Proadrenomedullin Predicts Severe Disease in Children With Suspected Community-acquired Pneumonia

Abstract

Background Proadrenomedullin (proADM), a vasodilatory peptide with antimicrobial and anti-inflammatory properties, predicts severe outcomes in adults with community-acquired pneumonia (CAP) to a greater degree than C-reactive protein and procalcitonin. We evaluated the ability of proADM to predict disease severity across a range of clinical outcomes in children with suspected CAP. Methods We performed a prospective cohort study of children 3 months to 18 years with CAP in the emergency department (ED). Disease severity was defined as: mild (discharged home), mild-moderate (hospitalized but not moderate-severe or severe), moderate-severe (e.g., hospitalized with supplemental oxygen, broadening of antibiotics, complicated pneumonia), and severe (e.g., vasoactive infusions, chest drainage, severe sepsis). Outcomes were examined using proportional odds logistic regression within the cohort with suspected CAP and in a subset with radiographic CAP. Results Among 369 children, median proADM increased with disease severity [mild: median 0.53 nmol/L (IQR:0.43, 0.73), mild-moderate: 0.56 nmol/L (IQR:0.45, 0.71), moderate-severe: 0.61 nmol/L (IQR:0.47, 0.77), severe: 0.70 nmol/L (IQR:0.55, 1.04) (p=.002)]. ProADM was significantly associated with increased odds of developing severe outcomes (suspected CAP odds ratio (OR) 1.68 [95% CI, 1.2, 2.36], radiographic CAP OR 2.11 [95% CI, 1.36, 3.38]) adjusted for age, fever duration, antibiotic use, and pathogen. ProADM had an area under the ROC curve (AUC) of 0.64 (95%CI, 0.56,0.72) in those with suspected CAP and AUC 0.77 (95% CI, 0.68,0.87) in radiographic CAP. Conclusions ProADM was associated with severe disease and discriminated moderately well children who developed severe disease from those who did not, particularly in radiographic CAP.

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

“…In the recent past biomarker guided antibiotic therapy of LRTI was one research focus in infectious disease [ 9 , 27 ]. Copeptin and MR-proADM have shown to discriminate between mild and severe LRTI in children if measured on first presentation to an emergency department [ 16 , 20 ]. Assuming that children with severe LRTI are more likely to have bacterial infection in need of antibiotic treatment, copeptin and MR-proADM could be used to start or withhold empiric antibiotic treatment.…”

“…In recent studies MR-proADM was able to predict LRTI complications, such as pleural effusions and bacteremia [ 18 , 20 , 21 ]. In the present study IV administration of antibiotics was associated with higher MR-proADM concentrations on day 1, and ICU admission was associated with a slow increase in MR-proADM, indicating a persistent inflammatory state.…”

“…MR-proADM is a 48-amino acid fragment split from the adrenomedullin precursor pre-pro-adrenomedullin in a 1:1 ratio. MR-proADM reflects the adrenomedullin translation and was studied in pediatric LRTI in recent years in the context of assessing infectious disease severity [ 18 , 20 , 21 ]. Kinetic profiles on MR-proADM have been found to add prognostic value for predicting adverse outcome in adult LRTI [ 22 ], but have not been evaluated in children so far.…”

Predictive and Prognostic Utility of the Serum Level of Resistin-Like Molecule Beta for Risk Stratification in Patients with Community-Acquired Pneumonia

“…Our results show the addition of RELM-β to a clinical severity scoring method significantly improved their prognostic accuracy. ProADM is considered an excellent single predictor of short-term and long-term mortality [ 19 ]. In this study, the level of proADM was not better than that of RELM-β in predicting SCAP and 30-day mortality.…”

“…In the current study, we hypothesized that higher RELM-β levels could indicate poor prognosis and mortality within 30 days. In addition, proadrenomedullin (proADM), a vasodilatory peptide with antimicrobial and anti-inflammatory properties, has shown promise in predicting illness severity in sepsis and lower respiratory tract infections in adults [ 19 ]. The level of proADM was also measured, and the predictive performance was evaluated and compared with that of RELM-β.…”