Pathophysiology of Bronchial Asthma
The pathophysiology of bronchial asthma is categorized by three different but connected entities – chronic inflammation, smooth muscle dysfunction and remodeling of the airways. Accordingly, the treatment of bronchial asthma should take into account the presence of these three entities and the fact that the disease is associated with short-lived symptoms that can be prevented or reversed by bronchodilators. Another important factor is that asthma is characterized by the presence of exacerbations that can be treated or reversed by anti-inflammatory drugs, and the presence of airway remodeling has to be considered in order for the identification of an appropriate treatment aimed at the prevention of its development.
Owing to their well-known anti-inflammatory properties, inhaled corticosteroids (ICS) are considered by current management guidelines as a first-line treatment. However, optimal control of the disease may be achieved by the addition of long-acting β2-agonists (LABAs) to the ICS treatment. Moreover, the use of the leukotriene receptor antagonists (LTRAs) has been relatively licensed as first-line monotherapy or as add-on therapy in patients whose asthma is uncontrolled by ICS. Finally, anticholinergic, xantines, and anti immunoglobin E (IgE) agents are used in the therapy of asthma, and new strategies, including the use of anti-tumour necrosis factor agents, are currently under evaluation.
Several studies have demonstrated the down regulatory effect exerted by ICS on many inflammatory cells and mediators within the airways of patients with asthma. The number of mast cells, macrophages, eosinophils, and T-lymphocytes is significantly reduced in bronchial biopsies from asthmatic patients after ICS treatment – this reduction is related to the ICS-mediated inhibition of the cytokines responsible for their recruitment from the blood circulation and for their activation.
LABAs are currently used in combination with ICS to provide further relief of airway obstruction and the prevention of asthma exacerbations. They exert a significant bronchodilatatory effect by the direct stimulation of β2-receptors on airway smooth muscles, which leads to relaxation. These receptors are present on the smooth muscle of all airways from the trachea to the terminal bronchioles.
It is widely accepted that the combined administration of ICS and LABAs may target complementary aspects of asthma pathophysiology. It has been shown that LABAs, other than exerting effects on ASMs, are able to balance the effects of ICS on inflammatory cells and mediators. In this regard, LABAs have a direct influence on ICS action by exerting an effect on glucocorticoid receptors (GR), by priming GR for ensuing steroid binding and by promoting the translocation of the GR–steroid complex from the cytosol into the nucleus.
Although the precise mechanism of the action of ICS and of many other drugs used in the asthma therapy is not completely known, in recent decades the management of the treatment of asthmatic patients has been successfully improved. This has been possible because the cellular and molecular mechanisms involved in the bronchial inflammation have been studied and characterized. Many drugs are now available to interact with these mechanisms in order to provide the asthmatic patient with a better quality of life. This goal can be achieved only by the multifaceted approach to the therapy of bronchial asthma.