The development of respiratory inflammation in children

Abstract

With the rising world burden of asthma, it is crucial to define the early events that lead to chronic inflammation and airway remodelling. Chronic airway inflammation appears to be the culmination of both local epithelial dysfunction and a more generalised immune dysregulation that results in allergic predisposition. A number of antenatal and early postnatal events may contribute to this. However, although a systemic propensity for allergic responses (typically food allergy) frequently pre-exists in children who go on to develop asthma, there is still uncertainty over whether epithelial changes occur as a primary event or whether these are consequent to this evolving systemic propensity for type 2 T-helper cell allergic responses. Many children with asthma already show many of the features of chronic airway inflammation, with epithelial desquamation, inflammatory cell infiltrates, subepithelial basement membrane thickening and fibrosis, goblet cell hyperplasia and smooth muscle hypertrophy. These changes can be evident before asthma is diagnosed, and there is also evidence that airway inflammation and early remodelling can progress in a subclinical state. New studies suggest that early airway damage is irreversible and that subsequent lung function is 'set' in the first years of life. These observations highlight the need to identify affected or at-risk children early and to develop interventions that can abort or prevent ongoing airway inflammation and remodelling.