Chronic Inflammation. Chronic inflammation of the airways appears invariably to accompany the clinical syndrome of asthma. Inflammation seen in asthma is mainly located in the larger conducting airways, and although small airways can be affected in more severe forms of the disease, the lung parenchyma is not affected (Xxxxxx 2008). Asthmatic lungs typically show hyperinflation, mucus plugging in the airways, clusters of sloughed epithelial cells, and crystalline precipitates of eosinophil derived proteins (Renauld 2001). In asthma there is chronic inflammation of the respiratory tract, which is mediated by the increased expression of multiple inflammatory proteins, including cytokines, chemokines, adhesion molecules, inflammatory enzymes and receptors. In acute episodes or exacerbations the intensity of this inflammation increases (Xxxxxx 2008). Persistent inflammation in bronchial tissues, along with the ensuing activation of epithelial, subepithelial, and smooth muscle cells, presumably results in the structural changes known as airway remodelling (Xxxx et al. 2005). Chronic uncontrolled airways inflammation and airway remodelling remain the suggested mechanisms by which severe persistent asthma develops (Xxxx et al. 2005).
Chronic Inflammation. All cells of the airways, including eosinophils, T cells, mast cells, macrophages, and epithelial cells are involved in the chronic inflammation of asthma (82). Although eosinophilic inflammation plays a central role in the disease, it is not specific to asthma (83). Moreover, a sub-type of non-eosinophilic asthma has been described (84). The number of bronchial eosinophils has been associated with the severity of asthma (85). Eosinophils are potentially harmful in asthma through the release of highly toxic products (MBP, ECP, EDN and oxygen free radicals). The role of IL-5 in the observed eosinophilia in asthma is important: IL-5 regulates the development and differentiation of eosinophils, stimulates the release of eosinophils from the bone marrow into the peripheral circulation and is involved in the activation and survival of eosinophils (86). Interestingly, a study investigating the role of anti-IL-5 challenged the central place of eosinophils in asthma. In this study, a monoclonal antibody against IL-5 reduced the levels of eosinophils in blood and sputum of patients with asthma. However, it had no effect on early and late allergen response or airway hyperresponsiveness (87). Therefore, it may be questionable whether eosinophils and airway hyperresponsiveness are causally related in asthma. T cells are likely to play a role in controlling the chronic inflammation through the release of Th2-cytokines (88). The majority of T cells are CD4+ cells, whereas CD8+ cells are less frequently identified, even during exacerbations of asthma (89). The frequency of cytokine producing CD4+ and CD8+ cells is similar and is increased as compared with normals (90;91). Interestingly, following glucocorticoid withdrawal, eosinophils are elevated in all patients, whereas increases in airway T cells (both CD4+ and CD8+) were found in only those who developed an exacerbation (92). There is growing interest for the role of CD8+ T-cells in asthma. A cross-sectional relationship between CD8+ T-cells and the outcome of asthma has been observed in patients with fatal asthma (93). Furthermore, increased cytokine production of sputum CD8+ T-cells has been shown to be related with disease severity in patients with asthma (93). Antigen specific CD8+ T-cells in the lungs demonstrate a high cytotoxic activity and proliferate rapidly (94). These specific effector/memory T cells can be rapidly activated by antigens, like allergens and viruses (95). In the host response to virus infect...
