Basic Mechanisms Underpinning Severe Childhood Asthma

  • Sejal SaglaniEmail author


The immunopathogenesis of allergic asthma in children with controlled, mild-moderate disease is a Th2-driven eosinophilia, which is treated effectively in the majority of patients with maintenance inhaled steroid therapy. However, there is a small group of children with very severe disease that remain poorly controlled, with frequent exacerbations despite maximal doses of inhaled steroids and, in some cases, despite maintenance systemic steroids. These children, who are known to be adherent of their prescribed therapy, and in whom all modifiable factors that contribute to poor control such as persistent allergen exposure have been addressed, have severe therapy-resistant asthma (STRA).

The airway pathology that is characteristic of STRA in children includes eosinophilic inflammation. This is accompanied by abnormal structural changes of the airway wall, collectively termed remodelling, including increased thickness of the sub-epithelial reticular basement membrane and increased airway smooth muscle mass. However, the inflammatory and remodelling phenotype can also be very variable between patients. All studies demonstrate a large degree of variability within groups of patients with severe asthma. Therefore, it is apparent that each patient has a specific pathophysiological phenotype incorporating different degrees of airway inflammation, remodelling and lung function abnormalities, which in turn determine the clinical manifestation of disease. The pathophysiological heterogeneity of STRA suggests a single mechanistic pathway will not explain the disease and a single therapeutic strategy of “one size fits all” is unlikely to be successful. It is therefore necessary to investigate mechanisms that mediate sub-phenotypes of disease.


Pulmonary immunity Eosinophils IL-5 Mast cells Lymphoid cells Neutrophils Airway smooth muscle Severe therapy-resistant asthma (STRA) Steroid resistance Innate immunity Phenotype Add-on therapy Pre-school wheeze Eosinophilic inflammation Gene-environment interaction Microbiome 


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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Paediatric Respiratory MedicineNational Heart & Lung Institute, Imperial College LondonLondonUK
  2. 2.Department of Respiratory PaediatricsRoyal Brompton HospitalLondonUK

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