Asthma: a simple concept but in reality a complex disease
Version of Record online: 26 MAY 2011
© 2011 The Author. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation
European Journal of Clinical Investigation
Volume 41, Issue 12, pages 1339–1352, December 2011
How to Cite
Holgate, S. T. (2011), Asthma: a simple concept but in reality a complex disease. European Journal of Clinical Investigation, 41: 1339–1352. doi: 10.1111/j.1365-2362.2011.02534.x
- Issue online: 16 NOV 2011
- Version of Record online: 26 MAY 2011
- Received 20 June 2010; accepted 30 March 2011
- Allergic inflammation;
- stratified medicine;
Eur J Clin Invest 2011; 41 (12): 1339–1352
Background Asthma is a disorder of the conducting airways that contract too easily and too much to cause variable airflow obstruction with symptoms of wheeze, cough, chest tightness and shortness of breath. Based on this knowledge, initial treatments were directed to dilating the contracted airways with anticholinergic and adrenergic drugs. The recognition that allergic-type inflammation underlay the hyperresponsive airways in asthma led to the introduction of anti-inflammatory drugs such as sodium cromoglicate and corticosteroids. Over the 2 decades that followed, these drugs have been progressively improved by increasing their therapeutic index and duration of action.
Methods A review of the recent literature indicates that since the 1980s, the explosive increase in knowledge of the cell and mediator mechanisms of asthma has only led to modest improvements in therapy including the introduction of leukotriene modifiers and a blocking monoclonal antibody against IgE. Indeed, biologics targeting allergic cytokines and effector cells have on the whole proven disappointing despite initial promise being shown in animal models.
Results Part of the difficulty lies in the oversimplified concept that asthma is only driven by allergic processes when in reality there are many environmental causes and triggers and the view that it is a homogeneous disorder only varying in severity.
Conclusions The more recent views that asthma is a complex disorder made up of different subtypes with differing causes, treatment responses and natural histories creates a new opportunity for stratified medicine in which therapies acting upstream selectively target specific disease subtypes identified by specific diagnostic biomarkers.