Lower serum GPX4 and GSH/GSSG ratio are associated with poor prognosis in severe community-acquired pneumonia
Abstract Objectives Disruption of redox homeostasis and ferroptosis have been increasingly implicated in the pathogenesis of inflammatory lung injury. Glutathione peroxidase 4 (GPX4) and the ratio of reduced to oxidized glutathione (GSH/GSSG) are key regulators in this process. However, the clinical...
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BMC
2025-08-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-03038-9 |
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| author | Wei Zhu Kunyu Wang Xiaolei Xing Xinxin Xu Yonghui Liang Ke Wang |
| author_facet | Wei Zhu Kunyu Wang Xiaolei Xing Xinxin Xu Yonghui Liang Ke Wang |
| author_sort | Wei Zhu |
| collection | DOAJ |
| description | Abstract Objectives Disruption of redox homeostasis and ferroptosis have been increasingly implicated in the pathogenesis of inflammatory lung injury. Glutathione peroxidase 4 (GPX4) and the ratio of reduced to oxidized glutathione (GSH/GSSG) are key regulators in this process. However, the clinical significance of ferroptotic factors in severe community-acquired pneumonia (CAP) is still lacking. This study investigated the prognostic value of serum glutathione peroxidase 4 (GPX4) and the GSH/GSSG ratio in severe CAP. Methods A prospective cohort of 267 ICU-admitted severe CAP patients (2021–2023) was analyzed. Serum GPX4 and GSH/GSSG were measured within 24 h of admission. Patients were grouped by 30-day survival. Statistical analyses included comparative tests, Spearman correlation, ROC curves, Kaplan–Meier survival, and multivariate logistic regression. Results Among 267 patients, 79 (29.6%) died within 90 days. Deceased patients had significantly lower GPX4 and GSH/GSSG (both P < 0.001). GPX4 was lower in COVID-19 cases (P = 0.022), while GSH/GSSG showed no such difference. GPX4 and GSH/GSSG were moderately correlated (r = 0.301, P < 0.001). ROC analysis showed good predictive accuracy for 30-day mortality, with an AUC of 0.778 for GPX4, 0.780 for GSH/GSSG, and 0.841 for their combination. Kaplan–Meier analysis indicated lower survival with reduced GPX4 or GSH/GSSG (P < 0.01). Multivariate analysis identified lower GPX4, GSH/GSSG, COVID-19, higher SOFA scores, prolonged ICU stay, and mechanical ventilation as independent mortality risk factors. Conclusions Lower serum GPX4 and GSH/GSSG ratios are associated with increased mortality in severe CAP. |
| format | Article |
| id | doaj-art-41ca7358d110428682b103bf11c015e9 |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-41ca7358d110428682b103bf11c015e92025-08-24T11:14:58ZengBMCEuropean Journal of Medical Research2047-783X2025-08-0130111010.1186/s40001-025-03038-9Lower serum GPX4 and GSH/GSSG ratio are associated with poor prognosis in severe community-acquired pneumoniaWei Zhu0Kunyu Wang1Xiaolei Xing2Xinxin Xu3Yonghui Liang4Ke Wang5Department of Critical Care Medicine, Tianyou Hospital Affiliated to Wuhan University of Science and TechnologyNursing Department, Tianyou Hospital Affiliated to Wuhan University of Science and TechnologyIntegrated Department, Wuhan University of Science and Technology School of Medicine, Wuhan University of Science and TechnologyDepartment of Critical Care Medicine, Tianyou Hospital Affiliated to Wuhan University of Science and TechnologyDepartment of Critical Care Medicine, Tianyou Hospital Affiliated to Wuhan University of Science and TechnologyDepartment of Critical Care Medicine, Tianyou Hospital Affiliated to Wuhan University of Science and TechnologyAbstract Objectives Disruption of redox homeostasis and ferroptosis have been increasingly implicated in the pathogenesis of inflammatory lung injury. Glutathione peroxidase 4 (GPX4) and the ratio of reduced to oxidized glutathione (GSH/GSSG) are key regulators in this process. However, the clinical significance of ferroptotic factors in severe community-acquired pneumonia (CAP) is still lacking. This study investigated the prognostic value of serum glutathione peroxidase 4 (GPX4) and the GSH/GSSG ratio in severe CAP. Methods A prospective cohort of 267 ICU-admitted severe CAP patients (2021–2023) was analyzed. Serum GPX4 and GSH/GSSG were measured within 24 h of admission. Patients were grouped by 30-day survival. Statistical analyses included comparative tests, Spearman correlation, ROC curves, Kaplan–Meier survival, and multivariate logistic regression. Results Among 267 patients, 79 (29.6%) died within 90 days. Deceased patients had significantly lower GPX4 and GSH/GSSG (both P < 0.001). GPX4 was lower in COVID-19 cases (P = 0.022), while GSH/GSSG showed no such difference. GPX4 and GSH/GSSG were moderately correlated (r = 0.301, P < 0.001). ROC analysis showed good predictive accuracy for 30-day mortality, with an AUC of 0.778 for GPX4, 0.780 for GSH/GSSG, and 0.841 for their combination. Kaplan–Meier analysis indicated lower survival with reduced GPX4 or GSH/GSSG (P < 0.01). Multivariate analysis identified lower GPX4, GSH/GSSG, COVID-19, higher SOFA scores, prolonged ICU stay, and mechanical ventilation as independent mortality risk factors. Conclusions Lower serum GPX4 and GSH/GSSG ratios are associated with increased mortality in severe CAP.https://doi.org/10.1186/s40001-025-03038-9GPX4GSH/GSSGSevere pneumoniaFerroptosisCOVID-19 |
| spellingShingle | Wei Zhu Kunyu Wang Xiaolei Xing Xinxin Xu Yonghui Liang Ke Wang Lower serum GPX4 and GSH/GSSG ratio are associated with poor prognosis in severe community-acquired pneumonia European Journal of Medical Research GPX4 GSH/GSSG Severe pneumonia Ferroptosis COVID-19 |
| title | Lower serum GPX4 and GSH/GSSG ratio are associated with poor prognosis in severe community-acquired pneumonia |
| title_full | Lower serum GPX4 and GSH/GSSG ratio are associated with poor prognosis in severe community-acquired pneumonia |
| title_fullStr | Lower serum GPX4 and GSH/GSSG ratio are associated with poor prognosis in severe community-acquired pneumonia |
| title_full_unstemmed | Lower serum GPX4 and GSH/GSSG ratio are associated with poor prognosis in severe community-acquired pneumonia |
| title_short | Lower serum GPX4 and GSH/GSSG ratio are associated with poor prognosis in severe community-acquired pneumonia |
| title_sort | lower serum gpx4 and gsh gssg ratio are associated with poor prognosis in severe community acquired pneumonia |
| topic | GPX4 GSH/GSSG Severe pneumonia Ferroptosis COVID-19 |
| url | https://doi.org/10.1186/s40001-025-03038-9 |
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