Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2020

  -

  Now

  Sapporo Medical University School of Medicine   Department of Respiratory Medicine and Allergology   Associate Professor

• 2015

  -

  2020

  Sapporo Medical University School of Medicine   Department of Respiratory Medicine and Allergology   Lecturer

• 2009

  -

  2015

  Sapporo Medical University   School of Medicine   助教

Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Respiratory medicine  

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University School of Medicine   Department of Respiratory Medicine and Allergology   Associate Professor  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• 非感染性肺障害

• 呼吸器感染症

• ブレオマイシン肺障害モデル

• ブレオマイシン

• 肺サーファクタント

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Papers 【 display / non-display 】

Papers 【 display / non-display 】

• 当院改修時におけるアスペルギルス対策の評価

  黒沼 幸治, 中江 舞美, 韮澤 慎也, 富樫 篤生, 藤谷 好弘, 齋藤 充史, 高橋 聡

  感染症学雑誌 ( (一社)日本感染症学会 )  98 ( 2 ) 281 - 281  2024.03

• The impact of respiratory reactance in oscillometry on survival in patients with idiopathic pulmonary fibrosis.

  Tatsuru Ishikawa, Hirotaka Nishikiori, Yuki Mori, Keiko Fujino, Atsushi Saito, Mamoru Takahashi, Koji Kuronuma, Shiro Hinotsu, Hirofumi Chiba

  BMC pulmonary medicine   24 ( 1 ) 10 - 10  2024.01  [International journal]

  　View Summary

  BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. Pulmonary function tests (PFTs) aid in evaluating the disease status of IPF. The clinical significance of oscillometry measurements in interstitial lung diseases has recently been reported. Our previous study showed that respiratory reactance (Xrs) measured by oscillometry reflected disease severity and predicted subsequent lung capacity decline in patients with IPF. However, the direct impact of Xrs on survival needs to be determined, and there are currently no reference values in oscillometry to predict prognosis. Therefore, this study aimed to investigate the association between oscillometry measurements, particularly Xrs, and survival in patients with IPF and to determine the cutoff values of Xrs that predict 3-year survival. METHODS: We analyzed the relationship between the measured values of PFT and oscillometry derived from 178 patients with IPF. Univariate and multivariate Cox proportional hazards analyses were performed to investigate the relationships between clinical indices at the time of the first oscillometry and survival. We performed the time-dependent receiver operating characteristic (ROC) curve analysis to set the optimized cutoff values of Xrs for 3-year survival prediction. We examined the discriminating power of cutoff values of Xrs on survival using the Kaplan-Meier method and the log-rank test. RESULTS: Xrs components, especially in the inspiratory phase (In), significantly correlated with the PFT values. In the multivariate analyses, Xrs (all of reactance at 5 Hz [X5], resonant frequency [Fres], and low-frequency reactance area [ALX] in the inspiratory phase) had a significant impact on survival (X5, p = 0.003; Fres, p = 0.016; ALX, p = 0.003) independent of age, sex, and other prognostic factors derived from the univariate analysis. The area under the ROC curve was 0.765, 0.759, and 0.766 for X5 In, Fres In, and ALX In, with cutoff values determined at - 0.98, 10.67, and 5.32, respectively. We found significant differences in survival after dividing patients using each of the cutoff values of Xrs. CONCLUSIONS: In patients with IPF, Xrs measured by oscillometry significantly impacted survival. We also determined the cutoff values of Xrs to discriminate patients with poor prognoses.

  DOI PubMed

• 手洗器の水栓口や給水システムの汚染による緑膿菌の感染伝播

  藤谷 好弘, 中江 舞美, 佐藤 勇樹, 韮澤 慎也, 富樫 篤生, 齋藤 充史, 黒沼 幸治, 高橋 聡

  感染症学雑誌 ( (一社)日本感染症学会 )  98 ( 1 ) 119 - 119  2024.01

• Factors affecting the sensitivity of quantitative severe acute respiratory syndrome coronavirus 2 antigen test.

  Yuki Sato, Ryosei Murai, Ryo Kobayashi, Atsuo Togashi, Yoshihiro Fujiya, Koji Kuronuma, Satoshi Takahashi

  Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   29 ( 8 ) 754 - 758  2023.08  [International journal]

  　View Summary

  INTRODUCTION: The accuracy of nucleic acid amplification tests (NAATs) is affected by various factors; however, studies examining the factors affecting the accuracy of quantitative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen test (QAT) are limited. METHODS: A total of 347 nasopharyngeal samples were collected from patients with coronavirus disease 2019 (COVID-19), and the date of onset was obtained from the electronic medical records. The SARS-CoV-2 antigen level was measured using Lumipulse Presto SARS-CoV-2 Ag (Presto), while NAAT was performed using the Ampdirect 2019-nCoV Detection Kit. RESULTS: Presto had a sensitivity rate of 95.1% (95% confidence interval: 92.8-97.4) in detecting the SARS-CoV-2 antigen in 347 samples. The number of days from symptom onset to sample collection was negatively correlated with the amount of antigen (r = -0.515) and sensitivity of Presto (r = -0.711). The patients' age was lower in the Presto-negative samples (median age, 39 years) compared with that in the Presto-positive samples (median age, 53 years; p < 0.01). A significant positive correlation was observed between age (excluding teenagers) and Presto sensitivity (r = 0.764). Meanwhile, no association was found between the mutant strain, sex, and Presto results. CONCLUSION: Presto is useful for the accurate diagnosis of COVID-19 owing to its high sensitivity when the number of days from symptom onset to sample collection is within 12 days. Furthermore, age may affect the results of Presto, and this tool has a relatively low sensitivity in younger patients.

  DOI PubMed

• COVID-19患者における血清レクチン値についての検討

  竹中 遥, 齋藤 充史, 黒沼 幸治, 千葉 弘文

  日本肺サーファクタント・界面医学会雑誌 ( 日本肺サーファクタント・界面医学会 )  54   28 - 29  2023.08

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 手洗器の水栓口や給水システムの汚染による緑膿菌の感染伝播

  藤谷好弘, 中江舞美, 佐藤勇樹, 韮澤慎也, 富樫篤生, 富樫篤生, 齋藤充史, 齋藤充史, 黒沼幸治, 黒沼幸治, 高橋聡, 高橋聡, 高橋聡

  日本感染症学会東日本地方会学術集会・日本化学療法学会東日本支部総会合同学会プログラム・抄録集   72nd-70th  2023

  J-GLOBAL

• Klebsiella pneumoniaeにおける遺伝子変異頻度と病原性の関連性評価

  上村幸二朗, 上村幸二朗, 佐藤豊孝, 佐藤豊孝, 佐藤豊孝, 黒沼幸治, 黒沼幸治, 高橋聡, 高橋聡, 横田伸一

  日本感染症学会東日本地方会学術集会・日本化学療法学会東日本支部総会合同学会プログラム・抄録集   71st-69th  2022

  J-GLOBAL

• 新型コロナウイルス感染症が北海道内の病院・診療所の診療に与えた影響に関するアンケート調査

  齋藤 充史, 千葉 弘文, 服部 健史, 黒沼 幸治, 中久保 祥, 鎌田 啓佑, 田代 典夫, 田中 裕士, 福家 聡, 今野 哲

  日本呼吸器学会誌 ( (一社)日本呼吸器学会 )  10 ( 3 ) 245 - 250  2021.05

  　View Summary

  北海道における新型コロナウイルス感染症(coronavirus disease 2019:COVID-19)流行の経験を全国の医療従事者と共有し、大病院と診療所/クリニックとの相違を明らかにすることで、今後の診療に役立てることを目的としてアンケート調査を実施した。診療所ではCOVID-19対策における物理的な制約や、経営的な影響、ストレスに感じる項目など、病院とは異なる影響や考え方があることが明らかとなった。今後それぞれの医療現場の立場・状況に応じてCOVID-19に対する方策を検討することの重要性が示唆された。(著者抄録)

• 免疫抑制療法中の間質性肺疾患患者における肺炎球菌ワクチンの効果の検討

  黒沼幸治, 本田宏幸, 本田宏幸, 齋藤充史, 小林智史, 錦織博貴, 佐藤豊孝, 横田伸一, 高橋弘毅

  日本化学療法学会雑誌   66 ( Supplement-A ) 378  2018.04

  J-GLOBAL

• マイクロバイオーム解析に基づく間質性肺炎の病態解明

  齋藤充史, 齋藤充史, 黒沼幸治, 小林智史, 本田宏幸, 錦織博貴, 高橋弘毅

  日本化学療法学会雑誌   66 ( Supplement-A ) 321  2018.04

  J-GLOBAL

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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• 肺マイクロバイオームの変容と自然免疫応答異常に注目したIPF病態の解明

  基盤研究(C)

  Project Year :

  2022.04

  -

  2025.03

   

  千葉 弘文, 齋藤 充史, 黒沼 幸治

• 肺マイクロバイオーム多様性喪失と肺サーファクタント蛋白質の免疫機構

  基盤研究(C)

  Project Year :

  2020.04

  -

  2023.03

   

  黒沼 幸治, 齋藤 充史, 千葉 弘文

  　View Summary

  肺内に豊富に存在する肺サーファクタント蛋白質は、様々な細菌と結合し下気道の自然免疫・感染防御の役割を担っている。マイクロバイオーム解析の進歩により、肺における微生物叢のホメオスタシス変化と様々な疾患との関連に注目が集まっている。高齢化に伴い繰り返す感染や慢性的な肺損傷による肺サーファク タント蛋白質の喪失は肺内微生物叢環境に異常をもたらすと考えられる。 肺サーファクタント蛋白質のうちSP-AとSP-Dは様々な細菌、真菌の菌体成分に結合し、オプソニン効果やToll様受容体を介した炎症制御、肺胞マクロファージ の活性化などの働きがあり、炎症を制御する。申請者らはこれまで、SP-AとSP-Dが肺炎球菌感染に対し、抗炎症作用と抗菌活性を有することを報告している。申請者らが報告した特発性肺線維 症における肺マイクロバイオームのDysbiosisは疾患予後とも密接に関連している。 マウスのBAL液のマイクロバイオームを検討したところ、25週齢のSP-A欠損マウスで多様性喪失(Dysbiosis)がみられた。 抗線維化薬であるピルフェニドンは光線過敏症や悪心を誘発し、ペラグラ様の病態を呈する。マウスに低ナイアシン食を与えてペラグラモデルを作成し、マウスのマイクロバイオームを解析したところ腸内細菌叢に変化がみられた。低ナイアシン食でBacteroidaceae、Streptococcaceaeの減少とRuminococcaceaeの増加を認めた。代謝産物の解析では尿中MNA、NMO、2-Py、4-Pyの減少を認めた。皮膚のアラキドン酸の分析でもHETEやEETの上昇を認め酸化脂肪酸の影響が示唆された。ピルフェニドンモデルマウスで今後マイクロバイオーム解析を行い、肺サーファクタント組成変化の解析と共に副作用の少ない新たな治療法を探索する。

• Pulmonary fibrosis treatment with pulmonary surfactant as a TLR regulatory molecule and HSP47 inhibition

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2017.04

  -

  2020.03

   

  Takahashi Hiroki

  　View Summary

  Objective: To develop a new therapeutic method for idiopathic pulmonary fibrosis under the hypothesis that surfactant protein (SP) -A supplementation and HSP47 siRNA suppress lung inflammation and fibrosis. Method: BLM was intratracheally administered to SP-A (-/-) and wild-type mice to prepare a lung injury / fibrosis model, and siRNA HSP47 was intravenously administered. Results: Inflammation and fibrosis were enhanced in SP-A deficient mice compared to wild type. In addition, siRNA HSP47 reduced lung injury and suppressed BLM-induced airway inflammation. Conclusion: SP-A supplementation and siRNA HSP47 suppressed the formation of lung injury / fibrotic lesions, and it was shown that the combination of both could be one of the new treatments for pulmonary fibrosis.

• Pulmonary collectin regulates the severity of Streptococcus pneumoniae infection

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2015.04

  -

  2018.03

   

  Kuronuma Koji

  　View Summary

  Pneumococcal infections tend to be severe, especially invasive pneumococcal infections also have a high mortality rate. Differences in the severity of pneumococcal infection caused by capsular serotypes have been reported by epidemiological studies. Our surveillance in Hokkaido has also revealed the serotype replacement of invasive pneumococcal infections which is related to the spread of pneumococcal vaccines. We confirmed that lung collectin specifically binds to pneumococcal components and activates macrophages and increases antibiotic activity by increasing the receptors necessary for phagocytosis of bacteria. It became clear that the relation with the regulatory factors such as vaccine effect, host immune status and pulmonary collectin is important as a pathological condition of pneumococcus.

• Suppression of pulmonary injury and fibrosis by applying new action of pulmonary surfactant protein

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2014.04

  -

  2017.03

   

  TAKAHASHI HIROKI, HASEGAWA YOSHIHIRO, SAITO ATSUSHI

  　View Summary

  This study was performed to clarify the importance of pulmonary surfactant protein (SP-A) as an inhibitor of lung injury / fibrosis and allergic airway inflammation and its mechanism, and to show the results that will be a bridge to the therapeutic strategy. In SP-A knockout mice, intrapulmonary inflammation and fibrosis were significantly enhanced under bleomycin stimulation compared with wild type mice. When SP-A was further administered from the respiratory tract, the inflammation was suppressed. Furthermore, in vitro experiments revealed that the inhibitory effect of SP-A against inflammation was based on the inhibition of binding of bleomycin and soluble Toll-like receptor (sTLR2). In addition, the effect of suppressing allergic reaction in respiratory tracts was also confirmed.

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