Abstract
Asthma is a chronic inflammatory disorder of the airways superimposed upon structural changes that include an increase in smooth muscle and airway wall remodeling. In addition to a background of chronic mediator release, asthma is characterized by considerable variations in airway function brought about by important interactions with the environment, including allergen, pollutant and virus exposure. At least in mild-moderate disease, cytokines released from Th2 cells appear important in orchestrating the inflammation. The situation in more severe disease is complicated by the superimposition of a Th1 on top of a Th2 response. Until recently, the only controller treatment for chronic asthma has been corticosteroids. However, identification of specific effector molecules in asthma has led to targeting of specific pathways by using cytokines and cytokine inhibitors. Administration of a monoclonal blocking antibody against IgE has been shown to be highly efficacious in severe allergic asthma, but enhancement of Th1 responses or attempts to reduce eosinophils using anti-interleukin-5 monoclonal antibodies have no clinical benefit. In more severe asthma, blockade of tumor necrosis factor-α using the decoy etanercept has revealed efficacy in a small open study supporting the view that Th1, in addition to Th2, pathways are important as the disease adopts a more severe phenotype. Thus, like atopic dermatitis, it is likely that asthma is not a single disease, but a group of disorders that differ in the relative contribution of specific pathophysiological pathways.
