A look at the pathogenesis of asthma: the need for a change in direction

While asthma is an inflammatory disorder of the conducting airways, most frequently therapeutics directed specifically at components of these pathways have had limited or no success in the clinic. Part of the problem lies in over-reliance on simple animal models of antigen sensitization and challenge to select therapeutic candidates, and partly because allergic mechanisms have been studied out of context of the formed elements that make up the structure of the airways such as the epithelium and underlying vasculature and mesenchyme. This review covers recent experience with some new therapeutics that include biologics and concludes by presenting a new paradigm for the disease that embraces heterogeneity and greater consideration of the role played by functionally active structural components. Since asthma was originally described in terms of reversible airflow obstruction, this moves away from placing inflammation at the center of the disease more towards a parallel involvement of the epithelial mesenchymal trophic unit to provide the context within which the inflammatory response occurs.