Defining Pediatric Asthma: Phenotypes to Endotypes and Beyond

Asthma is the most common chronic pediatric lung disease that has traditionally been defined as a syndrome of airway inflammation characterized by clinical symptoms of cough and wheeze. Highlighting the complex and heterogenous nature of asthma, this review summarizes recent advances in asthma classification that are based on pathobiology, and thereby directly addresses limitations of existent definitions of asthma. By reviewing and contrasting clinical and mechanistic features of adult and childhood asthma, the review summarizes key biomarkers that distinguish childhood asthma subtypes. While atopy and its severity are important features of childhood asthma, there is evidence to support the existence of a childhood asthma endotype distinct from the atopic endotype. Although biomarkers of non-atopic asthma are an area of future research, we summarize a clinical approach that includes existing measures of airway-specific and systemic measures of atopy, co-existing morbidities, and disease severity and control, in the definition of childhood asthma, to empower health care providers to better characterize asthma disease burden in children. Identification of biomarkers of non-atopic asthma and of the contribution of genetics and epigenetics to pediatric asthma burden remain a research need, which can potentially allow delivery of precision medicine to pediatric asthma.