Association between age and the host response in critically ill patients with sepsis
Issued Date
2022-12-01
Resource Type
ISSN
13648535
eISSN
1466609X
Scopus ID
2-s2.0-85143899605
Journal Title
Critical Care
Volume
26
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Critical Care Vol.26 No.1 (2022)
Suggested Citation
Michels E.H.A., Butler J.M., Reijnders T.D.Y., Cremer O.L., Scicluna B.P., Uhel F., Peters-Sengers H., Schultz M.J., Knight J.C., van Vught L.A., van der Poll T., de Beer F.M., Bos L.D.J., Glas G.J., Hoogendijk A.J., van Hooijdonk R.T.M., Horn J., Huson M.A., Schouten L.R.A., Straat M., Wieske L., Wiewel M.A., Witteveen E., Bonten M.J.M., Cremer O.M., Ong D.S.Y., Frencken J.F., Klouwenberg P.M.C.K., Koster‐Brouwer M.E., van de Groep K., Verboom D.M. Association between age and the host response in critically ill patients with sepsis. Critical Care Vol.26 No.1 (2022). doi:10.1186/s13054-022-04266-9 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/85198
Title
Association between age and the host response in critically ill patients with sepsis
Author(s)
Michels E.H.A.
Butler J.M.
Reijnders T.D.Y.
Cremer O.L.
Scicluna B.P.
Uhel F.
Peters-Sengers H.
Schultz M.J.
Knight J.C.
van Vught L.A.
van der Poll T.
de Beer F.M.
Bos L.D.J.
Glas G.J.
Hoogendijk A.J.
van Hooijdonk R.T.M.
Horn J.
Huson M.A.
Schouten L.R.A.
Straat M.
Wieske L.
Wiewel M.A.
Witteveen E.
Bonten M.J.M.
Cremer O.M.
Ong D.S.Y.
Frencken J.F.
Klouwenberg P.M.C.K.
Koster‐Brouwer M.E.
van de Groep K.
Verboom D.M.
Butler J.M.
Reijnders T.D.Y.
Cremer O.L.
Scicluna B.P.
Uhel F.
Peters-Sengers H.
Schultz M.J.
Knight J.C.
van Vught L.A.
van der Poll T.
de Beer F.M.
Bos L.D.J.
Glas G.J.
Hoogendijk A.J.
van Hooijdonk R.T.M.
Horn J.
Huson M.A.
Schouten L.R.A.
Straat M.
Wieske L.
Wiewel M.A.
Witteveen E.
Bonten M.J.M.
Cremer O.M.
Ong D.S.Y.
Frencken J.F.
Klouwenberg P.M.C.K.
Koster‐Brouwer M.E.
van de Groep K.
Verboom D.M.
Other Contributor(s)
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 < 50 years, showed decreased expression of genes involved in cytokine signaling, and innate and adaptive immunity, and increased expression of genes involved in hemostasis and endothelial cell activation. The diminished expression of gene pathways related to innate immunity and cytokine signaling in subjects ≥ 70 years was sepsis-induced, as healthy subjects ≥ 70 years showed enhanced expression of these pathways compared to healthy individuals < 50 years. Conclusions: This study provides novel evidence that older age is associated with relatively mitigated sepsis-induced endothelial cell activation and dysfunction, and a blood leukocyte transcriptome signature indicating impaired innate immune and cytokine signaling. These data suggest that age should be considered in patient selection in future sepsis trials targeting the immune system and/or the endothelial cell response. Graphical abstract: [Figure not available: see fulltext.]