Abstract

Background

Advanced age is associated with increased mortality in acute respiratory distress syndrome (ARDS) patients. Preclinical studies suggest that the host response to an injurious challenge is age-dependent. In ARDS patients, we investigated whether the association between age and mortality is mediated through age-related differences in the host response.

Methods

This was a prospective longitudinal observational cohort study, performed in the ICUs of two university-affiliated hospitals. The systemic host response was characterized in three predefined age-groups, based on the age-tertiles of the studied population: young (18 to 54 years, N = 209), middle-aged (55 to 67 years, N = 213), and elderly (67 years and older, N = 196). Biomarkers of inflammation, endothelial activation, and coagulation were determined in plasma obtained at the onset of ARDS. The primary outcome was 90-day mortality. A mediation analysis was performed to examine whether age-related differences in biomarker levels serve as potential causal pathways mediating the association between age and mortality.

Results

Ninety-day mortality rates were 30% (63/209) in young, 37% (78/213) in middle-aged, and 43% (84/196) in elderly patients. Middle-aged and elderly patients had a higher risk of death compared to young patients (adjusted odds ratio, 1.5 [95% confidence interval 1.0 to 2.3] and 2.1 [1.4 to 3.4], respectively). Relative to young patients, the elderly had significantly lower systemic levels of biomarkers of inflammation and endothelial activation. Tissue plasminogen activator, a marker of coagulation, was the only biomarker that showed partial mediation (proportion of mediation, 10 [1 to 28] %).

Conclusion

Little evidence was found that the association between age and mortality in ARDS patients is mediated through age-dependent differences in host response pathways. Only tissue plasminogen activator was identified as a possible mediator of interest.

Trial registration

This trial was registered at ClinicalTrials.gov (identifier NCT01905033, date of registration July 23, 2013).

Details

Title
Increased mortality in elderly patients with acute respiratory distress syndrome is not explained by host response
Author
Schouten, Laura R A 1   VIAFID ORCID Logo  ; Bos, Lieuwe D J 2 ; A Serpa Neto 3 ; van Vught, Lonneke A 4 ; Wiewel, Maryse A 4 ; Hoogendijk, Arie J 4 ; Bonten, Marc J M 5 ; Cremer, Olaf L 6 ; Horn, Janneke 2 ; van der Poll, Tom 4 ; Schultz, Marcus J 7 ; Roelie M Wösten-van Asperen 8 ; de Beer, F M 8 ; Bos, L D 8 ; Glas, G J 8 ; Horn, J 8 ; Hoogendijk, A J 8 ; van Hooijdonk, R T 8 ; Huson, M A 8 ; van der Poll, T 8 ; Scicluna, B P 8 ; Schouten, L R A 8 ; Schultz, M J 8 ; Straat, M 8 ; van Vught, L A 8 ; Wieske, L 8 ; Wiewel, M A 8 ; Witteveen, E 8 ; Bonten, M J M 8 ; Cremer, O L 8 ; Frencken, J F 8 ; van de Groep, K 8 ; Klein Klouwenberg, P M 8 ; Koster-Brouwer, M E 8 ; Ong, D S 8 ; Verboom, D M 8 

1  Department of Pediatric Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands 
2  Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands 
3  Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Critical Care Medicine, Hospital Israelita Albert Einstein, São Paulo, Brazil 
4  Center of Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands 
5  Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands 
6  Department of Intensive Care, University Medical Center Utrecht, Utrecht, the Netherlands 
7  Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Mahidol–Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand 
8  Department of Pediatric Intensive Care, University Medical Center Utrecht, Utrecht, the Netherlands 
Pages
1-20
Publication year
2019
Publication date
Oct 2019
Publisher
Springer Nature B.V.
e-ISSN
2197425X
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1186/s40635-019-0270-1
ProQuest document ID
2310471337
Copyright
Intensive Care Medicine Experimental is a copyright of Springer, (2019). All Rights Reserved., © 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.