Pleural fluid C-C class chemokines 22 and pleural effusion due to heart failure: a prospective and double-blind diagnostic accuracy test

Background Previous studies have indicated that C-C class chemokine ligand 22 (CCL22) is involved in the pathogenesis of tuberculous pleural effusion and malignant pleural effusion. However, the diagnostic role of pleural fluid CCL22 levels in patients with undiagnosed pleural effusions remains to b...

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Main Authors: Li Yan, Zhi-De Hu, Qianghua Zhou, Wen Zhao, José M Porcel, Su-Na Cha, Yan Niu, Jian-Xun Wen, Cheng Yan, Hong-Zhe Zhu, Ying-Jun Wang, Ling Hai, Ting-Wang Jiang, Wen-Qi Zheng
Format: Article
Language:English
Published: BMJ Publishing Group 2025-08-01
Series:BMJ Open Respiratory Research
Online Access:https://bmjopenrespres.bmj.com/content/12/1/e002823.full
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author Li Yan
Zhi-De Hu
Qianghua Zhou
Wen Zhao
José M Porcel
Su-Na Cha
Yan Niu
Jian-Xun Wen
Cheng Yan
Hong-Zhe Zhu
Ying-Jun Wang
Ling Hai
Ting-Wang Jiang
Wen-Qi Zheng
author_facet Li Yan
Zhi-De Hu
Qianghua Zhou
Wen Zhao
José M Porcel
Su-Na Cha
Yan Niu
Jian-Xun Wen
Cheng Yan
Hong-Zhe Zhu
Ying-Jun Wang
Ling Hai
Ting-Wang Jiang
Wen-Qi Zheng
author_sort Li Yan
collection DOAJ
description Background Previous studies have indicated that C-C class chemokine ligand 22 (CCL22) is involved in the pathogenesis of tuberculous pleural effusion and malignant pleural effusion. However, the diagnostic role of pleural fluid CCL22 levels in patients with undiagnosed pleural effusions remains to be elucidated.Methods We prospectively recruited patients with undiagnosed pleural effusion who visited two centres (Hohhot and Changshu) in China. Pleural biopsy, microbiological culture and effusion cytology were used to verify the cause of pleural effusion. Pleural fluid CCL22 levels were measured using an ELISA. The diagnostic accuracy of CCL22 for identifying heart failure (HF) was evaluated using a receiver operating characteristic (ROC) curve, and the net benefit of CCL22 was evaluated using decision curve analysis (DCA). Net benefit was defined as the benefit associated with true positives minus the harms associated with false positives at various threshold probabilities.Results We enrolled 153 and 58 patients in the Hohhot and Changshu cohorts, respectively. The cohort included 28 patients with HF and 183 patients with non-HF. Patients with HF had significantly lower pleural fluid CCL22 levels than non-HF patients. The area under the ROC curve (AUC) of CCL22 was 0.85 (95% CI: 0.77 to 0.93) in the Hohhot cohort and 0.87 (95% CI: 0.75 to 0.98) in the Changshu cohort. The AUC in the combined cohort was 0.85 (95% CI: 0.79 to 0.92), with a sensitivity of 0.82 (95% CI: 0.68 to 0.93) and a specificity of 0.73 (95% CI: 0.67 to 0.79) at the threshold of 150 ng/mL. DCA revealed a potential net benefit of pleural CCL22 determination in patients with undiagnosed pleural effusions.Conclusions Pleural fluid CCL22 may be a potential diagnostic marker for HF-related pleural effusion. Owing to the small sample size of this study, further studies with larger sample sizes are needed to validate our findings.
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spelling doaj-art-22b9f03910aa43e49e2163a24e7e7a972025-08-20T07:45:12ZengBMJ Publishing GroupBMJ Open Respiratory Research2052-44392025-08-0112110.1136/bmjresp-2024-002823Pleural fluid C-C class chemokines 22 and pleural effusion due to heart failure: a prospective and double-blind diagnostic accuracy testLi Yan0Zhi-De Hu1Qianghua Zhou2Wen Zhao3José M Porcel4Su-Na Cha5Yan Niu6Jian-Xun Wen7Cheng Yan8Hong-Zhe Zhu9Ying-Jun Wang10Ling Hai11Ting-Wang Jiang12Wen-Qi Zheng132 Key Laboratory for Biomarkers, Inner Mongolia Medical University, Hohhot, China2 Key Laboratory for Biomarkers, Inner Mongolia Medical University, Hohhot, China2 Key Laboratory for Biomarkers, Inner Mongolia Medical University, Hohhot, China2 Key Laboratory for Biomarkers, Inner Mongolia Medical University, Hohhot, China11 Pleural Medicine and Clinical Ultrasound Unit, Department of Internal Medicine, Arnau de Vilanova University Hospital, Lleida, Spain2 Key Laboratory for Biomarkers, Inner Mongolia Medical University, Hohhot, China2 Key Laboratory for Biomarkers, Inner Mongolia Medical University, Hohhot, China2 Key Laboratory for Biomarkers, Inner Mongolia Medical University, Hohhot, China2 Key Laboratory for Biomarkers, Inner Mongolia Medical University, Hohhot, China2 Key Laboratory for Biomarkers, Inner Mongolia Medical University, Hohhot, China2 Key Laboratory for Biomarkers, Inner Mongolia Medical University, Hohhot, China6 Department of Pathology, the College of Basic Medical Sicences, Inner Mongolia Medical University, Hohhot, China8 Department of Key Laboratory, Changshu No.2 People’s Hospital, Changshu, China2 Key Laboratory for Biomarkers, Inner Mongolia Medical University, Hohhot, ChinaBackground Previous studies have indicated that C-C class chemokine ligand 22 (CCL22) is involved in the pathogenesis of tuberculous pleural effusion and malignant pleural effusion. However, the diagnostic role of pleural fluid CCL22 levels in patients with undiagnosed pleural effusions remains to be elucidated.Methods We prospectively recruited patients with undiagnosed pleural effusion who visited two centres (Hohhot and Changshu) in China. Pleural biopsy, microbiological culture and effusion cytology were used to verify the cause of pleural effusion. Pleural fluid CCL22 levels were measured using an ELISA. The diagnostic accuracy of CCL22 for identifying heart failure (HF) was evaluated using a receiver operating characteristic (ROC) curve, and the net benefit of CCL22 was evaluated using decision curve analysis (DCA). Net benefit was defined as the benefit associated with true positives minus the harms associated with false positives at various threshold probabilities.Results We enrolled 153 and 58 patients in the Hohhot and Changshu cohorts, respectively. The cohort included 28 patients with HF and 183 patients with non-HF. Patients with HF had significantly lower pleural fluid CCL22 levels than non-HF patients. The area under the ROC curve (AUC) of CCL22 was 0.85 (95% CI: 0.77 to 0.93) in the Hohhot cohort and 0.87 (95% CI: 0.75 to 0.98) in the Changshu cohort. The AUC in the combined cohort was 0.85 (95% CI: 0.79 to 0.92), with a sensitivity of 0.82 (95% CI: 0.68 to 0.93) and a specificity of 0.73 (95% CI: 0.67 to 0.79) at the threshold of 150 ng/mL. DCA revealed a potential net benefit of pleural CCL22 determination in patients with undiagnosed pleural effusions.Conclusions Pleural fluid CCL22 may be a potential diagnostic marker for HF-related pleural effusion. Owing to the small sample size of this study, further studies with larger sample sizes are needed to validate our findings.https://bmjopenrespres.bmj.com/content/12/1/e002823.full
spellingShingle Li Yan
Zhi-De Hu
Qianghua Zhou
Wen Zhao
José M Porcel
Su-Na Cha
Yan Niu
Jian-Xun Wen
Cheng Yan
Hong-Zhe Zhu
Ying-Jun Wang
Ling Hai
Ting-Wang Jiang
Wen-Qi Zheng
Pleural fluid C-C class chemokines 22 and pleural effusion due to heart failure: a prospective and double-blind diagnostic accuracy test
BMJ Open Respiratory Research
title Pleural fluid C-C class chemokines 22 and pleural effusion due to heart failure: a prospective and double-blind diagnostic accuracy test
title_full Pleural fluid C-C class chemokines 22 and pleural effusion due to heart failure: a prospective and double-blind diagnostic accuracy test
title_fullStr Pleural fluid C-C class chemokines 22 and pleural effusion due to heart failure: a prospective and double-blind diagnostic accuracy test
title_full_unstemmed Pleural fluid C-C class chemokines 22 and pleural effusion due to heart failure: a prospective and double-blind diagnostic accuracy test
title_short Pleural fluid C-C class chemokines 22 and pleural effusion due to heart failure: a prospective and double-blind diagnostic accuracy test
title_sort pleural fluid c c class chemokines 22 and pleural effusion due to heart failure a prospective and double blind diagnostic accuracy test
url https://bmjopenrespres.bmj.com/content/12/1/e002823.full
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