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

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 41 巻 ( 2 ) 頁： 197 - 201 2022年2月

Overexpression of bone morphogenetic protein receptor type 2 suppresses transforming growth factor beta-induced profibrotic responses in lung fibroblasts 査読有り国際共著国際誌

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

EXPERIMENTAL LUNG RESEARCH 48 巻 ( 1 ) 頁： 35 - 51 2022年1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：Experimental Lung Research

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.

DOI： 10.1080/01902148.2021.2024301

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 61 巻 ( 2 ) 頁： 233 - 236 2022年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：一般社団法人日本内科学会

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.

DOI： 10.2169/internalmedicine.8163-21

Size and surface modification of silica nanoparticles affect the severity of lung toxicity by modulating endosomal ROS generation in macrophages 国際誌

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. 査読有り国際誌

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 160 巻 ( 4 ) 頁： 1372 - 1376 2021年10月

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

PARTICLE AND FIBRE TOXICOLOGY 18 巻 ( 1 ) 頁： 21 - 21 2021年6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：Particle and Fibre Toxicology

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.

DOI： 10.1186/s12989-021-00415-0

Impact of post-capillary pulmonary hypertension on mortality in interstitial lung disease 国際誌

Teramachi, R; Taniguchi, H; Kondoh, Y; Kimura, T; Kataoka, K; Yokoyama, T; Furukawa, T; Yagi, M; Sakamoto, K; Hashimoto, N; Hasegawa, Y

RESPIRATORY INVESTIGATION 59 巻 ( 3 ) 頁： 342 - 349 2021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：Respiratory Investigation

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.

DOI： 10.1016/j.resinv.2020.12.010

The Importance of Appropriate Diagnosis in the Practical Management of Chronic Obstructive Pulmonary Disease 国際誌

Hashimoto Naozumi, Wakahara Keiko, Sakamoto Koji

DIAGNOSTICS 11 巻 ( 4 ) 2021年4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：Diagnostics

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.

DOI： 10.3390/diagnostics11040618

Long noncoding RNA TINCR is a novel regulator of human bronchial epithelial cell differentiation state 査読有り国際共著国際誌

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 9 巻 ( 3 ) 頁： e14727 2021年2月

Supplemental oxygen improves exercise capacity in IPF patients with exertional desaturation 査読有り国際誌

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

RESPIROLOGY 25 巻 ( 11 ) 頁： 1152 - 1159 2020年11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: 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.

DOI： 10.1111/resp.13829

Clinical burden of immune checkpoint inhibitor-induced pneumonitis 査読有り国際誌

Sakamoto Koji, Fukihara Jun, Morise Masahiro, Hashimoto Naozumi

RESPIRATORY INVESTIGATION 58 巻 ( 5 ) 頁： 305 - 319 2020年9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：Respiratory Investigation

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.

DOI： 10.1016/j.resinv.2020.05.008

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 9 巻 ( 増刊 ) 頁： 139 - 139 2020年8月

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年7月

Reply to "Prognostic Impact and Risk Factors of Immune-Related Pneumonitis in Patients With NoneSmall-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 21 巻 ( 3 ) 頁： E205 - E205 2020年5月

Acute exacerbations of fibrotic interstitial lung diseases 査読有り国際誌

Suzuki Atsushi, Kondoh Yasuhiro, Brown Kevin K., Johkoh Takeshi, Kataoka Kensuke, Fukuoka Junya, Kimura Tomoki, Matsuda Toshiaki, Yokoyama Toshiki, Fukihara Jun, Ando Masahiko, Tanaka Tomonori, Hashimoto Naozumi, Sakamoto Koji, Hasegawa Yoshinori

RESPIROLOGY 25 巻 ( 5 ) 頁： 525 - 534 2020年5月

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

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

NAGOYA JOURNAL OF MEDICAL SCIENCE 82 巻 ( 2 ) 頁： 301 - 313 2020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：Nagoya Journal of Medical Science

High-flow nasal cannula (HFNC) oxygen is a therapy that has demonstrated survival benefits in acute respiratory failure (ARF). However, the role of HFNC in ARF due to interstitial pneumonia (IP) is unknown. The aim of this study was to compare the effects of HFNC therapy and non-invasive positive pressure ventilation (NPPV) in ARF due to IP. This retrospective observational study included 32 patients with ARF due to IP who were treated with HFNC (n = 13) or NPPV (n = 19). The clinical characteristics, intubation rate and 30-day mortality were analyzed and compared between the HFNC group and the NPPV group. Predictors of 30-day mortality were evaluated using a logistic regression model. HFNC group showed higher mean arterial blood pressure (median 92 mmHg; HFNC group vs 74 mmHg; NPPV group) and lower APACHEII score (median 22; HFNC group vs 27; NPPV group) than NPPV group. There was no significant difference in the intubation rate at day 30 between the HFNC group and the NPPV group (8% vs 37%: p = 0.069); the mortality rate at 30 days was 23% and 63%, respectively. HFNC therapy was a significant determinant of 30-day mortality in univariate analysis, and was confirmed to be an independent significant determinant of 30-day mortality in multivariate analysis (odds ratio, 0.148; 95% confidence interval, 0.025-0.880; p = 0.036). Our findings suggest that HFNC therapy can be a possible option for respiratory management in ARF due to IP. The results observed here warrant further investigation of HFNC therapy in randomized control trials.

DOI： 10.18999/nagjms.82.2.301

Renewed Japanese spirometric reference variables and risk stratification for postoperative outcomes in COPD patients with resected lung cancer 査読有り国際誌

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

NAGOYA JOURNAL OF MEDICAL SCIENCE 81 巻 ( 3 ) 頁： 427 - 438 2019年8月

Repressive role of stabilized hypoxia inducible factor 1 alpha expression on transforming growth factor beta-induced extracellular matrix production in lung cancer cells 査読有り国際誌

Ando Akira, Hashimoto Naozumi, Sakamoto Koji, Omote Norihito, Miyazaki Shinichi, Nakahara Yoshio, Imaizumi Kazuyoshi, Kawabe Tsutomu, Hasegawa Yoshinori

CANCER SCIENCE 110 巻 ( 6 ) 頁： 1959 - 1973 2019年6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：Cancer Science

Activation of transforming growth factor β (TGF-β) combined with persistent hypoxia often affects the tumor microenvironment. Disruption of cadherin/catenin complexes induced by these stimulations yields aberrant extracellular matrix (ECM) production, characteristics of epithelial-mesenchymal transition (EMT). Hypoxia-inducible factors (HIF), the hallmark of the response to hypoxia, play differential roles during development of diseases. Recent studies show that localization of cadherin/catenin complexes at the cell membrane might be tightly regulated by protein phosphatase activity. We aimed to investigate the role of stabilized HIF-1α expression by protein phosphatase activity on dissociation of the E-cadherin/β-catenin complex and aberrant ECM expression in lung cancer cells under stimulation by TGF-β. By using lung cancer cells treated with HIF-1α stabilizers or carrying doxycycline-dependent HIF-1α deletion or point mutants, we investigated the role of stabilized HIF-1α expression on TGF-β-induced EMT in lung cancer cells. Furthermore, the underlying mechanisms were determined by inhibition of protein phosphatase activity. Persistent stimulation by TGF-β and hypoxia induced EMT phenotypes in H358 cells in which stabilized HIF-1α expression was inhibited. Stabilized HIF-1α protein expression inhibited the TGF-β-stimulated appearance of EMT phenotypes across cell types and species, independent of de novo vascular endothelial growth factor A (VEGFA) expression. Inhibition of protein phosphatase 2A activity abrogated the HIF-1α-induced repression of the TGF-β-stimulated appearance of EMT phenotypes. This is the first study to show a direct role of stabilized HIF-1α expression on inhibition of TGF-β-induced EMT phenotypes in lung cancer cells, in part, through protein phosphatase activity.

DOI： 10.1111/cas.14027

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 査読有り

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 150 巻頁： 15-20 2019年4月

Multidimensional improvement in connective tissue disease-associated interstitial lung disease: Two courses of pulse dose methylprednisolone followed by low-dose prednisone and tacrolimus 査読有り国際誌

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

RESPIROLOGY 23 巻 ( 11 ) 頁： 1041 - 1048 2018年11月

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 143 巻頁： 147-152 2018年10月

Performance of the St George's Respiratory Questionnaire in patients with connective tissue disease-associated interstitial lung disease 査読有り国際誌

Suzuki Atsushi, Kondoh Yasuhiro, Swigris Jeffrey J., Ando Masahiko, Kimura Tomoki, Kataoka Kensuke, Yamano Yasuhiko, Furukawa Taiki, Numata Mari, Sakamoto Koji, Hasegawa Yoshinori

RESPIROLOGY 23 巻 ( 9 ) 頁： 851 - 859 2018年9月

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

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

CLINICAL RESPIRATORY JOURNAL 12 巻 ( 3 ) 頁： 895 - 903 2018年3月

Hashimoto Naozumi, Ando Akira, Iwano Shingo, Sakamoto Koji, Okachi Shotaro, Matsuzaki Asuka, Okada Yu, Wakai Kenji, Yokoi Kohei, Hasegawa Yoshinori

BMC PULMONARY MEDICINE 18 巻 ( 1 ) 頁： 2 2018年1月

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 51 巻 ( 1 ) 2018年1月

Pirfenidone as salvage treatment for refractory bleomycin-induced lung injury: a case report of seminoma 査読有り国際誌

Sakamoto Koji, Ito Satoru, Hashimoto Naozumi, Hasegawa Yoshinori

BMC CANCER 17 巻 ( 1 ) 頁： 526 2017年8月

Aging Impairs Alveolar Macrophage Phagocytosis and Increases Influenza-Induced Mortality in Mice. 査読有り国際誌

Wong CK, Smith CA, Sakamoto K, Kaminski N, Koff JL, Goldstein DR

Journal of immunology (Baltimore, Md. : 1950) 199 巻 ( 3 ) 頁： 1060 - 1068 2017年8月

Modified mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model. 査読有り国際誌

Huleihel L, Sellares J, Cardenes N, Álvarez D, Faner R, Sakamoto K, Yu G, Kapetanaki MG, Kaminski N, Rojas M

American journal of physiology. Lung cellular and molecular physiology 313 巻 ( 1 ) 頁： L92 - L103 2017年7月

Progression of mean pulmonary arterial pressure in idiopathic pulmonary fibrosis with mild to moderate restriction 査読有り国際誌

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

RESPIROLOGY 22 巻 ( 5 ) 頁： 986 - 990 2017年7月

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

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

Respirology (Carlton, Vic.) 22 巻 ( 4 ) 頁： 721-727 2017年5月

Soluble thrombomodulin in bronchoalveolar lavage fluid is an independent predictor of severe drug-induced lung injury 査読有り国際誌

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

RESPIROLOGY 22 巻 ( 4 ) 頁： 744 - 749 2017年5月

Validation of the prognostic value of MMP-7 in idiopathic pulmonary fibrosis. 査読有り国際誌

Tzouvelekis A, Herazo-Maya JD, Slade M, Chu JH, Deiuliis G, Ryu C, Li Q, Sakamoto K, Ibarra G, Pan H, Gulati M, Antin-Ozerkis D, Herzog EL, Kaminski N

Respirology (Carlton, Vic.) 22 巻 ( 3 ) 頁： 486 - 493 2017年4月

Hemosiderin-laden macrophages are an independent factor correlated with pulmonary vascular resistance in idiopathic pulmonary fibrosis: a case control study 査読有り国際誌

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

BMC PULMONARY MEDICINE 17 巻 ( 1 ) 頁： 30 2017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：BMC Pulmonary Medicine

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 16.3mmHg and pulmonary vascular resistance (PVR) of 1.55 Wood units. HLM score was positively correlated with mPAP (ρ=0.204; p=0.038) and PVR (ρ=0.349, p<0.001). In multivariate analysis, 6-min walk distance (standardized partial regression coefficient [β], 0.391; p<0.001), minimum oxygen saturation during 6-min walk distance (β, 0.294; p=0.001) and HLM score (β, 0.265; p=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

SH2 Domain-Containing Phosphatase-2 Is a Novel Antifibrotic Regulator in Pulmonary Fibrosis. 査読有り国際共著国際誌

Tzouvelekis A, Yu G, Lino Cardenas CL, Herazo-Maya JD, Wang R, Woolard T, Zhang Y, Sakamoto K, Lee H, Yi JS, DeIuliis G, Xylourgidis N, Ahangari F, Lee PJ, Aidinis V, Herzog EL, Homer R, Bennett AM, Kaminski N

American journal of respiratory and critical care medicine 195 巻 ( 4 ) 頁： 500 - 514 2017年2月

The St. George's Respiratory Questionnaire as a prognostic factor in IPF 査読有り国際誌

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

RESPIRATORY RESEARCH 18 巻 ( 1 ) 頁： 18 2017年1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：Respiratory Research

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 66years 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%, 580m, 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<.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. Trial registration: This study was retrospective, observational study, so it is not applicable.

DOI： 10.1186/s12931-017-0503-3

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

Exercise hypoxaemia as a predictor of pulmonary hypertension in COPD patients without severe resting hypoxaemia. 査読有り

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

Respirology (Carlton, Vic.) 22 巻 ( 1 ) 頁： 120-125 2017年1月

Exogenous induction of unphosphorylated PTEN reduces TGFβ-induced extracellular matrix expressions in lung fibroblasts. 査読有り

25 巻 ( 1 ) 頁： 86-97 2017年1月

Depression Is Significantly Associated with the Health Status in Patients with Idiopathic Pulmonary Fibrosis. 査読有り

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

Internal medicine (Tokyo, Japan) 56 巻 ( 13 ) 頁： 1637-1644 2017年

Omote, N; Hashimoto, N; Morise, M; Sakamoto, K; Miyazaki, S; Ando, A; Nakahara, Y; Hasegawa, Y

INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE 12 巻頁： 3541 - 3547 2017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：International Journal of COPD

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

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

PULMONARY REHABILITATION IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS: COMPARISON WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE 査読有り

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 34 巻 ( 4 ) 頁： 283 - 289 2017年

Pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis: comparison with chronic obstructive pulmonary disease. 査読有り国際誌

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 34 巻 ( 4 ) 頁： 283 - 289 2017年

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 34 巻 ( 4 ) 頁： 283 - 289 2017年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Sarcoidosis Vasculitis and Diffuse Lung Diseases

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.