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Inflammatory Markers at Hospital Discharge Predict Subsequent Mortality after Pneumonia and Sepsis

¹ The Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory, ² Department of Critical Care Medicine, and ³ Department of Biostatistics, Graduate School of Pubic Health, University of Pittsburgh, Pittsburgh, Pennsylvania; ⁴ Beulah Hinds Center for Lung Studies, Section of Pulmonary and Critical Care Medicine, Norwalk Hospital, Norwalk, Connecticut; and ⁵ Department of Emergency Medicine, Detroit Receiving Hospital, Wayne State University School of Medicine, Detroit, Michigan

Correspondence and requests for reprints should be addressed to Derek C. Angus, M.D., M.P.H., Department of Critical Care Medicine, University of Pittsburgh, 604 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261. E-mail: angusdc{at}upmc.edu

Rationale: Survivors of hospitalization for community-acquired pneumonia (CAP) are at increased risk of cardiovascular events, repeat infections, and death in the following months but the cause is unknown.

Objectives: To investigate whether persistent inflammation, defined as elevating circulating inflammatory markers at hospital discharge, is associated with subsequent outcomes.

Methods: Prospective cohort study at 28 sites.

Measurements and Main Results: We used standard criteria to define CAP and the National Death Index to determine all-cause and cause-specific 1-year mortality. At hospital discharge, 1,799 subjects (77.5%) were alive and vital signs had returned to normal in 1,512 (87%) subjects. The geometric means (±SD) for circulating IL-6 and IL-10 concentrations were 6.9 (±1) pg/ml and 1.2 (±1.1) pg/ml. At 1 year, 307 (17.1%) subjects had died. Higher IL-6 and IL-10 concentrations at hospital discharge were associated with an increased risk of death, which gradually fell over time. Using Gray's survival model, the associations were independent of demographics, comorbidities, and severity of illness (for each log-unit increase, the range of adjusted hazard ratios [HRs] for IL-6 were 1.02–1.46, P < 0.0001, and for IL-10 were 1.17–1.44, P = 0.01). The ranges of HRs for each log-unit increase in IL-6 and IL-10 concentrations among subjects who did and did not develop severe sepsis were 0.95–1.27 and 1.07–1.55, respectively. High IL-6 concentrations were associated with death due to cardiovascular disease, cancer, infections, and renal failure (P = 0.008).

Conclusions: Despite clinical recovery, many patients with CAP leave hospital with ongoing subclinical inflammation, which is associated with an increased risk of death.

Key Words: cytokines • mortality • pneumonia • IL-6 • IL-10

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Reasons for increased long-term mortality among hospital survivors of pneumonia are not known. What This Study Adds to the Field Persistent inflammation, defined as elevated circulating levels of IL-6 and IL-10 at hospital discharge after community-acquired pneumonia, is associated with all-cause and cause-specific mortality over one year, despite resolution of clinical signs of an acute infection.

 

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