Defining pediatric asthma: phenotypes to endotypes and beyond

Abstract

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 heterogeneous 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 the contribution of genetics and epigenetics to pediatric asthma burden remains a research need, which can potentially allow delivery of precision medicine to pediatric asthma. IMPACT: This review highlights asthma as a complex and heterogeneous disease and discusses recent advances in the understanding of the pathobiology of asthma to demonstrate the need for a more nuanced definitions of asthma. We review current knowledge of asthma phenotypes and endotypes and put forth an approach to endotyping asthma that may be useful for defining asthma for clinical care as well as for future research studies in the realm of personalized medicine for asthma.

Figure 1.. Approach for defining asthma for children.

We propose the use of the following approach for defining asthma in children. Health care providers have the tools at hand to define asthma severity (red box) and control (green box), as per the NHLBI guidelines, based on symptom frequency and medication use. In addition, the providers should identify presence of comorbidities (yellow box) that have been associated with asthma burden, define the atopic status of the patient (blue box), and the pattern of pulmonary function testing (purple box). Together, these details can be funneled into personalized definition of asthma for any given patient. Examples of asthma definitions for individual patients using this approach are included in grey text within the funnel.