Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis.
BACKGROUND
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.


OBJECTIVE
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.


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.
Yende
Sachin
S
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.
D'Angelo
Gina
G
Kellum
John A
JA
Weissfeld
Lisa
L
Fine
Jonathan
J
Welch
Robert D
RD
Kong
Lan
L
Carter
Melinda
M
Angus
Derek C
DC
D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D017714:Community-Acquired Infections / Q000097:blood / Q000401:mortality / Q000628:therapy; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010351:Patient Discharge; D011014:Pneumonia / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D011237:Predictive Value of Tests; D020127:Recovery of Function / Q000502:physiology; D018805:Sepsis / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D015996:Survival Rate; D016896:Treatment Outcome
D015850:Interleukin-6; D016753:Interleukin-10