A prospective cohort study of periostin as a serum biomarker in patients with idiopathic pulmonary fibrosis treated with nintedanib

Masaki Okamoto; Kiminori Fujimoto; Takeshi Johkoh; Atsushi Kawaguchi; Hiroshi Mukae; Noriho Sakamoto; Takashi Ogura; Satoshi Ikeda; Yasuhiro Kondoh; Yasuhiko Yamano; Kosaku Komiya; Kenji Umeki; Hirotaka Nishikiori; Yoshinori Tanino; Toru Tsuda; Naoki Arai; Masamichi Komatsu; Susumu Sakamoto; Kazuhiro Yatera; Yoshikazu Inoue; Yasunari Miyazaki; Seishu Hashimoto; Yasuo Shimizu; Hironao Hozumi; Hiroshi Ohnishi; Tomohiro Handa; Noboru Hattori; Tomoo Kishaba; Motoyasu Kato; Minoru Inomata; Hiroshi Ishii; Naoki Hamada; Satoshi Konno; Yoshiaki Zaizen; Arata Azuma; Takafumi Suda; Kenji Izuhara; Tomoaki Hoshino

doi:10.1038/s41598-023-49180-4

A prospective cohort study of periostin as a serum biomarker in patients with idiopathic pulmonary fibrosis treated with nintedanib

Sci Rep. 2023 Dec 27;13(1):22977. doi: 10.1038/s41598-023-49180-4.

Authors

Masaki Okamoto^{1

2}, Kiminori Fujimoto³, Takeshi Johkoh⁴, Atsushi Kawaguchi⁵, Hiroshi Mukae⁶, Noriho Sakamoto⁶, Takashi Ogura⁷, Satoshi Ikeda⁷, Yasuhiro Kondoh⁸, Yasuhiko Yamano⁸, Kosaku Komiya⁹, Kenji Umeki¹⁰, Hirotaka Nishikiori¹¹, Yoshinori Tanino¹², Toru Tsuda¹³, Naoki Arai¹⁴, Masamichi Komatsu¹⁵, Susumu Sakamoto¹⁶, Kazuhiro Yatera¹⁷, Yoshikazu Inoue¹⁸, Yasunari Miyazaki¹⁹, Seishu Hashimoto²⁰, Yasuo Shimizu²¹, Hironao Hozumi²², Hiroshi Ohnishi²³, Tomohiro Handa²⁴, Noboru Hattori²⁵, Tomoo Kishaba²⁶, Motoyasu Kato²⁷, Minoru Inomata²⁸, Hiroshi Ishii²⁹, Naoki Hamada³⁰, Satoshi Konno³¹, Yoshiaki Zaizen³², Arata Azuma³³, Takafumi Suda²², Kenji Izuhara³⁴, Tomoaki Hoshino³²

Affiliations

¹ Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan. okamoto_masaki@med.kurume-u.ac.jp.
² Department of Respirology, NHO Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka, 810-0065, Japan. okamoto_masaki@med.kurume-u.ac.jp.
³ Department of Radiology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
⁴ Department of Radiology, Kansai Rosai Hospital, Inabasou 3-1-69, Amagasaki, Hyogo, 660-0064, Japan.
⁵ Education and Research Center for Community Medicine, Faculty of Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
⁶ Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
⁷ Division of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomiokahigashi, Yokohama, Kanagawa-ku, Kanagawa, 236-0051, Japan.
⁸ Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake, Seto, Aichi, 489-0065, Japan.
⁹ Respiratory Medicine and Infectious Diseases, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan.
¹⁰ Department of Respiratory Medicine, Tenshindo Hetsugi Hospital, 5956 Nakahetsugi, Oita, 879-7761, Japan.
¹¹ Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, South-1-West-16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.
¹² Department of Pulmonary Medicine, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
¹³ Kirigaoka Tsuda Hospital, 3-9-20 Kirigaoka, Kitakyushu, Fukuoka, 802-0052, Japan.
¹⁴ Department of Respiratory Medicine, National Hospital Organization Ibarakihigashi National Hospital, 825 Terunuma, Tokai-mura, Ibaraki, 319-1113, Japan.
¹⁵ First Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
¹⁶ Department of Respiratory Medicine, Toho University Omori Medical Center, 6-11-1 Omorinishi, Tokyo, 143-8541, Japan.
¹⁷ Department of Respiratory Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Kitakyushu, Fukuoka, 807-8555, Japan.
¹⁸ Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nagasone-cho, Sakai, Osaka, 591-8555, Japan.
¹⁹ Department of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Tokyo, 113-8510, Japan.
²⁰ Department of Respiratory Medicine, Tenri Hospital, 200 Mishima-cho, Tenri, Nara, 632-8552, Japan.
²¹ Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi, 321-0293, Japan.
²² Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka, 431-3192, Japan.
²³ Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University, 185-1 Kohasu, Nankoku, Kochi, 783-8505, Japan.
²⁴ Department of Advanced Medicine for Respiratory Failure, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
²⁵ Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
²⁶ Department of Respiratory Medicine, Okinawa Chubu Hospital, 281 Miyazato, Uruma, Okinawa, 904-2293, Japan.
²⁷ Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Tokyo, 113-8421, Japan.
²⁸ Department of Respiratory Medicine, Japanese Red Cross Medical Center, 4-1-22 Hiroo, Tokyo, 150-8935, Japan.
²⁹ Department of Respiratory Medicine, Fukuoka University Chikushi Hospital, 1-1-1 Zokumyouin, Chikushino, Fukuoka, 818-8502, Japan.
³⁰ Department of Respiratory Medicine, Fukuoka University Hospital, 7-45-1 Nanakuma, Fukuoka, 814-0180, Japan.
³¹ Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, N15W7 Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
³² Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
³³ Respirology and Clinical Research Center, Mihara General Hospital and Nippon Medical School, Tokorozawa, Saitama, 359-0045, Japan.
³⁴ Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, 5-1-1 Nabeshima, Saga, 849-8501, Japan.

Abstract

This study investigated the utility of periostin, a matricellular protein, as a prognostic biomarker in patients with idiopathic pulmonary fibrosis (IPF) who received nintedanib. Monomeric and total periostin levels were measured by enzyme-linked immunosorbent assay in 87 eligible patients who participated in a multicenter prospective study. Forty-three antifibrotic drug-naive patients with IPF described in previous studies were set as historical controls. Monomeric and total periostin levels were not significantly associated with the change in forced vital capacity (FVC) or diffusing capacity of the lungs for carbon monoxide (D_LCO) during any follow-up period. Higher monomeric and total periostin levels were independent risk factors for overall survival in the Cox proportional hazard model. In the analysis of nintedanib effectiveness, higher binarized monomeric periostin levels were associated with more favorable suppressive effects on decreased vital capacity (VC) and D_LCO in the treatment group compared with historical controls. Higher binarized levels of total periostin were associated with more favorable suppressive effects on decreased D_LCO but not VC. In conclusion, higher periostin levels were independently associated with survival and better therapeutic effectiveness in patients with IPF treated with nintedanib. Periostin assessments may contribute to determining therapeutic strategies for patients with IPF.

Publication types

Multicenter Study

MeSH terms

Biomarkers
Humans
Idiopathic Pulmonary Fibrosis* / drug therapy
Periostin*
Prospective Studies
Treatment Outcome
Vital Capacity

Substances

nintedanib
Periostin
Biomarkers

Grants and funding

19K08637/Grant-in-Aid for Scientific Research