Severe asthma in children

Abstract:

Asthma in children is a complex and heterogeneous disease where genetic and environmental factors play an interacting role. Asthma phenotype changes during child development, requiring continual reassessment of the disease. Although the majority of children with asthma respond well to standard therapy, a significant proportion (4.5%) of children with severe asthma do not respond well to conventional therapy. Factors which contribute to the severity of asthma are comorbidities, socioeconomic issues, environmental influences (e.g. tobacco smoke, allergens and other harmful factors), psychological issues and poor response to the treatment. Severe asthma may be divided into „difficult-to-control astma“ and „therapy-resistant severe asthma“. Viral infections, particularly rhinovirus (RV) and respiratory-syncytial virus (RSV), can trigger further development of asthma and are responsible for the exacerbation of asthma. They damage the epithelium of the bronchi and their affect on the secretion of interferon-beta (IFN-β) and interferon gamma (IFN-γ) is crucial. Severe asthma is considered to be a specific type of asthma. There is an increased number of neutrophils in small airways along with structural changes. Remodeling of the airway is present, along with changes in pulmonary epithelium, basal membrane, smooth muscles, blood vessels and mucous glands, resulting in impaired pulmonary function. Polymorphism of genes, particularly those involved with the corticosteroid pathway (CHRH1-corticotropin-releasing hormone receptor 1), plays an important role in severe asthma. Interaction between gene polymorphism and the environment results in non-eosinophilic asthma or mixed eosinophilic/neutrophilic asthma. Understanding of specific pathophysiological mechanisms is needed for phenotype-specific treatment of asthma in children. 

Key words:
asthma; child; corticosteroids; phenotype; severe asthma