34 - The Immunopathogenesis of Asthma

Abstract

Asthma develops as a result of the interplay of genetic susceptibility and environmental exposures on the lungs and immune system. Asthma in school-age children is predominantly associated with the development of allergic sensitization and the pathological features of eosinophilic airway inflammation and structural airway wall changes, collectively termed airway remodeling. The clinical manifestation of disease is heterogeneous but includes symptoms of breathlessness and wheeze, which result from bronchoconstriction. Acute attacks in children commonly result from respiratory infections, especially with rhinovirus and respiratory syncytial virus in early life. The focus of this chapter is to discuss the basic immunological mechanisms that underpin the pathophysiology of school-age asthma, with specific focus on the close interactions between innate and adaptive immune responses in driving disease. The immunopathology of specific clinical manifestations of disease, including exacerbations and preschool wheezing disorders, will also be discussed, and mechanisms that are unique to the developing pediatric airway and that cannot be extrapolated from adult disease will be highlighted. There is increasing evidence for interactions between the environment and host microbiome in determining susceptibility or protection from asthma. Current knowledge of the immunopathology underlying disease protection will also be discussed.