Updated on 2025/03/07

写真a

 
SAKAMOTO Koji
 
Organization
Nagoya University Hospital Respiratory Medicine Lecturer of hospital
Title
Lecturer of hospital
Contact information
メールアドレス

Degree 1

  1. 博士(医学) ( 2012.7   名古屋大学 ) 

Research Interests 3

  1. interstitial lung disease

  2. pulmonary fibrosis

  3. acute lung injury

Research Areas 1

  1. Life Science / Respiratory medicine

Current Research Project and SDGs 2

  1. 肺線維症の病態解明と新規治療開発

  2. 細胞外微粒子の呼吸器への影響

Research History 1

  1. Nagoya University   Nagoya University Hospital Respiratory Medicine   Lecturer of hospital

    2022.12

Education 2

  1. Nagoya University   Graduate School, Division of Medical Sciences

    - 2012.3

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    Country: Japan

  2. Nagoya University   Graduate School, Division of Medical Sciences

    - 2012.3

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    Country: Japan

Professional Memberships 5

  1. 日本呼吸器学会

  2. 日本アレルギー学会

  3. American Thoracic Society

  4. 日本内科学会

  5. American Thoracic Society

Awards 4

  1. Young Innovator Award

    2022   JST-CREST[細胞外微粒子]   呼吸中の細胞外小胞を利用した新しい診断指標の開発

    阪本考司

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  2. International Session Award

    2017  

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    Award type:Award from international society, conference, symposium, etc.  Country:Japan

  3. The I.M. Rosenzweig Junior Investigator Award

    2016   Pulmonary Fibrosis Foundation  

    Koji Sakamoto

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    Award type:Award from publisher, newspaper, foundation, etc.  Country:United States

  4. Scientific Abstract Award

    2014   American Thoracic Society  

    Koji Sakamoto

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    Award type:Award from international society, conference, symposium, etc.  Country:United States

 

Papers 89

  1. BMP3b is a Novel Anti-Fibrotic Molecule Regulated by Meflin in Lung Fibroblasts International journal

    Atsushi Suzuki, Koji Sakamoto, Yoshio Nakahara, Atsushi Enomoto, Jun Hino, Akira Ando, Masahide Inoue, Yukihiro Shiraki, Norihito Omote, Masahiro Kusaka, Jun Fukihara, Naozumi Hashimoto

    American Journal of Respiratory Cell and Molecular Biology   Vol. 67 ( 4 ) page: 446 - 458   2022.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:American Thoracic Society  

    DOI: 10.1165/rcmb.2021-0484OC

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  2. Fibroblasts positive for meflin have anti-fibrotic property in pulmonary fibrosis. International coauthorship International journal

    Yoshio Nakahara, Naozumi Hashimoto, Koji Sakamoto, Atsushi Enomoto, Taylor S Adams, Toyoharu Yokoi, Norihito Omote, Sergio Poli, Akira Ando, Keiko Wakahara, Atsushi Suzuki, Masahide Inoue, Akitoshi Hara, Yasuyuki Mizutani, Kazuyoshi Imaizumi, Tsutomu Kawabe, Ivan O Rosas, Masahide Takahashi, Naftali Kaminski, Yoshinori Hasegawa

    The European respiratory journal   Vol. 58 ( 6 )   2021.12

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    The prognosis of elderly individuals with idiopathic pulmonary fibrosis (IPF) remains poor. Fibroblastic foci, in which aggregates of proliferating fibroblasts and myofibroblasts are involved, are the pathological hallmark lesions in IPF to represent focal areas of active fibrogenesis. Fibroblast heterogeneity in fibrotic lesions hampers the discovery of the pathogenesis of pulmonary fibrosis. Therefore, to determine of the pathogenesis of IPF, identification of functional fibroblasts is warranted. This study was aimed to determine the role of fibroblasts positive for meflin, identified as a potential marker for mesenchymal stromal cells, during the development of pulmonary fibrosis. We characterised meflin-positive cells in a single cell atlas established by single-cell RNA sequencing (scRNA-seq)-based profiling of 243 472 cells from 32 IPF lungs and 29 normal lung samples. scRNA-seq combined with in situ RNA hybridisation identified proliferating fibroblasts positive for meflin in fibroblastic foci, not dense fibrosis, of fibrotic lungs in IPF patients. We determined the role of fibroblasts positive for meflin using bleomycin (BLM)-induced pulmonary fibrosis. A BLM-induced lung fibrosis model for meflin-deficient mice showed that fibroblasts positive for meflin had anti-fibrotic property to prevent pulmonary fibrosis. Although transforming growth factor-β-induced fibrogenesis and cell senescence with senescence-associated secretory phenotype were exacerbated in fibroblasts via the repression or lack of meflin, these were inhibited in meflin-deficient fibroblasts with meflin reconstitution. These findings provide evidence to show the biological importance of meflin expression on fibroblasts and myofibroblasts in the active fibrotic region of pulmonary fibrosis.

    DOI: 10.1183/13993003.03397-2020

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  3. Serum mitochondrial DNA predicts the risk of acute exacerbation and progression of IPF. Reviewed International coauthorship International journal

    Koji Sakamoto, Taiki Furukawa, Yasuhiko Yamano, Kensuke Kataoka, Ryo Teramachi, Anjali Walia, Atsushi Suzuki, Masahide Inoue, Yoshio Nakahara, Changwan Ryu, Naozumi Hashimoto, Yasuhiro Kondoh

    The European respiratory journal   Vol. 57 ( 1 )   2021.1

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    DOI: 10.1183/13993003.01346-2020

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  4. Prognostic Impact and Risk Factors of Immune-Related Pneumonitis in Patients With Non-Small-Cell Lung Cancer Who Received Programmed Death 1 Inhibitors. Reviewed International journal

    Jun Fukihara, Koji Sakamoto, Junji Koyama, Takayasu Ito, Shingo Iwano, Masahiro Morise, Masahiro Ogawa, Yasuhiro Kondoh, Tomoki Kimura, Naozumi Hashimoto, Yoshinori Hasegawa

    Clinical lung cancer   Vol. 20 ( 6 ) page: 442 - +   2019.11

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    INTRODUCTION: Pneumonitis is one of the immune-related adverse events of programmed death 1 (PD-1) inhibitors that sometimes cause lethal outcomes. Although some recent reports have described PD-1 inhibitors as more effective in non-small-cell lung cancer (NSCLC) patients with immune-related adverse events than in those without, few data are available on the prognosis of those treated with PD-1 inhibitors who developed immune-related pneumonitis (IRP). Additionally, the robust risk factors of IRP have not been well elucidated. PATIENTS AND METHODS: A retrospective review of patients with recurrent or advanced NSCLC who took a PD-1 inhibitor (nivolumab or pembrolizumab monotherapy) between January 2016 and March 2018 was undertaken. Radiologic findings such as unilateral infiltration were also defined as IRP as long as they were deemed relevant to PD-1 inhibitors. RESULTS: Twenty-seven (16%) of 170 patients developed IRP. Although 22 (81%) of 27 patients with IRP recovered with drug cessation with or without corticosteroid therapy, 8-week landmark analysis showed the overall survival after administration of the PD-1 inhibitor was significantly shorter in patients with IRP than in those without (8.7 vs. 23.0 months, P = .015). Patients with IRP tended to not receive next-line treatment and choose best supportive care after cessation of PD-1 inhibitor therapy. In the multivariate analysis, pembrolizumab (vs. nivolumab) and low serum albumin were independent risk factors for IRP. CONCLUSION: Development of IRP was correlated with poor prognosis in patients with NSCLC. Further study is necessary for establishing the best prediction and management strategies for IRP.

    DOI: 10.1016/j.cllc.2019.07.006

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  5. Prognostic Awareness and Knowledge of Acute Exacerbation in Patients Dying with Interstitial Lung Disease: A Nationwide Survey. Reviewed International journal

    Takafumi Koyauchi, Tomoyuki Fujisawa, Mitsunori Miyashita, Masanori Mori, Tatsuya Morita, Shusuke Yazawa, Norimichi Akiyama, Satoshi Hagimoto, Yoshinobu Matsuda, Ryo Tachikawa, Hideki Yasui, Masaru Suzuki, Yuichiro Asai, Manabu Ono, Yuichiro Kimura, Shinya Ohkouchi, Yoshinori Tanino, Keishi Sugino, Tomoya Tateishi, Motoyasu Kato, Atsushi Miyamoto, Yoshinobu Saito, Susumu Sakamoto, Masato Kono, Koshi Yokomura, Shiro Imokawa, Koji Sakamoto, Yuko Waseda, Tomohiro Handa, Noboru Hattori, Kazuki Anabuki, Kazuhiro Yatera, Yuki Shundo, Tomoaki Hoshino, Noriho Sakamoto, Yasuhiro Kondoh, Hiromi Tomioka, Keisuke Tomii, Yoshikazu Inoue, Takafumi Suda

    Annals of the American Thoracic Society   Vol. 22 ( 3 ) page: 395 - 402   2025.3

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    RATIONALE: Accurate prognostic awareness (PA) and knowledge of the disease are critical for decision-making regarding treatment options, advance care planning, and end-of-life care. However, they have not been investigated in patients with interstitial lung disease (ILD). OBJECTIVES: To determine the prevalence of patients with ILD who have accurate PA and/or knowledge of acute exacerbation. In addition, to determine whether accurate PA is associated with end-of-life medical interventions and quality of dying and death. METHODS: Through a nationwide bereavement survey, we examined the prevalence of accurate PA and knowledge of acute exacerbation (AE) in patients with ILD who died in acute general hospitals between January 2018 and February 2020. Patients' PA and knowledge were assessed from the perspective of the bereaved. We also quantified the quality of dying and death from the perspective of the bereaved using three scales, the Good Death Inventory, the Quality of Dying and Death (QODD) questionnaire, and the single-item QODD overall score, and obtained information on end-of-life interventions from the electronic medical record. We examined the associations of accurate PA with end-of-life interventions and quality of dying and death. RESULTS: A total of 296 patients whose caregivers completed questionnaires were analyzed. One hundred sixty-three patients (55.1%, 95% confidence interval [CI] = 49.2-60.8) who died of ILD had accurate PA and 138 (46.9%, 95% CI = 35.9-47.4) recognized that their disease could have AE. Multivariate regression analysis showed that accurate PA was associated with significantly fewer intensive care unit (ICU) deaths (odds ratio = 0.28, 95% CI = 0.10-0.82, P = 0.02). Patients with accurate PA had better quality of dying and death on all the three scales. CONCLUSIONS: Approximately half of the patients who died of ILD did not recognize that their disease could lead to death or AE. The lower number of ICU deaths and better quality of dying and death in patients with accurate PA suggest the potential benefits of obtaining accurate PA in patients with ILD.

    DOI: 10.1513/AnnalsATS.202405-495OC

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  6. Metagenomic Analysis of Lung Microbiome in Patients With Interstitial Lung Diseases and Sarcoidosis: An Experimental Study Reviewed

    Takeuchi, S; Kawada, J; Suzuki, A; Sakamoto, K; Fukuda, Y; Horiba, K; Suzuki, T; Torii, Y; Shindo, Y; Ito, Y

    HEALTH SCIENCE REPORTS   Vol. 8 ( 2 ) page: e70328   2025.2

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    Background and Aims: Interactions between the lung microbiome and pulmonary epithelium plays a pivotal role in shaping immunity in the lung. Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung disease (ILD). Some patients with IPF develop episodic acute exacerbations often associated with microbial dysbiosis in the lungs. This study aimed to investigate etiologic agents as well as the lung microbiome in patients with ILDs and sarcoidosis. Methods: This study analyzed 31 patients divided into the IPF (IPF-stable, n = 12), acute exacerbation of ILDs (AE-ILDs, n = 6), and sarcoidosis (n = 13) groups. Bronchoalveolar lavage fluid (BALF) samples were analyzed by RNA-based metagenomic next-generation sequencing (NGS) on an Illumina platform. Results: In total, 87 pathogens were detected using metagenomic NGS at the genus level. Prevotella, Streptococcus, and Veillonella dominated the BALF microbial communities, and sequence reads of these bacteria were abundant, especially in the sarcoidosis group. Conversely, only a small number of bacterial reads were detected in the AE-ILDs group, and the overall proportion of microbial composition differed from that of the other groups. No significant difference was found in community diversity (α-diversity) among the groups, whereas the structural similarity of the microflora (β-diversity) differed significantly between the AE-ILDs and sarcoidosis groups. Conclusions: Bacterial sequence reads in BALF were smaller in both the IPF-stable and AE-ILD groups than in the sarcoidosis group. Dysbiosis in the lung microbiome has been observed in patients with AE-ILD and may be related to the progression of inflammation.

    DOI: 10.1002/hsr2.70328

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  7. 知っておきたい間質性肺疾患の基本~病態生理から治療・合併症・呼吸ケアの注意点まで~

    阪本 考司

    日本呼吸ケア・リハビリテーション学会誌   Vol. 34 ( supplement ) page: 87s_2 - 87s_2   2024.10

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:一般社団法人 日本呼吸ケア・リハビリテーション学会  

    DOI: 10.15032/jsrcr.34.supplement_87s_2

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  8. Mitochondrial DNA in bronchoalveolar lavage fluid is associated with the prognosis of idiopathic pulmonary fibrosis: a single cohort study. Reviewed International journal

    Jun Fukihara, Koji Sakamoto, Yoshiki Ikeyama, Taiki Furukawa, Ryo Teramachi, Kensuke Kataoka, Yasuhiro Kondoh, Naozumi Hashimoto, Makoto Ishii

    Respiratory research   Vol. 25 ( 1 ) page: 202 - 202   2024.5

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    BACKGROUND: Extracellular mitochondrial DNA (mtDNA) is released from damaged cells and increases in the serum and bronchoalveolar lavage fluid (BALF) of idiopathic pulmonary fibrosis (IPF) patients. While increased levels of serum mtDNA have been reported to be linked to disease progression and the future development of acute exacerbation (AE) of IPF (AE-IPF), the clinical significance of mtDNA in BALF (BALF-mtDNA) remains unclear. We investigated the relationships between BALF-mtDNA levels and other clinical variables and prognosis in IPF. METHODS: Extracellular mtDNA levels in BALF samples collected from IPF patients were determined using droplet-digital PCR. Levels of extracellular nucleolar DNA in BALF (BALF-nucDNA) were also determined as a marker for simple cell collapse. Patient characteristics and survival information were retrospectively reviewed. RESULTS: mtDNA levels in serum and BALF did not correlate with each other. In 27 patients with paired BALF samples obtained in a stable state and at the time of AE diagnosis, BALF-mtDNA levels were significantly increased at the time of AE. Elevated BALF-mtDNA levels were associated with inflammation or disordered pulmonary function in a stable state (n = 90), while being associated with age and BALF-neutrophils at the time of AE (n = 38). BALF-mtDNA ≥ 4234.3 copies/µL in a stable state (median survival time (MST): 42.4 vs. 79.6 months, p < 0.001) and ≥ 11,194.3 copies/µL at the time of AE (MST: 2.6 vs. 20.0 months, p = 0.03) were associated with shorter survival after BALF collection, even after adjusting for other known prognostic factors. On the other hand, BALF-nucDNA showed different trends in correlation with other clinical variables and did not show any significant association with survival time. CONCLUSIONS: Elevated BALF-mtDNA was associated with a poor prognosis in both IPF and AE-IPF. Of note, at the time of AE, it sharply distinguished survivors from non-survivors. Given the trends shown by analyses for BALF-nucDNA, the elevation of BALF-mtDNA might not simply reflect the impact of cell collapse. Further studies are required to explore the underlying mechanisms and clinical applications of BALF-mtDNA in IPF.

    DOI: 10.1186/s12931-024-02828-9

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  9. Mild elevation of pulmonary vascular resistance predicts mortality regardless of mean pulmonary artery pressure in mild interstitial lung disease. Reviewed International journal

    Tomonori Sato, Taiki Furukawa, Ryo Teramachi, Jun Fukihara, Yasuhiko Yamano, Toshiki Yokoyama, Toshiaki Matsuda, Kensuke Kataoka, Tomoki Kimura, Koji Sakamoto, Makoto Ishii, Yasuhiro Kondoh

    Thorax   Vol. 79 ( 5 ) page: 422 - 429   2024.5

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    BACKGROUND: Pulmonary hypertension (PH) is defined by elevated mean pulmonary arterial pressure (MPAP), and elevated pulmonary vascular resistance (PVR) reflects pulmonary vascular abnormalities. The clinical significance of non-severe PH in patients with various interstitial lung diseases (ILDs) has not been fully elucidated. We aimed to investigate the clinical significance of MPAP and PVR for mortality in patients with newly diagnosed ILD. METHODS: We retrospectively analysed consecutive patients with ILD at initial evaluations that included right heart catheterisation from 2007 to 2018. These patients were classified by MPAP and PVR using the 2022 the European Society of Cardiology (ESC)/the European Respiratory Society (ERS) guidelines for PH. The clinical significance of MPAP and PVR for mortality was analysed. RESULTS: Among 854 patients, 167 (19.6%) had MPAP>20 mm Hg. The proportion of patients with PVR>2 Wood units (WU) among those with MPAP≤20 mm Hg, 20<MPAP<25 mm Hg, and ≥25 mm Hg were 26.2%, 60.4% and 86.4%, respectively. In Cox proportional hazards analyses with adjustment for ILD-Gender, Age and Physiology Index, PVR but not MPAP was associated with a higher mortality rate (HR 1.37, 95% CI 1.23 to 1.52, p<0.0001; HR 0.98, 95% CI 0.96 to 1.01, p=0.1671, respectively). PVR>2 WU was associated with a higher mortality rate (HR 1.61, 95% CI 1.28 to 2.02, p<0.0001) even in a group with MPAP≤20 mm Hg. CONCLUSIONS: Mild elevation of PVR was associated with a higher mortality rate in patients with newly diagnosed ILD, even in those with MPAP≤20 mm Hg.

    DOI: 10.1136/thorax-2023-220179

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  10. Rapidly progressive interstitial lung disease with positive anti-MDA5 antibody as an immune-related complication of nivolumab: A case report. Reviewed

    Kato S, Sakamoto K, Sato T, Kobayashi T, Shindo Y, Morise M, Iwama S, Arima H, Ishii M.

    Respiratory Investigation   Vol. 62 ( 2 ) page: 313 - 316   2024.2

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    DOI: 10.1016/j.resinv.2024.01.009.

  11. Cohort study to evaluate prognostic factors in idiopathic pulmonary fibrosis patients introduced to oxygen therapy. Reviewed

    Kataoka K, Oda K, Takizawa H, Ogura T, Miyamoto A, Inoue Y, Akagawa S, Hashimoto S, Kishaba T, Sakamoto K, Hamada N, Kuwano K, Nakayama M, Ebina M, Enomoto N, Miyazaki Y, Atsumi K, Izumi S, Tanino Y, Ishii H, Ohnishi H, Suda T, Kondoh Y.

    Scientific Reports   Vol. 13 ( 1 ) page: 13664   2023.8

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    DOI: 10.1038/s41598-023-40508-8

  12. Inhalation adherence for asthma and COPD improved during the COVID-19 pandemic: a questionnaire survey at a university hospital in Japan. International journal

    Eriko Fukutani, Keiko Wakahara, Saya Nakamura, Eito Yokoi, Akira Yoshimi, Masayuki Miyazaki, Mariko Nakamura, Yuichiro Shindo, Koji Sakamoto, Shotaro Okachi, Ichidai Tanaka, Nobuyuki Hamajima, Yukihiro Noda, Naozumi Hashimoto, Makoto Ishii

    The Journal of asthma : official journal of the Association for the Care of Asthma     page: 1 - 12   2023.5

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    Background: Good adherence to an inhaled medication protocol is necessary for the management of asthma and chronic obstructive pulmonary disease (COPD), and several interventions to improve adherence have been reported. However, the impact of patient life changes and psychological aspects on treatment motivation is obscure. Here, we investigated changes in inhaler adherence during the COVID-19 pandemic and how lifestyle and psychological changes affected it.Methods: Seven-hundred sixteen adult patients with asthma and COPD who had visited Nagoya University Hospital between 2015 and 2020 were selected. Among them, 311 patients had received instruction at a pharmacist-managed clinic (PMC). We distributed one-time cross-sectional questionnaires from January 12 to March 31, 2021. The questionnaire covered the status of hospital visits, inhalation adherence before and during the COVID-19 pandemic, lifestyles, medical conditions, and psychological stress. The Adherence Starts with Knowledge-12 (ASK-12) was used to assess adherence barriers.Results: Four-hundred thirty-three patients answered the questionnaire. Inhalation adherence was significantly improved in both diseases during the COVID-19 pandemic. The most common reason for improved adherence was fear of infection. Patients with improved adherence were more likely to believe that controller inhalers could prevent COVID-19 from becoming more severe. Improved adherence was more common in patients with asthma, those not receiving counseling at PMC, and those with poor baseline adherence.Conclusions: Inhalation adherence for asthma and COPD improved in the COVID-19 pandemic. The patients seemed to realize the necessity and benefits of the medication more strongly than before the pandemic, which motivated them to improve adherence.

    DOI: 10.1080/02770903.2023.2209173

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  13. Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease triggered by COVID-19: What is the best practice for treatment? Reviewed

    Yonezawa T, Suzuki A, Fukumitsu K, Katano T, Kako H, Ishii M, Niimi A, Imaizumi K, Sakamoto K, Omote N, Yamaguchi E.

    Respiratory Medicine Case Report   Vol. 43   page: 101857   2023.4

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    DOI: 10.1016/j.rmcr.2023.101857.

  14. Long-term effect of pulmonary rehabilitation in idiopathic pulmonary fibrosis: a randomised controlled trial. Reviewed International journal

    Kensuke Kataoka, Osamu Nishiyama, Takashi Ogura, Yoshihiro Mori, Ryo Kozu, Shinichi Arizono, Tohru Tsuda, Hiromi Tomioka, Keisuke Tomii, Koji Sakamoto, Hiroshi Ishimoto, Michiko Kagajo, Hiroyuki Ito, Kazuya Ichikado, Hajime Sasano, Seiichirou Eda, Machiko Arita, Yasuhiro Goto, Osamu Hataji, Satoshi Fuke, Ryota Shintani, Hirotsugu Hasegawa, Masahiko Ando, Tomoya Ogawa, Masashi Shiraishi, Fumiko Watanabe, Koichi Nishimura, Takuma Sasaki, Shinjiro Miyazaki, Hideo Saka, Yasuhiro Kondoh

    Thorax   Vol. 78 ( 8 ) page: 784 - 791   2023.4

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    BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterised by worsening dyspnoea and exercise intolerance. RESEARCH QUESTION: Does a long-term pulmonary rehabilitation improve exercise tolerance in patients with IPF treated with standard antifibrotic drugs, which are expected to reduce disease progression? METHODS: This open-label randomised controlled trial was performed at 19 institutions. Stable patients receiving nintedanib were randomised into pulmonary rehabilitation and control groups (1:1). The pulmonary rehabilitation group underwent initial rehabilitation which included twice-weekly sessions of monitored exercise training for 12 weeks, followed by an at-home rehabilitation programme for 40 weeks. The control group received usual care only, without pulmonary rehabilitation. Both groups continued to receive nintedanib. The primary and main secondary outcomes were change in 6 min walking distance (6MWD) and change in endurance time (using cycle ergometry) at week 52. RESULTS: Eighty-eight patients were randomised into pulmonary rehabilitation (n=45) and control (n=43) groups. Changes in 6MWD were -33 m (95% CI -65 to -1) and -53 m (95% CI -86 to -21) in the pulmonary rehabilitation and control groups, respectively, with no statistically significant difference (mean difference, 21 m (95% CI -25 to 66), p=0.38). Changes in endurance time were significantly better in the pulmonary rehabilitation (64 s, 95% CI -42.3 to 171)) than in the control (-123 s (95% CI -232 to -13)) group (mean difference, 187 s (95% CI 34 to 153), p=0.019). INTERPRETATION: Although pulmonary rehabilitation in patients taking nintedanib did not improve 6MWD in the long term, it led to prolonged improvement in endurance time. TRIAL REGISTRATION NUMBER: UMIN000026376.

    DOI: 10.1136/thorax-2022-219792

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  15. Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease triggered by COVID-19: What is the best practice for treatment? Reviewed International journal

    Toshiyuki Yonezawa, Atsushi Suzuki, Kensuke Fukumitsu, Takuma Katano, Hisashi Kako, Makoto Ishii, Akio Niimi, Kazuyoshi Imaizumi, Koji Sakamoto, Norihito Omote, Etsuro Yamaguchi

    Respiratory medicine case reports   Vol. 43   page: 101857 - 101857   2023

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    We present a case of 79-year-old female with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) developed an acute exacerbation (AE) triggered by coronavirus disease 2019 (COVID-19). The patient was unresponsive to a combination therapy of remdesivir, dexamethasone, and tocilizumab. Given that a recent multicenter cohort study reported ILD as a poor prognostic contributor in patients with RA and COVID-19, there may be potentially a certain number of patients with AE of RA-ILD triggered by COVID-19. This case highlights the need for a discussion how to treat these patients in a daily clinical practice.

    DOI: 10.1016/j.rmcr.2023.101857

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  16. DOCK2 is involved in the host genetics and biology of severe COVID-19. International journal

    Ho Namkoong, Ryuya Edahiro, Tomomi Takano, Hiroshi Nishihara, Yuya Shirai, Kyuto Sonehara, Hiromu Tanaka, Shuhei Azekawa, Yohei Mikami, Ho Lee, Takanori Hasegawa, Koji Okudela, Daisuke Okuzaki, Daisuke Motooka, Masahiro Kanai, Tatsuhiko Naito, Kenichi Yamamoto, Qingbo S Wang, Ryunosuke Saiki, Rino Ishihara, Yuta Matsubara, Junko Hamamoto, Hiroyuki Hayashi, Yukihiro Yoshimura, Natsuo Tachikawa, Emmy Yanagita, Takayoshi Hyugaji, Eigo Shimizu, Kotoe Katayama, Yasuhiro Kato, Takayoshi Morita, Kazuhisa Takahashi, Norihiro Harada, Toshio Naito, Makoto Hiki, Yasushi Matsushita, Haruhi Takagi, Ryousuke Aoki, Ai Nakamura, Sonoko Harada, Hitoshi Sasano, Hiroki Kabata, Katsunori Masaki, Hirofumi Kamata, Shinnosuke Ikemura, Shotaro Chubachi, Satoshi Okamori, Hideki Terai, Atsuho Morita, Takanori Asakura, Junichi Sasaki, Hiroshi Morisaki, Yoshifumi Uwamino, Kosaku Nanki, Sho Uchida, Shunsuke Uno, Tomoyasu Nishimura, Takashi Ishiguro, Taisuke Isono, Shun Shibata, Yuma Matsui, Chiaki Hosoda, Kenji Takano, Takashi Nishida, Yoichi Kobayashi, Yotaro Takaku, Noboru Takayanagi, Soichiro Ueda, Ai Tada, Masayoshi Miyawaki, Masaomi Yamamoto, Eriko Yoshida, Reina Hayashi, Tomoki Nagasaka, Sawako Arai, Yutaro Kaneko, Kana Sasaki, Etsuko Tagaya, Masatoshi Kawana, Ken Arimura, Kunihiko Takahashi, Tatsuhiko Anzai, Satoshi Ito, Akifumi Endo, Yuji Uchimura, Yasunari Miyazaki, Takayuki Honda, Tomoya Tateishi, Shuji Tohda, Naoya Ichimura, Kazunari Sonobe, Chihiro Tani Sassa, Jun Nakajima, Yasushi Nakano, Yukiko Nakajima, Ryusuke Anan, Ryosuke Arai, Yuko Kurihara, Yuko Harada, Kazumi Nishio, Tetsuya Ueda, Masanori Azuma, Ryuichi Saito, Toshikatsu Sado, Yoshimune Miyazaki, Ryuichi Sato, Yuki Haruta, Tadao Nagasaki, Yoshinori Yasui, Yoshinori Hasegawa, Yoshikazu Mutoh, Tomoki Kimura, Tomonori Sato, Reoto Takei, Satoshi Hagimoto, Yoichiro Noguchi, Yasuhiko Yamano, Hajime Sasano, Sho Ota, Yasushi Nakamori, Kazuhisa Yoshiya, Fukuki Saito, Tomoyuki Yoshihara, Daiki Wada, Hiromu Iwamura, Syuji Kanayama, Shuhei Maruyama, Takashi Yoshiyama, Ken Ohta, Hiroyuki Kokuto, Hideo Ogata, Yoshiaki Tanaka, Kenichi Arakawa, Masafumi Shimoda, Takeshi Osawa, Hiroki Tateno, Isano Hase, Shuichi Yoshida, Shoji Suzuki, Miki Kawada, Hirohisa Horinouchi, Fumitake Saito, Keiko Mitamura, Masao Hagihara, Junichi Ochi, Tomoyuki Uchida, Rie Baba, Daisuke Arai, Takayuki Ogura, Hidenori Takahashi, Shigehiro Hagiwara, Genta Nagao, Shunichiro Konishi, Ichiro Nakachi, Koji Murakami, Mitsuhiro Yamada, Hisatoshi Sugiura, Hirohito Sano, Shuichiro Matsumoto, Nozomu Kimura, Yoshinao Ono, Hiroaki Baba, Yusuke Suzuki, Sohei Nakayama, Keita Masuzawa, Shinichi Namba, Ken Suzuki, Yoko Naito, Yu-Chen Liu, Ayako Takuwa, Fuminori Sugihara, James B Wing, Shuhei Sakakibara, Nobuyuki Hizawa, Takayuki Shiroyama, Satoru Miyawaki, Yusuke Kawamura, Akiyoshi Nakayama, Hirotaka Matsuo, Yuichi Maeda, Takuro Nii, Yoshimi Noda, Takayuki Niitsu, Yuichi Adachi, Takatoshi Enomoto, Saori Amiya, Reina Hara, Yuta Yamaguchi, Teruaki Murakami, Tomoki Kuge, Kinnosuke Matsumoto, Yuji Yamamoto, Makoto Yamamoto, Midori Yoneda, Toshihiro Kishikawa, Shuhei Yamada, Shuhei Kawabata, Noriyuki Kijima, Masatoshi Takagaki, Noah Sasa, Yuya Ueno, Motoyuki Suzuki, Norihiko Takemoto, Hirotaka Eguchi, Takahito Fukusumi, Takao Imai, Munehisa Fukushima, Haruhiko Kishima, Hidenori Inohara, Kazunori Tomono, Kazuto Kato, Meiko Takahashi, Fumihiko Matsuda, Haruhiko Hirata, Yoshito Takeda, Hidefumi Koh, Tadashi Manabe, Yohei Funatsu, Fumimaro Ito, Takahiro Fukui, Keisuke Shinozuka, Sumiko Kohashi, Masatoshi Miyazaki, Tomohisa Shoko, Mitsuaki Kojima, Tomohiro Adachi, Motonao Ishikawa, Kenichiro Takahashi, Takashi Inoue, Toshiyuki Hirano, Keigo Kobayashi, Hatsuyo Takaoka, Kazuyoshi Watanabe, Naoki Miyazawa, Yasuhiro Kimura, Reiko Sado, Hideyasu Sugimoto, Akane Kamiya, Naota Kuwahara, Akiko Fujiwara, Tomohiro Matsunaga, Yoko Sato, Takenori Okada, Yoshihiro Hirai, Hidetoshi Kawashima, Atsuya Narita, Kazuki Niwa, Yoshiyuki Sekikawa, Koichi Nishi, Masaru Nishitsuji, Mayuko Tani, Junya Suzuki, Hiroki Nakatsumi, Takashi Ogura, Hideya Kitamura, Eri Hagiwara, Kota Murohashi, Hiroko Okabayashi, Takao Mochimaru, Shigenari Nukaga, Ryosuke Satomi, Yoshitaka Oyamada, Nobuaki Mori, Tomoya Baba, Yasutaka Fukui, Mitsuru Odate, Shuko Mashimo, Yasushi Makino, Kazuma Yagi, Mizuha Hashiguchi, Junko Kagyo, Tetsuya Shiomi, Satoshi Fuke, Hiroshi Saito, Tomoya Tsuchida, Shigeki Fujitani, Mumon Takita, Daiki Morikawa, Toru Yoshida, Takehiro Izumo, Minoru Inomata, Naoyuki Kuse, Nobuyasu Awano, Mari Tone, Akihiro Ito, Yoshihiko Nakamura, Kota Hoshino, Junichi Maruyama, Hiroyasu Ishikura, Tohru Takata, Toshio Odani, Masaru Amishima, Takeshi Hattori, Yasuo Shichinohe, Takashi Kagaya, Toshiyuki Kita, Kazuhide Ohta, Satoru Sakagami, Kiyoshi Koshida, Kentaro Hayashi, Tetsuo Shimizu, Yutaka Kozu, Hisato Hiranuma, Yasuhiro Gon, Namiki Izumi, Kaoru Nagata, Ken Ueda, Reiko Taki, Satoko Hanada, Kodai Kawamura, Kazuya Ichikado, Kenta Nishiyama, Hiroyuki Muranaka, Kazunori Nakamura, Naozumi Hashimoto, Keiko Wakahara, Koji Sakamoto, Norihito Omote, Akira Ando, Nobuhiro Kodama, Yasunari Kaneyama, Shunsuke Maeda, Takashige Kuraki, Takemasa Matsumoto, Koutaro Yokote, Taka-Aki Nakada, Ryuzo Abe, Taku Oshima, Tadanaga Shimada, Masahiro Harada, Takeshi Takahashi, Hiroshi Ono, Toshihiro Sakurai, Takayuki Shibusawa, Yoshifumi Kimizuka, Akihiko Kawana, Tomoya Sano, Chie Watanabe, Ryohei Suematsu, Hisako Sageshima, Ayumi Yoshifuji, Kazuto Ito, Saeko Takahashi, Kota Ishioka, Morio Nakamura, Makoto Masuda, Aya Wakabayashi, Hiroki Watanabe, Suguru Ueda, Masanori Nishikawa, Yusuke Chihara, Mayumi Takeuchi, Keisuke Onoi, Jun Shinozuka, Atsushi Sueyoshi, Yoji Nagasaki, Masaki Okamoto, Sayoko Ishihara, Masatoshi Shimo, Yoshihisa Tokunaga, Yu Kusaka, Takehiko Ohba, Susumu Isogai, Aki Ogawa, Takuya Inoue, Satoru Fukuyama, Yoshihiro Eriguchi, Akiko Yonekawa, Keiko Kan-O, Koichiro Matsumoto, Kensuke Kanaoka, Shoichi Ihara, Kiyoshi Komuta, Yoshiaki Inoue, Shigeru Chiba, Kunihiro Yamagata, Yuji Hiramatsu, Hirayasu Kai, Koichiro Asano, Tsuyoshi Oguma, Yoko Ito, Satoru Hashimoto, Masaki Yamasaki, Yu Kasamatsu, Yuko Komase, Naoya Hida, Takahiro Tsuburai, Baku Oyama, Minoru Takada, Hidenori Kanda, Yuichiro Kitagawa, Tetsuya Fukuta, Takahito Miyake, Shozo Yoshida, Shinji Ogura, Shinji Abe, Yuta Kono, Yuki Togashi, Hiroyuki Takoi, Ryota Kikuchi, Shinichi Ogawa, Tomouki Ogata, Shoichiro Ishihara, Arihiko Kanehiro, Shinji Ozaki, Yasuko Fuchimoto, Sae Wada, Nobukazu Fujimoto, Kei Nishiyama, Mariko Terashima, Satoru Beppu, Kosuke Yoshida, Osamu Narumoto, Hideaki Nagai, Nobuharu Ooshima, Mitsuru Motegi, Akira Umeda, Kazuya Miyagawa, Hisato Shimada, Mayu Endo, Yoshiyuki Ohira, Masafumi Watanabe, Sumito Inoue, Akira Igarashi, Masamichi Sato, Hironori Sagara, Akihiko Tanaka, Shin Ohta, Tomoyuki Kimura, Yoko Shibata, Yoshinori Tanino, Takefumi Nikaido, Hiroyuki Minemura, Yuki Sato, Yuichiro Yamada, Takuya Hashino, Masato Shinoki, Hajime Iwagoe, Hiroshi Takahashi, Kazuhiko Fujii, Hiroto Kishi, Masayuki Kanai, Tomonori Imamura, Tatsuya Yamashita, Masakiyo Yatomi, Toshitaka Maeno, Shinichi Hayashi, Mai Takahashi, Mizuki Kuramochi, Isamu Kamimaki, Yoshiteru Tominaga, Tomoo Ishii, Mitsuyoshi Utsugi, Akihiro Ono, Toru Tanaka, Takeru Kashiwada, Kazue Fujita, Yoshinobu Saito, Masahiro Seike, Hiroko Watanabe, Hiroto Matsuse, Norio Kodaka, Chihiro Nakano, Takeshi Oshio, Takatomo Hirouchi, Shohei Makino, Moritoki Egi, Yosuke Omae, Yasuhito Nannya, Takafumi Ueno, Kazuhiko Katayama, Masumi Ai, Yoshinori Fukui, Atsushi Kumanogoh, Toshiro Sato, Naoki Hasegawa, Katsushi Tokunaga, Makoto Ishii, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga, Yukinori Okada

    Nature   Vol. 609 ( 7928 ) page: 754 - +   2022.9

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    Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1-5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.

    DOI: 10.1038/s41586-022-05163-5

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  17. A comprehensible machine learning tool to differentially diagnose idiopathic pulmonary fibrosis from other chronic interstitial lung diseases

    Taiki Furukawa, Shintaro Oyama, Hideo Yokota, Yasuhiro Kondoh, Kensuke Kataoka, Takeshi Johkoh, Junya Fukuoka, Naozumi Hashimoto, Koji Sakamoto, Yoshimune Shiratori, Yoshinori Hasegawa

    Respirology   Vol. 27 ( 9 ) page: 739 - 746   2022.9

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    DOI: 10.1111/resp.14310

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    Other Link: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/resp.14310

  18. CINS: Cell Interaction Network inference from Single cell expression data. Reviewed International coauthorship International journal

    Ye Yuan, Carlos Cosme Jr, Taylor Sterling Adams, Jonas Schupp, Koji Sakamoto, Nikos Xylourgidis, Matthew Ruffalo, Jiachen Li, Naftali Kaminski, Ziv Bar-Joseph

    PLoS computational biology   Vol. 18 ( 9 ) page: e1010468   2022.9

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    Studies comparing single cell RNA-Seq (scRNA-Seq) data between conditions mainly focus on differences in the proportion of cell types or on differentially expressed genes. In many cases these differences are driven by changes in cell interactions which are challenging to infer without spatial information. To determine cell-cell interactions that differ between conditions we developed the Cell Interaction Network Inference (CINS) pipeline. CINS combines Bayesian network analysis with regression-based modeling to identify differential cell type interactions and the proteins that underlie them. We tested CINS on a disease case control and on an aging mouse dataset. In both cases CINS correctly identifies cell type interactions and the ligands involved in these interactions improving on prior methods suggested for cell interaction predictions. We performed additional mouse aging scRNA-Seq experiments which further support the interactions identified by CINS.

    DOI: 10.1371/journal.pcbi.1010468

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  19. The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force. Reviewed International journal

    Qingbo S Wang, Ryuya Edahiro, Ho Namkoong, Takanori Hasegawa, Yuya Shirai, Kyuto Sonehara, Hiromu Tanaka, Ho Lee, Ryunosuke Saiki, Takayoshi Hyugaji, Eigo Shimizu, Kotoe Katayama, Masahiro Kanai, Tatsuhiko Naito, Noah Sasa, Kenichi Yamamoto, Yasuhiro Kato, Takayoshi Morita, Kazuhisa Takahashi, Norihiro Harada, Toshio Naito, Makoto Hiki, Yasushi Matsushita, Haruhi Takagi, Masako Ichikawa, Ai Nakamura, Sonoko Harada, Yuuki Sandhu, Hiroki Kabata, Katsunori Masaki, Hirofumi Kamata, Shinnosuke Ikemura, Shotaro Chubachi, Satoshi Okamori, Hideki Terai, Atsuho Morita, Takanori Asakura, Junichi Sasaki, Hiroshi Morisaki, Yoshifumi Uwamino, Kosaku Nanki, Sho Uchida, Shunsuke Uno, Tomoyasu Nishimura, Takashri Ishiguro, Taisuke Isono, Shun Shibata, Yuma Matsui, Chiaki Hosoda, Kenji Takano, Takashi Nishida, Yoichi Kobayashi, Yotaro Takaku, Noboru Takayanagi, Soichiro Ueda, Ai Tada, Masayoshi Miyawaki, Masaomi Yamamoto, Eriko Yoshida, Reina Hayashi, Tomoki Nagasaka, Sawako Arai, Yutaro Kaneko, Kana Sasaki, Etsuko Tagaya, Masatoshi Kawana, Ken Arimura, Kunihiko Takahashi, Tatsuhiko Anzai, Satoshi Ito, Akifumi Endo, Yuji Uchimura, Yasunari Miyazaki, Takayuki Honda, Tomoya Tateishi, Shuji Tohda, Naoya Ichimura, Kazunari Sonobe, Chihiro Tani Sassa, Jun Nakajima, Yasushi Nakano, Yukiko Nakajima, Ryusuke Anan, Ryosuke Arai, Yuko Kurihara, Yuko Harada, Kazumi Nishio, Tetsuya Ueda, Masanori Azuma, Ryuichi Saito, Toshikatsu Sado, Yoshimune Miyazaki, Ryuichi Sato, Yuki Haruta, Tadao Nagasaki, Yoshinori Yasui, Yoshinori Hasegawa, Yoshikazu Mutoh, Tomoki Kimura, Tomonori Sato, Reoto Takei, Satoshi Hagimoto, Yoichiro Noguchi, Yasuhiko Yamano, Hajime Sasano, Sho Ota, Yasushi Nakamori, Kazuhisa Yoshiya, Fukuki Saito, Tomoyuki Yoshihara, Daiki Wada, Hiromu Iwamura, Syuji Kanayama, Shuhei Maruyama, Takashi Yoshiyama, Ken Ohta, Hiroyuki Kokuto, Hideo Ogata, Yoshiaki Tanaka, Kenichi Arakawa, Masafumi Shimoda, Takeshi Osawa, Hiroki Tateno, Isano Hase, Shuichi Yoshida, Shoji Suzuki, Miki Kawada, Hirohisa Horinouchi, Fumitake Saito, Keiko Mitamura, Masao Hagihara, Junichi Ochi, Tomoyuki Uchida, Rie Baba, Daisuke Arai, Takayuki Ogura, Hidenori Takahashi, Shigehiro Hagiwara, Genta Nagao, Shunichiro Konishi, Ichiro Nakachi, Koji Murakami, Mitsuhiro Yamada, Hisatoshi Sugiura, Hirohito Sano, Shuichiro Matsumoto, Nozomu Kimura, Yoshinao Ono, Hiroaki Baba, Yusuke Suzuki, Sohei Nakayama, Keita Masuzawa, Shinichi Namba, Takayuki Shiroyama, Yoshimi Noda, Takayuki Niitsu, Yuichi Adachi, Takatoshi Enomoto, Saori Amiya, Reina Hara, Yuta Yamaguchi, Teruaki Murakami, Tomoki Kuge, Kinnosuke Matsumoto, Yuji Yamamoto, Makoto Yamamoto, Midori Yoneda, Kazunori Tomono, Kazuto Kato, Haruhiko Hirata, Yoshito Takeda, Hidefumi Koh, Tadashi Manabe, Yohei Funatsu, Fumimaro Ito, Takahiro Fukui, Keisuke Shinozuka, Sumiko Kohashi, Masatoshi Miyazaki, Tomohisa Shoko, Mitsuaki Kojima, Tomohiro Adachi, Motonao Ishikawa, Kenichiro Takahashi, Takashi Inoue, Toshiyuki Hirano, Keigo Kobayashi, Hatsuyo Takaoka, Kazuyoshi Watanabe, Naoki Miyazawa, Yasuhiro Kimura, Reiko Sado, Hideyasu Sugimoto, Akane Kamiya, Naota Kuwahara, Akiko Fujiwara, Tomohiro Matsunaga, Yoko Sato, Takenori Okada, Yoshihiro Hirai, Hidetoshi Kawashima, Atsuya Narita, Kazuki Niwa, Yoshiyuki Sekikawa, Koichi Nishi, Masaru Nishitsuji, Mayuko Tani, Junya Suzuki, Hiroki Nakatsumi, Takashi Ogura, Hideya Kitamura, Eri Hagiwara, Kota Murohashi, Hiroko Okabayashi, Takao Mochimaru, Shigenari Nukaga, Ryosuke Satomi, Yoshitaka Oyamada, Nobuaki Mori, Tomoya Baba, Yasutaka Fukui, Mitsuru Odate, Shuko Mashimo, Yasushi Makino, Kazuma Yagi, Mizuha Hashiguchi, Junko Kagyo, Tetsuya Shiomi, Satoshi Fuke, Hiroshi Saito, Tomoya Tsuchida, Shigeki Fujitani, Mumon Takita, Daiki Morikawa, Toru Yoshida, Takehiro Izumo, Minoru Inomata, Naoyuki Kuse, Nobuyasu Awano, Mari Tone, Akihiro Ito, Yoshihiko Nakamura, Kota Hoshino, Junichi Maruyama, Hiroyasu Ishikura, Tohru Takata, Toshio Odani, Masaru Amishima, Takeshi Hattori, Yasuo Shichinohe, Takashi Kagaya, Toshiyuki Kita, Kazuhide Ohta, Satoru Sakagami, Kiyoshi Koshida, Kentaro Hayashi, Tetsuo Shimizu, Yutaka Kozu, Hisato Hiranuma, Yasuhiro Gon, Namiki Izumi, Kaoru Nagata, Ken Ueda, Reiko Taki, Satoko Hanada, Kodai Kawamura, Kazuya Ichikado, Kenta Nishiyama, Hiroyuki Muranaka, Kazunori Nakamura, Naozumi Hashimoto, Keiko Wakahara, Sakamoto Koji, Norihito Omote, Akira Ando, Nobuhiro Kodama, Yasunari Kaneyama, Shunsuke Maeda, Takashige Kuraki, Takemasa Matsumoto, Koutaro Yokote, Taka-Aki Nakada, Ryuzo Abe, Taku Oshima, Tadanaga Shimada, Masahiro Harada, Takeshi Takahashi, Hiroshi Ono, Toshihiro Sakurai, Takayuki Shibusawa, Yoshifumi Kimizuka, Akihiko Kawana, Tomoya Sano, Chie Watanabe, Ryohei Suematsu, Hisako Sageshima, Ayumi Yoshifuji, Kazuto Ito, Saeko Takahashi, Kota Ishioka, Morio Nakamura, Makoto Masuda, Aya Wakabayashi, Hiroki Watanabe, Suguru Ueda, Masanori Nishikawa, Yusuke Chihara, Mayumi Takeuchi, Keisuke Onoi, Jun Shinozuka, Atsushi Sueyoshi, Yoji Nagasaki, Masaki Okamoto, Sayoko Ishihara, Masatoshi Shimo, Yoshihisa Tokunaga, Yu Kusaka, Takehiko Ohba, Susumu Isogai, Aki Ogawa, Takuya Inoue, Satoru Fukuyama, Yoshihiro Eriguchi, Akiko Yonekawa, Keiko Kan-O, Koichiro Matsumoto, Kensuke Kanaoka, Shoichi Ihara, Kiyoshi Komuta, Yoshiaki Inoue, Shigeru Chiba, Kunihiro Yamagata, Yuji Hiramatsu, Hirayasu Kai, Koichiro Asano, Tsuyoshi Oguma, Yoko Ito, Satoru Hashimoto, Masaki Yamasaki, Yu Kasamatsu, Yuko Komase, Naoya Hida, Takahiro Tsuburai, Baku Oyama, Minoru Takada, Hidenori Kanda, Yuichiro Kitagawa, Tetsuya Fukuta, Takahito Miyake, Shozo Yoshida, Shinji Ogura, Shinji Abe, Yuta Kono, Yuki Togashi, Hiroyuki Takoi, Ryota Kikuchi, Shinichi Ogawa, Tomouki Ogata, Shoichiro Ishihara, Arihiko Kanehiro, Shinji Ozaki, Yasuko Fuchimoto, Sae Wada, Nobukazu Fujimoto, Kei Nishiyama, Mariko Terashima, Satoru Beppu, Kosuke Yoshida, Osamu Narumoto, Hideaki Nagai, Nobuharu Ooshima, Mitsuru Motegi, Akira Umeda, Kazuya Miyagawa, Hisato Shimada, Mayu Endo, Yoshiyuki Ohira, Masafumi Watanabe, Sumito Inoue, Akira Igarashi, Masamichi Sato, Hironori Sagara, Akihiko Tanaka, Shin Ohta, Tomoyuki Kimura, Yoko Shibata, Yoshinori Tanino, Takefumi Nikaido, Hiroyuki Minemura, Yuki Sato, Yuichiro Yamada, Takuya Hashino, Masato Shinoki, Hajime Iwagoe, Hiroshi Takahashi, Kazuhiko Fujii, Hiroto Kishi, Masayuki Kanai, Tomonori Imamura, Tatsuya Yamashita, Masakiyo Yatomi, Toshitaka Maeno, Shinichi Hayashi, Mai Takahashi, Mizuki Kuramochi, Isamu Kamimaki, Yoshiteru Tominaga, Tomoo Ishii, Mitsuyoshi Utsugi, Akihiro Ono, Toru Tanaka, Takeru Kashiwada, Kazue Fujita, Yoshinobu Saito, Masahiro Seike, Hiroko Watanabe, Hiroto Matsuse, Norio Kodaka, Chihiro Nakano, Takeshi Oshio, Takatomo Hirouchi, Shohei Makino, Moritoki Egi, Yosuke Omae, Yasuhito Nannya, Takafumi Ueno, Tomomi Takano, Kazuhiko Katayama, Masumi Ai, Atsushi Kumanogoh, Toshiro Sato, Naoki Hasegawa, Katsushi Tokunaga, Makoto Ishii, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga, Yukinori Okada

    Nature communications   Vol. 13 ( 1 ) page: 4830 - 4830   2022.8

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    Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.

    DOI: 10.1038/s41467-022-32276-2

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  20. COVID-19-Triggered Acute Exacerbation of IPF, an Underdiagnosed Clinical Entity With Two-Peaked Respiratory Failure: A Case Report and Literature Review Reviewed International journal

    Goto Yosuke, Sakamoto Koji, Fukihara Jun, Suzuki Atsushi, Omote Norihito, Ando Akira, Shindo Yuichiro, Hashimoto Naozumi

    FRONTIERS IN MEDICINE   Vol. 9   page: 815924   2022.2

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Frontiers in Medicine  

    Because severe coronavirus disease 2019 (COVID-19) affects the respiratory system and develops into respiratory failure, patients with pre-existing chronic lung disorders, such as idiopathic pulmonary fibrosis (IPF), are thought to be at high risk of death. Patients with IPF often suffer from a lethal complication, acute exacerbation (AE), a significant part of which is assumed to be triggered by respiratory viral infection. However, whether mild to moderate COVID-19 can trigger AE in patients with IPF remains unknown. This is the case report of a 60-year-old man with a 4-year history of IPF who successfully recovered from moderate COVID-19 but subsequently developed more severe respiratory failure, which was considered to be a COVID-19-triggered acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). It is important to be aware of the risk of AE-IPF after COVID-19 and to properly manage this deadly complication of IPF. Recent literature reporting cases with chronic interstitial lung diseases which developed respiratory failure by complications with COVID-19 is also reviewed and discussed.

    DOI: 10.3389/fmed.2022.815924

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  21. 肺線維症の病態に関連する2つの新規マーカー分子:メフリンとミトコンドリアDNA

    阪本 考司, 橋本 直純, 中原 義夫, 古川 大記

    呼吸器内科   Vol. 41 ( 2 ) page: 197 - 201   2022.2

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  22. Overexpression of bone morphogenetic protein receptor type 2 suppresses transforming growth factor beta-induced profibrotic responses in lung fibroblasts Reviewed International coauthorship International journal

    Fukihara Jun, Maiolo Suzanne, Kovac Jessica, Sakamoto Koji, Wakahara Keiko, Hashimoto Naozumi, Reynolds Paul N.

    EXPERIMENTAL LUNG RESEARCH   Vol. 48 ( 1 ) page: 35 - 51   2022.1

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    Purpose of the study: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. As the efficacy of currently available antifibrotics is limited, development of new therapies is warranted. Transforming growth factor (TGF)-β plays a central role in the pathogenesis of IPF through mechanisms such as promoting the production of extracellular matrix by fibroblasts. Conversely, bone morphogenetic proteins (BMPs) are known to be antifibrotic and may counterbalance TGF-β signaling via BMP receptor type 2 (BMPR2). However, little is known about the expression status of BMPR2 and its function in pulmonary fibrosis, and manipulation of BMPR2 expression has never been attempted. In this study, we aimed at evaluating the effectiveness of BMPR2 upregulation for modulating the imbalance of the TGF-β/BMP axis and reduce the profibrotic changes in lung fibroblasts. Materials and Methods: We investigated BMPR2 expression in pulmonary fibrosis and TGF-β/BMP signaling in lung fibroblasts. Then we evaluated the impact of BMPR2 upregulation using adenoviral transduction on TGF-β-induced Smad2/3 phosphorylation and fibronectin production in lung fibroblasts. Results: BMPR2 was distributed in airway epithelium and alveolar walls in rat lungs. BMPR2 expression was decreased in fibrotic lesions in the lungs of rats with bleomycin-induced pulmonary fibrosis and in human lung fibroblasts (HLFs) stimulated with TGF-β. Although Smad2/3 phosphorylation and fibronectin production were not suppressed solely by BMPs, phosphorylated Smad2/3 was decreased in BMPR2-transduced cells even without BMP stimulation. Fibronectin was decreased only when BMPR2-transduced HLFs were stimulated with BMP7 (but not BMP4). Similar results were also observed in IPF patient HLFs and rat lung fibroblasts. Conclusions: BMPR2 expression was reduced in fibrotic lungs and lung fibroblasts stimulated with TGF-β. BMPR2 transduction to lung fibroblasts reduced Smad2/3 phosphorylation, and reduced fibronectin production when treated with BMP7. Upregulation of BMPR2 may be a possible strategy for treating pulmonary fibrosis.

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  23. Successful Treatment with High-dose Steroids for Acute Exacerbation of Idiopathic Pulmonary Fibrosis Triggered by COVID-19

    Omote Norihito, Kanemitsu Yoshihiro, Inoue Takahiro, Yonezawa Toshiyuki, Ichihashi Takuji, Shindo Yuichiro, Sakamoto Koji, Ando Akira, Suzuki Atsushi, Niimi Akio, Ito Satoru, Imaizumi Kazuyoshi, Hashimoto Naozumi

    Internal Medicine   Vol. 61 ( 2 ) page: 233 - 236   2022

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    <p>We herein report a case of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) triggered by COVID-19. An 87-year-old woman tested positive for COVID-19 on a polymerase chain reaction test, and computed tomography revealed ground-glass opacity (GGO) superimposed on a background pattern consistent with usual interstitial pneumonia. Considering these data, we diagnosed her with AE-IPF. She experienced worsening of dyspnea and expansion of the GGO. Therefore, we introduced high-dose steroids (methylprednisolone 250 mg/day for 3 days). After the treatment, the pulmonary infiltrates improved. She was discharged from our hospital without severe disability. High-dose steroids can be a viable treatment option for AE-IPF triggered by COVID-19. </p>

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  24. The Effect of Pirfenidone on the Prescription of Antibiotics and Antitussive Drugs in Patients With Idiopathic Pulmonary Fibrosis: A Post Hoc Exploratory Analysis of Phase III Clinical Trial. Reviewed International journal

    Suzuki A, Sakaguchi H, Sakamoto K, Ebina M, Azuma A, Ogura T, Taguchi Y, Suga M, Takahashi H, Sugiyama Y, Kudoh S, Nukiwa T, Miyazawa S, Kondoh Y

    Chest   Vol. 160 ( 4 ) page: 1372 - 1376   2021.10

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  25. Size and surface modification of silica nanoparticles affect the severity of lung toxicity by modulating endosomal ROS generation in macrophages. International journal

    Masahide Inoue, Koji Sakamoto, Atsushi Suzuki, Shinya Nakai, Akira Ando, Yukihiko Shiraki, Yoshio Nakahara, Mika Omura, Atsushi Enomoto, Ikuhiko Nakase, Makoto Sawada, Naozumi Hashimoto

    Particle and fibre toxicology   Vol. 18 ( 1 ) page: 21 - 21   2021.6

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    BACKGROUND: As the application of silica nanomaterials continues to expand, increasing chances of its exposure to the human body and potential harm are anticipated. Although the toxicity of silica nanomaterials is assumed to be affected by their physio-chemical properties, including size and surface functionalization, its molecular mechanisms remain unclear. We hypothesized that analysis of intracellular localization of the particles and subsequent intracellular signaling could reveal a novel determinant of inflammatory response against silica particles with different physico-chemical properties. RESULTS: We employed a murine intratracheal instillation model of amorphous silica nanoparticles (NPs) exposure to compare their in vivo toxicities in the respiratory system. Pristine silica-NPs of 50 nm diameters (50 nm-plain) induced airway-centered lung injury with marked neutrophilic infiltration. By contrast, instillation of pristine silica particles of a larger diameter (3 μm; 3 μm-plain) significantly reduced the severity of lung injury and neutrophilic infiltration, possibly through attenuated induction of neutrophil chemotactic chemokines including MIP2. Ex vivo analysis of alveolar macrophages as well as in vitro assessment using RAW264.7 cells revealed a remarkably lower cellular uptake of 3 μm-plain particles compared with 50 nm-plain, which is assumed to be the underlying mechanism of attenuated immune response. The severity of lung injury and neutrophilic infiltration was also significantly reduced after intratracheal instillation of silica NPs with an amine surface modification (50 nm-NH2) when compared with 50 nm-plain. Despite unchanged efficacy in cellular uptake, treatment with 50 nm-NH2 induced a significantly attenuated immune response in RAW264.7 cells. Assessment of intracellular redox signaling revealed increased reactive oxygen species (ROS) in endosomal compartments of RAW264.7 cells treated with 50 nm-plain when compared with vehicle-treated control. In contrast, augmentation of endosomal ROS signals in cells treated with 50 nm-NH2 was significantly lower. Moreover, selective inhibition of NADPH oxidase 2 (NOX2) was sufficient to inhibit endosomal ROS bursts and induction of chemokine expressions in cells treated with silica NPs, suggesting the central role of endosomal ROS generated by NOX2 in the regulation of the inflammatory response in macrophages that endocytosed silica NPs. CONCLUSIONS: Our murine model suggested that the pulmonary toxicity of silica NPs depended on their physico-chemical properties through distinct mechanisms. Cellular uptake of larger particles by macrophages decreased, while surface amine modification modulated endosomal ROS signaling via NOX2, both of which are assumed to be involved in mitigating immune response in macrophages and resulting lung injury.

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  26. Impact of post-capillary pulmonary hypertension on mortality in interstitial lung disease. International journal

    Ryo Teramachi, Hiroyuki Taniguchi, Yasuhiro Kondoh, Tomoki Kimura, Kensuke Kataoka, Toshiki Yokoyama, Taiki Furukawa, Mitsuaki Yagi, Koji Sakamoto, Naozumi Hashimoto, Yoshinori Hasegawa

    Respiratory investigation   Vol. 59 ( 3 ) page: 342 - 349   2021.5

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    BACKGROUND: Pulmonary hypertension (PH) influences mortality in patients with interstitial lung disease (ILD). Almost all studies on patients with ILD, have focused on the clinical impact of pre-capillary PH on survival. Therefore, little is known about the influence of post-capillary PH. We aimed to assess the prevalence of post-capillary PH and its clinical impact on survival in patients with ILD, followed by comparison with pre-capillary PH. METHODS: This retrospective study enrolled 1152 patients with ILD who were diagnosed with PH using right heart catheterization between May 2007 and December 2015. We analyzed the demographics and composite outcomes (defined as death from any cause or lung transplantation) of patients with post-capillary PH and compared them with patients with pre-capillary PH. RESULTS: Thirty-two (20%) of the 157 patients with ILD-PH were diagnosed with post-capillary PH. Patients with post-capillary PH had significantly lower modified Medical Research Council scores, higher diffusion capacity for carbon monoxide, higher resting PaO2, lower pulmonary vascular resistance (PVR), and higher lowest oxygen saturation during the 6-min walk test compared to those with pre-capillary PH. Cardiovascular diseases were associated with a higher risk of mortality in patients with post-capillary PH. Multivariate Cox proportional hazards analysis demonstrated no significant difference between the composite outcomes in pre-capillary and post-capillary PH, while PVR and the ILD Gender-Age-Physiology Index were significantly associated with the composite outcome. CONCLUSIONS: We found that approximately one-fifth of patients with ILD-PH were diagnosed with post-capillary PH, and that PVR and not post-capillary PH was associated with mortality.

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  27. The Importance of Appropriate Diagnosis in the Practical Management of Chronic Obstructive Pulmonary Disease. International journal

    Naozumi Hashimoto, Keiko Wakahara, Koji Sakamoto

    Diagnostics (Basel, Switzerland)   Vol. 11 ( 4 )   2021.4

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    Chronic obstructive pulmonary disease (COPD) is projected to continue to contribute to an increase in the overall worldwide burden of disease until 2030. Therefore, an accurate assessment of the risk of airway obstruction in patients with COPD has become vitally important. Although the Global Initiative for Chronic Obstructive Lung Disease (GOLD), the American Thoracic Society (ATS) and European Respiratory Society (ERS), and the Japanese Respiratory Society (JRS) provide the criteria by which to diagnose COPD, many studies suggest that it is in fact underdiagnosed. Its prevalence increases, while the impact of COPD-related systemic comorbidities is also increasingly recognized in clinical aspects of COPD. Although a recent report suggests that spirometry should not be used to screen for airflow limitation in individuals without respiratory symptoms, the early detection of COPD in patients with no, or few, symptoms is an opportunity to provide appropriate management based on COPD guidelines. Clinical advances have been made in pharmacotherapeutic approaches to COPD. This article provides a current understanding of the importance of an appropriate diagnosis in the real-world management of COPD.

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  28. Long noncoding RNA TINCR is a novel regulator of human bronchial epithelial cell differentiation state Reviewed International coauthorship International journal

    Omote Norihito, Sakamoto Koji, Li Qin, Schupp Jonas C., Adams Taylor, Ahangari Farida, Chioccioli Maurizio, DeIuliis Giuseppe, Hashimoto Naozumi, Hasegawa Yoshinori, Kaminski Naftali

    PHYSIOLOGICAL REPORTS   Vol. 9 ( 3 ) page: e14727   2021.2

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  29. Supplemental oxygen improves exercise capacity in IPF patients with exertional desaturation. Reviewed International journal

    Shinichi Arizono, Taiki Furukawa, Hiroyuki Taniguchi, Koji Sakamoto, Tomoki Kimura, Kensuke Kataoka, Tomoya Ogawa, Fumiko Watanabe, Yasuhiro Kondoh

    Respirology (Carlton, Vic.)   Vol. 25 ( 11 ) page: 1152 - 1159   2020.11

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    BACKGROUND AND OBJECTIVE: The efficacy of supplemental oxygen during exercise remains unclear for patients with IPF, as there have been conflicting results from recent prospective studies with small sample sizes. METHODS: This prospective, single-blind, randomized, crossover trial evaluated the efficacy of supplemental oxygen compared with placebo air during exercise in consecutive patients with IPF without resting hypoxaemia at initial evaluation. Patients with <90% SpO2 in a 6MWT using room air were randomly assigned to a CWRET at 80% of peak work rate with oxygen or placebo air gas via nasal cannula at 4 L/min. The primary endpoint was the effect of supplemental oxygen on endurance time. RESULTS: We recruited 72 consecutive patients (median age: 66.5 years, % FVC: 84.6%, % DLCO : 61.4%). Supplemental oxygen significantly increased the endurance time (340-424 s; P < 0.001) and minimum SpO2 (88.0-94.0%; P < 0.001) compared with placebo air. Furthermore, supplemental oxygen significantly improved dyspnoea and leg fatigue. In a multivariate linear regression analysis, the endurance time on air was an independent explanatory variable of the improvement rate of endurance time (P = 0.02). CONCLUSION: In mild-moderate IPF with exercise-induced hypoxaemia even without resting hypoxaemia, supplemental oxygen during exercise improved the endurance time, desaturation and subjective symptoms. Patients with shorter endurance times with placebo air showed better improvement with supplemental oxygen.

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  30. Clinical burden of immune checkpoint inhibitor-induced pneumonitis. Reviewed International journal

    Koji Sakamoto, Jun Fukihara, Masahiro Morise, Naozumi Hashimoto

    Respiratory investigation   Vol. 58 ( 5 ) page: 305 - 319   2020.9

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    Immune checkpoint inhibitors (ICIs) have been a breakthrough in medical oncology. However, many patients experience a novel type of adverse drug reaction that has a unique clinical presentation, called immune-related adverse events (irAEs). A breakdown of self-tolerance and an exaggerated autoimmune reaction by the host are assumed to be the underlying mechanisms. Therefore, special attention to the optimal diagnosis and management is required. Among the various effects of irAE, pneumonitis has been recognized as an important manifestation because of its high morbidity and mortality. As the application of ICIs is expanding to a wider variety of tumor types, as well as its use with cytotoxic agents and radiation, clinicians are highly likely to encounter this complication. In this review, we will summarize the current understanding of the underlying mechanisms, incidence, risk factors, optimal diagnostic workup, and management of ICI-related pneumonitis (IRP). We will also review fundamental information on drug-induced lung toxicity in the oncology setting. In addition, research perspectives focused on better risk stratification and management to avoid serious complications in the future are presented.

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  31. 肺線維症 新規治療に関する基礎研究 肺線維症の病態形成におけるメフリンの役割

    中原 義夫, 橋本 直純, 阪本 考司, 榎本 篤

    日本呼吸器学会誌   Vol. 9 ( 増刊 ) page: 139 - 139   2020.8

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  32. Acute Exacerbation of Pleuroparenchymal Fibroelastosis Secondary to Allogenic Hematopoietic Stem Cell Transplantation.

    Murakami Y, Sakamoto K, Okumura Y, Suzuki A, Mii S, Sato M, Yokoi T, Hashimoto N, Hasegawa Y

    Internal medicine (Tokyo, Japan)     2020.7

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  33. Reply to "Prognostic Impact and Risk Factors of Immune-Related Pneumonitis in Patients With Non-Small-Cell Lung Cancer Who Received Programmed Death-1 Inhibitors". Reviewed International journal

    Jun Fukihara, Koji Sakamoto, Junji Koyama, Takayasu Ito, Shingo Iwano, Masahiro Morise, Masahiro Ogawa, Yasuhiro Kondoh, Tomoki Kimura, Naozumi Hashimoto, Yoshinori Hasegawa

    Clinical lung cancer   Vol. 21 ( 3 ) page: E205 - E205   2020.5

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    DOI: 10.1016/j.cllc.2019.11.013

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  34. Acute exacerbations of fibrotic interstitial lung diseases. Reviewed International journal

    Suzuki A, Kondoh Y, Brown KK, Johkoh T, Kataoka K, Fukuoka J, Kimura T, Matsuda T, Yokoyama T, Fukihara J, Ando M, Tanaka T, Hashimoto N, Sakamoto K, Hasegawa Y

    Respirology (Carlton, Vic.)   Vol. 25 ( 5 ) page: 525 - 534   2020.5

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    DOI: 10.1111/resp.13682

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  35. High-flow nasal cannula therapy for acute respiratory failure in patients with interstitial pneumonia: a retrospective observational study. International journal

    Omote N, Matsuda N, Hashimoto N, Nishida K, Sakamoto K, Ando A, Nakahara Y, Nishikimi M, Higashi M, Matsui S, Hasegawa Y

    Nagoya journal of medical science   Vol. 82 ( 2 ) page: 301 - 313   2020.5

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  36. <Editors' Choice> Renewed Japanese spirometric reference variables and risk stratification for postoperative outcomes in COPD patients with resected lung cancer. Reviewed International journal

    Yu Okada, Naozumi Hashimoto, Shingo Iwano, Koji Kawaguchi, Takayuki Fukui, Koji Sakamoto, Kenji Wakai, Kohei Yokoi, Yoshinori Hasegawa

    Nagoya journal of medical science   Vol. 81 ( 3 ) page: 427 - 438   2019.8

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    Although the lower limit of normal (LLN) of FEV1/FVC detects at-risk patients for postoperative outcomes among Japanese chronic obstructive pulmonary disease (COPD) patients with resected lung cancer, there was a lack of a Japanese reference equation to calculate the LLN of FEV1/FVC. Renewed Japanese spirometric reference variables might enable us to verify clinical impact of the LLN of FEV1/FVC among the Japanese population. To evaluate the clinical impact of the LLN of FEV1/FVC by using this renewed reference, data were retrospectively analyzed from 609 newly diagnosed lung cancer patients who had undergone thoracic surgery between 2006 and 2011. The combined assessment of the 0.70 fixed ratio and the LLN of the FEV1/FVC ratio classified the 609 subjects into the COPD (214 subjects), non-COPD (337 subjects), and in-between (58 subjects) groups, respectively. All of the relative odds ratios (ORs) of postoperative outcomes for the comparison between the in-between and non-COPD groups did not show significant confidence intervals (CIs). On the other hand, the adjusted ORs of postoperative outcomes for the COPD group versus the non-COPD group were 2.840 (95% CI: 1.824-4.421) for prolonged oxygen therapy (POT), 1.836 (95% CI: 1.166-2.890) for prolonged postoperative stays, and 1.637 (95% CI: 1.007-2.663) for combined complications. Adjusted comparisons of POT between the in-between and COPD groups also showed a significant relative OR of 2.984 (95% CI: 1.447-6.153). A standardized assessment of the LLN of FEV1/FVC by a renewed Japanese spirometric reference provides risk stratification for postoperative outcomes in the population.

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  37. Repressive role of stabilized hypoxia inducible factor 1α expression on transforming growth factor β-induced extracellular matrix production in lung cancer cells. Reviewed International journal

    Ando A, Hashimoto N, Sakamoto K, Omote N, Miyazaki S, Nakahara Y, Imaizumi K, Kawabe T, Hasegawa Y

    Cancer science   Vol. 110 ( 6 ) page: 1959 - 1973   2019.6

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  38. Performance of the COPD Assessment Test in patients with connective tissue disease-associated interstitial lung disease

    Suzuki Atsushi, Kondoh Yasuhiro, Swigris Jeffrey James, Matsuda Toshiaki, Kimura Tomoki, Kataoka Kensuke, Ando Masahiko, Hashimoto Naozumi, Sakamoto Koji, Hasegawa Yoshinori

    RESPIRATORY MEDICINE   Vol. 150   page: 15-20   2019.4

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  39. Multidimensional improvement in connective tissue disease-associated interstitial lung disease: Two courses of pulse dose methylprednisolone followed by low-dose prednisone and tacrolimus. Reviewed International journal

    Yamano Y, Taniguchi H, Kondoh Y, Ando M, Kataoka K, Furukawa T, Johkoh T, Fukuoka J, Sakamoto K, Hasegawa Y

    Respirology (Carlton, Vic.)   Vol. 23 ( 11 ) page: 1041 - 1048   2018.11

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  40. Outcomes with newly proposed classification of acute respiratory deterioration in idiopathic pulmonary fibrosis

    Teramachi Ryo, Kondoh Yasuhiro, Kataoka Kensuke, Taniguchi Hiroyuki, Matsuda Toshiaki, Kimura Tomoki, Yokoyama Toshiki, Yamano Yasuhiko, Furukawa Taiki, Sakamoto Koji, Hashimoto Naozumi, Hasegawa Yoshinori

    RESPIRATORY MEDICINE   Vol. 143   page: 147-152   2018.10

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  41. Performance of the St George's Respiratory Questionnaire in patients with connective tissue disease-associated interstitial lung disease. Reviewed International journal

    Suzuki A, Kondoh Y, Swigris JJ, Ando M, Kimura T, Kataoka K, Yamano Y, Furukawa T, Numata M, Sakamoto K, Hasegawa Y

    Respirology (Carlton, Vic.)   Vol. 23 ( 9 ) page: 851 - 859   2018.9

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  42. Prognostic evaluation by oxygenation with positive end-expiratory pressure in acute exacerbation of idiopathic pulmonary fibrosis: A retrospective cohort study.

    Suzuki A, Taniguchi H, Ando M, Kondoh Y, Kimura T, Kataoka K, Matsuda T, Yokoyama T, Sakamoto K, Hasegawa Y

    The clinical respiratory journal   Vol. 12 ( 3 ) page: 895 - 903   2018.3

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  43. Thin-section computed tomography-determined usual interstitial pneumonia pattern affects the decision-making process for resection in newly diagnosed lung cancer patients: a retrospective study Reviewed

    Hashimoto N, Ando A, Iwano S, Sakamoto K, Okachi S, Matsuzaki A, Okada Y, Wakai K, Yokoi K, Hasegawa Y

    BMC Pulm Med   Vol. 18 ( 1 ) page: 2   2018.1

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    DOI: 10.1186/s12890-017-0565-5

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  44. A scoring system to predict the elevation of mean pulmonary arterial pressure in idiopathic pulmonary fibrosis

    Furukawa Taiki, Kondoh Yasuhiro, Taniguchi Hiroyuki, Yagi Mitsuaki, Matsuda Toshiaki, Kimura Tomoki, Kataoka Kensuke, Johkoh Takeshi, Ando Masahiko, Hashimoto Naozumi, Sakamoto Koji, Hasegawa Yoshinori

    EUROPEAN RESPIRATORY JOURNAL   Vol. 51 ( 1 )   2018.1

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  45. Pirfenidone as salvage treatment for refractory bleomycin-induced lung injury: a case report of seminoma Reviewed International journal

    Koji Sakamoto, Satoru Ito, Naozumi Hashimoto, Yoshinori Hasegawa

    BMC CANCER   Vol. 17 ( 1 ) page: 526   2017.8

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    Background: Bleomycin-induced lung injury, a major complication of chemotherapy for germ cell tumors, occasionally fails to respond to the standard treatment with corticosteroids and develops into severe respiratory insufficiency. Little is known about salvage treatment for refractory cases.
    Case presentation: A 63-year-old man who had been diagnosed with stage I seminoma and undergone a high orchiectomy 1 year previously developed swelling of his left iliac lymph node and was diagnosed with a recurrence of the seminoma. He was administered a standard chemotherapy regimen of cisplatin, etoposide, and bleomycin. At the end of second cycle, he developed a dry cough and fever that was accompanied by newly-identified bilateral infiltrates on chest X-ray. Despite initiation of oral prednisolone, his exertional dyspnea and decline in pulmonary functions continued to be aggravated. High-dose pulse treatment with methylprednisolone was introduced and improved his symptoms and radiologic findings. However, the maintenance dose of oral prednisolone allowed reactivation of the disease with evidence of newly-developed bilateral lung opacities on high-resolution CT scans. Considering his glucose intolerance and cataracts as complications of corticosteroid treatment, administration of pirfenidone was initiated with the patient's consent. Pirfenidone at 1800 mg/day was well tolerated, and resolved his symptoms and abnormal opacities on a chest CT scan. Subsequently, the dose of prednisolone was gradually tapered without worsening of the disease. At the most recent follow-up, he was still in complete remission of seminoma with a successfully tapered combination dose of prednisolone and pirfenidone.
    Conclusions: Pirfenidone, a novel oral agent with anti-inflammatory and -fibrotic properties, should be considered as a salvage drug for refractory cases of bleomycin-induced lung injury.

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  46. Aging Impairs Alveolar Macrophage Phagocytosis and Increases Influenza-Induced Mortality in Mice Reviewed International journal

    Christine K. Wong, Candice A. Smith, Koji Sakamoto, Naftali Kaminski, Jonathan L. Koff, Daniel R. Goldstein

    JOURNAL OF IMMUNOLOGY   Vol. 199 ( 3 ) page: 1060 - 1068   2017.8

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    Influenza viral infections often lead to increased mortality in older people. However, the mechanisms by which aging impacts immunity to influenza lung infection remain unclear. We employed a murine model of influenza infection to identify these mechanisms. With aging, we found reduced numbers of alveolar macrophages, cells essential for lung homeostasis. We also determined that these macrophages are critical for influenza-induced mortality with aging. Furthermore, aging vastly alters the transcriptional profile and specifically downregulates cell cycling pathways in alveolar macrophages. Aging impairs the ability of alveolar macrophages to limit lung damage during influenza infection. Moreover, aging decreases alveolar macrophage phagocytosis of apoptotic neutrophils, downregulates the scavenging receptor CD204, and induces retention of neutrophils during influenza infection. Thus, aging induces defective phagocytosis by alveolar macrophages and increases lung damage. These findings indicate that therapies that enhance the function of alveolar macrophages may improve outcomes in older people infected with respiratory viruses.

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  47. Modified mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model Reviewed International journal

    Luai Huleihel, Jacobo Sellares, Nayra Cardenes, Diana Alvarez, Rosa Faner, Koji Sakamoto, Guoying Yu, Maria G. Kapetanaki, Naftali Kaminski, Mauricio Rojas

    AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY   Vol. 313 ( 1 ) page: L92 - L103   2017.7

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    Although different preclinical models have demonstrated a favorable role for bone marrow-derived mesenchymal stem cells (B-MSC) in preventing fibrosis, this protective effect is not observed with late administration of these cells, when fibrotic changes are consolidated. We sought to investigate whether the late administration of B-MSCs overexpressing microRNAs (miRNAs) let-7d (antifibrotic) or miR-154 (profibrotic) could alter lung fibrosis in a murine bleomycin model. Using lentiviral vectors, we transduced miRNAs (let-7d or miR-154) or a control sequence into human B-MSCs. Overexpression of let-7d or miR-154 was associated with changes in the mesenchymal properties of B-MSCs and in their cytokine expression. Modified B-MSCs were intravenously administered to mice at day 7 after bleomycin instillation, and the mice were euthanized at day 14. Bleomycin-injured animals that were treated with let-7d cells were found to recover quicker from the initial weight loss compared with the other treatment groups. Interestingly, animals treated with miR-154 cells had the lowest survival rate. Although a slight reduction in collagen mRNA levels was observed in lung tissue from let-7d mice, no significant differences were observed in Ashcroft score and OH-proline. However, the distinctive expression in cytokines and CD45-positive cells in the lung suggests that the differential effects observed in both miRNA mice groups were related to an effect on the immunomodulation function. Our results establish the use of miRNA-modified mesenchymal stem cells as a potential future research in lung fibrosis.

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  48. Progression of mean pulmonary arterial pressure in idiopathic pulmonary fibrosis with mild to moderate restriction Reviewed International journal

    Ryo Teramachi, Hiroyuki Taniguchi, Yasuhiro Kondoh, Masahiko Ando, Tomoki Kimura, Kensuke Kataoka, Atsushi Suzuki, Taiki Furukawa, Koji Sakamoto, Yoshinori Hasegawa

    RESPIROLOGY   Vol. 22 ( 5 ) page: 986 - 990   2017.7

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    Background and objectiveElevation of mean pulmonary arterial pressure (MPAP) is associated with poor prognosis in patients with idiopathic pulmonary fibrosis (IPF), yet the progression of MPAP in patients with IPF has not been sufficiently elucidated. We evaluated serial changes in MPAP and its determinants in patients with IPF with mild to moderate restriction.
    MethodsWe retrospectively reviewed patients with IPF who underwent initial evaluations including right heart catheterization (RHC) in our institute from May 2007 to December 2013 with follow-up RHC at least 1year later. Patients with forced vital capacity (FVC)&lt;50% predicted or those with pulmonary artery wedge pressure&gt;15mm Hg were excluded.
    ResultsA total of 95 patients were included. Median follow-up time of second RHC was 1.8years. MPAP increased significantly at follow-up (from 16.8 to 20.2mm Hg; P&lt;0.001), and annual change in MPAP (MPAP) was 1.8mm Hg/year. In multiple regression analysis, the lowest oxygen saturation (SpO(2) ) at 6-min walk test (6MWT) was an independent predictor of MPAP. When adjusted for age, sex, baseline MPAP and FVC % predicted, MPAP was a significant predictor of mortality (hazard ratio: 1.21; P=0.001).
    ConclusionMPAP was significantly associated with desaturation in the 6MWT, and with increased mortality in patients with IPF with mild to moderate restriction.
    We reviewed patients with idiopathic pulmonary fibrosis with mild to moderate restriction and showed that mean pulmonary arterial pressure (MPAP) was progressive. The lowest oxygen saturation (SpO(2) ) in the 6-min walk test at baseline was an independent predictor of annual change in MPAP.

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  49. Soluble thrombomodulin in bronchoalveolar lavage fluid is an independent predictor of severe drug-induced lung injury Reviewed International journal

    Atsushi Suzuki, Hiroyuki Taniguchi, Yasuhiro Kondoh, Masahiko Ando, Naohiro Watanabe, Tomoki Kimura, Kensuke Kataoka, Toshiki Yokoyama, Koji Sakamoto, Yoshinori Hasegawa

    RESPIROLOGY   Vol. 22 ( 4 ) page: 744 - 749   2017.5

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    Background and objectiveDrug-induced lung injury (DLI) can result from a vast number of agents, and sometimes presents findings similar to those of acute respiratory distress syndrome (ARDS). Previous studies have reported that circulating levels of soluble thrombomodulin (TM) reflect endothelial injuries, which play key roles in the development of ARDS. We hypothesized that endothelial injuries are an important aspect of pathogenesis in severe DLI. The primary aim of this study was to examine the associations between soluble TM and disease severity in DLI patients.
    MethodsOf the 2580 patients who underwent a bronchoalveolar lavage (BAL) procedure at Tosei General Hospital between May 2007 and February 2015, we retrospectively analysed the data of 68 DLI patients. Soluble TM in plasma and BAL fluid (BALF), and other biomarkers were included in our analysis.
    ResultsAt the time of diagnosis, 39 patients (57%) had respiratory failure (partial pressure of oxygen/inspiratory oxygen fraction ratio, PaO2 /FiO(2) ratio&lt;300). There was a significant negative linear correlation between the PaO2 /FiO(2) ratio and soluble TM in BALF (r=-0.448, P&lt;0.001). In a stepwise multiple regression analysis, soluble TM in BALF and surfactant protein D (SP-D) were the only independent determinants of the PaO2 /FiO(2) ratio. Additionally, in a multivariate logistic regression model, soluble TM in BALF (adjusted OR (aOR): 7.48, 95% CI: 1.60-34.98) and SP-D (aOR: 5.31, 95% CI: 1.40-20.15) was an independent predictor of respiratory failure (PaO2 /FiO(2) ratio&lt;300).
    ConclusionSoluble TM in BALF is an independent predictor of severe DLI. These findings underscore the importance of pulmonary endothelial injuries in the pathogenesis of severe DLI.
    Soluble thrombomodulin in bronchoalveolar lavage is an independent predictor of severe drug-induced lung injury (DLI). Pulmonary endothelial injuries are an important aspect of pathogenesis in severe DLI.

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  50. COPD Assessment Test for measurement of health status in patients with idiopathic pulmonary fibrosis: A cross-sectional study. Reviewed

    Matsuda T, Taniguchi H, Ando M, Kondoh Y, Kimura T, Kataoka K, Sakamoto K, Suzuki A, Furukawa T, Hasegawa Y

    Respirology (Carlton, Vic.)   Vol. 22 ( 4 ) page: 721-727   2017.5

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    DOI: 10.1111/resp.12936

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  51. Validation of the prognostic value of MMP-7 in idiopathic pulmonary fibrosis Reviewed International journal

    Argyris Tzouvelekis, Jose D. Herazo-Maya, Martin Slade, Jen-Hwa Chu, Giuseppe Deiuliis, Changwan Ryu, Qin Li, Koji Sakamoto, Gabriel Ibarra, Hongyi Pan, Mridu Gulati, Danielle Antin-Ozerkis, Erica L. Herzog, Naftali Kaminski

    RESPIROLOGY   Vol. 22 ( 3 ) page: 486 - 493   2017.4

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    Background and objective: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis and variable clinical course. Although matrix metalloproteinase-7 (MMP-7) is emerging as an important IPF biomarker, reproducibility across studies is unclear. We aimed to determine whether a previously reported prognostic threshold for MMP-7 was predictive of mortality in an independent cohort of IPF patients.
    Methods: MMP-7 concentrations obtained from heparinized plasma samples were determined by ELISA in 97 patients with IPF and 41 healthy controls. The association of the previously published heparin plasma MMP-7 threshold of 12.1 ng/mL with all-cause mortality or transplant-free survival (TFS) was determined, either as an independent biomarker or as part of the modified personal clinical and molecular mortality index (m-PCMI).
    Results: MMP-7 plasma concentrations were significantly higher in IPF patients compared to healthy controls (14.40 +/- 6.55 ng/mL vs 6.03 +/- 2.51 ng/mL, P &lt; 0.001). The plasma MMP-7 threshold of 12.1 ng/mL was significantly associated with both all-cause mortality and TFS (unadjusted Cox proportional hazard ratio (HR) = 25.85 and 15.49, 95% CI: 10.91-61.23 and 5.41-44.34, respectively, P &lt; 0.001). MMP-7 concentrations, split by 12.1 ng/mL, were significantly (P &lt; 0.05) predictive of mortality and TFS after adjusting for age, gender, smoking and baseline pulmonary function parameters, in a multivariate Cox proportional hazards model. MMP-7 concentrations were negatively correlated with diffusing lung capacity of carbon monoxide (DLCO) (r = -0.21, P = 0.02), and positively with a mortality risk scoring system (GAP) that combines age, gender, forced vital capacity (FVC) and DLCO (r = 0.32, P = 0.001).
    Conclusion: This study confirms that MMP-7 concentrations could be used to accurately predict outcomes across cohorts and centres, when similar collection protocols are applied.

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  52. Hemosiderin-laden macrophages are an independent factor correlated with pulmonary vascular resistance in idiopathic pulmonary fibrosis: a case control study Reviewed International journal

    Jun Fukihara, Hiroyuki Taniguchi, Masahiko Ando, Yasuhiro Kondoh, Tomoki Kimura, Kensuke Kataoka, Taiki Furukawa, Takeshi Johkoh, Junya Fukuoka, Koji Sakamoto, Yoshinori Hasegawa

    BMC PULMONARY MEDICINE   Vol. 17 ( 1 ) page: 30   2017.2

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    Background: Increases in hemosiderin-laden macrophages (HLM) are reported to be observed in idiopathic pulmonary fibrosis (IPF). According to a recent study, significant correlation between hemosiderin deposition in the lung tissue of IPF and pulmonary hypertension evaluated by echocardiography has been suspected. In this study, we aimed to evaluate whether HLM in bronchoalveolar lavage fluid (BALF) is a factor correlated with pulmonary hemodynamic parameters evaluated by right heart catheterization in patients with IPF.
    Methods: Initial data from 103 consecutive patients with IPF who underwent surgical lung biopsy between November 2007 and March 2014 were retrospectively analyzed. The "HLM score" of BALF was established by dividing the number of Perls' Prussian blue stain positive macrophages by the total number of macrophages counted.
    Results: BALF showed an elevated HLM score (38.2%). Right heart catheterization revealed mean pulmonary arterial pressure (mPAP) of 16.3 mmHg and pulmonary vascular resistance (PVR) of 1.55 Wood units. HLM score was positively correlated with mPAP (rho = 0.204; rho = 0.038) and PVR (rho = 0.349, rho &lt; 0.001). In multivariate analysis, 6-min walk distance (standardized partial regression coefficient [beta], -0.391; p &lt; 0.001), minimum oxygen saturation during 6-min walk distance (beta, -0.294; rho = 0.001) and HLM score (beta, 0.265; rho = 0.002) were independently correlated with PVR.
    Conclusions: HLM score in BALF is an independent factor correlated with PVR in patients with IPF.

    DOI: 10.1186/s12890-017-0376-8

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  53. SH2 Domain-Containing Phosphatase-2 Is a Novel Antifibrotic Regulator in Pulmonary Fibrosis Reviewed International coauthorship International journal

    Argyrios Tzouvelekis, Guoying Yu, Christian L. Lino Cardenas, Jose D. Herazo-Maya, Rong Wang, Tony Woolard, Yi Zhang, Koji Sakamoto, Hojin Lee, Jae-Sung Yi, Giuseppe Deluliis, Nikolaos Xylourgidis, Farida Ahangari, Patty J. Lee, Vassilis Aidinis, Erica L. Herzog, Robert Homer, Anton M. Bennett, Naftali Kaminski

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 195 ( 4 ) page: 500 - 514   2017.2

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    Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic fatal lung disease with dismal prognosis and no cure. The potential role of the ubiquitously expressed SH2 domain-containing tyrosine phosphatase-2 (SHP2) as a therapeutic target has not been studied in IPF.
    Objectives: To determine the expression, mechanistic role, and potential therapeutic usefulness of SHP2 in pulmonary fibrosis.
    Methods: The effects of SHP2 overexpression and inhibition on fibroblast response to profibrotic stimuli were analyzed in vitro in primary human and mouse lung fibroblasts. In vivo therapeutic effects were assessed in the bleomycin model of lung fibrosis by SHP2-lentiviral administration and transgenic mice carrying a constitutively active SHP2 mutation.
    Measurements and Main Results: SHP2 was down-regulated in lungs and lung fibroblasts obtained from patients with IPF. Immunolocalization studies revealed that SHP2 was absent within fibroblastic foci. Loss of SHP2 expression or activity was sufficient to induce fibroblast-to-myofibroblast differentiation in primary human lung fibroblasts. Overexpression of constitutively active SHP2 reduced the responsiveness offibroblasts to profibrotic stimuli, including significant reductions in cell survival and myofibroblast differentiation. SHP2 effects were mediated through deactivation of fibrosis-relevant tyrosine kinase and serine/threonine kinase signaling pathways. Mice carrying the Noonan syndrome-associated gain-of-function SHP2 mutation (SHP2(D61G/+)) were resistant to bleomycin-induced pulmonary fibrosis. Restoration of SHP2 levels in vivo through lentiviral delivery blunted bleomycin-induced pulmonary fibrosis.
    Conclusions: Our data suggest that SHP2 is an important regulator of fibroblast differentiation, and its loss as observed in IPF facilitates profibrotic phenotypic changes. Augmentation of SHP2 activity or expression should be investigated as a novel therapeutic strategy for IPF.

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  54. The St. George's Respiratory Questionnaire as a prognostic factor in IPF Reviewed International journal

    Taiki Furukawa, Hiroyuki Taniguchi, Masahiko Ando, Yasuhiro Kondoh, Kensuke Kataoka, Osamu Nishiyama, Takeshi Johkoh, Junya Fukuoka, Koji Sakamoto, Yoshinori Hasegawa

    RESPIRATORY RESEARCH   Vol. 18 ( 1 ) page: 18   2017.1

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    Background: It is unclear whether health related quality of life (HRQL) may have a predictive value for mortality in idiopathic pulmonary fibrosis (IPF). We investigated the relationship between HRQL assessed using the St. George's Respiratory Questionnaire (SGRQ) and survival time in patients with IPF, and tried to determine a clinical meaningful cut off value to predict poorer survival rates.
    Methods: We retrospectively analyzed consecutive patients with IPF who underwent an initial evaluation from May 2007 to December 2012. The diagnosis of IPF was made according to the 2011 international consensus guidelines. We used Cox proportional hazard models to identify independent predictors for mortality rate in patients with IPF.
    Results: We examined 182 eligible cases, average age was 66 years old, and 86% were male. Mean levels of percent predicted FVC, DLco, six-minute-walk test distance, and the SGRQ total score were around 80%, 58%, 580 m, and 34 points. On multivariate analysis, the SGRQ total score (hazard ratio [HR], 1.012; 95% confidence interval [CI] 1.001-1.023; P = .029) and percent predicted FVC (HR, 0.957; 95% CI 0.944-0.971, P &lt; .001) were independent predictors for mortality rate. Moreover, a score higher than 30 points in the SGRQ total score showed higher mortality rate (HR, 2.047; 95% CI, 1.329-3.153; P = .001).
    Conclusions: The SGRQ total score was one of independent prognostic factors in patients with IPF. Total scores higher than 30 points were associated with higher mortality rates.

    DOI: 10.1186/s12931-017-0503-3

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  55. Exercise hypoxaemia as a predictor of pulmonary hypertension in COPD patients without severe resting hypoxaemia. Reviewed

    Nakahara Y, Taniguchi H, Kimura T, Kondoh Y, Arizono S, Nishimura K, Sakamoto K, Ito S, Ando M, Hasegawa Y

    Respirology (Carlton, Vic.)   Vol. 22 ( 1 ) page: 120-125   2017.1

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    DOI: 10.1111/resp.12863

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  56. Exogenous induction of unphosphorylated PTEN reduces TGFβ-induced extracellular matrix expressions in lung fibroblasts. Reviewed

      Vol. 25 ( 1 ) page: 86-97   2017.1

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    DOI: 10.1111/wrr.12506

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  57. Depression Is Significantly Associated with the Health Status in Patients with Idiopathic Pulmonary Fibrosis. Reviewed

    Matsuda T, Taniguchi H, Ando M, Kondoh Y, Kimura T, Kataoka K, Nishimura K, Nishiyama O, Sakamoto K, Hasegawa Y

    Internal medicine (Tokyo, Japan)   Vol. 56 ( 13 ) page: 1637-1644   2017

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    DOI: 10.2169/internalmedicine.56.7019

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  58. Impact of mild to moderate COPD on feasibility and prognosis in non-small cell lung cancer patients who received chemotherapy

    Norihito Omote, Naozumi Hashimoto, Masahiro Morise, Koji Sakamoto, Shinichi Miyazaki, Akira Ando, Yoshio Nakahara, Yoshinori Hasegawa

    INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE   Vol. 12   page: 3541 - 3547   2017

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    Background: Non-small cell lung cancer (NSCLC) is the predominant cause of death in patients with COPD, and the severity of COPD in NSCLC patients is classified mainly as mild to moderate. Most advanced NSCLC patients with mild to moderate COPD are treated with chemotherapy; however, the feasibility for and prognosis after chemotherapy of these patients are not well understood. The aim of this study was to elucidate the impact of mild to moderate COPD on the feasibility for and prognosis after chemotherapy in NSCLC patients.
    Patients and methods: A retrospective review was performed on 268 NSCLC patients who received first-line chemotherapy from 2009 to 2014 in our institution. Finally, 85 evaluable patients were included in this study. The clinical characteristics, toxicity profile, objective response rate, and prognosis were analyzed and compared between patients with mild to moderate COPD and those without COPD (non-COPD).
    Results: Forty-three patients were classified as COPD (27 cases mild and 16 cases moderate) and 42 patients as non-COPD. The COPD group were older and had fewer never-smokers than the non-COPD group. The objective response rate did not differ between groups (p=0.14). There was no significant difference in overall survival between COPD and non-COPD groups (15.0 and 17.0 months, log-rank test p= 0.57). In the multivariate Cox's proportional hazard model, the adjusted hazard ratio (HRadj) was statistically significant for male sex (HRadj =5.382, 95% CI: 1.496-19.359; p=0.010), pathological diagnosis of adenocarcinoma (HRadj =0.460, 95% CI: 0.223-0.948; p=0.035), and epithelial growth factor receptor negative mutation (HRadj =6.040, 95% CI: 1.158-31.497; p=0.033), but not for the presence of COPD (HRadj =0.661, 95% CI: 0.330-1.325; p=0.24). Toxicity profile in COPD group was favorable, as in the non-COPD group.
    Conclusion: Mild to moderate COPD did not have a significant deleterious impact on toxicity and prognosis in NSCLC patients.

    DOI: 10.2147/COPD.S149456

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  59. PULMONARY REHABILITATION IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS: COMPARISON WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE Reviewed

    Arizono Shinichi, Taniguchi Hiroyuki, Sakamoto Koji, Kondoh Yasuhiro, Kimura Tomoki, Kataoka Kensuke, Ogawa Tomoya, Watanabe Fumiko, Tabira Kazuyuki, Kozu Ryo

    SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES   Vol. 34 ( 4 ) page: 283 - 289   2017

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  60. Pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis: comparison with chronic obstructive pulmonary disease. Reviewed International journal

    Arizono S, Taniguchi H, Sakamoto K, Kondoh Y, Kimura T, Kataoka K, Ogawa T, Watanabe F, Tabira K, Kozu R

    Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG   Vol. 34 ( 4 ) page: 283 - 289   2017

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    DOI: 10.36141/svdld.v34i4.5549

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  61. Pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis: Comparison with chronic obstructive pulmonary disease

    Arizono S., Taniguchi H., Sakamoto K., Kondoh Y., Kimura T., Kataoka K., Ogawa T., Watanabe F., Tabira K., Kozu R.

    Sarcoidosis Vasculitis and Diffuse Lung Diseases   Vol. 34 ( 4 ) page: 283 - 289   2017

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    Background: While the efficacy of pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) has been well established, emerging evidence also suggests its benefit in idiopathic pulmonary fibrosis (IPF). However, the differences and similarities between how PR affects diseases with different physiologies remain unknown. Objective: This study aimed to compare the efficacy of PR in COPD and IPF patients by performing multifactorial evaluation with various exercise capacity measurements, and dyspnea and health-related quality of life (QoL) assessment. Methods: Twenty-two IPF patients (%vital capacity: 72%) and 27 COPD patients (%forced expiratory volume1: 43%) were recruited. Subjects who completed a 10-week outpatient PR program were analyzed. We assessed five exercise capacity indicators (6-minute walking distance, incremental shuttle walking distance, endurance time, peak work rate, and peak values for oxygen uptake [peak VO2]), dyspnea (Baseline Dyspnea Index: BDI), and health-related QoL (St. George's Respiratory Questionnaire: SGRQ) at baseline and immediately following completion of the PR program. Results: After 10 weeks of PR, all exercise capacity measurements, except VO2, as well as BDI and SGRQ score improved significantly (p<0.05) in both disease groups. The magnitude of the observed changes in each outcome, assessed by the effect size, was comparable between IPF and COPD patients. This was also true for endurance time, the measurement most responsive to PR, with a large effect size. Conclusions: PR can result in comparable improvements in exercise capacity, including endurance time, and dyspnea and HRQoL in both IPF and COPD patients after 10 weeks of exercise training.

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  62. Impact of Thin-Section Computed Tomography-Determined Combined Pulmonary Fibrosis and Emphysema on Outcomes Among Patients With Resected Lung Cancer. Reviewed

    Hashimoto N, Iwano S, Kawaguchi K, Fukui T, Fukumoto K, Nakamura S, Mori S, Sakamoto K, Wakai K, Yokoi K, Hasegawa Y

    The Annals of thoracic surgery   Vol. 102 ( 2 ) page: 440-7   2016.8

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    DOI: 10.1016/j.athoracsur.2016.03.014

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  63. Mean pulmonary arterial pressure as a prognostic indicator in connective tissue disease associated with interstitial lung disease: a retrospective cohort study. Reviewed

    Takahashi K, Taniguchi H, Ando M, Sakamoto K, Kondoh Y, Watanabe N, Kimura T, Kataoka K, Suzuki A, Ito S, Hasegawa Y

    BMC pulmonary medicine   Vol. 16 ( 1 ) page: 55   2016.4

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    DOI: 10.1186/s12890-016-0207-3

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  64. Hypoxia-induced modulation of PTEN activity and EMT phenotypes in lung cancers. Reviewed

    Kohnoh T, Hashimoto N, Ando A, Sakamoto K, Miyazaki S, Aoyama D, Kusunose M, Kimura M, Omote N, Imaizumi K, Kawabe T, Hasegawa Y

    Cancer cell international   Vol. 16   page: 33   2016

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    DOI: 10.1186/s12935-016-0308-3

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  65. Biomarkers in the Evaluation and Management of Idiopathic Pulmonary Fibrosis. Reviewed

    Tzouvelekis A, Herazo-Maya J, Sakamoto K, Bouros D

    Current topics in medicinal chemistry   Vol. 16 ( 14 ) page: 1587-98   2016

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  66. Lung-Dominant Connective Tissue Disease: Clinical, Radiologic, and Histologic Features. Reviewed

    Omote N, Taniguchi H, Kondoh Y, Watanabe N, Sakamoto K, Kimura T, Kataoka K, Johkoh T, Fujimoto K, Fukuoka J, Otani K, Nishiyama O, Hasegawa Y

    Chest   Vol. 148 ( 6 ) page: 1438-1446   2015.12

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    DOI: 10.1378/chest.14-3174

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  67. Direct regulation of transforming growth factor β-induced epithelial-mesenchymal transition by the protein phosphatase activity of unphosphorylated PTEN in lung cancer cells. Reviewed

      Vol. 106 ( 12 ) page: 1693-704   2015.12

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    DOI: 10.1111/cas.12831

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  68. Recombinant Human Thrombomodulin in Acute Exacerbation of Idiopathic Pulmonary Fibrosis. Reviewed

    Kataoka K, Taniguchi H, Kondoh Y, Nishiyama O, Kimura T, Matsuda T, Yokoyama T, Sakamoto K, Ando M

    Chest   Vol. 148 ( 2 ) page: 436-443   2015.8

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    DOI: 10.1378/chest.14-2746

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  69. Risk stratification by the lower limit of normal of FEV1/FVC for postoperative outcomes in patients with COPD undergoing thoracic surgery. Reviewed

    Osuka S, Hashimoto N, Sakamoto K, Wakai K, Yokoi K, Hasegawa Y

    Respiratory investigation   Vol. 53 ( 3 ) page: 117-23   2015.5

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    DOI: 10.1016/j.resinv.2015.01.005

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  70. Broader criteria of undifferentiated connective tissue disease in idiopathic interstitial pneumonias. Reviewed

    Kondoh Y, Johkoh T, Fukuoka J, Arakawa H, Tanaka T, Watanabe N, Sakamoto K, Kataoka K, Kimura T, Taniguchi H

    Respiratory medicine   Vol. 109 ( 3 ) page: 389-96   2015.3

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    DOI: 10.1016/j.rmed.2015.01.009

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  71. Endurance time is the most responsive exercise measurement in idiopathic pulmonary fibrosis. Reviewed

    Arizono S, Taniguchi H, Sakamoto K, Kondoh Y, Kimura T, Kataoka K, Ogawa T, Watanabe F, Nishiyama O, Nishimura K, Kozu R, Tabira K

    Respiratory care   Vol. 59 ( 7 ) page: 1108-15   2014.7

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    DOI: 10.4187/respcare.02674

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  72. Let-7d microRNA affects mesenchymal phenotypic properties of lung fibroblasts. Reviewed

    Huleihel L, Ben-Yehudah A, Milosevic J, Yu G, Pandit K, Sakamoto K, Yousef H, LeJeune M, Coon TA, Redinger CJ, Chensny L, Manor E, Schatten G, Kaminski N

    American journal of physiology. Lung cellular and molecular physiology   Vol. 306 ( 6 ) page: L534-42   2014.3

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    DOI: 10.1152/ajplung.00149.2013

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  73. Crizotinib-induced acute interstitial lung disease in a patient with EML4-ALK positive non-small cell lung cancer and chronic interstitial pneumonia. Reviewed

    Watanabe N, Nakahara Y, Taniguchi H, Kimura T, Kondoh Y, Kataoka K, Sakamoto K

    Acta oncologica (Stockholm, Sweden)   Vol. 53 ( 1 ) page: 158-60   2014.1

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    DOI: 10.3109/0284186X.2013.802838

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  74. Efficacy of combined therapy with cyclosporin and low-dose prednisolone in interstitial pneumonia associated with connective tissue disease. Reviewed

    Watanabe N, Sakamoto K, Taniguchi H, Kondoh Y, Kimura T, Kataoka K, Ono K, Fukuoka J, Nishiyama O, Hasegawa Y

    Respiration; international review of thoracic diseases   Vol. 87 ( 6 ) page: 469-77   2014

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    DOI: 10.1159/000358098

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  75. Significance of pulmonary arterial pressure as a prognostic indicator in lung-dominant connective tissue disease. Reviewed

    Suzuki A, Taniguchi H, Watanabe N, Kondoh Y, Kimura T, Kataoka K, Matsuda T, Yokoyama T, Sakamoto K, Nishiyama O, Hasegawa Y

    PloS one   Vol. 9 ( 9 ) page: e108339   2014

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    DOI: 10.1371/journal.pone.0108339

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  76. Endobronchial ultrasound transbronchial needle aspiration in older people. Reviewed

    Okachi S, Imai N, Imaizumi K, Hase T, Shindo Y, Sakamoto K, Aso H, Wakahara K, Hashimoto I, Ito S, Hashimoto N, Sato M, Kondo M, Hasegawa Y

    Geriatrics & gerontology international   Vol. 13 ( 4 ) page: 986-92   2013.10

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    DOI: 10.1111/ggi.12043

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  77. Quadriceps weakness contributes to exercise capacity in nonspecific interstitial pneumonia. Reviewed

    Watanabe F, Taniguchi H, Sakamoto K, Kondoh Y, Kimura T, Kataoka K, Ogawa T, Arizono S, Nishiyama O, Hasegawa Y

    Respiratory medicine   Vol. 107 ( 4 ) page: 622-8   2013.4

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    DOI: 10.1016/j.rmed.2012.12.013

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  78. Pulmonary hypertension as a prognostic indicator at the initial evaluation in idiopathic pulmonary fibrosis. Reviewed

    Kimura M, Taniguchi H, Kondoh Y, Kimura T, Kataoka K, Nishiyama O, Aso H, Sakamoto K, Hasegawa Y

    Respiration; international review of thoracic diseases   Vol. 85 ( 6 ) page: 456-63   2013

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  79. Involvement of TGFβ-induced phosphorylation of the PTEN C-terminus on TGFβ-induced acquisition of malignant phenotypes in lung cancer cells. Reviewed

      Vol. 8 ( 11 ) page: e81133   2013

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    DOI: 10.1371/journal.pone.0081133

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  80. Predictors of the need to initiate noninvasive ventilation in stable outpatients with acute exacerbation of chronic obstructive pulmonary disease. Reviewed

    Taga S, Taniguchi H, Watanabe N, Kondoh Y, Kimura T, Kataoka K, Aso H, Sakamoto K, Hasegawa Y

    Internal medicine (Tokyo, Japan)   Vol. 52 ( 16 ) page: 1781-6   2013

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    PubMed

  81. Differential modulation of surfactant protein D under acute and persistent hypoxia in acute lung injury. Reviewed

    Sakamoto K, Hashimoto N, Kondoh Y, Imaizumi K, Aoyama D, Kohnoh T, Kusunose M, Kimura M, Kawabe T, Taniguchi H, Hasegawa Y

    Am J Physiol Lung Cell Mol Physiol.   Vol. 303 ( 1 ) page: L43-53   2012.7

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  82. Acute exacerbation of IPF following diagnostic bronchoalveolar lavage procedures.

    Sakamoto K, Taniguchi H, Kondoh Y, Wakai K, Kimura T, Kataoka K, Hashimoto N, Nishiyama O, Hasegawa Y.

    Respir Med   Vol. 106 ( 3 ) page: 436-42   2012

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  83. Involvement of the transcription factor twist in phenotype alteration through epithelial-mesenchymal transition in lung cancer cells.

    Nakashima H, Hashimoto N, Aoyama D, Kohnoh T, Sakamoto K, Kusunose M, Imaizumi K, Takeyama Y, Sato M, Kawabe T, Hasegawa Y.

    Mol Carcinog   Vol. 51   page: 400-410   2012

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  84. Risk factors of acute exacerbation of idiopathic pulmonary fibrosis. Reviewed

    Kondoh Y, Taniguchi H, Katsuta T, Kataoka K, Kimura T, Nishiyama O, Sakamoto K, Johkoh T, Nishimura M, Ono K, Kitaichi M.

    Sarcoidosis Vasc Diffuse Lung Dis   Vol. 27   page: 103-110   2010

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  85. Serum KL-6 in fibrotic NSIP: Correlations with physiologic and radiologic parameters.

    Sakamoto K, Taniguchi H, Kondoh Y, Johkoh T, Sumikawa H, Kimura T, Nishiyama O, Kato K, Kataoka K, Ono K, Kitaichi M, Hasegawa Y.

    Respir Med   Vol. 104   page: 127-133   2009

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  86. Acute exacerbation of idiopathic pulmonary fibrosis as the initial presentation of the disease.

    Sakamoto K, Taniguchi H, Kondoh Y, Ono K, Hasegawa Y, Kitaichi M.

    Eur Respir Rev   Vol. 18   page: 129-132.   2009

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  87. 原発性肺クリプトコッカス症の臨床的検討 Reviewed

    阪本 考司, 麻生 裕紀, 横山 俊樹, 加藤 景介, 西山 理, 木村 智樹, 近藤 康博, 谷口 博之

    感染症学雑誌   Vol. 4   page: 403-407   2007.7

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  88. びまん性肺疾患に対する外科的肺生検の検討 合併症、診断効率と早期死亡について

    阪本 考司, 横山 俊樹, 麻生 裕紀, 岩木 舞, 野間 聖, 加藤 景介, 西山 理, 木村 智樹, 近藤 康博, 谷口 博之

    日本呼吸器学会雑誌   Vol. 44 ( 10 ) page: 675-680   2006.10

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  89. 化学療法を施行したIV期非小細胞肺癌におけるQuality of Life

    西山 理, 谷口 博之, 近藤 康博, 木村 智樹, 加藤 景介, 野間 聖, 岩木 舞, 麻生 裕紀, 阪本 考司, 清水 淳市

    日本呼吸器学会雑誌   Vol. 44 ( 5 ) page: 368-373   2006.5

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▼display all

MISC 46

  1. 間質性肺炎における病因・病態の新展開 Epigenome(noncoding RNAを含む) Invited

    阪本 考司

    日本呼吸器学会誌   Vol. 7 ( 増刊 ) page: 39 - 39   2018.3

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  2. 知っておきたい間質性肺疾患の基本 病態生理から治療・合併症・呼吸ケアの注意点まで

    阪本 考司

    日本呼吸ケア・リハビリテーション学会誌   Vol. 34 ( Suppl. ) page: 87s - 87s   2024.10

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  3. 【職業性・環境関連呼吸器疾患】大気・室内環境汚染と呼吸器疾患 PM2.5と呼吸器疾患

    阪本 考司

    呼吸器内科   Vol. 45 ( 5 ) page: 488 - 493   2024.5

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  4. びまん性肺疾患における末梢ヘルパーT細胞の解析

    横井 英人, 若原 恵子, 中村 さや, 福谷 衣里子, 阪本 考司, 石井 誠

    日本呼吸器学会誌   Vol. 13 ( 増刊 ) page: 369 - 369   2024.3

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  5. デジタルPCRで測定したBAL中ミトコンドリアDNAコピー数は特発性肺線維症患者の予後を予測する

    池山 賢樹, 富貴原 淳, 阪本 考司, 片岡 健介, 古川 大記, 寺町 涼, 橋本 直純, 近藤 康博, 石井 誠

    日本呼吸器学会誌   Vol. 13 ( 増刊 ) page: 341 - 341   2024.3

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  6. シリカナノ粒子による肺傷害モデルに対するNOX2阻害ペプチドを用いた新規治療の効果と作用機序の検討

    日下 真宏, 阪本 考司, 池山 賢樹, 近藤 友喜, 森 裕太, 石井 誠

    日本呼吸器学会誌   Vol. 13 ( 増刊 ) page: 297 - 297   2024.3

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  7. 間質性肺疾患の酸素療法と病診連携 Invited

    阪本 考司

    日本呼吸器学会誌   Vol. 13 ( 増刊 ) page: 150 - 150   2024.3

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  8. 医学観点からの生体膜分子呼応と疾患制御 微粒子曝露による肺傷害の重症度を決定づける肺免疫細胞におけるエンドソーム内の活性酸素種の制御機構 Invited

    阪本 考司, 日下 真宏, 井上 正英, 中瀬 生彦, 澤田 誠

    日本生化学会大会プログラム・講演要旨集   Vol. 96回   page: [2S07m - 04]   2023.10

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  9. 指定難病患者データを用いたわが国における閉塞性細気管支炎の実態に関する調査

    橋本 直純, 阪本 考司, 若原 恵子

    日本呼吸器学会誌   Vol. 12 ( 5 ) page: 240 - 245   2023.9

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    閉塞性細気管支炎(bronchiolitis obliterans:BO)は呼吸不全をきたす難治性呼吸器疾患であり,わが国で指定難病に登録された.本研究は指定難病患者データを解析することでBOの臨床的特徴と生活状況の実態を明らかにすることを目的とした.91例の臨床調査個人票の情報から15例の新規認定者と36例の更新認定者のデータを解析し,典型的な臨床的特徴とさまざまな行動制限や精神症状を伴う生活状況の実態が確認できた.特発性BOは希少疾患であり,病態解明のために特発性BOと二次性BOを対象とした包括的で疾患領域横断的なレジストリ構築が必要と考えられた.(著者抄録)

  10. 【間質性肺炎・肺線維症アップデート】肺線維化の細胞分子機序

    阪本 考司

    現代医学   Vol. 70 ( 1 ) page: 47 - 52   2023.6

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  11. COVID-19感染を契機に発症したIPF急性増悪の2例

    福田 夏帆, 表 紀仁, 阪本 考司, 森瀬 昌宏, 岡地 祥太郎, 松井 利憲, 鈴木 淳, 日下 真宏, 池山 賢樹, 若原 恵子, 石井 誠

    日本呼吸器学会誌   Vol. 12 ( 増刊 ) page: 383 - 383   2023.3

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  12. 線維性間質性肺疾患に合併する肺癌の臨床的検討

    日下 真宏, 鈴木 淳, 阪本 考司, 表 紀仁, 池山 賢樹, 石井 誠

    日本呼吸器学会誌   Vol. 12 ( 増刊 ) page: 292 - 292   2023.3

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  13. 特発性肺線維症の新規バイオマーカーミトコンドリアDNA絶対定量法の開発

    池山 賢樹, 富貴原 淳, 阪本 考司, 片岡 健介, 古川 大記, 鈴木 淳, 日下 真宏, 表 紀仁, 橋本 直純, 近藤 康博, 石井 誠

    日本呼吸器学会誌   Vol. 12 ( 増刊 ) page: 241 - 241   2023.3

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  14. びまん性肺疾患 稀なびまん性肺疾患 指定難病患者データを用いた本邦における閉塞性細気管支炎の実態に関する調査

    橋本 直純, 阪本 考司, 若原 恵子

    日本呼吸器学会誌   Vol. 12 ( 増刊 ) page: 204 - 204   2023.3

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  15. 【治療とケアを全部きちんとていねいに 間質性肺炎「超」入門】(Part.1)総論 間質性肺炎の「キホン」を知ろう

    阪本 考司

    みんなの呼吸器Respica   Vol. 20 ( 4 ) page: 448 - 451   2022.8

  16. ウェアラブルディスプレイを用いた気管支鏡下生検時の迅速細胞診(ROSE)支援システムの構築

    岡地 祥太郎, 伊藤 貴康, 松澤 令子, 佐藤 和秀, 阪本 考司, 森瀬 昌宏, 若原 恵子, 橋本 直純

    気管支学   Vol. 44 ( Suppl. ) page: S228 - S228   2022.5

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  17. 喘息・COPDにおける吸入デバイスとアドヒアランスの検討

    福谷 衣里子, 若原 恵子, 中村 さや, 横井 英人, 吉見 陽, 宮崎 雅之, 進藤 有一郎, 阪本 考司, 岡地 祥太郎, 田中 一大, 浜島 信之, 野田 幸裕, 橋本 直純

    日本呼吸器学会誌   Vol. 11 ( 増刊 ) page: 213 - 213   2022.4

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  18. COVID-19パンデミックによる活動制限がもたらす慢性閉塞性肺疾患への影響

    伊勢 裕子, 馬嶋 俊, 安藤 啓, 浅野 周一, 木村 元宏, 福谷 衣里子, 横井 英人, 表 紀仁, 岡地 祥太郎, 阪本 考司, 進藤 有一郎, 若原 恵子, 橋本 直純

    日本呼吸器学会誌   Vol. 11 ( 増刊 ) page: 200 - 200   2022.4

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  19. 筋疲労と呼吸困難を指標に運動負荷量を設定した運動療法により、運動耐容能とQOLの改善が得られた間質性肺炎合併の抗MDA5抗体陽性皮膚筋炎患者の1例

    那須 崇史, 水野 陽太, 中島 裕貴, 岩瀬 結介, 井上 貴行, 後藤 洋輔, 阪本 考司, 永谷 元基

    国立大学リハビリテーション   Vol. 43   page: 44 - 48   2022.4

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    間質性肺炎を合併する抗MDA5抗体陽性皮膚筋炎患者(40歳代男性)に対し、筋疲労と呼吸困難の指標に修正ボルグスケールを用いて運動負荷量を設定した運動療法を実施し、運動耐容能と呼吸困難QOLの改善が得られた症例について報告した。

    Other Link: https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J07494&link_issn=&doc_id=20220524550009&doc_link_id=%2Fda4unive%2F2022%2F004300%2F010%2F0044-0048%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fda4unive%2F2022%2F004300%2F010%2F0044-0048%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  20. 肺線維症の病態に関連する2つの新規マーカー分子:メフリンとミトコンドリアDNA

    阪本 考司, 橋本 直純, 中原 義夫, 古川 大記

    呼吸器内科   Vol. 41 ( 2 ) page: 197 - 201   2022.2

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  21. 【呼吸器症候群(第3版)-その他の呼吸器疾患を含めて-】その他 原発性線毛機能不全症

    阪本 考司

    日本臨床   Vol. 別冊 ( 呼吸器症候群III ) page: 398 - 401   2021.10

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  22. 【呼吸器症候群(第3版)-その他の呼吸器疾患を含めて-】びまん性肺疾患 じん肺および室内・大気環境汚染による肺疾患 大気環境汚染による肺疾患

    阪本 考司

    日本臨床   Vol. 別冊 ( 呼吸器症候群III ) page: 255 - 258   2021.10

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  23. 貪食小胞内の活性酸素制御はシリカナノ粒子誘導肺障害の新たな治療標的になる

    阪本 考司, 井上 正英, 鈴木 淳, 安藤 啓, 橋本 直純

    日本呼吸器学会誌   Vol. 10 ( 増刊 ) page: 167 - 167   2021.4

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  24. 非晶質性シリカナノ粒子による肺毒性の検討

    井上 正英, 阪本 考司, 鈴木 淳, 中原 義夫, 橋本 直純, 澤田 誠, 長谷川 好規

    日本呼吸器学会誌   Vol. 9 ( 増刊 ) page: 239 - 239   2020.8

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  25. Supplemental oxygen improves exercise capacity in IPF patients with exertional desaturation Reviewed

    Arizono S, Furukawa T, Taniguchi H, Sakamoto K, Kimura T, Kataoka K, Ogawa T, Watanabe F, Kondoh Y

    Respirology (Carlton, Vic.)     2020.5

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    DOI: 10.1111/resp.13829

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  26. High-flow nasal cannula therapy for acute respiratory failure in patients with interstitial pneumonia: a retrospective observational study Reviewed

    Omote N, Matsuda N, Hashimoto N, Nishida K, Sakamoto K, Ando A, Nakahara Y, Nishikimi M, Higashi M, Matsui S, Hasegawa Y

    Nagoya journal of medical science   Vol. 82 ( 2 ) page: 301-313   2020.5

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    DOI: 10.18999/nagjms.82.2.301

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  27. Silica Nanoparticle Induced Lung Injury in Mice: Dissecting Relative Contribution of Its Size and Surface Modification

    Inoue M., Sakamoto K., Suzuki A., Nakahara Y., Hashimoto N., Hasegawa Y., Sawada M.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 201   2020

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  28. The Role of Meflin Expression in Fibroblasts During Development of Pulmonary Fibrosis

    Hashimoto N., Nakahara Y., Sakamoto K., Enomoto A., Yokoi T., Suzuki A., Inoue M., Wakahara K., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 201   2020

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  29. Single-Cell RNAseq of Aging Mouse Lungs Reveals Global and Cell-Specific Inflammatory Aberrations

    Cosme C. Jr., McDonough J. E., Adams T., Schupp J. C., Omote N., Ahangari F., Deluliis G., Sakamoto K., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 201   2020

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  30. Serum CRP Decrease Has Predictive Value for LongTerm Disease Control by PD-1/ PD-L1 Inhibitors in Patients with NSCLC

    Matsuzawa R., Morise M., Tanaka I., Koyama J., Kimura T., Kondoh Y., Hase T., Sakamoto K., Hashimoto N., Hasegawa Y.

    JOURNAL OF THORACIC ONCOLOGY   Vol. 14 ( 10 ) page: S716 - S716   2019.10

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  31. The new-defined mesenchymal stromal/stem cell marker has a protective role in the development of acute lung injury

    Nakahara Yoshio, Hashimoto Naozumi, Sakamoto Koji, Ando Akira, Inoue Masahide, Suzuki Atsushi, Enomoto Atsushi, Hasegawa Yoshinori

    EUROPEAN RESPIRATORY JOURNAL   Vol. 54   2019.9

  32. Renewed Japanese spirometric reference variables and risk stratification for postoperative outcomes in COPD patients with resected lung cancer Reviewed

    Okada Y, Hashimoto N, Iwano S, Kawaguchi K, Fukui T, Sakamoto K, Wakai K, Yokoi K, Hasegawa Y

    Nagoya journal of medical science   Vol. 81 ( 3 ) page: 427-438   2019.8

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    DOI: 10.18999/nagjms.81.3.427

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  33. Repressive role of stabilized hypoxia inducible factor 1α expression on transforming growth factor β-induced extracellular matrix production in lung cancer cells Reviewed

    Ando A, Hashimoto N, Sakamoto K, Omote N, Miyazaki S, Nakahara Y, Imaizumi K, Kawabe T, Hasegawa Y

    Cancer science   Vol. 110 ( 6 ) page: 1959-1973   2019.6

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    DOI: 10.1111/cas.14027

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  34. Recurrent Acute Exacerbations of Fibrotic Interstitial Lung Diseases

    Suzuki A., Kondoh Y., Brown K. K., Kimura T., Kataoka K., Matsuda T., Yokoyama T., Ando M., Hashimoto N., Sakamoto K., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 199   2019

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  35. TINCR, a Long Intergenic Noncoding RNA Decreased in IPF, Is a Novel Regulator of Airway Epithelial Cell Differentiation

    Omote N., Sakamoto K., Li Q., Schupp J. C., Adams T., Ahangari F., Chioccioli M., Xylourgidis N., DeIuliis G., Hashimoto N., Hasegawa Y., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 199   2019

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  36. 膠原病関連間質性肺疾患におけるThe COPD Assessment Testを用いた健康状態評価

    鈴木 淳, 近藤 康博, 松田 俊明, 木村 智樹, 片岡 健介, 山野 泰彦, 橋本 直純, 阪本 考司, 長谷川 好規

    日本呼吸ケア・リハビリテーション学会誌   Vol. 28 ( Suppl. ) page: 245s - 245s   2018.10

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  37. 【呼吸器病学TOPICS 2017-18】細胞・分子生物学 間質性肺炎における長鎖ノンコーディングRNA

    阪本 考司

    分子呼吸器病   Vol. 22 ( 1 ) page: 8 - 11   2018.3

  38. 抗PD-1抗体による薬剤性肺障害の検討

    富貴原 淳, 阪本 考司, 森瀬 昌宏, 長谷川 好規

    日本呼吸器学会誌   Vol. 7 ( 増刊 ) page: 236 - 236   2018.3

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  39. 間質性肺疾患による急性呼吸不全に対するハイフローネーザルの有効性

    表 紀仁, 松田 直之, 橋本 直純, 阪本 考司, 東 倫子, 長谷川 好規

    日本集中治療医学会雑誌   Vol. 25 ( Suppl. ) page: [O35 - 5]   2018.2

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    Language:English   Publisher:(一社)日本集中治療医学会  

  40. Risk Factor Evaluation of Programmed Death 1 Inhibitor Related Pneumonitis in Patients with Non-Small Cell Lung Cancer

    Fukihara J., Sakamoto K., Iwano S., Morise M., Hashimoto N., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 197   2018

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  41. Pathogenesis of bronchiolitis obliterans : recent progress

      Vol. 31 ( 5 ) page: 436 - 442   2017.5

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  42. 肺非結核性抗酸菌症に対する気管支鏡検査についての検討

    岡地 祥太郎, 長谷 哲成, 進藤 有一郎, 麻生 裕紀, 阪本 考司, 森瀬 昌宏, 若原 恵子, 橋本 直純, 佐藤 光夫, 近藤 征史, 長谷川 好規

    気管支学   Vol. 39 ( Suppl. ) page: S303 - S303   2017.5

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    Language:Japanese   Publisher:(一社)日本呼吸器内視鏡学会  

  43. Unphosphorylated Pten Inhibits Tgf beta-Induced Aberrant Cell Motility In Epithelial Cells Via Differential Phosphatase Activities

    Hashimoto N., Sakamoto K., Miyazaki S., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 195   2017

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  44. The Impact Of CT-Detected Usual Interstitial Pneumonia Pattern As The Decision-Making Factor For Treatment Of Lung Cancer

    Ando A., Hashimoto N., Sakamoto K., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 195   2017

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  45. Single Cell Rna-Sequencing Reveals Distinct Effects Of Inhibition Of Fendrr, A Long Non-Coding Rna Implicated In Fibroblast To Myofibroblast Differentiation

    Adams T., Sakamoto K., Ahangari F., Munivar A., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 195   2017

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  46. Risk Stratification For Airflow Obstruction-Related Outcomes Based On A Renewed Japanese Spirometric Reference By Using The Lambda-Mu-Sigma Method

    Hashimoto N., Okada Y., Sakamoto K., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 195   2017

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Presentations 39

  1. Prognostic Prediction for Patients With Idiopathic Interstitial Pneumonia: Nationwide Prospective Registry, Japanese Idiopathic Interstitial Pneumonias (JIPS) Registry (NEJ030) International conference

    Arai, T; Okuda, R; Ogura, T; Hisata, S; Baba, T; Kondoh, Y; Suda, T; Johkoh, T; Iwasawa, T; Nakamura, Y; Tomii, K; Miyamoto, A; Kasai, T; Tanaka, T; Abe, M; Izumi, S; Yamauchi, H; Sakamoto, K; Koga, Y; Kimura, M; Kishaba, T; Suzuki, S; Hara, H; Yokomura, K; Ichiyasu, H; Nakagawa, H; Arita, M; Ishimoto, H; Yamasaki, K; Nishiyama, O; Tanino, Y; Hashimoto, D; Morita, S; Nukiwa, T; Kobayashi, K

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2024.5.1 

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    Event date: 2024.5

    Language:English   Presentation type:Oral presentation (general)  

  2. mtDNA in bronchoalveolar lavage fluid is a prognostic factor for IPF and AE-IPF International conference

    Fukihara, J; Sakamoto, K; Furukawa, T; Teramachi, R; Ikeyama, Y; Kataoka, K; Kondoh, Y; Hashimoto, N; Ishii, M

    EUROPEAN RESPIRATORY JOURNAL  2023.9.9 

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    Event date: 2023.9

    Language:English   Presentation type:Oral presentation (general)  

    DOI: 10.1183/13993003.congress-2023.PA1236

  3. Effect of telomere length and TERT/TERC rare variants on survival in Japanese patients with idiopathic interstitial pneumonias :Genetic predisposition study from the Japanese Idiopathic Interstitial Pneumonias (JIPS) Registry (NEJ036A)

    Hisata, S; Tanino, Y; Okuda, R; Ogura, T; Isshiki, T; Horimasu, Y; Hamada, N; Arai, N; Tsubata, Y; Suda, T; Horio, Y; Ishikawa, N; Kondoh, Y; Toyoshima, M; Ishii, H; Abe, M; Kato, M; Tanigawa, M; Tomioka, H; Chiba, H; Arai, T; Nishioka, Y; Hattori, N; Hoshino, T; Shimizu, Y; Sakamoto, K; Ishikawa, S; Mieno, MN; Baba, T; Miyazaki, Y; Nukiwa, T; Kobayashi, K; Suzuki, T; Hagiwara, K

    EUROPEAN RESPIRATORY JOURNAL  2024.9 

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    Event date: 2024.9

    Language:English   Presentation type:Oral presentation (general)  

    DOI: 10.1183/13993003.congress-2024.OA2867

  4. FENDRR LNCRNA Knockout Leads to Age-associated Senescence Signature in Mouse Lung Endothelial Cells International conference

    De Man, R; Cosme, C ; Adams, T; Ahangari, F; Manning, EP; Sakamoto, K; Kaminski, N

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2024.5.1 

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    Event date: 2024.5

    Language:English   Presentation type:Oral presentation (general)  

  5. Novel Treatment With NOX2 Inhibitory Peptide for Lung Injury Caused by Silica Nanoparticles Exposure: Its Efficacy and Underlying Mechanism International conference

    Kusaka, M; Sakamoto, K; Sato, T; Kondo, Y; Mori, Y; Ikeyama, Y; Suzuki, A; Hashimoto, N; Ishii, M

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2024.5.1 

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    Event date: 2024.5

    Language:English   Presentation type:Oral presentation (general)  

  6. Meflin-BMP3b Axis Is a Novel Anti-Fibrotic Pathway Against TGF-β-Induced Lung Fibrogenesis International conference

    Suzuki, A; Sakamoto, K; Nakahara, Y; Enomoto, A; Hino, J; Ando, A; Inoue, M; Omote, N; Kusaka, M; Fukihara, J; Hashimoto, N

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2022.5.1 

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    Event date: 2022.5

    Language:English   Presentation type:Oral presentation (general)  

  7. Late Breaking Abstract - Long-term Effect of Pulmonary Rehabilitation under Nintedanib treatment in Idiopathic Pulmonary Fibrosis (FITNESS study) International conference

    Ogura, T; Mori, Y; Kataoka, K; Nishiyama, O; Ando, M; Arizono, S; Ogawa, T; Shiraki, A; Ichikado, K; Ishimoto, H; Ito, H; Sakamoto, K; Tomii, K; Tomioka, H; Tsuda, T; Kozu, R; Kondoh, Y

    EUROPEAN RESPIRATORY JOURNAL  2021.9.5 

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    Event date: 2021.9

    Language:English   Presentation type:Oral presentation (general)  

    DOI: 10.1183/13993003.congress-2021.RCT2905

  8. Assessment of Circulating Mitochondrial DNA as a Liquid Biomarker in Acute Exacerbation of Idiopathic Pulmonary Fibrosis International conference

    Sakamoto K., Furukawa T., Yamano Y., Teramachi R., Kataoka K., Hashimoto N., Kondoh Y., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 

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    Event date: 2019

    Language:English   Presentation type:Poster presentation  

  9. Possible UIP Pattern with Traction Bronchiectasis on HRCT: Prognostic Impact in IIP International conference

    Fukihara J., Kondoh Y., Kimura T., Kataoka K., Matsuda T., Yokoyama T., Furukawa T., Johkoh T., Fukuoka J., Sakamoto K., Hashimoto N., Hasegawa Y., Brown K. K.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 

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    Event date: 2018

    Language:English   Presentation type:Poster presentation  

  10. Lung Epithelium Overexpressed Noncoding Rna (leon): A Potential Regulator Of Epithelial Gene Expression In Idiopathic Pulmonary Fibrosis International conference

    Guardela B. Juan, Herazo-Maya J. D., Sakamoto K., Li Q., Deluliis G., Yan X., Prasse A., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 

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    Event date: 2017

    Language:English   Presentation type:Poster presentation  

  11. Performance Of The Saint George's Respiratory Questionnaire (sgrq) In Patients With Connective Tissue Disease-Associated Interstitial Lung Disease (ctd-Ild) International conference

    Suzuki A., Taniguchi H., Kondoh Y., Swigris J. J., Yamano Y., Furukawa T., Numata-Nakamura M., Sakamoto K., Ando M., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 

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    Event date: 2017

    Language:English   Presentation type:Poster presentation  

  12. Transduction of PTEN with mutated its C-terminal phosphorylation sites inhibits TGFb- induced phe notype alterations through epithelial-mesenchymal transition International conference

    K. Sakamoto, N. Hashimoto, D. Aoyama, M. Kusunose, M. Kimura, T. Kohnoh, K. Imaizumi, Y. Hasegawa.

    American Thoracic Society 2012 International Conference 

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    Event date: 2012

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  13. Acute Exacerbation of IPF Following Bronchoalveolar Lavage Procedures International conference

    K. Sakamoto, H. Taniguchi, Y. Kondoh, K. Wakai, T. Kimura, K. Kataoka, N. Hashimoto, O. Nishiyama, Y. Hasegawa.

    Chest 2011 Annual Congress 

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    Event date: 2011

    Language:English   Presentation type:Oral presentation (general)  

    Country:United States  

  14. Modulated Expression Of Surfactant Protein D In Acute Lung Injury Might Be Associated With Epithelial-Mesenchymal Transition In Epithelial Cells International conference

    K. Sakamoto, N. Hashimoto, K. Imaizumi, H. Taniguchi, Y. Kondoh, T. Kohnoh, D. Aoyama, T. Ogawa, Y. Hasegawa.

    American Thoracic Society 2011 International Conference 

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    Event date: 2011

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  15. Modulated expression of surfactant protein D in acute lung injury might be associated with epithelial-mesenchymal transition in epithelial cells. International conference

    K. Sakamoto, N. Hashimoto, Y. Hasegawa.

    FASEB Summer Research Conferences 2010 

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    Event date: 2010

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  16. EMT-Related Gene, Twist, for Phenotype Change in Lung Cancer Cells International conference

    K. Sakamoto, N. Hashimoto, K. Imaizumi, H. Nakashima, T. Kohnoh, D. Aoyama, T. Ogawa, Y. Hasegawa.

    American Thoracic Society 2010 International Conference 

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    Event date: 2010

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  17. Lung Epithelium Overexpressed Noncoding Rna (leon): A Potential Regulator Of Epithelial Gene Expression In Idiopathic Pulmonary Fibrosis International conference

    Guardela B. Juan, Herazo-Maya J. D, Sakamoto K, Li Q, Deluliis G, Yan X, Prasse A, Kaminski N

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2017 

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    Language:English   Presentation type:Poster presentation  

  18. Loss of lncRNA FENDRR Induces Senescence in Adult Mouse Lungs International coauthorship International conference

    Xylourgidis N., Sakamoto K., Schupp J. C., Adams T., DeIuliis G., Omote N., Hashimoto N., Hasegawa Y., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2019 

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  19. Long Non-Coding RNA TINCR Is a Novel Regulator of Human Bronchial Epithelial Cell Differentiation International coauthorship International conference

    Omote N., Sakamoto K., Li Q., Schupp J. C., Adams T., Ahangari F., Chioccioli M., Hashimoto N., Hasegawa Y., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020 

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  20. Increased Circulating Mitochondrial DNA Content Predicts Fatal Complication and Worse Prognosis in Idiopathic Pulmonary Fibrosis International conference

    Sakamoto K., Furukawa T., Yamano Y., Teramachi R., Suzuki A., Nakahara Y., Inoue M., Kataoka K., Hashimoto N., Kondoh Y., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020 

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    Language:English   Presentation type:Oral presentation (general)  

  21. Exogenous Induction Of Unphosphorylated Tumor Suppressor Phosphatase And Tensin Homolog Deleted On Chromosome 10 Modulates Transforming Growth Factor beta-Induced Extracellular Matrix Expression In Lung Fibroblasts International conference

    Omote N., Hashimoto N., Kimura M., Miyazaki S., Ando A., Sakamoto K., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2017 

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  22. Exogenous induction of unphosphorylated PTEN reduces TGF beta-induced extracellular matrix expressions in lung fibroblasts International conference

    Motohiro Kimura, Naozumi Hashimoto, Masaaki Kusunose, Daisuke Aoyama, Koji Sakamoto, Shinichi Miyazaki, Akira Ando, Norihiro Omote, Kazuyoshi Imaizumi, Tsutomu Kawabe, Yoshinori Hasegawa

    WOUND REPAIR AND REGENERATION  2017  WILEY

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    Presentation type:Poster presentation  

    Transforming growth factor beta (TGF beta) plays an important role in regulating aberrant extracellular matrix (ECM) production from alveolar/epithelial cells (AECs) and fibroblasts in pulmonary fibrosis. Although the tumor suppressor gene phosphatase and tensin homologue deleted from chromosome 10 (PTEN) can negatively control many TGF beta-activated signaling pathways via the phosphatase activity, hyperactivation of the TGF beta-related signaling pathways is often observed in fibrosis. Loss of PTEN expression might cause TGF beta-induced ECM production. In addition, TGF beta was recently shown to induce loss of PTEN enzymatic activity by phosphorylating the PTEN C-terminus. Therefore, we hypothesized that exogenous transfer of unphosphorylated PTEN (PTEN4A) might lead to reduce TGF beta-induced ECM expression in not only epithelial cells but also fibroblasts. Adenovirus-based exogenous PTEN4A induction successfully reduced TGF beta-induced fibronectin expression and retained beta-catenin at the cell membrane in human epithelial cells. Exogenous unphosphorylated PTEN also attenuated TGF beta-induced ECM production and inhibited TGF beta-induced b-catenin translocation in a human fibroblast cell line and in mouse primary isolated lung fibroblasts. Conversely, TGF beta-induced a-smooth muscle actin expression did not seem to be inhibited in these fibroblasts. Our data suggest that exogenous administration of unphosphorylated PTEN might be a promising strategy to restore TGF beta-induced loss of PTEN activity and reduce aberrant TGF beta-induced ECM production from epithelial cells and fibroblasts in lung fibrosis as compared with wild-type PTEN induction.

    Scopus

    PubMed

  23. Assessment of Circulating Mitochondrial DNA as a Liquid Biomarker in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

    Sakamoto K, Furukawa T, Yamano Y, Teramachi R, Kataoka K, Hashimoto N, Kondoh Y, Hasegawa Y

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2019 

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    Language:English   Presentation type:Poster presentation  

  24. Performance Of The Saint George's Respiratory Questionnaire (sgrq) In Patients With Connective Tissue Disease-Associated Interstitial Lung Disease (ctd-Ild) International conference

    Suzuki A, Taniguchi H, Kondoh Y, Swigris J. J, Yamano Y, Furukawa T, Numata-Nakamura M, Sakamoto K, Ando M, Hasegawa Y

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2017 

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    Language:English   Presentation type:Poster presentation  

  25. TINCR, a Long Intergenic Noncoding RNA Decreased in IPF, Is a Novel Regulator of Airway Epithelial Cell Differentiation International coauthorship International conference

    Omote N., Sakamoto K., Li Q., Schupp J. C., Adams T., Ahangari F., Chioccioli M., Xylourgidis N., DeIuliis G., Hashimoto N., Hasegawa Y., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2019 

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    Language:English   Presentation type:Oral presentation (general)  

  26. The Role of Meflin Expression in Fibroblasts During Development of Pulmonary Fibrosis International conference

    Hashimoto N., Nakahara Y., Sakamoto K., Enomoto A., Yokoi T., Suzuki A., Inoue M., Wakahara K., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020 

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  27. The new-defined mesenchymal stromal/stem cell marker has a protective role in the development of acute lung injury International conference

    Nakahara Yoshio, Hashimoto Naozumi, Sakamoto Koji, Ando Akira, Inoue Masahide, Suzuki Atsushi, Enomoto Atsushi, Hasegawa Yoshinori

    EUROPEAN RESPIRATORY JOURNAL  2019.9.28 

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  28. The hypoxia-inducible factor 1a protein stabilizers inhibit transforming growth factor beta-induced extracellular matrix proteins in epithelial cells and fibroblasts International conference

    Ando Akira, Hashimoto Naozumi, Sakamoto Koji, Hasegawa Yoshinori

    EUROPEAN RESPIRATORY JOURNAL  2018.9.15 

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  29. Single-Cell RNAseq of Aging Mouse Lungs Reveals Global and Cell-Specific Inflammatory Aberrations International coauthorship International conference

    Cosme C. Jr., McDonough J. E., Adams T., Schupp J. C., Omote N., Ahangari F., Deluliis G., Sakamoto K., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020 

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  30. Silica Nanoparticle Induced Lung Injury in Mice: Dissecting Relative Contribution of Its Size and Surface Modification International coauthorship International conference

    Inoue M., Sakamoto K., Suzuki A., Nakahara Y., Hashimoto N., Hasegawa Y., Sawada M.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020 

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  31. Serum CRP Decrease Has Predictive Value for LongTerm Disease Control by PD-1/ PD-L1 Inhibitors in Patients with NSCLC International conference

    Matsuzawa R., Morise M., Tanaka I., Koyama J., Kimura T., Kondoh Y., Hase T., Sakamoto K., Hashimoto N., Hasegawa Y.

    JOURNAL OF THORACIC ONCOLOGY  2019.10 

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  32. Recurrent Acute Exacerbations of Fibrotic Interstitial Lung Diseases International conference

    Suzuki A., Kondoh Y., Brown K. K., Kimura T., Kataoka K., Matsuda T., Yokoyama T., Ando M., Hashimoto N., Sakamoto K., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2019 

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    Language:English   Presentation type:Oral presentation (general)  

  33. Possible UIP Pattern with Traction Bronchiectasis on HRCT: Prognostic Impact in IIP International coauthorship International conference

    Fukihara J, Kondoh Y, Kimura T, Kataoka K, Matsuda T, Yokoyama T, Furukawa T, Johkoh T, Fukuoka J, Sakamoto K, Hashimoto N, Hasegawa Y, Brown K. K

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2018 

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  34. Pirfenidone Delays the Prescription of Concomitant Drugs in Patients with Idiopathic Pulmonary Fibrosis: Post-Hoc Analysis of Japanese Phase III Clinical Trial International conference

    Suzuki A., Sakaguchi H., Ebina M., Azuma A., Ogura T., Taguchi Y., Suga M., Takahashi H., Sugiyama Y., Kudoh S., Nukiwa T., Miyazawa S., Sakamoto K., Kondoh Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020 

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    Language:English   Presentation type:Oral presentation (general)  

  35. The new-defined mesenchymal stromal/stem cell marker has a protective role in the development of acute lung injury International conference

    Nakahara Yoshio, Hashimoto Naozumi, Sakamoto Koji, Ando Akira, Inoue Masahide, Suzuki Atsushi, Enomoto Atsushi, Hasegawa Yoshinori

    EUROPEAN RESPIRATORY JOURNAL  2019.9.28 

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  36. Immune checkpoint inhibitor for advanced or recurrent non-small cell lung cancer patients with poor performance status International conference

    Koyama Junji, Kimura Tomoki, Oi Hajime, Yamano Yasuhiko, Yokoyama Toshiki, Matsuda Toshiaki, Kataoka Kensuke, Matsuzawa Reiko, Fukihara Jun, Sakamoto Koji, Morise Masahiro, Hashimoto Naozumi, Kondoh Yasuhiro, Hasegawa Yoshinori

    ANNALS OF ONCOLOGY  2019.10 

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    Language:English   Presentation type:Poster presentation  

    DOI: 10.1093/annonc/mdz343.108

  37. EVALUATING THE BONE MORPHOGENETIC PROTEIN PATHWAY IN PULMONARY FIBROSIS International conference

    Fukihara J., Maiolo S., Savaglia J., Sakamoto K., Hashimoto N., Hasegawa Y., Reynolds P.

    RESPIROLOGY  2020.6 

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  38. The Critical Role of Meflin-Positive Fibroblasts Against Acute Lung Injury

    Hashimoto N., Sakamoto K., Nakahara Y., Omote N., Ando A., Inoue M., Suzuki A., Fukihara J., Kusaka M., Wakahara K., Enomoto A.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2022.5.1 

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    Language:English   Presentation type:Oral presentation (general)  

  39. Meflin-BMP3b Axis Is a Novel Anti-Fibrotic Pathway Against TGF-beta-Induced Lung Fibrogenesis International conference

    Suzuki A., Sakamoto K., Nakahara Y., Enomoto A., Hino J., Ando A., Inoue M., Omote N., Kusaka M., Fukihara J., Hashimoto N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2022.5.1 

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    Language:English   Presentation type:Symposium, workshop panel (public)  

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Research Project for Joint Research, Competitive Funding, etc. 5

  1. 標的分子Xに対する急性肺傷害治療ペプチドの探索

    2024.10 - 2026.9

    国立研究開発法人日本医療研究開発機構  創薬ブースター(創薬支援ネットワーク) 

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    Authorship:Principal investigator 

  2. 急性肺傷害及び続発性肺線維化を標的とした新規ペプチド薬吸入療法の開発

    2024.4 - 2025.3

    先端研究支援経費 

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    Authorship:Principal investigator  Grant type:Competitive

  3. 呼気に含まれる微粒子解析による革新的非侵襲呼吸器疾患診断技術の検証

    2024.4 - 2025.3

    橋渡し研究プログラム 

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    Grant type:Competitive

  4. 異常上皮細胞から再考した肺線維症の病態形成と二次発癌の機序の解明

    2021.12

    GSK ジャパン  2021年度 GSK ジャパン研究助成 

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    Authorship:Principal investigator  Grant type:Other

    Grant amount:\2000000

  5. 新規内因性抗線維化因子メフリンを用いた肺線維症新規治療開発

    2021.4 - 2023.3

    ベーリンガーインゲルハイム研究助成プログラム 

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    Authorship:Principal investigator  Grant type:Competitive

KAKENHI (Grants-in-Aid for Scientific Research) 7

  1. identification of its origin, cell-fate, and mechanisms of novel antifibrotic cell population in the lung

    Grant number:24K02457  2024.4 - 2027.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\18460000 ( Direct Cost: \14200000 、 Indirect Cost:\4260000 )

  2. Development of an efficient method for direct reprogramming of lung epithelial cells by transcription factors.

    Grant number:24K02113  2024.4 - 2028.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Authorship:Coinvestigator(s)  Grant type:Competitive

  3. 間質性肺炎急性増悪病態における新規病的微小環境因子・ミトコンドリアDNAの役割

    Grant number:21K08202  2021.4 - 2024.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    阪本 考司, 芳川 豊史, 若原 恵子, 橋本 直純, 猪股 弥生

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    特発性肺線維症(IPF)は中高年に発症する進行性難治性の肺疾患である。急性増悪はIPF患者の約4割に突然発症する死亡率の高い合併症であるが、原因が分かっておらず発症の予測や治療法の開発が進んでいない。我々は最近、IPF患者さんの体液中のミトコンドリアDNAの増加が急性増悪の発症を予測しうることを発見した。これにヒントを得た本研究は、急性増悪発症のメカニズムとして肺に存在するマクロファージの異常活性化とミトコンドリアの代謝異常が関与していると仮定して、新たに急性増悪の動物モデルを作成し治療標的と診断法の開発を目指します。

  4. 好塩基球を介した2型炎症調節機構の解明ーアレルギー性・好酸球性肺疾患と肺恒常性

    Grant number:21K08456  2021.4 - 2024.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    若原 恵子, 阪本 考司, 橋本 直純

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    Authorship:Coinvestigator(s) 

    本研究では、2型炎症が創傷治癒と恒常性維持、アレルギー・好酸球性疾患の正・負の両面に関わっていることに注目し、そのコントロールを行っている細胞が好塩基球であるという仮説のもと、好塩基球のフェノタイプ(病原性・非病原性)を探索すること、フェノタイプを調節する因子を探ることを目的としている。特に呼吸器疾患に注目し、肺・気道における好塩基球の役割について検討を行う。

  5. Immune-pathological diagnostic artificial intelligence development research for pulmonary fibrosis using fibrotic foci-specific enhanced micro-CT

    Grant number:20K21599  2020.7 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Exploratory)

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    Authorship:Coinvestigator(s)  Grant type:Competitive

  6. 呼吸器疾患患者に対するリハビリテーション方策(振動刺激療法)の新規開拓

    Grant number:20K10709  2020.4 - 2024.3

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    井上 貴行

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    従来のリハビリテーション(リハ)の主要な方策は運動療法であるが、呼吸器疾患患者には軽労作でも重度の低酸素症状を来す患者や循環動態の不安定な患者など積極的な運動療法が行えない症例が数多く存在するため、運動療法の代替手段の開発が必要となっている。一方、振動刺激(VS)には筋萎縮の抑制や筋力の増大などの効果があることが報告されており、運動療法の代替手段となり得ることが実証されつつある。そこで本研究は、呼吸器疾患患者に対してVSを用いたリハを行うことで、筋萎縮や筋力、体力、日常生活動作、生活の質の低下を予防および抑制、さらには改善する効果が得られるかを網羅的に無作為化比較対照試験により検証する。

  7. 老化関連長鎖ノンコーディングRNAの制御による肺線維症難治性の克服

    Grant number:18K15948  2018.4 - 2022.3

    日本学術振興会  科学研究費助成事業  若手研究

    阪本 考司

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    加齢関連難治肺疾患である肺線維症において、線維化誘導性の細胞老化に陥った線維芽細胞が難治性の病態形成に寄与するとの仮説から、新規の細胞運命決定である長鎖ノンコーディングRNA(lncRNA)に注目し、同病態の線維芽細胞の細胞老化を制御するlncRNA群を同定することで疾患の新たな治療介入標的や疾患のバイオマーカーにすることを目指している。R2年度は以下の研究を進めた。
    lncRNAの発現調節による細胞表現型制御:昨年度に同定したIPF関連lncRNAの一つXを線維芽細胞に形質導入し、向線維化性や細胞老化の表現型を評価したところ、lncRNA-Xの発現回復はIPF由来の老化線維芽細胞においてp16/p21などの老化関連制御因子の発現抑制を誘導することが分かった。さらに、lncRNA-Xの遺伝子欠損マウスを作成し、その肺の表現型を評価した。lncRNA-X欠失細胞の肺組織では老化関連βガラクトシダーゼ染色陽性の老化細胞の増多が認められた。さらにlncRNA-X欠失マウスにブレオマイシンを用いて肺線維症を誘導し、線維化の程度を検討している。
    さらにIPFの病態形成に関わる新たな機能性lncRNA候補を同定したため、予備的な機能解析を開始した。
    また細胞老化により病態形成を媒介するミトコンドリアDNAの肺線維症へ寄与を解析した。ミトコンドリア代謝異常を反映して、IPFの患者由来の血清ではミトコンドリアDNAの濃度が上昇しており、その増多がIPF患者の不良な予後、および急性増悪の発症と相関することを発見した。
    バイオマーカーの検索のための臨床検体収集は、コロナウイルスの蔓延による受診抑制、臨床検体への取り扱いの制限などで遅れている。
    研究計画を一年延長して最終年度は血清からのlncRNA定量検出を進める。マウスモデルについては新たに細胞老化に関わる経路を制御する因子の欠損マウスでの解析を進める。

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Teaching Experience (On-campus) 10

  1. 臓器別臨床講義 呼吸器

    2024

  2. 臓器別臨床講義 呼吸器

    2023

  3. 現代医学入門

    2023

  4. 臓器別臨床講義 呼吸器

    2022

  5. 臓器別臨床講義 呼吸器

    2021

  6. 生涯健康と医学「大気環境と呼吸器疾患」

    2020

  7. 臓器別臨床講義 呼吸器

    2020

  8. 臓器別臨床講義 呼吸器

    2019

  9. 臓器別臨床講義 呼吸器

    2018

  10. 臓器別臨床講義 呼吸器

    2017

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Social Contribution 1

  1. 特発性間質性肺炎~最新の治療と日常生活の注意点について~

    Role(s):Lecturer

    名古屋市瑞穗保健センター  難病講演会  2018.7

Media Coverage 4

  1. The cells combating a deadly lung disease Internet

    American Association for the Advancement of Science (AAAS)  EurekAlert  https://www.eurekalert.org/news-releases/773991  2021.7

  2. ナノ素材による健康被害のメカニズムが明らかに Internet

    名古屋大学 学術研究・産学官連携推進本部  名大研究フロントライン  https://www.youtube.com/watch?v=QKIcuDphFQc&t=1s  2021.7

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    Author:Other 

  3. 人工微粒子、細胞に有害活性酸素 肺の炎症原因に、名古屋大 Internet

    共同通信  地方紙と共同通信のよんななニュース  https://nordot.app/778048216281759744?c=39546741839462401  2021.6

  4. 名古屋大、指定難病「特発性肺線維症」の疾患進行の運命を握る線維芽細胞を世界で初めて同定~特発性肺線維症克服へ向けての新展開~ Internet

    日経バイオテク  https://bio.nikkeibp.co.jp/atcl/release/21/05/31/10796/  2021.5

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    Author:Other