Oral vs inhaled asthma therapy. Pros, cons and combinations

A number of oral and inhaled drugs are available for the long term management of patients with persistent asthma, yet the disease continues to be associated with significant morbidity and mortality. Over the past years, inhaled glucocorticoids have become established as a cornerstone of maintenance therapy because of their demonstrated clinical efficacy, ability to reduce bronchial inflammation and good tolerability. Other inhaled drugs (e.g. sodium cromoglycate, nedocromil, long-acting beta 2 agonists) also play a role in the long term treatment of patients with asthma. However, many patients (especially children and the elderly) find inhalers difficult to use, and poor inhalation technique can affect the amount of drug reaching the lungs and response to therapy. Oral drug administration is simple, but, until recently, oral asthma therapy has primarily consisted of sustained-release theophylline and glucocorticoids. Theophylline has a narrow therapeutic index, necessitating regular monitoring of serum drug concentrations, and long term oral glucocorticoid therapy is associated with potentially serious adverse events including osteoporosis with bone fracture. The recent development of orally administered leukotriene receptor antagonists (e.g. zafirlukast) and 5-lipoxygenase inhibitors (e.g. zileuton) offers novel mechanisms of action and potential solutions to compliance issues associated with regular administration of inhaled asthma therapy. These drugs have demonstrated efficacy as maintenance therapy in patients with asthma and, importantly, lack the adverse effects associated with long term systemic glucocorticoid therapy. Further clinical trials and the increasing use of these new therapies will help to establish the precise role of orally administered leukotriene receptor antagonists and 5-lipoxygenase inhibitors in the long term management of patients with asthma.