The role of allergy in the development of airway inflammation in children.

The primary immune response to allergens is the prototypic T-helper cell type 2 (Th2) response. This occurs prenatally, favoured by the normal Th2-skewed immune response of pregnancy. The immune system matures during the early years of life. The immune responses, primarily determined by genetic susceptibility, are also influenced by exposure to allergens and infections, which may reverse their direction. Although wheezing is observed before 2 years of age, this is usually not attributable to allergy, and the majority of the wheezers do not develop asthma. The development of allergic asthma can be considered to be a two-stage process. The first stage involves the development of allergen-specific immunological memory against inhaled allergens. This happens in childhood and polarises the immune response towards a Th2 phenotype. These individuals are therefore more prone to developing allergic inflammation. Stage two involves the consolidation and maintenance of this polarised Th2 response, leading to a state of chronic airway inflammation. This second phase is influenced by various factors, for example respiratory viral infections, repeated indoor and outdoor allergen exposure, environmental tobacco smoke and air pollutants. The persistent airway inflammation leads to tissue remodelling and airway hyperresponsiveness, the clinical sine qua non of asthma.