A nationwide multicenter study of the Cochlin tomo-protein detection test: clinical characteristics of perilymphatic fistula cases

Abstract

Objective: To investigate the positive rate for the Cochlin tomo-protein (CTP: an inner ear-specific protein) detection test among patients with inner ear-related clinical manifestations and evaluate the clinical characteristics of definite perilymphatic fistula (PLF).

Methods: We have performed an ELISA-based CTP detection test using middle ear lavage (MEL) samples from 497 cases of suspected PLF enrolled from 70 clinical centers nationwide between 2014 and 2015. In addition to the CTP-positive rate, audio-vestibular symptoms were compared between CTP-positive and -negative cases.

Results: 8–50% of patients in category 1 (trauma, middle and inner ear disease cases), and about 20% of those in categories 2, 3 and 4 (external origin antecedent events, internal origin antecedent events, and without antecedent event, respectively) were positive for CTP. In category 1 cases, the earlier tested samples showed a higher CTP-positive rate, whereas no differences were observed in categories 2, 3 or 4. The characteristic clinical features in the earlier tested cases were nystagmus and fistula sign in CTP test-positive cases in category 1, and streaming water-like tinnitus in those in categories 2, 3 and 4.

Conclusion: The present study clarified that CTP detection test-positive patients exist at considerable rates among patients with inner ear-related manifestations.

Chinese abstract

目的: 探讨对具有内耳相关临床表现的病人所进行的Cochlin断层蛋白 (CTP: 内耳特有性蛋白) 检测的阳性率, 并评估确定的外淋巴瘘 (PLF) 的临床特征。

方法: 我们对从2014年至2015年间在全国范围70个临床中心招募的疑有PLF的497个病例所得到的中耳灌洗 (MEL) 样品进行了基于ELISA的CTP检测试验。除CTP阳性率外, 对音频前庭症状在CTP阳性和阴性病例之间进行了比较。

结果: 类别1 (创伤、中耳和内耳病例) 中的8-50％的患者, 以及类别2、3和4 (分别指: 外部起源前因事件、内部起源前因事件、以及没有先前事件) 中的约20％, 都呈CTP阳性。在1类病例中, 较早测试的样品显示较高的CTP阳性率, 而在类别2、3或4中没有观察到差异。早期测试病例中的特点性临床特征是, 在类别1中, CTP测试阳性病例中的眼球震颤和瘘迹象, 以及在类别2、3和4中的流水样耳鸣。

结论: 本研究说明, 在内耳相关表现的患者中, CTP检测阳性患者占相当大的比例。

Keywords:

• Perilymphatic fistula
• perilymph
• Cochlin isoform
• hearing loss
• vestibular symptom
• vertigo
• tinnitus
• ELISA
• biomarker

Acknowledgements

This work was supported by the Ministry of Health and Welfare, Japan (http://www.mhlw.go.jp/english/) and a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (http://www.mext.go.jp/english/). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank Mr. Koichi Toyoda, Industry-University Cooperation Advisor at Saitama Medical University for helping us to establish this clinical trial.

We thank the participants of the consortium for the Multicenter investigator-initiated trial of the CTP detection test: Dr. Yuichiro Horibe (Aichi Medical University), Dr. Teruyuki Satoh (Akita University), Dr. Kan Kishibe (Asahikawa Medical University), Dr. Nobuyoshi Tsuzuki (Japanese Red Cross Ashikaga Hospital), Dr. Shin-ichi Haginomori (Osaka Medical College), Dr. Yuko Kataoka (Okayama University), Dr. Yuko Suzuka (Kanazawa Medical University), Dr. Hitoshi Sugimoto (Kanazawa University), Dr. Kenji Ishii (Kamio Memorial Hospital), Dr. Seiya Goto (Kariya Toyota General Hospital), Dr. Hiroshi Shinohara, Dr. Hironari Shimizu and Dr. Saeko Yoshida (Kawakita General Hospital), Dr. Susumu Baba (Kansai Medical University), Dr. Hiroshi Hosono and Dr. Hajime Sano (Kitasato University), Dr. Rie Kanai (Medical Research Institute Kitano Hospital), Dr. Toru Seo (Kinki University), Dr. Norio Yamamoto (Kyoto University), Dr. Masako Masuda (Kumamoto University), Dr. Ryouta Mihashi (Kurume University School of Medicine), Dr. Katsumasa Takahashi (Gunma University), Dr. Takashi Nabekura (Miyazaki Prefectural Miyazaki hospital), Dr. Taisuke Kobayashi (Kochi Medical School), Dr. Hidekane Yoshimura, Dr. Satoshi Iwasaki and Dr. Yoh-ichiro Iwasa (International University of Health and Welfare MITA Hospital), Dr. Yutaka Isogai (Speech, Language and Hearing Center, International University of Health and Welfare Clinic), Dr. Takayuki Morikawa (Komatsuzaki Hospital), Dr. Koichiro Wasano (Japanese Red Cross Shizuoka Hospital), Dr. Masayuki Shirakura (Jichi Medical University Saitama Medical Center), Dr. Sei Kobayashi (Showa University), Dr. Hiroaki Suzuki (Shinshu University) Dr. Kunihiko Makino and Dr. Kana Lee (Shin-Suma General Hospital), Dr. Itomi Nishijima (Sannoh Hospital), Dr. Koichi Kure (Seirei Yokohama Hospital), Dr. Kenichi Ando (Takayama Red Cross Hospital), Dr. Shintaro Fujimura, Dr. Tsuyoshi Kojima, Dr. Tetsuro Kobayashi and Dr. Ryusuke Hori (Tenri Hospital), Dr. Akinobu Kakigi (Tokyo University), Dr. Kyoko Shirai and Dr. Noriko Nagai (Tokyo Medical University), Dr. Yoshihiro Noguchi, Dr. Ken Kitamura, Dr. Yoshiyuki Kawashima and Dr. Masatoki Takahashi (Tokyo Medical and Dental University), Dr. Manabu Komori (The Jikei University School of Medicine), Dr. Fumie Kaneko, Dr. Hana Mori and Dr. Hiroshi Sunose (Tokyo Women's Medical University, Medical Center East), Dr. Masanori Ishii (Japan Community Healthcare Organization Tokyo Shinjuku Medical Center), Dr. Yurika Kimura (Tokyo Metropolitan Geriatric Hospital), Dr. Sota Yamaguchi (Toho University Ohashi Medical Center), Dr. Noriaki Takeda (Tokushima University School of Medicine), Dr. Takashi Kashiwagi and Dr. Satoru Fukami (Dokkyo Medical University), Dr. Yasuomi Kunimoto, Dr. Junko Kuya and Dr. Hiroaki Yazama (Tottori University), Dr. Fujisaka Michirou (Toyama University), Dr. Tadao Yoshida (Nagoya University Graduate School of Medicine), Dr. Toshimitsu Nemoto (Japanese Red Cross Narita Hospital), Dr. Makoto Miura and Dr. Saki Yabuuchi (Japanese Red Cross Society Wakayama Medical Center), Dr. Nozomu Wakayama (Nippon Medical School Musashikosugi Hospital), Dr. Kunihiro Mizuta (Hamamatsu University School of Medicine), Dr. Takeshi Morita (Hyogo Prefectural Amagasaki Hospital), Dr. Akira Sasaki (Hirosaki University Graduate School of Medicine), Dr. Tetsuko Ueno (Fukuoka University School of Medicine), Dr. Yukio Nomoto (Fukushima Medical University), Dr. Shigehiro Ueyama (Funai Ear Nose Throat Clinic), Dr. Yasuo Hosoda, Dr. Makiko Ohtani and Dr. Takeo Nonoda (Hosoda Ear Clinic), Dr. Shinya Morita (Hokkaido University Graduate School of Medicine), Dr. Hiroshi Sakaida (Mie University Graduate School of Medicine), Dr. Yuko Hata and Dr. Katsuhiro Tsutsumiuchi (Mitsui Memorial Hospital), Dr. Keiji Matsuda and Dr. Takahiro Nakajima (Miyazaki University), Dr. Toshinori Kubota (Yamagata University Faculty of Medicine), Dr. Kazuma Sugahara (Yamaguchi University Hospital), Dr. Shuichiro Endo and Dr. Kyousuke Hatsushika (University of Yamanashi), Dr. Makito Tanabe (Yamamoto Ear Surgicenter), Dr. Shigeki Tsuchihashi and Dr. Masanobu Hiraoka (Wakayama Medical University)

Disclosure statement

Saitama Medical University has the patent for this CTP ELISA test. The development of this CTP ELISA test was performed in collaboration with Biomedical Laboratories under license from and with the technical assistance of Saitama Medical University with royalties.

The authors did not receive funding from SRL (Special Reference Laboratories) Inc.

This relationship had no influence on results.

Additional information

Funding

This work was supported by the Ministry of Health Labour and Welfare, Japan (http://www.mhlw.go.jp/english/) and a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (http://www.mext.go.jp/english/).