Xanthines--symptomatic or prophylactic in asthma?

Perhaps xanthines should not be classified as bronchodilators because their clinical efficacy may reflect their antiinflammatory properties more than smooth muscle relaxation. Xanthines inhibit late phase airway reactions induced by allergen or chemical sensitizers. But, they offer little protection against methacholine-, histamine, or allergen-induced immediate bronchoconstriction and any protection seen is unrelated to the extent of the initial bronchodilatation. The antiinflammatory effects of xanthines include stabilization of a variety of inflammatory cells that are present in asthmatic airways. Another potentially important effect is the increase in number, and activity, of "suppressor" T-lymphocytes. Xanthines may also stabilize the barrier functions of both the airway epithelium and the airway microvessel (venular) wall. As a result less cellular and plasma-derived mediators are released, less plasma is exuded into the airway wall and less plasma enters the airway lumen. Penetration of inhaled macromolecules across the epithelium and into the airway wall may also be reduced. Future prospects for xanthines are interesting. A novel xanthine which lacks adenosine antagonist activity, enprofylline, has been shown to exert potent antiasthma actions without producing several of the excitatory, extrapulmonary, theophylline-like effects. We are only now starting to learn how xanthines actually work in the inflamed asthmatic and bronchitic airway. Nevertheless, the currently available data show that xanthines are likely to be more prophylactic than symptomatic in the treatment of asthma and chronic obstructive airway disease.