論文 - 南宮　湖

B49 NON-TUBERCULOUS MYCOBACTERIAL DISEASE AND CASE REPORTS: Laboratory Based Survey For Pulmonary Non-Tuberculous Mycobacteriosis In Japan: 2012-213

K Morimoto, N Hasegawa, K Izumi, H Namkoong, K Uchimura, Y Hoshino, ...

American Journal of Respiratory and Critical Care Medicine 193, 1 2016年

A53 RESPIRATORY FAILURE: RISK FACTORS AND OUTCOMES IN ARDS: The Berlin Definition Criteria Of Ards Severity Is Associated With Prognosis And Fibroproliferative Changes On High …

T Kamo, S Tasaka, T Suzuki, T Asakura, S Suzuki, K Yagi, H Namkoong, ...

American Journal of Respiratory and Critical Care Medicine 193, 1 2016年

D32 PNEUMONIA: The Histone Deacetylase Inhibitor Trichostatin A Protects Mice Against Lethal Post-Influenza Pneumococcal Infection

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

American Journal of Respiratory and Critical Care Medicine 193, 1 2016年

Laboratory Based Survey For Pulmonary Non-Tuberculous Mycobacteriosis In Japan: 2012-213

K Morimoto, N Hasegawa, K Izumi, H Namkoong, K Uchimura, Y Hoshino, ...

B49. NON-TUBERCULOUS MYCOBACTERIAL DISEASE AND CASE REPORTS, A3719-A3719 2016年

Obesity Worsens The Outcome Of Influenza Virus Infection Via Impaired IFN-Beta Induction And Reduced Expressions Of Antimicrobial Peptides In Mice

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

C57. CELLULAR/MOLECULAR MECHANISMS AND TRANSLATIONAL ASPECTS OF RESPIRATORY … 2016年

症例で学ぶ非結核性抗酸菌症 (第 1 回) 人間ドックで異常を指摘された中葉舌区陰影

南宮湖， 倉島篤行， 長谷川直樹

呼吸と循環= Respiration and circulation 64 (1), 79-82 2016年

Theory and strategy for Pneumococcal vaccines in the elderly

H Namkoong, M Ishii, Y Funatsu, Y Kimizuka, K Yagi, T Asami, T Asakura, ...

Human vaccines & immunotherapeutics 12 (2), 336-343 12 （ 2 ） 336 - 43 2016年

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Pneumonia is the fourth-leading cause of death globally, and Streptococcus pneumoniae is the most important causative pathogen. Because the incidence of pneumococcal diseases is likely to increase with the aging society, we should determine an optimal strategy for pneumococcal vaccination. While consensus indicates that 23-valent pneumococcal polysaccharide vaccine prevents invasive pneumococcal diseases (IPD), its effects on community-acquired pneumonia (CAP) remain controversial. Recently, a 13-valent pneumococcal conjugate vaccine (PCV13) was released. The latest clinical study (CAPiTA study) showed that PCV13 reduced vaccine-type CAP and IPD. Based on these results, the Advisory Committee on Immunization Practices recommended initial vaccination with PCV13 for the elderly. Scientific evidence regarding immunosenescence is needed to determine a more ideal vaccination strategy for the elderly with impaired innate and adaptive immunity. Continuing research on the cost effectiveness of new vaccine strategies considering constantly changing epidemiology is also warranted.

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The Histone Deacetylase Inhibitor Trichostatin A Protects Mice Against Lethal Post-Influenza Pneumococcal Infection

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

D32. PNEUMONIA, A6722-A6722 2016年

The Berlin Definition Criteria Of Ards Severity Is Associated With Prognosis And Fibroproliferative Changes On High-Resolution CT

T Kamo, S Tasaka, T Suzuki, T Asakura, S Suzuki, K Yagi, H Namkoong, ...

A53. RESPIRATORY FAILURE: RISK FACTORS AND OUTCOMES IN ARDS, A1838-A1838 2016年

Refractory tenosynovitis with ‘rice bodies’ in the hand due to Mycobacterium intracellulare

H Namkoong, K Fukumoto, I Hongo, N Hasegawa

Infection 44 (3), 393-394 2016年

Pharmacokinetics of intravenous peramivir in the airway epithelial lining fluid of healthy volunteers

Y Funatsu, S Tasaka, T Asami, H Namkoong, H Fujiwara, O Iketani, ...

Antiviral Therapy 21 (7), 621-625 21 （ 7 ） 621 - 625 2016年

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BACKGROUND: Some subtypes of influenza virus, such as H5N1 and H7N9, cause severe viral pneumonia, for which the intraluminal concentration of the anti-influenza agent in the airway is critical. However, the pharmacokinetics of peramivir, the only available injectable neuraminidase inhibitor formulation, in the airway epithelial lining fluid (ELF) remains unclear. In this study, we aimed to determine the time course of peramivir in the pharyngeal ELF, bronchial ELF and plasma of healthy volunteers using bronchoscopic microsampling technique. METHODS: Six healthy volunteers were studied. After baseline plasma sampling, 0.3 g peramivir was intravenously injected over 0.5 h. ELF was obtained from the upper and lower airways using bronchoscopic microsampling at the end of the infusion (0.5 h) and after 1.0, 1.5, 2.0, 2.5, 3.0, 4.0 and 5.0 h. The concentrations of peramivir in the ELFs and in the plasma were quantified by LC/MS/MS analysis. RESULTS: The mean maximum concentration (Cmax) in pharyngeal ELF, bronchial ELF and plasma was 1.20 ±0.42, 9.60 ±2.30 and 50.52 ±17.51 ng/ml, respectively. The penetration ratio at Cmax in pharyngeal and bronchial ELFs was 2.4 and 19.0, respectively. The ratio of the area under the curve from 0 to infinity in pharyngeal and bronchial ELFs was 4.8 and 39.1 mg•min/l, respectively. CONCLUSIONS: The time course of peramivir concentration in the ELFs revealed that concentrations above the 50% inhibitory concentration value of influenza were achieved in the upper and lower airways. Therefore, peramivir could be an important treatment option for influenza viral pneumonia.

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Health-related quality of life is inversely correlated with C-reactive protein and age in Mycobacterium avium complex lung disease: a cross-sectional analysis of 235 patients

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

Respiratory Research 16 (1), 1-9 16   145 - 145 2015年12月

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BACKGROUND: Mycobacterium avium complex (MAC) lung diseases generally cause chronic disease in immunocompetent hosts. Although a few studies have examined health-related quality of life (HRQL) in patients with MAC lung disease, there have been no large studies. This study aimed to evaluate HRQL and its correlation with clinical outcomes in MAC lung disease. METHODS: A cross-sectional study was conducted at Keio University Hospital to investigate the factors associated with HRQL in pulmonary nontuberculous mycobacterial diseases. MAC lung diseases were diagnosed according to the 2007 ATS/IDSA guidelines for nontuberculous mycobacterial diseases. The 36-item short form health survey (SF-36) was administered to assess clinical outcomes. Clinical variables included treatment status, latest haematological data, and bacterial smear and culture results. RESULTS: The SF-36 scores for the 235 patients (median age, 69 years; 45 men and 190 women) with MAC lung disease, except for the bodily pain and mental health subscale scores, were significantly lower than the Japanese population norms. In the multivariable analyses, current treatment for MAC and a positive sputum smear or culture within the past year were significantly associated with lower SF-36 scores. C-reactive protein (CRP) and age showed stronger inverse correlations with SF-36 scores. CONCLUSIONS: HRQL, especially the physical component, was impaired in patients with MAC lung diseases; this appears to be related with current treatment status, positive sputum smear or culture within the previous year, and particularly CRP and age. Further studies including qualitative assessments are needed to investigate the efficacy of CRP as a marker for progression or treatment response in MAC lung disease. TRIAL REGISTRATION: Clinical trial registered with UMIN ( UMIN000007964 ).

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Dry pleurisy complicating solitary pulmonary nodules caused by Mycobacterium avium: a case report

T Asakura, M Ishii, M Haraguchi, I Kamiyama, M Kohno, H Sakamaki, ...

Journal of Medical Case Reports 9 (1), 1-4 9   238 - 238 2015年10月

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INTRODUCTION: Mycobacterium avium complex (MAC) lung disease presenting as a solitary pulmonary nodule (MAC-SPN) is often asymptomatic, is more common in middle to old age, and mimics lung cancer or tuberculoma. We report herein a case of MAC-SPN in an immunocompetent young adult patient, presenting with persistent chest pain and a subacutely progressive nodule with high intense (18)F-fluorodeoxyglucose uptake. Histological examination of resected specimens revealed pleurisy, which is a rare finding of MAC-SPN. CASE PRESENTATION: A 36-year-old Japanese male presented with chest pain and a subacutely progressive pulmonary nodule. Positron emission tomography-computed tomography showed high intense (18)F-fluorodeoxyglucose uptake in the nodule. Owing to his continuous chest pain and subacutely progressive nodules, wedge resection was performed using video-assisted thoracoscopic surgery. Histological examination revealed an epithelioid granuloma and pleurisy, and the lung tissue culture was positive for mycobacteria identified as M. avium. CONCLUSION: This is the first report of MAC-SPN occurring with persistent chest pain, suggesting that MAC should be considered in the differential diagnosis of a solitary pulmonary nodule, even for patients who experience persistent chest pain. As in the present case, surgical resection with video-assisted thoracoscopic surgery is a reasonable approach to the diagnosis and treatment of MAC-SPN with possible malignancy, especially as MAC can be diagnosed using resected lung tissue culture with histological confirmation.

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Successful resumption of tocilizumab for rheumatoid arthritis after resection of a pulmonary Mycobacterium avium complex lesion: a case report

H Namkoong, S Tasaka, M Akiyama, K Yagi, M Ishii, K Suzuki, M Kohno, ...

BMC Pulmonary Medicine 15 (1), 1-6 15   126 - 126 2015年10月

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BACKGROUND: Biological agents inhibiting TNF-α and other molecules involved in inflammatory cascade have been increasingly used to treat rheumatoid arthritis (RA). However, it remains controversial whether biological agents can be used safely in a patient with an underlying chronic infectious disease. CASE PRESENTATION: A 63-year-old woman who had been treated with tocilizumab (TCZ), anti-interleukin-6 receptor antibody, for RA presented to our outpatient clinic due to hemoptysis. She was diagnosed with pulmonary Mycobacterium avium complex (MAC) infection, and high-resolution computed tomography (HRCT) showed a single cavitary lesion in the right upper lobe. After diagnosis of pulmonary MAC disease, TCZ was discontinued and combination chemotherapy with clarithromycin, rifampicin, ethambutol and amikacin was started for MAC pulmonary disease. Since the lesion was limited in the right upper lobe as a single cavity formation, she underwent right upper lobectomy. As her RA symptoms were deteriorated around the operation, TCZ was resumed. After resumption of TCZ, her RA symptoms improved and a recurrence of pulmonary MAC infection has not been observed for more than 1 year. CONCLUSION: This case suggested that TCZ could be safely reintroduced after the resection of a pulmonary MAC lesion. Although the use of biological agents is generally contraindicated in patients with pulmonary MAC disease, especially in those with a fibrocavitary lesion, a multimodality intervention for MAC including both medical and surgical approaches may enable introduction or resumption of biological agents.

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Adjunctive systemic corticosteroids for hospitalized community-acquired pneumonia: systematic review and meta-analysis 2015 update

N Horita, T Otsuka, S Haranaga, H Namkoong, M Miki, N Miyashita, ...

Scientific reports 5 (1), 14061 5   14061 - 14061 2015年09月

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Previous randomized controlled trials (RCTs) and meta-analyses evaluated the efficacy and safety of adjunctive corticosteroids for community-acquired pneumonia (CAP). However, the results from them had large discrepancies. The eligibility criteria for the current meta-analysis were original RCTs written in English as a full article that evaluated adjunctive systemic corticosteroids adding on antibiotic therapy targeting typical and/or atypical pathogen for treating hospitalized human CAP cases. Four investigators independently searched for eligible articles through PubMed, Embase, and Cochrane databases. Random model was used. The heterogeneity among original studies and subgroups was evaluated with the I(2) statistics. Of 54 articles that met the preliminary criteria, we found 10 eligible RCTs comprising 1780 cases. Our analyses revealed following pooled values by corticosteroids. OR for all-cause death: 0.80 (95% confidence interval (95% CI) 0.53-1.21) from all studies; 0.41 (95% CI 0.19-0.90) from severe-case subgroup; 0.21 (95% CI 0.0-0.74) from intensive care unit (ICU) subgroup. Length of ICU stay: -1.30 days (95% CI (-3.04)-0.44). Length of hospital stay: -0.98 days (95% CI (-1.26)-(-0.71)). Length to clinical stability: -1.16 days (95% CI (-1.73)-(-0.58)). Serious complications do not seem to largely increase by steroids. In conclusion, adjunctive systemic corticosteroids for hospitalized patients with CAP seems preferred strategies.

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Immune reconstitution inflammatory syndrome due to Mycobacterium avium complex successfully followed up using 18 F-fluorodeoxyglucose positron emission tomography-computed tomography in a patient with human immunodeficiency virus infection: A case report.

Ho Namkoong, Hiroshi Fujiwara, Makoto Ishii, Kazuma Yagi, Mizuha Haraguchi, Masako Matsusaka, Shoji Suzuki, Takanori Asakura, Takahiro Asami, Fumitake Saito, Koichi Fukunaga, Sadatomo Tasaka, Tomoko Betsuyaku, Naoki Hasegawa

BMC medical imaging 15   24 - 24 2015年07月

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BACKGROUND: In human immunodeficiency virus (HIV)-infected patients, immune reconstitution inflammatory syndrome (IRIS) due to nontuberculous mycobacteria (NTM) infection is one of the most difficult types of IRIS to manage. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has been suggested as a useful tool for evaluating the inflammatory status of HIV-infected patients. We present the first case of Mycobacterium avium complex (MAC)-associated IRIS (MAC-IRIS) that was successfully followed up using 18F-FDG PET/CT. CASE PRESENTATION: A 44-year-old homosexual Japanese man was referred to our hospital with fever and dyspnea. He was diagnosed with Pneumocystis jiroveci pneumonia and found to be HIV positive. After the initiation of combined antiretroviral therapy (cART), the patient's mediastinal and bilateral hilar lymphadenopathy gradually enlarged, and bilateral infiltrates appeared in the upper lung fields. 18F-FDG PET/CT was performed five months after the initiation of cART and showed intense accumulation of fluorodeoxyglucose (FDG) corresponding to the lesions of infiltration as well as the mediastinal and bilateral hilar lymphadenopathy. A bronchial wash culture and pathology findings led to a diagnosis of MAC-IRIS. Anti-mycobacterial chemotherapy with rifampicin, ethambutol, clarithromycin, and levofloxacin was started. One year after the chemotherapy was initiated, there was a significant reduction in FDG uptake in the area of the lesions except in the mediastinal lymph node. This implied incomplete resolution of the MAC-IRIS-related inflammation. Anti-mycobacterial chemotherapy was continued because of the residual lesion. To date, the patient has not experienced a recurrence of MAC-IRIS, a period of nine months. CONCLUSION: We present a case of MAC-IRIS in an HIV-infected patient whose disease activity was successfully followed up using 18F-FDG PET/CT. Our data suggest that 18F-FDG PET/CT is useful for evaluating the disease activity of NTM-IRIS and assessing the appropriate duration of anti-mycobacterial chemotherapy for NTM-IRIS in HIV-infected patients.

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Fatal fulminant pneumonia caused by methicillin-sensitive Staphylococcus aureus negative for major high-virulence factors following influenza B virus infection

K Masaki, M Ishii, M Anraku, H Namkoong, R Miyakawa, T Nakajima, ...

The American Journal of Case Reports 16, 454 16   454 - 8 2015年07月

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BACKGROUND: Increasing evidence has indicated that Staphylococcus aureus pneumonia complicated with influenza virus infection is often fatal. In these cases, disease severity is typically determined by susceptibility to antimicrobial agents and the presence of high-virulence factors that are produced by Staphylococcus aureus, such as Panton-Valentine leukocidin (PVL). CASE REPORT: We describe a rare case of fatal community-acquired pneumonia caused by methicillin-sensitive Staphylococcus aureus (MSSA), which did not secrete major high-virulence factors and coexisted with influenza type B infection. The 32-year-old previously healthy male patient presented with dyspnea, high fever, and cough. His roommate had been diagnosed with influenza B virus infection 3 days earlier. Gram-positive clusters of cocci were detected in the patient's sputum; therefore, he was diagnosed with severe pneumonia and septic shock, and was admitted to the intensive care unit. Despite intensive antibiotic and antiviral treatment, he died of multiple organ failure 5 days after admission. His blood culture from the admission was positive for MSSA, and further analysis revealed that the strain was negative for major high-virulence factors, including PVL and enterotoxins, although influenza B virus RNA was detected by PCR. CONCLUSIONS: Physicians should pay special attention to patients with pneumonia following influenza and Staphylococcus aureus infection, as it may be fatal, even if the Staphylococcus aureus strain is PVL-negative and sensitive to antimicrobial agents.

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Recurrence of disseminated Mycobacterium avium complex disease in a patient with anti-gamma interferon autoantibodies by reinfection

T Nishimura, Y Fujita-Suzuki, M Yonemaru, K Ohkusu, T Sakagami, ...

Journal of Clinical Microbiology 53 (4), 1436-1438 53 （ 4 ） 1436 - 8 2015年04月

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We report a case of recurrent disseminated Mycobacterium avium complex (DMAC) disease with anti-gamma interferon autoantibodies. To our knowledge, this is the first reported case caused by reinfection with a separate isolate of M. avium. DMAC disease activity was monitored using serum IgG antibody titers against lipid antigens extracted from a MAC strain.

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The diagnostic usefulness of 18F-fluorodoxyglucose-positron emission tomography/CT in SAPHO syndrome

H Namkoong, M Ishii, S Tasaka, T Betsuyaku

Case Reports 2015, bcr2015209394 2015 2015年03月

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Comparison of the immunogenicity and safety of polysaccharide and protein-conjugated pneumococcal vaccines among the elderly aged 80 years or older in Japan: an open-labeled randomized study.

Ho Namkoong, Yohei Funatsu, Kazunori Oishi, Yukihiro Akeda, Rika Hiraoka, Kei Takeshita, Takahiro Asami, Kazuma Yagi, Yoshifumi Kimizuka, Makoto Ishii, Sadatomo Tasaka, Yukio Suzuki, Satoshi Iwata, Tomoko Betsuyaku, Naoki Hasegawa

Vaccine 33 （ 2 ） 327 - 32 2015年01月

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An open-labeled randomized study was conducted to compare the immunogenicity and safety of polysaccharide (PPV23) or protein-conjugated pneumococcal vaccine (PCV7) among the elderly aged 80 years or older. A total of 105 nursing home residents were enrolled in this study. We analyzed the geometric mean concentration (GMC) of serotype-specific immunoglobulin G (IgG) and the geometric mean titer (GMT) of the opsonization index (OI) for serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. The GMCs of serotype-specific IgG and the GMTs of the OI significantly increased one month after vaccination in both groups for all seven serotypes evaluated. In the PCV7 group, study subjects with serotypes 4, 9V, 18C, and 23F exhibited statistically significant elevations in both serotype-specific IgGs and OIs compared to those of the PPV23 group. Both vaccines were tolerated without any severe adverse events, and no differences in systemic adverse events were observed between the two groups, although adverse reactions such as redness and localized swelling were more common in the PCV7 group. Our data demonstrated that the GMCs of serotype-specific IgG and the GMTs of the OI were higher in the PCV7 group compared to those in the PPV23 group. Our study also confirmed the safety of both the PCV7 and PPV23 vaccines in elderly people aged 80 years or older.

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