Asthma translational medicine: report card.

Over the last 30 years, scientific research into asthma has focused almost exclusively on one component of the disorder - airway inflammation - as being the key underlying feature. These studies have provided a remarkably detailed and comprehensive picture of the events following antigen challenge that lead to an influx of T cells and eosinophils in the airways. Indeed, in basic research, even the term "asthma" has become synonymous with a T helper 2 cell-mediated disorder. From this cascade of cellular activation processes and mediators that have been identified it has been possible to pinpoint critical junctures for therapeutic intervention, leading experimentalists to produce therapies that are very effective in decreasing airway inflammation in animal models. Many of these compounds have now completed early Phase 2 "proof-of-concept" clinical trials so the translational success of the basic research model can be evaluated. This commentary discusses clinical results from 39 compounds and biologics acting at 23 different targets, and while 6 of these drugs can be regarded as a qualified success, none benefit the bulk of asthma sufferers. Despite this disappointing rate of success, the same immune paradigm and basic research models, with a few embellishments to incorporate newly identified cells and mediators, continue to drive target identification and drug discovery efforts. It is time to re-evaluate the focus of these efforts.