論文 - 南宮　湖

Clarithromycin expands CD11b+Gr-1+ cells via the STAT3/Bv8 axis to ameliorate lethal endotoxic shock and post-influenza bacterial pneumonia

H Namkoong, M Ishii, H Fujii, K Yagi, T Asami, T Asakura, S Suzuki, ...

PLoS Pathogens 14 (4), e1006955 14 （ 4 ） e1006955 2018年04月

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Macrolides are used to treat various inflammatory diseases owing to their immunomodulatory properties; however, little is known about their precise mechanism of action. In this study, we investigated the functional significance of the expansion of myeloid-derived suppressor cell (MDSC)-like CD11b+Gr-1+ cells in response to the macrolide antibiotic clarithromycin (CAM) in mouse models of shock and post-influenza pneumococcal pneumonia as well as in humans. Intraperitoneal administration of CAM markedly expanded splenic and lung CD11b+Gr-1+ cell populations in naïve mice. Notably, CAM pretreatment enhanced survival in a mouse model of lipopolysaccharide (LPS)-induced shock. In addition, adoptive transfer of CAM-treated CD11b+Gr-1+ cells protected mice against LPS-induced lethality via increased IL-10 expression. CAM also improved survival in post-influenza, CAM-resistant pneumococcal pneumonia, with improved lung pathology as well as decreased interferon (IFN)-γ and increased IL-10 levels. Adoptive transfer of CAM-treated CD11b+Gr-1+ cells protected mice from post-influenza pneumococcal pneumonia. Further analysis revealed that the CAM-induced CD11b+Gr-1+ cell expansion was dependent on STAT3-mediated Bv8 production and may be facilitated by the presence of gut commensal microbiota. Lastly, an analysis of peripheral blood obtained from healthy volunteers following oral CAM administration showed a trend toward the expansion of human MDSC-like cells (Lineage-HLA-DR-CD11b+CD33+) with increased arginase 1 mRNA expression. Thus, CAM promoted the expansion of a unique population of immunosuppressive CD11b+Gr-1+ cells essential for the immunomodulatory properties of macrolides.

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[Tuberculous Pleurisy Diagnosed by Thoracoscopic Lung Biopsy].

Jun Yamamoto, Miho Nishiura, Takanori Ohata, Ho Namkoong, Shinji Sakaguchi, Fumitake Saito, Hideki Yuki

Kyobu geka. The Japanese journal of thoracic surgery 71 （ 3 ） 169 - 172 2018年03月

査読有り,  ISSN  0021-5252

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A 44-year-old woman was referred to our hospital with pleural effusion and unknown fever. Mycobacterium tuberculosis was not detected by culture of pleural effusion and sputum and gastric fluid. Pleural fluid was serous and exudative, and cytological examination showed no malignant cells. Computed tomography revealed a little pleural thickening of the right middle lobe and massive pleural effusion. As acute pleurisy was suspected based on the findings of imaging studies, thoracoscopy was performed under general anesthesia. Many yellowish-white, small nodules were seen on the parietal pleura, and white small nodule were seen on the visceral pleura of the right middle lobe. Mycobacterium tuberculosis was not detected by culture and polymerase chain reaction for Mycobacterium tuberculosis( TB-PCR) of parietal pleura and pleural effusion, but was detected by only culture and TB-PCR of visceral pleura, yielding a diagnosis of tuberculous pleurisy. Her symptoms improved and the right pleural effusion decreased with isoniazid (INH), rifampicin (RFP), ethambutol (EB) and pyrazinamide(PZA) treatment.

Anti-inflammatory roles of mesenchymal stromal cells during acute Streptococcus pneumoniae pulmonary infection in mice

T Asami, M Ishii, H Namkoong, K Yagi, S Tasaka, T Asakura, S Suzuki, ...

Cytotherapy 20 (3), 302-313 20 （ 3 ） 302 - 313 2018年03月

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BACKGROUND: Pneumonia is the fourth leading cause of death worldwide, and Streptococcus pneumoniae is the most commonly associated pathogen. Increasing evidence suggests that mesenchymal stromal cells (MSCs) have anti-inflammatory roles during innate immune responses such as sepsis. However, little is known about the effect of MSCs on pneumococcal pneumonia. METHODS: Bone marrow-derived macrophages (BMDMs) were stimulated with various ligands in the presence or absence of MSC-conditioned medium. For in vivo studies, mice intranasally-inoculated with S. pneumoniae were intravenously treated with MSCs or vehicle, and various parameters were assessed. RESULTS: After stimulation with toll-like receptor (TLR) 2, TLR9 or TLR4 ligands, or live S. pneumoniae, TNF-α and interleukin (IL)-6 levels were significantly decreased, whereas IL-10 was significantly increased in BMDMs cultured in MSC-conditioned medium. In mice, MSC treatment decreased the number of neutrophils in bronchoalveolar lavage fluid (BALF) after pneumococcal infection, and this was associated with a decrease in myeloperoxidase activity in the lungs. Levels of proinflammatory cytokines, including TNF-α, IL-6, GM-CSF and IFN-γ, were significantly lower in MSC-treated mice, and the bacterial load in the lung after pneumococcal infection was significantly reduced. In addition, histopathologic analysis confirmed a decrease in the number of cells recruited to the lungs; however, lung edema, protein leakage into the BALF and levels of the antibacterial protein lipocalin 2 in the BALF were comparable between the groups. CONCLUSIONS: These results indicate that MSCs could represent a potential therapeutic application for the treatment of pneumonia caused by S. pneumoniae.

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Clinical characteristics of pulmonary Mycobacterium lentiflavum disease in adult patients

K Yagi, K Morimoto, M Ishii, H Namkoong, S Okamori, T Asakura, ...

International Journal of Infectious Diseases 67, 65-69 67   65 - 69 2018年02月

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BACKGROUND: Mycobacterium lentiflavum is a slow-growing non-tuberculous Mycobacterium that is often associated with an immunocompromised state and cervical lymphadenitis in young children. However, little is known about the clinical importance of pulmonary infection with M. lentiflavum in adults. METHODS: The medical records of all adults who met the diagnostic criteria of pulmonary M. lentiflavum disease at Keio University Hospital and Fukujuji Hospital from 2001 to 2015 were reviewed. In addition, the PubMed database was searched to identify further reported cases in non-HIV adults. RESULTS: Five cases of pulmonary M. lentiflavum disease were identified in the medical records search and 11 additional cases were identified in the literature review. Eleven of the total 16 cases were female, and 15 of 16 cases showed a nodular/bronchiectatic pattern on chest computed tomography imaging. No cases showed an aggressive clinical course of pulmonary M. lentiflavum disease, although one patient died of an exacerbation of underlying vasculitis and bacterial pneumonia. CONCLUSIONS: The clinical characteristics of pulmonary M. lentiflavum disease in adult patients were identified. This disease mainly affects females, displays a nodular/bronchiectatic pattern on chest computed tomography imaging, and does not demonstrate an aggressive clinical course. Further larger studies are needed to reveal detailed clinical features.

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Clinical evaluation of the immunochromatographic system using silver amplification for the rapid detection of Mycoplasma pneumoniae

H Namkoong, M Yamazaki, M Ishizaki, I Endo, N Harada, M Aramaki, ...

Scientific Reports 8 (1), 1-7 8 （ 1 ） 1430 - 1430 2018年01月

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Mycoplasma pneumoniae infection is conventionally diagnosed using serum antibody testing, microbial culture, and genetic testing. Recently, immunochromatography-based rapid mycoplasma antigen test kits have been developed and commercialised for rapid diagnosis of M. pneumoniae infection. However, as these kits do not provide sufficient sensitivity and specificity, a rapid test kit with improved accuracy is desired. The present prospective study evaluated a rapid M. pneumoniae diagnostic system utilizing a newly developed silver amplification immunochromatography (SAI) system. We performed dilution sensitivity test and the prospective clinical study evaluating the SAI system. The subjects of the clinical study included both children and adults. All patients suspected to have mycoplasma pneumonia (169 patients) were sequentially enrolled. Twelve patients did not agree to participate and 157 patients were enrolled in the study. The results demonstrate excellent performance of this system with 90.4% sensitivity and 100.0% specificity compared with real-time polymerase chain reaction. When compared with loop-mediated isothermal amplification (LAMP) methods, the results also demonstrate a high performance of this system with 93.0% sensitivity and 100.0% specificity. The SAI system uses a dedicated device for automatic analysis and reading, making it highly objective, and requires less human power, supporting its usefulness in clinical settings.

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Mycobacterium triplex pulmonary disease with acquired macrolide resistance in immunocompetent patients.

Matsuda S, Suzuki S, Morimoto K, Aono A, Nishio K, Asakura T, Sasaki Y, Namkoong H, Nishimura T, Ogata H, Hasegawa N, Kurashima A, Ishii M, Goto H

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 24 （ 6 ） 671 - 672 2018年01月

査読有り,  ISSN  1198-743X

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A fulminant case of acute respiratory distress syndrome associated with Mycoplasma Pneumonia treated with nasal high-flow oxygen therapy

N Kawakami, H Namkoong, T Ohata, S Sakaguchi, F Saito, H Yuki

Case Reports in Critical Care 2018 （Hindawi Limited）  2018   1067593 - 1067593 2018年

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Introduction: The prognosis of mycoplasma pneumonia in adults is generally favorable, but a few patients show progression to acute respiratory distress syndrome (ARDS). We have described the management of a patient who showed progression of mycoplasma pneumonia to ARDS. Presentation of Case: A 26-year-old male patient with no significant past medical or social history presented with a 5-day history of fever. Following this, he was diagnosed with bacterial pneumonia and treated with tazobactam/piperacillin; however, he showed little clinical improvement with this treatment approach. We diagnosed the patient with mycoplasma pneumonia with an antigen test and treated him with azithromycin and prednisolone. Despite the appropriate antimicrobial therapy, his symptoms worsened and therefore we changed his oxygen therapy from a reservoir mask to nasal high-flow oxygen in addition to minocycline. Consequently, with this treatment, he recovered from severe mycoplasma pneumonia. Discussion: In patients with severe pneumonia who experience respiratory failure, it has been reported that nasal high-flow oxygen therapy is not inferior to noninvasive positive pressure ventilation therapy regarding intubation rate. In this case, induction of nasal high-flow oxygen therapy led to avoidance of ventilator management. This is a valuable case report highlighting the optimal outcome of nasal high-flow oxygen therapy in a fulminant case of acute respiratory distress syndrome. Conclusion: In patients who present with severe mycoplasma pneumonia with respiratory failure, nasal high-flow oxygen therapy can help reduce the needs for ventilator management including intubation.

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Comparison of antipseudomonal β-lactams for febrile neutropenia empiric therapy: systematic review and network meta-analysis: authors' reply

N Horita, Y Shibata, H Watanabe, H Namkoong, T Kaneko

Clinical Microbiology and Infection 24 (6), 664-665 2018年

Comparison of antipseudomonal β-lactams for febrile neutropenia empiric therapy: authors' response

N Horita, Y Shibata, H Watanabe, H Namkoong, T Kaneko

Clinical Microbiology and Infection 24 (3), 325 2018年

Analysis of Adverse Drug Events in Pulmonary Mycobacterium Avium Complex Disease Using the Japanese Adverse Drug Event Report (JADER) Database

H Namkoong, Y Takahashi, M Ishii, T Asakura, S Suzuki, H Kamata, ...

A106. NTM CLINICAL AND TRANSLATIONAL SCIENCE, A2595-A2595 2018年

ADAM17 protects mice against elastase-induced emphysema via inactivation of CD62L

S Suzuki, M Ishii, T Asakura, H Namkoong, S Okamori, K Yagi, H Kamata, ...

European Respiratory Journal 52 (suppl 62) 2018年

Impact of six-minute walk test on health-related quality of life in pulmonary Mycobacterium avium complex disease

K Yagi, T Asakura, H Namkoong, S Suzuki, T Asami, S Okamori, ...

European Respiratory Journal 52 (suppl 62) 2018年

Mycobacterium abscessus pulmonary disease: individual patient data meta-analysis

N Kwak, MP Dalcolmo, CL Daley, G Eather, R Gayoso, N Hasegawa, ...

대한결핵및호흡기학회 추계학술발표초록집 126, 150-150 2018年

Tuberculous Pleurisy Diagnosed by Thoracoscopic Lung Biopsy

J Yamamoto, M Nishiura, T Ohata, H Namkoong, S Sakaguchi, F Saito, ...

Kyobu geka. The Japanese Journal of Thoracic Surgery 71 (3), 169-172 2018年

The Protective Role of a Disintegrin and Metalloprotease (ADAM) 10 During Severe Influenza Virus Infection

S Okamori, M Ishii, T Asakura, S Suzuki, T Kusumoto, H Kamata, ...

B62. LUNG CYTOPROTECTION AND IMMUNITY DURING INFECTIONS, A3841-A3841 2018年

The Development of Lung Cancer During Follow-Up of Patients with Mycobacterium Avium Complex Lung Disease

T Kusumoto, T Asakura, S Suzuki, S Okamori, H Namkoong, H Fujiwara, ...

A58. NON-TUBERCULOUS MYCOBACTERIA: OFF THE BEATEN TRACK, A1983-A1983 2018年

Sphingosine 1-phosphate receptor modulator ONO-4641 stimulates CD11b+ Gr-1+ cell expansion and inhibits lymphocyte infiltration in the lungs to ameliorate murine pulmonary …

T Asakura, M Ishii, H Namkoong, S Suzuki, S Kagawa, K Yagi, T Komiya, ...

Mucosal Immunology 11 (6), 1606-1620 2018年

Quantitative Assessment of Erector Spinae Muscles in Patients with Mycobacterium Avium Complex Lung Disease: Relationship of Disease Severity and Prognosis

T Asakura, S Suzuki, S Okamori, T Kusumoto, H Namkoong, K Yagi, ...

A106. NTM CLINICAL AND TRANSLATIONAL SCIENCE, A2598-A2598 2018年

Impact of chronic Pseudomonas aeruginosa infection on health-related quality of life in Mycobacterium avium complex lung disease

H Kamata, T Asakura, S Suzuki, H Namkoong, K Yagi, Y Funatsu, ...

BMC Pulmonary Medicine 17, 1-9 17 （ 1 ） 198 - 198 2017年12月

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BACKGROUND: In bronchiectasis patients, chronic Pseudomonas aeruginosa (PA) infection has been associated with worse health-related quality of life (HRQL), but little is known about Mycobacterium avium complex lung disease (MACLD) patients in this context. This study aimed to evaluate HRQL and investigate the impact of chronic PA infection in MACLD patients. METHODS: This cross-sectional study was conducted using the Registry of Prospective Cohort Study including MACLD patients. The 36-item Short-Form health survey (SF-36) and St. George's Respiratory Questionnaire (SGRQ) were administered to assess clinical outcomes. Clinical variables included treatment and sputum culture status, pulmonary function tests, cavitary lesions, and modified Reiff scores on high-resolution computed tomography. RESULTS: The study included 244 MACLD patients (median age, 68 years; 196 women), 19 of whom had chronic PA infection. Modified Reiff score was higher in patients with chronic infection than in those without (P = 0.028). Regarding SF-36 scores, physical functioning subscale scores were significantly lower in patients with chronic infection (P = 0.029). Additionally, SGRQ symptoms, impact, and total scores were significantly higher in patients with chronic infection. During analysis of covariance comparisons, SGRQ symptoms and impact scores were significantly higher for patients with chronic infection (P = 0.043 and 0.021, respectively). CONCLUSIONS: MACLD patients with chronic PA infection exhibited significantly higher SGRQ scores, indicating impaired HRQL. Chronic PA infection was significantly associated with the severity of bronchiectasis.

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Comparison of antipseudomonal β-lactams for febrile neutropenia empiric therapy: systematic review and network meta-analysis.

Horita N, Shibata Y, Watanabe H, Namkoong H, Kaneko T

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases （ELSEVIER SCI LTD）  23 （ 10 ） 723 - 729 2017年10月

査読有り,  ISSN  1198-743X

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Objectives: To compare the effectiveness and safety of antipseudomonal beta-lactam empiric monotherapy for febrile neutropenia by network meta-analysis.
Methods: Searches using Pubmed, Cochrane CENTRAL, EMBASE and Web of Science Core Collection were carried out in June 2016. English articles, non-English articles, full-length articles, short articles and conference abstracts were allowed. Eligible trial design was a parallel-group individual randomization. We included febrile neutropenia adult and paediatric patients undergoing chemotherapy for either solid tumours or haematological malignancies and treated with intravenous antipseudomonal beta-lactams for initial empiric therapy. Protocol was registered with PROSPERO ID 42016043377.
Results: Of 1275 articles detected by the search, 50 studies with 10 872 patients were finally included. Among the guideline-recommended cefepime, meropenem, imipenem/cilastatin, piperacillin/tazobactam and ceftazidime; imipenem/cilastatin showed the highest odds of treatment success without modification, which was the primary endpoint, based on the random-effect model network analysis. Ceftazidime was related to lower treatment success rate without modification compared with imipenem/cilastatin with OR of 0.71 (95% CI 0.57-0.89, p 0.006). Imipenem/cilastatin showed the lowest odds of all-cause death. Patients treated with cefepime had higher risk for all-cause death compared with those treated with imipenem/cilastatin (OR 2.05, 95% CI 1.11-3.78, p 0.029). Any adverse event was significantly more prevalent in the imipenem/cilastatin arm; however, there was no difference concerning adverse events leading to discontinuation.
Conclusions: Imipenem/cilastatin, piperacillin/tazobactam and meropenem may be reasonable first-choice medications for empiric therapy of febrile neutropenia. (C) 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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