SAITO Atsushi

写真a

Affiliation

School of Medicine, Department of Respiratory Medicine and Allergology

Job title

Lecturer
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Research Experience 【 display / non-display 】

  • 2022.04
    -
    Now

    Sapporo Medical University, School of Medicine   Respiratory Medicine and Allergology   Assistant Professor, Lecturer

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    DEPUTY DIRECTOR, Division of Infection Control

  • 2019.10
    　
    　

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

  • 2015.08
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    2019.09

    Sapporo Medical University   Biochemistry and Respiratory Medicine   Assistant Professor

  • 2013.04
    -
    2015.07

    University of Cincinnati   Division of Pulmonary, Critical Care & Sleep Medicine   postdoc fellow

    postdoc fellow

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Professional Memberships 【 display / non-display 】

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    THE JAPANESE RESPIRATORY SOCIETY

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    American thoracic society

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    THE JAPAN SOCIETY FOR RESPIRATORY ENDOSCOPY

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    THE JAPANESE SOCIETY OF INTERNAL MEDICINE

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    日本感染症学会

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Research Areas 【 display / non-display 】

  • Life sciences   Respiratory medicine  

  • Life sciences   Medical biochemistry  

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Affiliation 【 display / non-display 】

  • Sapporo Medical University Hospital   Division of Infection Control   Deputy Director  

  • Sapporo Medical University, School of Medicine   Respiratory Medicine and Allergology   Assistant Professor, Lecturer  

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Research Interests 【 display / non-display 】

  • IPF

  • Collectin Defensin Legionella

  • Surfactant protein D

  • Pulmonary alveolar microlithiasis

  • Surfactant protein A

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Papers 【 display / non-display 】

  • Rapid and Integrated Bacterial Evolution Analysis unveils gene mutations and clinical risk of Klebsiella pneumoniae

    Kojiro Uemura, Toyotaka Sato, Soh Yamamoto, Noriko Ogasawara, Jirachaya Toyting, Kotaro Aoki, Akira Takasawa, Masayuki Koyama, Atsushi Saito, Takayuki Wada, Kaho Okada, Yurie Yoshida, Koji Kuronuma, Chie Nakajima, Yasuhiko Suzuki, Motohiro Horiuchi, Kenichi Takano, Satoshi Takahashi, Hirofumi Chiba, Shin-ichi Yokota

    Nature Communications    2025.03

    DOI

  • Management of anti-melanoma differentiation-associated gene 5 antibody-induced refractory dermatomyositis complicated by interstitial pneumonia using tofacitinib and its outcomes: a case report.

    Yui Imai, Takafumi Yorozuya, Taku Hatakeyama, Takumi Nishimaki, Tomoyuki Takahashi, Tatsuru Ishikawa, Shun Kondoh, Yuichiro Asai, Yuki Mori, Atsushi Saito, Hirotaka Nishikiori, Michiko Hosaka, Hirofumi Chiba

    Journal of medical case reports   18 ( 1 ) 471 - 471  2024.09  [International journal]

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    BACKGROUND: Clinical amyopathic dermatomyositis is characterized by cutaneous symptoms but lacks muscle symptoms. Anti-melanoma differentiation-associated gene 5 antibodies are frequently found in Japanese patients with clinical amyopathic dermatomyositis. Patients with rapidly progressive interstitial lung disease with positive anti-melanoma differentiation-associated gene 5 antibodies have poor prognoses, and majority of them are treated with combination immunosuppressive therapy; however, the best treatment is yet to be determined. CASE PRESENTATION: A 52-year-old Asian male patient presented with a chief complaint of dyspnea on exertion. He had a typical skin rash and rapidly progressive interstitial pneumonia. Additionally, anti-melanoma differentiation-associated gene 5 antibodies were detected; therefore, he was diagnosed with dermatomyositis-associated interstitial pneumonia. Respiratory failure worsened despite administering steroid pulse therapy, tacrolimus, and cyclophosphamide. Consequently, plasma exchange was performed on day 13 of admission. After a slight improvement, the patient's respiratory failure worsened. Thus, cyclophosphamide was replaced by tofacitinib on day 28. Although respiratory failure improved and the progression of interstitial pneumonia seemed under control, βD-glucan level increased and Aspergillus antigen was detected on day 49. Micafungin and voriconazole were administered, but the patient succumbed to worsening respiratory failure on day 61. The pathological autopsy revealed multiple nodular lesions with cavity formation in both lungs and the presence of Aspergillus with severe neutrophilic infiltration and necrosis, which supported the diagnosis of invasive pulmonary aspergillosis. CONCLUSION: The patient with anti-melanoma differentiation-associated gene 5 antibody-related rapidly progressive interstitial lung disease, whose disease was difficult to control after the administration of triple immunosuppressive therapy (steroids, tacrolimus, and cyclophosphamide), showed good response with tofacitinib. Unfortunately, the patient died of invasive pulmonary aspergillosis owing to severe immunosuppression; thus, the signs of complications should be promptly detected.

    DOI PubMed

  • Therapeutic effect of long-acting muscarinic antagonist for treating uncontrolled asthma assessed using impulse oscillometry.

    Hiroyuki Sugawara, Atsushi Saito, Saori Yokoyama, Hirofumi Chiba

    Respiratory research   25 ( 1 ) 300 - 300  2024.08  [International journal]

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    BACKGROUND: In recent years, the incorporation of LAMAs into asthma therapy has been expected to enhance symptom control. However, a significant number of patients with asthma continue to experience poorly managed symptoms. There have been limited investigations on LAMA-induced airway alterations in asthma treatment employing IOS. In this study, we administered a LAMA to patients with poorly controlled asthma, evaluated clinical responses and respiratory function, and investigated airway changes facilitated by LAMA treatments using the IOS. METHODS: Of a total of 1282 consecutive patients with asthma, 118 exhibited uncontrolled symptoms. Among them, 42 switched their treatment to high-dose fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) (ICS/LABA/LAMA). The patients were then assessed using AHQ-33 or LCQ and ACT. Spirometry parameters (such as FEV1 or MMEF) and IOS parameters (such as R20 or AX) were measured and compared before and after exacerbations and the addition of LAMA. RESULTS: Of the 42 patients, 17 who switched to FF/UMEC/VI caused by dyspnea exhibited decreased pulmonary function between period 1 and baseline, followed by an increase in pulmonary function between baseline and period 2. Significant differences were observed in IOS parameters such as R20, R5-R20, Fres, or AX between period 1 and baseline as well as between baseline and period 2. Among the patients who switched to inhaler due to cough, 25 were classified as responders (n = 17) and nonresponders (n = 8) based on treatment outcomes. Among nonresponders, there were no significant differences in spirometry parameters such as FEV1 or PEF and IOS parameters such as R20 or AX between period 1 and baseline. However, among responders, significant differences were observed in all IOS parameters, though not in most spirometry parameters, between period 1 and baseline. Furthermore, significant differences were noted between baseline and period 2 in terms of FEV1, %MMEF, %PEF, and all IOS parameters. CONCLUSION: ICS/LABA/LAMA demonstrates superiority over ICS/LABA in improving symptoms and lung function, which is primarily attributed to the addition of LAMA. Additionally, IOS revealed the effectiveness of LAMA across all airway segments, particularly in the periphery. Hence, LAMA can be effective against various asthma phenotypes characterized by airway inflammation, even in real-world cases.

    DOI PubMed

  • N-glycan on N262 of FGFR3 regulates the intracellular localization and phosphorylation of the receptor.

    Hashimoto, U, Fujitani, N, Uehara, Y, Okamoto, H, Saito, A, Ito, F, Ariki, S, Shiratsuchi, A, Hasegawa, Y, Takahashi, M

    Biochim. Biophys. Acta Gen. Subj.   1868 ( 4 ) 130565 - 130565  2024.04  [Refereed]

    DOI

  • 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]

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    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

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Misc 【 display / non-display 】

  • JANISでは把握が困難な中小規模病院における緑膿菌の薬剤耐性の状況

    藤谷 好弘, 富樫 篤生, 齋藤 充史, 黒沼 幸治, 高橋 聡

    日本感染症学会総会・学術講演会・日本化学療法学会学術集会合同学会プログラム・抄録集 ( 日本感染症学会・日本化学療法学会 )  98回・72回   np255 - np255  2024.05

  • 喘息増悪時のLAMA追加による臨床効果とIOSを用いた有効性の検討

    菅原 洋行, 齋藤 充史, 横山 早織, 千葉 弘文

    日本呼吸器学会誌 ( (一社)日本呼吸器学会 )  13 ( 増刊 ) 325 - 325  2024.03

  • 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

  • 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

    J-GLOBAL

  • 結核の診断に時間を要した肺外結核の2例

    小林 拓海, 齋藤 充史, 小玉 賢太郎, 高橋 守, 黒沼 幸治, 千葉 弘文

    日本呼吸器学会誌 ( (一社)日本呼吸器学会 )  13 ( 増刊 ) 395 - 395  2024.03

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Awards 【 display / non-display 】

  • Young Researcher's Award

    2017.10   The Japanese Medical Society for Lung Surfactant and Biological Interface   ナトリウムリン酸共輸送体欠損マウスを用いた肺胞微石症の病態解析

    Winner： Atsushi Saito

  • Abstract Award

    2015.05   American thoracic society   Development of biomarkers and treatment strategies in the Npt2b-/- preclinical mouse model of Pulmonary Alveolar Microlithiasis.

    Winner： Atsushi Saito

  • 優秀講演賞

    2011.08   第48回日本生化学会北海道支部例会   サーファクタント蛋白質Aはhuman beta defensin 3の肺胞上皮細胞に対する傷害活性を抑制する

    Winner： 齋藤 充史

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    http://www.jbs-hokkaido.jp/r_meeting/backnumber.php?eid=00002&division=2

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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

  • Elucidation of pathogenesis of interactable lung diseases associated with dysregulated lipid metabolism

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2022.04
    -
    2025.03
     

    高宮 里奈, 齋藤 充史

  • 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
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    2023.03
     

    黒沼 幸治, 齋藤 充史, 千葉 弘文

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    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。

  • 複合的オミクス解析を用いて探る、肺胞微石症の分子病態と新規治療法の開発

    基盤研究(C)

    Project Year :

    2020.04
    -
    2023.03
     

    齋藤 充史, 藤谷 直樹, 高宮 里奈

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    申請者は希少難治性呼吸器疾患に興味を持ち研究を進めてきた。その一環として肺胞微石症に対するマウスモデルを作製し新治療法の開発に取り組み (Sci Trans Med, 2015)、また特発性肺線維症に対する新たな視点として肺マイクロバイオームに着目した (Resp Res, 2018)。近年、こうした生体分子を網羅的に解 析するオミクス解析の技術が急速に進展し、糖尿病、癌などの領域で有用な分子標的が数多く見つかっている。しかし希少疾患においては対象が限られることや 予算の関係からオミクス解析の報告は極めて限定される。そのため、本研究では、申請者らが経験豊富なオミクス解析技術と肺胞微石症マウスモデルを用い、病 態の分子基盤の解明・確立と臨床に直結するトランスレーショナルな成果を創出する。本研究の結果、当該技術が他の希少肺疾患の病態の分子基盤に関する研究 の現状を打破する先駆技術と位置づけられ、希少難治性呼吸器疾患克服研究の推進に貢献することを目指す。 本年度は新型コロナウイルス感染症の蔓延に伴う臨床業務が増大したこともありやや研究は遅れているものの、データは揃いつつあるため論文投稿に向けて現在 進行中である。

  • The quality of lipid component of pulmonary surfactant in lung diseases

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2019.04
    -
    2022.03
     

    高宮 里奈, 齋藤 充史

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    ブレオマイシン誘発性肺線維化モデルを用い、リン脂質分解酵素ホスホリパーゼ A2の網羅的発現解析を行なった。肺胞洗浄液中に含まれる細胞（炎症細胞）を用いた解析では、Pla2g4c, Pla2g2d, Pla2g3, Pla2g12aなどの分泌型のsPLA2の発現が亢進することがわかった。一方、肺内では、sPLA2であるPla2g10, 細胞質型のcPLA2であるPla2g4a, カルシウム非依存性のiPLA2である Pnpla6の発現が亢進することがわかった。Pla2g4a (cPLA2 alpha)はアラキドン酸代謝を担う主要酵素であることから、その下流の酵素の発現を検証したところ、肺内で炎症により誘導されるCOX2の発現が亢進していることがわかった。そこで次に、このサンプルを用いリピドミクス解析を行った。その結果、肺胞洗浄液中、肺内両者で、アラキドン酸、エイコサペンタエン酸、ドコサヘキサエン酸の、いずれの高度不飽和脂肪酸の産生も亢進が認められた。そこで、その下流にある脂質メディエータの産生について検証を行ったところPGD2, 15deoxy PGJ2, PGE2, LXA4などの炎症性の脂質メディエータの産生の亢進が認められた。また、肺胞洗浄液中の肺サーファクタントの主成分であるジパルミトイルホスファチジルコリン(DPPC)の産生量には変化は認められなかったが、PE, PIは増加傾向にありLPE, LPIの産生の増加が顕著に認めれた。一方、肺内では PCは全体的に減少傾向にあり、その下流の一部のLPCが増加していた。また、PG、LPGの産生量の増加が認められた。以上の結果から、ブレオマイシン誘発性繊維化モデルにおいて、肺内の脂質環境が変わっていることが分かった。

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Presentations 【 display / non-display 】

  • Pulmonary collectins provide a first line of defense against L. Pneumophila through inhibiting their type IV secretion system.

    Atsushi Saito

    European Respiratory Society International Congress 2017 

    Presentation date： 2017.09

  • The therapeutic strategy for Pulmonary alveolar microlithiasis

    Atsushi Saito  [Invited]

    The Japanese Medical Society for Lung Surfactant and Biological Interface 

    Presentation date： 2017.10

  • 14) Low Phosphate Diet Arrests and Reverses Lung Injury in Mice with Pulmonary Alveolar Microlithiasis

    Rare Lung Diseases Research Conference 

    Presentation date： 2016.09

  • Development Of Biomarkers And Treatment Strategies In The Npt2b-/- Preclinical Mouse Model Of Pulmonary Alveolar Microlithiasis

    Atsushi Saito

    American Thoracic Society Annual Conference 

    Presentation date： 2015.05

  • SHH-Cre Driven Knockout Of Npt2b Results In Pulmonary Alveolar Microlithiasis And Loss Of Phosphate Transport In Alveolar Epitherial Type II Cells

    Atsushi Saito

    American Thoracic Society Annual Conference 

    Presentation date： 2014.05

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Teaching Experience 【 display / non-display 】

  • Respiratory Medicine  

    2019.10
    -
    Now
     

  • 生化学  

    札幌医科大学  

    2015.08
    -
    2019.09
     

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