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

Erin L Vanzant, Rachael E Hilton, Cecilia M Lopez, Jianyi Zhang, Ricardo F Ungaro, Lori F Gentile, Benjamin E Szpila, Ronald V Maier, Joseph Cuschieri, Azra Bihorac, Christiaan Leeuwenburgh, Frederick A Moore, Henry V Baker, Lyle L Moldawer, Scott C Brakenridge, Philip A Efron

We wished to characterize the relationship of advanced age to clinical outcomes and to transcriptomic responses after severe blunt traumatic injury with hemorrhagic shock. We performed epidemiological, cytokine, and transcriptomic analyses on a prospective, multi-center cohort of 1,928 severely injured patients. We found that there was no difference in injury severity between the aged (age ≥55, n = 533) and young (age <55, n = 1395) cohorts. However, aged patients had more comorbidities. Advanced age was associated with more severe organ failure, infectious complications, ventilator days, and intensive care unit length of stay, as well as, an increased likelihood of being discharged to skilled nursing or long-term care facilities. Additionally, advanced age was an independent predictor of a complicated recovery and 28-day mortality. Acutely after trauma, blood neutrophil genome-wide expression analysis revealed an attenuated transcriptomic response as compared to the young; this attenuated response was supported by the patients' plasma cytokine and chemokine concentrations. Later, these patients demonstrated gene expression changes consistent with simultaneous, persistent pro-inflammatory and immunosuppressive states. We concluded that advanced age is one of the strongest non-injury related risk factors for poor outcomes after severe trauma with hemorrhagic shock and is associated with an altered and unique peripheral leukocyte genomic response. As the general population's age increases, it will be important to individualize prediction models and therapeutic targets to this high risk cohort.