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Original research
Prospective nationwide multicentre cohort study of the clinical significance of autoimmune features in idiopathic interstitial pneumonias
  1. Noriyuki Enomoto1,
  2. Sakae Homma2,
  3. Naohiko Inase3,
  4. Yasuhiro Kondoh4,
  5. Takeshi Saraya5,
  6. Hajime Takizawa5,
  7. Yoshikazu Inoue6,
  8. Hiroshi Ishii7,
  9. Yoshio Taguchi8,
  10. Shinyu Izumi9,
  11. Yasuhiko Yamano4,
  12. Yoshinori Tanino10,
  13. Yasuhiko Nishioka11,
  14. Mikio Toyoshima12,
  15. Koshi Yokomura13,
  16. Shiro Imokawa14,
  17. Naoki Koshimizu15,
  18. Takehisa Sano16,
  19. Taisuke Akamatsu17,
  20. Hiroshi Mukae18,
  21. Motoyasu Kato19,
  22. Naoki Hamada20,
  23. Hirofumi Chiba21,
  24. Shinobu Akagawa22,
  25. Shigeo Muro23,
  26. Hironori Uruga24,
  27. Hiroyuki Matsuda25,
  28. Yusuke Kaida26,
  29. Miho Kanai27,
  30. Kazutaka Mori28,
  31. Masafumi Masuda28,
  32. Hironao Hozumi1,
  33. Tomoyuki Fujisawa1,
  34. Yutaro Nakamura1,
  35. Noriyoshi Ogawa29,
  36. Takafumi Suda1
  1. 1Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
  2. 2Department of Advanced and Integrated Interstitial Lung Diseases Research, School of Medicine, Toho University, Tokyo, Japan
  3. 3Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan
  4. 4Department of Respiratory Medicine and Allergy, Tosei General Hospital, Aichi, Japan
  5. 5Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan
  6. 6Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan
  7. 7Department of Respiratory Medicine, Fukuoka University Hospital, Fukuoka, Japan
  8. 8Department of Respiratory Medicine, Tenri Hospital, Nara, Japan
  9. 9Department of Respiratory Medicine, National Center for Global Health and Medicine, Tokyo, Japan
  10. 10Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan
  11. 11Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
  12. 12Department of Respiratory Medicine, Hamamatsu Rosai Hospital, Hamamatsu, Japan
  13. 13Department of Respiratory Medicine, Respiratory Disease Center, Seirei Mikatahara General Hospital, Hamamatsu, Japan
  14. 14Department of Respiratory Medicine, Iwata City Hospital, Iwata, Japan
  15. 15Department of Respiratory Medicine, Fujieda Municipal General Hospital, Fujieda, Japan
  16. 16Department of Respiratory Medicine, Shizuoka City Shizuoka Hospital, Shizuoka, Japan
  17. 17Department of Respiratory Medicine, Shizuoka General Hospital, Shizuoka, Japan
  18. 18Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  19. 19Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
  20. 20Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  21. 21Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan
  22. 22Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, Tokyo, Japan
  23. 23Department of Respiratory Medicine, Nara Medical University, Nara, Japan
  24. 24Department of Respiratory Medicine, Respiratory Center, Toranomon Hospital, Tokyo, Japan
  25. 25Department of Respiratory Medicine, Japanese Red Cross Shizuoka Hospital, Shizuoka, Japan
  26. 26Department of Respiratory Medicine, Enshu Hospital, Hamamatsu, Japan
  27. 27Respiratory and Allergy Medicine, National Hospital Organization Tenryu Hospital, Hamamatsu, Japan
  28. 28Respiratory Medicine, Shizuoka City Shimizu Hospital, Shizuoka, Japan
  29. 29Division of Immunology and Rheumatology, Department of Internal Medicine 3, Hamamatsu University School of Medicine, Hamamatsu, Japan
  1. Correspondence to Dr Noriyuki Enomoto, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan; norieno{at}hama-med.ac.jp

Abstract

Background Some patients with idiopathic interstitial pneumonia (IIP) show autoimmune features. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept in these patients. However, retrospective studies reported conflicting results of its prognosis. Therefore, this study was conducted to prospectively evaluate the clinical significance of autoimmune features in patients with IIP.

Methods This nationwide multicentre study prospectively enrolled consecutive patients with IIP. At the diagnosis, we systematically evaluated 63 features suggestive of connective tissue diseases using a checklist including symptoms/signs and autoantibodies, which contained most items of the IPAF criteria and followed up with the patients. Clinical phenotypes were included in a cluster analysis.

Results In 376 patients with IIP enrolled, 70 patients (18.6%) met the IPAF criteria. The proportion of patients with IPAF was significantly lower in idiopathic pulmonary fibrosis (IPF) than in non-IPF (6.0% vs 24.3%, respectively). During a median observation period of 35 months, patients with IPAF more frequently developed systemic autoimmune diseases and had less frequent acute exacerbation of IIPs than patients with non-IPAF. IPAF diagnosis was significantly associated with better survival and was an independent positive prognostic factor in total and patients with non-IPF. Cluster analysis by similarity of clinical phenotypes identified a cluster in which there was a higher number of women, and patients had more autoimmune features and a better prognosis than other clusters.

Interpretation These observations suggest that some patients with IIP show autoimmune features with distinct characteristics and favourable prognosis. However, we were not able to determine the appropriate therapies for these patients.

  • connective tissue disease associated lung disease
  • idiopathic pulmonary fibrosis
  • interstitial fibrosis

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Footnotes

  • Contributors NE and TSu contributed to the study conception and design. NE, SH, NI, YK, TS, HT, YI, HI, YT, SIz, YY, YT, YN, MT, KY, SIm, NK, TSa, TA, HMu, MK, NH, HC, SA, SM, HU, HMa, YK, MK, KM, MM, HH, TF and YN contributed acquisition of data. NE, KM and NO analysed and interpreted the data. NE drafted the manuscript. SH, NI, YK, TS, HT, YI, HI, YT, SI, YY, YT, YN, MT, KY, SI, NK, ST, TA, HM, MK, NH, HC, SA, SM, HU, HM, YK, MK, KM, MM, HH, TF, YN, NO and TS contributed to critical revision for important intellectual content. NE, SH, NI, YK, TS, HT, YI, HI, YT, SI, YY, YT, YN, MT, KY, SI, NK, TSa, TA, HM, MK, NH, HC, SA, SM, HU, HM, YK, MK, KM, MM, HH, TF, YN, NO and TSu approved the final version of manuscript to be published.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests YK has received personal fees from Asahi Kasei Pharma Corp., from Boehringer Ingelheim Co., Ltd., from Janssen Pharmaceutical K.K., from Eisai Inc., from Kyorin Pharmaceutical Co., Ltd., from Mitsubishi Tanabe Pharma, from Novartis Pharma K.K., and from Shionogi & Co., outside the submitted work. YI has received grants from Japanese ministry of Health, Labour, and Welfare, grants from Japan Agency for Medical Research and Development, and lecture fee from Boehringer Ingelheim and Shionogi outside the submitted work. YN has received grants and personal fees from Nippon Boehringer Ingelheim Co., Ltd., grants and personal fees from MSD K.K., grants and personal fees from Ono Pharmaceutical Co., Ltd., grants and personal fees from Taiho Pharmaceutical Co., Ltd., grants and personal fees from Chugai Pharmaceutical Co., Ltd., grants and personal fees from Asahi Kaesi Pharma Corporation, grants and personal fees from Eli Lilly Japan K.K., and grants from Bonac Corporation, outside the submitted work. HM has received grants and personal fees from Daiichi Sankyo, grants and personal fees from MSD, grants and personal fees from Sumitomo Dainippon Pharma, grants and personal fees from Taisho Toyama Pharmaceutical, grants and personal fees from Astellas Pharma, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Shionogi, grants from Taiho Pharmaceutical, grants from Ono Pharmaceutical, grants from Takeda Pharmaceutical, grants from Eli Lilly Japan, grants from Novartis Pharma, grants from Fujifilm Pharma, grants from Meiji Seika Pharma, grants from Toyama Chemical, grants from Eisai, grants from Chugai Pharmaceutical, personal fees from Pfizer, personal fees from Kyorin Pharmaceutical, and personal fees from AstraZeneca, outside the submitted work. TS has received lecture fees from Boehringer Ingelheim and Shionogi, outside the submitted work.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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