The iatrogenic effect of successful ICS therapy on the progress of asthma research

This month’s issue features an editorial by Jeffrey Drazen, MD (J Allergy Clin Immunol 2012;129:1200-1201). Dr. Drazen presents the intriguing argument that our success in treating asthma with inhaled corticosteroids (ICS) has hampered significantly our ability to discern the complex, heterogeneous pathophysiology of the disease.

He briefly reviews for the reader the lengthy history of medicine’s attempts to understand and classify asthma, with reference to the JACI's 2011-2012 Asthma: Current Status and Future Directions series, which featured contributions from leaders in the field of asthma on topics such as asthma’s natural history and clinical presentation, gaps in diagnosis and treatment response, and new targets for therapy based on asthma genotypes. Dr. Drazen commends the efforts that have been made over the years, but notes that for all the research that’s been done, little true progress in early detection and prevention has resulted.

His argument is predicated on the observation that ICS efficacy for treating the inflammatory component of asthma is not specific to a single pathway and, thus, doesn’t inform the mechanisms of asthma biology. Notable work on anti-cytokine therapies for asthma is discussed, with the observation that its success has been less than expected. Drazen comments that these trials have demonstrated sensitive subgroups, but there are limited diagnostics available to identify them.

With a nod to a point raised in Stephen Holgate’s article in the JACI series (J Allergy Clin Immunol 2011;128:495-505), Dr. Drazen supports the idea that the immune dysfunction theory of asthma may need to be discarded in favor of focus on structural abnormality fundamental to the epithelium.

Drazen concludes by deflecting the idea that ICS therapy is the perfect treatment precisely because asthma is so heterogenous. He insists that understanding the specifics of asthma pathology and targeting those elements directly is the patient-centered mandate.