Pathogenesis and prevention strategies of severe asthma exacerbations in children

Abstract

Exacerbations of asthma in children are most frequently precipitated by respiratory infections with a seasonal pattern. However, management takes little account of the underlying infective or other precipitant abnormality. Interactions between environmental triggers, the airway microbiome and innate immune responses are key determinants of exacerbations. Elevated innate cytokines interleukin (IL)-33 and IL-25, and abnormal molecular responses in the interferon pathway are associated with rhinoviral infections. Exacerbations caused by fungal allergens also induce IL-33, highlighting this as an attractive therapeutic target. An equal contribution of bacterial and viral infection during exacerbations, particularly in preschool children, has become increasingly apparent, but some organisms may be protective. Investigation of mechanisms underlying infection-related exacerbations especially in preschool children is needed.Progressive loss of lung function from exacerbations is most pronounced in children aged 6-11 years, and low FEV1 is now recognized as a key predictor for the development of chronic obstructive pulmonary disease and premature death. Although prevention of exacerbations is critical, suboptimal patient education, prescription and adherence to maintenance therapy, and a lack of predictive biomarkers, remain key unaddressed issues in children. Precipitants and predictors of exacerbations, together with the child's age and clinical phenotype, need to be used to achieve individualized management in preference to the current uniform approach for all.