Background

Chronic obstructive pulmonary disease (COPD) is characterized by abnormal epithelial repair resulting in a hypercoagulable state with intra-alveolar accumulation of fibrin and alveolar basement membrane destruction. This study aimed to investigate if the combination of two serological biomarkers evaluating these pathological processes could improve the prediction of mortality risk compared to single biomarkers.

Methods

Matrix metalloproteinase-mediated degradation of the type IV collagen α3 chain (C4Ma3), located in the alveolar basement membrane, and plasmin-mediated degradation of crosslinked fibrin (X-FIB), an end-product of fibrinogen, were assessed serologically in a subset of the ECLIPSE cohort (n = 982). Biomarker data were dichotomized into high versus low at the median. Cox regression and Kaplan-Meier curves were used to analyze the predictive value of having one or two high biomarkers for all-cause mortality over two years.

Results

COPD participants with high levels of two biomarkers were at significantly higher risk of all-cause mortality with a hazard ratio of 7.66 (95% CI 1.75–33.48; p = 0.007) while participants with one high biomarker were not at significantly higher risk (HR 3.79 [95% CI 0.85–16.94]; p = 0.08).

Conclusions

A combination of serological biomarkers of alveolar basement membrane destruction and clot resolution was predictive of all-cause mortality in COPD. The combination of two different pathological aspects may strengthen prognostic accuracy and could be used in conjunction with clinical assessment to guide treatment decisions.

中文翻译：

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结合血凝块分解和肺泡基底膜破坏的生物标志物可预测ECLIPSE COPD队列的死亡率

背景

慢性阻塞性肺疾病（COPD）的特征是异常的上皮修复导致高凝状态，肺泡内纤维蛋白蓄积和肺泡基底膜破坏。这项研究旨在调查评估这些病理过程的两种血清学生物标志物的组合是否可以比单一生物标志物改善对死亡风险的预测。

方法

在一个亚组中通过血清学评估了基质金属蛋白酶介导的位于肺泡基底膜上的IV型胶原α3链（C4Ma3）的降解以及纤溶酶介导的纤维蛋白原终产物交联纤维蛋白（X-FIB）的降解。 ECLIPSE群组的人数（n = 982）。将生物标志物数据分为中位数为高与低。使用Cox回归和Kaplan-Meier曲线来分析拥有一种或两种高生物标志物的两年全因死亡率的预测价值。

结果

两种生物标志物含量高的COPD参与者全因死亡率显着较高，危险比为7.66（95％CI 1.75–33.48； p = 0.007），而一种生物标志物含量高的参与者并未显着较高的风险（HR 3.79 [95％CI 0.85-16.94]； p = 0.08）。

结论

肺泡基底膜破坏和凝块消融的血清学生物标志物的组合预示了COPD的全因死亡率。两种不同病理学方面的结合可以增强预后的准确性，并且可以与临床评估结合使用以指导治疗决策。