研究者詳細 - 阪本　考司

Fibroblasts positive for meflin have anti-fibrotic properties in pulmonary fibrosis 国際共著国際誌

Nakahara, Y; Hashimoto, N; Sakamoto, K; Enomoto, A; Adams, TS; Yokoi, T; Omote, N; Poli, S; Ando, A; Wakahara, K; Suzuki, A; Inoue, M; Hara, A; Mizutani, Y; Imaizumi, K; Kawabe, T; Rosas, IO; Takahashi, M; Kaminski, N; Hasegawa, Y

EUROPEAN RESPIRATORY JOURNAL 58 巻 ( 6 ) 2021年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：European Respiratory Journal

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 characterized 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 hybridization 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

Metagenomic Analysis of Lung Microbiome in Patients With Interstitial Lung Diseases and Sarcoidosis: An Experimental Study 査読有り

Serum mitochondrial DNA predicts the risk of acute exacerbation and progression of idiopathic pulmonary fibrosis 査読有り国際共著国際誌

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

EUROPEAN RESPIRATORY JOURNAL 57 巻 ( 1 ) 2021年1月

Prognostic Impact and Risk Factors of Immune-Related Pneumonitis in Patients With Non-Small-Cell Lung Cancer Who Received Programmed Death 1 Inhibitors 査読有り国際誌

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

CLINICAL LUNG CANCER 20 巻 ( 6 ) 頁： 442 - + 2019年11月

Prognostic Awareness and Knowledge of Acute Exacerbation in Patients Dying with Interstitial Lung Disease: A Nationwide Survey. 査読有り国際誌

Koyauchi T, Fujisawa T, Miyashita M, Mori M, Morita T, Yazawa S, Akiyama N, Hagimoto S, Matsuda Y, Tachikawa R, Yasui H, Suzuki M, Asai Y, Ono M, Kimura Y, Ohkouchi S, Tanino Y, Sugino K, Tateishi T, Kato M, Miyamoto A, Saito Y, Sakamoto S, Kono M, Yokomura K, Imokawa S, Sakamoto K, Waseda Y, Handa T, Hattori N, Anabuki K, Yatera K, Shundo Y, Hoshino T, Sakamoto N, Kondoh Y, Tomioka H, Tomii K, Inoue Y, Suda T

Annals of the American Thoracic Society 22 巻 ( 3 ) 頁： 395 - 402 2025年3月

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

HEALTH SCIENCE REPORTS 8 巻 ( 2 ) 頁： e70328 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Health Science Reports

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

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 34 巻 ( supplement ) 頁： 87s_2 - 87s_2 2024年10月

Mitochondrial DNA in bronchoalveolar lavage fluid is associated with the prognosis of idiopathic pulmonary fibrosis: a single cohort study 査読有り国際誌

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

RESPIRATORY RESEARCH 25 巻 ( 1 ) 頁： 202 - 202 2024年5月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Respiratory Research

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

Mild elevation of pulmonary vascular resistance predicts mortality regardless of mean pulmonary artery pressure in mild interstitial lung disease 査読有り国際誌

Sato, T; Furukawa, T; Teramachi, R; Fukihara, J; Yamano, Y; Yokoyama, T; Matsuda, T; Kataoka, K; Kimura, T; Sakamoto, K; Ishii, M; Kondoh, Y

THORAX 79 巻 ( 5 ) 頁： 422 - 429 2024年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Thorax

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

Inhalation adherence for asthma and COPD improved during the COVID-19 pandemic: a questionnaire survey at a university hospital in Japan 国際誌

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

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

Respiratory Investigation 62 巻 ( 2 ) 頁： 313 - 316 2024年2月

Cohort study to evaluate prognostic factors in idiopathic pulmonary fibrosis patients introduced to oxygen therapy. 査読有り

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 13 巻 ( 1 ) 頁： 13664 2023年8月

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

JOURNAL OF ASTHMA 頁： 1 - 12 2023年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Asthma

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

Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease triggered by COVID-19: What is the best practice for treatment? 査読有り

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 43 巻頁： 101857 2023年4月

Long-term effect of pulmonary rehabilitation in idiopathic pulmonary fibrosis: a randomised controlled trial. 査読有り国際誌

Kataoka K, Nishiyama O, Ogura T, Mori Y, Kozu R, Arizono S, Tsuda T, Tomioka H, Tomii K, Sakamoto K, Ishimoto H, Kagajo M, Ito H, Ichikado K, Sasano H, Eda S, Arita M, Goto Y, Hataji O, Fuke S, Shintani R, Hasegawa H, Ando M, Ogawa T, Shiraishi M, Watanabe F, Nishimura K, Sasaki T, Miyazaki S, Saka H, Kondoh Y, FITNESS study Collaborators

Thorax 78 巻 ( 8 ) 頁： 784 - 791 2023年4月

Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease triggered by COVID-19: What is the best practice for treatment? 査読有り国際誌

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 REPORTS 43 巻頁： 101857 - 101857 2023年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Respiratory Medicine Case Reports

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

<i>DOCK2</i> is involved in the host genetics and biology of severe COVID-19 国際誌

Namkoong, H; Edahiro, R; Takano, T; Nishihara, H; Shirai, Y; Sonehara, K; Tanaka, H; Azekawa, S; Mikami, Y; Lee, H; Hasegawa, T; Okudela, K; Okuzaki, D; Motooka, D; Kanai, M; Naito, T; Yamamoto, K; Wang, QBS; Saiki, R; Ishihara, R; Matsubara, Y; Hamamoto, J; Hayashi, H; Yoshimura, Y; Tachikawa, N; Yanagita, E; Hyugaji, T; Shimizu, E; Katayama, K; Kato, Y; Morita, T; Takahashi, K; Harada, N; Naito, T; Hiki, M; Matsushita, Y; Takagi, H; Aoki, R; Nakamura, A; Harada, S; Sasano, H; Kabata, H; Masaki, K; Kamata, H; Ikemura, S; Chubachi, S; Okamori, S; Terai, H; Morita, A; Asakura, T; Sasaki, J; Morisaki, H; Uwamino, Y; Nanki, K; Uchida, S; Uno, S; Nishimura, T; Ishiguro, T; Isono, T; Shibata, S; Matsui, Y; Hosoda, C; Takano, K; Nishida, T; Kobayashi, Y; Takaku, Y; Takayanagi, N; Ueda, S; Tada, A; Miyawaki, M; Yamamoto, M; Yoshida, E; Hayashi, R; Nagasaka, T; Arai, S; Kaneko, Y; Sasaki, K; Tagaya, E; Kawana, M; Arimura, K; Takahashi, K; Anzai, T; Ito, S; Endo, A; Uchimura, Y; Miyazaki, Y; Honda, T; Tateishi, T; Tohda, S; Ichimura, N; Sonobe, K; Sassa, CT; Nakajima, J; Nakano, Y; Nakajima, Y; Anan, R; Arai, R; Kurihara, Y; Harada, Y; Nishio, K; Ueda, T; Azuma, M; Saito, R; Sado, T; Miyazaki, Y; Sato, R; Haruta, Y; Nagasaki, T; Yasui, Y; Hasegawa, Y; Mutoh, Y; Kimura, T; Sato, T; Takei, R; Hagimoto, S; Noguchi, Y; Yamano, Y; Sasano, H; Ota, S; Nakamori, Y; Yoshiya, K; Saito, F; Yoshihara, T; Wada, D; Iwamura, H; Kanayama, S; Maruyama, S; Yoshiyama, T; Ohta, K; Kokuto, H; Ogata, H; Tanaka, Y; Arakawa, K; Shimoda, M; Osawa, T; Tateno, H; Hase, I; Yoshida, S; Suzuki, S; Kawada, M; Horinouchi, H; Saito, F; Mitamura, K; Hagihara, M; Ochi, J; Uchida, T; Baba, R; Arai, D; Ogura, T; Takahashi, H; Hagiwara, S; Nagao, G; Konishi, S; Nakachi, I; Murakami, K; Yamada, M; Sugiura, H; Sano, H; Matsumoto, S; Kimura, N; Ono, Y; Baba, H; Suzuki, Y; Nakayama, S; Masuzawa, K; Namba, S; Suzuki, K; Naito, Y; Liu, YC; Takuwa, A; Sugihara, F; Wing, JB; Sakakibara, S; Hizawa, N; Shiroyama, T; Miyawaki, S; Kawamura, Y; Nakayama, A; Matsuo, H; Maeda, Y; Nii, T; Noda, Y; Niitsu, T; Adachi, Y; Enomoto, T; Amiya, S; Hara, R; Yamaguchi, Y; Murakami, T; Kuge, T; Matsumoto, K; Yamamoto, Y; Yamamoto, M; Yoneda, M; Kishikawa, T; Yamada, S; Kawabata, S; Kijima, N; Takagaki, M; Sasa, N; Ueno, Y; Suzuki, M; Takemoto, N; Eguchi, H; Fukusumi, T; Imai, T; Fukushima, M; Kishima, H; Inohara, H; Tomono, K; Kato, K; Takahashi, M; Matsuda, F; Hirata, H; Takeda, Y; Koh, H; Manabe, T; Funatsu, Y; Ito, F; Fukui, T; Shinozuka, K; Kohashi, S; Miyazaki, M; Shoko, T; Kojima, M; Adachi, T; Ishikawa, M; Takahashi, K; Inoue, T; Hirano, T; Kobayashi, K; Takaoka, H; Watanabe, K; Miyazawa, N; Kimura, Y; Sado, R; Sugimoto, H; Kamiya, A; Kuwahara, N; Fujiwara, A; Matsunaga, T; Sato, Y; Okada, T; Hirai, Y; Kawashima, H; Narita, A; Niwa, K; Sekikawa, Y; Nishi, K; Nishitsuji, M; Tani, M; Suzuki, J; Nakatsumi, H; Ogura, T; Kitamura, H; Hagiwara, E; Murohashi, K; Okabayashi, H; Mochimaru, T; Nukaga, S; Satomi, R; Oyamada, Y; Mori, N; Baba, T; Fukui, Y; Odate, M; Mashimo, S; Makino, Y; Yagi, K; Hashiguchi, M; Kagyo, J; Shiomi, T; Fuke, S; Saito, H; Tsuchida, T; Fujitani, S; Takita, M; Morikawa, D; Yoshida, T; Izumo, T; Inomata, M; Kuse, N; Awano, N; Tone, M; Ito, A; Nakamura, Y; Hoshino, K; Maruyama, J; Ishikura, H; Takata, T; Odani, T; Amishima, M; Hattori, T; Shichinohe, Y; Kagaya, T; Kita, T; Ohta, K; Sakagami, S; Koshida, K; Hayashi, K; Shimizu, T; Kozu, Y; Hiranuma, H; Gon, Y; Izumi, N; Nagata, K; Ueda, K; Taki, R; Hanada, S; Kawamura, K; Ichikado, K; Nishiyama, K; Muranaka, H; Nakamura, K; Hashimoto, N; Wakahara, K; Sakamoto, K; Omote, N; Ando, A; Kodama, N; Kaneyama, Y; Maeda, S; Kuraki, T; Matsumoto, T; Yokote, K; Nakada, TA; Abe, R; Oshima, T; Shimada, T; Harada, M; Takahashi, T; Ono, H; Sakurai, T; Shibusawa, T; Kimizuka, Y; Kawana, A; Sano, T; Watanabe, C; Suematsu, R; Sageshima, H; Yoshifuji, A; Ito, K; Takahashi, S; Ishioka, K; Nakamura, M; Masuda, M; Wakabayashi, A; Watanabe, H; Ueda, S; Nishikawa, M; Chihara, Y; Takeuchi, M; Onoi, K; Shinozuka, J; Sueyoshi, A; Nagasaki, Y; Okamoto, M; Ishihara, S; Shimo, M; Tokunaga, Y; Kusaka, Y; Ohba, T; Isogai, S; Ogawa, A; Inoue, T; Fukuyama, S; Eriguchi, Y; Yonekawa, A; Kan-o, K; Matsumoto, K; Kanaoka, K; Ihara, S; Komuta, K; Inoue, Y; Chiba, S; Yamagata, K; Hiramatsu, Y; Kai, H; Asano, K; Oguma, T; Ito, Y; Hashimoto, S; Yamasaki, M; Kasamatsu, Y; Komase, Y; Hida, N; Tsuburai, T; Oyama, B; Takada, M; Kanda, H; Kitagawa, Y; Fukuta, T; Miyake, T; Yoshida, S; Ogura, S; Abe, S; Kono, Y; Togashi, Y; Takoi, H; Kikuchi, R; Ogawa, S; Ogata, T; Ishihara, S; Kanehiro, A; Ozaki, S; Fuchimoto, Y; Wada, S; Fujimoto, N; Nishiyama, K; Terashima, M; Beppu, S; Yoshida, K; Narumoto, O; Nagai, H; Ooshima, N; Motegi, M; Umeda, A; Miyagawa, K; Shimada, H; Endo, M; Ohira, Y; Watanabe, M; Inoue, S; Igarashi, A; Sato, M; Sagara, H; Tanaka, A; Ohta, S; Kimura, T; Shibata, Y; Tanino, Y; Nikaido, T; Minemura, H; Sato, Y; Yamada, Y; Hashino, T; Shinoki, M; Iwagoe, H; Takahashi, H; Fujii, K; Kishi, H; Kanai, M; Imamura, T; Yamashita, T; Yatomi, M; Maeno, T; Hayashi, S; Takahashi, M; Kuramochi, M; Kamimaki, I; Tominaga, Y; Ishii, T; Utsugi, M; Ono, A; Tanaka, T; Kashiwada, T; Fujita, K; Saito, Y; Seike, M; Watanabe, H; Matsuse, H; Kodaka, N; Nakano, C; Oshio, T; Hirouchi, T; Makino, S; Egi, M; Omae, Y; Nannya, Y; Ueno, T; Katayama, K; Ai, M; Fukui, Y; Kumanogoh, A; Sato, T; Hasegawa, N; Tokunaga, K; Ishii, M; Koike, R; Kitagawa, Y; Kimura, A; Imoto, S; Miyano, S; Ogawa, S; Kanai, T; Fukunaga, K; Okada, Y

NATURE 609 巻 ( 7928 ) 頁： 754 - + 2022年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nature

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

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

Furukawa, T; Oyama, S; Yokota, H; Kondoh, Y; Kataoka, K; Johkoh, T; Fukuoka, J; Hashimoto, N; Sakamoto, K; Shiratori, Y; Hasegawa, Y

RESPIROLOGY 27 巻 ( 9 ) 頁： 739 - 746 2022年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Respirology

Background and objective: Idiopathic pulmonary fibrosis (IPF) has poor prognosis, and the multidisciplinary diagnostic agreement is low. Moreover, surgical lung biopsies pose comorbidity risks. Therefore, using data from non-invasive tests usually employed to assess interstitial lung diseases (ILDs), we aimed to develop an automated algorithm combining deep learning and machine learning that would be capable of detecting and differentiating IPF from other ILDs. Methods: We retrospectively analysed consecutive patients presenting with ILD between April 2007 and July 2017. Deep learning was used for semantic image segmentation of HRCT based on the corresponding labelled images. A diagnostic algorithm was then trained using the semantic results and non-invasive findings. Diagnostic accuracy was assessed using five-fold cross-validation. Results: In total, 646,800 HRCT images and the corresponding labelled images were acquired from 1068 patients with ILD, of whom 42.7% had IPF. The average segmentation accuracy was 96.1%. The machine learning algorithm had an average diagnostic accuracy of 83.6%, with high sensitivity, specificity and kappa coefficient values (80.7%, 85.8% and 0.665, respectively). Using Cox hazard analysis, IPF diagnosed using this algorithm was a significant prognostic factor (hazard ratio, 2.593; 95% CI, 2.069–3.250; p < 0.001). Diagnostic accuracy was good even in patients with usual interstitial pneumonia patterns on HRCT and those with surgical lung biopsies. Conclusion: Using data from non-invasive examinations, the combined deep learning and machine learning algorithm accurately, easily and quickly diagnosed IPF in a population with various ILDs.

DOI： 10.1111/resp.14310

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/resp.14310

CINS: Cell Interaction Network inference from Single cell expression data. 査読有り国際共著国際誌

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 18 巻 ( 9 ) 頁： e1010468 2022年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force. 査読有り国際誌

Wang QS, Edahiro R, Namkoong H, Hasegawa T, Shirai Y, Sonehara K, Tanaka H, Lee H, Saiki R, Hyugaji T, Shimizu E, Katayama K, Kanai M, Naito T, Sasa N, Yamamoto K, Kato Y, Morita T, Takahashi K, Harada N, Naito T, Hiki M, Matsushita Y, Takagi H, Ichikawa M, Nakamura A, Harada S, Sandhu Y, Kabata H, Masaki K, Kamata H, Ikemura S, Chubachi S, Okamori S, Terai H, Morita A, Asakura T, Sasaki J, Morisaki H, Uwamino Y, Nanki K, Uchida S, Uno S, Nishimura T, Ishiguro T, Isono T, Shibata S, Matsui Y, Hosoda C, Takano K, Nishida T, Kobayashi Y, Takaku Y, Takayanagi N, Ueda S, Tada A, Miyawaki M, Yamamoto M, Yoshida E, Hayashi R, Nagasaka T, Arai S, Kaneko Y, Sasaki K, Tagaya E, Kawana M, Arimura K, Takahashi K, Anzai T, Ito S, Endo A, Uchimura Y, Miyazaki Y, Honda T, Tateishi T, Tohda S, Ichimura N, Sonobe K, Sassa CT, Nakajima J, Nakano Y, Nakajima Y, Anan R, Arai R, Kurihara Y, Harada Y, Nishio K, Ueda T, Azuma M, Saito R, Sado T, Miyazaki Y, Sato R, Haruta Y, Nagasaki T, Yasui Y, Hasegawa Y, Mutoh Y, Kimura T, Sato T, Takei R, Hagimoto S, Noguchi Y, Yamano Y, Sasano H, Ota S, Nakamori Y, Yoshiya K, Saito F, Yoshihara T, Wada D, Iwamura H, Kanayama S, Maruyama S, Yoshiyama T, Ohta K, Kokuto H, Ogata H, Tanaka Y, Arakawa K, Shimoda M, Osawa T, Tateno H, Hase I, Yoshida S, Suzuki S, Kawada M, Horinouchi H, Saito F, Mitamura K, Hagihara M, Ochi J, Uchida T, Baba R, Arai D, Ogura T, Takahashi H, Hagiwara S, Nagao G, Konishi S, Nakachi I, Murakami K, Yamada M, Sugiura H, Sano H, Matsumoto S, Kimura N, Ono Y, Baba H, Suzuki Y, Nakayama S, Masuzawa K, Namba S, Shiroyama T, Noda Y, Niitsu T, Adachi Y, Enomoto T, Amiya S, Hara R, Yamaguchi Y, Murakami T, Kuge T, Matsumoto K, Yamamoto Y, Yamamoto M, Yoneda M, Tomono K, Kato K, Hirata H, Takeda Y, Koh H, Manabe T, Funatsu Y, Ito F, Fukui T, Shinozuka K, Kohashi S, Miyazaki M, Shoko T, Kojima M, Adachi T, Ishikawa M, Takahashi K, Inoue T, Hirano T, Kobayashi K, Takaoka H, Watanabe K, Miyazawa N, Kimura Y, Sado R, Sugimoto H, Kamiya A, Kuwahara N, Fujiwara A, Matsunaga T, Sato Y, Okada T, Hirai Y, Kawashima H, Narita A, Niwa K, Sekikawa Y, Nishi K, Nishitsuji M, Tani M, Suzuki J, Nakatsumi H, Ogura T, Kitamura H, Hagiwara E, Murohashi K, Okabayashi H, Mochimaru T, Nukaga S, Satomi R, Oyamada Y, Mori N, Baba T, Fukui Y, Odate M, Mashimo S, Makino Y, Yagi K, Hashiguchi M, Kagyo J, Shiomi T, Fuke S, Saito H, Tsuchida T, Fujitani S, Takita M, Morikawa D, Yoshida T, Izumo T, Inomata M, Kuse N, Awano N, Tone M, Ito A, Nakamura Y, Hoshino K, Maruyama J, Ishikura H, Takata T, Odani T, Amishima M, Hattori T, Shichinohe Y, Kagaya T, Kita T, Ohta K, Sakagami S, Koshida K, Hayashi K, Shimizu T, Kozu Y, Hiranuma H, Gon Y, Izumi N, Nagata K, Ueda K, Taki R, Hanada S, Kawamura K, Ichikado K, Nishiyama K, Muranaka H, Nakamura K, Hashimoto N, Wakahara K, Koji S, Omote N, Ando A, Kodama N, Kaneyama Y, Maeda S, Kuraki T, Matsumoto T, Yokote K, Nakada TA, Abe R, Oshima T, Shimada T, Harada M, Takahashi T, Ono H, Sakurai T, Shibusawa T, Kimizuka Y, Kawana A, Sano T, Watanabe C, Suematsu R, Sageshima H, Yoshifuji A, Ito K, Takahashi S, Ishioka K, Nakamura M, Masuda M, Wakabayashi A, Watanabe H, Ueda S, Nishikawa M, Chihara Y, Takeuchi M, Onoi K, Shinozuka J, Sueyoshi A, Nagasaki Y, Okamoto M, Ishihara S, Shimo M, Tokunaga Y, Kusaka Y, Ohba T, Isogai S, Ogawa A, Inoue T, Fukuyama S, Eriguchi Y, Yonekawa A, Kan-O K, Matsumoto K, Kanaoka K, Ihara S, Komuta K, Inoue Y, Chiba S, Yamagata K, Hiramatsu Y, Kai H, Asano K, Oguma T, Ito Y, Hashimoto S, Yamasaki M, Kasamatsu Y, Komase Y, Hida N, Tsuburai T, Oyama B, Takada M, Kanda H, Kitagawa Y, Fukuta T, Miyake T, Yoshida S, Ogura S, Abe S, Kono Y, Togashi Y, Takoi H, Kikuchi R, Ogawa S, Ogata T, Ishihara S, Kanehiro A, Ozaki S, Fuchimoto Y, Wada S, Fujimoto N, Nishiyama K, Terashima M, Beppu S, Yoshida K, Narumoto O, Nagai H, Ooshima N, Motegi M, Umeda A, Miyagawa K, Shimada H, Endo M, Ohira Y, Watanabe M, Inoue S, Igarashi A, Sato M, Sagara H, Tanaka A, Ohta S, Kimura T, Shibata Y, Tanino Y, Nikaido T, Minemura H, Sato Y, Yamada Y, Hashino T, Shinoki M, Iwagoe H, Takahashi H, Fujii K, Kishi H, Kanai M, Imamura T, Yamashita T, Yatomi M, Maeno T, Hayashi S, Takahashi M, Kuramochi M, Kamimaki I, Tominaga Y, Ishii T, Utsugi M, Ono A, Tanaka T, Kashiwada T, Fujita K, Saito Y, Seike M, Watanabe H, Matsuse H, Kodaka N, Nakano C, Oshio T, Hirouchi T, Makino S, Egi M, Omae Y, Nannya Y, Ueno T, Takano T, Katayama K, Ai M, Kumanogoh A, Sato T, Hasegawa N, Tokunaga K, Ishii M, Koike R, Kitagawa Y, Kimura A, Imoto S, Miyano S, Ogawa S, Kanai T, Fukunaga K, Okada Y

Nature communications 13 巻 ( 1 ) 頁： 4830 - 4830 2022年8月

COVID-19-Triggered Acute Exacerbation of IPF, an Underdiagnosed Clinical Entity With Two-Peaked Respiratory Failure: A Case Report and Literature Review 査読有り国際誌

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

FRONTIERS IN MEDICINE 9 巻頁： 815924 2022年2月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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