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Copyright ©ERS Journals Ltd 2002
Scientific rationale for inhaled combination therapy with long-acting ß2-agonists and corticosteroids
National Heart and Lung Institute, Imperial College, London, UK
CORRESPONDENCE: P.J. Barnes, Dept of Thoracic Medicine, National Heart & Lung Institute, Imperial College, Dovehouse Street, London, SW3 6LY, UK. Fax: 44 2073515675
Keywords: asthma, budesonide, fluticasone propionate, formoterol, salmeterol
Received: September 27, 2001
Accepted October 2, 2001
Abstract
The addition of an inhaled long-acting ß2-agonist (LABA) to an inhaled corticosteroid (ICS) gives optimal control of asthma in most patients and two fixed combination inhalers (salmeterol/fluticasone and formoterol/budesonide) are increasingly used as a convenient controller in patients with persistent asthma. There is a strong scientific rationale for the combination of these two drug classes.
ICS suppress the chronic inflammation of asthma and reduce airway hyperresponsiveness and this is achieved at low doses in most patients. LABA act on different aspects of the pathophysiology of asthma. In addition to their bronchodilator action, LABA also inhibit mast cell mediator release, plasma exudation and may reduce sensory nerve activation. Thus these two classes of drug address complementary aspects of the pathophysiology of asthma that neither drug class is able to achieve alone.
There are several positive interactions between LABA and ICS. Corticosteroids increase the expression of ß2-receptors by increasing gene transcription. Experimentally this protects against the loss of ß2-receptors in response to long-term exposure to ß2-agonists. While this is unlikely to be important in bronchodilator responses to ß2-agonists, in view of the large ß-receptor reserve, it is probably important in preventing loss of ß-agonist effects on the nonbronchodilator actions of LABA discussed earlier. ß2-Agonists may potentiate the molecular mechanism of corticosteroid actions, with increased nuclear localization of glucocorticoid receptors and additive or sometimes synergistic suppression of inflammatory mediator release. Thus LABA and ICS may optimize each others beneficial actions in the airways, but the low systemic effects of these drugs do not result in any increase in adverse effects.
Long-acting ß2-agonists corticosteroid inhaler therapy is therefore a logical advance and results in effective control of asthma in the majority of patients without significant adverse effects. This simplified approach to long-term asthma therapy has a strong scientific rationale.
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