Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis.
Angus DC, Kellum JA, Arena V, Cooper GF, Delude RL, Feingold E, Ferrell R, Fine MJ, Finegold D, Fink MP, Kong L, Krichevsky A, Martino M, Pinsky MR, Rahim M, Roberts MS, Schaefer A, Weissfeld LA, Wood KA, Yealy DM, Wunderink RG, Fine JM, Tracey KJ, Wang H, Yang L, Christie J, Bucala R, Werdmann M, Nunnink K, Bernstein LH, Scherzer H, Haddad R, Grant R, Papa R, St Clair C, Reynholds B, Walshon J, Null T, Friedman L, Pappu S, Graff LM, Bennett N, Buono D, Jacobs B, McNamme M, Wolf S, Carius M, Belden C, Scinto L, Nair S, Holland S, Flynn E, Riordan R, Degutis LC, Olson N, Jatlow P, Siegel M, Welch R, Waselewsky D, Dunne R, Kruse J, Bilicki K, Rivers E, Shah K, Dooley C, Anderson J, Laman D, Mostoufi M, Ergas S, Betcher K, Furman A, Rocker E, MacLeod B, Rolniak S, Borochovitz D, Greer K, Riley P, Gaudio F, Maggi G, Hufnagel M, DeLuca C, Grogan A, Basheda S, Clark M, Campbell TP, Morrow D, Fiehler PC, Geyer S, Heath R, Casey S, Yee E, Krifcher C, Moldovan J, Moldovan J, Pagano A, Castor E, Kumar RK, Hewitt L, Knestaut L, Chaudhry R, Probst R, Kristan W, Campbell L, Hewlett C, Provenzano M, Kuzma J, Delbridge T, Murcek MA, Wells A, Solot J, Waddell L, Becich M, Weinberg J, Rosenbloom J, Joyce C, Khasnabis S, Strimlan CV, Nicholas J, Morris A, Gorsha N, Patti M, Singh J, Naples M, Wunderink R, Jones C, Kessler L, Young TL, Bowman MV, Carter M, Gigler J, Auble TE, Darnley A, Greenwald K, Guzik LJ, Hebda S, Hoteck T, McCaw M, Mandich LA, Powell TA, Shaufl A, Sterling H, Woods H, Martinez J, Tang X, Greenhouse D, He S, Kreke J, Saka G, Visweswaran S, Yuan X.
Source
The Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory, Department of Critical Care Medicine, Graduate School of Pubic Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Abstract
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.
- PMID:
- 18369199
- [PubMed - indexed for MEDLINE]
- PMCID: PMC2720087
Free PMC ArticleFigure 1.
Subject disposition for the entire Genetic and Inflammatory Markers of Sepsis (GenIMS) cohort. CAP = community-acquired pneumonia.
Am J Respir Crit Care Med. Am J Respir Crit Care Med;177(11):1242-1247.
Figure 2.
Failure plots for circulating IL-6 (A) and IL-10 (B) concentrations and mortality over 1 year. High and low concentrations are the 10th and 90th percentiles of cytokine concentrations. Using the Gray's model, the hazard ratios are estimated over 10 intervals (with 11 time nodes) over 1 year and hazard ratios over five representative periods are shown. P values are obtained from the Gray's survival model.
Am J Respir Crit Care Med. Am J Respir Crit Care Med;177(11):1242-1247.
Figure 3.
Varying hazard ratios with 95% confidence intervals (CI) for IL-6 (A) and IL-10 (B) and risk of death over 1 year. The hazard ratios are shown over 10 intervals (with 11 time nodes), based on the Gray's model. For IL-6, the 95% CI is above 1 for 100 days, whereas for IL-10 the 95% CI is above 1 for 177 days or approximately 6 months.
Am J Respir Crit Care Med. Am J Respir Crit Care Med;177(11):1242-1247.
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