Midregional proadrenomedullin as a prognostic tool in community-acquired pneumonia

Abstract

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.

Figures

Figure 1

Flow diagram of study.

Figure 2

Distribution of MR-proADM levels and other markers by PSI class. Lower and upper limits of boxes indicate the 25th and 75th percentiles; horizontal lines indicate the 50th percentiles, and crosses (+) within boxes indicate the mean values. The lines extending from the boxes indicate the entire range of values, except for four outlier values in the MR-proADM box plots (14.7, 15.4, 16.9, and 20.9 nmol/L) and two outlier values in the leukocyte count box plots (63/mL, 359/mL). The extreme leukocyte count outlier (359/mL) was excluded from box-plot analyses.

Figure 3

Kaplan-Meier survival curves by MR-proADM quartile.

Figure 4

Receiver operating characteristic curve analysis of MR-proADM, PSI, and a combined model of MR-proADM and PSI. Outcome is 30-day mortality. Adding MR-proADM to PSI did not significantly increase the AUC.

Figure 5

Kaplan-Meier survival curves by PSI class and MR-proADM quartile. In PSI classes I to III, mortality was low, and stratification by MR-proADM quartile did not provide additional information. In PSI classes IV/V, patients in the highest proADM quartile had the highest mortality.