Young and Aged Blunt Trauma Patients Display Major Differences in Circulating Inflammatory Mediator Profiles after Severe Injury

doi:10.1016/j.jamcollsurg.2018.10.019

Journal of the American College of Surgeons

Volume 228, Issue 2, February 2019, Pages 148-160.e7

Presented at the 41^st Annual Conference on Shock, Scottsdale, AZ, June 2018. Presented at the American College of Surgeons 104th Annual Clinical Congress, Scientific Forum, Boston, MA, October 2018.

https://doi.org/10.1016/j.jamcollsurg.2018.10.019 Get rights and content

Background

Aging is accompanied by alterations in immune functions. How these changes translate into levels of circulating inflammatory mediators and network expression after severe trauma is not well characterized. To address this, we compared time-dependent changes in the levels of an extensive biomarker panel in cohorts of severely injured young and aged adults.

Study Design

Cohorts of young (18 to 30 years old, n = 115) and aged (65 to 90 years old, n = 101) blunt trauma patients admitted to the ICU with plasma sampled 3 times within the first 24 hours and daily from day 1 to day 7 were assayed for 30 inflammatory biomarkers using Luminex analyzer. Stringently matched groups controlling for sex ratio and Injury Severity Score (n = 56 young vs n = 56 aged) were generated. Data were analyzed using 2-way ANOVA, area under the curve analysis, Dynamic Bayesian Network inference, and Dynamic Network Analysis.

Results

In the overall cohorts, the young group had a significantly higher Injury Severity Score, which was associated with higher circulating levels of 18 inflammatory mediators from admission to day 7. The aged group had higher levels of C-X-C motif chemokine ligand 10/interferon gamma-induced protein 10 and C-X-C motif chemokine ligand 9/monokine induced by gamma interferon. In groups that were matched for Injury Severity Score, the significantly higher levels of interferon gamma-induced protein 10 and monokine induced by gamma interferon persisted in the aged. Dynamic Bayesian Network revealed interferon gamma-induced protein 10 and monokine induced by gamma interferon as key mediators in the aged, and Dynamic Network Analysis revealed higher network complexity in the aged.

Conclusions

These findings indicate that differences in the early inflammatory networks between young and aged trauma patients are not simply a suppression of pro-inflammatory responses in the aged, but are characterized by a major shift in the mediator profile patterns with high levels of CXC chemokines in the aged.

Section snippets

Subjects and blood sampling

Blunt trauma patients were enrolled in this study after University of Pittsburgh IRB approval and informed consent. Inclusion criteria were age 18 years or older, admission to the ICU, and expectation to survive beyond initial 24 hours after injury. Exclusion criteria were isolated head injury, brain death criteria, and pregnancy. Plasma was sampled 3 times within the first 24 hours, starting with the initial blood draw on arrival, and then daily from day (D)1 to D7 after injury.

Data collection

Demographic and

Demographics and clinical outcomes

The overall study cohort was 472 blunt trauma survivors admitted to the ICU of a single Level I trauma center, described previously.¹⁷ To compare the circulating inflammatory profiles between young and aged trauma patients, patients between 18 to 30 years (young, n = 115) and 65 to 90 years (aged, n = 101) were identified for analysis (Table 1). Overall, males were predominant in both groups, but comprised a significantly greater proportion in the young (p = 0.01). In terms of mechanism of

Discussion

Normal aging is associated with changes in immune function commonly viewed as a decline of adaptive immune responses and an increase in baseline inflammation.³ Regardless of the definition used to categorize patients as aged, advanced age has been shown to be an independent predictor of adverse outcomes after severe traumatic injury.6, 20 By comparing young and aged adult patients, we were able to identify differences in pattern-specific mediator levels between young and aged trauma victims.

Author contributions

Study conception and design: Lamparello, Namas, Abdul-Malak, Vodovotz, Billiar

Acquisition of data: Lamparello, Namas, Abdul-Malak

Analysis and interpretation of data: Lamparello, Namas, Abdul-Malak

Drafting of manuscript: Lamparello, Namas, Vodovotz, Billiar

Critical revision: Lamparello, Namas, Vodovotz, Billiar

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: CME questions for this article available at http://jacscme.facs.org

: Disclosure Information: Authors have nothing to disclose. Timothy J Eberlein, Editor-in-Chief, has nothing to disclose.

: Support: NIH grant P50-GM-53789.

: Drs Lamparello and Namas contributed equally to this work.

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Original scientific articleYoung and Aged Blunt Trauma Patients Display Major Differences in Circulating Inflammatory Mediator Profiles after Severe Injury

Background

Study Design

Results

Conclusions

Section snippets

Subjects and blood sampling

Data collection

Demographics and clinical outcomes

Discussion

Author contributions

Age Res Rev

Immunity

Immunol Allergy Clin N Am

Injury

J Allergy Clin Immunol

Cytokine

Cell Immunol

Mech Ageing Dev

Experimental Gerontol

A genomic storm in critically injured humans

J Experiment Med

Aging and proinflammatory cytokines

Curr Opinion Hematol

Early predictors of postinjury multiple organ failure

Arch Surg

A detailed characterization of the dysfunctional immunity and abnormal myelopoiesis induced by severe shock and trauma in the aged

J Immunol

Advanced age is associated with worsened outcomes and a unique genomic response in severely injured patients with hemorrhagic shock

Crit Care

Trauma in the elderly: intensive care unit resource use and outcome

J Trauma

Practice management guidelines for geriatric trauma: the EAST Practice Management Guidelines Work Group

J Trauma

An Aging World: 2015. International Population Reports, P95/16-1

Original scientific article
Young and Aged Blunt Trauma Patients Display Major Differences in Circulating Inflammatory Mediator Profiles after Severe Injury