Papers - Namkoong, Ho

National policies for paediatric universal BCG vaccination were associated with decreased mortality due to COVID-19.

Risa Ebina-Shibuya, Nobuyuki Horita, Ho Namkoong, Takeshi Kaneko

Respirology (Carlton, Vic.) 25 ( 8 ) 898 - 899 2020.08

Accepted

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Current national policies for infant universal bacille Calmette-Guérin vaccination were associated with lower mortality from coronavirus disease 2019.

Risa Ebina-Shibuya, Nobuyuki Horita, Ho Namkoong, Takeshi Kaneko

Clinical and experimental vaccine research 9 ( 2 ) 179 - 182 2020.07

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An exciting debate has emerged whether bacille Calmette-Guérin (BCG) vaccination is effective for the coronavirus disease 2019 (COVID-19) pandemic. Some advocated that BCG-vaccinated people are less suffered from the virus because BCG vaccination is recommendedin COVID-19 high burden countries. However, the others objected because this seemingly attractive relationship is explainable with confounding factors. In a multiple regression with 171 countries adjusting socioeconomical and climatic covariates, countries with current universal pediatric BCG policy were associated with 30-fold (95% confidence interval, 17-52) decrease of COVID-19 mortality per population compared to countries without the policy.

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Detection of the early stage of spontaneous hemopneumothorax by CT attenuation values.

Yukiko Koike, Ho Namkoong, Sotaro Otake, Hisao Asamura

Clinical case reports 8 ( 7 ) 1321 - 1322 2020.07

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Spontaneous hemopneumothorax is potentially fatal and can mimic spontaneous pneumothorax when changes in vital signs and bloody discharge from the chest tube are absent. Attenuation values at computed tomography may help detect this condition.

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ADAM17 protects against elastase-induced emphysema by suppressing CD62L+ leukocyte infiltration in mice.

Shoji Suzuki, Makoto Ishii, Takanori Asakura, Ho Namkoong, Satoshi Okamori, Kazuma Yagi, Hirofumi Kamata, Tatsuya Kusumoto, Shizuko Kagawa, Ahmed E Hegab, Masaki Yoda, Keisuke Horiuchi, Naoki Hasegawa, Tomoko Betsuyaku

American journal of physiology. Lung cellular and molecular physiology 318 ( 6 ) L1172-L1182 2020.06

Accepted

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Pulmonary emphysema is a major manifestation of chronic obstructive pulmonary disease and is associated with chronic pulmonary inflammation caused by cigarette smoking, with contributions from immune cells such as neutrophils, macrophages, and lymphocytes. Although matrix metalloproteinases are well known to contribute to emphysema progression, the role of a disintegrin and metalloproteinase (ADAM) family proteins, other major metalloproteinases, in disease pathogenesis is largely unknown. ADAM17 is a major sheddase that cleaves various cell surface proteins, including CD62L, an adhesion molecule that plays a critical role in promoting the migration of immune cells to the site of inflammation. In the present study, we aimed to investigate the potential role of ADAM17 and CD62L in the development of elastase-induced emphysema. Control and Adam17flox/flox/Mx1-Cre (Adam17ΔMx1) mice (8-10 wk old) were intratracheally injected with 5 units of porcine pancreas elastase and monitored for 35 days after injection. Lung alveolar destruction was evaluated by analyzing the mean linear intercepts of lung tissue specimens and by histopathological examination. Mean linear intercepts data indicated that the degree of elastase-induced emphysema was significantly more severe in Adam17ΔMx1 mice. Furthermore, flow cytometry showed that CD62L+ neutrophil, CD62L+ macrophage, and CD62L+ B lymphocyte numbers were significantly increased in Adam17ΔMx1 mice. Moreover, the pharmacological depletion of CD62L+ cells with a CD62L-neutralizing antibody ameliorated the extent of emphysema in Adam17ΔMx1 mice. Collectively, these results suggest that ADAM17 possibly suppresses the progression of emphysema by proteolytically processing CD62L in immune cells and that ADAM17 and CD62L could be novel therapeutic targets for treating pulmonary emphysema.

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A decade of Gottron's papules, inverse Gottron's papules and mechanic's hand in anti-MDA5-associated interstitial lung disease with clinically amyopathic dermatomyositis.

Naoki Kawakami, Haruka Eda, Miho Nishiura, Ayaka Chaya, Fumitake Saito, Ho Namkoong

Oxford medical case reports 2020 ( 6 ) omaa039 2020.06

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Cavitary lesions emerged rapidly in Pseudomonas aeruginosa pneumonia.

Naoki Kawakami, Shin Ohara, Ho Namkoong

Clinical case reports (Wiley)  8 ( 3 ) 576 - 577 2020.03

Accepted

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Pseudomonas aeruginosa should be highly considered as a causative pathogen, when patients deteriorate rapidly despite community-acquired pathogen, and the radiological findings display a rapid emergence of cavitary lung lesions especially among patients at high risk of P aeruginosa pneumonia.

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Cardiac tamponade secondary to empyema.

Naoki Kawakami, Kohei Kushimoto, Fumitake Saito, Ho Namkoong

Clinical case reports (Wiley)  8 ( 3 ) 574 - 575 2020.03

Accepted

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A 70-year-old male presented with a 1-month history of malaise and fever. He was diagnosed with chronic empyema and went into shock by cardiac tamponade after treatment. This case shows that even chronic empyema can cause cardiac tamponade. It should be considered as differential diagnoses of shock after empyema treatment.

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Co-infection with SARS-CoV-2 and influenza A virus

S Azekawa, H Namkoong, K Mitamura, Y Kawaoka, F Saito

IDCases 20, e00775  2020

IL-6 and G-CSF production resulting from lung cancer in an HIV patient.

Naoki Kawakami, Ho Namkoong, Katsunori Masaki, Yutaka Kurebayashi, Masayuki Shimoda, Hiroshi Kotani, Hiroshi Fujiwara, Naoki Hasegawa

IDCases 19   e00693 2020

Accepted

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Increasing reports have noted an increased prevalence of lung cancer in human immunodeficiency virus (HIV)-positive patients with poor prognosis. A 51-year-old HIV-positive man was diagnosed with stage IV squamous cell lung cancer. He had high grade spike intermittent fever and persistent elevation of the white blood cell count as well as C-reactive protein (CRP) levels. Although we suspected opportunistic infections, we did not detect any infection. The autopsy showed positive immunostaining for Interleukin-6 (IL-6) in plasma cells of the stromal regions and G-CSF in tumor cells, which were considered responsible for his significant tumor fever, leukocytosis and high titers of CRP. This case report highlights the need to consider cytokine-producing tumor as a differential diagnosis of fever and high inflammatory status in HIV-positive cancer patients.

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Host Genetic Analysis of Pulmonary NTM Disease and Non-CF Bronchietasis

H Namkoong, Y Omae, T Asakura, M Ishii, S Suzuki, K Morimoto, ...

C16. NTM DISEASE-NEW DATA AND CHANGING PARADIGMS, A4491-A4491  2020

Hidden disseminated extracutaneous AIDS-related Kaposi sarcoma.

Naoki Kawakami, Ho Namkoong, Masayuki Shimoda, Hiroshi Kotani, Hiroshi Fujiwara, Naoki Hasegawa

IDCases 19   e00716 2020

Accepted

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A 68-year-old man with past medical history of multiple cerebral infarctions presented to our hospital with subacute paresis. His vital signs on presentation were normal, and his physical examination, other than his neurological findings, was unremarkable. Neurological examinations suggested cerebellar ataxia. Laboratory testing confirmed positive for human immunodeficiency virus (HIV) infection. His CD4-positive lymphocyte count was 45/μL, and HIV-RNA was 2.3 × 105 copies/mL. Brain computed tomography (CT) scan revealed multiple mass lesions and brain magnetic resonance imaging (MRI) with fluid-attenuated inversion-recovery (FLAIR) revealed periventricular hyperintensities, which suggested multiple malignant lymphoma and HIV encephalopathy. His state of consciousness had gradually worsened. Eventually, he died one month after admission. The autopsy unexpectedly showed disseminated Kaposi's sarcoma (KS). KS lesions were found in the stomach, small intestine, liver, spleen, mesentery and lungs. KS was not observed on his skin. Gross findings revealed multiple nodular lesions in each organ, and hematoxylin and eosin staining showed proliferation of spindle cells with vascular proliferation. Immunostaining was positive both for endothelial marker (CD31 and von Willebrand factor) and lymphatic endothelial marker (D2-40), which were consistent with KS.KS is the most common tumor in AIDS patients. It is caused by the human herpes-virus 8 infection. It manifests an indolent clinical course and mostly involves cutaneous lesions over the lower limbs, trunk and oral cavity. In this case, autopsy revealed disseminated KS pathologically, which was unrecognized before his death. This case highlights the possible existence of disseminated KS even without its cutaneous findings.

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Frequency of Bronchiectasis Related Variants in an Idiopathic Pulmonary Nontuberculous Mycobacteria (PNTM) Population in the National Institute of Allergy and Infectious …

K Kumar, M Similuk, M Walkiewicz, H Namkoong, A Oler, D Veltri, ...

C16. NTM DISEASE-NEW DATA AND CHANGING PARADIGMS, A4493-A4493  2020

Etiology and Health-Related Quality of Life in Non-Cystic Fibrosis Bronchiectasis and Nontuberculous Mycobacterial Pulmonary Disease: The First Analysis of the Japanese …

T Asakura, K Morimoto, A Ito, S Suzuki, E Morino, Y Oshitani, T Nakagawa, ...

B106. BREAKTHROUGHS IN NTM DIAGNOSIS AND TREATMENT, A4370-A4370  2020

Concern over a COVID-19-related BCG shortage

H Namkoong, N Horita, R Ebina-Shibuya

Int J Tuberc Lung Dis 24 (6), 642-643  2020

Multisystem inflammatory syndrome in children (MIS-C) with COVID-19: insights from simultaneous familial Kawasaki disease cases

R Ebina-Shibuya, H Namkoong, Y Shibuya, N Horita

International Journal of Infectious Diseases 97, 371-373  2020

Prevalence and Risk Factors for Osteoporosis in Patients with Pulmonary Nontuberculous Mycobacterial Disease

H Tanaka, T Asakura, S Suzuki, S Okamori, T Kusumoto, T Ogawa, ...

B106. BREAKTHROUGHS IN NTM DIAGNOSIS AND TREATMENT, A4361-A4361  2020

National policies for paediatric universal BCG vaccination were associated with decreased mortality due to COVID‐19

R Ebina‐Shibuya, N Horita, H Namkoong, T Kaneko

Respirology (Carlton, Vic.) 25 (8), 898  2020

Buffalo Chest Syndrome Following Esophagectomy.

Naoki Kawakami, Ho Namkoong

Internal medicine (Tokyo, Japan) 58 ( 16 ) 2413 - 2413 2019.08

Accepted

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Mycobacterium abscessus pulmonary disease: individual patient data meta-analysis.

Nakwon Kwak, Margareth Pretti Dalcolmo, Charles L Daley, Geoffrey Eather, Regina Gayoso, Naoki Hasegawa, Byung Woo Jhun, Won-Jung Koh, Ho Namkoong, Jimyung Park, Rachel Thomson, Jakko van Ingen, Sanne M H Zweijpfenning, Jae-Joon Yim

The European respiratory journal 54 ( 1 )  2019.07

Accepted

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Treatment of Mycobacterium abscessus pulmonary disease (MAB-PD), caused by M. abscessus subsp. abscessus, M. abscessus subsp. massiliense or M. abscessus subsp. bolletii, is challenging.We conducted an individual patient data meta-analysis based on studies reporting treatment outcomes for MAB-PD to clarify treatment outcomes for MAB-PD and the impact of each drug on treatment outcomes. Treatment success was defined as culture conversion for ≥12 months while on treatment or sustained culture conversion without relapse until the end of treatment.Among 14 eligible studies, datasets from eight studies were provided and a total of 303 patients with MAB-PD were included in the analysis. The treatment success rate across all patients with MAB-PD was 45.6%. The specific treatment success rates were 33.0% for M. abscessus subsp. abscessus and 56.7% for M. abscessus subsp. massiliense For MAB-PD overall, the use of imipenem was associated with treatment success (adjusted odds ratio (aOR) 2.65, 95% CI 1.36-5.10). For patients with M. abscessus subsp. abscessus, the use of azithromycin (aOR 3.29, 95% CI 1.26-8.62), parenteral amikacin (aOR 1.44, 95% CI 1.05-1.99) or imipenem (aOR 7.96, 95% CI 1.52-41.6) was related to treatment success. For patients with M. abscessus subsp. massiliense, the choice among these drugs was not associated with treatment outcomes.Treatment outcomes for MAB-PD are unsatisfactory. The use of azithromycin, amikacin or imipenem was associated with better outcomes for patients with M. abscessus subsp. abscessus.

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Obesity worsens the outcome of influenza virus infection associated with impaired type I interferon induction in mice.

Ho Namkoong, Makoto Ishii, Hideki Fujii, Takahiro Asami, Kazuma Yagi, Shoji Suzuki, Shuhei Azekawa, Sadatomo Tasaka, Naoki Hasegawa, Tomoko Betsuyaku

Biochemical and biophysical research communications 513 ( 2 ) 405 - 411 2019.05

Accepted

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Increasing evidence indicates that obesity is a risk factor for increased severity of influenza virus infection. However, its precise immunological mechanism is not fully understood. To investigate this, diet-induced obese (DIO) mice were established by feeding C57BL/6 male mice a high-fat diet for 16 weeks. DIO and lean control mice were infected intranasally with 3000 pfu of influenza A virus (IAV) (PR8/H1N1). Interestingly, we found adipose tissue located along the bronchus in naïve DIO mice. In addition, the Nos2 level was significantly higher and Arg1 level was significantly lower in lung macrophages of naïve DIO mice, consistent with an M1-skewed phenotype. The survival rate and body weight of DIO mice infected with IAV were significantly lower than those of lean control mice and associated with higher viral load in the lungs of DIO mice. Histopathological analysis demonstrated higher numbers of inflammatory cells in the lungs of DIO mice after IAV infection. Levels of cytokines, including TNF-α, IL-6, IL-10, and type I IFN (IFN-α and IFN-β), in bronchoalveolar lavage fluid (BALF) were altered after IAV infection; in particular, IFN-α and IFN-β levels were significantly suppressed in the BALF of DIO mice. In vitro, bone marrow-derived macrophages were stimulated with ligands of toll-like receptor (TLR) 7/8, a pattern recognition receptor for single-stranded RNA, and levels of TNF-α, IL-6, and IL-10 were similarly altered. In addition, levels of IFN-α and IFN-β were significantly lower in culture supernatants of alveolar macrophages sorted from naïve DIO mice and infected with IAV, compared to those in macrophages sorted from lean control mice. Collectively, these results suggest that macrophages may be the main contributors to poor outcomes of influenza virus infection in obesity.

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