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Preinfection Systemic Inflammatory Markers and Risk of Hospitalization Due to Pneumonia

CRISMA Laboratory (Clinical Research, Investigation, and Systems Modeling of Acute Illness), Department of Critical Care Medicine, and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Infectious Disease, St. Jude Children's Research Hospital, Memphis, Tennessee; Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Division of General Internal Medicine, University of California, San Francisco, California; Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland; and Sticht Center on Aging, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Correspondence and requests for reprints should be addressed to Sachin Yende, M.D., M.S., Department of Critical Care Medicine, 3550 Terrace Street, Pittsburgh PA 15261. E-mail: yendes{at}upmc.edu

Rationale: Elevated proinflammatory cytokines are associated with severity of pneumonia, but the role of preinfection cytokine levels in the predisposition to pneumonia in humans is less clear.

Objective: To ascertain role of preinfection inflammatory markers on susceptibility to community-acquired pneumonia (CAP).

Methods: Longitudinal analysis over 6.5 yr of a cohort that consisted of 70- to 79-yr-old well-functioning elderly individuals.

Measurements: Association between preinfection tumor necrosis factor (TNF), interleukin 6 (IL-6), and C-reactive protein (CRP) levels and CAP requiring hospitalization.

Results: Of the 3,075 participants, 161 (5.2%) developed at least one episode of CAP requiring hospitalization over a median duration of 3.3 yr. The highest tertiles of TNF (> 3.7 pg/ml) and IL-6 (> 2.4 pg/ml) were associated with increased risk of CAP, and the adjusted odds ratios were 1.6 (95% confidence interval [CI], 1.02–2.7) and 1.7 (95% CI, 1.1–2.8), respectively. The adjusted risk of CAP with at least one of these markers in the highest tertile was 1.6 (95% CI, 1.1–2.3). TNF and IL-6 levels in the highest tertile had a synergistic effect (p = 0.01 for interaction), and risk of CAP for both markers in the highest tertile was 2.8 (95% CI, 1.8–4.3). An FEV₁ of 50% or less of predicted was associated with the highest risk of CAP (adjusted odds ratio, 3.6; 95% CI, 2.3–5.6). Furthermore, TNF and IL-6 levels modified risk of CAP in participants with coexisting medical conditions and history of smoking.

Conclusion: In the well-functioning elderly subjects, preinfection systemic levels of TNF and IL-6 were associated with higher risk of CAP requiring hospitalization in smokers and those with coexisting medical conditions.

Key Words: inflammatory markers • interleukin 6 • tumor necrosis factor • pneumonia

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