Prognostic value of mid-regional pro-adrenomedullin (MR-proADM) in patients with community-acquired pneumonia: a systematic review and meta-analysis

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Abstract

Background

The early identification of patients at risk of dying from community-acquired pneumonia (CAP) is critical for their treatment and for defining hospital resource consumption. Mid-regional pro-adrenomedullin (MR-proADM) has been extensively investigated for its prognostic value in CAP. However, the results are conflicting. The purpose of the present meta-analysis was to explore the diagnostic accuracy of MR-proADM for predicting mortality in patients suffering from CAP, particularly emergency department (ED) patients.

Method

We systematically searched the PubMed, Embase, Web of Knowledge and Cochrane databases. Studies were included if a 2 × 2 contingency table could be constructed based on both the MR-proADM level and the complications or mortality of patients diagnosed with CAP. The prognostic accuracy of MR-proADM in CAP was assessed using the bivariate meta-analysis model. We used the Q-test and I ² index to evaluate heterogeneity.

Results

MR-proADM displayed moderate diagnostic accuracy for predicting complications in CAP, with an overall area under the SROC curve (AUC) of 0.74 (95 % CI: 0.70–0.78). Eight studies with a total of 4119 patients in the emergency department (ED) were included. An elevated MR-proADM level was associated with increased risk of death from CAP (RR 6.16, 95 % CI 4.71–8.06); the I ² value was 0.0 %, and a fixed-effects model was used to pool RR. The pooled sensitivity and specificity were 0.74 (95 % CI: 0.67–0.79) and 0.73 (95 % CI: 0.70–0.77), respectively. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 2.8 (95 % CI, 2.3–3.3) and 0.36 (95 % CI, 0.29–0.45), respectively. In addition, the diagnostic odds ratio (DOR) was 8 (95 % CI, 5–11), and the overall area under the SROC curve was 0.76 (95 % CI, 0.72–0.80).

Conclusions

Our study has demonstrated that MR-proADM is predictive of increased complications and higher mortality rates in patients suffering from CAP. Future studies are warranted to determine the prognostic accuracy of MR-proADM in conjunction with severity scores or other biomarkers and to determine an optimal cut-off level.

Electronic supplementary material

The online version of this article (doi:10.1186/s12879-016-1566-3) contains supplementary material, which is available to authorized users.

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Joachim Struck, Nils Morgenthaler, Andreas Bergmann … (2005)

Adrenomedullin (ADM) is a potent vasodilatory peptide, and circulating concentrations have been described for several disease states, including dysfunction of the cardiovascular system and sepsis. Reliable quantification has been hampered by the short half-life, the existence of a binding protein, and physical properties. Here we report the technical evaluation of an assay for midregional pro-ADM (MR-proADM) that does not have these problems. MR-proADM was measured in a sandwich immunoluminometric assay using 2 polyclonal antibodies to amino acids 45-92 of proADM. The reference interval was defined in EDTA plasma of 264 healthy individuals (117 male, 147 female), and increased MR-proADM concentrations were found in 95 patients with sepsis and 54 patients with cardiovascular disease. The assay has an analytical detection limit of 0.08 nmol/L, and the interassay CV was 0.12 nmol/L. The assay was linear on dilution with undisturbed recovery of the analyte. EDTA-, heparin-, and citrate-plasma samples were stable (<20% loss of analyte) for at least 3 days at room temperature, 14 days at 4 degrees C, and 1 year at -20 degrees C. MR-proADM values followed a gaussian distribution in healthy individuals with a mean (SD) of 0.33 (0.07) nmol/L (range, 0.10-0.64 nmol/L), without significant difference between males or females. The correlation coefficient for MR-proADM vs age was 0.50 (P < 0.001). MR-proADM was significantly (P < 0.001) increased in patients with cardiovascular disease [median (range), 0.56 (0.08-3.9) nmol/L] and patients with sepsis [3.7 (0.72-25.4) nmol/L]. MR-proADM is stable in plasma of healthy individuals and patients. MR-proADM measurements may be useful for evaluating patients with sepsis, systemic inflammation, or heart failure.

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Author and article information

Contributors

Jie Cao: 983206309@qq.com

Journal

Journal ID (nlm-ta): BMC Infect Dis

Journal ID (iso-abbrev): BMC Infect. Dis

Title: BMC Infectious Diseases

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2334

Publication date (Electronic): 26 May 2016

Publication date PMC-release: 26 May 2016

Publication date Collection: 2016

Volume: 16

Electronic Location Identifier: 232

Affiliations

[ ]Department of Respiratory Medicine, Tianjin Medical University General Hospital, Tianjin, 300070 China

[ ]Medical School, Nankai University, 94 Weijin Road, Tianjin, 300071 China

[ ]Department of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 China

Article

Publisher ID: 1566

DOI: 10.1186/s12879-016-1566-3

PMC ID: 4881068

PubMed ID: 27230573

SO-VID: df1881c3-866d-435c-8445-5217d1ea5efd

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.