Department of Pulmonary and Critical Care Medicine, Shenzhen Hospital, Peking University, Lianhua road No. 1120, Shenzhen, 518036, Guangdong, China.
Department of Pulmonary and Critical Care Medicine, The Eighth Affiliated Hospital (Shenzhen Futian), Sun Yat-sen University, Shenzhen, 518033, Guangdong, China.
Respir Res. 2020 Jul 20;21(1):192. doi: 10.1186/s12931-020-01457-2.
Severity of community-acquired pneumonia (CAP) depends on microbial pathogenicity, load and virulence, and immune responses. The Infectious Disease Society of America and the American Thoracic Society (IDSA/ATS) minor criteria responsible for clinical triage of patients with CAP are of unequal weight in predicting mortality. It is unclear whether the IDSA/ATS major/minor criteria might be strongly and positively associated with the immune responses. It is warranted to explore this intriguing hypothesis.
A prospective cohort study of 404 CAP patients was performed. Cold-inducible RNA-binding protein (CIRP) levels were measured using a sandwich-based enzyme-linked immunosorbent assay. The receiver operating characteristic curves were created and the areas under the curves were calculated to illustrate and compare the accuracy of the indices.
Severe CAP patients meeting the major criteria had the highest plasma concentrations of CIRP. The more the number of most predictive minor criteria strongly associated to mortality, i.e. arterial oxygen pressure/fraction inspired oxygen ≤ 250 mmHg, confusion, and uremia, present, the higher the CIRP level. Interestingly, the patients with non-severe CAP meeting the most predictive minor criteria demonstrated unexpectedly higher CIRP level compared with the patients with severe CAP not fulfilling the criteria. Procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein (CRP), sequential organ failure assessment (SOFA) and pneumonia severity index (PSI) scores, and mortality confirmed similar intriguing patterns. CIRP was strongly linked to PCT, IL-6, CRP, minor criteria, SOFA and PSI scores, and mortality (increased odds ratio 3.433). The pattern of sensitivity, specificity, positive predictive value, and Youden's index of CIRP ≥ 3.50 ng/mL for predicting mortality was the optimal. The area under the receiver operating characteristic curve of CIRP was the highest among the indices.
CIRP levels were strongly correlated with the IDSA/ATS major/minor criteria. CIRP might determine the severity and the presences of major/minor criteria and best predicted mortality, and a CIRP of ≥ 3.50 ng/mL might be more valuable cut-off value for severe CAP, suggesting that CIRP might be a novel and intriguing biomarker for pneumonia to monitor host response and predict mortality, which might have implications for more accurate clinical triage decisions.
社区获得性肺炎（CAP）的严重程度取决于微生物的致病性、负荷和毒力以及免疫反应。美国传染病学会和美国胸科学会（IDSA/ATS）负责 CAP 患者临床分诊的次要标准对死亡率的预测权重不等。目前尚不清楚 IDSA/ATS 主要/次要标准是否与免疫反应密切相关。有必要探讨这一有趣的假说。
对 404 例 CAP 患者进行前瞻性队列研究。采用基于夹心的酶联免疫吸附试验检测冷诱导 RNA 结合蛋白（CIRP）水平。绘制受试者工作特征曲线并计算曲线下面积，以说明和比较各指标的准确性。
符合主要标准的重症 CAP 患者的血浆 CIRP 浓度最高。与死亡率密切相关的最具预测性的次要标准数量越多，即动脉血氧分压/吸入氧分数≤250mmHg、意识障碍和尿毒症，CIRP 水平越高。有趣的是，符合最具预测性的次要标准的非重症 CAP 患者的 CIRP 水平明显高于不符合这些标准的重症 CAP 患者。降钙素原（PCT）、白细胞介素-6（IL-6）、C 反应蛋白（CRP）、序贯器官衰竭评估（SOFA）和肺炎严重指数（PSI）评分和死亡率证实了类似的有趣模式。CIRP 与 PCT、IL-6、CRP、次要标准、SOFA 和 PSI 评分和死亡率密切相关（优势比增加 3.433）。CIRP≥3.50ng/mL 预测死亡率的敏感性、特异性、阳性预测值和约登指数的模式为最佳。CIRP 的受试者工作特征曲线下面积在各指标中最高。
CIRP 水平与 IDSA/ATS 主要/次要标准密切相关。CIRP 可能决定严重程度和主要/次要标准的存在，并能最好地预测死亡率，CIRP≥3.50ng/mL 可能是重症 CAP 更有价值的截断值，表明 CIRP 可能是一种新型的、有趣的肺炎生物标志物，用于监测宿主反应和预测死亡率，这可能对更准确的临床分诊决策具有重要意义。
