The kinetic profiles of copeptin and mid regional proadrenomedullin (MR-proADM) in pediatric lower respiratory tract infections

Philipp Baumann, Aline Fuchs, Verena Gotta, Nicole Ritz, Gurli Baer, Jessica M Bonhoeffer, Michael Buettcher, Ulrich Heininger, Gabor Szinnai, Jan Bonhoeffer, ProPAED study group, Philipp Baumann, Aline Fuchs, Verena Gotta, Nicole Ritz, Gurli Baer, Jessica M Bonhoeffer, Michael Buettcher, Ulrich Heininger, Gabor Szinnai, Jan Bonhoeffer, ProPAED study group

Abstract

Background: Kinetics of copeptin and mid regional proadrenomedullin (MR-proADM) during febrile pediatric lower respiratory tract infections (LRTI) are unknown. We aimed to analyze kinetic profiles of copeptin and MR-proADM and the impact of clinical and laboratory factors on those biomarkers.

Methods: This is a retrospective post-hoc analysis of a randomized controlled trial, evaluating procalcitonin guidance for antibiotic treatment of LRTI (ProPAED-study). In 175 pediatric patients presenting to the emergency department plasma copeptin and MR-proADM concentrations were determined on day 1, 3, and 5. Their association with clinical characteristics and other inflammatory biomarkers were tested by non-linear mixed effect modelling.

Results: Median copeptin and MR-proADM values were elevated on day 1 and decreased during on day 3 and 5 (-26%; -34%, respectively). The initial concentrations of MR-proADM at inclusion were higher in patients receiving antibiotics intravenously compared to oral administration (difference 0.62 pmol/L, 95%CI 0.44;1.42, p<0.001). Intensive care unit (ICU) admission was associated with a daily increase of MR-proADM (increase/day 1.03 pmol/L, 95%CI 0.43;1.50, p<0.001). Positive blood culture in patients with antibiotic treatment and negative results on nasopharyngeal aspirates, or negative blood culture were associated with a decreasing MR-proADM (decrease/day -0.85 pmol/L, 95%CI -0.45;-1.44), p<0.001).

Conclusion: Elevated MR-proADM and increases thereof were associated with ICU admission suggesting the potential as a prognostic factor for severe pediatric LRTI. MR-proADM might only bear limited value for decision making on stopping antibiotics due to its slow decrease. Copeptin had no added value in our setting.

Conflict of interest statement

Copeptin proAVP and MR-proADM test kits were provided by B.R.A.H.M.S. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Copeptin and MR-proADM concentrations over…
Fig 1. Copeptin and MR-proADM concentrations over the study period.
Distribution and change in copeptin (pmol/L) and MR-proADM (nmol/L) concentrations for patients over 5 study days. Boxes represent the interquartile range (IQR). Solid lines are the median, 25th and 75th quantile and whiskers equal 25th quantile -1.5 IQR and 75th quantile +1.5 IQR.
Fig 2. Correlation between copeptin and MR-proADM…
Fig 2. Correlation between copeptin and MR-proADM concentrations and pro-and anti-inflammatory markers at study inclusion.
IL: interleukin; TNF: tumor necrosis factor; INF: interferon; IP-10: interferon-gamma induced protein 10 kD, CRP: c-reactive protein; PCT: procalcitonin; MR-proADM: mid regional proadrenomedullin.

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