolution CT scores. RESULTS: We analyzed 27 patients with MAC-LD, 6 with the fibrocavitary form and 21 with the nodular bronchiectatic form on high-resolution CT. Serum CXC motif ligand 10 (CXCL10) concentration was significantly elevated in patients with the fibrocavitary form (p = 0.008). CXCL10 levels correlated with body mass index (r = - 0.60, p = 0.0008), serum albumin concentration (r = - 0.45, p = 0.016) and high-resolution CT scores (r = 0.61, p = 0.0006). Among 14 patients initially untreated, antibiotic therapy was initiated for five during the study period. CXCL10 concentration was significantly higher in these patients (p = 0.046), and receiver operating characteristic analysis for CXCL10 concentration on treatment initiation produced an area under the curve of 0.844, with a sensitivity of 100%, specificity of 66.7%, and cut-off value of 366.5 pg/mL. CONCLUSION: We revealed cytokine profiles in patients with MAC-LD. Serum CXCL10 levels probably reflect the severity of MAC-LD. Our findings suggest that CXCL10 concentration may be a promising biomarker for managing treatment for patients with MAC disease of the lung.

DOI： 10.1186/s12879-019-3888-4

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本結核・非結核性抗酸菌症学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Although the blockade of programmed cell death 1 (PD-1)/PD-ligand (L) 1 has demonstrated promising and durable clinical responses for non-small-cell lung cancers (NSCLCs), NSCLC patients with epidermal growth factor receptor (EGFR) mutations responded poorly to PD-1/PD-L1 inhibitors. Previous studies have identified several predictive biomarkers, including the expression of PD-L1 on tumor cells, for PD-1/PD-L1 blockade therapies in NSCLC patients; however, the usefulness of these biomarkers in NSCLCs with EGFR mutations has not been elucidated. The present study was conducted to evaluate the predictive biomarkers for PD-1/PD-L1 inhibitors in EGFR-mutated NSCLCs. We retrospectively analyzed 9 patients treated with nivolumab for EGFR-mutated NSCLCs. All but one patient received EGFR-tyrosine kinase inhibitors before nivolumab treatment. The overall response rate and median progression-free survival were 11% and 33 days (95% confidence interval (CI); 7 to 51), respectively. Univariate analysis revealed that patients with a good performance status (P = 0.11; hazard ratio (HR) 0.183, 95% CI 0.0217 to 1.549), a high density of CD4+ T cells (P = 0.136; HR 0.313, 95% CI 0.045 to 1.417) and a high density of Foxp3+ cells (P = 0.09; HR 0.264, 95% CI 0.0372 to 1.222) in the tumor microenvironment tended to have longer progression-free survival with nivolumab. Multivariate analysis revealed that a high density of CD4+ T cells (P = 0.005; HR<0.001, 95% CI <0.001 to 0.28) and a high density of Foxp3+ cells (P = 0.003; HR<0.001, 95% CI NA) in tumor tissues were strongly correlated with better progression-free survival. In contrast to previous studies in wild type EGFR NSCLCs, PD-L1 expression was not associated with the clinical benefit of anti-PD-1 treatment in EGFR-mutated NSCLCs. The current study indicated that immune status in the tumor microenvironment may be important for the effectiveness of nivolumab in NSCLC patients with EGFR mutations.

DOI： 10.1371/journal.pone.0215292

PubMed

researchmap

Language：Japanese   Publisher：新潟歯学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.5664/jcsm.7368

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

researchmap

Language：Japanese   Publisher：(NPO)日本肺癌学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Presepsin is a widely recognized biomarker for sepsis. However, little is known about the usefulness of presepsin in invasive fungal infection. The aim of this study was to determine the plasma levels of presepsin in fungal bloodstream infections and to investigate whether it reflects the disease severity, similar to its utility in bacterial infections. METHODS: We prospectively measured presepsin in plasma samples from participants with fungemia from April 2016 to December 2017. The associations of C-reactive protein, procalcitonin, and presepsin concentrations with the severity of fungemia were statistically analyzed. In vitro assay was performed by incubating Escherichia coli, Candida albicans, and lipopolysaccharide to whole blood cells collected from healthy subjects; after 3 h, the presepsin concentration was measured in the supernatant and was compared among the bacteria, fungi, and LPS groups. RESULTS: Presepsin was increased in 11 patients with fungal bloodstream infections. Serial measurement of presepsin levels demonstrated a prompt decrease in 7 patients in whom treatment was effective, but no decrease or further increase in the patients with poor improvement. Additionally, presepsin concentrations were significantly correlated with the Sequential Organ Failure Assessment score (r = 0.89, p < 0.001). In vitro assay with co-incubation of C. albicans and human whole blood cells indicated that the viable cells of C. albicans caused an increase in presepsin, as seen with E. coli. CONCLUSIONS: Plasma presepsin levels increased in patients with fungal bloodstream infection, with positive association with the disease severity. Presepsin could be a useful biomarker of sepsis secondary to fungal infections.

DOI： 10.1371/journal.pone.0206089

PubMed

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Lung Cancer Society  

Objective. Sarcoidosis is a systemic disease that causes the formation of noncaseating epithelioid granuloma in various organs and which often exhibits hilar and mediastinal lymphadenopathy. Among lung cancer patients with sarcoidosis or sarcoid reactions, it is difficult to evaluate the lymph node status and stage by CT and FDG-PET/CT scans. In this study, we examined the usefulness of EBUS-TBNA in the staging of the lung cancer in patients with sarcoidosis or sarcoid reactions. Materials and Methods. We evaluated the effectiveness of EBUS-TBNA in lung cancer patients with sarcoidosis or sarcoid reactions from January 2009 to December 2016. Results. We found 4 patients who were diagnosed with lung cancer accompanied by sarcoidosis and sarcoid reactions by EBUS-TBNA. All of these patients had hilar and mediastinal lymphadenopathy. EBUS-TBNA was useful for the differential diagnosis of lymph-node metastasis of lung cancer. Three of the 4 patients were diagnosed with stage I non-small cell lung cancer and surgery was performed in 2 cases. The histopathological examination of the surgical specimens confirmed that these patients had sarcoid reactions with no lymph-node metastasis. One of the 4 patients was diagnosed with stage III non-small cell lung cancer with systemic sarcoidosis. Conclusion. EBUS-TBNA seems to be useful for the evaluation of the lymph-node status of lung cancer patients with sarcoidosis and sarcoid reactions.

DOI： 10.2482/haigan.58.88

Scopus

researchmap

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

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 poly-somnography (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. (C) 2017 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.sleep.2017.01.020

Web of Science

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Kokuseido Publishing Co. Ltd  

A 57-year-old man complained of an acute onset of left shoulder pain and subsequent dyspnea in the supine position. Orthopedic, neurological, and cardio- logic work up failed to identify the cause of his symptoms. After experiencing orthopnea for 5 months, he was admitted to our hospital He was diagnosed with a bilateral phrenic nerve paralysis based on paradoxical breathing, a bilateral diaphragm elevation on radiographic imaging, and a restrictive ventilatory defect. Polysomnography showed a severe obstructive sleep apnea pattern. Arterial blood gas analysis revealed hypercapnic respiratory failure. After nocturnal non-invasive positive pressure ventilation therapy, his dyspnea promptly improved in association with less carbon dioxide retention. Furthermore, in two years, his pulmonary function also improved and returned to the normal range. Eventually, phrenic nerve involvement of neuralgic amyotrophy (NA) without any other muscle involvement was considered the causative disease. In this case, the complication of sleep-disordered breathing made it difficult to diagnose NA early in the course. NA should be con-sidered in the differential diagnosis for phrenic nerve paralysis or hypercapnic respiratory failure.

Scopus

researchmap

Language：Japanese   Publisher：克誠堂出版(株)  

researchmap

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J01060&link_issn=&doc_id=20161214110010&doc_link_id=%2Fad3nkrsd%2F2016%2F007512%2F011%2F1420-1426%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fad3nkrsd%2F2016%2F007512%2F011%2F1420-1426%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

BACKGROUND: Sudden death in multiple system atrophy (MSA) usually occurs during sleep and was therefore attributed to suffocation resulting from vocal cord abductor paralysis, a characteristic laryngeal finding of MSA. This led to the use of tracheostomy and noninvasive positive pressure ventilation (NPPV) for the prevention of sudden death. However, neither method has been able to prevent sudden death, and both have occasionally precipitated treatment-related complications, including central sleep apneas and exacerbation of floppy epiglottis. Therefore, it is important to determine the mechanisms and prevention of sudden death in MSA. METHODS: We reviewed the literature on the mechanisms and prevention of sudden death in patients with MSA. RESULTS: Sudden death in MSA is hypothesized to be a consequence of disordered central respiration, suffocation caused by sputum and food, upper airway obstruction from NPPV acting on a floppy epiglottis, cardiac autonomic disturbance, or a combination of these factors. CONCLUSION: Various factors may be involved in the mechanism of sudden death in MSA. A multidisciplinary approach is needed to prevent sudden death, and this requires an organized system of several medical specialties. Neurologists require a cooperative network that includes experts in otorhinolaryngology, sleep medicine, dysphagia rehabilitation, and cardiology.

DOI： 10.1016/j.parkreldis.2016.04.011

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Several multifactorial risk indexes have been proposed by Western countries for identifying patients at a high risk of developing postoperative pulmonary complications (PPC). However, there is no consensus on how to evaluate the risk of PPC and what multifactorial risk index should be adapted for Japanese patients. This study aimed at clarifying the utility of risk indexes to predict PPC following digestive surgeries in Japanese patients. METHODS: We retrospectively analyzed 892 patients who underwent digestive surgeries under general anesthesia in Niigata University Medical and Dental Hospital between January 2009 and March 2011. PPC was defined as postoperative respiratory failure and postoperative pneumonia. We calculated three risk indexes (respiratory failure risk index (RFRI), postoperative pneumonia risk index, and PPC risk score), and compared them between the PPC group and the non-PPC group. A receiver operating characteristic (ROC) curve analysis was employed to compare the usefulness of each index. RESULTS: PPC developed in 55 patients (6.2%). All risk indexes were significantly higher in the PPC group than the non-PPC group. The category classification of the risk scores demonstrated a significant tendency to increase the incidence rate of PPC. In the ROC analysis, the area under the curve for RFRI was 0.762 (95% CI 0.697-0.826), which was the highest value observed among these indexes. CONCLUSIONS: Multifactorial risk indexes are useful tools for identifying Japanese patients at a high risk of developing PPC following digestive surgeries. Of the risk indexes evaluated in this study, RFRI is potentially the most accurate in predicting PPC.

DOI： 10.1016/j.resinv.2014.12.004

PubMed

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)  

A 65-year-old woman with left chest pain, back pain, and palpitation that had persisted for 2 months was referred to our hospital. Computed tomography of her chest showed an anterior mediastinal tumor with mediastinal lymphadenopathy, left pleural effusion, and pericardial effusion. Endobronchial ultrasound-guided transbronchial needle aspiration of the subcarinal lymphadenopathy was performed. The pathological findings and other examinations such as bone scintigraphy suggested advanced thymic cancer (stage IV b according to the Masaoka classification of thymic epithelial tumors). The patient was treated with combination chemotherapy of carboplatin(area under the curve [AUC]=6, 656 mg/body, day 1) and weekly paclitaxel (70 mg/m², 100 mg/body, days 1, 8, and 15). After 4 cycles of chemotherapy, a partial response was achieved and the pericardial effusion disappeared. The patient did not experience any severe toxicity, except for grade 1 nausea, grade 2 anemia, and grade 2 alopecia. Weekly paclitaxel combined with carboplatin appears to be a useful regimen with minimal toxicity for advanced thymic cancer.

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

researchmap

Language：Japanese   Publisher：(一社)日本睡眠学会  

researchmap

Language：Japanese   Publisher：(一社)日本睡眠学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本内科学会  

researchmap

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER TOKYO  

We tested the hypothesis that fasting affects hypoxic ventilatory responses through metabolic changes via histamine H1 receptors. Wild-type (WT) and histamine H1 receptor knockout (H1RKO) mice were studied in fed and fasted states. In the fed WT, hypoxic-gas exposure elicited an increase and a subsequent decline in ventilation (hypoxic ventilatory decline or HVD). HVD was influenced by fasting in breathing pattern with metabolic rate. Fasting elicited hypoglycemia, a drop in R, and increases in free fatty acid and ketone bodies in the serum. In H1RKO, HVD was blunted in the fed state, but it appeared in the fasted state. There was a minimal drop in R following fasting and a low triglyceride concentration. Thus, fasting affects HVD through a change in energy mobilization from glucose to lipid metabolism. Histamine H1 receptors are involved in HVD during fed and fasted states, resulting in adaptation to the environmental conditions.

DOI： 10.1007/s12576-010-0124-9

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Central histamine has crucial roles in circadian rhythm, ventilation, and the balance of energy metabolism via H1 receptors. We focused on the variation in ventilatory responses to hypoxia between light and dark periods, and the requirement of histamine H1 receptors for the circadian variation, using wild-type (WT) and histamine H1 receptor-knockout (H1RKO) mice. In WT mice, minute ventilation (V(E)) during hypoxia was higher in the dark period than in the light period. In H1RKO mice, changes in V(E) between photoperiods were minimal because V(E) increased relative to VO(2) (particularly in the light period). H1RKO mice showed metabolic acidosis, and increased levels of ketone bodies in blood during the light period. These data suggested that changes in V(E) during hypoxia vary between light and dark periods, and that H1 receptors have a role in the circadian variation in V(E) through control of acid-base status and metabolism in mice.

DOI： 10.1007/978-1-4419-5692-7_47

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AND OBJECTIVE: Thixotropy conditioning of inspiratory muscles changes the end-expiratory position of the respiratory system during resting breathing. We examined the immediate effects of thixotropy conditioning of inspiratory muscles on chest wall inflation induced by CPAP. METHODS: A cross-over design study was performed in 13 healthy men. Operating chest wall volume (Vcw) was measured by respiratory inductive plethysmography. Conditioning consisting of a 5 s inspiratory effort at a mask pressure of -20 cm H(2)O was performed under CPAP (10 cm H(2)O) at three Vcw values to change the muscle length at which conditioning occurred: (i) FRC at a CPAP of 10 cm H(2)O (FRC(10)); (ii) FRC at a CPAP of 0 cm H(2)O (FRC(0)); and (iii) RV at a CPAP of 10 cm H(2)O (RV(10)). RESULTS: CPAP (10 cm H(2)O) increased FRC by 0.60-0.70 L. Decreases in operating Vcw were noted after conditioning at RV(10), which decreased end-expiratory Vcw by 0.16 +/- 0.12 L and end-inspiratory Vcw by 0.20 +/- 0.14 L at 180 s (P < 0.01). Inspiratory capacity (1.59 +/- 0.45 L) and inspiratory reserve volume (1.18 +/- 0.40 L) were greater than preconditioning values (1.44 +/- 0.49 L and 0.99 +/- 0.41 L, respectively; P < 0.01). Conditioning at FRC(0) also decreased operating Vcw significantly, but conditioning at FRC(10) did not change operating Vcw. CONCLUSIONS: Thixotropy conditioning of inspiratory muscles performed below inflated FRC decreased the level of CPAP-induced inflation.

DOI： 10.1111/j.1440-1843.2007.01228.x

PubMed

researchmap

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

We tested the hypothesis that the biphasic ventilatory response to poikilocapnic hypoxia shows circadian variation and contribution of histamine H1 receptors in mice. Initial increases in ventilation were augmented during dark periods. H1 receptors had no major relationship with circadian variation, but affected the declined phase.

DOI： 10.2170/physiolsci.SC002408

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER PHYSIOLOGICAL SOC  

Ventilation oscillates throughout a day in parallel with oscillations in metabolic rate. Histamine affects ventilation and the balance of the energy metabolism via H1 receptors in the brain. We tested the hypothesis that the ventilatory response to hypoxia varies between light and dark periods and that histamine H1 receptors are required for the circadian variation, using wild- type ( WT) and histamine H1 receptor knockout ( H1RKO) mice. Mice were exposed to hypoxic gas ( 7% O-2 + 3% CO2 in N-2) during light and dark periods. Ventilation initially increased and then declined. In WT mice, minute ventilation ( V. E) during hypoxia was higher in the dark period than in the light period, which was an upward shift along with the baseline ventilation. Hypoxia decreased the metabolic rate, whereas O2 consumption ( V. O2) and CO2 excretion were higher in the dark period than in the light period. However, in H1RKO mice, changes in V. E during hypoxia between light and dark periods were minimal, because V. E was increased relative to V. O2, particularly in the light period. In H1RKO mice, the HCO3- concentration and base excess values were increased in arterial blood, and the level of ketone bodies was increased in the serum, indicating that metabolic acidosis occurred. Respiratory compensation takes part in the V. E increase relative to V. O2 during hypoxia. These results suggested that changes in V. E during hypoxia vary between light and dark periods and that H1 receptors play a role in circadian variation in V. E through control of the acid- base status and metabolism in mice.

DOI： 10.1152/ajpregu.00318.2007

Web of Science

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Inspiratory muscle conditioning at a lower or higher lung volume based on the principles of muscle thixotropy causes acute changes in end-expiratory chest wall and lung volumes. The present study aimed to demonstrate the time course of effects of this conditioning on both end-expiratory chest wall volume and thoracoabdominal synchrony. We measured chest wall motion with respiratory induction plethysmography at 0.5, 1, 2, 3, and 6 min after conditioning at three different lung volumes in 15 healthy men. After conditioning at total lung capacity - 20% inspiratory capacity, increases in end-expiratory chest wall volume were significant at 0.5, 1, and 2 min (P < 0.05), being most obvious at 0.5 min (Delta 0.24 +/- 0.20 liter). After conditioning at residual volume, reductions in end-expiratory chest wall volume were significant at any time point (P < 0.05), being most obvious at 0.5 min (Delta 0.16 +/- 0.08 liter). Conditioning at functional residual capacity had little effect on the volume. Spirometric inspiratory capacity at 6 min after conditioning at residual volume (2.68 +/- 0.35 liter) was higher than the baseline value (2.53 +/- 0.31 liter, P < 0.05). Reductions in the phase angle, quantified by the Konno-Mead diagram, occurred after conditioning at residual volume at any time point (P < 0.05), being most obvious at 2 min (Delta 3.47 +/- 3.02 degrees). In conclusion, there is a 6-min time course of changes in end-expiratory chest wall volume after conditioning. More synchronous motion between the rib cage and abdomen occurs after conditioning at residual volume.

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The role of central histamine in the hypoxic ventilatory response was examined in conscious wild-type (WT) and histamine type1 receptor-knockout (H1RKO) mice. Hypoxic gas (7% O(2) and 3% CO(2) in N(2)) exposure initially increased and then decreased ventilation, referred to as hypoxic ventilatory decline (HVD). The initial increase in ventilation did not differ between genotypes. However, H1RKO mice showed a blunted HVD, in which mean inspiratory flow was greater than that in WT mice. O(2) consumption (V(O2)) and CO(2) excretion were reduced 10min after hypoxic gas exposure in both genotypes, but (V(O2)) was greater in H1RKO mice than in WT mice. The ratio of minute ventilation to (V(O2)) during HVD did not differ between genotypes, indicating that ventilation is adequately controlled according to metabolic demand in both mice. Peripheral chemoreceptor sensitivity did not differ between genotypes. We conclude that central histamine contributes via the H1 receptor to changes in metabolic rate during hypoxia to increase HVD in conscious mice.

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Histaminergic neurons in the hypothalamus are well documented as being involved in the control of autonomic functions, such as the balance of energy metabolism and circadian rhythm. We tested the hypothesis that an activation of the histamine type-1 (H1) receptor is required for the control of ventilation during the course of a day in free-moving mice. Ventilation, aerobic metabolism, and electroencephalogram were measured by a whole-body-plethysmograph, a magnetic-type mass spectrometry system, and a telemetry system, respectively, in H1 receptor-knockout (H1RKO) and wild-type mice. Both genotypes showed daily oscillations in minute ventilation (V(E)) and oxygen consumption (VO(2)), with greater values during the dark period compared to the light period. In the latter, H1RKO mice showed increased V(E) and CO(2) excretion (VCO(2)) relative to wild-type mice, and V(E) was comparable to the VCO(2) increase. However, there was no change in VO(2) in H1RKO mice, suggesting that differences in VCO(2) between genotypes are responsible for differences in V(E) during the light period. During the dark period, VCO(2) was elevated in H1RKO mice compared with WT mice. Because there was no difference in V(E), the ratio of V(E) to VCO(2) was reduced in H1RKO mice. Electroencephalogram results suggested that this might be due to a depressed arousal state in H1RKO mice because the ratio of delta to theta band power spectrum densities was greater in H1RKO mice than in wild-type mice. We concluded that histamine modulates ventilation by affecting metabolism and arousal state via H1 receptors.

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Thixotropy conditioning of inspiratory muscles consisting of maximal inspiratory effort performed at an inflated lung volume is followed by an increase in end-expiratory position of the rib cage in normal human subjects. When performed at a deflated lung volume, conditioning is followed by a reduction in end-expiratory position. The present study was performed to determine whether changes in end-expiratory chest wall and lung volumes occur after thixotropy conditioning. We first examined the acute effects of conditioning on chest wall volume during subsequent five-breath cycles using respiratory inductive plethysmography (n = 8). End-expiratory chest wall volume increased after conditioning at an inflated lung volume (P < 0.05), which was attained mainly by rib cage movements. Conditioning at a deflated lung volume was followed by reductions in end-expiratory chest wall volume, which was explained by rib cage and abdominal volume changes (P < 0.05). End-expiratory esophageal pressure decreased and increased after conditioning at inflated and deflated lung volumes, respectively (n = 3). These changes in end-expiratory volumes and esophageal pressure were greatest for the first breath after conditioning. We also found that an increase in spirometrically determined inspiratory capacity (n = 13) was maintained for 3 min after conditioning at a deflated lung volume, and a decrease for 1 min after conditioning at an inflated lung volume. Helium-dilution end-expiratory lung volume increased and decreased after conditioning at inflated and deflated lung volumes, respectively (both P < 0.05; n = 11). These results suggest that thixotropy conditioning changes end-expiratory volume of the chest wall and lung in normal human subjects.

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本内科学会  

researchmap

Language：Japanese   Publisher：(NPO)日本肺癌学会  

researchmap

Language：Japanese   Publisher：(NPO)日本肺癌学会  

researchmap

Language：Japanese   Publisher：(NPO)日本肺癌学会  

researchmap

Language：Japanese   Publisher：(NPO)日本肺癌学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

researchmap

Language：Japanese   Publisher：(一社)日本睡眠学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本内科学会  

researchmap

Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

背景.気管支静脈瘤は稀な疾患であり,その治療法は確立されていない.症例.78歳,女性.小児期より気管支拡張症を罹患し,膿胸の既往があった.6年前から喀血を繰り返し,計3回の気管支動脈塞栓術が行われていた.今回,喀血を契機に入院し,止血薬投与を受けたが大量喀血を来したため,気管挿管の上で人工呼吸管理となった.左下横隔動脈と左気管支動脈をゼラチンスポンジで塞栓し,止血を得た.その際の選択的動脈造影で左下横隔動脈と肺静脈との動静脈シャントを認めた.気管支鏡で観察すると,左上下葉支分岐部に気管支静脈瘤がみられ,出血源と考えられた.動脈塞栓術の2週後の気管支鏡では同部位の瘤は退縮していた.その後,再喀血なく自宅退院した.結論.気管支静脈瘤は気管支拡張症や動脈塞栓に関連して発症する可能性があり,喀血時は気管支鏡による確認が必要である.治療として異常シャントの塞栓術が有効と考えられた.(著者抄録)

researchmap

Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J00298&link_issn=&doc_id=20211216270004&doc_link_id=%2Fcf0brond%2F2021%2F004306%2F005%2F0589-0594%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcf0brond%2F2021%2F004306%2F005%2F0589-0594%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(NPO)日本肺癌学会  

researchmap

Language：Japanese   Publisher：(NPO)日本肺癌学会  

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

researchmap

Language：Japanese   Publisher：(NPO)日本肺癌学会  

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：Japanese   Publisher：(NPO)日本肺癌学会  

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：Japanese   Publisher：(NPO)日本肺癌学会  

researchmap

Language：Japanese   Publisher：(NPO)日本肺癌学会  

researchmap

Language：Japanese   Publisher：(株)ライフ・サイエンス  

・閉塞性睡眠時無呼吸(OSA)の診断と重症度は睡眠ポリグラフ検査(PSG)による無呼吸低呼吸指数(AHI)に基づいて行われ、OSAによる日中の眠気などの臨床症状が強い症例、および中〜重症例では持続陽圧呼吸(CPAP)療法が第一選択であり、治療することが推奨されている。また、CPAPが使用できない症例では口腔内装置など代替治療が行われる。いわゆるパターン化された診療形式である。このアプローチは、様々なリスク因子、病態生理学的要因、臨床症状の違いによるOSAの多様性は考慮されていない。・今までの仮説に基づく研究から、コンピュータの発達とデータを蓄積し、データ分析に基づく研究により多種の所見による類似性を有するサブグループ分けをすることで、予後や治療反応性に違いがあることが示された。フェノタイプからエンドタイプの推定や、合併症の生じやすさを判断できれば、患者個々に合わせた個別化医療への道につながる可能性がある。本稿では、現在提唱されているOSAのフェノタイプについて解説した。(著者抄録)

researchmap

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J04991&link_issn=&doc_id=20201015080002&doc_link_id=%2Fai5slepd%2F2020%2F001403%2F003%2F0273-0279%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai5slepd%2F2020%2F001403%2F003%2F0273-0279%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本内科学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

researchmap

Language：Japanese   Publisher：(一社)日本睡眠学会  

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

researchmap

Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

researchmap

Language：Japanese  

症例は52歳、男性。慢性骨髄性白血病(CML)に対してX-4年からメシル酸イマチニブ(imatinib mesylate、以下イマチニブ)、X-2年からニロチニブ、X-1年からダサチニブを開始された。X年11月ごろより息切れが出現し、胸部X線、胸部CTで浸潤影、両側胸水を認めた。抗菌薬と利尿剤を開始されたが改善を認めず、当科を紹介受診した。経気管支肺生検で得られた生検組織で肺胞腔内にポリープ状線維化巣を認め、器質化肺炎と診断した。ダサチニブを中止してステロイド治療を行い、臨床症状、画像所見の改善を認めた。その後CMLに対して、イマチニブ、ニロチニブを投与したが治療効果を認めなかった。ステロイド併用下でダサチニブを再投与し、器質化肺炎の再燃なくCMLをコントロールすることができた。ダサチニブによる器質化肺炎はまれであり、これまで報告はない。ステロイド治療によりダサチニブの再投与が可能であった器質化肺炎の症例を経験したので、文献的考察を含め報告する。(著者抄録)

researchmap

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00296&link_issn=&doc_id=20180528410016&doc_link_id=%2Fab8gtkrc%2F2018%2F004505%2F017%2F0851-0854%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2018%2F004505%2F017%2F0851-0854%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

researchmap

Language：Japanese   Publisher：(NPO)日本肺癌学会  

目的. サルコイドーシスやサルコイド反応は肺門・縦隔リンパ節腫大を呈し、これらを合併した肺癌症例には、リンパ節病変の評価が治療方針決定上で問題となる。本研究では、これらサルコイド反応合併肺癌症例の病期診断におけるEBUS-TBNAの有用性を検討した。対象と方法. 2009年1月から2016年12月に気管支鏡検査を実施され、サルコイドーシス/サルコイド反応と肺癌の合併と診断された症例におけるEBUS-TBNAの有効性について検討した。結果. EBUS-TBNAにより、サルコイドーシス/サルコイド反応と肺癌との合併と診断された症例は4例であった。造影CT、FDG-PET/CTでは癌のリンパ節転移とサルコイドーシス/サルコイド反応の鑑別は困難であった。4例中3例はI期の非小細胞肺癌と診断され、2例は手術が施行された。術後検体でも転移はなく、granulomaが認められたことから、サルコイド反応と診断された。4例中1例は全身性サルコイドーシスに合併したIII期の肺癌症例であった。結論. サルコイドーシス/サルコイド反応合併肺癌症例におけるN因子の評価に、EBUS-TBNAは有用であると考えられる。(著者抄録)

researchmap

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J01244&link_issn=&doc_id=20180515270004&doc_link_id=%2Fec7jaluc%2F2018%2F005802%2F004%2F0088-0092%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fec7jaluc%2F2018%2F005802%2F004%2F0088-0092%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：(NPO)日本睡眠歯科学会  

researchmap

Language：Japanese   Publisher：(NPO)日本睡眠歯科学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

researchmap

Language：Japanese   Publisher：(公社)日本矯正歯科学会  

researchmap

Language：Japanese   Publisher：(一社)日本睡眠学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：English  

The adoptive transfer of effector T cells combined with lymphodepletion has demonstrated promising antitumor effects in mice and humans, although the availability of tumor-specific T cells is limited. We and others have also demonstrated that the transfer of polyclonal naïve T cells induces tumor-specific effector T cells and enhances antitumor immunity after lymphodepletion. Because tumors have been demonstrated to induce immunosuppressive networks and regulate the function of T cells, obtaining a sufficient number of fully functional naïve T cells that are able to differentiate into tumor-specific effector T cells remains difficult. To establish culture methods to obtain a large number of polyclonal T cells that are capable of differentiating into tumor-specific effector T cells, naïve T cells were activated with anti-CD3 mAbs in vitro. These cells were stimulated with IL-2 and IL-7 for the CD8 subset or with IL-7 and IL-23 for the CD4 subset. Transfer of these hyperexpanded T cells after lymphodepletion showed significant antitumor efficacy, and tumor-specific effector T cells were primed from these expanded T cells in tumor-bearing hosts. Moreover, these ex vivo-expanded T cells maintained T cell receptor diversity and showed long-term persistence of memory against specific tumors. Further analyses revealed that combination therapy consisting of vaccination with dendritic cells that were co-cultured with irradiated whole tumor cells and the transfer of ex vivo-expanded T cells significantly enhanced antitumor immunity. These results indicate that the transfer of ex vivo-expanded polyclonal T cells can be combined with other immunotherapies and augment antitumor effects.

DOI： 10.1371/journal.pone.0183976

PubMed

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

症例1は75歳、男性。症例2は64歳、男性。いずれも、術後再発非小細胞肺癌に対する胸部照射後に出現した浸潤影を放射線肺炎と診断し、ステロイド治療を行った。陰影は急速に増大したために抗菌薬治療を行ったが不応性であった。喀痰または肺洗浄検体よりアスペルギルス属を検出し、その後長期にわたる抗真菌薬治療を必要とした。呼吸器内科医として日常遭遇する可能性が高く、鑑別診断に慎重を要する2症例と考えられ報告する。(著者抄録)

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J05953&link_issn=&doc_id=20161205180012&doc_link_id=%2Fci6respo%2F2016%2F000506%2F012%2F0341-0345%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fci6respo%2F2016%2F000506%2F012%2F0341-0345%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本睡眠学会  

researchmap

Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

researchmap

Language：Japanese   Publisher：(一社)日本睡眠学会  

researchmap

Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

researchmap

Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

researchmap

Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(NPO)日本肺癌学会  

researchmap

Language：Japanese   Publisher：新潟医学会  

症例は71歳、男性。X-3年9月13日から左肺腺癌に対しゲフィチニブの内服治療を開始された。X年2月21日に腹痛、嘔吐を主訴に当科を受診。腹部造影CTで小腸腸管壁内ガス像および腹腔内遊離ガス像を指摘された。ゲフィチニブによる腸管気腫症と診断され、内服を中止し保存的治療で軽快した。ゲフィチニブ中止後、原病の増悪を認めたためX年4月15日からエルロチニブの内服を開始した。エルロチニブ内服開始後も腸管気腫症の再燃はなく、腫瘍の縮小を認めた。ゲフィチニブによる腸管気腫症は過去2例の報告のみである。今回我々は、ゲフィチニブにて腸管気腫症を発症し、エルロチニブにて安全に治療を再開可能であった症例を経験した。極めて稀な症例であり、文献的考察を含め報告した。(著者抄録)

CiNii Article

CiNii Books

researchmap

Other Link： http://hdl.handle.net/10191/44200

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

researchmap

Language：Japanese   Publisher：(一社)日本睡眠学会  

researchmap

Language：Japanese   Publisher：(一社)日本睡眠学会  

researchmap

Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J00298&link_issn=&doc_id=20150521230355&doc_link_id=%2Fcf0brond%2F2015%2F0037s1%2F355%2F5267-5267%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcf0brond%2F2015%2F0037s1%2F355%2F5267-5267%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(株)癌と化学療法社  

症例は65歳、女性。約2ヵ月間続く左胸背部痛と動悸を主訴に前医を受診した。胸部CTで前縦隔腫瘤、縦隔リンパ節腫脹、左胸水、心嚢液貯留を認め、当院に紹介された。気管分岐下リンパ節に対する超音波気管支内視鏡下針生検および全身検索にて胸腺癌(正岡分類IVb期)と診断した。carboplatin(CBDCA)+weekly paclitaxel(PTX)療法を4サイクル施行後、腫瘍は著明に縮小し、心嚢液減少、左胸水消失を認めた。grade 1の嘔気、grade 2の貧血と脱毛以外に重篤な副作用は認められなかった。毒性が少なく、かつ腫瘍縮小効果が得られる治療法として、CBDCA+weekly PTX療法は胸腺癌に対する有用な治療選択肢の一つと考えられた。(著者抄録)

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J00296&link_issn=&doc_id=20141222420018&doc_link_id=%2Fab8gtkrc%2F2014%2F004113%2F019%2F2607-2609%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2014%2F004113%2F019%2F2607-2609%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：新潟医学会  

症例は54歳、男性。非小細胞肺癌(腺癌)、stage IV、上皮成長受容体遺伝子変異陽性と診断された。3次化学療法目的に入院した際、発熱、嘔気、低ナトリウム血症などの症状を認められた。血中コルチゾル低値、血中ACTH高値などから、急性副腎不全と診断した。両側副腎に巨大な肺癌の転移巣を認めており、副腎不全の原因と考えられた。ヒドロコルチゾン投与で症状は速やかに軽快した。肺癌は高率に副腎転移を来すが、両側副腎転移により副腎不全に至った報告例は少ない。我々は肺癌の両側副腎転移により副腎不全を来し、ステロイドホルモン補充により化学療法を再開しえた症例を経験したため、文献的考察を加え報告する。(著者抄録)

CiNii Article

CiNii Books

researchmap

Other Link： http://hdl.handle.net/10191/43959

Language：Japanese   Publisher：日本看護学会 ; 2015-  

CiNii Article

researchmap

Other Link： http://search.jamas.or.jp/link/ui/2015205635

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

researchmap

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

researchmap

Language：Japanese   Publisher：(一社)日本睡眠学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publisher：(一社)日本呼吸器学会  

researchmap

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：(株)メディカ出版  

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：The Japan Society for Respiratory Care and Rehabilitation  

DOI： 10.15032/jsrcr.21.1_30

CiNii Article

CiNii Books

researchmap

Other Link： http://search.jamas.or.jp/link/ui/2011352296

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

researchmap

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (other)  

researchmap

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：SPRINGER TOKYO  

Web of Science

researchmap