Treating Asthma as an Inflammatory Disease: The Role of ICS in Treating Asthma

Treating Asthma as an Inflammatory Disease: The Role of ICS in Treating AsthmaMyofibroblasts are thought to play a central role in remodeling by propagating and amplifying signals from the bronchial epithelium into the deeper layers of the submucosa through release of soluble mediators. Myofibroblasts are classically characterized by the presence of filaments of a smooth-muscle actin. Local fibroblasts are the most likely progenitors of myofibroblasts, although it has been proposed that myofibroblasts are derived from peripheral blood-derived progenitors known as fibrocytes. Airway myofibroblasts and smooth muscle lie in close proximity, and numbers of myofibroblast-like cells are increased in the lamina reticularis of asthmatic patients after allergen challenge. The phenotype of the myofibroblast is intermediate between the fibroblast and the smooth-muscle cell, and it is thought that myofibroblasts might contribute directly to increased smooth-muscle mass. Both fibroblast and myofibroblast numbers have been shown to increase when subjects are challenged with antigen (Fig 3).

Similarly, airway smooth-muscle cells in culture have been shown to proliferate significantly faster in patients with asthma than those from control subjects (Fig 4), although this has not been shown in vivo. In cartilaginous airways, patients who have died from asthma also have greater total wall, inner wall, outer wall, smooth-muscle, mucus gland, and cartilage areas in their airways than those of patients with and those without asthma dying suddenly of nonrespiratory causes (p < 0.05).
A study of human lung fibroblasts suggests that interleukin (IL)-4 and IL-13 are involved in activating different subsets of lung fibroblasts in the pathogenesis of asthma and also in the remodeling processes.

It is now believed that remodeling may occur earlier in the disease process than originally thought, and preliminary data indicate that early use of antiinflammatory therapy might limit airway remodeling. Evidence suggests that ICS may reduce subepithelial collagen deposition in asthma and decrease the differentiation of fibroblasts to myofibroblasts.
Inflammation is hypothesized to be an early and persistent component of asthma. Consequently, therapy to suppress inflammation must be used in the long term. Evidence suggests that early intervention with antiinflammatory therapy may modify the disease process, and corticosteroids are considered the most potent and consistently effective long-term control medication for asthma. Even in intermittent asthma, inflammation is always present, suggesting that treatment with ICS should be continuous to be most effective.


Figure 3. Change in cell numbers in biopsies from patients challenged with diluent or allergen.


Figure 4. Airway smooth-muscle cell proliferation is increased in asthma. Cell numbers from patients with asthma (n = 12) were significantly increased at days 3, 5, and 7 compared with those from nonasthmatic patients (n = 10; p < 0.05). Reproduced with permission.

This entry was posted in Asthma and tagged allergic rhinitis, asthma, corticosteroids, inflammation, remodeling.