The Effects of Age on Inflammatory and Coagulation-Fibrinolysis Response in Patients Hospitalized for Pneumonia

Abstract

ObjectiveTo determine whether inflammatory and hemostasis response in patients hospitalized for pneumonia varies by age and whether these differences explain higher mortality in the elderly.MethodsIn an observational cohort of subjects with community-acquired pneumonia (CAP) recruited from emergency departments (ED) in 28 hospitals, we divided subjects into 5 age groups (<50, 51–64, 65–74, 75–84, and ≥85). We measured circulating levels of inflammatory (TNF, IL-6, and IL-10), hemostasis (D-dimer, Factor IX, thrombin-antithrombin complex, antithrombin and plasminogen-activator inhibitor-1), and cell-surface markers (TLR-2, TLR-4, and HLA-DR) during the first week of hospitalization and at discharge and compared 90-day mortality. We used logistic regression to compare odds ratios (OR) for 90-day mortality between age groups, adjusting for differences in pre-infection factors alone and then additionally adjusting for immune markers.ResultsOf 2,183 subjects, 495, 444, 403, 583, and 258 subjects were <50, 51–64, 65–74, 75–84, and ≥85 years of age, respectively. Large age-related differences were observed in 90-day mortality (0.82% vs. 3.2% vs. 6.4% vs. 12.8% vs. 13.6%, p<0.01). No age-related differences in inflammatory and cell surface markers occurred during the first week. Older subjects had higher pro-coagulant markers on ED presentation and over first week (p≤0.03), but these differences were modest (1.0–1.7-fold differences). Odds of death for older adults changed minimally in models incorporating differences in hemostasis and inflammatory markers (for subjects ≥85 compared to those <50, OR = 4.36, when adjusted for pre-infection factors and OR = 3.49 when additionally adjusted for hemostasis markers). At discharge, despite clinical recovery as evidenced by normal vital signs in >85% subjects, older subjects had modestly increased hemostasis markers and IL-6 levels (p<0.01).ConclusionsModest age-related increases in coagulation response occur during hospitalization for CAP; however these differences do not explain the large differences in mortality. Despite clinical recovery, immune resolution may be delayed in older adults at discharge.

Infection Hospitalization Increases Risk of Dementia in the Elderly*

“…Our results suggest that an episode of infection accelerates dementia. A potential mechanism to explain this association could be persistent inflammation in the systemic circulation or in the brain or due to activation of other aspects of the innate immune response, as evidenced in observational human studies (4–9, 13–15) and in animal models (10–12, 45). For example, a single lipopolysaccharide injection in animals causes chronic neuroinflammation, long-term cognitive deficits, and accelerates neurodegenerative conditions (10–12).…”

Age-Related Differences in Biomarkers of Acute Inflammation During Hospitalization for Sepsis

“…However, few studies longitudinally report age-related differences in inflammatory biomarkers, as most studies have been cross-sectional at variable times during their hospital course. Existing data are contradictory on whether older adults have greater or suppressed acute inflammation and whether this contributes to the poorer outcomes of severe sepsis in older adults (7, 8, 15, 16). In this study, we analyzed six novel biomarkers of inflammation measured serially for 72 hours as part of a large, multicenter longitudinal cohort of emergency department (ED) patients admitted for sepsis (14).…”

Is community-acquired pneumonia an independent risk factor for cardiovascular disease?

“…MILBRANDT et al [47] identified that significant pro-thrombotic effects and elevation of coagulation markers persisted throughout hospital stay and occurred even in patients with clinically very mild pneumonia. Data from the same group also suggest that elevation of coagulation markers is greatest in elderly patients with pneumonia, the group at greatest cardiovascular risk [48].…”