Pathogenesis and Prevention Strategies of Severe Asthma Exacerbations in Children

James Cook; Sejal Saglani


Curr Opin Pulm Med. 2016;22(1):25-31. 

In This Article

Abstract and Introduction


Purpose of review 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.

Recent findings 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.

Summary 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.


Although asthma exacerbations can be defined in different ways, any increase in asthma symptoms that requires escalation of treatment, unscheduled medical assessment and an associated deterioration in lung function may be considered an exacerbation.[1] The ERS/ATS severe asthma guidelines define a severe exacerbation in patients over 6 years of age as a deterioration requiring the administration of systemic corticosteroids for 3 or more days, whereas a serious exacerbation is defined as the requirement of hospital admission.[2]

Asthma exacerbations represent a substantial challenge with associated morbidity and mortality, in addition to being expensive to treat and contributing significantly to the overall cost of asthma care.[3] Less well appreciated is their long-term influence on lung health. The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study is a large prospective cohort study examining associations between asthma exacerbations and lung function. A total of 2429 participants with severe or difficult to treat asthma aged 6 years and above were observed prospectively for 3 years to determine associations between exacerbations and annual change in lung function. Exacerbations were associated with progressive loss of lung function, with the most pronounced effect in children aged between 6 and 11 years (net 12-month change in post bronchodilator percentage predicted FEV1 by exacerbation history was 3%).[4] A consequent lower peak FEV1 in early adulthood is now known to be an important predictor for the development of chronic obstructive pulmonary disease (COPD) and premature death.[5,6]

Preventing asthma exacerbations in order to conserve lung function and to prevent morbidity and mortality are essential goals of paediatric asthma management. This can only be achieved if the basics of asthma management and education are addressed. The National Review of Asthma Deaths (NRAD) in the United Kingdom has recently shown fatal exacerbations in children were predominantly caused by low utility of maintenance treatment and unavailable asthma management plans with clear guidance on recognition and initial management of an exacerbation.[7] Addressing the basics of asthma care is therefore the cornerstone to prevent exacerbations.

The aim of this review is to consider the importance of mechanisms underlying asthma exacerbations and to propose the potential utility of exacerbation phenotype-specific management in the future. Also, to consider factors essential to prevent exacerbations, with a specific focus on the basics of asthma education and management to prevent severe exacerbations and the associated decline in lung function.