Papers - Namkoong, Ho

Beta-lactam plus macrolides or beta-lactam alone for community-acquired pneumonia: A systematic review and meta-analysis.

Nobuyuki Horita, Tatsuya Otsuka, Shusaku Haranaga, Ho Namkoong, Makoto Miki, Naoyuki Miyashita, Futoshi Higa, Hiroshi Takahashi, Masahiro Yoshida, Shigeru Kohno, Takeshi Kaneko

Respirology (Carlton, Vic.) 21 ( 7 ) 1193 - 200 2016.10

Accepted

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It is unclear whether in the treatment of community-acquired pneumonia (CAP) beta-lactam plus macrolide antibiotics lead to better survival than beta-lactam alone. We report a systematic review and meta-analysis. Trials and observational studies published in English were included, if they provided sufficient data on odds ratio for all-cause mortality for a beta-lactam plus macrolide regimen compared with beta-lactam alone. Two investigators independently searched for eligible articles. Of 514 articles screened, 14 were included: two open-label randomized controlled trials (RCTs) comprising 1975 patients, one non-RCT interventional study comprising 1011 patients and 11 observational studies comprising 33 332 patients. Random-model meta-analysis yielded an odds ratio for all-cause death for beta-lactam plus macrolide compared with beta-lactam alone of 0.80 (95% CI 0.69-0.92, P = 0.002) with substantial heterogeneity (I(2)  = 59%, P for heterogeneity = 0.002). Severity-based subgroup analysis and meta-regression revealed that adding macrolide had a favourable effect on mortality only for severe CAP. Of the two RCTs, one suggested that macrolide plus beta-lactam lead to better outcome compared with beta-lactam alone, while the other did not. Subgrouping based on study design, that is, RCT versus non-RCT, which was almost identical to subgrouping based on severity, revealed substantial inter-subgroup heterogeneity. Compared with beta-lactam alone, beta-lactam plus macrolide may decrease all-cause death only for severe CAP. However, this conclusion is tentative because this was based mainly on observational studies.

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Histone Deacetylase Inhibition Protects Mice Against Lethal Postinfluenza Pneumococcal Infection.

Kazuma Yagi, Makoto Ishii, Ho Namkoong, Hideki Fujii, Takahiro Asami, Shoji Suzuki, Takanori Asakura, Kosuke Mizoguchi, Tetsuro Kamo, Sadatomo Tasaka, Satoshi Iwata, Steven L Kunkel, Naoki Hasegawa, Tomoko Betsuyaku

Critical care medicine 44 ( 10 ) e980-7 2016.10

Accepted

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OBJECTIVES: Secondary bacterial pneumonia following influenza virus infection is associated with high mortality, but the mechanism is largely unknown. Epigenetic gene regulation appears to play key roles in innate and adaptive immunity. We hypothesized that histone acetylation, a major epigenetic mechanism associated with transcriptionally active chromatin, might contribute to the poor outcome of postinfluenza pneumonia. DESIGN: Prospective experimental study. SETTING: University research laboratory. SUBJECTS: C57BL/6 male mice. INTERVENTIONS: Mice were infected intranasally with 1.0 × 10 colony-forming units of Streptococcus pneumoniae, 7 days after intranasal inoculation with five plaque-forming units of influenza virus A/H1N1/PR8/34. The mice were intraperitoneally injected with the histone deacetylase inhibitor trichostatin A (1 mg/kg) or vehicle once a day from 1 hour after pneumococcal infection throughout the course of the experiment. The primary outcome was survival rate. MEASUREMENTS AND MAIN RESULTS: Trichostatin A significantly suppressed histone deacetylase activity and significantly improved the survival rate of mice (56.3%) after postinfluenza pneumococcal infection when compared with vehicle-treated mice (20.0%), which was associated with a significant decrease in the total cell count of the bronchoalveolar lavage fluid. The interleukin-1β level in the serum and the number of natural killer cells in the lungs were significantly lower in the trichostatin A-treated group. CONCLUSIONS: The histone deacetylase inhibitor trichostatin A protects mice against postinfluenza pneumonia possibly through multiple factors, including decreasing local cell recruitment into the lungs and suppressing systemic inflammation.

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Clinical characteristics of pulmonary Mycobacterium scrofulaceum disease in 2001-2011: A case series and literature review.

Shoji Suzuki, Eriko Morino, Makoto Ishii, Ho Namkoong, Kazuma Yagi, Takanori Asakura, Takahiro Asami, Hiroshi Fujiwara, Yoshifumi Uwamino, Tomoyasu Nishimura, Sadatomo Tasaka, Tomoko Betsuyaku, Jin Takasaki, Satoshi Iwata, Naoki Hasegawa

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 22 ( 9 ) 611 - 6 2016.09

Accepted

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BACKGROUND: Mycobacterium scrofulaceum is a well-known pathogen associated with cervical lymphadenitis in children. However, pulmonary M. scrofulaceum disease is a rare condition with unknown clinical features. The present study aimed to clarify the clinical features of pulmonary M. scrofulaceum disease described in recent cases and reports. METHODS: We reviewed the medical records of all adult patients with pulmonary M. scrofulaceum disease at Keio University Hospital and the National Center for Global Health and Medicine Center Hospital between 2001 and 2011. We also conducted a review of the PubMed database to identify additional cases of pulmonary M. scrofulaceum disease in adults. RESULTS: Our study identified 8 cases of pulmonary M. scrofulaceum disease at the 2 identified institutions during our study period. Most cases were diagnosed in middle-aged and elderly men with underlying pulmonary diseases such as chronic obstructive pulmonary disease and Mycobacterium avium complex lung disease, as well as those with a history of pulmonary tuberculosis. In contrast, most previously reported cases identified through our literature review had a history of dust inhalation or underlying silicosis. Three of 8 cases at our institutions and 20 of 23 cases from the literature were treated with combination therapies. CONCLUSIONS: We conclude that in the recent histories of our institutions, pulmonary M. scrofulaceum disease has mainly occurred in patients with chronic pulmonary diseases. We further conclude that combination therapies that include clarithromycin might yield better patient outcomes.

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Clinical efficacy and safety of multidrug therapy including thrice weekly intravenous amikacin administration for Mycobacterium abscessus pulmonary disease in outpatient settings: a case series.

Ho Namkoong, Kozo Morimoto, Tomoyasu Nishimura, Hiromu Tanaka, Hiroaki Sugiura, Yoshitake Yamada, Atsuko Kurosaki, Takanori Asakura, Shoji Suzuki, Hiroshi Fujiwara, Kazuma Yagi, Makoto Ishii, Sadatomo Tasaka, Tomoko Betsuyaku, Yoshihiko Hoshino, Atsuyuki Kurashima, Naoki Hasegawa

BMC infectious diseases 16   396 - 396 2016.08

Accepted

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BACKGROUND: Mycobacterium abscessus (M. abscessus) pulmonary disease is a refractory chronic infectious disease. Options for treating M. abscessus pulmonary disease are limited, especially in outpatient settings. Among parenteral antibiotics against M. abscessus, intravenous amikacin (AMK) is expected to be an effective outpatient antimicrobial therapy. This study evaluated the clinical efficacy and safety of intravenous AMK therapy in outpatients with M. abscessus pulmonary disease. METHODS: This retrospective chart review of cases of M. abscessus pulmonary disease evaluated patient background data, AMK dosage and duration, sputum conversion, clinical symptoms radiological findings, and adverse events. M. massiliense was excluded on the basis of multiplex PCR assay. RESULTS: Thirteen patients (2 men and 11 women) with M. abscessus pulmonary disease were enrolled at 2 hospitals. The median age at the initiation of intravenous AMK treatment was 65 years (range: 50-86 years). Patients received a median AMK dose of 12.5 mg/kg (range: 8.3-16.2 mg/kg) for a median duration of 4 months (range: 3-9 months). The addition of intravenous AMK led to sputum conversion in 10 of 13 patients, and 8 patients continued to have negative sputum status 1 year after treatment. Approximately half of the patients showed improvement on chest high-resolution computed tomography. There were no severe adverse events such as ototoxicity, vestibular toxicity, and renal toxicity. CONCLUSIONS: Thrice weekly intravenous AMK administration in outpatient settings is effective and safe for patients with M. abscessus pulmonary disease.

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Pneumothorax associated with nontuberculous mycobacteria: A retrospective study of 69 patients.

Masako Ueyama, Takanori Asakura, Kozo Morimoto, Ho Namkoong, Shuichi Matsuda, Takeshi Osawa, Makoto Ishii, Naoki Hasegawa, Atsuyuki Kurashima, Hajime Goto

Medicine 95 ( 29 ) e4246 2016.07

Accepted

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The incidence of nontuberculous mycobacterial pulmonary disease (NTMPD) is increasing worldwide. Secondary spontaneous pneumothorax occurs as a complication of underlying lung disease and is associated with higher morbidity, mortality, and recurrence than primary spontaneous pneumothorax. We here investigated the clinical features and long-term outcomes of pneumothorax associated with NTMPD.We conducted a retrospective study on consecutive adult patients with pneumothorax associated with NTMPD at Fukujuji Hospital and Keio University Hospital from January 1992 to December 2013. We reviewed the medical records of 69 such patients to obtain clinical characteristics, radiological findings, and long-term outcomes, including pneumothorax recurrence and mortality.The median age of the patients was 68 years; 34 patients were women. The median body mass index was 16.8 kg/m. Underlying pulmonary diseases mainly included chronic obstructive pulmonary disease and pulmonary tuberculosis. On computed tomography, nodules and bronchiectasis were observed in 46 (98%) and 45 (96%) patients, respectively. Consolidation, pleural thickening, interlobular septal thickening, and cavities were most common, and observed in 40 (85%), 40 (85%), 37 (79%), and 36 (77%) patients, respectively. Regarding pneumothorax treatment outcomes, complete and incomplete lung expansion were observed in 49 patients (71%) and 15 patients (22%), respectively. The survival rate after pneumothorax was 48% at 5 years. By the end of the follow-up, 33 patients had died, and the median survival was 4.4 years with a median follow-up period of 1.7 years. The rate of absence of recurrence after the first pneumothorax was 59% at 3 years. By the end of the follow-up, 18 patients had experienced pneumothorax recurrence. Furthermore, 12/18 patients (66%) with recurrent pneumothorax died during the study period. Twenty-three patients (70%) died because of NTMPD progression. Low body mass index (BMI) was a negative prognostic factor for pneumothorax associated with NTMPD in multivariate analysis (HR 0.79, 95% CI 0.64-0.96; P = 0.018)Patients with pneumothorax associated with NTMPD have advanced disease, a high rate of pneumothorax recurrence, and poor prognosis, regardless of the pneumothorax treatment used. Further improvements in early diagnosis of NTMPD and appropriate management in both NTMPD and NTMPD-associated pneumothorax are needed.

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Epidemiology of Pulmonary Nontuberculous Mycobacterial Disease, Japan.

Ho Namkoong, Atsuyuki Kurashima, Kozo Morimoto, Yoshihiko Hoshino, Naoki Hasegawa, Manabu Ato, Satoshi Mitarai

Emerging infectious diseases 22 ( 6 ) 1116 - 7 2016.06

Accepted

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Refractory tenosynovitis with 'rice bodies' in the hand due to Mycobacterium intracellulare.

Ho Namkoong, Keizo Fukumoto, Igen Hongo, Naoki Hasegawa

Infection 44 ( 3 ) 393 - 4 2016.06

Accepted

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Pneumococcal Infection Aggravates Elastase-Induced Emphysema via Matrix Metalloproteinase 12 Overexpression.

Saeko Takahashi, Makoto Ishii, Ho Namkoong, Ahmed E Hegab, Takahiro Asami, Kazuma Yagi, Mamoru Sasaki, Mizuha Haraguchi, Minako Sato, Naofumi Kameyama, Takanori Asakura, Shoji Suzuki, Sadatomo Tasaka, Satoshi Iwata, Naoki Hasegawa, Tomoko Betsuyaku

The Journal of infectious diseases 213 ( 6 ) 1018 - 30 2016.03

Accepted

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BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (COPD)--typically caused by bacterial or viral infection--is associated with poor prognosis and emphysema progression through unknown mechanisms. We aimed to elucidate the mechanisms responsible for the poor prognosis and emphysema progression associated with COPD exacerbation. METHODS: We established a mouse model mimicking acute human COPD exacerbation, wherein mice with elastase-induced emphysema were intranasally infected with Streptococcus pneumoniae. RESULTS: In mice with elastase-induced emphysema, infection with S. pneumoniae resulted in increased mortality, an increased number of inflammatory cells in bronchoalveolar lavage fluid (BALF), and increased matrix metalloproteinase 12 (MMP-12) production in the lungs, as well as enhanced emphysema progression. The increased MMP-12 production was mostly due to alveolar type II cells, alveolar macrophages, and lymphocytes that aggregated around vessels and bronchioles. Dexamethasone treatment suppressed the mortality rate and number of inflammatory cells in BALF but not emphysema progression, possibly owing to the failure of MMP-12 suppression in the lungs, whereas treatment with the MMP inhibitor ONO-4817 dramatically suppressed both mortality rate and emphysema progression. CONCLUSIONS: These results suggest that MMP-12 production during COPD exacerbation results in increased mortality and emphysema progression. Our study identifies MMP-12 as a target to prevent further aggravation of COPD.

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Disseminated Mycobacterium marinum Infection With a Destructive Nasal Lesion Mimicking Extranodal NK/T Cell Lymphoma: A Case Report.

Takanori Asakura, Makoto Ishii, Taku Kikuchi, Kaori Kameyama, Ho Namkoong, Noboru Nakata, Kayoko Sugita, Sadatomo Tasaka, Takayuki Shimizu, Yoshihiko Hoshino, Shinichiro Okamoto, Tomoko Betsuyaku, Naoki Hasegawa

Medicine 95 ( 11 ) e3131 2016.03

Accepted

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Mycobacterium marinum is a ubiquitous waterborne organism that mainly causes skin infection in immunocompetent patients, and its disseminated infection is rare. Extranodal NK/T cell lymphoma, nasal type (ENKL) usually localizes at the nasal and/or paranasal area, but occasionally disseminates into the skin/soft tissue and gastrointestinal tract. Compromised immunity is a risk factor for developing nontuberculous mycobacterial (NTM) infection and malignant lymphoma, and the 2 diseases may share similar clinical presentation; however, only a few reports have described NTM infection mimicking malignant lymphoma.A 43-year-old Japanese man presented to our hospital complaining of multiple progressive skin nodules and purulent nasal discharge for 3 weeks. He was diagnosed with Crohn disease with refractory enteropathic arthritis and has been treated with anti-tumor necrosis factor alpha agents for 25 years. Fiberoptic nasal examination revealed septal perforation with hemorrhagic mucus and purulent rhinorrhea. Histological examination of the nasal septum revealed the infiltration of atypical medium-to-large-sized cells with erosion. The cells were positive for cytoplasmic CD3, granzyme B, and Epstein-Barr virus-encoded small RNA. Histological examination of the skin nodules and auricle also showed infiltration of atypical lymphocytes. The patient was tentatively diagnosed with ENKL, and chemotherapy was considered. However, the skin lesions decreased in size after discontinuation of immunosuppressive agents and minocycline administration. Two weeks later, nasal septum and lavage fluid and left leg skin cultures were positive for M marinum, and minocycline was discontinued. The skin and the nasal lesions improved after 2 months. To the best of our knowledge, this is the first case of disseminated M marinum infection with a destructive nasal lesion mimicking ENKL. The differentiation between M marinum infection and ENKL is clinically important because misdirected treatment leads to a poor prognosis. NTM infections including M marinum should be considered in differential diagnosis of ENKL. Bacterial cultures, pathological analysis, and close monitoring are required for the differentiation of ENKL and disseminated M marinum infection; both are serious diseases and early diagnostic distinction between them and immediate appropriate treatment will improve the patient's prognosis.

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Blue-Black Trachea as a Result of Minocycline-induced Hyperpigmentation.

Takanori Asakura, Shigenari Nukaga, Ho Namkoong, Kazuma Yagi, Shoji Suzuki, Makoto Ishii, Sadatomo Tasaka, Tomoko Betsuyaku, Naoki Hasegawa

American journal of respiratory and critical care medicine 193 ( 3 ) e5-6 2016.02

Accepted

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Fournier's gangrene: a surgical emergency.

Ho Namkoong, Makoto Ishii, Masayuki Koizumi, Tomoko Betsuyaku

Infection 44 ( 1 ) 143 - 4 2016.02

Accepted

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3-Deazaneplanocin A-An Inhibitor Of Histone Methyltransferase Ezh2-Exacerbates Elastase-Induced Emphysema In Mice

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

C70. THE NEXT NEW THERAPEUTIC TARGET? TRANSLATIONAL STUDIES OF COPD …  2016

C70 THE NEXT NEW THERAPEUTIC TARGET? TRANSLATIONAL STUDIES OF COPD THERAPIES: 3-Deazaneplanocin A-An Inhibitor Of Histone Methyltransferase Ezh2-Exacerbates Elastase-Induced …

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

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

C57 CELLULAR/MOLECULAR MECHANISMS AND TRANSLATIONAL ASPECTS OF RESPIRATORY INFECTIONS: Obesity Worsens The Outcome Of Influenza Virus Infection Via Impaired Ifn-Beta Induction …

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

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

C105 RESPIRATORY FAILURE: MECHANISTIC INSIGHTS FROM LUNG INJURY MODELS: Critical Role Of The Prostaglandin D2 Receptor Crth2 In Acute Lung Injury Caused By Lipopolysaccharide …

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

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

Blue–Black Trachea as a Result of Minocycline-induced Hyperpigmentation

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

American journal of respiratory and critical care medicine 193 (3), e5-e6  2016

Beta‐lactam plus macrolides or beta‐lactam alone for community‐acquired pneumonia: A systematic review and meta‐analysis

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

Respirology 21 (7), 1193-1200  2016

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

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

Clinical characteristics of pulmonary Mycobacterium scrofulaceum disease in 2001–2011: a case series and literature review

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

Journal of Infection and Chemotherapy 22 (9), 611-616  2016