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

doi:10.1186/s40635-019-0270-1

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

Research output: Contribution to journal › Article › Academic › peer-review

1 Downloads (Pure)

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).

Original language	English
Article number	58
Number of pages	10
Journal	Intensive Care Medicine Experimental
Volume	7
Issue number	1
DOIs	https://doi.org/10.1186/s40635-019-0270-1
Publication status	Published - 29 Oct 2019

Keywords

ARDS
aging
biomarker
critical care
host response
intensive care
mediation
outcome

Access to Document

10.1186/s40635-019-0270-1

schoutenFinal published version, 1.11 MB

Cite this

@article{0a105e7cf8ff42c9a4b99e9b74d164f0,

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

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).",

keywords = "ARDS, aging, biomarker, critical care, host response, intensive care, mediation, outcome",

author = "Schouten, {Laura R A} and Bos, {Lieuwe D J} and {Serpa Neto}, A and {van Vught}, {Lonneke A} and Wiewel, {Maryse A} and Hoogendijk, {Arie J} and Bonten, {Marc J M} and Cremer, {Olaf L} and Janneke Horn and {van der Poll}, Tom and Schultz, {Marcus J} and {W{\"o}sten-van Asperen}, {Roelie M}",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = oct,

day = "29",

doi = "10.1186/s40635-019-0270-1",

language = "English",

volume = "7",

journal = "Intensive Care Medicine Experimental",

issn = "2197-425X",

publisher = "Springer Science + Business Media",

number = "1",

}

TY - JOUR

T1 - Increased mortality in elderly patients with acute respiratory distress syndrome is not explained by host response

AU - Schouten, Laura R A

AU - Bos, Lieuwe D J

AU - Serpa Neto, A

AU - van Vught, Lonneke A

AU - Wiewel, Maryse A

AU - Hoogendijk, Arie J

AU - Bonten, Marc J M

AU - Cremer, Olaf L

AU - Horn, Janneke

AU - van der Poll, Tom

AU - Schultz, Marcus J

AU - Wösten-van Asperen, Roelie M

PY - 2019/10/29

Y1 - 2019/10/29

N2 - 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).

AB - 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).

KW - ARDS

KW - aging

KW - biomarker

KW - critical care

KW - host response

KW - intensive care

KW - mediation

KW - outcome

U2 - 10.1186/s40635-019-0270-1

DO - 10.1186/s40635-019-0270-1

M3 - Article

C2 - 31664603

SN - 2197-425X

VL - 7

JO - Intensive Care Medicine Experimental

JF - Intensive Care Medicine Experimental

IS - 1

M1 - 58

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this