New targets for drug development in asthma

Summary Asthma is a chronic inflammatory disease that affects about 300 million people worldwide, a total that is expected to rise to about 400 million over the next 15–20 years. Most asthmatic individuals respond well to the currently available treatments of inhaled corticosteroids and β-adrenergic agonists; however, 5–10% have severe disease that responds poorly. Improved knowledge of asthma mechanisms has led to the recognition of different asthma phenotypes that might reflect distinct types of inflammation, explaining the effectiveness of anti-leucotrienes and the anti-IgE monoclonal antibody omalizumab in some patients. However, more knowledge of the inflammatory mechanisms within the airways is required. Improvements in available therapies—such as the development of fast-onset, once-a-day combination drugs with better safety profiles—will occur. Other drugs, such as inhaled p38 MAPK inhibitors and anti-oxidants, that target specific pathways or mediators could prove useful as monotherapies, but could also, in combination with corticosteroids, reduce the corticosteroid insensitivity often seen in severe asthma. Biological agents directed against the interleukin-13 pathway and new immunoregulatory agents that modulate functions of T-regulatory and T-helper-17 cells are likely to be successful. Patient-specific treatments will depend on the development of discriminatory handprints of distinct asthma subtypes and are probably over the horizon. Although a cure is unlikely to be developed in the near future, a greater understanding of disease mechanisms could bring such a situation nearer to reality.