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- Title
Increased mortality in elderly patients with acute respiratory distress syndrome is not explained by host response.
- Authors
Schouten, Laura R. A.; Bos, Lieuwe D. J.; Serpa Neto, A.; van Vught, Lonneke A.; Wiewel, Maryse A.; Hoogendijk, Arie J.; Bonten, Marc J. M.; Cremer, Olaf L.; Horn, Janneke; van der Poll, Tom; Schultz, Marcus J.; Wösten-van Asperen, Roelie M.; the MARS consortium; de Beer, F. M.; Bos, L. D.; Glas, G. J.; Horn, J.; Hoogendijk, A. J.; van Hooijdonk, R. T.; Huson, M. A.
- 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).
- Subjects
ADULT respiratory distress syndrome; TISSUE plasminogen activator; OLDER patients; MORTALITY
- Publication
Intensive Care Medicine Experimental, 2019, Vol 7, Issue 1, pN.PAG
- ISSN
2197-425X
- Publication type
Article
- DOI
10.1186/s40635-019-0270-1