title: The effects of age on inflammatory and coagulation-fibrinolysis response in patients hospitalized for pneumonia.
abstract: OBJECTIVE
  To determine whether inflammatory and hemostasis response in patients hospitalized for pneumonia varies by age and whether these differences explain higher mortality in the elderly.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  Of 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).
  
  
  CONCLUSIONS
  Modest 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.
authors.affiliation: The Clinical Research, Investigation, and Systems Modeling of Acute Illness Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Sachin
authors.initials: S
authors.lastname: Kale
authors.forename: Sachin
authors.initials: S
authors.lastname: Yende
authors.forename: Lan
authors.initials: L
authors.lastname: Kong
authors.forename: Amy
authors.initials: A
authors.lastname: Perkins
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
authors.forename: Abbe N
authors.initials: AN
authors.lastname: Vallejo
authors.forename: Derek C
authors.initials: DC
authors.lastname: Angus
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000990:Antithrombin III / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D001779:Blood Coagulation Factors / Q000032:analysis*; D005164:Factor IX / Q000032:analysis; D005260:Female; D005342:Fibrinolysis; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010447:Peptide Hydrolases / Q000032:analysis; D011014:Pneumonia / Q000097:blood* / Q000401:mortality / Q000628:therapy; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001779:Blood Coagulation Factors; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C046193:antithrombin III-protease complex; D016753:Interleukin-10; D000990:Antithrombin III; D005164:Factor IX; D010447:Peptide Hydrolases