Aerosolized corticosteroid

In rat asthma models, aerosolized corticosteroid inhibits all the structural changes induced by repeated allergen challenge, including increase of ASM mass, but does not reverse established change. Whether there is an additional benefit of the combination of ICS and long-acting adrenoreceptor agonist has not been proven in airway remodeling, with the exception Sublingual Cialis of the reported improvement of vascular remodeling. ICS is reported to reduce bronchial vascular remodeling in patients with COPD.

Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are lipid mediators synthesized from arachidonic acid. Montelukast has been shown to inhibit the increase of ASM mass, goblet cell metaplasia, and epithelial cell hyperplasia in a rat model of allergic asthma. Exogenous administration of LTD4 reproduces these effects. Montelukast inhibits but also reverses the increase of ASM mass and subepithelial fibrosis in a mouse asthma model. No studies of the effect of leukotriene modifiers have been performed in human subjects with respect to airway remodeling.

Somewhat surprisingly, tiotropium, a long-acting muscarinic receptor antagonist, inhibited the increase of ASM mass and goblet cell metaplasia in allergen-challenged guinea pigs and mice. In animal COPD models, tiotropium has been shown to inhibit goblet cell metaplasia, mucin production, and vascular remodeling but to have no effect on airspace enlargement. Although bronchoconstriction per se may release growth-promoting molecules from airway epithelium, it is not clear whether the effects of tiotropium are mediated by affecting airway mechanics or through predominantly biochemical processes. The effect of tiotropium on airway remodeling has not been evaluated in human subjects.

T helper (Th) lymphocytes are present in airways of patients with asthma and synthesize and release the signature cytokines IL-4, IL-5, and IL-13. They modulate the airway inflammatory response, causing eosinophilia, enhancing IgE synthesis, and promoting airway hyperresponsiveness. Animal experiments have implicated IL-13 in goblet cell metaplasia and subepithelial collagen deposition using IL-13-deficient mice and by administration of IL-13 itself or of molecules neutralizing its effects. IL-13 causes up-regulation of contractile processes in ASMC but may not influence ASM mass. However, clinical trials have shown little or no effect of anti-IL-13 antibody therapy on lung function, which may or may not be a suitable surrogate for airway remodeling.