Peukert Konrad, Seeliger Benjamin, Fox Mario, Feuerborn Caroline, Sauer Andrea, Schuss Patrick, Schneider Matthias, David Sascha, Welte Tobias, Putensen Christian, Wilhelm Christoph, Steinhagen Folkert, Bode Christian
Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.
Department of Respiratory Medicine and German Centre of Lung Research (DZL), Hannover Medical School, Carl-Neuberg-Str. 1, 30635 Hannover, Germany.
J Clin Med. 2021 Feb 12;10(4):737. doi: 10.3390/jcm10040737.
Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome with multiple underlying diseases. Particularly epithelial damage results from direct (e.g., pneumonia) rather than indirect lung injury (e.g., nonpulmonary sepsis), which is more likely associated with endothelial damage. Hence, targeting ARDS patients based on their molecular phenotypes is a promising approach to improve outcome. With regard to distinct inflammatory responses and subsequent lung damage in direct ARDS due to the causing pathogen, we quantified markers of epithelial and endothelial damage and pro-inflammatory cytokines in patients with ARDS triggered by bacterial, viral, and atypical pathogen pneumonia or indirect ARDS. The serum levels of interleukin-6 (IL-6) and interleukin-8 (IL-8), lung epithelial injury markers surfactant protein D (SP-D), and soluble receptor for advanced glycation end-products (sRAGE) as well as endothelial injury marker angiopoietin-2 (Ang-2) from 49 patients with distinct types of ARDS were analyzed by multiplex immunoassay. Epithelial damage marker SP-D was significantly higher in direct ARDS caused by viral and atypical pathogens in contrast to ARDS caused by typical bacterial pneumonia and nonpulmonary sepsis. In contrast, sRAGE levels did not differ due to the causing pathogen. Patients with atypical pathogen pneumonia related ARDS showed significantly lower Ang-2 levels compared to patients with viral and indirect ARDS. Patients with viral and atypical pneumonia related ARDS possessed significantly lower serum IL-6 levels compared to bacterial pneumonia related ARDS and IL-6 levels in atypical pneumonia related ARDS were significantly lower than in indirect ARDS. Current findings report a potential difference in ARDS biomarkers due to the underlying disease and pathogen.
急性呼吸窘迫综合征（ARDS）是一种具有多种潜在疾病的异质性综合征。特别是上皮损伤是由直接（如肺炎）而非间接肺损伤（如非肺部脓毒症）导致的，间接肺损伤更可能与内皮损伤相关。因此，根据ARDS患者的分子表型进行靶向治疗是改善预后的一种有前景的方法。关于由致病病原体引起的直接ARDS中不同的炎症反应及随后的肺损伤，我们对由细菌、病毒和非典型病原体肺炎引发的ARDS患者或间接ARDS患者的上皮和内皮损伤标志物以及促炎细胞因子进行了量化。通过多重免疫测定分析了49例不同类型ARDS患者的血清白细胞介素-6（IL-6）和白细胞介素-8（IL-8）水平、肺上皮损伤标志物表面活性蛋白D（SP-D）和晚期糖基化终产物可溶性受体（sRAGE）以及内皮损伤标志物血管生成素-2（Ang-2）。与典型细菌性肺炎和非肺部脓毒症引起的ARDS相比，病毒和非典型病原体引起的直接ARDS中的上皮损伤标志物SP-D显著更高。相比之下，sRAGE水平不因致病病原体而有所不同。与病毒和间接ARDS患者相比，非典型病原体肺炎相关ARDS患者的Ang-2水平显著更低。与细菌性肺炎相关ARDS患者相比，病毒和非典型肺炎相关ARDS患者的血清IL-6水平显著更低，且非典型肺炎相关ARDS中的IL-6水平显著低于间接ARDS中的水平。目前的研究结果表明，由于潜在疾病和病原体的不同，ARDS生物标志物存在潜在差异。
