Therapeutic Targets in Bronchial Asthma Pathophysiology

Abstract

The current model for bronchial asthma emphasizes chronic, ongoing airway inflammation resulting in airway hyper-reactivity as a fundamental process. To better understand the mechanisms involved in this unique inflammation, this article contains a review of the key cellular elements and the molecular participants that are thought to play a major role in the disease process. Included is information on the recruited cell population—mast cells, eosinophils, CD4+ lymphocytes, macrophages, and resident cells particularly the epithelial cell. Molecular participants discussed include tryptase, cytokines, chemokines, and adhesion molecules. Furthermore, modulators of the airway response, including the nonadrenergic, noncholinergic system and phosphodiesterase isoenzymes, particularly PDE4, are discussed in terms of their potential role in airway inflammation. Based on these observations, several models are presented that could result in the asthma phenotype, and specific novel therapeutic strategies are suggested that could provide significant advances in reversing or preventing chronic airway inflammation. Several of these approaches that are currently in the early phase of clinical trials are showing promising results.