Treating Asthma as an Inflammatory Disease: Allergic Asthma

The mast cell is a key player in the early allergic response that typically starts within minutes of exposure to an appropriate antigen. Acute symptoms peak within 10 to 15 min and typically resolve within 60 min of exposure to an adequate dose of antigen, Studies by Brightling et al and Carroll et al indicate that there is microlocalization of mast cells in the airway smooth muscle, suggesting that interactions between mast cells and smooth-muscle cells are critical for the development of the disordered airway function found in asthma. The mast cell surface-bound Ig E (IgE) is cross-linked by the antigen, leading to mast cell activation and release of potent mediators, such as histamine, leukotrienes, prostaglandin D2, bradykinin, and platelet-activating factor. This results in airway smooth-muscle contraction, edema, and enhanced mucous secretions leading to airflow limitation and acute asthma symptoms, such as nasal discharge, sneezing, bronchocon-striction, and skin weal and flare. Typically, an early phase response may induce a 25% reduction in FEV1. A conjunctival allergen challenge study has also shown increased levels of tryptase in the early phase allergic response. read

The late phase response, which peaks 4 to 6 h after an allergen challenge, is typified by recruitment of T-cells and B-cells and eosinophils. In particular, T-helper type 2 cells secrete cytokines, contributing to eosinophil recruitment and activation, IgE production, mucous secretion, and expression of adhesion molecules, such as vascular cell adhesion molecule-1, which is essential for selective recruitment of eosinophils, and intercellular adhesion molecule (ICAM)-1, which is expressed on epithelial cells only on allergen exposure and is considered a hallmark of ongoing allergic inflammation. Eosinophils contain potent mediators, including major basic protein, eosinophil cationic protein, eosinophil-derived neurotoxin, and eosinophil peroxidase, all of which can induce airway damage and contribute to airway hyperresponsiveness. Eosinophils also have the capacity to generate other important factors, such as leukotrienes, cytokines, matrix metalloproteinase, and reactive oxygen species, which could contribute to airway obstruction and injury. Late and ongoing allergic symptoms include nasal congestion, ongoing asthma, and urticaria. Typically, a late phase response may induce a 75% reduction in FEV1.

This entry was posted in Asthma and tagged allergic rhinitis, asthma, corticosteroids, inflammation, remodeling.