Naoki Nishiyama1, Masahiro Masuo2, Yoshihisa Nukui3, Tomoya Tateishi4, Mitsuhiro Kishino5, Ukihide Tateishi6, Kaori Morota7, Kazuyuki Ohbo8, Yasunari Miyazaki9. 1. Department of Respiratory Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. Electronic address: nispulm@tmd.ac.jp. 2. Department of Respiratory Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. Electronic address: masupulm@tmd.ac.jp. 3. Department of Respiratory Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. Electronic address: nukui.pulm@gmail.com. 4. Department of Respiratory Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. Electronic address: tateishi.pulm@tmd.ac.jp. 5. Department of Diagnostic Radiology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. Electronic address: ksnmrad@tmd.ac.jp. 6. Department of Diagnostic Radiology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. Electronic address: ttisdrnm@tmd.ac.jp. 7. Scientific Affairs, Diagnostics Division, Abbott Japan LLC, 3-5-27 Mita Minato-ku, Tokyo, 108-6305, Japan. Electronic address: kaori.morota@abbott.com. 8. Department of Histology and Cell Biology, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. Electronic address: kohbo@yokohama-cu.ac.jp. 9. Department of Respiratory Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. Electronic address: miyazaki.pilm@tmd.ac.jp.
Abstract
BACKGROUND: The clinical course and prognosis of progressive fibrosing interstitial lung diseases (PF-ILDs) vary between individuals. Notably, predictive serum biomarkers for disease management are needed. Serum human epididymis protein 4 (HE4) is reportedly elevated in patients with idiopathic pulmonary fibrosis (IPF); however, its clinical utility remains unknown. We evaluated the potential of serum HE4 as a biomarker for patients with PF-ILD. METHODS: Serum HE4 was measured in a retrospective study consisting of 34 patients with PF-ILD and 40 healthy volunteers. The relationship between serum HE4 levels and clinical parameters or prognosis was investigated. To validate the significance of results obtained, a prospective observational study was performed in 37 patients presenting PF-ILD and 40 control patients without PF-ILD. RESULTS: Serum HE4 levels were higher in patients with PF-ILD than in healthy volunteers (P < 0.01). Moreover, serum HE4 levels correlated with the extent of honeycombing on chest high-resolution computed tomography (r = 0.41, P = 0.015). In multivariate analysis using the Cox proportional hazard model, higher HE4 levels (>238 pmol/L) were associated with an elevated mortality risk; hazard ratio (HR) 7.27, 95% CI 1.56-34.0, P = 0.01 in the derivation cohort; HR 44.3, 95% CI 4.19-468, P < 0.01 in validation cohort. CONCLUSIONS: Serum HE4 levels may serve as a new diagnostic and prognostic biomarker for patients with PF-ILD.
BACKGROUND: The clinical course and prognosis of progressive fibrosing interstitial lung diseases (PF-ILDs) vary between individuals. Notably, predictive serum biomarkers for disease management are needed. Serum human epididymis protein 4 (HE4) is reportedly elevated in patients with idiopathic pulmonary fibrosis (IPF); however, its clinical utility remains unknown. We evaluated the potential of serum HE4 as a biomarker for patients with PF-ILD. METHODS: Serum HE4 was measured in a retrospective study consisting of 34 patients with PF-ILD and 40 healthy volunteers. The relationship between serum HE4 levels and clinical parameters or prognosis was investigated. To validate the significance of results obtained, a prospective observational study was performed in 37 patients presenting PF-ILD and 40 control patients without PF-ILD. RESULTS: Serum HE4 levels were higher in patients with PF-ILD than in healthy volunteers (P < 0.01). Moreover, serum HE4 levels correlated with the extent of honeycombing on chest high-resolution computed tomography (r = 0.41, P = 0.015). In multivariate analysis using the Cox proportional hazard model, higher HE4 levels (>238 pmol/L) were associated with an elevated mortality risk; hazard ratio (HR) 7.27, 95% CI 1.56-34.0, P = 0.01 in the derivation cohort; HR 44.3, 95% CI 4.19-468, P < 0.01 in validation cohort. CONCLUSIONS: Serum HE4 levels may serve as a new diagnostic and prognostic biomarker for patients with PF-ILD.