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已发表论文
重症监护病房中慢性阻塞性肺疾病合并脓毒症患者经白蛋白校正阴离子间隙的预后价值：一项 MIMIC-IV 队列研究
Authors Zhang B, Bai J, Wang H, Huang F , Miao L , Wang J, Zhou L
Received 23 June 2025
Accepted for publication 26 October 2025
Published 10 December 2025 Volume 2025:20 Pages 3979—3992
DOI https://doi.org/10.2147/COPD.S544857
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Dr Jill Ohar
Baiquan Zhang,1,* Jiayu Bai,2,* Huanqin Wang,1 Fengxiang Huang,1 Lijun Miao,1 Jing Wang,1 Lu Zhou1
1Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Lu Zhou, Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China, Email sqzhoulu@163.com
Purpose: Chronic obstructive pulmonary disease (COPD) patients are at increased risk of sepsis, a condition associated with high mortality. The anion gap (AG) is commonly used to assess acid–base disturbances, but its reliability declines in hypoalbuminemia. The albumin-corrected anion gap (ACAG) may provide greater accuracy, yet its prognostic value in COPD patients with sepsis, defined according to Sepsis-3 criteria, remains unclear.
Patients and Methods: This retrospective cohort study analyzed 2072 ICU patients with COPD and sepsis from the Medical Information Mart for Intensive Care IV (MIMIC-IV). Cox regression models evaluated the association between ACAG and mortality, Kaplan–Meier curves illustrated survival differences, restricted cubic splines examined nonlinear relationships, and subgroup analyses assessed consistency across strata. Receiver operating characteristic (ROC) curves compared the predictive performance of ACAG, AG, and serum albumin.
Results: Elevated ACAG was independently associated with both short- and long-term mortality. In fully adjusted models, each 1 mmol/L increase in ACAG was linked to higher risk of 28-day mortality (HR 1.064, 95% CI 1.042– 1.086, P < 0.001) and 365-day mortality (HR 1.065, 95% CI 1.043– 1.087, P < 0.001). A threshold effect was observed at ≥ 19.25 mmol/L, above which mortality risk increased markedly (28-day HR 1.336, 95% CI 1.126– 1.586, P = 0.001; 365-day HR 1.429, 95% CI 1.208– 1.691, P < 0.001). Kaplan–Meier survival analysis confirmed significant differences (log-rank P < 0.0001), and ROC analysis demonstrated that ACAG provided superior discrimination compared with AG and albumin for both 28-day (AUC = 0.734) and 365-day mortality (AUC = 0.696). Associations were consistent across clinical subgroups without significant interactions.
Conclusion: Elevated ACAG was an independent predictor of 28-day and 365-day all-cause mortality in critically ill patients with COPD and sepsis. An inflection point of approximately 19.25 mmol/L identified a clinically meaningful threshold for risk stratification. As a simple and widely accessible parameter, ACAG may facilitate threshold-based triage and individualized management in this high-risk population, though external validation in multicenter prospective cohorts is warranted.
Keywords: COPD, sepsis, ACAG, mortality, ICU, MIMIC-IV
1Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Lu Zhou, Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China, Email sqzhoulu@163.com
Purpose: Chronic obstructive pulmonary disease (COPD) patients are at increased risk of sepsis, a condition associated with high mortality. The anion gap (AG) is commonly used to assess acid–base disturbances, but its reliability declines in hypoalbuminemia. The albumin-corrected anion gap (ACAG) may provide greater accuracy, yet its prognostic value in COPD patients with sepsis, defined according to Sepsis-3 criteria, remains unclear.
Patients and Methods: This retrospective cohort study analyzed 2072 ICU patients with COPD and sepsis from the Medical Information Mart for Intensive Care IV (MIMIC-IV). Cox regression models evaluated the association between ACAG and mortality, Kaplan–Meier curves illustrated survival differences, restricted cubic splines examined nonlinear relationships, and subgroup analyses assessed consistency across strata. Receiver operating characteristic (ROC) curves compared the predictive performance of ACAG, AG, and serum albumin.
Results: Elevated ACAG was independently associated with both short- and long-term mortality. In fully adjusted models, each 1 mmol/L increase in ACAG was linked to higher risk of 28-day mortality (HR 1.064, 95% CI 1.042– 1.086, P < 0.001) and 365-day mortality (HR 1.065, 95% CI 1.043– 1.087, P < 0.001). A threshold effect was observed at ≥ 19.25 mmol/L, above which mortality risk increased markedly (28-day HR 1.336, 95% CI 1.126– 1.586, P = 0.001; 365-day HR 1.429, 95% CI 1.208– 1.691, P < 0.001). Kaplan–Meier survival analysis confirmed significant differences (log-rank P < 0.0001), and ROC analysis demonstrated that ACAG provided superior discrimination compared with AG and albumin for both 28-day (AUC = 0.734) and 365-day mortality (AUC = 0.696). Associations were consistent across clinical subgroups without significant interactions.
Conclusion: Elevated ACAG was an independent predictor of 28-day and 365-day all-cause mortality in critically ill patients with COPD and sepsis. An inflection point of approximately 19.25 mmol/L identified a clinically meaningful threshold for risk stratification. As a simple and widely accessible parameter, ACAG may facilitate threshold-based triage and individualized management in this high-risk population, though external validation in multicenter prospective cohorts is warranted.
Keywords: COPD, sepsis, ACAG, mortality, ICU, MIMIC-IV