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In this systematic review and meta-analysis, we aimed to explore ideal ARDS biomarkers which can reflect pathophysiology features precisely and better identify at-risk patients and predict mortality. Web of Science, PubMed, Embase, OVID, and the Cochrane Library were systematically searched for studies assessing the reliability of pulmonary-originated epithelial proteins in ARDS. A total of 32 studies appeared eligible for meta-analysis, including 2654 ARDS\/ALI patients in this study. In the at-risk patients\u2019 identification group, the highest pooled effect size was observed in Krebs von den Lungren-6 (KL-6) (SMD: 1.17 [95% CI: 0.55, 1.79]), followed by club cell proteins 16 (CC16) (SMD: 0.74 [95% CI: 0.01, 1.46]), and surfactant proteins-D (SP-D) (SMD: 0.71 [95% CI: 0.57, 0.84]). For the mortality prediction group, CC16 exhibited the largest effect size with SMD of 0.92 (95% CI: 0.42, 1.43). Meanwhile, the summary receiver operating characteristic (SROC) of CC16 for ARDS diagnosis reached an AUC of 0.80 (95% CI: 0.76, 0.83). In conclusion, this study provides a ranking system for pulmonary-originated epithelial biomarkers according to their association with distinguishing at-risk patients and predicting mortality. In addition, the study provides evidence for the advantage of biomarkers over traditional diagnostic criteria. The performance of biomarkers may help to clinically improve the ARDS diagnosis and mortality prediction.<\/jats:p>","DOI":"10.3390\/ijms24076090","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T03:50:21Z","timestamp":1679629821000},"page":"6090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Circulating Pulmonary-Originated Epithelial Biomarkers for Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"24","author":[{"given":"Huishu","family":"Lin","sequence":"first","affiliation":[{"name":"Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China"},{"name":"Wenzhou Safety (Emergency) Institute, Tianjin University, Wenzhou 325000, China"},{"name":"Tianjin Key Laboratory of Disaster Medicine Technology, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qisijing","family":"Liu","sequence":"additional","affiliation":[{"name":"Research Institute of Public Health, School of Medicine, Nankai University, Tianjin 300381, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China"},{"name":"Wenzhou Safety (Emergency) Institute, Tianjin University, Wenzhou 325000, China"},{"name":"Tianjin Key Laboratory of Disaster Medicine Technology, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziquan","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China"},{"name":"Wenzhou Safety (Emergency) Institute, Tianjin University, Wenzhou 325000, China"},{"name":"Tianjin Key Laboratory of Disaster Medicine Technology, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Cui","sequence":"additional","affiliation":[{"name":"Wenzhou Safety (Emergency) Institute, Tianjin University, Wenzhou 325000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penghui","family":"Li","sequence":"additional","affiliation":[{"name":"School of Environmental Science and Safety Engineering, Tianjin University of Technology, Tianjin 300384, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojun","family":"Fan","sequence":"additional","affiliation":[{"name":"Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China"},{"name":"Wenzhou Safety (Emergency) Institute, Tianjin University, Wenzhou 325000, China"},{"name":"Tianjin Key Laboratory of Disaster Medicine Technology, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1141-9646","authenticated-orcid":false,"given":"Liqiong","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China"},{"name":"Wenzhou Safety (Emergency) Institute, Tianjin University, Wenzhou 325000, China"},{"name":"Tianjin Key Laboratory of Disaster Medicine Technology, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1001\/jama.2016.0291","article-title":"Epidemiology, Patterns of Care, and Mortality for Patients with Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries","volume":"315","author":"Bellani","year":"2016","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Rizzo, A.N., Aggarwal, N.R., Thompson, B.T., and Schmidt, E.P. 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