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Introduction: The clinical phenotype of severe acute asthma at the pediatric intensive care unit (PICU) is highly heterogeneous. However, current treatment is still based on a 'one-size-fits-all approach'., Areas Covered: We aim to give a comprehensive description of the clinical characteristics of pediatric patients with severe acute asthma admitted to the PICU and available immunological biomarkers, providing the first steps toward precision medicine for this patient population. A literature search was performed using PubMed for relevant studies on severe acute (pediatric) asthma., Expert Opinion: Omics technologies should be used to investigate the relationship between cellular molecules and pathways, and their clinical phenotypes. Inflammatory phenotypes might guide bedside decisions regarding the use of corticosteroids, neutrophil modifiers and/or type of beta-agonist. A next step toward precision medicine should be inclusion of these patients in clinical trials on biologics.