SELECTED ARTICLES FROM THE RECENT LITERATURE 2004

12/9/04

Drug development strategies in asthma

Summary
Background - The world-wide prevalence of asthma has been steadily increasing with attendant marked increase in economic burden (e.g., two-fold increases in annual asthma-related costs in the USA from 1990 to 1998). This increase, particularly in economically highly developed countries, has come in the face of what many investigators consider to be a greater number of effective anti-asthma medications.

Findings - A group of leading investigators of childhood asthma have commented about this situation. They pointed out that the current therapy of asthma is based on the concept that airway inflammation is the principle pathogenic event in asthma. However, with increasing duration of disease (particularly into adulthood) there are resultant pathology in the airways that is resistant to anti-inflammation approaches, particularly those treatments directed against individual mediators (e.g., anti-leukotriene drugs). Thus, symptoms may be reduced but asthma pathogenesis continues. Also, attempts to reverse the effects of Th2 immune type predominance (such as anti-IL4, anti-IL5 and anti-IgE therapies) have led to only relatively modest, if any, benefit in established asthma. Therefore, the authors urged a change in drug development approaches (and attitudes of drug licensing authorities) to try to halt the progression from acute to chronic asthma when the disease first manifests in childhood. Much of the data to support this approach is already in hand. What is needed is an informed debate about the relative risks vs potential benefits of this approach.

Reference
Nature Immunology 2004;7:695-698

Editor's Comments
These thoughtful, and sometimes provocative comments by seven highly experienced and regarded asthma investigators are worth serious consideration. Of course, a major challenge in trying to arrest the progression of asthma in early childhood is the fact that a sizable percentage of wheezing in pre-school age children will remit spontaneously by age 4-5 years although these children may be at risk for recurrence of asthma later in life. One would need a reliable marker in those wheezing young children which ones will progress to asthma (and would warrant the early intervention proposed by the authors).

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