Treatments in Respiratory Medicine

, Volume 3, Issue 5, pp 279–289 | Cite as

Combination Therapy of Long-Acting β2-Adrenoceptor Agonists and Corticosteroids for Asthma

Leading Article

Abstract

Twice-daily combination therapy of inhaled corticosteroids and long-acting β2-adrenoceptor agonists (LABA) is now established as a most effective treatment for moderate to severe asthma and is available in a combined single inhaler. The benefits of combination therapy include better day-to-day control and a reduction in exacerbations compared with monotherapy with inhaled corticosteroids at a lower dose.

Total control of asthma, defined as no daytime or night-time symptoms, no use of rescue β2-adrenoceptor agonists (β2-agonists), no exacerbations and a peak flow rate of >80% predicted, may be achieved with the use of combined salmeterol/fluticasone in up to 41% of patients with moderate to severe asthma, compared with only 28% of patients treated with fluticasone alone. Adjustable maintenance dosing with budesonide/formoterol may provide better control when compared with fixed-dosing combination regimens. Other therapies combining effectively with inhaled corticosteroids include slow-release theophylline and leukotriene inhibitors, montelukast and zafirlukast, but LABA are the most efficacious.

Molecular interactions between corticosteroids and β2-adrenoceptors may underlie the clinical added benefits of combination therapy. Corticosteroids may increase the number of β2-adrenoceptors and their coupling with Gs proteins, while β2-agonists may induce glucocorticoid receptor nuclear translocation, activate transcription factor/enhancer binding protein C/EBPα together with corticosteroids, or phosphorylate corticosteroid receptors. The combination of corticosteroids and LABA potentiates inhibition of interleukin-8 and eotaxin release from human airway smooth muscle cells and granulocyte-macrophage colony-stimulating factor release from epithelial cells, and also the inhibition of airway smooth muscle cell proliferation.

It is important to determine whether there is a potentiating effect of combination therapy compared with corticosteroid treatment alone on airway inflammation and airway wall remodelling. Improvements in combination therapy include a once-daily preparation and possible combination of inhaled corticosteroids with newer drugs such as phosphodiesterase IV inhibitors.

Notes

Acknowledgment

No external source of funding or assistance was obtained for the preparation or writing of this review. Both authors have received funding from various pharmaceutical companies to research into the clinical effects of the compounds reviewed in this article.

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© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Imperial CollegeNational Heart and Lung InstituteLondonUK
  2. 2.Royal Brompton HospitalLondonUK

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