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1. Increased levels of circulating cell-free DNA in COVID-19 patients with respiratory failure

Author: Akihiko Tanaka, Katsuki Wakayama, Yosuke Fukuda, Shin Ohta, Tetsuya Homma, Koichi Ando, Yuji Nishihara, Ryuichi Nakano, Jing Zhao, Yuki Suzuki, Yoji Kyotani, Hisakazu Yano, Kei Kasahara, Kuei-Pin Chung, Hironori Sagara, Masanori Yoshizumi, and Kiichi Nakahira
Subjects: Medicine, Science
Abstract: Abstract Cell-free DNA (cfDNA) is released from injured cells and aggravates inflammation. Patients with coronavirus disease (COVID-19) often develop pneumonia and respiratory failure, and require oxygen therapy (OT), including mechanical ventilation (MV). It remains unclear whether cfDNA predicts the risk of receiving OT or MV in COVID-19 patients. Therefore, we hypothesized that circulating cfDNA levels could reflect the severity of respiratory failure and determine a therapeutic approach for oxygenation in patients with COVID-19. We analyzed cfDNA levels in serum samples from 95 hospitalized patients with COVID-19 at Showa University Hospital (Tokyo, Japan). cfDNA levels were assessed by measuring the copy numbers of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) using quantitative real-time PCR (qPCR). Both cf-nDNA and cf-mtDNA levels were negatively correlated with adjusted SpO2 for FiO2 (SpO2/FiO2 ratio). Elevated cf-nDNA and cf-mtDNA levels were associated with the requirement for OT or MV during patient admission. Multivariate logistic regression analysis revealed that cf-nDNA and cf-mtDNA levels were independent risk factors for OT and MV. These results suggest that both serum cf-nDNA and cf-mtDNA could serve as useful early biomarkers to indicate the necessity of OT or MV in patients with COVID-19.
Published: 2024
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2. Fetal Lung Cells Transfer Improves Emphysematous Change in a Mouse Model of Neutrophil Elastase-Induced Lung Emphysema

Author: Shin Ohta, Akihiko Tanaka, Tomoko Okazaki, Hatsuko Mikuni, Tomoki Uno, Yoshitaka Uchida, Tomoyuki Kimura, Yosuke Fukuda, Megumi Jinno, Kuniaki Hirai, Yoshito Miyata, Hideki Inoue, Tetsuya Homma, Mayumi Yamamoto, Shintaro Suzuki, and Hironori Sagara
Subjects: lung emphysema, mouse model, neutrophil elastase, fetal lung cell, regeneration, Biology (General), QH301-705.5
Abstract: Recently, several studies for lung regeneration have been reported. However, regenerating the lung tissue by the transfer of any cells directly to the lung has been hardly successful. The aim of this study was to evaluate the effect of fetal lung cells (FLCs) in a mouse model of lung emphysema. C57BL/6 mice were stimulated with neutrophil elastase (NE) intra-tracheally (i.t.) to generate lung emphysema. To collect fetal lung cells, C57BL/6-Tg (CAG-EGFP) mice were bred for 14 days. Before delivery, the bred mice were euthanized, and fetal lungs were harvested from the fetal mice and the cells were collected. The FLCs were transferred i.t. 24 h after the NE instillation. Four weeks after the NE instillation, mice were euthanized, and the samples were collected. The mean linear intercept (MLI) was significantly prolonged in the NE instillation group compared to the control group. However, in the FLCs transfer group stimulated with NE, the MLI became shorter than the NE-stimulated group without an FLCs transfer. This result shows that an FLCs transfer inhibited the progression of lung emphysema. Additionally, motility of the mice was also improved by the FLCs transfer. These results indicate that transfer of the FLCs, which were presumed to be progenitor cells for lung tissue, may improve the emphysematous change.
Published: 2022
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3. The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

Author: Qingbo S. Wang, Ryuya Edahiro, Ho Namkoong, Takanori Hasegawa, Yuya Shirai, Kyuto Sonehara, Hiromu Tanaka, Ho Lee, Ryunosuke Saiki, Takayoshi Hyugaji, Eigo Shimizu, Kotoe Katayama, Masahiro Kanai, Tatsuhiko Naito, Noah Sasa, Kenichi Yamamoto, Yasuhiro Kato, Takayoshi Morita, Kazuhisa Takahashi, Norihiro Harada, Toshio Naito, Makoto Hiki, Yasushi Matsushita, Haruhi Takagi, Masako Ichikawa, Ai Nakamura, Sonoko Harada, Yuuki Sandhu, Hiroki Kabata, Katsunori Masaki, Hirofumi Kamata, Shinnosuke Ikemura, Shotaro Chubachi, Satoshi Okamori, Hideki Terai, Atsuho Morita, Takanori Asakura, Junichi Sasaki, Hiroshi Morisaki, Yoshifumi Uwamino, Kosaku Nanki, Sho Uchida, Shunsuke Uno, Tomoyasu Nishimura, Takashri Ishiguro, Taisuke Isono, Shun Shibata, Yuma Matsui, Chiaki Hosoda, Kenji Takano, Takashi Nishida, Yoichi Kobayashi, Yotaro Takaku, Noboru Takayanagi, Soichiro Ueda, Ai Tada, Masayoshi Miyawaki, Masaomi Yamamoto, Eriko Yoshida, Reina Hayashi, Tomoki Nagasaka, Sawako Arai, Yutaro Kaneko, Kana Sasaki, Etsuko Tagaya, Masatoshi Kawana, Ken Arimura, Kunihiko Takahashi, Tatsuhiko Anzai, Satoshi Ito, Akifumi Endo, Yuji Uchimura, Yasunari Miyazaki, Takayuki Honda, Tomoya Tateishi, Shuji Tohda, Naoya Ichimura, Kazunari Sonobe, Chihiro Tani Sassa, Jun Nakajima, Yasushi Nakano, Yukiko Nakajima, Ryusuke Anan, Ryosuke Arai, Yuko Kurihara, Yuko Harada, Kazumi Nishio, Tetsuya Ueda, Masanori Azuma, Ryuichi Saito, Toshikatsu Sado, Yoshimune Miyazaki, Ryuichi Sato, Yuki Haruta, Tadao Nagasaki, Yoshinori Yasui, Yoshinori Hasegawa, Yoshikazu Mutoh, Tomoki Kimura, Tomonori Sato, Reoto Takei, Satoshi Hagimoto, Yoichiro Noguchi, Yasuhiko Yamano, Hajime Sasano, Sho Ota, Yasushi Nakamori, Kazuhisa Yoshiya, Fukuki Saito, Tomoyuki Yoshihara, Daiki Wada, Hiromu Iwamura, Syuji Kanayama, Shuhei Maruyama, Takashi Yoshiyama, Ken Ohta, Hiroyuki Kokuto, Hideo Ogata, Yoshiaki Tanaka, Kenichi Arakawa, Masafumi Shimoda, Takeshi Osawa, Hiroki Tateno, Isano Hase, Shuichi Yoshida, Shoji Suzuki, Miki Kawada, Hirohisa Horinouchi, Fumitake Saito, Keiko Mitamura, Masao Hagihara, Junichi Ochi, Tomoyuki Uchida, Rie Baba, Daisuke Arai, Takayuki Ogura, Hidenori Takahashi, Shigehiro Hagiwara, Genta Nagao, Shunichiro Konishi, Ichiro Nakachi, Koji Murakami, Mitsuhiro Yamada, Hisatoshi Sugiura, Hirohito Sano, Shuichiro Matsumoto, Nozomu Kimura, Yoshinao Ono, Hiroaki Baba, Yusuke Suzuki, Sohei Nakayama, Keita Masuzawa, Shinichi Namba, Takayuki Shiroyama, Yoshimi Noda, Takayuki Niitsu, Yuichi Adachi, Takatoshi Enomoto, Saori Amiya, Reina Hara, Yuta Yamaguchi, Teruaki Murakami, Tomoki Kuge, Kinnosuke Matsumoto, Yuji Yamamoto, Makoto Yamamoto, Midori Yoneda, Kazunori Tomono, Kazuto Kato, Haruhiko Hirata, Yoshito Takeda, Hidefumi Koh, Tadashi Manabe, Yohei Funatsu, Fumimaro Ito, Takahiro Fukui, Keisuke Shinozuka, Sumiko Kohashi, Masatoshi Miyazaki, Tomohisa Shoko, Mitsuaki Kojima, Tomohiro Adachi, Motonao Ishikawa, Kenichiro Takahashi, Takashi Inoue, Toshiyuki Hirano, Keigo Kobayashi, Hatsuyo Takaoka, Kazuyoshi Watanabe, Naoki Miyazawa, Yasuhiro Kimura, Reiko Sado, Hideyasu Sugimoto, Akane Kamiya, Naota Kuwahara, Akiko Fujiwara, Tomohiro Matsunaga, Yoko Sato, Takenori Okada, Yoshihiro Hirai, Hidetoshi Kawashima, Atsuya Narita, Kazuki Niwa, Yoshiyuki Sekikawa, Koichi Nishi, Masaru Nishitsuji, Mayuko Tani, Junya Suzuki, Hiroki Nakatsumi, Takashi Ogura, Hideya Kitamura, Eri Hagiwara, Kota Murohashi, Hiroko Okabayashi, Takao Mochimaru, Shigenari Nukaga, Ryosuke Satomi, Yoshitaka Oyamada, Nobuaki Mori, Tomoya Baba, Yasutaka Fukui, Mitsuru Odate, Shuko Mashimo, Yasushi Makino, Kazuma Yagi, Mizuha Hashiguchi, Junko Kagyo, Tetsuya Shiomi, Satoshi Fuke, Hiroshi Saito, Tomoya Tsuchida, Shigeki Fujitani, Mumon Takita, Daiki Morikawa, Toru Yoshida, Takehiro Izumo, Minoru Inomata, Naoyuki Kuse, Nobuyasu Awano, Mari Tone, Akihiro Ito, Yoshihiko Nakamura, Kota Hoshino, Junichi Maruyama, Hiroyasu Ishikura, Tohru Takata, Toshio Odani, Masaru Amishima, Takeshi Hattori, Yasuo Shichinohe, Takashi Kagaya, Toshiyuki Kita, Kazuhide Ohta, Satoru Sakagami, Kiyoshi Koshida, Kentaro Hayashi, Tetsuo Shimizu, Yutaka Kozu, Hisato Hiranuma, Yasuhiro Gon, Namiki Izumi, Kaoru Nagata, Ken Ueda, Reiko Taki, Satoko Hanada, Kodai Kawamura, Kazuya Ichikado, Kenta Nishiyama, Hiroyuki Muranaka, Kazunori Nakamura, Naozumi Hashimoto, Keiko Wakahara, Sakamoto Koji, Norihito Omote, Akira Ando, Nobuhiro Kodama, Yasunari Kaneyama, Shunsuke Maeda, Takashige Kuraki, Takemasa Matsumoto, Koutaro Yokote, Taka-Aki Nakada, Ryuzo Abe, Taku Oshima, Tadanaga Shimada, Masahiro Harada, Takeshi Takahashi, Hiroshi Ono, Toshihiro Sakurai, Takayuki Shibusawa, Yoshifumi Kimizuka, Akihiko Kawana, Tomoya Sano, Chie Watanabe, Ryohei Suematsu, Hisako Sageshima, Ayumi Yoshifuji, Kazuto Ito, Saeko Takahashi, Kota Ishioka, Morio Nakamura, Makoto Masuda, Aya Wakabayashi, Hiroki Watanabe, Suguru Ueda, Masanori Nishikawa, Yusuke Chihara, Mayumi Takeuchi, Keisuke Onoi, Jun Shinozuka, Atsushi Sueyoshi, Yoji Nagasaki, Masaki Okamoto, Sayoko Ishihara, Masatoshi Shimo, Yoshihisa Tokunaga, Yu Kusaka, Takehiko Ohba, Susumu Isogai, Aki Ogawa, Takuya Inoue, Satoru Fukuyama, Yoshihiro Eriguchi, Akiko Yonekawa, Keiko Kan-o, Koichiro Matsumoto, Kensuke Kanaoka, Shoichi Ihara, Kiyoshi Komuta, Yoshiaki Inoue, Shigeru Chiba, Kunihiro Yamagata, Yuji Hiramatsu, Hirayasu Kai, Koichiro Asano, Tsuyoshi Oguma, Yoko Ito, Satoru Hashimoto, Masaki Yamasaki, Yu Kasamatsu, Yuko Komase, Naoya Hida, Takahiro Tsuburai, Baku Oyama, Minoru Takada, Hidenori Kanda, Yuichiro Kitagawa, Tetsuya Fukuta, Takahito Miyake, Shozo Yoshida, Shinji Ogura, Shinji Abe, Yuta Kono, Yuki Togashi, Hiroyuki Takoi, Ryota Kikuchi, Shinichi Ogawa, Tomouki Ogata, Shoichiro Ishihara, Arihiko Kanehiro, Shinji Ozaki, Yasuko Fuchimoto, Sae Wada, Nobukazu Fujimoto, Kei Nishiyama, Mariko Terashima, Satoru Beppu, Kosuke Yoshida, Osamu Narumoto, Hideaki Nagai, Nobuharu Ooshima, Mitsuru Motegi, Akira Umeda, Kazuya Miyagawa, Hisato Shimada, Mayu Endo, Yoshiyuki Ohira, Masafumi Watanabe, Sumito Inoue, Akira Igarashi, Masamichi Sato, Hironori Sagara, Akihiko Tanaka, Shin Ohta, Tomoyuki Kimura, Yoko Shibata, Yoshinori Tanino, Takefumi Nikaido, Hiroyuki Minemura, Yuki Sato, Yuichiro Yamada, Takuya Hashino, Masato Shinoki, Hajime Iwagoe, Hiroshi Takahashi, Kazuhiko Fujii, Hiroto Kishi, Masayuki Kanai, Tomonori Imamura, Tatsuya Yamashita, Masakiyo Yatomi, Toshitaka Maeno, Shinichi Hayashi, Mai Takahashi, Mizuki Kuramochi, Isamu Kamimaki, Yoshiteru Tominaga, Tomoo Ishii, Mitsuyoshi Utsugi, Akihiro Ono, Toru Tanaka, Takeru Kashiwada, Kazue Fujita, Yoshinobu Saito, Masahiro Seike, Hiroko Watanabe, Hiroto Matsuse, Norio Kodaka, Chihiro Nakano, Takeshi Oshio, Takatomo Hirouchi, Shohei Makino, Moritoki Egi, Yosuke Omae, Yasuhito Nannya, Takafumi Ueno, Tomomi Takano, Kazuhiko Katayama, Masumi Ai, Atsushi Kumanogoh, Toshiro Sato, Naoki Hasegawa, Katsushi Tokunaga, Makoto Ishii, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga, and Yukinori Okada
Subjects: Science
Abstract: Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.
Published: 2022
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4. Characteristics of and reasons for patients with chronic obstructive pulmonary disease to continue smoking, quit smoking, and switch to heated tobacco products

Author: Kuniaki Hirai, Akihiko Tanaka, Tetsuya Homma, Tomoko Kawahara, Naruhito Oda, Hatsuko Mikuni, Yoshitaka Uchida, Haruhisa Saito, Yosuke Fukuda, Akiko Fujiwara, Yoko Sato, Tomoki Uno, Hideki Inoue, Shin Ohta, Fumihiro Yamaguchi, Shintaro Suzuki, Tsukasa Ohnishi, and Hironori Sagara
Subjects: chronic obstructive pulmonary disease, cigarettes, smoking, heated tobacco products, Diseases of the respiratory system, RC705-779, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Introduction Smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and smoking cessation is the most effective treatment for patients with COPD. However, few studies have investigated the continuation/cessation of smoking and heated tobacco products (HTP) in patients with COPD. The objective of this study was to examine the characteristics of patients with COPD, those who are current smokers and those who switched from cigarettes to HTP, and to examine the reason for the continuation or cessation of smoking. Methods This multicenter, cross-sectional study included 411 outpatients with COPD. Data for this study were part of a study conducted for a comprehensive evaluation of the smoking status and clinical factors in patients with COPD and their families. Results Logistic regression analysis revealed that a younger age, longer duration of smoking, fewer daily cigarettes, and lower modified Medical Research Council (mMRC) dyspnea score, and a lower Simplified Nutritional Appetite Questionnaire (SNAQ) score for appetite, were characteristics of current smokers (age OR=0.94; duration of smoking OR=1.07; number of cigarettes per day OR=0.94; mMRC OR=0.68; SNAQ OR=0.83; p
Published: 2021
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5. Clinical features and mechanism of liver injury in patients with mild or moderate coronavirus disease 2019

Author: Kuniyo Gomi, Takayoshi Ito, Fumihiro Yamaguchi, Yoshito Kamio, Yoshinori Sato, Hiroyoshi Mori, Kei Endo, Takashi Abe, Shunsuke Sakakura, Kouji Kobayashi, Ken Shimada, Jun Noda, Tarou Hibiki, Shin Ohta, Hironori Sagara, Akihiko Tanaka, Megumi Jinno, Masataka Yamawaki, Fumiya Nishimoto, Kazuaki Inoue, and Masatsugu Nagahama
Subjects: coronavirus disease 2019, liver injury, liver‐infiltrating lymphocytes, severe acute respiratory syndrome coronavirus 2, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Abstract Background and Aim We aimed to identify clinical features that suggest that coronavirus disease 2019 (COVID‐19) should be a differential diagnosis in patients presenting with a chief complaint of fever and abnormal liver function. Methods We retrospectively studied the presence or absence of abnormal liver function in 216 patients diagnosed with mild–moderate severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection between February and September 2020. Results Abnormal liver function was observed in 51 patients with mild–moderate COVID‐19. The median peak aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were 57.5, 75.5, and 332.5 U/L, respectively. The median number of days from symptom onset to peak AST, ALT, and LDH were 8.5, 9, and 8.5, respectively. The median peak LDH/AST ratio was 9.0. Low lymphocyte‐to‐white blood cell ratio and elevated LDH were found to be independent contributing factors for intensive care unit (ICU) admission on a multivariate analysis. Conclusions AST‐predominant AST/ALT/LDH elevation peaking 8–9 days after symptom onset and not accompanied by elevated alkaline phosphatase or gamma‐glutamyl transferase may be a useful clinical feature for differentiating COVID‐19 from other diseases. Since the median LDH/AST ratio was 9.0, it seems that the abnormal liver function caused by SARS‐CoV‐2 is an indirect damage to liver cells due to elevated cytokine levels caused by liver‐infiltrating lymphocytes. SARS‐CoV‐2 infection should be considered in patients presenting with a chief complaint of fever and liver injury; those with a high lymphocyte‐to‐white blood cell ratio or and a high LDH/AST ratio may be admitted to the ICU.
Published: 2021
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6. Evaluating the effect of aromatherapy on a stress marker in healthy subjects

Author: Chiaki Takagi, Saori Nakagawa, Naoto Hirata, Shin Ohta, and Sadahiko Shimoeda
Subjects: Aromatherapy, Stress, Complementary and alternative medicine, Secretory immunoglobulin A, Noradrenaline, Therapeutics. Pharmacology, RM1-950, Pharmacy and materia medica, RS1-441
Abstract: Abstract Background/purpose Chemotherapy is important for cancer treatment, but patients’ physical and mental stress may lead to unfavorable pain control, an increase in the risk of relapse, and a reduction in the quality of life (QOL). Recently, aromatherapy has been performed in addition to palliative care in many countries, such as Japan and the United States, but scientific evidence remains insufficient. To investigate the usefulness of aromatherapy as complementary and alternative medicine, we evaluated its influence on the immune and autonomic nervous systems. Methods We instructed healthy volunteers to inhale aroma oil at bedtime for 6 weeks, and measured changes in the salivary level of secretory immunoglobulin A (s-IgA). Furthermore, blood was collected in addition to saliva in some healthy volunteers, and the blood level of noradrenaline (NA) was measured to examine its relationship to changes in the salivary s-IgA level. Results Aromatherapy with lavender and grapefruit oils significantly increased the salivary s-IgA level: lavender oil increased 3.5-fold (p = 0.03), and grapefruit oil increased 2.55-fold (p = 0.04). On lavender oil inhalation, there was a weak, positive correlation between changes in the salivary s-IgA level and those in the blood NA level (R2 = 0.24). Conclusion The results showed that aromatherapy with lavender and grapefruit oils reduced stress by acting on the immune and autonomic nervous systems in healthy volunteers. In the future, its clinical usefulness must be investigated through similar examination in patients in whom the stress level may be high.
Published: 2019
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7. Combination treatment of short-course systemic corticosteroid and favipiravir in a successfully treated case of critically ill COVID-19 pneumonia with COPD

Author: Hideki Inoue, Megumi Jinno, Shin Ohta, Yasunari Kishino, Tomoko Kawahara, Hatsuko Mikuni, Haruna Sato, Mayumi Yamamoto, Yoko Sato, Chisato Onitsuka, Yuiko Goto, Hitoshi Ikeda, Hiroki Sato, Tomoki Uno, Yoshitaka Uchida, Tomoyuki Kimura, Yoshito Miyata, Kuniaki Hirai, Tetsuya Homma, Yoshio Watanabe, Sojiro Kusumoto, Shintaro Suzuki, Issei Tokimatsu, Akihiko Tanaka, and Hironori Sagara
Subjects: COVID-19, SARS-CoV-2, COPD, Favipiravir, Systemic corticosteroid, Pneumonia, Diseases of the respiratory system, RC705-779
Abstract: Use of systemic corticosteroids for the treatment for coronavirus disease 2019 (COVID-19) among chronic obstructive pulmonary disease (COPD) patients is not well described. A 58-year-old man with fever and progressive dyspnea was admitted to the Showa University Hospital, and showed severe respiratory failure which needed mechanical ventilation. His chest computed tomography scanning showed emphysema and bilateral ground-glass opacity caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. He received 30 mg prednisolone for five days with antiviral drug of favipiravir, and was successfully extubated on day five. A SARS-CoV-2 polymerase chain reaction (PCR) test became negative on day 15. He was discharged on day 21. Serum IgM and IgG antibodies against SARS-CoV-2 converted to positive on day 7 and they kept positive on day 54 for both IgM and IgG. Combination treatment of short-course systemic corticosteroid and favipiravir might improve the prognosis for critically ill COVID-19 pneumonia with COPD without negative influence on viral clearance or antibody production.
Published: 2020
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8. Predicting future risk of exacerbations in Japanese patients with adult asthma: A prospective 1-year follow up study

Author: Akihiko Tanaka, Tomoki Uno, Haruna Sato, Megumi Jinno, Kuniaki Hirai, Yoshito Miyata, Munehiro Yamaguchi, Shin Ohta, Tetsuya Homma, Mayumi Yamamoto, Shintaro Suzuki, Takuya Yokoe, and Hironori Sagara
Subjects: Asthma control, Exacerbation, FeNO, Future risk, Pulmonary function test, Immunologic diseases. Allergy, RC581-607
Abstract: Background: To avoid future risk is a definitive goal of long-term asthma management. Exacerbations are considered to be the most relevant future risk in real life asthma management. Few comparative studies have evaluated the risk factors associated with exacerbations in Japanese patients with asthma. Methods: We performed the prospective 1-year follow up study in Japanese patients with adult asthma. A total of 189 patients with asthma were enrolled and followed up for 1 year. Finally, 181 patients completed the study protocol. Results: Of 181 patients, 43 patients (23.8%) had exacerbations during the follow-up period. Among the 45 patients who had exacerbations during the preceding year, 32 patients (71.1%) had exacerbations. Prevalence of patients with previous exacerbations and those with previous admissions were significantly higher in patients with exacerbations than those with no exacerbation. Logistic regression analysis also identified a significant association between exacerbations during the follow-up period and exacerbations during the preceding year, admissions during the preceding 3 years, ACT score below 20, low %FVC (
Published: 2017
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9. Prevalence and clinical features of asthma-COPD overlap in patients with COPD not using inhaled corticosteroids

Author: Kuniaki Hirai, Akihiko Tanaka, Tetsuya Homma, Tomoko Kawahara, Naruhito Oda, Hatsuko Mikuni, Yoshitaka Uchida, Tomoki Uno, Yoshito Miyata, Hideki Inoue, Shin Ohta, Fumihiro Yamaguchi, Shintaro Suzuki, and Hironori Sagara
Subjects: Immunologic diseases. Allergy, RC581-607
Published: 2021
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10. Roles of Early Mobilization Program in Preventing Muscle Weakness and Decreasing Psychiatric Disorders in Patients with Coronavirus Disease 2019 Pneumonia: A Retrospective Observational Cohort Study

Author: Toru Kotani, Mizuki Sugiyama, Fumika Matsuzaki, Kota Kubodera, Jin Saito, Mika Kaneki, Atsuko Shono, Hiroko Maruo, Maiko Mori, Shin Ohta, and Fumihito Kasai
Subjects: postintensive care syndrome, coronavirus disease 2019, acute respiratory failure, Medicine
Abstract: Although many coronavirus 2019 patients have experienced persistent symptoms and a long-term decline in quality of life after discharge, the details of these persistent symptoms and the effect of early rehabilitation are still unclear. We conducted a single-center, retrospective observational study to investigate the prevalence of persistent symptoms three months after discharge from the intensive care unit by checking the medical records. All patients received an early mobilization program. Four out of 13 patients (31%) had postintensive care syndrome. No patients had muscle weakness, and 11 patients (85%) returned to their previous work. However, psychiatric disorder, such as anxiety (23%) and posttraumatic stress disorder (15%), were observed. Eleven patients claimed persistent symptoms, including fatigue and numbness in the extremities. Our results suggest that the implementation of an early rehabilitation program plays some role in preventing muscle weakness and that decreasing psychiatric disorders should be a next target of patient care in the intensive care unit.
Published: 2021
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11. Correlation of Arterial CO2 and Respiratory Impedance Values among Subjects with COPD

Author: Tomoki Uno, Tetsuya Homma, Masahiko Shigemura, Yosuke Fukuda, Tomoyuki Kimura, Chihiro Onitsuka, Tomoko Kawahara, Hiroki Sato, Kaho Akimoto, Hiromitsu Suganuma, Ayaka Kashima, Shigenori Yamamoto, Takaya Ebato, Tomohiro Matsunaga, Keisuke Kaneko, Hatsuko Mikuni, Haruna Sato, Yoshitaka Uchida, Akiko Fujiwara, Naota Kuwahara, Ryo Manabe, Hitomi Ida, Kuniaki Hirai, Yoshito Miyata, Megumi Jinno, Shin Ohta, Yasunari Kishino, Hideki Inoue, Mayumi Yamamoto, Yoshio Watanabe, Sojiro Kusumoto, Koichi Ando, Shintaro Suzuki, Akihiko Tanaka, Tohru Ohmori, and Hironori Sagara
Subjects: CO2, hypercapnia, FOT, Medicine
Abstract: Chronic obstructive pulmonary disease (COPD) is a respiratory illness characterized by airflow limitation and chronic respiratory symptoms with a global prevalence estimated to be more than 10% in 2010 and still on the rise. Furthermore, hypercapnic subject COPD leads to an increased risk of mortality, morbidity, and poor QoL (quality of life) than normocapnic subjects. Series of studies showed the usefulness of the forced oscillation technique (FOT) to measure small airway closure. Traditional findings suggested that hypercapnia may not be the main treating targets, but recent findings suggested that blood stream CO2 may lead to a worse outcome. This study aimed to seek the relationship between CO2 and small airway closure by using FOT. Subjects with COPD (n = 124; hypercapnia 22 and normocapnia 102) were analyzed for all pulmonary function values, FOT values, and arterial blood gas analysis. Student’s t-test, Spearman rank correlation, and multi linear regression analysis were used to analyze the data. COPD subjects with hypercapnia showed a significant increase in R5, R20, Fres, and ALX values, and a greater decrease in X5 value than normocapnic patients. Also, multiple linear regression analysis showed R5 was associated with hypercapnia. Hypercapnia may account for airway closure among subjects with COPD and this result suggests treating hypercapnia may lead to better outcomes for such a subject group.
Published: 2020
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12. Inhibition of Virus-Induced Cytokine Production from Airway Epithelial Cells by the Late Addition of Budesonide

Author: Tetsuya Homma, Yosuke Fukuda, Yoshitaka Uchida, Tomoki Uno, Megumi Jinno, Yasunari Kishino, Mayumi Yamamoto, Hiroki Sato, Kaho Akimoto, Keisuke Kaneko, Akiko Fujiwara, Haruna Sato, Kuniaki Hirai, Yoshito Miyata, Hideki Inoue, Shin Ohta, Yoshio Watanabe, Sojiro Kusumoto, Koichi Ando, Shintaro Suzuki, Toshimitsu Yamaoka, Akihiko Tanaka, Tohru Ohmori, and Hironori Sagara
Subjects: budesonide, thymic stromal lymphopoietin (tslp), rhinovirus, epithelial cells, Medicine (General), R5-920
Abstract: Background: Viral infection is the main cause of asthma and COPD (chronic obstructive pulmonary disease) exacerbation and accumulate inflammatory cells to airway tissue. We have reported poly I:C, a mimic product of the virus and ligand of toll-like receptor 3 (TLR3), induced inflammatory chemokines from airway epithelial cells and found prior incubation with corticosteroids diminishes the effect of TLR3 activation. In clinical practice, mild asthma is recommended as-needed budesonide (BUD) when symptoms occur following a viral infection, etc. However, many questions still surround BUD’s usefulness if taken after a virus has already infected airway tissue. Objective: The aim of this study was to investigate the inhibitory effects of BUD on inflammatory cytokines induced by viral infection. Methods: Normal human bronchial epithelial (NHBE) cells were stimulated with poly I:C or infected with human rhinovirus-16 (HRV16) and BUD was added after the initial stimulation. Expression of both thymic stromal lymphopoietin (TSLP) and CCL26/eotaxin-3 was quantified by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Knockdown study was performed. Results: Pre-or post-incubation with BUD inhibited both poly I:C- and HRV16-induced mRNAs and proteins of both thymic stromal lymphopoietin (TSLP) and CCL26 with significance. Knockdown of the glucocorticoid receptor diminished these effects of BUD. Under the same conditions of BUD’s experiment, post-incubation with neither fluticasone propionate nor dexamethasone suppressed expression of both TSLP and CCL26, which induced by poly I:C. Conclusion: Post-addition of BUD inhibited the virus-induced TSLP and CCL26 from the airway epithelial cells. These results suggest that inhalation of BUD after viral infection has beneficial effects on asthma. Conclusion: Late addition of BUD may benefit among patient with viral infection and type 2 allergic airway disease such as asthma.
Published: 2020
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13. A Model of Left Ventricular Dysfunction Complicated by CAWS Arteritis in DBA/2 Mice

Author: Naoto Hirata, Ken-ichi Ishibashi, Tatsuya Usui, Jiro Yoshioka, Satoru Hata, Yoshiyuki Adachi, Noriko Nagi-Miura, Shin Ohta, and Naohito Ohno
Subjects: Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: It was reported previously that a Candida albicans water-soluble fraction (CAWS), including a mannoprotein and β-glucan complex, has strong potency in inducing fatal necrotizing arteritis in DBA/2 mice. In this study, histopathological changes and cardiac function were investigated in this system. One mg/day of CAWS was given to DBA/2 mice via peritoneal injection for five days. The CAWS-treated DBA/2 mice were induced aortitis and died at an incidence of 100% within several weeks. Histological findings included stenosis in the left ventricular outflow tract (LVOT) and severe inflammatory changes of the aortic valve with fibrinoid necrosis. Cardiomegaly was observed and heart weight increased 1.62 fold (𝑃
Published: 2012
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14. Long-term follow-up of production of IgM and IgG antibodies against SARS-CoV-2 among patients with COVID-19

Author: Tomohiro Matsunaga, Shin Ohta, Fumihiro Yamaguchi, Shunsuke Sakakura, Takashi Abe, Kosuke Suzuki, Yusuke Kuroda, Yusuke Kakiuchi, Naota Kuwahara, Akiko Fujiwara, Tomoko Okazaki, Hatsuko Mikuni, Tomoki Uno, Yoshitaka Uchida, Yosuke Fukuda, Tomoyuki Kimura, Megumi Jinno, Kuniaki Hirai, Yoshito Miyata, Yasunari Kishino, Hideki Inoue, Tetsuya Homma, Sojiro Kusumoto, Shintaro Suzuki, Akihiko Tanaka, Issei Tokimatsu, and Hironori Sagara
Subjects: General Medicine
Published: 2023

15. Idiopathic pulmonary fibrosis is associated with common genetic variants and limited rare variants

Author: Anna L. Peljto, Rachel Z. Blumhagen, Avram D. Walts, Jonathan Cardwell, Julia Powers, Tamera J. Corte, Joanne L. Dickinson, Ian Glaspole, Yuben P. Moodley, Martina Koziar Vasakova, Elisabeth Bendstrup, Jesper R. Davidsen, Raphael Borie, Bruno Crestani, Philippe Dieude, Francesco Bonella, Ulrich Costabel, Gunnar Gudmundsson, Seamas C. Donnelly, Jim Egan, Michael T. Henry, Michael P. Keane, Marcus P. Kennedy, Cormac McCarthy, Aoife N. McElroy, Joshua A. Olaniyi, Katherine M. A. O’Reilly, Luca Richeldi, Paolo M. Leone, Venerino Poletti, Francesco Puppo, Sara Tomassetti, Valentina Luzzi, Nurdan Kokturk, Nesrin Mogulkoc, Christine A. Fiddler, Nikhil Hirani, R. Gisli Jenkins, Toby M. Maher, Philip L. Molyneaux, Helen Parfrey, Rebecca Braybrooke, Timothy S. Blackwell, Peter D. Jackson, Steven D. Nathan, Mary K. Porteous, Kevin K. Brown, Jason D. Christie, Harold R. Collard, Oliver Eickelberg, Elena E. Foster, Kevin F. Gibson, Marilyn Glassberg, Daniel J. Kass, Jonathan A. Kropski, David Lederer, Angela L. Linderholm, Jim Loyd, Susan K. Mathai, Sydney B. Montesi, Imre Noth, Justin M. Oldham, Amy J. Palmisciano, Cristina A. Reichner, Mauricio Rojas, Jesse Roman, Neil Schluger, Barry S. Shea, Jeffrey J. Swigris, Paul J. Wolters, Yingze Zhang, Cecilia M. A. Prele, Juan I. Enghelmayer, Maria Otaola, Christopher J. Ryerson, Mauricio Salinas, Martina Sterclova, Tewodros H. Gebremariam, Marjukka Myllärniemi, Roberto G. Carbone, Haruhiko Furusawa, Masaki Hirose, Yoshikazu Inoue, Yasunari Miyazaki, Ken Ohta, Shin Ohta, Tsukasa Okamoto, Dong Soon Kim, Annie Pardo, Moises Selman, Alvaro U. Aranda, Moo Suk Park, Jong Sun Park, Jin Woo Song, Maria Molina-Molina, Lurdes Planas-Cerezales, Gunilla Westergren-Thorsson, Albert V. Smith, Ani W. Manichaikul, John S. Kim, Stephen S. Rich, Elizabeth C. Oelsner, R. Graham Barr, Jerome I. Rotter, Josee Dupuis, George O’Connor, Ramachandran S. Vasan, Michael H. Cho, Edwin K. Silverman, Marvin I. Schwarz, Mark P. Steele, Joyce S. Lee, Ivana V. Yang, Tasha E. Fingerlin, and David A. Schwartz
Subjects: Pulmonary and Respiratory Medicine, Whole Genome Sequencing, Settore MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO, Critical Care and Intensive Care Medicine, Interstitial Lung Disease, TOPMed, Telomerase, Genetic Association Studies
Abstract: Rationale: Idiopathic pulmonary fibrosis is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to non-genetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants genome-wide may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ≤0.01) within genes or regions. We also identified individual variants that are influential within genes and estimated the heritability of IPF based on rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP-heritability of IPF was estimated to be 32% (s.e. 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.
Published: 2023

16. Efficacy and safety of intramuscular administration of tixagevimab-cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial

Author: Hugh Montgomery, F D Richard Hobbs, Francisco Padilla, Douglas Arbetter, Alison Templeton, Seth Seegobin, Kenneth Kim, Jesus Abraham Simón Campos, Rosalinda H Arends, Bryan H Brodek, Dennis Brooks, Pedro Garbes, Julieta Jimenez, Gavin C K W Koh, Kelly W Padilla, Katie Streicher, Rolando M Viani, Vijay Alagappan, Menelas N Pangalos, Mark T Esser, Wakana Abe, Tania Adan De Varona, Daria Adiatullina, Daniel Aguilar Zapata, Kevin Ahlers, Carolina Aimo, Ayoade Akere, Elena Akimova, Jorge Alatorre Alexander, Logan Aldrich, Ismael Ali Garcia, Karim Ali García, Lee Allison, Rosa Alonso Zuñiga, Ivan Aloysius, Javier Altclas, Andres Alvarisqueta, Martti Antila, Camila Anton, Elisabet Árboix Alamo, Samir Arora, Ramón Alejandro Avilés Felix, Natalya Bakhtina, Varenka Barbero-Becerra, Armando Barragan-Reyes, Alejandro Barreira, Mitchell Barrett, Jiri Beran, Nikolett Berki, Viktoria Berki, Richard Betten, Claudia Binelli, Lenka Brunzová, Cecilia Bussolari, Karianna Byargeon, Justyna Bytnar, Carlos Camberos, Pedro Campos Corzo, Grazia Cannon, Valentina Canovi, Simone Carla da Rosa, Ana Caroline Moser, Luis Carrera Rivas, Marcelo Martin Casas, Paulo Castañeda-Méndez, Ana Cavalcante, Eugenia Cherepova, Alexei Chermenskii, Lauren Clark, Mauro Codeluppi, Flavia Coelho, Belinda Contreras, Alex Cran, Taylor Dao, Chrisette Dharma, Cosimo Di Castri, Victoria Diaz Balocchi, Omar Durán, Kara Earl, Adam Ellery, Tomoko Endo, Andrea Everding, Rainald Fischer, Benedito Fonseca, Chelsea C. Franklin, Susan-Beatrice Franz, Anna Fumagalli, Mauricio Galindo-Amaya, Mariagiulia Galli, Laura Gerna, Karolly Gil Ureña, Henrikki Gomes Antila, Laura Ines Gomes Maricato, Gabriela Goncalvez, Martin Gonzalez, Jesús González-Lama, Stephen Granier, Jacob Granier, Stephan Grunwald, David Guardeño-Ropero, Monica Guberti, Sridhar Guduri, Carolina Guerrero García, Jehad Haggiagi, Kacie Hale, Toshimasa Hayashi, Maiara Hermes, Dante Hernandez Colin, Yuji Hirai, Masayuki Hojo, Tetsuya Homma, Billy Hour, Andreas Huber, Diego Iacovelli, Noriomi Ishibashi, Yutaro Iwabe, Shinyu Izumi, Arne Jessen, Heiko Jessen, Wilner Jeudy, Marta Jiménez Marcos, Rebecca Johnson, Eva Juárez-Hernández, Kiyomi Kabasawa, Katarzyna Kamińska, Megumi Kawabe, Angela Kemp, Oleg Khmelnitskiy, Carina Klassen, Olena Kobrynska, Pavel Koleckar, Stephanie Korn, Marc Kornmann, Viktor Kostenko, Evgenii Kovalchuk, Yana Kovalchuk, Tim Kümmerle, Ulrike Lachmund, Kerstin Lammersmann, Flávio Lastebasse, Ivana Lattuada, Felicitas Lauer, Kyrylo Lebed, Olga Lebed, Diego Lecona-Garcia, Maria Christina Leoni, Marina Lima, Raymond Little, Holly Little, Andrea Lizardi-Díaz, Michele Lobo-Becker, Francesco Luppi, Veronica Macias, Shigefumi Maesaki, Cristiano Magnaghi, Annalisa Mancini, Stanisław Mazur, Tatiana Melnikova, Sergio Menchaca, Ibrahim Menendez-Perez, Ewa Międlar, Shuuichi Mizunuma, Anastasiya Mochalova, Mihad Mohamed, Theresa Moll, Camila Montalvo, Amber Mottola, Birgit Mück, Rebeca Mussi Brugnolli, Akanksha Nanda, Dörthe Neuner, Agatha Ngwueke, Sebastian Noe, Martin Novacek, Laura Nuzzolo-Shihadeh, Emeka Obiekwe, Isaias G. Ocampo Gaytán, Norio Ohmagari, Shin Ohta, Ptuonye Onyewuchi, Iurii Pankov, Maurício Pedrosa, Yael Peré, Alejandro Pereyra, Eliana Perez, Eduardo Perez-Alba, Paloma Perpiña Lozano, Tanya Perrei, Dena Peterson, Ligia Pierroti, Felipe Pineda-Cárdenas, Teresa Plascencia Sanchez, Camila Poletti, Chiara Pomaranzi, Lisette Portes, Nils Postel, Monica Ramirez, Isabel Ramírez, Miguel Ramirez-Baena, Mahadev Ramjee, Giovanna Ratti, Jackie Reeve, Petr Reichert, Petra Reichertová, Edgar Alejandro Reyes Garcia, Celso Ricardo, Nicomedes Rodríguez Rodríguez, Jaun Roldán Sánchez, Matilde Romero-Lopez, Tyrone Rosales, Harvey Rosales, Mohamed Roshan, Simran Roshan, Patrizia Rovere Querini, Heather Rutter, Sadaf Sachwani, Hironori Sagara, Jun Sakai, Nina Samson, José Héctor Sánchez Mijangos, Liliana Sánchez, Ana Sánchez-González, Micko Sandford, Laura Santana, Felipe Santos de Carvalho, Reiko Sasao, Lubna Sato, Elizabeth Scheuermann, Olaf Schmidt, Masafumi Seki, Safia Shaikh, Daishi Shimada, Masaharu Shinkai, Masahiro Shinoda, Jackie Smith, Fernando Solorzano, Silvia Soncini, Katalin Soregine, Erica Sosa, Olalekan Sowade, Veronika Špinková, Ruth Staniford, Iska Steigemann, Vivien Steiner, Vladimir Strelkov, Cintya R. Suárez Pineda, Hiroki Suenaga, Shintaro Suzaki, Hannah Swayze, Yuji Tada, Yuichiro Takeshita, Yasuo Takiguchi, Akihiko Tanaka, Norihito Tarumoto, Albina Tatarintseva, Michelle Taubert, Elizaveta Terenya, César Tinoco, Tomohiro Tomiyasu, Gladys Torres-Vidal, Gabriela Trejo-Aguiar, Kenji Tsushima, Emma Tunstall, Caterina Turrà, Yoandy Valdes, Nelly Valencia Castro, Guilherme Visconti, Giordano Vitali, Apinya Vutikullird, Jezdancher Watti, Doreen Werth, Cheyanne Wilson, Philippe Wilson, Amy Workman, Pamela Wörle, Christoph Wyen, Yoshiko Yamaguchi, and Kei Yamamoto
Subjects: Adult, Pulmonary and Respiratory Medicine, Treatment Outcome, Double-Blind Method, SARS-CoV-2, Outpatients, Antibodies, Monoclonal, Humans, Middle Aged, COVID-19 Drug Treatment
Abstract: Background: Early intramuscular administration of SARS-CoV-2-neutralising monoclonal antibody combination, tixagevimab–cilgavimab, to non-hospitalised adults with mild to moderate COVID-19 has potential to prevent disease progression. We aimed to evaluate the safety and efficacy of tixagevimab–cilgavimab in preventing progression to severe COVID-19 or death. Methods: TACKLE is an ongoing, phase 3, randomised, double-blind, placebo-controlled study conducted at 95 sites in the USA, Latin America, Europe, and Japan. Eligible participants were non-hospitalised adults aged 18 years or older with a laboratory-confirmed SARS-CoV-2 infection (determined by RT-PCR or an antigen test) from any respiratory tract specimen collected 3 days or less before enrolment and who had not received a COVID-19 vaccination. A WHO Clinical Progression Scale score from more than 1 to less than 4 was required for inclusion and participants had to receive the study drug 7 days or less from self-reported onset of mild to moderate COVID-19 symptoms or measured fever. Participants were randomly assigned (1:1) to receive either a single tixagevimab–cilgavimab 600 mg dose (two consecutive 3 mL intramuscular injections, one each of 300 mg tixagevimab and 300 mg cilgavimab) or placebo. Randomisation was stratified (using central blocked randomisation with randomly varying block sizes) by time from symptom onset, and high-risk versus low-risk of progression to severe COVID-19. Participants, investigators, and sponsor staff involved in the treatment or clinical evaluation and monitoring of the participants were masked to treatment-group assignments. The primary endpoints were severe COVID-19 or death from any cause through to day 29, and safety. This study is registered with ClinicalTrials.gov, NCT04723394. Findings: Between Jan 28, 2021, and July 22, 2021, 1014 participants were enrolled, of whom 910 were randomly assigned to a treatment group (456 to receive tixagevimab–cilgavimab and 454 to receive placebo). The mean age of participants was 46·1 years (SD 15·2). Severe COVID-19 or death occurred in 18 (4%) of 407 participants in the tixagevimab–cilgavimab group versus 37 (9%) of 415 participants in the placebo group (relative risk reduction 50·5% [95% CI 14·6–71·3]; p=0·0096). The absolute risk reduction was 4·5% (95% CI 1·1–8·0; p Interpretation: A single intramuscular tixagevimab–cilgavimab dose provided statistically and clinically significant protection against progression to severe COVID-19 or death versus placebo in unvaccinated individuals and safety was favourable. Treating mild to moderate COVID-19 earlier in the disease course with tixagevimab–cilgavimab might lead to more favourable outcomes.
Published: 2022

17. Comprehensive Gene Expression Signature Using RNA-Seq in Airways of Mouse Model of Severe Asthma with Fungal Sensitization

Author: Hironori Sagara, Yoshitaka Uchida, Tomoki Uno, Shintaro Suzuki, Yoshito Miyata, Akihiko Tanaka, Kaho Akimoto, Shin Ohta, Hitoshi Ikeda, Tetsuya Homma, Mayumi Yamamoto, Kuniaki Hirai, Hideki Inoue, Yosuke Fukuda, Tomoko Kawahara, and Hiroki Sato
Subjects: Receptor complex, Immunology, Inflammation, Respiratory Mucosa, Biology, Mice, Downregulation and upregulation, Gene expression, medicine, Animals, Immunology and Allergy, RNA-Seq, medicine.diagnostic_test, Gene Expression Profiling, Fungi, Alternaria, Computational Biology, General Medicine, Allergens, Immunohistochemistry, Mucus, Asthma, Eosinophils, Disease Models, Animal, Gene Ontology, Bronchoalveolar lavage, Gene Expression Regulation, biology.protein, Airway Remodeling, Respiratory epithelium, Female, Immunization, medicine.symptom, Antibody, Transcriptome, Bronchoalveolar Lavage Fluid
Abstract: Introduction: Inhalation of fungal allergens induces airway epithelial damage following airway inflammation and excessive mucus secretion, which can lead to severe asthma with fungal sensitization (SAFS). Comprehensive gene expression analysis in Alternaria-exposed mouse airways, a model of SAFS, has not been conducted. Methods: BALB/c mice received intranasal administration of Alternaria extract or phosphate-buffered saline twice a week for 6 weeks. Lung sections and bronchoalveolar lavage fluid were obtained to assess airway inflammation. RNA-Seq in the central airway was performed, and gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were conducted for pathway analyses. An in vitro experiment using human airway epithelial cell 16HBE14o- was performed to validate the RNA-Seq findings. Results: Eosinophilic airway inflammation with mucus overproduction and airway remodeling was observed in mice exposed to Alternaria. RNA-Seq analysis revealed 403 upregulated and 108 downregulated genes in airways of Alternaria-exposed mice. In GO analysis, the functions of immunoglobulin (Ig) receptor binding, Ig production, inflammatory response, and T-cell activation were upregulated, while those of keratinization and defense response to other organisms were downregulated. GSEA revealed positive enrichment in T-cell receptor complex, immunological synapse, antigen binding, mast cell activation, and Ig receptor binding, and negative enrichment in keratinization and cornification in Alternaria-exposed mice relative to control. Alternaria exposure to 16HBE14o- cells validated the downregulation of epithelial keratinization-related genes, including SPRR1A, SPRR1B, and KRT6B. Conclusion: RNA-Seq analysis showed that Alternaria exposure induced inflammatory response and impaired defense mechanisms in mice airway epithelium, which might be therapeutic targets for SAFS.
Published: 2021

18. Clinical features and mechanism of liver injury in patients with mild or moderate coronavirus disease 2019

Author: Megumi Jinno, Kazuaki Inoue, Hiroyoshi Mori, Ken Shimada, Kei Endo, Fumiya Nishimoto, Tarou Hibiki, Shin Ohta, Shunsuke Sakakura, Hironori Sagara, Fumihiro Yamaguchi, Kouji Kobayashi, Takashi Abe, Akihiko Tanaka, Yoshito Kamio, Yoshinori Sato, Kuniyo Gomi, Jun Noda, Masataka Yamawaki, Takayoshi Ito, and Masatsugu Nagahama
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, RC799-869, Gastroenterology, law.invention, Blood cell, chemistry.chemical_compound, coronavirus disease 2019, law, Lactate dehydrogenase, Internal medicine, medicine, liver‐infiltrating lymphocytes, Liver injury, Hepatology, business.industry, Original Articles, Diseases of the digestive system. Gastroenterology, medicine.disease, Intensive care unit, digestive system diseases, Elevated alkaline phosphatase, medicine.anatomical_structure, Cytokine, chemistry, Original Article, Differential diagnosis, medicine.symptom, business, liver injury, severe acute respiratory syndrome coronavirus 2
Abstract: Background and Aim We aimed to identify clinical features that suggest that coronavirus disease 2019 (COVID‐19) should be a differential diagnosis in patients presenting with a chief complaint of fever and abnormal liver function. Methods We retrospectively studied the presence or absence of abnormal liver function in 216 patients diagnosed with mild–moderate severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection between February and September 2020. Results Abnormal liver function was observed in 51 patients with mild–moderate COVID‐19. The median peak aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were 57.5, 75.5, and 332.5 U/L, respectively. The median number of days from symptom onset to peak AST, ALT, and LDH were 8.5, 9, and 8.5, respectively. The median peak LDH/AST ratio was 9.0. Low lymphocyte‐to‐white blood cell ratio and elevated LDH were found to be independent contributing factors for intensive care unit (ICU) admission on a multivariate analysis. Conclusions AST‐predominant AST/ALT/LDH elevation peaking 8–9 days after symptom onset and not accompanied by elevated alkaline phosphatase or gamma‐glutamyl transferase may be a useful clinical feature for differentiating COVID‐19 from other diseases. Since the median LDH/AST ratio was 9.0, it seems that the abnormal liver function caused by SARS‐CoV‐2 is an indirect damage to liver cells due to elevated cytokine levels caused by liver‐infiltrating lymphocytes. SARS‐CoV‐2 infection should be considered in patients presenting with a chief complaint of fever and liver injury; those with a high lymphocyte‐to‐white blood cell ratio or and a high LDH/AST ratio may be admitted to the ICU., Aspartate aminotransferase (AST)‐predominant AST/alanine aminotransferase/lactate dehydrogenase (LDH) elevation peaking 8–9 days after symptom onset and not accompanied by elevated alkaline phosphatase or gamma‐glutamyl transferase may be a useful clinical feature for differentiating coronavirus disease 2019 from other diseases. Since the median LDH/AST ratio was 9.0, it seems that the abnormal liver function caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an indirect damage to liver cells due to elevated cytokine levels caused by liver‐infiltrating lymphocytes. SARS‐CoV‐2 infection should be considered in patients presenting with a chief complaint of fever and liver injury.
Published: 2021

19. Author response for 'Clinical significance of pre‐diabetes, undiagnosed diabetes, and diagnosed diabetes on clinical outcomes in COVID‐19: Integrative analysis from the Japan COVID‐19 Task Force'

Author: null Takahiro Fukushima, null Shotaro Chubachi, null Ho Namkoong, null Takanori Asakura, null Hiromu Tanaka, null Ho Lee, null Shuhei Azekawa, null Yukinori Okada, null Ryuji Koike, null Akinori Kimura, null Seiya Imoto, null Satoru Miyano, null Seishi Ogawa, null Takanori Kanai, null Koichi Fukunaga, null Shiro Otake, null Kensuke Nakagawara, null Atsuho Morita, null Mayuko Watase, null Kaori Sakurai, null Takuya Kusumoto, null Katsunori Masaki, null Hiroki Kabata, null Hirofumi Kamata, null Makoto Ishii, null Naoki Hasegawa, null Kazuhisa Takahashi, null Norihiro Harada, null Toshio Naito, null Makoto Hiki, null Yasushi Matsushita, null Haruhi Takagi, null Ryousuke Aoki, null Ai Nakamura, null Sonoko Harada, null Hitoshi Sasano, null Shinnosuke Ikemura, null Satoshi Okamori, null Hideki Terai, null Junichi Sasaki, null Hiroshi Morisaki, null Yoshifumi Uwamino, null Kosaku Nanki, null Yohei Mikami, null Sho Uchida, null Shunsuke Uno, null Rino Ishihara, null Yuta Matsubara, null Tomoyasu Nishimura, null Takunori Ogawa, null Toshiro Sato, null Tetsuya Ueda, null Masanori Azuma, null Ryuichi Saito, null Toshikatsu Sado, null Yoshimune Miyazaki, null Ryuichi Sato, null Yuki Haruta, null Tadao Nagasaki, null Yoshinori Yasui, null Yoshinori Hasegawa, null Soichiro Ueda, null Ai Tada, null Masayoshi Miyawaki, null Masaomi Yamamoto, null Eriko Yoshida, null Reina Hayashi, null Tomoki Nagasaka, null Sawako Arai, null Yutaro Kaneko, null Kana Sasaki, null Takashi Ishiguro, null Taisuke Isono, null Shun Shibata, null Yuma Matsui, null Chiaki Hosoda, null Kenji Takano, null Takashi Nishida, null Yoichi Kobayashi, null Yotaro Takaku, null Noboru Takayanagi, null Etsuko Tagaya, null Masatoshi Kawana, null Ken Arimura, null Yasushi Nakamori, null Kazuhisa Yoshiya, null Fukuki Saito, null Tomoyuki Yoshihara, null Daiki Wada, null Hiromu Iwamura, null Syuji Kanayama, null Shuhei Maruyama, null Takanori Hasegawa, null Kunihiko Takahashi, null Tatsuhiko Anzai, null Satoshi Ito, null Akifumi Endo, null Yuji Uchimura, null Yasunari Miyazaki, null Takayuki Honda, null Tomoya Tateishi, null Shuji Tohda, null Naoya Ichimura, null Kazunari Sonobe, null Chihiro Tani Sassa, null Jun Nakajima, null Masumi Ai, null Takashi Yoshiyama, null Ken Ohta, null Hiroyuki Kokuto, null Hideo Ogata, null Yoshiaki Tanaka, null Kenichi Arakawa, null Masafumi Shimoda, null Takeshi Osawa, null Yasushi Nakano, null Yukiko Nakajima, null Ryusuke Anan, null Ryosuke Arai, null Yuko Kurihara, null Yuko Harada, null Kazumi Nishio, null Yoshikazu Mutoh, null Tomonori Sato, null Reoto Takei, null Satoshi Hagimoto, null Yoichiro Noguchi, null Yasuhiko Yamano, null Hajime Sasano, null Sho Ota, null Yusuke Suzuki, null Sohei Nakayama, null Keita Masuzawa, null Tomomi Takano, null Kazuhiko Katayama, null Koji Murakami, null Mitsuhiro Yamada, null Hisatoshi Sugiura, null Hirohito Sano, null Shuichiro Matsumoto, null Nozomu Kimura, null Yoshinao Ono, null Hiroaki Baba, null Rie Baba, null Daisuke Arai, null Takayuki Ogura, null Hidenori Takahashi, null Shigehiro Hagiwara, null Genta Nagao, null Shunichiro Konishi, null Ichiro Nakachi, null Hiroki Tateno, null Isano Hase, null Shuichi Yoshida, null Shoji Suzuki, null Miki Kawada, null Hirohisa Horinouchi, null Fumitake Saito, null Keiko Mitamura, null Masao Hagihara, null Junichi Ochi, null Tomoyuki Uchida, null Ryuya Edahiro, null Yuya Shirai, null Kyuto Sonehara, null Tatsuhiko Naito, null Kenichi Yamamoto, null Shinichi Namba, null Ken Suzuki, null Takayuki Shiroyama, null Yuichi Maeda, null Takuro Nii, null Yoshimi Noda, null Takayuki Niitsu, null Yuichi Adachi, null Takatoshi Enomoto, null Saori Amiya, null Reina Hara, null Toshihiro Kishikawa, null Shuhei Yamada, null Shuhei Kawabata, null Noriyuki Kijima, null Masatoshi Takagaki, null Noa Sasa, null Yuya Ueno, null Motoyuki Suzuki, null Norihiko Takemoto, null Hirotaka Eguchi, null Takahito Fukusumi, null Takao Imai, null Munehisa Fukushima, null Haruhiko Kishima, null Hidenori Inohara, null Kazunori Tomono, null Kazuto Kato, null Haruhiko Hirata, null Yoshito Takeda, null Atsushi Kumanogoh, null Naoki Miyazawa, null Yasuhiro Kimura, null Reiko Sado, null Hideyasu Sugimoto, null Akane Kamiya, null Naota Kuwahara, null Akiko Fujiwara, null Tomohiro Matsunaga, null Yoko Sato, null Takenori Okada, null Takashi Inoue, null Toshiyuki Hirano, null Keigo Kobayashi, null Hatsuyo Takaoka, null Koichi Nishi, null Masaru Nishitsuji, null Mayuko Tani, null Junya Suzuki, null Hiroki Nakatsumi, null Hidefumi Koh, null Tadashi Manabe, null Yohei Funatsu, null Fumimaro Ito, null Takahiro Fukui, null Keisuke Shinozuka, null Sumiko Kohashi, null Masatoshi Miyazaki, null Tomohisa Shoko, null Mitsuaki Kojima, null Tomohiro Adachi, null Motonao Ishikawa, null Kenichiro Takahashi, null Kazuyoshi Watanabe, null Yoshihiro Hirai, null Hidetoshi Kawashima, null Atsuya Narita, null Kazuki Niwa, null Yoshiyuki Sekikawa, null Hisako Sageshima, null Yoshihiko Nakamura, null Kota Hoshino, null Junichi Maruyama, null Hiroyasu Ishikura, null Tohru Takata, null Takashi Ogura, null Hideya Kitamura, null Eri Hagiwara, null Kota Murohashi, null Hiroko Okabayashi, null Takao Mochimaru, null Shigenari Nukaga, null Ryosuke Satomi Yoshitaka Oyamada, null Nobuaki Mori, null Tomoya Baba, null Yasutaka Fukui, null Mitsuru Odate, null Shuko Mashimo, null Yasushi Makino, null Kazuma Yagi, null Mizuha Hashiguchi, null Junko Kagyo, null Tetsuya Shiomi, null Kodai Kawamura, null Kazuya Ichikado, null Kenta Nishiyama, null Hiroyuki Muranaka, null Kazunori Nakamura, null Satoshi Fuke, null Hiroshi Saito, null Tomoya Tsuchida, null Shigeki Fujitani, null Mumon Takita, null Daiki Morikawa, null Toru Yoshida, null Takehiro Izumo, null Minoru Inomata, null Naoyuki Kuse, null Nobuyasu Awano, null Mari Tone, null Akihiro Ito, null Toshio Odani, null Masaru Amishima, null Takeshi Hattori, null Yasuo Shichinohe, null Takashi Kagaya, null Toshiyuki Kita, null Kazuhide Ohta, null Satoru Sakagami, null Kiyoshi Koshida, null Morio Nakamura, null Koutaro Yokote, null Taka‐Aki Nakada, null Ryuzo Abe, null Taku Oshima, null Tadanaga Shimada, null Kentaro Hayashi, null Tetsuo Shimizu, null Yutaka Kozu, null Hisato Hiranuma, null Yasuhiro Gon, null Namiki Izumi, null Kaoru Nagata, null Ken Ueda, null Reiko Taki, null Satoko Hanada, null Naozumi Hashimoto, null Keiko Wakahara, null Koji Sakamoto, null Norihito Omote, null Akira Ando, null Yu Kusaka, null Takehiko Ohba, null Susumu Isogai, null Aki Ogawa, null Takuya Inoue, null Nobuhiro Kodama, null Yasunari Kaneyama, null Shunsuke Maeda, null Takashige Kuraki, null Takemasa Matsumoto, null Masahiro Harada, null Takeshi Takahashi, null Hiroshi Ono, null Toshihiro Sakurai, null Takayuki Shibusawa, null Yusuke Kawamura, null Akiyoshi Nakayama, null Hirotaka Matsuo, null Yoshifumi Kimizuka, null Akihiko Kawana, null Tomoya Sano, null Chie Watanabe, null Ryohei Suematsu, null Makoto Masuda, null Aya Wakabayashi, null Hiroki Watanabe, null Suguru Ueda, null Masanori Nishikawa Ayumi Yoshifuji, null Kazuto Ito, null Saeko Takahashi, null Kota Ishioka, null Yusuke Chihara, null Mayumi Takeuchi, null Keisuke Onoi, null Jun Shinozuka, null Atsushi Sueyoshi, null Yoji Nagasaki, null Masaki Okamoto, null Sayoko Ishihara, null Masatoshi Shimo, null Yoshihisa Tokunaga, null Masafumi Watanabe, null Sumito Inoue, null Akira Igarashi, null Masamichi Sato, null Nobuyuki Hizawa, null Yoshiaki Inoue, null Shigeru Chiba, null Kunihiro Yamagata, null Yuji Hiramatsu, null Hirayasu Kai, null Satoru Fukuyama, null Yoshihiro Eriguchi, null Akiko Yonekawa, null Keiko Kano, null Koichiro Matsumoto, null Kensuke Kanaoka, null Shoichi Ihara, null Kiyoshi Komuta, null Koichiro Asano, null Tsuyoshi Oguma, null Yoko Ito, null Satoru Hashimoto, null Masaki Yamasaki, null Yu Kasamatsu, null Yuko Komase, null Naoya Hida, null Takahiro Tsuburai, null Baku Oyama, null Yuichiro Kitagawa, null Tetsuya Fukuta, null Takahito Miyake, null Shozo Yoshida, null Shinji Ogura, null Minoru Takada, null Hidenori Kanda, null Shinji Abe, null Yuta Kono, null Yuki Togashi, null Hiroyuki Takoi, null Ryota Kikuchi, null Shinichi Ogawa, null Tomouki Ogata, null Shoichiro Ishihara, null Arihiko Kanehiro, null Shinji Ozaki, null Yasuko Fuchimoto, null Sae Wada, null Nobukazu Fujimoto, null Kei Nishiyama, null Mariko Terashima, null Satoru Beppu, null Kosuke Yoshida, null Osamu Narumoto, null Hideaki Nagai, null Nobuharu Ooshima, null Mitsuru Motegi, null Akira Umeda, null Kazuya Miyagawa, null Hisato Shimada, null Mayu Endo, null Yoshiyuki Ohira, null Hironori Sagara, null Akihiko Tanaka, null Shin Ohta, null Tomoyuki Kimura, null Yoko Shibata, null Yoshinori Tanino, null Takefumi Nikaido, null Hiroyuki Minemura, null Yuki Sato, null Yuichiro Yamada, null Takuya Hashino, null Masato Shinoki, null Hajime Iwagoe, null Hiroshi Takahashi, null Kazuhiko Fujii, null Hiroto Kishi, null Tomoo Ishii, null Masayuki Kanai, null Tomonori Imamura, null Tatsuya Yamashita, null Masakiyo Yatomi, null Toshitaka Maeno, null Shinichi Hayashi, null Mai Takahashi, null Mizuki Kuramochi, null Isamu Kamimaki, null Yoshiteru Tominaga, null Mitsuyoshi Utsugi, null Akihiro Ono, null Toru Tanaka, null Takeru Kashiwada, null Kazue Fujita, null Yoshinobu Saito, null Masahiro Seike, null Masahiro Kanai, null Ryunosuke Saiki, null Takayoshi Hyugaji, null Eigo Shimizu, null Kotoe Katayama, null Satoru Miyawaki, null Meiko Takahashi, null Fumihiko Matsuda, null Yosuke Omae, null Yasuhito Nannya, null Takafumi Ueno, null Yuko Kitagawa, null Katsushi Tokunaga, and null The Japan COVID‐19 Task Force
Published: 2022

20. Downregulation of type III interferons in patients with severe COVID‐19

Author: Shin Ohta, Fukuda Yosuke, Mayumi Yamamoto, Hideki Inoue, Hironori Sagara, Tomoyuki Kimura, Shintaro Suzuki, Yoko Sato, Akihiko Tanaka, Yuiko Goto, Tetsuya Homma, Sojiro Kusumoto, Chisato Onitsuka, Kuniaki Hirai, and Hitoshi Ikeda
Subjects: Male, Chemokine, medicine.medical_treatment, Gastroenterology, Severity of Illness Index, SARS‐CoV‐2, Interferon Lambda, chemistry.chemical_compound, 0302 clinical medicine, cytokine, 030212 general & internal medicine, biology, Pulmonary Surfactant-Associated Protein A, Interleukin, Middle Aged, Pulmonary Surfactant-Associated Protein D, Pathophysiology, Infectious Diseases, Cytokine, C-Reactive Protein, 030211 gastroenterology & hepatology, Female, Chemokines, Adult, medicine.medical_specialty, Short Communication, Short Communications, Down-Regulation, macromolecular substances, type III interferon, Fibrin Fibrinogen Degradation Products, 03 medical and health sciences, COVID‐19, Virology, Internal medicine, Lactate dehydrogenase, Severity of illness, medicine, Humans, Aged, L-Lactate Dehydrogenase, business.industry, SARS-CoV-2, Interleukins, C-reactive protein, chemokine, Mucin-1, COVID-19, Fibrinogen, Ferritin, IFN‐lambda, chemistry, Ferritins, biology.protein, Interferons, business
Abstract: Coronavirus disease 2019 (COVID‐19) is globally rampant, and to curb the growing burden of this disease, in‐depth knowledge about its pathophysiology is needed. This was an observational study conducted at a single center to investigate serum cytokine and chemokine levels of COVID‐19 patients, based on disease severity. We included 72 consecutive COVID‐19 patients admitted to our hospital from March 21 to August 31, 2020. Patients were divided into Mild‐Moderate I (mild) and Moderate II‐Severe (severe) groups based on the COVID‐19 severity classification developed by the Ministry of Health, Labor and Welfare (MHLW) of Japan. We compared the patient characteristics as well as the serum cytokine and chemokine levels on the day of admission between the two groups. Our findings indicated that the severe group had significantly higher levels of serum fibrinogen, d‐dimer, lactate dehydrogenase, C‐reactive protein, ferritin, Krebs von den Lungen‐6, surfactant protein (SP)‐D, and SP‐A than the mild group. Strikingly, the levels of interleukin (IL)‐28A/interferon (IFN)‐λ2 were significantly lower in the severe group than in the mild group. We believe that reduced levels of type III interferons (IFN‐λs) and alterations in the levels of other cytokines and chemokines may impact the severity of the disease.
Published: 2021

21. Serum creatinine/cystatin C ratio as a surrogate marker for sarcopenia in patients with chronic obstructive pulmonary disease

Author: Yoshito Miyata, Shintaro Suzuki, Kaho Akimoto, Yuiko Goto, Tetsuya Homma, Hideki Inoue, Kuniaki Hirai, Akihiko Tanaka, Uchida Yoshitaka, Tomoki Uno, Shin Ohta, and Hironori Sagara
Subjects: Male, 0301 basic medicine, Sarcopenia, medicine.medical_specialty, Exacerbation, Pulmonary disease, 030209 endocrinology & metabolism, Critical Care and Intensive Care Medicine, Severity of Illness Index, Gastroenterology, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, In patient, Prospective Studies, Cystatin C, Aged, Aged, 80 and over, Creatinine, COPD, 030109 nutrition & dietetics, Nutrition and Dietetics, Hand Strength, biology, Surrogate endpoint, business.industry, Reproducibility of Results, medicine.disease, chemistry, biology.protein, business, Biomarkers
Abstract: Sarcopenia is common in patients with chronic obstructive pulmonary disease (COPD). Serum creatinine/cystatin C (Cr/CysC) ratio has attracted attention as a surrogate marker for sarcopenia but has not been adequately studied in patients with COPD. Thus, the purpose of this study was to investigate the validity of serum Cr/CysC ratio as a predictor of sarcopenia, evaluate a statistical cut-off value, and assess the relationship between Cr/CysC ratio and clinical factors.In this prospective observational study, we enrolled 234 male outpatients with COPD. We determined the relevance of serum Cr/CysC ratio as a surrogate maker for sarcopenia by comparing it with various biomarkers and prospectively investigated the relationship of Cr/CysC ratio with the annual exacerbation rate.Serum Cr/CysC was significantly correlated with handgrip strength (r = 0.53, P 0.01) and muscle mass (r = 0.44, P 0.01). The area under the curve for sarcopenia was significantly larger for serum Cr/CysC ratio than for other biomarkers (Cr/CysC: 0.87, CysC: 0.63, Cr: 0.61, albumin: 0.57). Multivariate analysis showed no significant difference in the frequency of acute exacerbations between patients in the low- and high-Cr/CysC group, defined by the cutoff value 0.71; however, the frequency of severe acute exacerbations was significantly higher in the low-Cr/CysC group.Serum Cr/CysC ratio can be used accurately, inexpensively, and easily to evaluate sarcopenia in male patients with COPD. Our study shows that patients with Cr/CysC below 0.71 have poor physical clinical factors and are at high risk of severe acute COPD exacerbations.
Published: 2021

22. Interleukin-34 induces pulmonary inflammation in a murine model of lipopolysaccharide-induced acute lung injury

Author: Takaya Ebato, Shin Ohta, Munehiro Yamaguchi, Hatsuko Mikuni, Hitoshi Ikeda, Megumi Jinno, Kuniaki Hirai, Yoshito Miyata, Hideki Inoue, Tetsuya Homma, Mayumi Yamamoto, Shintaro Suzuki, Akihiko Tanaka, and Hironori Sagara
Published: 2021

23. Usefulness of Ninjin'yoeito for Chronic Obstructive Pulmonary Disease Patients with Frailty

Author: Kaho Akimoto, Sojiro Kusumoto, Ayaka Kashima, Shin Ohta, Tomohiro Matsunaga, Hiromitsu Suganuma, Shintaro Suzuki, Kuniaki Hirai, Akihiko Tanaka, Takaya Ebato, Hiroki Sato, Shigenori Yamamoto, Yoshito Miyata, Hironori Sagara, Tetsuya Homma, and Hideki Inoue
Subjects: Male, medicine.medical_specialty, Pulmonary disease, Anxiety, Severity of Illness Index, Poor quality, Pulmonary Disease, Chronic Obstructive, Japan, Internal medicine, Risk of mortality, Humans, Medicine, Prospective Studies, Fatigue, Aged, COPD, Frailty, business.industry, Middle Aged, medicine.disease, Intervention studies, Treatment Outcome, Mood, Complementary and alternative medicine, Quality of Life, Female, business, Drugs, Chinese Herbal
Abstract: Objectives: Frail patients with chronic obstructive pulmonary disease (COPD) have a higher risk of mortality, mood disorder, and poor quality of life (QOL). There are few intervention studies in fr...
Published: 2020

24. The Effect of Bronchoconstriction by Methacholine Inhalation in a Murine Model of Asthma

Author: Yoshio Watanabe, Hiromitsu Suganuma, Megumi Jinno, Akihiko Tanaka, Yoshito Miyata, Kuniaki Hirai, Haruna Sato, Ayaka Kashima, Hitomi Ida, Shin Ohta, Mayumi Yamamoto, Tomoyuki Kimura, Tetsuya Homma, Hironori Sagara, Shintaro Suzuki, and Tomoki Uno
Subjects: Ovalbumin, Bronchoconstriction, medicine.medical_treatment, Immunology, Mice, Transforming Growth Factor beta, Administration, Inhalation, medicine, Animals, Humans, Immunology and Allergy, Lung, Methacholine Chloride, Asthma, Mice, Inbred BALB C, Goblet cell, Inhalation, medicine.diagnostic_test, business.industry, Macrophages, General Medicine, Allergens, respiratory system, medicine.disease, respiratory tract diseases, Eosinophils, Disease Models, Animal, medicine.anatomical_structure, Bronchoalveolar lavage, Cytokine, Female, Methacholine, medicine.symptom, business, medicine.drug
Abstract: Introduction: Bronchoconstriction was recently shown to cause airway remodeling and induce allergic airway inflammation in asthma. However, the mechanisms how mechanical stress via bronchoconstriction could induce airway inflammation and remodeling remain unclear. Objective: We investigated the effect of bronchoconstriction induced by methacholine inhalation in a murine model of asthma. Methods: BALB/c female mice were sensitized and challenged with ovalbumin (OVA), followed by treatment with methacholine by a nebulizer twice a day for 7 days. Twenty-four hours after the last methacholine treatment, the bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The BALF was analyzed for total and differential cell counts and cytokine levels. The lung tissues were analyzed for goblet cell metaplasia, thickness of the smooth muscle, and lung fibrosis. The expression of cytokines in the lung was also examined. Results: OVA sensitization and challenge induced infiltration of total cells, macrophages, and eosinophils in the BALF along with goblet cell metaplasia and increased airway smooth muscle hypertrophy. Seven days after the last OVA challenge, untreated mice achieved reduction in airway inflammation, while methacholine maintained the number of BALF total cells, macrophages, and eosinophils. The percentage of goblet cells and the thickness of airway smooth muscle were also maintained by methacholine. Moreover, the treatment of methacholine induced the expression of transforming growth factor (TGF)-β in the lung. This result indicates that the production of TGF-β is involved in induction of airway remodeling caused by bronchoconstriction with methacholine. Conclusions: Repeated bronchoconstriction caused by methacholine inhalation elicited allergic airway inflammation and airway remodeling.
Published: 2020

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

Author: Qingbo S. Wang, Ryuya Edahiro, Ho Namkoong, Takanori Hasegawa, Yuya Shirai, Kyuto Sonehara, Hiromu Tanaka, Ho Lee, Ryunosuke Saiki, Takayoshi Hyugaji, Eigo Shimizu, Kotoe Katayama, Masahiro Kanai, Tatsuhiko Naito, Noah Sasa, Kenichi Yamamoto, Yasuhiro Kato, Takayoshi Morita, Kazuhisa Takahashi, Norihiro Harada, Toshio Naito, Makoto Hiki, Yasushi Matsushita, Haruhi Takagi, Masako Ichikawa, Ai Nakamura, Sonoko Harada, Yuuki Sandhu, Hiroki Kabata, Katsunori Masaki, Hirofumi Kamata, Shinnosuke Ikemura, Shotaro Chubachi, Satoshi Okamori, Hideki Terai, Atsuho Morita, Takanori Asakura, Junichi Sasaki, Hiroshi Morisaki, Yoshifumi Uwamino, Kosaku Nanki, Sho Uchida, Shunsuke Uno, Tomoyasu Nishimura, Takashri Ishiguro, Taisuke Isono, Shun Shibata, Yuma Matsui, Chiaki Hosoda, Kenji Takano, Takashi Nishida, Yoichi Kobayashi, Yotaro Takaku, Noboru Takayanagi, Soichiro Ueda, Ai Tada, Masayoshi Miyawaki, Masaomi Yamamoto, Eriko Yoshida, Reina Hayashi, Tomoki Nagasaka, Sawako Arai, Yutaro Kaneko, Kana Sasaki, Etsuko Tagaya, Masatoshi Kawana, Ken Arimura, Kunihiko Takahashi, Tatsuhiko Anzai, Satoshi Ito, Akifumi Endo, Yuji Uchimura, Yasunari Miyazaki, Takayuki Honda, Tomoya Tateishi, Shuji Tohda, Naoya Ichimura, Kazunari Sonobe, Chihiro Tani Sassa, Jun Nakajima, Yasushi Nakano, Yukiko Nakajima, Ryusuke Anan, Ryosuke Arai, Yuko Kurihara, Yuko Harada, Kazumi Nishio, Tetsuya Ueda, Masanori Azuma, Ryuichi Saito, Toshikatsu Sado, Yoshimune Miyazaki, Ryuichi Sato, Yuki Haruta, Tadao Nagasaki, Yoshinori Yasui, Yoshinori Hasegawa, Yoshikazu Mutoh, Tomoki Kimura, Tomonori Sato, Reoto Takei, Satoshi Hagimoto, Yoichiro Noguchi, Yasuhiko Yamano, Hajime Sasano, Sho Ota, Yasushi Nakamori, Kazuhisa Yoshiya, Fukuki Saito, Tomoyuki Yoshihara, Daiki Wada, Hiromu Iwamura, Syuji Kanayama, Shuhei Maruyama, Takashi Yoshiyama, Ken Ohta, Hiroyuki Kokuto, Hideo Ogata, Yoshiaki Tanaka, Kenichi Arakawa, Masafumi Shimoda, Takeshi Osawa, Hiroki Tateno, Isano Hase, Shuichi Yoshida, Shoji Suzuki, Miki Kawada, Hirohisa Horinouchi, Fumitake Saito, Keiko Mitamura, Masao Hagihara, Junichi Ochi, Tomoyuki Uchida, Rie Baba, Daisuke Arai, Takayuki Ogura, Hidenori Takahashi, Shigehiro Hagiwara, Genta Nagao, Shunichiro Konishi, Ichiro Nakachi, Koji Murakami, Mitsuhiro Yamada, Hisatoshi Sugiura, Hirohito Sano, Shuichiro Matsumoto, Nozomu Kimura, Yoshinao Ono, Hiroaki Baba, Yusuke Suzuki, Sohei Nakayama, Keita Masuzawa, Shinichi Namba, Takayuki Shiroyama, Yoshimi Noda, Takayuki Niitsu, Yuichi Adachi, Takatoshi Enomoto, Saori Amiya, Reina Hara, Yuta Yamaguchi, Teruaki Murakami, Tomoki Kuge, Kinnosuke Matsumoto, Yuji Yamamoto, Makoto Yamamoto, Midori Yoneda, Kazunori Tomono, Kazuto Kato, Haruhiko Hirata, Yoshito Takeda, Hidefumi Koh, Tadashi Manabe, Yohei Funatsu, Fumimaro Ito, Takahiro Fukui, Keisuke Shinozuka, Sumiko Kohashi, Masatoshi Miyazaki, Tomohisa Shoko, Mitsuaki Kojima, Tomohiro Adachi, Motonao Ishikawa, Kenichiro Takahashi, Takashi Inoue, Toshiyuki Hirano, Keigo Kobayashi, Hatsuyo Takaoka, Kazuyoshi Watanabe, Naoki Miyazawa, Yasuhiro Kimura, Reiko Sado, Hideyasu Sugimoto, Akane Kamiya, Naota Kuwahara, Akiko Fujiwara, Tomohiro Matsunaga, Yoko Sato, Takenori Okada, Yoshihiro Hirai, Hidetoshi Kawashima, Atsuya Narita, Kazuki Niwa, Yoshiyuki Sekikawa, Koichi Nishi, Masaru Nishitsuji, Mayuko Tani, Junya Suzuki, Hiroki Nakatsumi, Takashi Ogura, Hideya Kitamura, Eri Hagiwara, Kota Murohashi, Hiroko Okabayashi, Takao Mochimaru, Shigenari Nukaga, Ryosuke Satomi, Yoshitaka Oyamada, Nobuaki Mori, Tomoya Baba, Yasutaka Fukui, Mitsuru Odate, Shuko Mashimo, Yasushi Makino, Kazuma Yagi, Mizuha Hashiguchi, Junko Kagyo, Tetsuya Shiomi, Satoshi Fuke, Hiroshi Saito, Tomoya Tsuchida, Shigeki Fujitani, Mumon Takita, Daiki Morikawa, Toru Yoshida, Takehiro Izumo, Minoru Inomata, Naoyuki Kuse, Nobuyasu Awano, Mari Tone, Akihiro Ito, Yoshihiko Nakamura, Kota Hoshino, Junichi Maruyama, Hiroyasu Ishikura, Tohru Takata, Toshio Odani, Masaru Amishima, Takeshi Hattori, Yasuo Shichinohe, Takashi Kagaya, Toshiyuki Kita, Kazuhide Ohta, Satoru Sakagami, Kiyoshi Koshida, Kentaro Hayashi, Tetsuo Shimizu, Yutaka Kozu, Hisato Hiranuma, Yasuhiro Gon, Namiki Izumi, Kaoru Nagata, Ken Ueda, Reiko Taki, Satoko Hanada, Kodai Kawamura, Kazuya Ichikado, Kenta Nishiyama, Hiroyuki Muranaka, Kazunori Nakamura, Naozumi Hashimoto, Keiko Wakahara, Sakamoto Koji, Norihito Omote, Akira Ando, Nobuhiro Kodama, Yasunari Kaneyama, Shunsuke Maeda, Takashige Kuraki, Takemasa Matsumoto, Koutaro Yokote, Taka-Aki Nakada, Ryuzo Abe, Taku Oshima, Tadanaga Shimada, Masahiro Harada, Takeshi Takahashi, Hiroshi Ono, Toshihiro Sakurai, Takayuki Shibusawa, Yoshifumi Kimizuka, Akihiko Kawana, Tomoya Sano, Chie Watanabe, Ryohei Suematsu, Hisako Sageshima, Ayumi Yoshifuji, Kazuto Ito, Saeko Takahashi, Kota Ishioka, Morio Nakamura, Makoto Masuda, Aya Wakabayashi, Hiroki Watanabe, Suguru Ueda, Masanori Nishikawa, Yusuke Chihara, Mayumi Takeuchi, Keisuke Onoi, Jun Shinozuka, Atsushi Sueyoshi, Yoji Nagasaki, Masaki Okamoto, Sayoko Ishihara, Masatoshi Shimo, Yoshihisa Tokunaga, Yu Kusaka, Takehiko Ohba, Susumu Isogai, Aki Ogawa, Takuya Inoue, Satoru Fukuyama, Yoshihiro Eriguchi, Akiko Yonekawa, Keiko Kan-o, Koichiro Matsumoto, Kensuke Kanaoka, Shoichi Ihara, Kiyoshi Komuta, Yoshiaki Inoue, Shigeru Chiba, Kunihiro Yamagata, Yuji Hiramatsu, Hirayasu Kai, Koichiro Asano, Tsuyoshi Oguma, Yoko Ito, Satoru Hashimoto, Masaki Yamasaki, Yu Kasamatsu, Yuko Komase, Naoya Hida, Takahiro Tsuburai, Baku Oyama, Minoru Takada, Hidenori Kanda, Yuichiro Kitagawa, Tetsuya Fukuta, Takahito Miyake, Shozo Yoshida, Shinji Ogura, Shinji Abe, Yuta Kono, Yuki Togashi, Hiroyuki Takoi, Ryota Kikuchi, Shinichi Ogawa, Tomouki Ogata, Shoichiro Ishihara, Arihiko Kanehiro, Shinji Ozaki, Yasuko Fuchimoto, Sae Wada, Nobukazu Fujimoto, Kei Nishiyama, Mariko Terashima, Satoru Beppu, Kosuke Yoshida, Osamu Narumoto, Hideaki Nagai, Nobuharu Ooshima, Mitsuru Motegi, Akira Umeda, Kazuya Miyagawa, Hisato Shimada, Mayu Endo, Yoshiyuki Ohira, Masafumi Watanabe, Sumito Inoue, Akira Igarashi, Masamichi Sato, Hironori Sagara, Akihiko Tanaka, Shin Ohta, Tomoyuki Kimura, Yoko Shibata, Yoshinori Tanino, Takefumi Nikaido, Hiroyuki Minemura, Yuki Sato, Yuichiro Yamada, Takuya Hashino, Masato Shinoki, Hajime Iwagoe, Hiroshi Takahashi, Kazuhiko Fujii, Hiroto Kishi, Masayuki Kanai, Tomonori Imamura, Tatsuya Yamashita, Masakiyo Yatomi, Toshitaka Maeno, Shinichi Hayashi, Mai Takahashi, Mizuki Kuramochi, Isamu Kamimaki, Yoshiteru Tominaga, Tomoo Ishii, Mitsuyoshi Utsugi, Akihiro Ono, Toru Tanaka, Takeru Kashiwada, Kazue Fujita, Yoshinobu Saito, Masahiro Seike, Hiroko Watanabe, Hiroto Matsuse, Norio Kodaka, Chihiro Nakano, Takeshi Oshio, Takatomo Hirouchi, Shohei Makino, Moritoki Egi, Yosuke Omae, Yasuhito Nannya, Takafumi Ueno, Tomomi Takano, Kazuhiko Katayama, Masumi Ai, Atsushi Kumanogoh, Toshiro Sato, Naoki Hasegawa, Katsushi Tokunaga, Makoto Ishii, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga, and Yukinori Okada
Subjects: Multidisciplinary, Membrane Glycoproteins, Quantitative Trait Loci, General Physics and Astronomy, COVID-19, General Chemistry, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Japan, Viral infection, Humans, Lectins, C-Type, Gene expression, Receptors, Immunologic, Transcriptomics, Genome-Wide Association Study
Abstract: Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection., 「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.
Published: 2021

26. β2‐adrenoceptor agonist inhalation induced paroxysmal atrial fibrillation and tachycardia in a patient with severe bronchial asthma

Author: Kenji Momo, Tadanori Sasaki, Hironori Sagara, Shigenori Yamamoto, Haruki Funakoshi, Tomoki Uno, Takaya Ebato, Shin Ohta, and Keinosuke Okazaki
Subjects: Pharmacology, Tachycardia, medicine.medical_specialty, Inhalation, business.industry, Paroxysmal atrial fibrillation, Adrenoceptor agonist, medicine.disease, Internal medicine, Cardiology, medicine, Pharmacology (medical), medicine.symptom, business, Asthma
Published: 2021

27. Serum cystatin C and CRP are early predictive biomarkers for emergence of hypoxia in COVID-19

Author: Yoshito Miyata, Hideki Inoue, Kuniaki Hirai, Fumihiro Ishikawa, Shin Ohta, Haruna Sato, Kaoru Mochizuki, Takaya Ebato, Hatsuko Mikuni, Tomoyuki Kimura, Yosuke Fukuda, Yasunari Kishino, Tetsuya Homma, Hideto Oyamada, Sojiro Kusumoto, Mayumi Yamamoto, Shintaro Suzuki, Yuko Udaka, Akihiko Tanaka, Keiko Ishino, Yuji Kiuchi, and Hironori Sagara
Subjects: C-Reactive Protein, Predictive Value of Tests, Humans, COVID-19, General Medicine, Cystatin C, Biomarkers, Retrospective Studies
Abstract: In Japan, during the coronavirus disease 2019 (COVID-19) pandemic, patients with non-hypoxia are recommended to recuperate at home or in pre-hospital facilities. However, it was observed that unexpected hypoxia may occur and become severe subsequently in patients whose symptoms were initially expected to improve naturally. The aim of this study is to validate biomarkers that can predict at an early stage the emergence of hypoxia in COVID-19 patients without hypoxia.We retrospectively enrolled 193 patients with COVID-19, excluding patients with hypoxia and severe disease from the onset. Participants were classified into two groups according to the emergence of hypoxia during the clinical course, and the laboratory data were compared to identify biomarkers that could predict early the emergence of hypoxia.The areas under the curve for serum cystatin C (CysC) and C-reactive protein (CRP) levels for the emergence of hypoxia during the clinical course were higher than those for other biomarkers (CysC, 0.84 and CRP, 0.83). Multivariate analysis showed that high serum CysC and CRP levels were associated with the emergence of hypoxia during the clinical course.Elevated serum CysC and CRP levels were associated with the emergence of hypoxia during the clinical course in COVID-19 patients without hypoxia. These findings may help determine the need for hospitalization in initially non-hypoxic COVID-19 patients.
Published: 2021

28. Influence of Home Robots on Stress Relief Effectiveness in Communication between People Meeting for the First Time.

Author: Chiyomi Okamoto, Yuichiro Kurone, Chiaki Takagi, Naoto Hirata, Saori Nakagawa, Eiichi Tachikawa, Shin Ohta, and Sadahiko Shimoeda
Subjects: AUTONOMIC nervous system, ROBOTS, ANIMAL-assisted therapy, ROBOT control systems, VISUAL analog scale, SALIVA
Abstract: Introduction: Animal-assisted therapy, a complementary and alternative therapy to relieve the patient's stress, has been demonstrated to be fairly effective, although it can be implemented in limited medical institutions. We, therefore, substituted a robot for animals to examine its stress-relieving effects. Methods: Twenty-four healthy volunteers randomly assigned to the robot intervention and control groups chatted for 10 minutes. Before and after chatting, we conducted a questionnaire survey on their mental status using the Visual Analog Scale (VAS), evaluated the balance of the autonomic nervous system based on the analysis of heart rate variability, and measured the salivary levels of oxytocin and secretory immunoglobulin A. Results: Neither the VAS nor the salivary levels of physiologically active substances were significantly different between the groups. However, the balance of the autonomic nervous system showed a significant increase in the indices of parasympathetic nerve activity in the male subjects of the intervention group. Discussion: Short-term intervention did not sufficiently demonstrate the effects of robots in relieving stress, presumably because the stress relief effects of robot may be associated with the feelings of "attachment" and "trust." Conclusions: A long-term intervention study should be conducted to examine the usefulness of robots in relieving stress and improving the quality of life. If the usefulness of robot-assisted therapy is clarified, it could be widely implemented in clinical settings as an alternative to animal-assisted therapy. [ABSTRACT FROM AUTHOR]
Published: 2022

29. Roles of Early Mobilization Program in Preventing Muscle Weakness and Decreasing Psychiatric Disorders in Patients with Coronavirus Disease 2019 Pneumonia: A Retrospective Observational Cohort Study

Author: Maiko Mori, Toru Kotani, Shin Ohta, Kota Kubodera, Atsuko Shono, Fumika Matsuzaki, Mizuki Sugiyama, Jin Saito, Mika Kaneki, Hiroko Maruo, and Fumihito Kasai
Subjects: medicine.medical_specialty, Article, law.invention, 03 medical and health sciences, coronavirus disease 2019, 0302 clinical medicine, Quality of life, law, medicine, 030212 general & internal medicine, Psychiatry, acute respiratory failure, business.industry, Medical record, Muscle weakness, 030208 emergency & critical care medicine, Retrospective cohort study, General Medicine, medicine.disease, Intensive care unit, Pneumonia, postintensive care syndrome, Anxiety, Medicine, medicine.symptom, business, Cohort study
Abstract: Although many coronavirus 2019 patients have experienced persistent symptoms and a long-term decline in quality of life after discharge, the details of these persistent symptoms and the effect of early rehabilitation are still unclear. We conducted a single-center, retrospective observational study to investigate the prevalence of persistent symptoms three months after discharge from the intensive care unit by checking the medical records. All patients received an early mobilization program. Four out of 13 patients (31%) had postintensive care syndrome. No patients had muscle weakness, and 11 patients (85%) returned to their previous work. However, psychiatric disorder, such as anxiety (23%) and posttraumatic stress disorder (15%), were observed. Eleven patients claimed persistent symptoms, including fatigue and numbness in the extremities. Our results suggest that the implementation of an early rehabilitation program plays some role in preventing muscle weakness and that decreasing psychiatric disorders should be a next target of patient care in the intensive care unit.
Published: 2021
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30. Japan COVID-19 Task Force: a nation-wide consortium to elucidate host genetics of COVID-19 pandemic in Japan

Author: Shuichi Yoshida, Yoshihiro Hirai, Hiroshi Takahashi, Yoshiyuki Sekikawa, Saeko Takahashi, Yoshitaka Oyamada, Shunsuke Uno, Koutaro Yokote, Kunihiko Takahashi, Shigenari Nukaga, Yoshinao Ono, Shoichiro Ishihara, Nozomu Kimura, Tomohiro Adachi, Shigeki Fujitani, Eri Hagiwara, Motoyuki Suzuki, Tomouki Ogata, Namiki Izumi, Shinji Abe, Etsuko Tagaya, Yoshinori Hasegawa, Yoshimune Miyazaki, Junichi Sasaki, Yoshinori Tanino, Seishi Ogawa, Yuki Togashi, Satoshi Fuke, Yoshiaki Inoue, Hideo Ogata, Masaomi Yamamoto, Hiroshi Saito, Jun Shinozuka, Sho Uchida, Masayoshi Miyawaki, Atsushi Kumanogoh, Koichiro Matsumoto, Yuko Kitagawa, Mayu Endo, Mitsuru Odate, Hiroki Tateno, Fumitake Saito, Mizuki Kuramochi, Shoji Suzuki, Koji Murakami, Kenichi Arakawa, Shozo Yoshida, Hitoshi Sasano, Keigo Kobayashi, Takuro Nii, Takashi Ishiguro, Ryuichi Saito, Yohei Mikami, Takashi Inoue, Haruhiko Kishima, Daisuke Arai, Takao Mochimaru, Minoru Takada, Yuya Ueno, Takehiro Izumo, Reina Hara, Nobuyuki Hizawa, Atsuho Morita, Takanori Hasegawa, Masahiro Seike, Hisako Sageshima, Takeshi Hattori, Shinichi Namba, Shuko Mashimo, Tomoya Tsuchida, Hiromu Tanaka, Naoki Miyazawa, Masatoshi Kawana, Shunichiro Konishi, Takatoshi Enomoto, Takuya Hashino, Hiroki Watanabe, Kentaro Hayashi, Sumito Inoue, Satoshi Hagimoto, Toru Yoshida, Akiko Fujiwara, Masaki Okamoto, Hiroki Kabata, Shuji Tohda, Baku Oyama, Norihiko Takemoto, Nobuyasu Awano, Makoto Hiki, Yasutaka Fukui, Takahiro Fukui, Keisuke Onoi, Yuichiro Yamada, Takayuki Shiroyama, Mayuko Tani, Hiroyuki Muranaka, Kazuhide Ohta, Yoshifumi Kimizuka, Hajime Iwagoe, Yasuko Fuchimo, Hiroki Nakatsumi, Hiroyuki Minemura, Hisatoshi Sugiura, Haruhi Takagi, Hiroyuki Kokuto, Yasuhiro Kimura, Masatoshi Takagaki, Yuki Sato, Masao Hagihara, Junko Kagyo, Yusuke Kawamura, Sayoko Ishihara, Akinori Kimura, Aki Ogawa, Hironori Sagara, Noa Sasa, Masahiro Kanai, Isano Hase, Takenori Okada, Akiyoshi Nakayama, Osamu Narumoto, Norihito Omote, Kazunori Tomono, Toshiro Sato, Hatsuyo Takaoka, Mayumi Takeuchi, Keiko Kan-o, Satoshi Okamori, Yukinori Okada, Yoshito Takeda, Kazuto Ito, Tatsuhiko Naito, Reina Hayashi, Toshikatsu Sado, Kazuya Ichikado, Yasushi Matsushita, Nobuaki Mori, Takashi Nishida, Toshitaka Maeno, Tomomi Takano, Soichiro Ueda, Tomoyasu Nishimura, Masaru Nishitsuji, Ryusuke Anan, Arihiko Kanehiro, Akira Umeda, Syuji Kanayama, Yosuke Omae, Tomoki Nagasaka, Koichi Nishi, Yoshiyuki Ohira, Fumimaro Ito, Toru Tanaka, Kenichiro Takahashi, Hidenori Kanda, Hidenori Inohara, Kaoru Nagata, Kei Nishiyama, Masafumi Watanabe, Katsunori Masaki, Ryuzo Abe, Hirofumi Kamata, Masahiro Harada, Chihiro Tani Sassa, Tomoya Sano, Shoichi Ihara, Tadashi Manabe, Takafumi Ueno, Takahito Fukusumi, Meiko Takahashi, Kyuto Sonehara, Kana Sasaki, Hiroyuki Takoi, Chie Watanabe, Takahiro Tsuburai, Tomonori Sato, Yoichi Kobayashi, Kazuhisa Takahashi, Yasushi Nakano, Kenichi Yamamoto, Takayoshi Hyugaji, Hirohito Sano, Ho Namkoong, Atsushi Sueyoshi, Naoya Ichimura, Yoshiteru Tominaga, Masaru Amishima, Ken Suzuki, Ken Ohta, Shigehiro Hagiwara, Masayuki Kanai, Kota Hoshino, Shuhei Kawabata, Mitsuhiro Yamada, Toshio Naito, Akihiro Ono, Yotaro Takaku, Yoko Sato, Satoru Miyano, Junichi Ochi, Yoshikazu Mutoh, Hiroaki Baba, Yoko Shibata, Tatsuya Yamashita, Yoko Ito, Hiromu Iwamura, Munehisa Fukushima, Saori Amiya, Takayuki Honda, Yuta Kono, Susumu Isogai, Ryuya Edahiro, Makoto Masuda, Hisato Shimada, Hideaki Nagai, Tomoya Baba, Fukuki Saito, Toshihiro Sakurai, Ryota Kikuchi, Yoichiro Noguchi, Tatsuhiko Anzai, Mizuha Hashiguchi, Masamichi Sato, Naoki Hasegawa, Yasunari Miyazaki, Tetsuya Ueda, Yasuhiko Yamano, Shinji Ozaki, Yoshinobu Saito, Takuya Inoue, Sohei Nakayama, Sawako Arai, Yu Kusaka, Miki Kawada, Yuko Kurihara, Daiki Wada, Isamu Kamimaki, Motonao Ishikawa, Sumiko Kohashi, Sae Wada, Kazuma Yagi, Rino Ishihara, Hiroko Okabayashi, Nobuhiro Kodama, Mai Takahashi, Kiyoshi Komuta, Yusuke Chihara, Yoshihiko Nakamura, Akifumi Endo, Shuichiro Matsumoto, Akira Igarashi, Shuhei Yamada, Akiko Yonekawa, Yukiko Nakajima, Sakamoto Koji, Kazue Fujita, Masakiyo Yatomi, Makoto Ishii, Ryuji Koike, Eigo Shimizu, Shigeru Chiba, Satoru Miyawaki, Shunsuke Maeda, Toshio Odani, Hideyasu Sugimoto, Masanori Nishikawa, Yoshinori Yasui, Akira Ando, Takayuki Shibusawa, Nobuharu Ooshima, Toshiyuki Kita, Satoru Fukuyama, Ai Tada, Mariko Terashima, Tadao Nagasaki, Rie Baba, Atsuya Narita, Takanori Ogawa, Tetsuo Shimizu, Ken Ueda, Yuki Haruta, Satoru Hashimoto, Ryohei Suematsu, Ho Lee, Ryosuke Satomi, Hirotaka Eguchi, Kota Ishioka, Ryousuke Aoki, Yusuke Suzuki, Takemasa Matsumoto, Kazunari Sonobe, Hisato Hiranuma, Hirayasu Kai, Kosuke Yoshida, Ayumi Yoshifuji, Takeru Kashiwada, Yuko Harada, Reoto Takei, Aya Wakabayashi, Tomohiro Matsunaga, Haruhiko Hirata, Hiroshi Morisaki, Yoshifumi Uwamino, Yoshihisa Tokunaga, Kazuki Niwa, Hidetoshi Kawashima, Hideki Terai, Kenji Takano, Mumon Takita, Yuko Komase, Masaki Yamasaki, Chiaki Hosoda, Takayuki Ogura, Shun Shibata, Mitsuru Motegi, Takeshi Takahashi, Takehiko Ohba, Shinichi Hayashi, Satoshi Ito, Yu Kasamatsu, Shinnosuke Ikemura, Tetsuya Fukuta, Koichiro Asano, Taka-aki Nakada, Kota Murohashi, Tomoyuki Uchida, Hirotaka Matsuo, Satoko Hanada, Kenta Nishiyama, Minoru Inomata, Nobukazu Fujimoto, Tomoya Tateishi, Mitsuaki Kojima, Kazuto Kato, Kazuhiko Katayama, Yuichi Maeda, Takashi Kagaya, Keiko Wakahara, Takashi Ogura, Yasuhiro Gon, Taku Oshima, Ken Arimura, Shuhei Maruyama, Mari Tone, Ryuichi Sato, Koichi Fukunaga, Hidefumi Koh, Yuichiro Kitagawa, Noboru Takayanagi, Masatoshi Miyazaki, Ichiro Nakachi, Akihiko Kawana, Toshiyuki Hirano, Yohei Funatsu, Yasushi Nakamori, Reiko Sado, Yasuo Shichinohe, Junya Suzuki, Yasunari Kaneyama, Takahito Miyake, Kunihiro Yamagata, Yasuhito Nannya, Shinichi Ogawa, Naoya Hida, Tsuyoshi Oguma, Kazunori Nakamura, Kosaku Nanki, Naozumi Hashimoto, Fumihiko Matsuda, Tomoyuki Kimura, Daiki Morikawa, Yuji Uchimura, Yoshiaki Tanaka, Kazuhisa Yoshiya, Takashige Kuraki, Yoshihiro Eriguchi, Tomohisa Shoko, Tadanaga Shimada, Yuji Hiramatsu, Akihiko Tanaka, Hideya Kitamura, Yutaka Kozu, Ryosuke Arai, Taisuke Isono, Yasushi Makino, Seiya Imoto, Yuichi Adachi, Yuma Matsui, Masato Shinoki, Kazumi Nishio, Keiko Mitamura, Tomonori Imamura, Masanori Azuma, Sonoko Harada, Hiroshi Ono, Kotoe Katayama, Masumi Ai, Keisuke Shinozuka, Reiko Taki, Junichi Maruyama, Takao Imai, Yutaro Kaneko, Kensuke Kanaoka, Sho Ota, Yoji Nagasaki, Toshihiro Kishikawa, Takayuki Niitsu, Hirohisa Horinouchi, Naoyuki Kuse, Tetsuya Shiomi, Jun Nakajima, Katsushi Tokunaga, Norihiro Harada, Keita Masuzawa, Noriyuki Kijima, Takeshi Osawa, Satoru Sakagami, Kazuhiko Fujii, Shotaro Chubachi, Tomoyuki Yoshihara, Yoshimi Noda, Hiroyasu Ishikura, Kiyoshi Koshida, Shin Ohta, Ai Nakamura, Naota Kuwahara, Shinji Ogura, Suguru Ueda, Akihiro Ito, Morio Nakamura, Tohru Takata, Yuya Shirai, Hidenori Takahashi, Eriko Yoshida, Satoru Beppu, Mitsuyoshi Utsugi, Masafumi Shimoda, Masatoshi Shimo, Tomoo Ishii, Takefumi Nikaido, Takanori Asakura, Kazuya Miyagawa, Takanori Kanai, Hiroto Kishi, Akane Kamiya, Genta Nagao, Kodai Kawamura, Ryunosuke Saiki, Takashi Yoshiyama, Hajime Sasano, Kazuyoshi Watanabe, and Yuta Matsubara
Subjects: Genetics, education.field_of_study, Population, Mendelian Randomization Analysis, Genome-wide association study, Odds ratio, Biology, medicine.disease, Obesity, Confidence interval, Minor allele frequency, Pandemic, medicine, education
Abstract: To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., LZTFL1, FOXP4, ABO, and IFNAR2), but also found a variant on 5p35 (rs60200309-A at DOCK2) that was significantly associated with severe COVID-19 in younger (-8 (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.
Published: 2021

31. Evaluating the effect of aromatherapy on a stress marker in healthy subjects

Author: Naoto Hirata, Saori Nakagawa, Shin Ohta, Chiaki Takagi, and Sadahiko Shimoeda
Subjects: Saliva, Aromatherapy, Palliative care, Lavender, Physiology, lcsh:RS1-441, Pharmacology (nursing), Lavender oil, Stress, 030226 pharmacology & pharmacy, Bedtime, lcsh:Pharmacy and materia medica, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Medicine, Pharmacology (medical), Inhalation, business.industry, lcsh:RM1-950, Secretory immunoglobulin A, lcsh:Therapeutics. Pharmacology, Complementary and alternative medicine, 030220 oncology & carcinogenesis, Noradrenaline, business, Research Article
Abstract: Background/purpose Chemotherapy is important for cancer treatment, but patients’ physical and mental stress may lead to unfavorable pain control, an increase in the risk of relapse, and a reduction in the quality of life (QOL). Recently, aromatherapy has been performed in addition to palliative care in many countries, such as Japan and the United States, but scientific evidence remains insufficient. To investigate the usefulness of aromatherapy as complementary and alternative medicine, we evaluated its influence on the immune and autonomic nervous systems. Methods We instructed healthy volunteers to inhale aroma oil at bedtime for 6 weeks, and measured changes in the salivary level of secretory immunoglobulin A (s-IgA). Furthermore, blood was collected in addition to saliva in some healthy volunteers, and the blood level of noradrenaline (NA) was measured to examine its relationship to changes in the salivary s-IgA level. Results Aromatherapy with lavender and grapefruit oils significantly increased the salivary s-IgA level: lavender oil increased 3.5-fold (p = 0.03), and grapefruit oil increased 2.55-fold (p = 0.04). On lavender oil inhalation, there was a weak, positive correlation between changes in the salivary s-IgA level and those in the blood NA level (R2 = 0.24). Conclusion The results showed that aromatherapy with lavender and grapefruit oils reduced stress by acting on the immune and autonomic nervous systems in healthy volunteers. In the future, its clinical usefulness must be investigated through similar examination in patients in whom the stress level may be high.
Published: 2019

32. Comparison of three frailty models and a sarcopenia model in elderly patients with chronic obstructive pulmonary disease

Author: Kuniaki Hirai, Ryo Manabe, Haruna Sato, Sojiro Kusumoto, Akihiko Tanaka, Keisuke Kaneko, Shin Ohta, Hironori Sagara, Fumihiro Yamaguchi, Tetsuya Homma, Tomoki Uno, and Shintaro Suzuki
Subjects: Male, Sarcopenia, medicine.medical_specialty, Frail Elderly, Psychological intervention, Pulmonary disease, Kihon checklist, Risk Assessment, Pulmonary Disease, Chronic Obstructive, Japan, Older patients, Quality of life, Risk Factors, Internal medicine, Outpatients, Prevalence, medicine, Humans, Geriatric Assessment, Aged, COPD, Frailty, business.industry, Prognosis, medicine.disease, Checklist, Cross-Sectional Studies, Mood disorders, Quality of Life, Female, business
Abstract: Aim Frailty and sarcopenia affect the prognosis and quality of life of patients with chronic obstructive pulmonary disease (COPD). However, it remains uncertain which model is the most suitable for evaluating vulnerability in patients with COPD. We evaluated the validity of three frailty models - the Kihon Checklist (KCL), the Japanese version of the Cardiovascular Health Study and the Study of Osteoporotic Fractures - and one sarcopenia model for older patients with COPD. Methods This cross-sectional study included 201 older (aged ≥65 years) outpatients with COPD. We used three frailty models and one sarcopenia model to identify their correlation with various indices that can evaluate the status of COPD and determine the most ideal model for evaluating vulnerability in patients with COPD. Results The highest prevalence of frailty (38%) and lowest prevalence of robustness (26%) were observed using the KCL. Although all models reflected the characteristics of COPD, the KCL yielded the strongest correlations with clinically important physical, psychological and prognostic indices. The KCL yielded statistically significant differences in almost all indices among the three intergroup comparisons (robust, pre-frailty and frailty). The KCL was superior in extracting mood disorders to the other models. Conclusion Although all investigated models were useful, the KCL was the most suitable for evaluating the frailty status and might enable interventions in patients with COPD. Geriatr Gerontol Int 2019; 19: 896-901.
Published: 2019

33. Inhibitory Effects of Chlorella Extract on Airway Hyperresponsiveness and Airway Remodeling in a Murine Model of Asthma

Author: Yoshito Miyata, Kuniaki Hirai, Sojiro Kusumoto, Tsukasa Ohnishi, Shin Ohta, Fumihiro Yamaguchi, Naota Kuwahara, Yoshitaka Uchida, Mayumi Yamamoto, Ryo Manabe, Tomoki Uno, Hiroko Mizuma, Shintaro Suzuki, Tetsuya Homma, Akihiko Tanaka, Munehiro Yamaguchi, Megumi Jinno, and Hironori Sagara
Subjects: Chlorella, biology, business.industry, Murine model, Immunology, Airway hyperresponsiveness, Medicine, Inhibitory postsynaptic potential, biology.organism_classification, Airway, business, medicine.disease, Asthma
Published: 2019

34. Characteristics of and reasons for patients with chronic obstructive pulmonary disease to continue smoking, quit smoking, and switch to heated tobacco products

Author: Hatsuko Mikuni, Hironori Sagara, Kuniaki Hirai, Yosuke Fukuda, Naruhito Oda, Shintaro Suzuki, Yoshitaka Uchida, Tomoko Kawahara, Yoko Sato, Akihiko Tanaka, Hideki Inoue, Tsukasa Ohnishi, Akiko Fujiwara, Fumihiro Yamaguchi, Shin Ohta, Tetsuya Homma, Haruhisa Saito, and Tomoki Uno
Subjects: medicine.medical_specialty, Health (social science), Younger age, medicine.medical_treatment, Medicine (miscellaneous), Pulmonary disease, Logistic regression, Quit smoking, smoking, chronic obstructive pulmonary disease, heated tobacco products, Diseases of the respiratory system, Internal medicine, Medicine, Effective treatment, In patient, RC254-282, COPD, RC705-779, business.industry, Public Health, Environmental and Occupational Health, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Smoking cessation, business, cigarettes, Research Paper
Abstract: Introduction Smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and smoking cessation is the most effective treatment for patients with COPD. However, few studies have investigated the continuation/cessation of smoking and heated tobacco products (HTP) in patients with COPD. The objective of this study was to examine the characteristics of patients with COPD, those who are current smokers and those who switched from cigarettes to HTP, and to examine the reason for the continuation or cessation of smoking. Methods This multicenter, cross-sectional study included 411 outpatients with COPD. Data for this study were part of a study conducted for a comprehensive evaluation of the smoking status and clinical factors in patients with COPD and their families. Results Logistic regression analysis revealed that a younger age, longer duration of smoking, fewer daily cigarettes, and lower modified Medical Research Council (mMRC) dyspnea score, and a lower Simplified Nutritional Appetite Questionnaire (SNAQ) score for appetite, were characteristics of current smokers (age OR=0.94; duration of smoking OR=1.07; number of cigarettes per day OR=0.94; mMRC OR=0.68; SNAQ OR=0.83; p
Published: 2021

35. Investigating Patient and Family Satisfaction with the Respiratory Status in Patients with Chronic Obstructive Pulmonary Disease

Author: Hatsuko Mikuni, Haruhisa Saito, Yoshito Miyata, Akihiko Tanaka, Tomoko Kawahara, Tsukasa Ohnishi, Shin Ohta, Hironori Sagara, Keisuke Kaneko, Akiko Fujiwara, Yuiko Goto, Fumihiro Yamaguchi, Yoshitaka Uchida, Tomoki Uno, Tetsuya Homma, Kuniaki Hirai, Naruhito Oda, and Shintaro Suzuki
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pulmonary disease, Family satisfaction, Personal Satisfaction, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Quality of life (healthcare), Surveys and Questionnaires, medicine, Humans, In patient, 030212 general & internal medicine, Intensive care medicine, COPD, business.industry, Healthy life expectancy, medicine.disease, Respiratory status, Cross-Sectional Studies, Dyspnea, 030228 respiratory system, Copd assessment test, Quality of Life, business
Abstract: The current chronic obstructive pulmonary disease (COPD) management aims to improve the patients' quality of life and healthy life expectancy; however, few studies have evaluated the level of satisfaction with the patients' current respiratory status in COPD patients and their families. This study aimed to examine the level of patient and family satisfaction with the patients' current respiratory status and to identify the clinical factors closely linked to dissatisfaction.This multicenter, cross-sectional study included 454 outpatients with COPD and 296 family members. Patients and families were allocated to the satisfied and dissatisfied groups based on their satisfaction with the patients' current respiratory status. Patients' health status, dyspnoea, appetite, respiratory function, and mood disorders were assessed.Among the participants of this study, 67% of patients and 60% of their families were dissatisfied with the patients' current respiratory status. The COPD assessment test (CAT) was the most sensitive marker of dissatisfaction compared to other clinical factors (p 0.01). The statistical cut-off value of CAT for predicting patient dissatisfaction was 11. CAT reflected patient dissatisfaction independent of age, sex, dyspnoea, appetite, mood disorders, body mass index, and respiratory function (odds ratio: CAT; 1.12 (1.07-1.19): p 0.01).Many patients and families are dissatisfied with the patients' respiratory status, and the patients' CAT score is useful to predict dissatisfaction. Our findings are consistent with the Global Initiative for Chronic Obstructive Lung Disease indicating that treatment should be enhanced in patients with a CAT score ≥10. Furthermore, treatment strategies targeting CAT may contribute to an improved patient satisfaction.
Published: 2021

36. An Extreme Auroral Electrojet Spike During 2023 April 24th Storm

Author: Ying Zou, Jesper W. Gjerloev, Shin Ohtani, Matt Friel, Jun Liang, Larry L. Lyons, Yangyang Shen, Jiang Liu, Li‐Jen Chen, Banafsheh Ferdousi, Alex Chartier, Sarah Vines, and Colin L. Waters
Subjects: auroral electrojet, geomagnetic storm, geomagnetic perturbation, solar wind pressure, diffuse aurora, ionospheric conductivity, Geology, QE1-996.5, Geophysics. Cosmic physics, QC801-809
Abstract: Abstract Abrupt variations of auroral electrojets can induce geomagnetically induced currents, and the ability to model and forecast them is a pressing goal of space weather research. We report an auroral electrojet spike event that is extreme in magnitude, explosive in nature, and global in spatial extent that occurred on 24 April 2023. The event serves as a fundamental test of our understanding of the response of the geospace system to solar wind dynamics. Our results illustrate new and important characteristics that are drastically different from existing knowledge. Most important findings include (a) the event was only of ∼5‐min duration and was limited to a narrow (2°–3°) band of diffuse aurora; (b) the longitudinal span covered the entire nightside sector, possibly extending to the dayside; (c) the trigger seems to be a transient solar wind dynamic pressure pulse. In comparison, substorms usually last 1–2 hr and span almost the entire latitudinal width of the auroral oval. Magnetic perturbation events (MPEs) span hundreds km in radius. Both substorms and MPEs are mainly driven by disturbances in the magnetotail. A possible explanation is that the pressure pulse compresses the magnetosphere and enhances diffuse precipitation of electrons and protons from the inner plasma sheet, which elevates the ionospheric conductivity and intensifies the auroral electrojet. Therefore, the event exhibits a potentially new type of geomagnetic disturbance and highlights a solar wind driver that is enormously influential in driving extreme space weather events.
Published: 2024
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37. β

Author: Haruki, Funakoshi, Kenji, Momo, Keinosuke, Okazaki, Takaya, Ebato, Shigenori, Yamamoto, Tomoki, Uno, Shin, Ohta, Hironori, Sagara, and Tadanori, Sasaki
Subjects: Tachycardia, Administration, Inhalation, Atrial Fibrillation, Humans, Receptors, Adrenergic, beta-2, Asthma
Published: 2020

38. Increased levels of circulating cell-free DNA in COVID-19 patients with respiratory failure

Author: Katsuki Wakayama, Kiichi Nakahira, Akihiko Tanaka, Yosuke Hukuda, Jing Zhao, Shin Ohta, Hironori Sagara, and Masanori Yoshizumi
Subjects: Applied Mathematics, General Mathematics
Published: 2022

39. [NEXT-GENERATION ARIA CARE PATHWAYS IN ALLERGIC RHINITIS]

Author: Yoshitaka, Okamoto, Ken, Ohta, Maho, Suzukawa, Shin, Ohta, Mitsuhiro, Okano, Daiju, Sakurai, and Hiroyuki, Tashimo
Subjects: Rhinitis, Allergic, Perennial, Humans, Immunotherapy, Rhinitis, Allergic
Published: 2020

40. The Relationship Between the 'Adherence Starts with Knowledge-20' Questionnaire and Clinical Factors in Patients with COPD: A Multi-Center, Cross-Sectional Study

Author: Hironori Sagara, Tomoko Kawahara, Akiko Fujiwara, Tomohiro Matsunaga, Fumihiro Yamaguchi, Shin Ohta, Hatsuko Mikuni, Tetsuya Homma, Hideki Inoue, Sojiro Kusumoto, Yoshito Miyata, Kaho Akimoto, Akihiko Tanaka, Keisuke Kaneko, Shintaro Suzuki, Kuniaki Hirai, and Tomoki Uno
Subjects: Male, medicine.medical_specialty, Respimat, Cross-sectional study, Hospital Anxiety and Depression Scale, Severity of Illness Index, ASK-20, inhaler, Pulmonary function testing, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Japan, Internal medicine, Surveys and Questionnaires, medicine, Humans, COPD, Respiratory function, 030212 general & internal medicine, adherence, Original Research, business.industry, Inhaler, General Medicine, medicine.disease, Obstructive lung disease, Cross-Sectional Studies, 030228 respiratory system, business
Abstract: Purpose Inhaler therapy is the mainstay of chronic obstructive pulmonary disease (COPD) management. Poor adherence causes disease exacerbation and affects patient mortality. Although the Adherence Starts with Knowledge-20 (ASK-20) questionnaire is a reliable tool for assessing medication adherence, the relationship between the ASK-20 and clinical factors in patients with COPD remains unknown. We investigated the relationship between the ASK-20 and clinical factors, and assessed real-world inhaler therapy use. Patients and Methods A multicenter, cross-sectional study of outpatients with COPD undergoing inhaler treatment who completed the ASK-20 questionnaire was performed. We investigated COPD-related health status using the COPD Assessment Test (CAT), psychological status using the Hospital Anxiety and Depression Scale (HADS-anxiety and HADS-depression), respiratory function, patient satisfaction levels, and real-world inhaler therapy use. Results Of the total 319 patients, 87% were male with a median age of 74 years. Most patients had mild or moderate COPD, according to Global Initiative for Chronic Obstructive Lung Disease stage. The total ASK-20 scores correlated significantly with the CAT, HADS-anxiety, and HADS-depression scores (r = 0.27, 0.33, and 0.29, respectively, p < 0.01). Multivariable analysis showed that CAT and HADS-anxiety scores had an independent and significant impact on the ASK-20 scores [β, standardized regression coefficient: 0.18 (95% CI, 0.03–0.35; p = 0.02), and 0.29 (95% CI, 0.17–0.42; p < 0.01), respectively]; however, the ASK-20 scores were not correlated with age, sex, body mass index, cohabitation, modified Medical Research Council Dyspnea Scale score, pulmonary function, disease duration, number of COPD exacerbations per year, comorbidities, inhaler numbers, nor inhaler components. Conclusion The ASK-20 scores in patients with COPD were significantly associated with CAT and HADS scores. In Japan, Respimat was prescribed to younger patients and patients with lower CAT scores. The ASK-20, a simple evaluation method, is useful for identifying clinical factors affecting adherence in patients with COPD.
Published: 2020

41. Correlation of Arterial CO2 and Respiratory Impedance Values among Subjects with COPD

Author: Hatsuko Mikuni, Masahiko Shigemura, Ayaka Kashima, Chihiro Onitsuka, Akiko Fujiwara, Kuniaki Hirai, Ryo Manabe, Sojiro Kusumoto, Tomoki Uno, Akihiko Tanaka, Mayumi Yamamoto, Tohru Ohmori, Yoshitaka Uchida, Yasunari Kishino, Megumi Jinno, Hideki Inoue, Tomoko Kawahara, Tomohiro Matsunaga, Yosuke Fukuda, Hiromitsu Suganuma, Keisuke Kaneko, Yoshio Watanabe, Koichi Ando, Hiroki Sato, Shin Ohta, Naota Kuwahara, Haruna Sato, Takaya Ebato, Shigenori Yamamoto, Hitomi Ida, Tetsuya Homma, Yoshito Miyata, Tomoyuki Kimura, Kaho Akimoto, Shintaro Suzuki, and Hironori Sagara
Subjects: CO2, medicine.medical_specialty, lcsh:Medicine, Article, Pulmonary function testing, 03 medical and health sciences, 0302 clinical medicine, Forced Oscillation Technique, Quality of life, Internal medicine, Linear regression, medicine, 030212 general & internal medicine, Normocapnia, Respiratory system, COPD, business.industry, lcsh:R, FOT, hypercapnia, General Medicine, medicine.disease, respiratory tract diseases, 030228 respiratory system, Cardiology, medicine.symptom, business, Hypercapnia
Abstract: Chronic obstructive pulmonary disease (COPD) is a respiratory illness characterized by airflow limitation and chronic respiratory symptoms with a global prevalence estimated to be more than 10% in 2010 and still on the rise. Furthermore, hypercapnic subject COPD leads to an increased risk of mortality, morbidity, and poor QoL (quality of life) than normocapnic subjects. Series of studies showed the usefulness of the forced oscillation technique (FOT) to measure small airway closure. Traditional findings suggested that hypercapnia may not be the main treating targets, but recent findings suggested that blood stream CO2 may lead to a worse outcome. This study aimed to seek the relationship between CO2 and small airway closure by using FOT. Subjects with COPD (n = 124, hypercapnia 22 and normocapnia 102) were analyzed for all pulmonary function values, FOT values, and arterial blood gas analysis. Student&rsquo, s t-test, Spearman rank correlation, and multi linear regression analysis were used to analyze the data. COPD subjects with hypercapnia showed a significant increase in R5, R20, Fres, and ALX values, and a greater decrease in X5 value than normocapnic patients. Also, multiple linear regression analysis showed R5 was associated with hypercapnia. Hypercapnia may account for airway closure among subjects with COPD and this result suggests treating hypercapnia may lead to better outcomes for such a subject group.
Published: 2020

42. Steroid-Sparing Effect of Mepolizumab in Asthmatic Patients with Chronic Eosinophilic Pneumonia

Author: Hironori Sagara, Shin Ohta, Megumi Jinno, Haruna Sato, Akihiko Tanaka, Hideki Inoue, Tetsuya Homma, and Yoshito Miyata
Subjects: medicine.medical_specialty, business.industry, Internal medicine, Steroid sparing, medicine, Asthmatic patient, Chronic eosinophilic pneumonia, business, Gastroenterology, Mepolizumab, medicine.drug
Published: 2020

43. The Repeated Bronchodilation by Salbutamol Inhalation Induced the Development of M2 Macrophages in Murine Model of Asthma

Author: Shin Ohta, Hitomi Ida, Kuniaki Hirai, Yusuke Watanabe, Hironori Sagara, Yoshito Miyata, Shintaro Suzuki, Yoshitaka Uchida, Tomoki Uno, Tomoyuki Kimura, Akihiko Tanaka, Sojiro Kusumoto, Yasunari Kishino, Tetsuya Homma, Mayumi Yamamoto, Hideki Inoue, Megumi Jinno, and Haruo Sato
Subjects: Inhalation, Murine model, business.industry, Bronchodilation, medicine, Salbutamol, Pharmacology, medicine.disease, business, Asthma, medicine.drug
Published: 2020

44. Eosinophilic Airway Inflammation and Activation of ERBB2 in Alternaria-Induced Asthma Mice Model

Author: Shintaro Suzuki, Shin Ohta, Hironori Sagara, Akihiko Tanaka, Hideki Inoue, Kaho Akimoto, and M. Matsuda
Subjects: biology, business.industry, Eosinophilic, Immunology, medicine, Airway inflammation, Alternaria, biology.organism_classification, medicine.disease, business, Asthma
Published: 2020

45. Investigation of Df Induced Asthma Model in Each Age of Mice

Author: Yoshito Miyata, Akihiko Tanaka, Tomoyuki Kimura, Yoshitaka Uchida, Yusuke Watanabe, Hironori Sagara, Tetsuya Homma, Megumi Jinno, Sojiro Kusumoto, Yasunari Kishino, Mayumi Yamamoto, Hideki Inoue, Hitomi Ida, Kuniaki Hirai, Shin Ohta, Haruo Sato, Shintaro Suzuki, and Tomoki Uno
Subjects: business.industry, Immunology, Medicine, Asthma model, business
Published: 2020

46. Inhibition of Virus-Induced Cytokine Production from Airway Epithelial Cells by the Late Addition of Budesonide

Author: Shin Ohta, Yasunari Kishino, Yosuke Fukuda, Akihiko Tanaka, Hironori Sagara, Tohru Ohmori, Yoshitaka Uchida, Keisuke Kaneko, Yoshito Miyata, Shintaro Suzuki, Tetsuya Homma, Mayumi Yamamoto, Yoshio Watanabe, Akiko Fujiwara, Hideki Inoue, Koichi Ando, Toshimitsu Yamaoka, Megumi Jinno, Sojiro Kusumoto, Haruna Sato, Tomoki Uno, Kuniaki Hirai, Hiroki Sato, and Kaho Akimoto
Subjects: 0301 basic medicine, Budesonide, Medicine (General), Chemokine, Thymic stromal lymphopoietin, budesonide, Rhinovirus, medicine.medical_treatment, viruses, Cell Culture Techniques, Respiratory Mucosa, Article, Proinflammatory cytokine, 03 medical and health sciences, R5-920, 0302 clinical medicine, Glucocorticoid receptor, Humans, Medicine, Respiratory Tract Infections, Dexamethasone, thymic stromal lymphopoietin (TSLP), rhinovirus, Picornaviridae Infections, biology, Chemokine CCL26, business.industry, General Medicine, epithelial cells, Bronchodilator Agents, respiratory tract diseases, 030104 developmental biology, Cytokine, 030228 respiratory system, Immunology, biology.protein, thymic stromal lymphopoietin (TSLP), rhinovirus, Cytokines, CCL26, business, medicine.drug
Abstract: Background: Viral infection is the main cause of asthma and COPD (chronic obstructive pulmonary disease) exacerbation and accumulate inflammatory cells to airway tissue. We have reported poly I:C, a mimic product of the virus and ligand of toll-like receptor 3 (TLR3), induced inflammatory chemokines from airway epithelial cells and found prior incubation with corticosteroids diminishes the effect of TLR3 activation. In clinical practice, mild asthma is recommended as-needed budesonide (BUD) when symptoms occur following a viral infection, etc. However, many questions still surround BUD&rsquo, s usefulness if taken after a virus has already infected airway tissue. Objective: The aim of this study was to investigate the inhibitory effects of BUD on inflammatory cytokines induced by viral infection. Methods: Normal human bronchial epithelial (NHBE) cells were stimulated with poly I:C or infected with human rhinovirus-16 (HRV16) and BUD was added after the initial stimulation. Expression of both thymic stromal lymphopoietin (TSLP) and CCL26/eotaxin-3 was quantified by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Knockdown study was performed. Results: Pre-or post-incubation with BUD inhibited both poly I:C- and HRV16-induced mRNAs and proteins of both thymic stromal lymphopoietin (TSLP) and CCL26 with significance. Knockdown of the glucocorticoid receptor diminished these effects of BUD. Under the same conditions of BUD&rsquo, s experiment, post-incubation with neither fluticasone propionate nor dexamethasone suppressed expression of both TSLP and CCL26, which induced by poly I:C. Conclusion: Post-addition of BUD inhibited the virus-induced TSLP and CCL26 from the airway epithelial cells. These results suggest that inhalation of BUD after viral infection has beneficial effects on asthma. Conclusion: Late addition of BUD may benefit among patient with viral infection and type 2 allergic airway disease such as asthma.
Published: 2020
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47. Combination treatment of short-course systemic corticosteroid and favipiravir in a successfully treated case of critically ill COVID-19 pneumonia with COPD

Author: Yoshio Watanabe, Shin Ohta, Tomoki Uno, Yoshito Miyata, Megumi Jinno, Hitoshi Ikeda, Haruna Sato, Yuiko Goto, Chisato Onitsuka, Issei Tokimatsu, Sojiro Kusumoto, Tomoyuki Kimura, Kuniaki Hirai, Tetsuya Homma, Yasunari Kishino, Tomoko Kawahara, Hiroki Sato, Shintaro Suzuki, Yoshitaka Uchida, Yoko Sato, Hatsuko Mikuni, Mayumi Yamamoto, Hideki Inoue, Hironori Sagara, and Akihiko Tanaka
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, Case Report, Favipiravir, Gastroenterology, MERS, middle east respiratory syndrome, 03 medical and health sciences, SRAS-CoV-2, severe acute respiratory syndrome coronavirus 2, 0302 clinical medicine, PCR, polymerase chain reaction, Internal medicine, medicine, COPD, SFTSV, severe fever with thrombocytopenia syndrome virus, ARDS, acute respiratory distress syndrome, COVID-19, coronavirus disease 2019, Mechanical ventilation, lcsh:RC705-779, Systemic corticosteroid, business.industry, SARS-CoV-2, GOLD, The Global Initiative for Chronic Obstructive Lung Disease, COVID-19, Pneumonia, lcsh:Diseases of the respiratory system, SpO2, peripheral capillary oxygen saturation, medicine.disease, ICU, intensive care unit, CT, computed tomography, respiratory tract diseases, 030228 respiratory system, Respiratory failure, COPD, chronic obstructive pulmonary disease, 030220 oncology & carcinogenesis, Prednisolone, CRP, C-reactive protein, Middle East respiratory syndrome, Corticosteroid, RSV, respiratory syncytial virus, business, medicine.drug, WBC, white blood cell
Abstract: Use of systemic corticosteroids for the treatment for coronavirus disease 2019 (COVID-19) among chronic obstructive pulmonary disease (COPD) patients is not well described. A 58-year-old man with fever and progressive dyspnea was admitted to the Showa University Hospital, and showed severe respiratory failure which needed mechanical ventilation. His chest computed tomography scanning showed emphysema and bilateral ground-glass opacity caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. He received 30 mg prednisolone for five days with antiviral drug of favipiravir, and was successfully extubated on day five. A SARS-CoV-2 polymerase chain reaction (PCR) test became negative on day 15. He was discharged on day 21. Serum IgM and IgG antibodies against SARS-CoV-2 converted to positive on day 7 and they kept positive on day 54 for both IgM and IgG. Combination treatment of short-course systemic corticosteroid and favipiravir might improve the prognosis for critically ill COVID-19 pneumonia with COPD without negative influence on viral clearance or antibody production.
Published: 2020

48. Oral meal intake as a prognostic predictor of community-acquired pneumonia: A retrospective cohort study

Author: Shin Ohta, Hironori Sagara, Hiromitsu Suganuma, Sojiro Kusumoto, Kaho Akimoto, Hiroki Sato, Tomoko Kawahara, Shintaro Suzuki, Hatsuko Mikuni, Keisuke Kaneko, Akihiko Tanaka, Kuniaki Hirai, and Tetsuya Homma
Subjects: 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Serum albumin, 03 medical and health sciences, 0302 clinical medicine, Community-acquired pneumonia, Internal medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Meals, Retrospective Studies, Meal, biology, business.industry, Mortality rate, Area under the curve, Retrospective cohort study, Pneumonia, medicine.disease, Prognosis, Confidence interval, Community-Acquired Infections, Hospitalization, Infectious Diseases, biology.protein, business
Abstract: The association between oral intake volume and prognosis has not been studied in hospitalized patients with community-acquired pneumonia (CAP).We retrospectively examined 503 hospitalized CAP patients to evaluate whether early-phase meal intake (EMI) (within the first 24 h after hospitalization) and maximum meal intake (MMI) (on the day during hospitalization) are useful prognostic predictors.Of the 503 patients, 40 (8.0%) died within 30 days. Area under the curve (AUC) for prognosis was comparable between EMI, A-DROP, and serum albumin [EMI: 0.80, 95% confidence interval (CI) 0.75-0.84; A-DROP: 0.77, 95% CI 0.71-0.83; Serum albumin: 0.72, 95% CI 0.64-0.79]. Mortality rate was1% in patients with EMI ≥ 50%. Univariate analysis showed that patients with EMI50% showed poor prognosis [odds ratio 53.4, 95% CI 7.2-392.2]. Multivariate analysis showed that EMI was an independent prognostic predictor [odds ratio 23.6, 95% CI 3.11-179.7]. AUC of MMI for prognosis was 0.94 (95% CI 0.91-0.96); mortality rate was1% for patients who ingested ≥50% of meals on any day during hospitalization. We defined ingesting ≥50% of meals on any day during hospitalization as oral intake stability. Multivariate analyses revealed an association between oral intake stability and prognosis. Odds ratio of oral intake stability for prognosis was higher than that of conventional evaluations (vital sign and CRP level stability). Fewer days were required to reach oral intake stability than to reach vital sign and CRP level stability.Oral intake is a simple, non-invasive, cost-free, and powerful prognostic predictor for patients with CAP.
Published: 2019

49. Tokyo Anti-Fibrosis in the Lung Research Project

Author: Maho Suzukawa, Shin Ohta, and Ken Ohta
Subjects: Anti fibrosis, Pathology, medicine.medical_specialty, Lung, medicine.anatomical_structure, business.industry, medicine, business
Published: 2019

50. Prevalence and clinical features of asthma-COPD overlap in patients with COPD not using inhaled corticosteroids

Author: Hatsuko Mikuni, Naruhito Oda, Shintaro Suzuki, Tomoko Kawahara, Tomoki Uno, Yoshito Miyata, Shin Ohta, Fumihiro Yamaguchi, Hironori Sagara, Akihiko Tanaka, Tetsuya Homma, Kuniaki Hirai, Hideki Inoue, and Yoshitaka Uchida
Subjects: Male, lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, MEDLINE, Inhaled corticosteroids, Comorbidity, Pulmonary Disease, Chronic Obstructive, Japan, Adrenal Cortex Hormones, Forced Expiratory Volume, Internal medicine, Administration, Inhalation, Prevalence, medicine, Humans, Immunology and Allergy, In patient, Asthma copd overlap, Aged, COPD, business.industry, General Medicine, medicine.disease, Asthma, Cross-Sectional Studies, Disease Progression, Female, lcsh:RC581-607, business
Published: 2021

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