Hepcidin predicts 5-year mortality after community-acquired pneumonia

Virtually all living organisms, including microbes and humans, depend on iron to survive and grow. During an infection, the plasma level of iron and several iron-related proteins change substantially. We hypothesized that iron and iron-related proteins could predict short- and long-term outcomes in community-acquired pneumonia. Blood samples from a prospective cohort of 267 in-patients with community-acquired pneumonia were analysed for hepcidin, ferritin, iron, transferrin, transferrin saturation, and soluble transferrin receptor at admission and 6-weeks post-discharge. Adverse short-term outcome was defined as admission to intensive care unit or death within 30 days, and long-term outcome was assessed as 5-year overall mortality. Logistic regression, Kaplan Meier survival curves, and Cox regression models with cut-offs at median for the potential biomarkers were used for statistical evaluation. Low admission levels of hepcidin predicted 5-year overall mortality, independently of age, sex, comorbid conditions, and anaemia. Low levels of ferritin at admission as well as low levels of iron and transferrin saturation and high levels of soluble transferrin receptor at the 6-week follow-up were predictors of 5-year overall mortality in univariable, but not in multivariable analyses. Neither of these potential biomarkers predicted adverse short-term outcomes. In hospitalized patients with community-acquired pneumonia, low levels of hepcidin at admission predicted 5-year overall mortality, but not short-term adverse outcome.几乎所有生命体，包括微生物与人类，均依赖铁元素以维持生存与增殖。机体发生感染时，血浆中铁及多种铁相关蛋白的水平会发生显著变化。我们提出研究假设：铁及铁相关蛋白可用于预测社区获得性肺炎（community-acquired pneumonia, CAP）患者的短期与长期转归。本研究针对267名社区获得性肺炎住院患者组成的前瞻性队列采集血液样本，分别于患者入院时及出院后6周检测铁调素（hepcidin）、铁蛋白（ferritin）、铁、转铁蛋白（transferrin）、转铁蛋白饱和度（transferrin saturation）及可溶性转铁蛋白受体（soluble transferrin receptor）的水平。本研究将不良短期转归定义为入院后30天内转入重症监护病房（intensive care unit, ICU）或死亡，长期转归则以5年总死亡率作为评估终点。统计分析采用逻辑回归、卡普兰-迈耶（Kaplan Meier）生存曲线法，以及以中位数作为临界值的考克斯（Cox）回归模型，对潜在生物标志物进行分析评估。入院时低水平的铁调素可独立于年龄、性别、合并症及贫血状态，预测患者的5年总死亡率。单变量分析结果显示，入院时低水平铁蛋白，以及出院后6周随访时检测到的低水平铁、低转铁蛋白饱和度与高水平可溶性转铁蛋白受体，均为5年总死亡率的预测因子；但多变量分析未发现上述关联具有统计学意义。上述潜在生物标志物均无法预测社区获得性肺炎患者的短期不良转归。综上，对于社区获得性肺炎住院患者，入院时低水平铁调素可预测其5年总死亡率，但无法预测短期不良转归。