Pereverzeva Liza, Uhel Fabrice, Peters Sengers Hessel, Cremer Olaf L, Schultz Marcus J, Bonten Marc M J, Scicluna Brendon P, van der Poll Tom
Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Meibergdreef 9, G2-129, 1105 AZ, Amsterdam, The Netherlands.
Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
Ann Intensive Care. 2021 Sep 28;11(1):142. doi: 10.1186/s13613-021-00930-5.
A delay in admission to the intensive care unit (ICU) of patients with community-acquired pneumonia (CAP) has been associated with an increased mortality. Decisions regarding interventions and eligibility for immune modulatory therapy are often made at the time of admission to the ICU. The primary aim of this study was to compare the host immune response measured upon ICU admission in CAP patients admitted immediately from the emergency department (direct ICU admission) with those who were transferred within 72 h after admission to the general ward (delayed ICU admission).
Sixteen host response biomarkers providing insight in pathophysiological mechanisms implicated in sepsis and blood leukocyte transcriptomes were analysed in patients with CAP upon ICU admission in two tertiary hospitals in the Netherlands.
Of 530 ICU admissions with CAP, 387 (73.0%) were directly admitted and 143 (27.0%) had a delayed admission. Patients with a delayed ICU admission were more often immunocompromised (35.0 versus 21.2%, P = .002) and had more malignancies (23.1 versus 13.4%, P = .011). Shock was more present in patients who were admitted to the ICU directly (46.6 versus 33.6%, P = .010). Delayed ICU admission was not associated with an increased hospital mortality risk (hazard ratio 1.25, 95% CI 0.89-1.78, P = .20). The plasma levels of biomarkers (n = 297) reflecting systemic inflammation, endothelial cell activation and coagulation activation were largely similar between groups, with exception of C-reactive protein, soluble intercellular adhesion molecule-1 and angiopoietin-1, which were more aberrant in delayed admissions compared to direct ICU admissions. Blood leukocyte transcriptomes (n = 132) of patients with a delayed ICU admission showed blunted innate and adaptive immune response signalling when compared with direct ICU admissions, as well as decreased gene expression associated with tissue repair and extracellular matrix remodelling pathways.
Blood leukocytes of CAP patients with delayed ICU admission show evidence of a more immune suppressive phenotype upon ICU admission when compared with blood leukocytes from patients directly transferred to the ICU.
Molecular Diagnosis and Risk Stratification of Sepsis (MARS) project, ClinicalTrials.gov identifier NCT01905033.
社区获得性肺炎（CAP）患者入住重症监护病房（ICU）的延迟与死亡率增加相关。关于干预措施和免疫调节治疗资格的决定通常在入住ICU时做出。本研究的主要目的是比较从急诊科直接入住ICU的CAP患者（直接入住ICU）与入住普通病房后72小时内转入ICU的患者（延迟入住ICU）在入住ICU时所测得的宿主免疫反应。
在荷兰的两家三级医院，对入住ICU的CAP患者分析了16种宿主反应生物标志物，这些标志物有助于深入了解脓毒症和血液白细胞转录组中涉及的病理生理机制。
在530例因CAP入住ICU的患者中，387例（73.0%）直接入住，143例（27.0%）延迟入住。延迟入住ICU的患者免疫功能低下的情况更常见（35.0%对21.2%，P = 0.002），且恶性肿瘤更多（23.1%对13.4%，P = 0.011）。直接入住ICU的患者休克情况更常见（46.6%对33.6%，P = 0.010）。延迟入住ICU与住院死亡风险增加无关（风险比1.25，95%可信区间0.89 - 1.78，P = .20）。反映全身炎症、内皮细胞活化和凝血活化的生物标志物（n = 297）血浆水平在两组之间大致相似，但C反应蛋白、可溶性细胞间黏附分子-1和血管生成素-1除外，与直接入住ICU相比，这些指标在延迟入住时更异常。与直接入住ICU相比，延迟入住ICU患者的血液白细胞转录组（n = 132）显示先天和适应性免疫反应信号减弱，以及与组织修复和细胞外基质重塑途径相关的基因表达降低。
与直接转入ICU的患者的血液白细胞相比，延迟入住ICU的CAP患者的血液白细胞在入住ICU时显示出更具免疫抑制表型的证据。
脓毒症的分子诊断和风险分层（MARS）项目，ClinicalTrials.gov标识符NCT01905033。
