Chest
Volume 136, Issue 3, September 2009, Pages 823-831
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Original Research
Community-Acquired Pneumonia
Midregional Proadrenomedullin as a Prognostic Tool in Community-Acquired Pneumonia

https://doi.org/10.1378/chest.08-1981Get rights and content

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 ≤ 8), urea ≥ 7 mmol/L, respiratory rate ≥ 30 breaths/min, BP < 90 mm Hg systolic or < 60 mm Hg diastolic, age ≥ 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.

Section snippets

Study Design and Setting

We conducted a multicenter, prospective cohort study of patients presenting to the EDs of 28 teaching and nonteaching hospitals in southwestern Pennsylvania, Connecticut, southern Michigan, and western Tennessee between November 2001 and November 2003 (Genetic and Inflammatory Markers of Sepsis [GenIMS]). GenIMS investigated the relationship between inflammatory molecule expression, clinical course, and outcome in patients with CAP and sepsis. As part of this aim, we sought to determine the

Baseline Characteristics

Of the 2,320 subjects enrolled in GenIMS, 1,653 (71.3%) had an MR-proADM level measured on the presenting day and formed the study cohort (Fig 1). Median time from ED admission to first blood sample collection was 1.3 h. Table 1 lists the baseline characteristics of the study cohort. We had complete ED PSI data in 1,385 of the 1,653 cohort subjects (84%). Subjects were predominantly white, and 39% were identified as being at high risk by PSI, with most subjects admitted to the hospital. The

Discussion

Our findings confirm the prognostic value of MR-proADM in patients with CAP, but we also note important differences from the original Swiss study. Although we also found that MR-proADM strongly correlated with PSI and mortality, we identified a lower optimal cutoff value in our study cohort. Furthermore, we observed that the prognostic utility of MR-proADM beyond PSI was limited to high-risk subjects.

Differences in study cohort and methodology may explain the differing findings. Our study

Conclusions

In our multicenter CAP cohort, MR-proADM level correlated with 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.

Acknowledgments

Author contributions: Drs. Huang, Angus, Weissfeld, Kellum, and Yealy conceived and designed the study, analyzed and interpreted the data, and provided important critical revisions of the article. Drs. Huang, Angus, and Yealy drafted the article. Drs. Huang, Angus, Kellum, and Yealy provided final approval. Dr. Weissfeld and Mr. Pugh provided statistical expertise, and they contributed to the analysis and interpretation of the data and the drafting of the article. Dr. Struck provided technical

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Funding/Support: Funding for this research was received from National Institute of General Medical Sciences grant No. R01 GM061992.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).

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