Effects of Inhaled Corticosteroids, Leukotriene Receptor Antagonists, or Both, Plus Long-Acting β2-Agonists on Asthma Pathophysiology: A Review of the Evidence

Chronic inflammation and smooth muscle dysfunction are consistent features of asthma, and are responsible for disease progression and airway remodelling. The development of chronic airway inflammation depends upon the recruitment and activation of inflammatory cells and the subsequent release of inflammatory mediators, including cytokines. Cellular and histological evaluation of drugs with anti-inflammatory activity, such as inhaled corticosteroids (ICSs), is achieved by analysing samples of lung tissue or biological fluids, obtained by techniques such as bronchial biopsy, bronchoalveolar lavage and sputum induction. These provide valuable information on the inflammatory processes occurring in the lung, although not all are equal in value. The beneficial effects of ICSs in asthma treatment are a consequence of their potent and broad anti-inflammatory properties. Furthermore, there have been promising results indicating that ICSs can reverse some of the structural changes that contribute to airway remodelling. Long-acting β2-agonists (LABAs) added to ICSs provide greater clinical efficacy than ICSs alone, suggesting the possibility of complementary activity on the pathophysiological mechanisms of asthma: inflammation and smooth muscle dysfunction. Leukotrienes play a part in the pathogenesis of asthma. Leukotriene receptor antagonists (LTRAs) directly inhibit bronchoconstriction and may have some anti-inflammatory effects, although the extent to which inhibiting one set of inflammatory mediators attenuates the inflammatory response is questionable. In concert with their effect on a broad variety of inflammatory mediators and cells, treatment with ICSs (including ICSs and LABAs) results in superior control of the pathophysiology of asthma and superior clinical efficacy as assessed by the greater improvements in pulmonary function and overall control of asthma compared with LTRAs.