Regulation of the coagulation cascade as a new therapeutic strategy for pulmonary injury following traumatic brain injury

• Project/Area Number: 18K16535
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Yasui Hideki 浜松医科大学, 臨床研究センター, 特任講師 (60804937)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 頭部外傷 / 肺障害 / 凝固障害 / 急性肺障害

Outline of Final Research Achievements

Extracranial complications frequently occur in patients with traumatic brain injury (TBI). Among them, pulmonary injury is a serious complication that affects the prognosis; however, its mechanism is unclear. In an animal model, activation of the coagulation cascade was seen immediately after TBI. Histological findings of lung injury were also observed immediately after TBI, and these findings were persistent at 60 minutes after TBI. Additionally, we observed a case of pulmonary injury accompanied by neither a catecholamine elevation nor a change in the systemic circulation, both of which have historically been considered to be mechanisms of pulmonary injury after TBI. We also observed a case involving activation of the coagulation cascade immediately after severe brain injury. These findings indicate that activation of the coagulation cascade might be related to the mechanism of lung injury after TBI.

Academic Significance and Societal Importance of the Research Achievements

頭部外傷は、死亡や身体障害につながる主要な要因であり、頭部外傷後に肺障害を合併することで予後がさらに悪化することが判明している。これまで肺障害の発症メカニズムとしては、頭部外傷後のカテコラミンストームとその後の循環動態の変化が主要な要因と考えられてきた。しかしながら、今回の研究では、頭部外傷後短時間のうちに、上記の現象とは無関係に肺障害を発症することが確認された。一方で、肺障害には凝固カスケードの活性化という新たな機序の関与が示唆され、頭部外傷の治療戦略を考えるうえで意義のある研究であり、更なる研究の継続をする意義があるものと考えられる。

Research Products

• [Journal Article] Association of the Geriatric Nutritional Risk Index with the survival of patients with non-small-cell lung cancer after platinum-based chemotherapy (2021)
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• [Journal Article] MET Amplification and Efficacy of Nivolumab in Patients With NSCLC. (2021)
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  • Journal Title: JTO Clin Res Rep. Volume: 2(11) Issue: 11 Pages: 100239-100239
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• [Journal Article] Radiological pleuroparenchymal fibroelastosis-like lesion in idiopathic interstitial pneumonias. (2021)
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• [Journal Article] Comparative assessment of NOIR-SS and ddPCR for ctDNA detection of EGFR L858R mutations in advanced L858R-positive lung adenocarcinomas. (2021)
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• [Journal Article] Serum S100A8 and S100A9 as prognostic biomarkers in acute exacerbation of idiopathic pulmonary fibrosis. (2021)
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• [Journal Article] Prognostic and Clinical Value of Cluster Analysis in Idiopathic Pleuroparenchymal Fibroelastosis Phenotypes (2021)
  • Author(s): Nakamura Yutaro、Mori Kazutaka、Enomoto Yasunori、Kono Masato、Sumikawa Hiromitsu、Johkoh Takeshi、Colby Thomas V.、et al.
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• [Journal Article] Simple method for detecting idiopathic interstitial pneumonias by measuring vertical lung length on chest X-ray. (2021)
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• [Journal Article] Cluster analysis-based clinical phenotypes of idiopathic interstitial pneumonias: associations with acute exacerbation and overall survival (2021)
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• [Journal Article] Clinical Significance of Interstitial Lung Disease and Its Acute Exacerbation in Microscopic Polyangiitis (2021)
  • Author(s): Hozumi H, Kono M, Hasegawa H, Yasui H, Suzuki Y, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Inui N, Nakamura Y, Yokomura K, Nakamura H, Suda T.
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• [Journal Article] Predictors for bronchoalveolar lavage recovery failure in diffuse parenchymal lung disease (2021)
  • Author(s): Koda K, Hozumi H, Yasui H, Suzuki Y, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Inui N, Nakamura Y, Suda T.
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• [Journal Article] Pneumothorax in Patients with Idiopathic Pleuroparenchymal Fibroelastosis: Incidence, Clinical Features, and Risk Factors (2021)
  • Author(s): Kono Masato、Nakamura Yutaro、Enomoto Yasunori、Yasui Hideki、Hozumi Hironao、Karayama Masato、Suzuki Yuzo、Furuhashi Kazuki、Miki Yoshihiro、Hashimoto Dai、Fujisawa Tomoyuki、Enomoto Noriyuki、Inui Naoki、Suda Takafumi
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• [Journal Article] Prednisolone and tacrolimus versus prednisolone and cyclosporin A to treat polymyositis/dermatomyositis‐associated ILD : A randomized, open‐label trial (2020)
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  • Journal Title: Respirology Volume: 26 Issue: 4 Pages: 370-377
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• [Journal Article] Erlotinib and bevacizumab in elderly patients ?75?years old with non-small cell lung cancer harboring epidermal growth factor receptor mutations (2020)
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  • Journal Title: Investigational New Drugs Volume: 39 Issue: 1 Pages: 210-216
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  • NAID: 120007143503
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• [Journal Article] Influenza A virus enhances ciliary activity and mucociliary clearance via TLR3 in airway epithelium. (2020)
  • Author(s): Kamiya Y, Fujisawa T, Katsumata M, Yasui H, Suzuki Y, Karayama M, Hozumi H, Furuhashi K, Enomoto N, Nakamura Y, Inui N, Setou M, Ito M, Suzuki T, Ikegami K, Suda T.
  • Journal Title: Respir Res. Volume: 21 Issue: 1 Pages: 282-282
  • DOI: 10.1186/s12931-020-01555-1
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• [Journal Article] Evaluation of Programmed Death Ligand 1 (PD-L1) Gene Amplification and Response to Nivolumab Monotherapy in Non-small Cell Lung Cancer (2020)
  • Author(s): Inoue Y, Yoshimura K, Nishimoto K, Inui N, Karayama M, Yasui H, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Asada K, Uto T, Fujii M, Matsui T, Matsuura S, Hashimoto D, Toyoshima M, Kusagaya H, Matsuda H, Inami N, Kaida Y, Niwa M, Ito Y, Sugimura H, Suda T.
  • Journal Title: JAMA Netw Open. Volume: 3(9) Issue: 9 Pages: e2011818-e2011818
  • DOI: 10.1001/jamanetworkopen.2020.11818
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• [Journal Article] Prognostic significance of forced vital capacity decline prior to and following antifibrotic therapy in idiopathic pulmonary fibrosis (2020)
  • Author(s): Aono Yuya、Nakamura Yutaro, et al.
  • Journal Title: Therapeutic Advances in Respiratory Disease Volume: 14
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• [Journal Article] Development of a novel T cell‐oriented vaccine using CTL/Th‐hybrid epitope long peptide and biodegradable microparticles, against an intracellular bacterium (2020)
  • Author(s): Tanaka Kazuki、Enomoto Noriyuki, et al.
  • Journal Title: Microbiology and Immunology Volume: 64 Issue: 10 Pages: 666-678
  • DOI: 10.1111/1348-0421.12836
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• [Journal Article] Pneumothorax in connective tissue disease-associated interstitial lung disease. (2020)
  • Author(s): Nishimoto K, Fujisawa T, Yoshimura K, Enomoto Y, Yasui H, Hozumi H, Karayama M, Suzuki Y, Furuhashi K, Enomoto N, Nakamura Y, Inui N, Sumikawa H, Johkoh T, Suda T.
  • Journal Title: PLoS One. Volume: 15(7) Issue: 7 Pages: e0235624-e0235624
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• [Journal Article] Acute exacerbation of unclassifiable idiopathic interstitial pneumonia: comparison with idiopathic pulmonary fibrosis (2020)
  • Author(s): Enomoto N, Naoi H, Aono Y, Katsumata M, Horiike Y, Yasui H, Karayama M, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Inui N, Nakamura Y, Suda T.
  • Journal Title: Ther Adv Respir Dis. Volume: 14
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• [Journal Article] Palliative Care for Idiopathic Pulmonary Fibrosis Patients: Pulmonary Physicians' View (2020)
  • Author(s): Akiyama N, Fujisawa T, Morita T, Mori K, Yasui H, Hozumi H, Suzuki Y, Karayama M, Furuhashi K, Enomoto N, Nakamura Y, Inui N, Suda T.
  • Journal Title: J Pain Symptom Manage. Volume: 60(5) Issue: 5 Pages: 933-940
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• [Journal Article] Comparison of Chest Compression Quality Using Wing Boards versus Walking Next to a Moving Stretcher: A Randomized Crossover Simulation Study (2020)
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  • Journal Title: J Clin Med. Volume: 9(5) Issue: 5 Pages: 1584-1584
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• [Journal Article] Assessment of Immune-Related Interstitial Lung Disease in Patients With NSCLC Treated with Immune Checkpoint Inhibitors: A Multicenter Prospective Study (2020)
  • Author(s): Suzuki Y, Karayama M, Uto T, Fujii M, Matsui T, Asada K, Kusagaya H, Kato M, Matsuda H, Matsuura S, Toyoshima M, Mori K, Ito Y, Koyauchi T, Yasui H, Hozumi H, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Suda T.
  • Journal Title: Journal of Thoracic Oncology Volume: S1556 Issue: 8 Pages: 1317-1327
  • DOI: 10.1016/j.jtho.2020.04.002
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• [Journal Article] Intravoxel incoherent motion magnetic resonance imaging for predicting the long-term efficacy of immune checkpoint inhibitors in patients with non-small-cell lung cancer. (2020)
  • Author(s): Karayama M, Yoshizawa N, Sugiyama M, Mori K, Yasui H, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Inui N, Goshima S, Suda T, Takehara Y.
  • Journal Title: Lung Cancer Volume: 143 Pages: 47-54
  • DOI: 10.1016/j.lungcan.2020.03.013
  • NAID: 120007041512
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• [Journal Article] Pulse oximetric saturation to fraction of inspired oxygen (SpO2/FIO2) ratio 24 hours after high-flow nasal cannula (HFNC) initiation is a good predictor of HFNC therapy in patients with acute exacerbation of interstitial lung disease. (2020)
  • Author(s): Koyauchi T, Yasui H, Enomoto N, Hasegawa H, Hozumi H, Suzuki Y, Karayama M, Furuhashi K, Fujisawa T, Nakamura Y, Inui N, Yokomura K, Suda T.
  • Journal Title: Therapeutic Advances in Respiratory Disease Volume: 14
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• [Journal Article] Macrophage Mannose Receptor CD206 Predicts Prognosis in Community-acquired Pneumonia (2019)
  • Author(s): Tsuchiya K, Suzuki Y, Yoshimura K, Yasui H, Karayama M, Hozumi H, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Yokomura K, Suda T.
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• [Journal Article] Prognostic factors for primary Sjögren's syndrome-associated interstitial lung diseases. (2019)
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  • Journal Title: Respiratory Medicine Volume: 159 Pages: 105811-105811
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• [Journal Article] Analysis of serum adiponectin and leptin in patients with acute exacerbation of idiopathic pulmonary fibrosis. (2019)
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• [Journal Article] Prognostic impact of an early marginal decline in forced vital capacity in idiopathic pulmonary fibrosis patients treated with pirfenidone. (2019)
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• [Journal Article] Clinical features of three-dimensional computed tomography-based radiologic phenotypes of chronic obstructive pulmonary disease. (2019)
  • Author(s): Karayama M, Inui N, Yasui H, Kono M, Hozumi H, Suzuki Y, Furuhashi K, Hashimoto D, Enomoto N, Fujisawa T, Nakamura Y, Watanabe H, Suda T.
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• [Journal Article] Successful classification of macrophage-mannose receptor CD206 in severity of anti-MDA5 antibody positive dermatomyositis associated ILD (2019)
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• [Journal Article] Physiological and morphological differences of airways between COPD and asthma?COPD overlap (2019)
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• [Journal Article] Clinical Significance of Serum Chitotriosidase Level in Anti-MDA5 Antibody?positive Dermatomyositis-associated Interstitial Lung Disease (2019)
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• [Journal Article] Olanzapine-containing antiemetic therapy for the prevention of carboplatin-induced nausea and vomiting. (2019)
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  • Author(s): Fujisawa T, Mori K, Mikamo M, Ohno T, Kataoka K, Sugimoto C, Kitamura H, Enomoto N, Egashira R, Sumikawa H, Iwasawa T, Matsushita S, Sugiura H, Hashisako M, Tanaka T, Terasaki Y, Kunugi S, Kitani M, Okuda R, Horiike Y, Enomoto Y, Yasui H, Hozumi H, Suzuki Y, Nakamura Y, Fukuoka J, Johkoh T, Kondoh Y, Ogura T,,, Suda T.
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  • Journal Title: Investigational New Drugs Volume: 印刷中 Issue: 3 Pages: 531-537
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• [Journal Article] Correlation of the modified Medical Research Council dyspnea scale with airway structure assessed by three-dimensional CT in patients with chronic obstructive pulmonary disease (2019)
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• [Journal Article] Low-dose Fluticasone Propionate in Combination With Salmeterol in Patients With Chronic Obstructive Pulmonary Disease. (2018)
  • Author(s): Yasui H, Inui N, Fujisawa T, Karayama M, Enomoto N, Nakamura Y, Kuroishi S, Ohba H, Yokomura K, Sato J, Sato M, Koshimizu N, Toyoshima M, Yamada T, Masuda M, Shirai T, Suda T.
  • Journal Title: Clin Med Insights Circ Respir Pulm Med. Volume: 12
  • DOI: 10.1177/1179548418771702
  • Peer Reviewed / Open Access
• [Journal Article] Neutrophil gelatinase-associated lipocalin in patients with sarcoidosis. (2018)
  • Author(s): Kato S, Inui N, Hozumi H, Inoue Y, Yasui H, Karayama M, Kono M, Suzuki Y, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Watanabe H, Suda T.
  • Journal Title: Respiratory Medicine Volume: 印刷中 Pages: S20-S23
  • DOI: 10.1016/j.rmed.2018.01.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Distinctive characteristics and prognostic significance of interstitial pneumonia with autoimmune features in patients with chronic fibrosing interstitial pneumonia. (2018)
  • Author(s): Yoshimura K, Kono M, Enomoto Y, Nishimoto K, Oyama Y, Yasui H, Hozumi H, Karayama M, Suzuki Y, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Sumikawa H, Johkoh T, Colby TV, Sugimura H, Suda T.
  • Journal Title: Respiratory Medicine Volume: 137 Pages: 167-175
  • DOI: 10.1016/j.rmed.2018.02.024
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Switch maintenance therapy with docetaxel and bevacizumab after induction therapy with cisplatin, pemetrexed, and bevacizumab in advanced non-squamous non-small cell lung cancer: a phase II study (2018)
  • Author(s): Nishimoto Koji、Karayama Masato、Inui Naoki、Yasui Hideki、Hozumi Hironao、Suzuki Yuzo、Furuhashi Kazuki、Fujisawa Tomoyuki、Enomoto Noriyuki、Nakamura Yutaro、Inami Nao、Matsuura Shun、Kaida Yusuke、Matsui Takashi、Asada Kazuhiro、Matsuda Hiroyuki、Fujii Masato、Toyoshima Mikio、Imokawa Shiro、Suda Takafumi
  • Journal Title: Medical Oncology Volume: 35 Issue: 7 Pages: 108-108
  • DOI: 10.1007/s12032-018-1172-x
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical significance of myeloperoxidase-anti-neutrophil cytoplasmic antibody in idiopathic interstitial pneumonias (2018)
  • Author(s): Hozumi Hironao、Oyama Yoshiyuki、Yasui Hideki、Suzuki Yuzo、Kono Masato、Karayama Masato、Furuhashi Kazuki、Enomoto Noriyuki、Fujisawa Tomoyuki、Inui Naoki、Nakamura Yutaro、Suda Takafumi
  • Journal Title: PLOS ONE Volume: 13 Issue: 6 Pages: e0199659-e0199659
  • DOI: 10.1371/journal.pone.0199659
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Differences in airway structural changes assessed by 3-dimensional computed tomography in asthma and asthma?chronic obstructive pulmonary disease overlap (2018)
  • Author(s): Niwa Mitsuru、Fujisawa Tomoyuki、Karayama Masato、Furuhashi Kazuki、Mori Kazutaka、Hashimoto Dai、Yasui Hideki、Suzuki Yuzo、Hozumi Hironao、Enomoto Noriyuki、Nakamura Yutaro、Inui Naoki、Suda Takafumi
  • Journal Title: Annals of Allergy, Asthma & Immunology Volume: 121 Issue: 6 Pages: 704-710.e1
  • DOI: 10.1016/j.anai.2018.08.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Macrophage mannose receptor, CD206, predict prognosis in patients with pulmonary tuberculosis (2018)
  • Author(s): Suzuki Yuzo、Shirai Masahiro、Asada Kazuhiro、Yasui Hideki、Karayama Masato、Hozumi Hironao、Furuhashi Kazuki、Enomoto Noriyuki、Fujisawa Tomoyuki、Nakamura Yutaro、Inui Naoki、Shirai Toshihiro、Hayakawa Hiroshi、Suda Takafumi
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 13129-13129
  • DOI: 10.1038/s41598-018-31565-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prophylactic aprepitant is better than salvage for carboplatin-based chemotherapy: a propensity score-matched analysis (2018)
  • Author(s): Karayama Masato、Inui Naoki、Tanaka Kazuki、Yasui Hideki、Hozumi Hironao、Suzuki Yuzo、Furuhashi Kazuki、Fujisawa Tomoyuki、Enomoto Noriyuki、Nakamura Yutaro、Suda Takafumi
  • Journal Title: Medical Oncology Volume: 35 Issue: 11 Pages: 139-139
  • DOI: 10.1007/s12032-018-1199-z
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] IL-17A Attenuates IFN-λ Expression by Inducing Suppressor of Cytokine Signaling Expression in Airway Epithelium (2018)
  • Author(s): Niwa Mitsuru、Fujisawa Tomoyuki、Mori Kazutaka、Yamanaka Katsumasa、Yasui Hideki、Suzuki Yuzo、Karayama Masato、Hozumi Hironao、Furuhashi Kazuki、Enomoto Noriyuki、Nakamura Yutaro、Inui Naoki、Suzuki Tetsuro、Maekawa Masato、Suda Takafumi
  • Journal Title: The Journal of Immunology Volume: 201 Issue: 8 Pages: 2392-2402
  • DOI: 10.4049/jimmunol.1800147
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Distinct profile and prognostic impact of body composition changes in idiopathic pulmonary fibrosis and idiopathic pleuroparenchymal fibroelastosis (2018)
  • Author(s): Suzuki Yuzo、Yoshimura Katsuhiro、Enomoto Yasunori、Yasui Hideki、Hozumi Hironao、Karayama Masato、Furuhashi Kazuki、Enomoto Noriyuki、Fujisawa Tomoyuki、Nakamura Yutaro、Inui Naoki、Suda Takafumi
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 14074-14074
  • DOI: 10.1038/s41598-018-32478-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Differences in clinical features of acute exacerbation between connective tissue disease-associated interstitial pneumonia and idiopathic pulmonary fibrosis (2018)
  • Author(s): Enomoto Noriyuki、Oyama Yoshiyuki、Enomoto Yasunori、Yasui Hideki、Karayama Masato、Kono Masato、Hozumi Hironao、Suzuki Yuzo、Furuhashi Kazuki、Fujisawa Tomoyuki、Inui Naoki、Nakamura Yutaro、Suda Takafumi
  • Journal Title: Chronic Respiratory Disease Volume: 16
  • DOI: 10.1177/1479972318809476
  • Peer Reviewed / Int'l Joint Research
• [Presentation] The Relationship between the Modified Medical Research Council (mMRC) Dyspnea Scale and Airway Structure Assessed by Three-dimensional CT in Patients with Chronic Obstructive Pulmonary Disease (2019)
  • Author(s): Yasui H, Inui N, Karayama M, Mori K, Hozumi H, Suzuki Y, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Suda T.
  • Organizer: American Thoracic Society 2019 International Conference
  • Int'l Joint Research