The secret life of steroids in asthma

Asthma is an inflammatory disease. Who is still questioning this paradigm? In the Global Initiative for Asthma (GINA) guidelines the disease is defined as a chronic inflammatory disorder of the airways 1. The evidence for this is overwhelming, and comes from observational studies as well as experimental models. The proof of the pudding has been provided by numerous studies with anti-inflammatory interventions. Ever since the early 1950s 2, the efficacy of both short courses and maintenance treatment with corticosteroids in asthma has been beyond any discussion 1. Hence, the evidence that inflammation is causally involved in the pathophysiology of asthma nicely meets Koch’s postulations. Therefore, it is no surprise that ever since this key mechanism of the disease was identified, many academic and industrial groups rushed to develop the most selective and potent anti-inflammatory compounds for suppression, prevention or perhaps even cure of the disease. Remarkably, during the past 20 yrs the development of new anti-inflammatory therapies for asthma has been less successful than was hoped and expected 3. Can’t we identify the responsible inflammatory targets? Should such targets be combined? Certainly, this cannot be excluded and deserves an even more intensive search. But, is it not frustrating to see our neighbour rheumatologists successfully testing and implementing one novel anti-inflammatory after the other 4? Of course, asthma is a complex disease, perhaps even more complex than arthritis. But what does that mean? If anything, that must be the key point. Complexity requires multi-dimensional approaches. Should we keep on addressing asthma as reductionists, or does the disease require a more integrative approach, by taking the elaborate dynamics of the organ and the organism into account rather than singling out molecular pathways? It seems that the puzzle of asthma demands the latter. Fortunately, we are moving on to …