International comparison of autoimmune pulmonary alveolar proteinosis:Platform of rare lung disease research

• Project/Area Number: 24406027
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 海外学術
• Research Field: Respiratory organ internal medicine
• Research Institution: Clinical Research Center, National Hospital Organization, Kinki-Chuo Chest Medical Center
• Principal Investigator: INOUE Yoshikazu 独立行政法人国立病院機構(近畿中央胸部疾患センター臨床研究センター), その他部局等, 臨床研究センター長 (90240895)
• Co-Investigator(Kenkyū-buntansha): NAKATS Koh 新潟大学, 医歯学総合病院, 教授 (80207802) ; KITAICHI Masanori 国立病院機構近畿中央胸部疾患センター, 臨床研究センター, 室長 (00161464) ; AKIRA Masanori 国立病院機構近畿中央胸部疾患センター, 臨床研究センター, 室長 (20393267) ; HIROSE Masaki 国立病院機構近畿中央胸部疾患センター, 臨床研究センター, 流動研究員 (90470195)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2014: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: 自己免疫性肺胞蛋白症 / 稀少肺疾患国際共同研究 / 診断 / 環境 / 肺胞蛋白症 / 抗GM-CSF自己抗体 / 国際情報交換 / 抗GM-CSF抗体

Outline of Final Research Achievements

(1) International research network of pulmonary alveolar proteinosis (PAP) (Rare lung research platform): Japan Korea (3 institutions), China(5 institutions) have established collaboration network (AsianPAP). International meetings were held at the Asian Pacific Respiratory Society. We keep contact with USA and EU PAP research groups.
(2) International standardization of the diagnosis of PAP: International validation and standardization of ELISA of anti GM-CSF antibodies was performed, and published J Immunol Methods. 2014. 402:57).
(3) An autoimmune PAP (APAP) international survey: 147 Chinese, 78 Korean, and 248 Japanese APAP patients were registered. In China, higher age, more sever patients were observed, and the antibody levels tend to be high. Japanese cohort revealed association between occupational and prognosis.

Research Products

• [Journal Article] A mathematical model to predict protein wash out kinetics during whole-lung lavage in autoimmune pulmonary alveolar proteinosis. (2015)
  • Author(s): Akasaka K, （12名略）， Tazawa R, (7名略) Nakata K.
  • Journal Title: Am J Physiol Lung Cell Mol Physiol Volume: 308 Issue: 2 Pages: 105-117
  • DOI: 10.1152/ajplung.00239.2014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pleuroparenchymal fibroelastosis from a consecutive database: a rare disease entity? (2015)
  • Author(s): Nakatani T, Arai T, Kitaichi M, Akira M, Tachibana K, Sugimoto C, Hirooka A, Tsuji T, Minomo S, Hayashi S, Inoue Y
  • Journal Title: Eur Respir J Volume: 45 Issue: 4 Pages: 1183-6
  • DOI: 10.1183/09031936.00214714
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Standardized serum GM-CSF autoantibody testing for the routine clinical diagnosis of autoimmune pulmonary alveolar proteinosis (2014)
  • Author(s): Uchida K, Nakata K, Carey B, Chalk C, Suzuki T, Sakagami T, Koch DE, Stevens C, Inoue Y, Yamada Y, Trapnell BC.
  • Journal Title: J Immunol Methods Volume: 402 Issue: 1-2 Pages: 57-70
  • DOI: 10.1016/j.jim.2013.11.011
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Development of microscopic polyangiitis-related pulmonary fibrosis in a patient with autoimmune pulmonary alveolar proteinosis (2014)
  • Author(s): Kinehara Y, Kida H, Inoue Y, Hirose M, Nakabayashi A, Takeuchi Y, Hayama Y, Fukushima K, Hirata H, Inoue K, Minami T, Nagatomo I, Takeda Y, Funakoshi T, Kijima T, Kumanogoh A
  • Journal Title: BMC Pulm Med Volume: 14 Issue: 1 Pages: 172-172
  • DOI: 10.1186/1471-2466-14-172
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Secondary pulmonary alveolar proteinosis complicating myelodysplastic syndrome results in worsening of prognosis: a retrospective cohort study in Japan (2014)
  • Author(s): Haruyuki Ishii, John F Seymour, Ryushi Tazawa, Yoshikazu Inoue, Naoyuki Uchida, Aya Nishida, Yoshihito Kogure, Takeshi Saraya, Keisuke Tomii, Toshinori Takada, Yuko Itoh, Masayuki Hojo, Toshio Ichiwata, Hajime Goto, Koh Nakata
  • Journal Title: BMC Pulmonary Medicine Volume: 14: 37 Issue: 1 Pages: 1471-2466
  • DOI: 10.1186/1471-2466-14-37
  • Peer Reviewed / Open Access
• [Journal Article] CYFRA 21-1 as a disease severity marker for autoimmune pulmonary alveolar proteinosis. (2014)
  • Author(s): Arai T, Inoue Y, Sugimoto C, Inoue Y, Nakao K, Takeuchi N, Matsumuro A, Hirose M, Nakata K, Hayashi S.
  • Journal Title: Respirology Volume: 19 Issue: 2 Pages: 246-252
  • DOI: 10.1111/resp.12210
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Duration of benefit in patients with autoimmune pulmonary alveolar proteinosis after inhaled granulocyte-macrophage colony-stimulating factor therapy. (2014)
  • Author(s): Tazawa R, Inoue Y, Arai T, Takada T, Kasahara Y, Hojo M, Ohkouchi S, Tsuchihashi Y, Yokoba M, Eda R, Nakayama H, Ishii H, Nei T, Morimoto K, Nasuhara Y, Ebina M, Akira M, Ichiwata T, Tatsumi K, Yamaguchi E, Nakata K.
  • Journal Title: Chest Volume: 145 Issue: 4 Pages: 729-737
  • DOI: 10.1378/chest.13-0603
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis (2014)
  • Author(s): Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, Cottin V, Flaherty KR, Hansell DM, Inoue Y, Kim DS, Kolb M, Nicholson AG, Noble PW, Selman M, Taniguchi H, Brun M, Le Maulf F, Girard M, Stowasser S, Schlenker-Herceg R, Disse B, Collard HR
  • Journal Title: N Engl J Med Volume: 29 Issue: 22 Pages: 2071-82
  • DOI: 10.1056/nejmoa1402584
  • Peer Reviewed / Open Access
• [Journal Article] Lymphatic manifestations of lymphangioleiomyomatosis (2014)
  • Author(s): Gupta R, Kitaichi M, Inoue Y, Kotloff R, McCormack FX
  • Journal Title: Lymphology Volume: 47 Pages: 106-17
  • Peer Reviewed
• [Journal Article] Design of the INPULSIS™ trials: two phase 3 trials of nintedanib in patients with idiopathic pulmonary fibrosis (2014)
  • Author(s): Richeldi L, Cottin V, Flaherty KR, Kolb M, Inoue Y, Raghu G, Taniguchi H, Hansell DM, Nicholson AG, Le Maulf F, Stowasser S, Collard HR
  • Journal Title: Respir Med Volume: 108 Issue: 7 Pages: 1023-30
  • DOI: 10.1016/j.rmed.2014.04.011
  • Peer Reviewed
• [Journal Article] Safety and pharmacokinetics of nintedanib and pirfenidone in idiopathic pulmonary fibrosis (2014)
  • Author(s): Ogura T, Taniguchi H, Azuma A, Inoue Y, Kondoh Y, Hasegawa Y, Bando M, Abe S, Mochizuki Y, Chida K, Klüglich M, Fujimoto T, Okazaki K, Tadayasu Y, Sakamoto W, Sugiyama Y
  • Journal Title: Eur Respir J Volume: 45 Issue: 5 Pages: 1382-92
  • DOI: 10.1183/09031936.00198013
  • Peer Reviewed
• [Journal Article] Organ Assessment Instrument Investigators TW. The WASOG Sarcoidosis Organ Assessment Instrument: An update of a previous clinical tool (2014)
  • Author(s): Judson MA, Costabel U, Drent M, Wells A, Maier L, Koth L, Shigemitsu H, Culver DA, Gelfand J, Valeyre D, Sweiss N, Crouser E, Morgenthau AS, Lower EE, Azuma A, Ishihara M, Morimoto S, Yamaguchi T, Shijubo N, Grutters JC, Rosenbach M, Li HP, Rottoli P, Inoue Y, Prasse A, Baughman RP
  • Journal Title: Sarcoidosis Vasc Diffuse Lung Dis Volume: 31 Pages: 19-27
  • Peer Reviewed
• [Journal Article] An intractable case of hermansky-pudlak syndrome (2014)
  • Author(s): Kanazu M, Arai T, Sugimoto C, Kitaichi M, Akira M, Abe Y, Hozumi Y, Suzuki T, Inoue Y
  • Journal Title: Intern Med Volume: 53 Pages: 2629-2634
  • NAID: 130004713242
  • Peer Reviewed
• [Journal Article] Predictors of the clinical effects of pirfenidone on idiopathic pulmonary fibrosis (2014)
  • Author(s): Arai T, Inoue Y, Sasaki Y, Tachibana K, Nakao K, Sugimoto C, Okuma T, Akira M, Kitaichi M, Hayashi S
  • Journal Title: Respir Investig Volume: 52 Issue: 2 Pages: 136-43
  • DOI: 10.1016/j.resinv.2013.09.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Tracheobronchial lesions in eosinophilic pneumonia (2014)
  • Author(s): Matsuda Y, Tachibana K, Sasaki Y, Tsuyuguchi K, Kitaichi M, Inoue Y
  • Journal Title: Respir Investig Volume: 52 Issue: 1 Pages: 21-7
  • DOI: 10.1016/j.resinv.2013.05.006
  • Peer Reviewed
• [Journal Article] Light chain (κ/λ) ratio of GM-CSF autoantibodies is associated with disease severity in autoimmune pulmonary alveolar proteinosis. (2013)
  • Author(s): Nei T, Urano S, Itoh Y, Kitamura N, Hashimoto A, Tanaka T, Motoi N, Kaneko C, Tazawa R, Nakagaki K, Arai T, Inoue Y, Nakata K.
  • Journal Title: Clin Immunol Volume: 149(3) Issue: 3 Pages: 357-364
  • DOI: 10.1016/j.clim.2013.10.002
  • Peer Reviewed
• [Journal Article] Direct evidence that GM-CSF inhalation improves lung clearance in pulmonary alveolar proteinosis (2012)
  • Author(s): Ohashi K, Sato A, Takada T, Arai T, Nei T, Kasahara Y, Motoi N, Hojo M, Urano S, Isii 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
  • Journal Title: Respir Med. Volume: 106 Pages: 284-293
  • Peer Reviewed
• [Journal Article] Reduced GM-CSF autoantibody in improved lung of autoimmune pulmonary alveolar proteinosis (2012)
  • 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
  • Journal Title: Eur Respir J. Volume: 39 Pages: 777-80
  • Peer Reviewed
• [Journal Article] Tetraspanin CD151 protects against pulmonary fibrosis by maintaining epithelial integrity. (2012)
  • Author(s): Tsujino K, Takeda Y, Arai T, Shintani Y, Inagaki R, Saiga H, Iwasaki T, Tetsumoto S, Jin Y, Ihara S, Minami T, Suzuki M, Nagatomo l, Inoue K, Kida H, Kijima T, Ito M, Kitaichi M, Inoue Y, Tachibana l, Takeda K, Okumura M, Hemler ME, Kumanogoh A
  • Journal Title: Am J Respir Crit Care Med. Volume: 186 Pages: 170-80
  • Peer Reviewed
• [Journal Article] A case of combined sarcoidosis and usual interstitial pneumonia (2012)
  • Author(s): Tachibana K, Arai T, Kagawa T, Minomo S, Akira M, Kitaichi M, Inoue Y
  • Journal Title: Intern Med. Volume: 51 Pages: 1893-7
  • NAID: 130002062237
  • Peer Reviewed
• [Journal Article] リンパ脈管筋腫症克服に向けて:患者とともに (2012)
  • Author(s): 井上義一
  • Journal Title: 呼吸と循環 Volume: 60 Pages: 355-62
• [Journal Article] リンパ脈筋腫症の新たな分子標的治療 (2012)
  • Author(s): 井上義一
  • Journal Title: 日本サルコイドーシス/肉芽腫性疾患学会雑誌 Volume: 32 Pages: 89-89
• [Presentation] Long term follow-up of serum autoantibody against GM-CSF levels in patients with autoimmune pulmonary alveolar proteinosis (2014)
  • Author(s): Matsumuro A, Hirose M, Arai T, Sugimoto C, Kitaichi M, Akira M, Inoue Y
  • Organizer: 19th Congress of Asian Pasific Society of Respirology
  • Place of Presentation: Bali, Indonesia
  • Year and Date: 2014-11-14
• [Presentation] Serum B cell activating factor belonging to the tumor necrosis factor family (BAFF) in Autoimmune Pulmonary Alveolar Proteinosis (2014)
  • Author(s): Hirose M, Matsumuro A, Arai T, Sugimoto C, Inoue Y
  • Organizer: 9th Congress of Asian Pasific Society of Respirology
  • Place of Presentation: Bali, Indonesia
  • Year and Date: 2014-11-14
• [Presentation] Clinical features and prognosis of 108 patients with lymphangioleiomyomatosis (2014)
  • Author(s): Inoue Y, Hirose M, Nakata K, Arai T, Sugimoto C, Matsuda Y, Takeuchi N, Hirooka A, Tachibana K, Matsumuro A, Honnma T, Kitaichi M, Akira M, Okada M, Hayashi S
  • Organizer: EUROPIAN RESPIRATORY SOCIETY INTERNATIONAL CONGRTSS 2014
  • Place of Presentation: Munich, Germany
  • Year and Date: 2014-09-06 – 2014-09-10
• [Presentation] B Cell Activating Factor Belonging To The Tumor Necrosis Factor Family In Autoimmune Pulmonary Alveolar Proteinosis (2014)
  • Author(s): Hirose M, Matsumuro A, Arai T, Sugimoto C, Kitaichi M, Akira M, Inoue Y
  • Organizer: ATS 2014 International Conference
  • Place of Presentation: Sun Diego, USA
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] Roles of bronchofiberscopy for the diagnosis of interstitial lung diseases (2014)
  • Author(s): Inoue. Y
  • Organizer: 18th WCBIP/WCBE
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2014-04-13 – 2014-04-16
  • Invited
• [Presentation] 肺胞蛋白症 (2013)
  • Author(s): 井上義一
  • Organizer: 第53回臨床呼吸機能講習会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Surveillance of whole lung lavage for autoimmune pulmonary alveolar proteinosis in Japan (2013)
  • Author(s): T. Ichiwata, S. Oh-ishi, K. Uchida, Y. Inoue, T. Arai, H. Ishii, K. Nakata
  • Organizer: Europian Respiratory Society Annul Congress 2013
  • Place of Presentation: Barcelona
• [Presentation] Vital Capacity And Recurrence After Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Inhalation Therapy For Pulmonary Alveolar Proteinosis (2013)
  • Author(s): Tazawa R, Arai T, Kasahara Y, Hojo M, Ohkouchi S, Eda R, Yokoba M, Tsuchihashi Y, Nei T, Nakayama H, Ishii H, Morimoto K, Nasuhara Y, Takada T, Ebina M, Yamaguchi E, Inoue Y, Nakata K
  • Organizer: American Thoracic Society International Conference 2013
  • Place of Presentation: Philadelphia
• [Presentation] Longitudinal Cohort Of Autoimmune Pulmonary Alveolar Proteinosis (2013)
  • Author(s): Inoue Y, Arai T, Nakata K, Yamaguchi E, Ichiwata T, Ebina M, Tazawa R, Ishii H, Setoguchi Y, Kitaichi M, Akira M, Tatsumi K, Nasuhara Y, Cho K, Tsuchihashi Y, Uchida K, Takada T, Nakayama H, Tomii K, Sugimoto C, Kohashi Y, Ohkouchi S, Kasahara Y, Morimoto K, Nakatani T, Tsuyuguchi K
  • Organizer: American Thoracic Society International Conference 2013
  • Place of Presentation: Philadelphia
• [Presentation] 稀少肺難病の克服に向けて
  • Author(s): 中田光
  • Organizer: 第53回日本呼吸器学会総会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Rare Lung Diseases Recent advances in rare lung diseases
  • Author(s): Costabel U, Inoue Y (Chair)
  • Organizer: 18th Congress of the Asian Pacific Society of Respirology
  • Place of Presentation: Yokohama
• [Book] 肺胞蛋白症 今日の診療のための ガイドライン外来診療 (2013)
  • Author(s): 新井徹，井上義一
  • Total Pages: 2
  • Publisher: 日経メディカル開発
• [Book] 肺胞蛋白症，別冊・医学のあゆみ (2013)
  • Author(s): 井上義一
  • Total Pages: 3
  • Publisher: 医歯薬出版株式会社
• [Remarks] 国立病院機構近畿中央胸部疾患センター
  • URL: http://www.hosp.go.jp/~kch/
• [Remarks] 日本肺胞蛋白研究グループ英語版ホームページ
  • URL: http://www.pap-guide.jp/en/index.html