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Serum S100A8 and S100A9 as prognostic biomarkers in acute exacerbation of idiopathic pulmonary fibrosis |
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| Institution: | 1. Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan;2. Health Administration Center, Hamamatsu University School of Medicine, Hamamatsu, Japan;3. Medical & Biological Laboratories Co., Ltd., Nagoya, Japan;4. Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan;1. Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City, Osaka 591-8555, Japan;2. Department of Pathology, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City, Osaka 591-8555, Japan;3. Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City, Osaka 591-8555, Japan;4. Department of Radiology, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City, Osaka 591-8555, Japan;5. Department of Respiratory Medicine, Kinki Central Hospital, Itami, Osaka 664-8533, Japan;1. Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake-cho, Seto, Aichi, 489-8642, Japan;2. Department of Respiratory Medicine, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki, Gifu, 503-8502, Japan;3. Department of Rehabilitation, Tosei General Hospital, 160 Nishioiwake-cho, Seto, Aichi, 489-8642, Japan;1. Laboratory for Wound Repair and Regenerative Surgery, Department of Surgery, Plastic Surgery Division, Northwestern University, Feinberg School of Medicine, Chicago, Illinois;2. Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;3. Department of Burns, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;1. 1st Academic Department of Respiratory Medicine, Medical School, National and Kapodistrian University of Athens, Hospital for Diseases of the Chest, “Sotiria”, Athens, Greece;2. Biomedical Sciences Research Center, “Alexander Fleming”, Division of Immunology, Athens, Greece;1. Respiratory Diseases and Lung Transplantation, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, Siena, Italy;2. Functional proteomics lab, Department of life sciences, University of Siena, Italy;3. Center for Interstitial and Rare Lung Disease, Department of Pulmonology, Ruhrlandklinik University Hospital, Essen, Germany;1. Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan;2. Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital, Ikoma, Nara 630-0293, Japan |
| Abstract: | BackgroundAcute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a devastating and life-threatening condition during its clinical course. Biomarkers for precisely anticipating the prognosis of AE-IPF remain to be fully established. The objective of this study was to clarify whether S100A8 and S100A9, which are calcium-binding proteins mainly produced by activated neutrophils, are significant prognostic biomarkers in AE-IPF.MethodsThirty-seven patients with AE-IPF who were diagnosed and treated at our hospital were retrospectively evaluated. The serum levels of S100A8 and S100A9 were measured using enzyme-linked immunosorbent assay, and the relationships between these levels and clinical parameters or prognosis were evaluated.ResultsThe serum levels of S100A8 (median 386.5 ng/mL) and S100A9 (median 60.2 ng/mL) in patients with AE-IPF were significantly higher than those in age-matched healthy controls and in patients at IPF diagnosis (p < 0.001 for all combinations). The serum levels of S100A8 negatively correlated with percent forced vital capacity (r = ?0.356, p = 0.049) and positively correlated with peripheral white blood cell number (r = 0.509, p = 0.002). Immunohistochemical staining of autopsy lung specimens showed that neutrophils, present mainly in the alveolar septum, were positive for S100A8 and S100A9. Patients with AE-IPF with higher levels of S100A8 or S100A9 showed significantly worse 3-month survival than those with lower levels (log-rank test, both p = 0.028). Finally, in multivariate analysis, the serum levels of both S100A8 and S100A9 were significant prognostic factors (hazard ratio 4.032, p = 0.023 and hazard ratio 4.327, p = 0.012).ConclusionThe serum levels of S100A8 and S100A9 at AE were significant prognostic biomarkers in patients with AE-IPF. |
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