Asthma: a simple concept but in reality a complex disease
Asthma: a simple concept but in reality a complex disease
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.
allergic inflammation, asthma, history, stratified medicine, treatment
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
26 May 2011
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Abstract
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.
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Published date: 26 May 2011
Keywords:
allergic inflammation, asthma, history, stratified medicine, treatment
Organisations:
Clinical & Experimental Sciences
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Local EPrints ID: 194671
URI: http://eprints.soton.ac.uk/id/eprint/194671
ISSN: 0014-2972
PURE UUID: 0cd30ad2-d6c0-48fc-8339-912703e38410
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Date deposited: 09 Aug 2011 13:24
Last modified: 14 Mar 2024 04:00
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