Risk factors for intensive care admission in children with severe acute asthma in the Netherlands: a prospective multicentre study.

RATIONALE: Severe acute asthma (SAA) can be fatal, but is often preventable. We previously observed in a retrospective cohort study, a three-fold increase in SAA paediatric intensive care (PICU) admissions between 2003 and 2013 in the Netherlands, with a significant increase during those years of numbers of children without treatment of inhaled corticosteroids (ICS). OBJECTIVES: To determine whether steroid-naïve children are at higher risk of PICU admission among those hospitalised for SAA. Furthermore, we included the secondary risk factors tobacco smoke exposure, allergic sensitisation, previous admissions and viral infections. METHODS: A prospective, nationwide multicentre study of children with SAA (2-18 years) admitted to all Dutch PICUs and four general wards between 2016 and 2018. Potential risk factors for PICU admission were assessed using logistic regression analyses. MEASUREMENTS AND MAIN RESULTS: 110 PICU and 111 general ward patients were included. The proportion of steroid-naïve children did not differ significantly between PICU and ward patients. PICU children were significantly older and more exposed to tobacco smoke, with symptoms >1 week prior to admission. Viral susceptibility was not a significant risk factor for PICU admission. CONCLUSIONS: Children with SAA admitted to a PICU were comparable to those admitted to a general ward with respect to ICS treatment prior to admission. Preventable risk factors for PICU admission were >7 days of symptoms without adjustment of therapy and exposure to tobacco smoke. Physicians who treat children with asthma must be aware of these risk factors.

Proenkephalin as a new biomarker for pediatric acute kidney injury - reference values and performance in children under one year of age.

Objectives Acute kidney injury (AKI) is common in critically ill children, but current biomarkers are suboptimal. Proenkephalin A 119-159 (PENK) is a promising new biomarker for AKI in adults, but pediatric data is lacking. We determined PENK reference intervals for healthy children, crucial for clinical implementation, and explored concentrations in critically ill infants aged under 1 year. Methods Observational cohort study in healthy infants and critically ill children aged 0-1 years. Reference values were determined using generalized additive models. Plasma PENK concentrations between healthy children and critically ill children with and without AKI, were compared using linear mixed modelling. The performance of PENK as AKI biomarker was compared to cystatin C (CysC) and ß-trace protein (BTP) using receiver-operating-characteristic (ROC) analysis. Results PENK concentrations in 100 healthy infants were stable during the first year of life (median 517.3 pmol/L). Median PENK concentrations in 91 critically ill children, were significantly higher in those with AKI (n=40) (KDIGO Stage 1 507.9 pmol/L, Stage 2 704.0 pmol/L, Stage 3 930.5 pmol/L) than non-AKI patients (n=51, 432.2 pmol/L) (p < 0.001). PENK appeared to relate better to AKI diagnosis than CysC and BTP (AUROC PENK 0.858, CysC 0.770 and BTP 0.711) in the first 24 h after recruitment. Conclusions PENK reference values are much higher in young infants than adults, but clearly discriminate between children with and without AKI, with comparable or better performance than CysC and BTP. Our results illustrate the importance of establishing age-normalized reference values and indicate PENK as a promising pediatric AKI biomarker.