Midregional proadrenomedullin as a prognostic tool in community-acquired pneumonia.
BACKGROUND
Midregional proadrenomedullin (MR-proADM) is a potential prognostic biomarker in patients with community-acquired pneumonia (CAP). Previous work has been hampered by sample size and illness spectrum limits. We sought to describe the pattern of MR-proADM in a broad CAP cohort, confirm its prognostic role, and compare its performance to procalcitonin, a novel biomarker of infection.


METHODS
We conducted a multicenter prospective cohort study in 28 community and teaching EDs. Patients with a clinical and radiographic diagnosis of CAP were enrolled. We stratified MR-proADM levels a priori into quartiles and quantified severity of illness using the pneumonia severity index (PSI); and confusion (abbreviated mental test score of <or= 8), urea >or= 7 mmol/L, respiratory rate >or= 30 breaths/min, BP < 90 mm Hg systolic or < 60 mm Hg diastolic, age >or= 65 years (CURB-65). The primary outcome was 30-day mortality.


RESULTS
A total of 1,653 patients formed the study cohort. MR-proADM levels consistently rose with PSI class and 30-day mortality (p < 0.001). MR-proADM had a higher area under the curve for 30-day mortality than procalcitonin (0.76 vs 0.65, respectively; p < 0.001), but adding MR-proADM to the PSI in all subjects minimally improved performance. Among low-risk subjects (PSI classes I to III), mortality was low and did not differ by MR-proADM quartile. However, among high-risk subjects (PSI class IV/V; n = 546), subjects in the highest MR-proADM quartile (n = 232; 42%) had higher 30-day mortality than those in MR-proADM quartiles 1 to 3 (23% vs 9%, respectively; p < 0.0001). Similar results were seen with CURB-65. MR-proADM and procalcitonin levels were generally concordant; only 6% of PSI class IV/V subjects in the highest MR-proADM quartile had very low procalcitonin levels (< 0.1 ng/mL).


CONCLUSIONS
In our multicenter CAP cohort, MR-proADM levels correlate with increasing severity of illness and death. High MR-proADM levels offer additional risk stratification in high-risk CAP patients, but otherwise MR-proADM levels do not alter PSI-based risk assessment in most CAP patients.
Huang
David T
DT
Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; Departments of Critical Care Medicine, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; Emergency Medicine, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA. Electronic address: huangdt@ccm.upmc.edu.
Angus
Derek C
DC
Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; Departments of Critical Care Medicine, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
Kellum
John A
JA
Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; Departments of Critical Care Medicine, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
Pugh
Nathan A
NA
Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
Weissfeld
Lisa A
LA
Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
Struck
Joachim
J
Research Department, BRAHMS AG, Biotechnology Centre, Hennigsdorf, Germany.
Delude
Russell L
RL
Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; Departments of Critical Care Medicine, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
Rosengart
Matthew R
MR
Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; Departments of Critical Care Medicine, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; Surgery, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
Yealy
Donald M
DM
Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; Emergency Medicine, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
D053607:Adrenomedullin / Q000097:blood*; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D017714:Community-Acquired Infections / Q000097:blood* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D011014:Pneumonia / Q000097:blood* / Q000401:mortality; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D012372:ROC Curve; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D014481:United States / Q000453:epidemiology
D015415:Biomarkers; C000606589:CALCA protein, human; D011498:Protein Precursors; C088633:proadrenomedullin; D053607:Adrenomedullin; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide