Association Between Extracellular Superoxide Dismutase Activity and 1-Year All-Cause Mortality in Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Prospective Cohort Study.

Haiqing Li,Heshen Tian,Ruiting Sun,Liping Wei,Mi Gao,Yumin Zhou,Zixiong Zeng,Juan Cheng,Pixin Ran,Shan Gong,Guoping Hu,Wei Hong,Yuqun Li,Fan Wu,Chunxiao Liang,Weitao Cao,Zihui Wang

doi:10.3389/fmed.2022.811975

Abstract

Background and ObjectivesAccumulating evidence suggests that oxidative stress is involved in the development of chronic obstructive pulmonary disease (COPD) and its progression. Activity of extracellular superoxide dismutase (ecSOD), the only extracellular enzyme eliminating superoxide radicals, has been reported to decline in acute exacerbations of COPD (AECOPD). However, the association between serum ecSOD activity and 1-year all-cause mortality in AECOPD patients remains unclear. The objective of our study was to explore the usefulness of ecSOD activity on admission in AECOPD as an objective predictor for 1-year all-cause mortality.MethodsWe measured serum ecSOD activity in AECOPD patients on admission in a prospective cohort study. We also recorded their laboratory and clinical data. Multivariate Cox regression was used to analyze the association between ecSOD activity and the risk of 1-year all-cause mortality. Restricted cubic spline curves were used to visualize the relationship between ecSOD activity and the hazard ratio of 1-year all-cause mortality.ResultsA total of 367 patients were followed up for 1 year, and 29 patients died during a 1-year follow-up period. Compared with survivors, the non-survivors were older (79.52 ± 8.39 vs. 74.38 ± 9.34 years old, p = 0.004) and had increased levels of tobacco consumption (47.07 ± 41.67 vs. 33.83 ± 31.79 pack-years, p = 0.037). Having an ecSOD activity ≤ 98.8 U/ml was an independent risk factor of 1-year all-cause mortality after adjustment for baseline differences, clinical variables and comorbidities [hazard ratio = 5.51, 95% confidence interval (CI): 2.35–12.95, p < 0.001].ConclusionLower serum ecSOD activity was a strong and independent predictor of 1-year all-cause mortality in AECOPD patients.

Highlights

Chronic obstructive pulmonary disease (COPD), a systemic inflammatory disease, is the third leading cause of mortality worldwide [1]
Having an extracellular superoxide dismutase (ecSOD) activity ≤ 98.8 U/ml was an independent risk factor of 1-year all-cause mortality after adjustment for baseline differences, clinical variables and comorbidities [hazard ratio = 5.51, 95% confidence interval (CI): 2.35–12.95, p < 0.001]
Previous studies showed that increased markers of oxidative stress such as malondialdehyde, advanced glycation end-products, 8-isoprostane, and 4-hydroxy2-nonenal were associated with a poor prognosis in COPD [8, 9]

Summary

Introduction

Chronic obstructive pulmonary disease (COPD), a systemic inflammatory disease, is the third leading cause of mortality worldwide [1]. Exacerbations of COPD accelerate the decline in lung function and cause progression of the disease, reduced physical activity, and an increased risk of death [2– 4]. Previous studies showed that increased markers of oxidative stress such as malondialdehyde, advanced glycation end-products, 8-isoprostane, and 4-hydroxy2-nonenal were associated with a poor prognosis in COPD [8, 9]. Another component of oxidative imbalance, antioxidants, have not been well explored in the prognosis of COPD. Accumulating evidence suggests that oxidative stress is involved in the development of chronic obstructive pulmonary disease (COPD) and its progression. The association between serum ecSOD activity and 1-year all-cause mortality in AECOPD patients remains unclear. The objective of our study was to explore the usefulness of ecSOD activity on admission in AECOPD as an objective predictor for 1-year all-cause mortality

Objectives

Methods

Results

Conclusion