Details of a Researcher - SAITO Atsushi

Papers - SAITO Atsushi

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臨床応用を目指した肺胞微石症の基礎および治療法の検討

齋藤充史, 高宮里奈, 藤谷直樹, 有木茂, 黒沼幸治, 千葉弘文, 高橋素子, 高橋弘毅

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 ) 51 32 - 33 2021.03

Characteristics of COVID-19 patients admitted into two hospitals in sapporo, Japan: Analyses and insights from two outbreak waves.

Takeshi Hattori, Atsushi Saito, Hirofumi Chiba, Koji Kuronuma, Masaru Amishima, Daisuke Morinaga, Yasuo Shichinohe, Yasuyuki Nasuhara, Satoshi Konno

Respiratory investigation 59 ( 2 ) 180 - 186 2021.01 [International journal]

BACKGROUND: Coronavirus disease (COVID-19) emerged in January 2020 in Sapporo city, and the outbreak has shown two peaks. METHODS: A total of 260 COVID-19 patients were enrolled and categorized into three groups according to the pandemic pattern, jobs and situation, and disease severity. We compared clinical characteristics according to these categories. RESULTS: We found two pandemic peaks, and the proportion of patients and health providers who were infected in other hospitals had increased in the latter two periods (period 2: 49.6%, period 3: 32.7%). Particularly, the proportion of infected health providers was 27% in period 2, and they tended to be younger females with a mild condition. Severity of the disease (requirement of oxygen and/or mechanical ventilation) was associated with advanced age, and all the patients who died during admission were over 60 years old. CONCLUSIONS: We reported the temporal dynamics and characteristics of the COVID-19 pandemic in Sapporo city, Japan. This survey from the viewpoint of the hospital provides a new insight into and a better guide for the further management of the COVID-19 pandemic.

DOI PubMed

Acute eosinophilic pneumonia accompanied with COVID-19: a case report.

Koutaro Murao, Atsushi Saito, Koji Kuronuma, Yoshihiro Fujiya, Satoshi Takahashi, Hirofumi Chiba

Respirology case reports 8 ( 9 ) e00683 2020.12 [International journal]

We report a case of acute eosinophilic pneumonia (AEP) triggered by coronavirus disease 2019 (COVID-19) infection. A 77-year-old man experienced left-sided chest pain and shortness of breath. Reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) revealed a positive result, and he was treated with favipiravir, ciclesonide, and lascufloxacin, but he showed poor improvement. On the other hand, computed tomography (CT) images were atypical for COVID-19 infection, and the elevation of eosinophil was found in blood and the fluid obtained by bronchoscopy. So, we clinically diagnosed this case as AEP. Administration of prednisolone dramatically improved the patient's clinical condition and chest radiograph findings, which were consistent with the clinical course of AEP. This case suggests the importance of considering the complications of AEP when treating patients with COVID-19 infection.

DOI PubMed

Acrolein in cigarette smoke attenuates the innate immune responses mediated by surfactant protein D.

Rina Takamiya, Motoko Takahashi, Toshitaka Maeno, Atsushi Saito, Masaki Kato, Takahiro Shibata, Koji Uchida, Shigeru Ariki, Miyako Nakano

Biochimica et biophysica acta. General subjects 1864 ( 11 ) 129699 - 129699 2020.11 [International journal]

BACKGROUND: Surfactant proteins (SP) A and D belong to collectin family proteins, which play important roles in innate immune response in the lung. We previously demonstrated that cigarette smoke (CS) increases the acrolein modification of SP-A, thereby impairing the innate immune abilities of this protein. In this study, we focused on the effects of CS and its component, acrolein, on the innate immunity role of another collectin, SP-D. METHODS: To determine whether aldehyde directly affects SP-D, we examined the lungs of mice exposed to CS for 1 week and detected aldehyde-modified SP-D using an aldehyde reactive probe. The structural changes in CS extract (CSE) or acrolein-exposed recombinant human (h)SP-D were determined by western blot, liquid chromatography-electrospray ionization tandem mass spectrometry, and blue native-polyacrylamide gel electrophoresis analyses. Innate immune functions of SP-D were determined by bacteria growth and macrophage phagocytosis. RESULTS: Aldehyde-modified SP-D as well as SP-A was detected in the lungs of mice exposed to CS for 1 week. Exposure of hSP-D to CSE or acrolein induced an increased higher-molecular -weight of hSP-D and acrolein induced modification of five lysine residues in hSP-D. These modifications led to disruption of the multimer structure of SP-D and attenuated its ability to inhibit bacterial growth and activate macrophage phagocytosis. CONCLUSION: CS induced acrolein modification in SP-D, which in turn induced structural and functional defects in SP-D. GENERAL SIGNIFICANCE: These results suggest that CS-induced structural and functional defects in SP-D contribute to the dysfunction of innate immune responses in the lung following CS exposure.

DOI PubMed

高周波凝固法が有効であった多発気管・気管支乳頭腫の1例

宮坂友紀, 宮島さつき, 関川元基, 佐々原正幸, 小玉賢太郎, 斎藤充史, 高橋守, 黒沼幸治, 千葉弘文

気管支学 ( (NPO)日本呼吸器内視鏡学会 ) 42 ( 6 ) 575 - 575 2020.11

オシメルチニブからエルロチニブに変更することでEGFR-TKIを継続し得た慢性心不全合併肺腺癌の一例

関川元基, 宮坂友紀, 林智宏, 小玉賢太郎, 齋藤充史, 宮島さつき, 高橋守, 千葉弘文

肺癌 ( (NPO)日本肺癌学会 ) 60 ( 6 ) 764 - 764 2020.10

治療開始7ヵ月後にParadoxical reactionを来した粟粒結核の1例

今井優衣, 宮島さつき, 鎌田弘毅, 佐々原正幸, 宮坂友紀, 林智弘, 小玉賢太郎, 吉川匠, 斎藤充史, 高橋守, 千葉弘文, 高橋弘毅

日本サルコイドーシス/肉芽腫性疾患学会雑誌 ( 日本サルコイドーシス ) 40 ( 1-2 ) 57 - 57 2020.10

肺胞微石症IIb型ナトリウムリン酸共輸送体(Npt2b)欠損マウスを用いた臨床応用に向けた肺胞微石症の病態解析

高宮里奈, 三木寿美, 村上誠, 高橋弘毅, 齋藤充史

日本生化学会大会プログラム・講演要旨集 ( (公社)日本生化学会 ) 93回 [P - 608] 2020.09

A retrospective analysis of usefulness of impulse oscillometry system in the treatment of asthma.

Hiroyuki Sugawara, Atsushi Saito, Saori Yokoyama, Kazunori Tsunematsu, Hirofumi Chiba, Hiroki Takahashi

Respiratory research 21 ( 1 ) 226 - 226 2020.08 [International journal]

BACKGROUND: Bronchial asthma (BA) has different phenotypes, and it requires a clinically effective subtype classification system. The impulse oscillometry system (IOS) is an emerging technique device used in respiratory functional tests. However, its efficacy has not been validated. Therefore, this study aimed to assess the relationship between BA and the IOS parameters, and the difference in the therapeutic effects of inhaled corticosteroids (ICSs) among the subtype classifications was evaluated using the IOS. METHODS: Of the 245 patients with bronchial asthma who were screened, 108 were enrolled in this study. These patients were divided based on three subtypes according to the IOS result as follows: central predominant type (n = 34), peripheral predominant type (n = 58), and resistless type (n = 16). Then, the following ICSs were randomly prescribed in daily medical care: coarse-particle ICS (fluticasone propionate [FP]), fine-particle ICS (mometasone furoate [MF]), and moderate-particle ICS (budesonide [BUD]). The treatment effects were assessed using the Asthma Health Questionnaire (AHQ) and the Asthma Control Test (ACT) and were compared among the three subtypes. RESULTS: In the central predominant type, the AHQ score of the MF group was significantly higher than that of the FP group (15.4 vs. 3.6, p < 0.01) and the BUD group (15.4 vs. 8.8, p < 0.05); the ACT score of the FP group was significantly higher than that of the MF and BUD groups (24.3 vs. 21.7, 22.3, respectively, p < 0.05) at 4 weeks after treatment. In the peripheral predominant type, the AHQ score of the FP group was significantly higher than that of the MF group (14.1 vs. 3.4, p < 0.05); the ACT score of the FP group was lower than that of the MF and BUD groups (22.8 vs. 24.6, 24.4, respectively, p < 0.01) at 4 weeks after treatment. CONCLUSIONS: An association was observed between IOS subtype classification and ICS particle size in terms of therapeutic efficacy in BA. This result indicates that the IOS could be an effective tool in the selection of ICS and the evaluation of the BA phenotype.

DOI PubMed

本邦における肺胞微石症の一症例とモデルマウスを用いた病態解析

齋藤充史, 高宮里奈, 有木茂, 黒沼幸治, 千葉弘文, 高橋弘毅

日本呼吸器学会誌 ( (一社)日本呼吸器学会 ) 9 ( 増刊 ) 254 - 254 2020.08

METの部位特異的糖鎖構造の解析

齋藤淳, 横山早織, 藤谷直樹, 齋藤充史, 有木茂, 千葉弘文, 高橋弘毅, 高橋素子

日本呼吸器学会誌 ( (一社)日本呼吸器学会 ) 9 ( 増刊 ) 303 - 303 2020.08

Real-world efficacy of the impulse oscillometry system for the management of bronchial asthma

Hiroyuki Sugawara, Atsushi Saito, Saori Yokoyama, Kazunori Tsunematsu, Hirofumi Chiba, Hiroki Takahashi

2020.04

DOI

Real-world efficacy of the impulse oscillometry system for the management of bronchial asthma

Hiroyuki Sugawara, Atsushi Saito, Saori Yokoyama, Kazunori Tsunematsu, Hirofumi Chiba, Hiroki Takahashi

2020.04

DOI

Comparison of therapeutic effects of inhaled corticosteroids on three subtypes of cough variant asthma as classified by the impulse oscillometry system

Hiroyuki Sugawara, Atsushi Saito, Saori Yokoyama, Kazunori Tsunematsu, Hiroki Takahashi

Respiratory Research ( Springer Science and Business Media {LLC} ) 20 ( 1 ) 41 2019.12 [Refereed]

DOI PubMed

Insufficient serum L-ficolin is associated with disease presence and extent of pulmonary Mycobacterium avium complex disease.

Kobayashi T, Kuronuma K, Saito A, Ikeda K, Ariki S, Saitou A, Otsuka M, Chiba H, Takahashi S, Takahashi M, Takahashi H

Respiratory research 20 ( 1 ) 224 - 224 2019.10 [Refereed] [International journal]

BACKGROUND: The incidence of infectious disease caused by nontuberculous mycobacteria is increasing worldwide. Pulmonary Mycobacterium avium complex (MAC) disease is difficult to treat with chemotherapy, and its mechanism of infection, infection route, disease onset, and severity remain unknown. Ficolins are oligomeric defense lectins. L-ficolin plays an important role in innate immunity. This study's aim was to identify L-ficolin's role in patients with pulmonary MAC disease. METHODS: Between April 2011 and September 2017, 61 Japanese patients with pulmonary MAC disease were seen at our hospital. A control group, comprising 30 healthy individuals, without respiratory disease were enrolled in our study. The relationship between serum L-ficolin levels and disease severity was assessed, and L-ficolin's antibacterial role was examined. RESULTS: Serum L-ficolin levels were significantly lower in patients with pulmonary MAC disease than in healthy subjects (1.69 ± 1.27 μg/ml vs. 3.96 ± 1.42 μg/ml; p < 0.001). The cut-off value, based on receiver operating characteristic (ROC) analysis results, was 2.48 μg/ml (area under the curve (AUC) 0.90, sensitivity and specificity 83.6 and 86.7%, respectively). Serum L-ficolin levels were significantly lower in the patients with nodular bronchiectatic type disease compared with the patients with fibrocavitary type disease and were lower in the high-resolution computed tomography high-scoring group compared with low-scoring group. An in vitro analysis showed that purified recombinant L-ficolin bound to M. avium and its major cell wall component, lipoarabinomannan, in a concentration-dependent manner. In addition, recombinant L-ficolin suppressed M. avium growth in a concentration-dependent manner. CONCLUSIONS: Insufficient serum L-ficolin is associated with disease progression in pulmonary MAC disease, and the level of serum L-ficolin is a possible biomarker. TRIAL REGISTRATION: This study is registered with UMIN ( UMIN000022392 ).

DOI PubMed

ErbB3の糖鎖による物性制御メカニズム

高橋素子, 加藤公児, 藤谷直樹, 斎藤充史, 和田芳直, 姚閔

日本生化学会大会プログラム・講演要旨集 ( (公社)日本生化学会 ) 92回 [1T10m - 01] 2019.09

Autoimmune Pulmonary Alveolar Proteinosis Diagnosed after Exposure to a Fire Extinguisher Containing Silica Powder.

Yorozuya T, Ikeda K, Chiba H, Saito A, Kuronuma K, Nishikiori H, Miyajima S, Takahashi M, Yoshikawa T, Takahashi Y, Taya T, Mori Y, Umeda Y, Otsuka M, Moriyama H, Takahashi H

Internal medicine (Tokyo, Japan) 58 ( 14 ) 2067 - 2072 2019.07 [Refereed] [Domestic journal]

We herein report a case of autoimmune pulmonary alveolar proteinosis (PAP) diagnosed after one-time exposure to silica powder. Owing to the misuse of a silica-containing fire extinguisher and the inhalation of large amounts of its powder, the patient experienced prolonged cough and visited our hospital. The findings of chest computed tomography and surgical lung biopsy specimens led to the diagnosis of PAP. Interestingly, the presence of anti-GM-CSF antibody was detected; therefore, both autoimmune characteristics and exposure to large amounts of silica may have caused the development of PAP in this patient. This case provides important insight into the mechanisms leading to the onset of PAP.

DOI PubMed

Characterization of distal airway stem-like cells expressing N-terminally truncated p63 and thyroid transcription factor-1 in the human lung.

Tanaka Y, Yamaguchi M, Hirai S, Sumi T, Tada M, Saito A, Chiba H, Kojima T, Watanabe A, Takahashi H, Sakuma Y

Experimental cell research 372 ( 2 ) 141 - 149 2018.11 [Refereed] [International journal]

Distal airway stem cells (DASCs) in the mouse lung can differentiate into bronchioles and alveoli. However, it remains unclear whether the same stem cells exist in the human lung. Here, we found that human lung epithelial (HuL) cells, derived from normal, peripheral lung tissue, in monolayer, mostly express both the N-terminally truncated isoform of p63 (∆Np63), a marker for airway basal cells, and thyroid transcription factor-1 (TTF-1), a marker for alveolar epithelial cells, even though these two molecules are usually expressed in a mutually exclusive way. Three-dimensionally cultured HuL cells differentiated to form bronchiole-like and alveolus-like organoids. We also uncovered a few bronchiolar epithelial cells expressing both ∆Np63 and TTF-1 in the human lung, suggesting that these cells are the cells of origin for HuL cells. Taken together, ΔNp63+ TTF-1+ peripheral airway epithelial cells are possibly the human counterpart of mouse DASCs and may offer potential for future regenerative medicine.

DOI PubMed

Response to pneumococcal vaccine in interstitial lung disease patients: Influence of systemic immunosuppressive treatment.

Koji Kuronuma, Hiroyuki Honda, Tessei Mikami, Atsushi Saito, Kimiyuki Ikeda, Mitsuo Otsuka, Hirofumi Chiba, Gen Yamada, Toyotaka Sato, Shin-Ichi Yokota, Hiroki Takahashi

Vaccine 36 ( 33 ) 4968 - 4972 2018.08 [Refereed] [International journal]

BACKGROUND: Interstitial lung diseases (ILD) are severe respiratory diseases, and ILD patients are treated with corticosteroid and immunosuppressive agents. However, it is unclear whether these medications influence the response of pneumococcal vaccine. OBJECTIVES: We examined the immunogenicity of pneumococcal vaccines (PPSV23 and PCV13) in ILD patients undergoing immunosuppressive treatment. METHODS: ILD patients who were regularly followed at the outpatient clinic were enrolled. Sera were collected before and 4-8 weeks after vaccination. Serotype-specific immunoglobulin G (IgG) concentrations against pneumococcal serotype 19F were measured by ELISA. RESULTS: IgG concentrations to serotype 19F were increased in all groups in response to the vaccine. Both PCV13 and PPSV23 induced IgG concentrations in patients immunized for the first time. Response rates for the ILD group were comparable with those for the ILD group undergoing corticosteroid therapy. Only idiopathic pulmonary fibrosis patients undergoing immunosuppressive therapy had a significantly lower response.

DOI PubMed

Impaired diversity of the lung microbiome predicts progression of idiopathic pulmonary fibrosis.

Youhei Takahashi, Atsushi Saito, Hirofumi Chiba, Koji Kuronuma, Kimiyuki Ikeda, Tomofumi Kobayashi, Shigeru Ariki, Motoko Takahashi, Yasushi Sasaki, Hiroki Takahashi

Respiratory research 19 ( 1 ) 34 - 34 2018.02 [Refereed] [International journal]

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe form of idiopathic interstitial pneumonias. Although IPF has not been thought to be associated with bacterial communities, recent papers reported the possible role of microbiome composition in IPF. The roles of microbiomes in respiratory functions and as clinical biomarkers for IPF remain unknown. In this study, we aim to identify the relationship between the microbial environment in the lung and clinical findings. METHODS: Thirty-four subjects diagnosed with IPF were included in this analysis. The 16S rDNA was purified from bronchoalveolar lavage fluid obtained at the time of diagnosis and analyzed using next-generation sequencing techniques to characterize the bacterial communities. Furthermore, microbiomes from mice with bleomycin-induced lung fibrosis were analyzed. RESULTS: The most prevalent lung phyla were Firmicutes, Proteobacteria and Bacteroidetes. Decreased microbial diversity was found in patients with low forced vital capacity (FVC) and early mortality. Additionally, the diversity and relative abundance of Firmicutes, Streptococcaceae, and Veillonellaceae were significantly associated with FVC, 6-min walk distance, and serum surfactant protein D. Bleomycin-induced lung fibrosis resulted in decrease of diversity and alteration of microbiota in PCoA analysis. These results support the observations in human specimens. CONCLUSIONS: This study identified relationships between specific taxa in BALF and clinical findings, which were also supported by experiments in a mouse model. Our data suggest the possibility that loss of microbial diversity is associated with disease activities of IPF.

DOI PubMed

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Papers - SAITO Atsushi