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Papers - Namkoong, Ho

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R-CHOP Chemotherapy for Disseminated Mycobacterium avium Complex Disease due to Anti-Interferon-Gamma Autoantibodies: A Case Report.

Shunsuke Uno, Eisuke Uehara, Toshiki Kimura, Takuro Sakagami, Ho Namkoong, Sho Uchida, Yoshifumi Uwamino, Naoki Hasegawa

Open forum infectious diseases 8 ( 6 ) ofab181 2021.06

ISSN 2328-8957

A 77-year-old Japanese man with disseminated Mycobacterium avium complex (MAC) disease due to anti-interferon-gamma autoantibodies received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy because of non-Hodgkin lymphoma complication. The hepatobiliary nodules due to MAC resolved with R-CHOP and multidrug antimycobacterial treatment. R-CHOP could serve as an alternative adjunctive therapy for patients with anti-interferon-gamma autoantibodies.

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The effect of adding immune checkpoint inhibitors on the risk of pneumonitis for solid tumours: a meta-analysis of phase III randomised controlled trials.

Yu Fujiwara, Nobuyuki Horita, Ho Namkoong, Matthew D Galsky

European journal of cancer (Oxford, England : 1990) 150 168 - 178 2021.06

ISSN 0959-8049

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become one of the standard treatment options for solid tumours; however, treatment-related adverse events, including pneumonitis, sometimes disrupt the ongoing treatment. To evaluate the impact of ICI addition on the risk of pneumonitis, a meta-analysis was conducted. METHODS: Phase III randomised controlled trials comparing ICIs and conventional therapy with conventional therapy alone were selected by searching databases, including PubMed, Embase, Web of Science and Cochrane Library. The odds ratio (OR) of any grade and grade III-V pneumonitis was calculated. Meta-analysis was performed to compare the incidence of pneumonitis between the treatment arm with additional ICIs and the arm with conventional therapy. RESULTS: A total of 25 randomised controlled trials (RCTs) representing 16,343 patients for grade I-V and 23 RCTs with 15,006 patients for grade III-V pneumonitis were analysed. Adding ICIs was associated with a significant increase in pneumonitis (grade I-V: OR, 2.67, 95% confidence interval [CI]: 2.12-3.37, grade III-V: OR, 1.83, 95% CI: 1.26-2.65). In subgroup analyses based on the mechanism of action of ICIs, cancer types (lung and non-lung cancer) and each ICI, no significant difference in heterogeneity was observed. CONCLUSIONS: Adding ICIs to the conventional treatment for solid tumours significantly increased both grade I-V and grade III-V pneumonitis regardless of the mechanisms of ICIs and cancer type. These results would be helpful for oncologists to choose the appropriate treatment options using ICIs, particularly for patients with known risk factors of pneumonitis or interstitial lung disease.

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Clinical Features and Prognosis of Nontuberculous Mycobacterial Pleuritis: A Multicenter Retrospective Study.

Kazuma Yagi, Akihiro Ito, Keiji Fujiwara, Eriko Morino, Isano Hase, Yasushi Nakano, Takanori Asakura, Koji Furuuchi, Atsuho Morita, Takahiro Asami, Ho Namkoong, Fumitake Saito, Kozo Morimoto, Makoto Ishii, Yasunori Sato, Hiroki Tateno, Kazumi Nishio, Yoshitaka Oyamada, Koichi Fukunaga, Haruhito Sugiyama, Tadashi Ishida, Atsuyuki Kurashima, Naoki Hasegawa

Annals of the American Thoracic Society 18 ( 9 ) 1490 - 1497 2021.04

ISSN 1546-3222

RATIONALE: The clinical features and prognosis of nontuberculous mycobacterial (NTM) pleuritis and pleural effusion combined with NTM lung disease (NTM-LD) remain unclear. OBJECTIVES: To investigate the clinical features and prognosis of NTM pleuritis. METHODS: This retrospective observational study included patients with NTM pleuritis from January 2001 to June 2018 across eight hospitals in Japan. NTM pleuritis was defined by a positive culture of NTM from pleural effusion. We matched patients with Mycobacterium complex lung disease (MAC-LD) without pleuritis by sex and age to obtain comparative data and investigated the association between clinical parameters and prognosis. RESULTS: We identified 64 patients with NTM pleuritis (median age, 73 years; 37 female). The median follow-up duration was 11 months, and 27 patients died. Patients with MAC pleuritis had a significantly worse survival compared to matched patients with MAC-LD without pleuritis. Multivariate analysis revealed that pleuritis (adjusted hazard ratio [aHR], 6.99; 95% confidence interval [CI], 2.58-19.00) and underlying pulmonary diseases (aHR, 3.01; 95% CI, 1.44-6.28) were independently associated with all-cause mortality in MAC-LD patients. CONCLUSIONS: The prognosis of MAC pleuritis is poorer than that of MAC-LD without pleuritis. Pleuritis is an independent prognostic factor in patients with MAC-LD.

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Postoperative Radiotherapy for Completely Resected Masaoka/Masaoka-Koga Stage II/III Thymoma Improves Overall Survival: An Updated Meta-Analysis of 4746 Patients.

Yudai Tateishi, Nobuyuki Horita, Ho Namkoong, Tatsuji Enomoto, Atsuya Takeda, Takeshi Kaneko

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 16 ( 4 ) 677 - 685 2021.04

INTRODUCTION: Our systematic review and meta-analysis aimed to evaluate the effect of postoperative radiotherapy (PORT) on completely resected Masaoka/Masaoka-Koga (M/MK) stage II/III thymomas. METHODS: We systematically searched four online databases and included studies that compared surgery alone versus surgery plus a PORT for completely resected M/MK stage II/III thymoma. The multivariate-adjusted hazard ratios (HRs) of overall survival (OS) and disease-free survival were evaluated as the primary and secondary end points, respectively. We performed a subgroup analysis for OS with respect to M/MK stage II, III, and inseparable II/III cases. A generic inverse variance meta-analysis using a random model was conducted. RESULTS: Five studies including 4746 patients (among them, 2408 patients received PORT) met our selection criteria. A meta-analysis of these five studies revealed that PORT was associated with a significantly better OS (HR = 0.68, 95% confidence interval [CI]: 0.57-0.83, p < 0.001, I2 = 0%, p for heterogeneity = 0.97). Subgroup analyses for M/MK stage II disease (HR = 0.63, 95% CI: 0.44-0.91, p = 0.01, I2 = 0%, p for heterogeneity = 0.80) and M/MK stage III disease (HR = 0.72, 95% CI: 0.55-0.95, p = 0.02, I2 = 0%, p for heterogeneity = 0.84) revealed similar results. PORT was not associated with an improved disease-free survival (HR = 0.96, 95% CI: 0.70-1.33, p = 0.83, I2 = 0%, p for heterogeneity = 0.72). CONCLUSIONS: Currently available evidence from observational studies suggests PORT for patients with completely resected M/MK stage II/III thymoma. A randomized trial is warranted.

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ABO blood group as a risk factor for tuberculosis: A network meta-analysis.

Hao Chen, Nobuyuki Horita, Hiromi Matsumoto, Ho Namkoong, Yu Hara, Nobuaki Kobayashi, Takeshi Kaneko

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 104 701 - 707 2021.03

BACKGROUND: Despite numerous studies on ABO blood group and risk of tuberculosis, no consensus has been reached. METHODS: We conducted a systematic review following the Meta-Analysis of Observational Studies in Epidemiology group statement. English language articles providing odds ratio data regarding tuberculosis risk among ABO groups were eligible. Least-squares approach random-model network and random-model pairwise meta-analyses were conducted. The protocol-specified primary outcome was tuberculosis risk among ABO groups in the form of odds ratios calculated via a network meta-analysis. RESULTS: We identified 28 studies with 30 populations comprising 15,664 patients with tuberculosis and 254,610 controls. Subjects with AB blood type had a higher risk of becoming infected with tuberculosis than those with blood type O (odds ratio (OR) = 1.26, 95% confidence interval (CI): 1.14-1.38), A (OR = 1.25, 95% CI: 1.14-1.38), and B (OR = 1.22, 95% CI: 1.11-1.34). Pairwise comparison revealed that AB blood type was a risk factor for tuberculosis with OR = 1.23 (95% CI: 1.02-1.48) compared to other blood types. Region-based subgroup analyses suggested that the AB blood group was a substantial risk in Africa (OR = 1.78, 95% CI: 1.39-2.28) and India (OR = 1.48, 95% CI: 1.14-1.92). CONCLUSIONS: AB blood group is a risk factor for tuberculosis of a substantial magnitude in Africa and India.

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Epidemiology of macrolide-resistant Mycoplasma pneumoniae by age distribution in Japan.

Naoki Kawakami, Ho Namkoong, Fumitake Saito, Masami Ishizaki, Masahiko Yamazaki, Keiko Mitamura

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 1 ) 45 - 48 2021.01

ISSN 1341-321X

INTRODUCTION: Mycoplasma pneumoniae (M. pneumoniae) is the major pathogen involved in community-acquired pneumonia in all age groups. Resistance to macrolides, the first-line treatment for M. pneumoniae infection, is a major global public health concern. However, studies evaluating macrolide-resistant M. pneumoniae infection simultaneously in all ages are limited. This study aimed to determine the prevalence and clinical characteristics of macrolide-resistant M. pneumoniae infection in terms of age distribution. METHODS: We enrolled 292 patients in Tokyo, Japan, who visited Eiju General Hospital or Zama Children's Clinic in 2015-2016. Patients were tested using real-time PCR for M. pneumoniae DNA. PCR-positive patients (n = 151) were further selected and sequentially divided into preschool-aged children (≤5 years, n = 31), school-aged children (6-15 years, n = 101), adolescents (16-19 years, n = 5), and adults (≥20 years, n = 14). We then analyzed the M. pneumoniae infection clinical characteristics, prevalence of macrolide-resistant infection, and 23S rRNA domain V resistance-associated mutation status. RESULTS: We found insignificant differences in the prevalence of macrolide-resistant M. pneumoniae infection among all groups, clinical characteristics, and resistance-associated mutation status in patients with macrolide-resistant M. pneumoniae infection. We also found statistically higher prevalence of mutation-positive (n = 85) M. pneumoniae in patients previously treated with macrolide compared to the mutation-negative group (n = 66); 63.8% vs 11.1% (p < 0.001), respectively. CONCLUSIONS: We found no significant differences in both clinical characteristics and prevalence of macrolide-resistant M. pneumoniae infection among all ages. Also, previous macrolide treatment contributes to drug-resistance.

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Hydroxychloroquine and chloroquine for treatment of coronavirus disease 19 (COVID-19): a systematic review and meta-analysis of randomized and non-randomized controlled trials.

Risa Ebina-Shibuya, Ho Namkoong, Nobuyuki Horita, Hideaki Kato, Yu Hara, Nobuaki Kobayashi, Takeshi Kaneko

Journal of thoracic disease 13 ( 1 ) 202 - 212 2021.01

Background: Although the US government approved hydroxychloroquine (HCQ) and chloroquine (CQ) for hospitalized coronavirus disease 19 (COVID-19) patients, some studies denied efficacy of HCQ and CQ. We aimed to evaluate HCQ/CQ treatment for COVID-19. Methods: Five databases were searched on April 15, 2020, without publication date restriction. We followed both Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology statement reporting recommendations. A random-model meta-analysis was conducted to pool odds ratio (OR) and hazard ratio (HR). The quality of evidence for each outcome and the final recommendation was assessed using the GRADE guidelines of the American College of Chest Physicians. Results: We identified four randomized controlled trials (RCTs) and four observational studies with 2,063 COVID-19 cases. All-cause mortality was not affected by the administration of HCQ/CQ [OR: 1.05, 95% confidence interval (CI): 0.53-2.09, P=0.89]. No improvement of viral clearance was found neither by time-to-event analysis (HR: 1.19, 95% CI: 0.74-1.94, P=0.47) nor frequency on day 7 (OR: 1.47, 95% CI: 0.33-6.63, P=0.62). HCQ/CQ treatment increased the risk of the any adverse event with OR of 3.56 (95% CI: 1.62-7.83, P=0.002). Conclusions: HCQ/CQ failed to decrease the all-cause mortality (very low quality evidence) and did not improve viral clearance (low or very low quality evidence) but increased the risk of any adverse event (moderate quality evidence). Routine administration of HCQ/CQ for COVID-19 patients is not recommended (weak recommendation, Grade 2C).

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Serum Krebs von den Lungen-6 level in the disease progression and treatment of Mycobacterium avium complex lung disease.

Takanori Asakura, Yoshifumi Kimizuka, Tomoyasu Nishimura, Shoji Suzuki, Ho Namkoong, Yohei Masugi, Yasunori Sato, Makoto Ishii, Naoki Hasegawa

Respirology (Carlton, Vic.) 26 ( 1 ) 112 - 119 2021.01

Accepted, ISSN 1323-7799

BACKGROUND AND OBJECTIVE: The lack of useful biomarkers reflecting the disease state limits the management of Mycobacterium avium complex lung disease (MAC-LD). We clarified the associations between serum KL-6 level, disease progression and treatment response. METHODS: Resected lung tissues from MAC-LD patients were immunostained for KL-6. We compared serum KL-6 levels between MAC-LD and healthy control or bronchiectasis patients without nontuberculous mycobacterial lung disease (NTM-LD). Serum KL-6 level was assessed in a prospective observational study at Keio University Hospital between May 2012 and May 2016. We investigated associations between serum KL-6 level and disease progression and treatment response in patients untreated for MAC-LD on registration (n = 187). RESULTS: The KL-6+ alveolar type 2 cell population in the lung and serum KL-6 level were significantly higher in MAC-LD patients than in controls. Serum KL-6 level in bronchiectasis patients without NTM-LD showed no significant increase. Of the 187 patients who did not receive treatment on registration, 53 experienced disease progression requiring treatment. Multivariable Cox analysis revealed that the serum KL-6 level (aHR: 1.18, P = 0.005), positive acid-fast bacilli smear (aHR: 2.64, P = 0.001) and cavitary lesions (aHR: 3.01, P < 0.001) were significantly associated with disease progression. The change in serum KL-6 (ΔKL-6) was significantly higher in the disease progression group; it decreased post-treatment, reflecting the negative sputum culture conversion. CONCLUSION: Serum KL-6 level is associated with disease progression and treatment response. Longitudinal assessment combined with AFB smear status and presence of cavitary lesions may aid MAC-LD management.

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Clinical characteristics of patients with coronavirus disease (COVID-19): preliminary baseline report of Japan COVID-19 Task Force, a nationwide consortium to investigate host …

H Tanaka, H Lee, A Morita, H Namkoong, S Chubachi, H Kabata, ...

International Journal of Infectious Diseases 113, 74-81 2021

Diagnostic accuracy of Aspergillus‐specific antibodies for chronic pulmonary aspergillosis: A systematic review and meta‐analysis

K Anan, Y Kataoka, S Okabayashi, R Yamamoto, H Namkoong, ...

Mycoses 64 (7), 701-715 2021

Genome-wide association study in patients with pulmonary Mycobacterium avium complex disease

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

European Respiratory Journal 58 (2) 2021

Incidence and Distinct Features of Immune Checkpoint Inhibitor-Related Myositis From Idiopathic Inflammatory Myositis: A Single-Center Experience With Systematic Literature Review and Meta-Analysis.

Naoki Hamada, Ayaka Maeda, Kaoru Takase-Minegishi, Yohei Kirino, Yumiko Sugiyama, Ho Namkoong, Nobuyuki Horita, Ryusuke Yoshimi, Hideaki Nakajima

Frontiers in immunology 12 803410 - 803410 2021

ISSN 1664-3224

Immune checkpoint inhibitor (ICI)-related myositis is a rare, potentially fatal condition that warrants further studies. Its incidence, clinical features, and prognosis remain poorly understood. To address these gaps, we conducted a systematic review and meta-analysis to evaluate the risk of myositis associated with ICI for solid tumors by analyzing phase III randomized controlled trials of anti-programmed death-1/ligand-1 (PD-1/PD-L1) and anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4). To complement this analysis with clinical data, we evaluated published ICI case reports along with cases from our institutional registry. This registry comprised 422 patients treated with ICIs alone or in combination from September 2014 to June 2021. The analysis revealed an incidence of ICI-related myositis in 6,838 patients in 18 randomized controlled trials of 0.38% (odds ratio 1.96; 95% confidence interval 1.02-3.75) for patients receiving ICIs compared with controls. Detailed analysis of 88 cases from the literature search and our registry showed that myositis induced by PD-1 inhibitors was more frequent than that induced by anti-CTLA-4 agents, revealing a clinically diverse trend including myasthenia gravis and myocarditis. Importantly, having ptosis at the time of onset was significantly associated with the development of concomitant myocarditis (odds ratio 3.81; 95% CI 1.48-9.83), which is associated with poor prognosis. Regarding treatment, most patients received glucocorticoids, and some received immunosuppressants. Our study revealed the incidence of ICI-mediated myositis and the clinical features of myocarditis, highlighting the need for recognition and early intervention.

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The best regimens for chemo-naïve incurable non-squamous non-small cell lung cancer with a programmed death-ligand 1, tumor proportion score 1–49%: a network meta-analysis

N Fukuda, N Horita, S Katakura, H Namkoong, A Kaneko, K Somekawa, ...

Translational Lung Cancer Research 10 (8), 3550 2021

Serum Krebs von den Lungen‐6 level in the disease progression and treatment of Mycobacterium avium complex lung disease

T Asakura, Y Kimizuka, T Nishimura, S Suzuki, H Namkoong, Y Masugi, ...

Respirology 26 (1), 112-119 2021

Mapping the human genetic architecture of COVID-19

Writing group Writing group leaders Pathak Gita A. 6 Andrews Shea J. 7 Kanai ...

Nature 600 (7889), 472-477 600 ( 7889 ) 472 - + 2021

ISSN 0028-0836

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Japan COVID-19 Task Force: a nation-wide consortium to elucidate host genetics of COVID-19 pandemic in Japan (preprint)

H Namkoong, R Edahiro, K Fukunaga, Y Shirai, K Sonehara, H Tanaka, ...

2021

Incidence and distinct features of immune checkpoint inhibitor-related myositis from idiopathic inflammatory myositis: a single-center experience with systematic literature …

N Hamada, A Maeda, K Takase-Minegishi, Y Kirino, Y Sugiyama, ...

Frontiers in Immunology 12, 803410 2021

Susceptibility of the obese population to COVID-19.

Takefumi Kimura, Ho Namkoong

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 101 380 - 381 2020.12

Obesity is a risk factor for disease severity in individuals with coronavirus disease (COVID-19). However, the increased susceptibility of this population to COVID-19 is unclear. We outline several underlying mechanisms that may explain the relationship between obesity and COVID-19 severity. Obesity has an adverse effect on respiratory physiology because increased intra-abdominal adipose tissue can interfere with lung expansion, resulting in reduced lung compliance. Further, fat accumulation in the soft tissue of the pharynx can increase inspiratory resistance, and obesity may be associated with sleep apnea. Obesity is associated with several defects in cell-mediated immunity, including increased levels of pro-inflammatory cytokines. Impaired adipocyte-mediated immune function results in chronically high leptin levels, low adiponectin levels, and anti-inflammatory adipokines. Reduced physical activity can impair several steps of the immune response to viruses. Obesity also promotes a hypercoagulable state, leading to severe consequences. These factors may synergistically play a role in promoting the severity of the disease in obese individuals. A better understanding of the mechanisms by which obesity contributes to the severity of COVID-19 is important for developing more effective treatments.

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Clinical characteristics of 345 patients with coronavirus disease 2019 in Japan: A multicenter retrospective study.

Makoto Ishii, Hideki Terai, Hiroki Kabata, Katsunori Masaki, Shotaro Chubachi, Hiroki Tateno, Morio Nakamura, Kazumi Nishio, Hidefumi Koh, Risa Watanabe, Soichiro Ueda, Takeshi Terashima, Yusuke Suzuki, Kazuma Yagi, Naoki Miyao, Naoto Minematsu, Takashi Inoue, Ichiro Nakachi, Ho Namkoong, Satoshi Okamori, Shinnosuke Ikemura, Hirofumi Kamata, Hiroyuki Yasuda, Ichiro Kawada, Naoki Hasegawa, Koichi Fukunaga

The Journal of infection 81 ( 5 ) e3-e5 2020.11

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Clinical significance of anti-glycopeptidolipid-core IgA antibodies in patients newly diagnosed with Mycobacterium avium complex lung disease.

Shuichi Matsuda, Takanori Asakura, Kozo Morimoto, Shoji Suzuki, Keiji Fujiwara, Koji Furuuchi, Takeshi Osawa, Ho Namkoong, Makoto Ishii, Atsuyuki Kurashima, Koichiro Tatsumi, Ken Ohta, Naoki Hasegawa, Yuka Sasaki

Respiratory medicine 171 106086 - 106086 2020.09

BACKGROUND: Although recent studies have identified anti-glycopeptidolipid (GPL)-core IgA antibodies as a serodiagnostic test for Mycobacterium avium complex lung disease (MAC-LD), this test shows insufficient sensitivity. This study aimed to determine the clinical utility of these antibodies in assessing disease progression and the clinical characteristics of MAC-LD patients with negative antibody results. METHODS: We retrospectively reviewed the medical records of consecutive newly diagnosed, untreated MAC-LD patients in two referral hospitals. We evaluated the association of anti-GPL-core IgA antibody results with disease progression requiring treatment and the factors associated with negative antibody results. RESULTS: In total, 229 patients (161 females; median age, 71 years; 185 with nodular/bronchiectatic disease phenotype; 69 with cavitary lesions) were enrolled; 146 patients (64%) were anti-GPL-core IgA antibody-positive. Radiological severity scores were associated with anti-GPL-core IgA antibody titers. During the median 364-day follow-up, 114 patients (49.8%) required treatment. Multivariate Cox proportional hazards analysis showed that positive anti-GPL-core IgA antibody results, a younger age, the absence of malignancy, and the presence of cavitary lesions were associated with disease progression requiring treatment. Multivariate logistic analysis revealed that significant factors related to the negative antibody results included underlying pulmonary disease, lower radiological scores, chronic sinusitis, and macrolide monotherapy. CONCLUSION: In addition to cavitary lesions, anti-GPL-core IgA antibody positivity was associated with disease progression requiring treatment. Physicians should carefully use anti-GPL-core IgA antibody results for the diagnosis of patients with underlying pulmonary disease, chronic sinusitis, macrolide monotherapy, and lower radiological severity.

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