Association between age and the host response in critically ill patients with sepsis

Autor: Erik H. A. Michels, Joe M. Butler, Tom D. Y. Reijnders, Olaf L. Cremer, Brendon P. Scicluna, Fabrice Uhel, Hessel Peters-Sengers, Marcus J. Schultz, Julian C. Knight, Lonneke A. van Vught, Tom van der Poll, MARS consortium
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Critical Care, Vol 26, Iss 1, Pp 1-16 (2022)
Druh dokumentu: article
ISSN: 1364-8535
DOI: 10.1186/s13054-022-04266-9
Popis: Abstract Background The association of ageing with increased sepsis mortality is well established. Nonetheless, current investigations on the influence of age on host response aberrations are largely limited to plasma cytokine levels while neglecting other pathophysiological sepsis domains like endothelial cell activation and function, and coagulation activation. The primary objective of this study was to gain insight into the association of ageing with aberrations in key host response pathways and blood transcriptomes in sepsis. Methods We analysed the clinical outcome (n = 1952), 16 plasma biomarkers providing insight in deregulation of specific pathophysiological domains (n = 899), and blood leukocyte transcriptomes (n = 488) of sepsis patients stratified according to age decades. Blood transcriptome results were validated in an independent sepsis cohort and compared with healthy individuals. Results Older age was associated with increased mortality independent of comorbidities and disease severity. Ageing was associated with lower endothelial cell activation and dysfunction, and similar inflammation and coagulation activation, despite higher disease severity scores. Blood leukocytes of patients ≥ 70 years, compared to patients
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