PMID- 31665737 OWN - NLM STAT- MEDLINE DCOM- 20200923 LR - 20200923 IS - 1423-0356 (Electronic) IS - 0025-7931 (Linking) VI - 98 IP - 6 DP - 2019 TI - Evaluation of the Diagnostic Efficacies of Serological Markers KL-6, SP-A, SP-D, CCL2, and CXCL13 in Idiopathic Interstitial Pneumonia. PG - 534-545 LID - 10.1159/000503689 [doi] AB - BACKGROUND: The objective of this study was to evaluate the diagnostic value of serological markers Krebs von den Lungen-6 (KL-6), surfactant protein-A (SP-A), SP-D, chemokine ligand 2 (CCL2), and chemokine 13 (CXCL13) in idiopathic interstitial pneumonia (IIP). METHODS: Patients with IIP aged 18-80 years from the First Affiliated Hospital of Guangzhou Medical University were enrolled in this retrospective case-control study. Data on the general patient characteristics, laboratory test results, chest high-resolution CT, and pulmonary function test results were collected. The diagnosis of idiopathic pulmonary fibrosis (IPF) was based on the international practice guidelines for the diagnosis and treatment of IPF, a collaborative effort published by the American Thoracic Society (ATS)/European Respiratory Association (ERS), Japanese Respiratory Society, and Latin American Thoracic Society. The diagnostic criteria of non-IPF (N-IPF) followed the consensus classification of the IIPs, which was jointly issued by the ATS and ERS in 2002. The diagnosis of interstitial pneumonia with autoimmune features (IPAF) was based on the official research statement on IPAF, which was jointly issued by the ATS and ERS in 2015. Serum levels of KL-6, SP-A, SP-D, CCL2, and CXCL13 were measured. The differences in the expression of these biomarkers and their correlation with the severity of the disease were analyzed. The sensitivity, specificity, cutoff value, and area under the curve (AUC) value for each of the indices were determined using the receiver operating characteristic (ROC) curve analysis. FINDINGS: Between September 2015 and October 2017, 69 patients with IIP. Of these patients, 19 had IPF, 23 had N-IPF, and 27 had IPAF. We also enrolled 20 age- and gender-matched patients with pneumonia and 15 uninfected individuals as normal control. The serum levels of KL-6, SP-A, -SP-D, CCL2, and CXCL13 were significantly higher in patients with IIP than in patients with pneumonia and the normal controls. The detection of these markers was found to have better diagnostic efficacy in patients with IIP than in those with pneumonia. Of these markers above, KL-6 had the highest diagnostic value (AUC 0.96, 95% CI 0.93-0.99). Based on a logistics regression analysis, the combination of KL-6, CCL2, and CXCL13 had an improved diagnostic efficacy for IIP. In patients with IIP, the serum levels of KL-6, SP-A, CCL2, and CXCL13 all showed a significant negative correlation with the diffusing capacity of the lungs for carbon monoxide (DLCO; r = -0.36, -0.37, -0.36, -0.30, respectively; all p < 0.05). Although their expression levels along with that of SP-D were elevated in patients with IPF, N-IPF, and IPAF, it was difficult to distinguish between these 3 conditions by detecting the 5 serum biomarkers together. Our findings indicate that the serum levels of KL-6, SP-A, SP-D, CCL2, and CXCL13 are notably elevated in patients with IIP and show significant correlation with the severity of interstitial lung lesions. Additionally, we further explore the diagnostic efficacy of 5 biomarkers in different types of IIP. It is the first time that the level of serum marker CXCL13 of N-IPF and IPAF patients was higher than IPF patients, which further enriched the study on serum markers for IIPs. Between September 2015 and October 2017, 69 patients with IIP. Of these patients, 19 had IPF, 23 had N-IPF, and 27 had IPAF. We also enrolled 20 age- and gender-matched patients with pneumonia and 15 uninfected individuals as normal control. The serum levels of KL-6, SP-A, SP-D, CCL2, and CXCL13 were significantly higher in patients with IIP than in patients with pneumonia and the normal controls. Of these markers above, KL-6 had the highest diagnostic value (AUC 0.96, 95% CI 0.93-0.99). Based on a logistics regression analysis, the combination of KL-6, CCL2, and CXCL13 had an improved diagnostic efficacy for IIP. In patients with IIP, the serum levels of KL-6, SP-A, CCL2, and CXCL13 all showed a significant negative correlation with the DLCO (r = -0.36, -0.37, -0.36, -0.30, respectively; all p < 0.05). Our findings indicate that the serum levels of KL-6, -SP-A, SP-D, CCL2, and CXCL13 are notably elevated in patients with IIP and show significant correlation with the severity of interstitial lung lesions. Additionally, we further explore the diagnostic efficacy of 5 biomarkers in different types of IIP. It is the first time that the level of serum marker CXCL13 of N-IPF and IPAF patients was higher than IPF patients, which further enrich the study on serum markers in IIPs. INTERPRETATION: Although the combined detection of KL-6, CCL3, and CXCL13 significantly improves the diagnosis of IIP, detection of all the 5 markers together is unable to distinguish between IPF, N-IPF, and IPAF. CI - (c) 2019 S. Karger AG, Basel. FAU - Xue, Mingshan AU - Xue M AD - Department of Allergy and Clinical Immunology, Gangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. FAU - Guo, Zijun AU - Guo Z AD - Guangdong Women and Children Hospital, Guangzhou, China. FAU - Cai, Chuanxu AU - Cai C AD - Department of Allergy and Clinical Immunology, Gangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. FAU - Sun, Baoqing AU - Sun B AD - Department of Allergy and Clinical Immunology, Gangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China, sunbaoqing@vip.163.com. FAU - Wang, Hongman AU - Wang H AD - The Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai, China. LA - eng PT - Evaluation Study PT - Journal Article DEP - 20191030 PL - Switzerland TA - Respiration JT - Respiration; international review of thoracic diseases JID - 0137356 RN - 0 (Biomarkers) RN - 0 (CCL2 protein, human) RN - 0 (CXCL13 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CXCL13) RN - 0 (MUC1 protein, human) RN - 0 (Mucin-1) RN - 0 (Pulmonary Surfactant-Associated Protein A) RN - 0 (Pulmonary Surfactant-Associated Protein D) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Area Under Curve MH - Biomarkers/blood MH - Case-Control Studies MH - Chemokine CCL2/*blood MH - Chemokine CXCL13/blood MH - China MH - Humans MH - Idiopathic Interstitial Pneumonias/*blood/*diagnosis MH - Logistic Models MH - Middle Aged MH - Mucin-1/*blood MH - Multivariate Analysis MH - Pulmonary Surfactant-Associated Protein A/*blood MH - Pulmonary Surfactant-Associated Protein D/*blood MH - ROC Curve MH - Reference Values MH - Retrospective Studies MH - Sensitivity and Specificity MH - Young Adult OTO - NOTNLM OT - CC chemokine ligand OT - Chemokine 13 OT - Idiopathic interstitial pneumonia OT - Krebs von den Lungen-6 OT - Pulmonary function OT - Surfactant protein-A OT - Surfactant protein-D EDAT- 2019/10/31 06:00 MHDA- 2020/09/24 06:00 CRDT- 2019/10/31 06:00 PHST- 2019/05/21 00:00 [received] PHST- 2019/09/24 00:00 [accepted] PHST- 2019/10/31 06:00 [pubmed] PHST- 2020/09/24 06:00 [medline] PHST- 2019/10/31 06:00 [entrez] AID - 000503689 [pii] AID - 10.1159/000503689 [doi] PST - ppublish SO - Respiration. 2019;98(6):534-545. doi: 10.1159/000503689. Epub 2019 Oct 30.