Human epididymis protein 4 is a new biomarker to predict the prognosis of progressive fibrosing interstitial lung disease |
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| Authors: | Naoki Nishiyama Masahiro Masuo Yoshihisa Nukui Tomoya Tateishi Mitsuhiro Kishino Ukihide Tateishi Kaori Morota Kazuyuki Ohbo Yasunari Miyazaki |
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| Affiliation: | 1. Department of Respiratory Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan;2. Department of Diagnostic Radiology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan;3. Scientific Affairs, Diagnostics Division, Abbott Japan LLC, 3-5-27 Mita Minato-ku, Tokyo, 108-6305, Japan;4. Department of Histology and Cell Biology, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan;1. Department of Respiratory Medicine, Ichinomiya-nishi Hospital, Ichinomiya, Japan;2. Department of Radiology, Ichinomiya-nishi Hospital, Ichinomiya, Japan;1. Nihon University School of Medicine, Division of Respiratory Medicine, Itabashi, Tokyo, Japan;2. Ishikawa Prefectural Central Hospital, Kanazawa, Ishikawa, Japan;3. Nagaoka Red Cross Hospital, Nagaoka, Niigata, Japan;4. AstraZeneca, Morristown, NJ, USA;5. AstraZeneca, Gaithersburg, MD, USA;6. AstraZeneca K.K., Osaka, Osaka, Japan;1. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan, 5-1-1 Nabeshima, Saga, Saga prefecture, 849-8501, Japan;2. Department of Otolaryngology, Head & Neck Surgery, Faculty of Medicine, Saga University, Saga, Japan, 5-1-1 Nabeshima, Saga, Saga prefecture, 849-8501, Japan;1. Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Hokkaido, Japan;2. Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan |
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| Abstract: | BackgroundThe 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 ?brosis (IPF); however, its clinical utility remains unknown. We evaluated the potential of serum HE4 as a biomarker for patients with PF-ILD.MethodsSerum 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.ResultsSerum 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.ConclusionsSerum HE4 levels may serve as a new diagnostic and prognostic biomarker for patients with PF-ILD. |
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| Keywords: | Human epididymis protein 4 Progressive fibrosing interstitial lung disease Honeycombing Prognosis Biomarker CHP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0040" }," $$" :[{" #name" :" text" ," _" :" chronic hypersensitivity pneumonia CTD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0050" }," $$" :[{" #name" :" text" ," _" :" connective tissue disease DLCO" },{" #name" :" keyword" ," $" :{" id" :" kwrd0060" }," $$" :[{" #name" :" text" ," _" :" diffusing capacity for carbon monoxide eGFR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0070" }," $$" :[{" #name" :" text" ," _" :" estimated glomerular filtration rate FEV1" },{" #name" :" keyword" ," $" :{" id" :" kwrd0080" }," $$" :[{" #name" :" text" ," _" :" forced expiratory volume FVC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0090" }," $$" :[{" #name" :" text" ," _" :" forced vital capacity HE4" },{" #name" :" keyword" ," $" :{" id" :" kwrd0100" }," $$" :[{" #name" :" text" ," _" :" human epididymis protein 4 HV" },{" #name" :" keyword" ," $" :{" id" :" kwrd0110" }," $$" :[{" #name" :" text" ," _" :" healthy volunteer HRCT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0120" }," $$" :[{" #name" :" text" ," _" :" high-resolution computed tomography IIPs" },{" #name" :" keyword" ," $" :{" id" :" kwrd0130" }," $$" :[{" #name" :" text" ," _" :" idiopathic interstitial pneumonias ILD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0140" }," $$" :[{" #name" :" text" ," _" :" interstitial lung disease IPF" },{" #name" :" keyword" ," $" :{" id" :" kwrd0150" }," $$" :[{" #name" :" text" ," _" :" idiopathic pulmonary ?brosis KL-6" },{" #name" :" keyword" ," $" :{" id" :" kwrd0160" }," $$" :[{" #name" :" text" ," _" :" Krebs von den Lungen 6 NSIP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0170" }," $$" :[{" #name" :" text" ," _" :" nonspecific interstitial pneumonia PF-ILD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0180" }," $$" :[{" #name" :" text" ," _" :" progressive fibrosing-interstitial lung disease SP-D" },{" #name" :" keyword" ," $" :{" id" :" kwrd0190" }," $$" :[{" #name" :" text" ," _" :" surfactant protein D UIP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0200" }," $$" :[{" #name" :" text" ," _" :" usual interstitial pneumonia VA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0210" }," $$" :[{" #name" :" text" ," _" :" alveolar volume |
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