From preschool wheezing to asthma: Immunological determinants

Abstract

Asthma represents a chronic respiratory disease affecting millions of children worldwide. The transition from preschool wheezing to school-age asthma involves a multifaceted interplay of various factors, including immunological aspects in early childhood. These factors include complex cellular interactions among different immune cell subsets, induction of pro-inflammatory mediators and the molecular impact of environmental factors like allergens or viral infections on the developing immune system. Furthermore, the activation of specific genes and signalling pathways during this early phase plays a pivotal role in the manifestation of symptoms and subsequent development of asthma. Early identification of the propensity or risk for asthma development, for example by allergen sensitisation and viral infections during this critical period, is crucial for understanding the transition from wheeze to asthma. Favourable immune regulation during a critical ‘window of opportunity’ in early childhood can induce persistent changes in immune cell behaviour. In this context, trained immunity, including memory function of innate immune cells, has significant implications for understanding immune responses, potentially shaping long-term immunological outcomes based on early-life environmental exposures. Exploration of these underlying immune mechanisms that drive disease progression will provide valuable insights to understand childhood asthma development. This will be instrumental to develop preventive strategies at different stages of disease development for (i) inhibiting progression from wheeze to asthma or (ii) reducing disease severity and (iii) uncovering novel therapeutic strategies and contributing to more tailored and effective treatments for childhood asthma. In the long term, this shall empower healthcare professionals to develop evidence-based interventions that reduce the burden of asthma for children, families and society overall.