Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, United Kingdom.
Leeds Institute of Health Sciences, School of Medicine, The University of Leeds, Leeds, United Kingdom.
J Infect Dis. 2022 Aug 26;226(3):554-562. doi: 10.1093/infdis/jiac186.
Many diseases are associated with chronic inflammation, resulting in widening application of anti-inflammatory therapies. Although they are effective as disease-modifying agents, these anti-inflammatory therapies increase the risk of serious infection; however, it remains unknown whether chronic systemic inflammation per se is also associated with fatal infection.
Using serum C-reactive protein (CRP) data from 461 052 UK Biobank participants, we defined incidence rate ratios (IRRs) for death from infection, cardiovascular disease, or other causes and adjusted for comorbidities and the use of anti-inflammatory therapies.
Systemic inflammation, defined as CRP ≥2 mg/L, was common in all comorbidities considered. After adjusting for confounding factors, systemic inflammation was associated with a higher IRR point estimate for infection death (1.70; 95% confidence interval [CI], 1.51-1.92) than cardiovascular (1.48; CI, 1.40-1.57) or other death (1.41; CI, 1.37-1.45), although CIs overlapped. C-reactive protein thresholds of ≥5 and ≥10 mg/L yielded similar findings, as did analyses in people with ≥2, but not <2, comorbidities.
Systemic inflammation per se identifies people at increased risk of infection death, potentially contributing to the observed risks of anti-inflammatory therapies in clinical trials. In future clinical trials of anti-inflammatory therapies, researchers should carefully consider risks and benefits in target populations, guided by research into mechanisms of infection risk.
许多疾病与慢性炎症有关，导致抗炎治疗的应用范围扩大。虽然这些抗炎疗法作为疾病修正药物是有效的，但它们会增加严重感染的风险；然而，目前尚不清楚慢性全身性炎症本身是否也与致命感染有关。
我们使用来自 461,052 名英国生物银行参与者的血清 C 反应蛋白 (CRP) 数据，定义了感染、心血管疾病或其他原因导致的死亡率的发病率比（IRR），并调整了合并症和抗炎治疗的使用情况。
在考虑的所有合并症中，全身性炎症（定义为 CRP≥2mg/L）很常见。在调整混杂因素后，全身性炎症与感染死亡的更高 IRR 点估计值相关（1.70；95%置信区间 [CI]，1.51-1.92），而与心血管疾病（1.48；CI，1.40-1.57）或其他死亡（1.41；CI，1.37-1.45）相比，尽管 CI 存在重叠。CRP 阈值≥5mg/L 和≥10mg/L 的结果相似，≥2 种但<2 种合并症的分析结果也是如此。
全身性炎症本身会识别出感染死亡风险增加的人群，这可能导致临床试验中观察到抗炎治疗的风险。在未来的抗炎治疗临床试验中，研究人员应根据感染风险机制的研究，在目标人群中仔细考虑风险和获益。
