2012 Fiscal Year Final Research Report
Pulmonary Alveolar Proteinosis (PAP) and Inhaled Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Therapy--ClinicalFeatures Predicting Response and Recurrence.
Project/Area Number |
22590852
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
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Research Institution | Niigata University |
Principal Investigator |
TAZAWA Ryushi 新潟大学, 医歯学総合病院, 講師 (70301041)
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Co-Investigator(Kenkyū-buntansha) |
NAKATA Koh 新潟大学, 医歯学総合病院, 教授 (80207802)
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Research Collaborator |
SUZUKI Takuji シンシナテイ小児病院医療センター, 研究員
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Project Period (FY) |
2010 – 2012
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Keywords | 肺胞蛋白症 / 吸入治療 / GM-CSF / 自己抗体 / バイオマーカー / 気管支肺胞洗浄 |
Research Abstract |
Autoimmune pulmonary alveolar proteinosis (aPAP) is caused by granulocyte/macrophage-colony stimulating factor (GM-CSF) autoantibodies in the lung. Previously, we reported that GM-CSF inhalation therapy improved alveolar-arterial oxygen difference and serum biomarkers of disease severity in these patients. To figure out predictive and prognostic factors for GM-CSF inhalation therapy in aPAP, we performed retrospective analyses of BALF obtained in aPAP patients before and after GM-CSF inhalation therapy. We confirmed that GM-CSF inhalation was associated with a decrease of GM-Ab in the BALF in improved lungs, which was probably due to the restoration of clearance, and that GM-CSF inhalation decreased the concentration of total protein and SP-A in BALF, and increase interleuki-17 and cancer antigen-125 in improved lung of autoimmune pulmonary alveolar proteinosis. Furthermore, through the post-treatment, 30-month observation, we concluded that inhaled GM-CSF therapy sustained remission in more than half of cases, and baseline %VC might be a prognostic factor for disease recurrence.
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[Journal Article] Runx1 deficiency in CD4+ T cells causes fatal autoimmune inflammatory lung disease due to spontaneous hyperactivation of cells2012
Author(s)
Wong WF, Kohu K, Nakamura A, Ebina M, Kikuchi T, Tazawa R, Tanaka K, Kon S, Funaki T, Sugahara-Tobinai A, Looi CY, Endo S, Funayama R, Kurokawa M, Habu S, Ishii N, Fukumoto M, Nakata K, Takai T, Satake M
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Journal Title
J Immunol
Volume: 188(11)
Pages: 5408-20
Peer Reviewed
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[Journal Article] Reduced GM-CSF autoantibody in improved lung of autoimmune pulmonary alveolar proteinosis2012
Author(s)
Ohashi K, Sato A, Takada T, Arai T, Kasahara Y, Hojo M, Nei T, Nakayama H, Motoi N, Urano S, Eda R, Yokoba M, Tsuchihashi Y, Nasuhara Y, Ishii H, Ebina M, Yamaguchi E, Inoue Y, Nakata K, Tazawa R
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Journal Title
Eur Respir J
Volume: 39(3)
Pages: 777-80
Peer Reviewed
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[Journal Article] IgM-type GM-CSF autoantibody is etiologically a bystander but associated with IgG-type autoantibody production in autoimmune pulmonary alveolar proteinosis2012
Author(s)
Nei T, Urano S, Motoi N, Takizawa J, Kaneko C, Kanazawa H, Tazawa R, Nakagaki K, Akagawa KS, Akasaka K, Ichiwata T, Azuma A, Nakata K
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Journal Title
Am J Physiol Lung Cell Mol Physiol
Volume: 302(9)
Pages: L959-64
Peer Reviewed
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[Journal Article] Direct evidence that GM-CSF inhalation improves lung clearance in pulmonary alveolar proteinosis2012
Author(s)
Ohashi K, Sato A, Takada T, Arai T, Nei T, Kasahara Y, Motoi N, Hojo M, Urano S, Ishii H, Yokoba M, Eda R, Nakayama H, Nasuhara Y, Tsuchihashi Y, Kaneko C, Kanazawa H, Ebina M, Yamaguchi E, Kirchner J, Inoue Y, Nakata K, Tazawa R
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Journal Title
Respir Med
Volume: 106(2)
Pages: 284-93
Peer Reviewed
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[Journal Article] Clinical features of secondary pulmonary alveolar proteinosis: pre-mortem cases in Japan2011
Author(s)
Ishii H, Tazawa R, Kaneko C, Saraya T, Inoue Y, Hamano E, Kogure Y, Tomii K, Terada M, Takada T, Hojo M, Nishida A, Ichiwata T, Trapnell BC, Goto H, Nakata K
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Journal Title
Eur Respir J
Volume: 37(2)
Pages: 465-8
Peer Reviewed
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[Journal Article] Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB2011
Author(s)
Tanaka T, Motoi N, Tsuchihashi Y, Tazawa R, Kaneko C, Nei T, Yamamoto T, Hayashi T, Tagawa T, Nagayasu T, Kuribayashi F,Ariyoshi K, Nakata K, Morimoto K
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Journal Title
J Med Genet
Volume: 48(3)
Pages: 205-9
Peer Reviewed
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[Journal Article] Inhaled granulocyte/macrophage-colony stimulating factor as therapy for pulmonary alveolar proteinosis2010
Author(s)
Tazawa R, Trapnell BC, Inoue Y, Arai T, Takada T, Nasuhara Y, Hizawa N, Kasahara Y, Tatsumi K, Hojo M, Ishii H, Yokoba M, Tanaka N, Yamaguchi E, Eda R, Tsuchihashi Y, Morimoto K, Akira M, Terada M, Otsuka J, Ebina M, Kaneko C, Nukiwa T, Krischer JP, Akazawa K, Nakata K
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Journal Title
Am J Respir Crit Care Med
Volume: 181
Pages: 1345-54
Peer Reviewed
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[Presentation] Pulmonary Alveolar Proteinosis (PAP) And Inhaled Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Therapy--Clinical Features Predicting Recurrence2012
Author(s)
Ryushi Tazawa, Toru Arai, Toshinori Takada, Yasunori Kasahara, Yoshiko Tsuchihashi, Takahito Nei, Masayuki Hojo, Hideaki Nakayama, Masanori Yokoba, Shinya Ohkouchi, Haruyuki Ishii, Ryosuke Eda, Yasuyuki Nasuhara, Masahito Ebina, Masanori Akira, Etsuro Yamaguchi, Yoshikazu Inoue, and Koh Nakata
Organizer
Am. J. Respir. Crit. Care Med
Year and Date
2012-05-23
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[Presentation] EffectOf Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Inhalation On Bronchoalveolar Lavage Fluid And Serum In Pulmonary Alveolar Proteinosis2011
Author(s)
Ryushi Tazawa, Kazumasa Ohashi, Atsuyasu Sato, Toru Arai, Yasunori Kasahara, Masayuki Hojo, Masanori Yokoba, Yoshiko Tsuchihashi, Haruyuki Ishii, Yasuyuki Nasuhara, Masahito Ebina, Toshinori Takada, Etsuro Yamaguchi, Yoshikazu Inoue, and Koh Nakata
Organizer
Am. J. Respir. Crit. Care Med
Year and Date
2011-05-15
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[Presentation] Trapnell. A Multicenter, International Evaluation Of Blood Testing For The Diagnosis Of Autoimmune Pulmonary Alveolar Proteinosis2011
Author(s)
Brenna Carey, Kanji Uchida, Koh Nakata, Ryushi Tazawa, Yoshikazu Inoue, Masaki Hirose, Mani S. Kavuru, Mary J. Thomassen, Maurizio Luisetti, Francesca Mariani, Ilaria Campo, Ulrich Costabel, Francesco Bonella, Rhonda Vandyke, Claudia Chalk, and Bruce C
Organizer
Am. J. Respir. Crit. Care Med
Year and Date
2011-05-15
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