Pathophysiology of asthma.

1. Our understanding of asthma and its therapy has changed markedly over the last few years, particularly with the application of molecular and cell biology and the discovery of new and more specific pharmacological tools. 2. Many inflammatory cells participate in the inflammatory process in asthma and mediate a complex mixture of mediators. Cytokines are of particular importance as mediators of chronic inflammation and the means by which cytokines amplify and perpetuate the inflammatory process is now emerging. Airway epithelial cells may be a particularly important source of cytokines and other mediators, such as nitric oxide and endothelin, and may be a major target cell for inhaled steroids, which are the most effective therapy for asthma currently available. 3. The inflammatory process in asthma results not only in bronchoconstriction, but also plasma exudation, the activation of neural mechanisms, mucus secretion. The chronic inflammation may lead to structural changes, including an increase in airway smooth muscle and fibrosis, that are essentially irreversible. There is increasing evidence that transcription factors, such as NF-kappa B, play a pivotal role in the expression of inflammatory genes in asthma and may be the major molecular target for glucocorticoids.