Prospects for improved therapy in chronic obstructive pulmonary disease by the use of levalbuterol.

Abstract

Like asthma, chronic obstructive pulmonary disease (COPD) is a chronic disease, the most prominent symptom of which is airway obstruction. Airway inflammation may be pathogenomic in both diseases, but only in COPD does inflammation predominate as a determinant of symptoms to make obstruction largely refractory to treatment. Despite a more limited degree of reversibility than in asthma, beta(2 )-agonists are used extensively to reduce airway obstruction and to achieve symptomatic improvement, with racemic albuterol being widely favored. In asthma, bronchodilation and bronchoprotection largely account for symptomatic benefit. In COPD, the capacity of racemic albuterol to ameliorate these symptoms is more limited and suppression of edema and of infiltration and activation of leukocytes acquire greater significance. During regular use of racemic albuterol in asthma, bronchoprotection diminishes progressively as hyperresponsiveness becomes increasingly pronounced, a process that is associated with an infiltration and activation of eosinophils. These paradoxic effects of racemic albuterol may be attributed to pharmacologic actions of the distomer, (S)-albuterol. As would be expected, homochiral (R)-albuterol (levalbuterol) is more potent and effective in asthma and may have significant advantages if used in COPD. A substantial (4-8-fold) reduction in the dose of levalbuterol anticipates lesser side effects and diminished risk in patients with cardiovascular disease. Additionally, the increased potency and duration of bronchodilation observed in asthma may extend to COPD. Finally, removal of the proinflammatory actions of (S)-albuterol may eliminate the persisting obstruction and decrease elastance that are associated with enhanced inflammation and may allow levalbuterol to suppress edema and diminish leukocyte activation more effectively.