New Directions in Therapy for Chronic Asthma
Theophylline, β-agonists, cromolyn sodium, and steroids are the mainstays of therapy for chronic asthma. Alternative treatment modalities for chronic asthma such as methotrexate, troleandomycin, and gold have been only partially successful, and the morbidity and mortality from asthma have been increasing despite the advent of these therapies. As such, several additional modes of treatment for chronic asthma are under investigation. The rationale for these therapies is based on the current knowledge of the pathogenesis of asthma. Inflammation and hyperresponsive-ness of the airways are the hallmark features of chronic asthma. These entities are believed to result from a complex interaction among inflammatory, structural, and neuronal cells and their soluble mediators in the airway. Many of the novel therapeutic agents for asthma under development target the actions of select cell types or their mediators, whereas the precise mechanism of action of other agents remains unknown. In this article, we review the rationale for and potential clinical efficacy of selected newer asthma therapies. We also discuss the information currently available regarding the clinical use of leukotriene antagonists, platelet-activating factor antagonists, the immunosuppressants cyclosporin A and FK-506, and loop diuretics. Finally, strategies using modulators of neuronal stimulation, potassium channel openers, phosphodiesterase isoenzyme inhibitors, and antiadhesion molecule antibodies in the therapy of chronic asthma are discussed.