Intensive Care Medicine Experimental (Oct 2019)

Increased mortality in elderly patients with acute respiratory distress syndrome is not explained by host response

  • Laura R. A. Schouten,
  • Lieuwe D. J. Bos,
  • A. Serpa Neto,
  • Lonneke A. van Vught,
  • Maryse A. Wiewel,
  • Arie J. Hoogendijk,
  • Marc J. M. Bonten,
  • Olaf L. Cremer,
  • Janneke Horn,
  • Tom van der Poll,
  • Marcus J. Schultz,
  • Roelie M. Wösten-van Asperen,
  • the MARS consortium

DOI
https://doi.org/10.1186/s40635-019-0270-1
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 20

Abstract

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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).

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