Long-acting beta2 agonists in the management of stable chronic obstructive pulmonary disease

Long-acting beta2 agonist bronchodilators (e.g. formoterol, salmeterol) are a new interesting therapeutic option for patients with chronic obstructive pulmonary disease (COPD). In the short term, both salmeterol and formoterol appear to be more effective than short-acting beta2 agonists, and in patients with stable COPD they are more effective than anticholinergic agents and theophylline. Regular treatment of patients with COPD with long-acting beta2 agonists can induce an improvement in the respiratory function and certain aspects of quality of life. Moreover, salmeterol seems to be better than ipratropium and theophylline in improving lung function at the recommended doses after a long term treatment. Use of combination therapy of a long-acting inhaled beta2 agonist and an anticholinergic agent or theophylline in patients with COPD has not been sufficiently studied. Combination of usual doses of ipratropium or oxitropium with usual doses of salmeterol or formoterol does not appear to improve pulmonary function, but this lack of improvement with the combination should not, in itself, prevent implementation of further therapeutic steps in patients responsive to an anticholinergic agent and/or salmeterol or formoterol administered singly. Neither formoterol nor salmeterol elicit significant cardiovascular effects in healthy individuals and patients with reversible airway obstruction. However, adverse cardiac events might occur in patients with COPD with pre-existing cardiac arrhythmias and hypoxaemia if they use long-acting 12 agonists, although the recommended single dose of salmeterol 50 microg or formoterol 12 microg ensures a relatively higher safety margin than formoterol 24 microg. The bronchodilatory effect of long-acting beta2 agonists seems to be fairly stable after regular treatment with these bronchodilators. Moreover, pre-treatment with a conventional dose of formoterol or salmeterol does not preclude the possibility of inducing further bronchodilation with salbutamol in patients with partially reversible COPD. All these findings support the use of long-acting beta2 agonist bronchodilators as first-line bronchodilator therapy for the long term treatment of airflow obstruction in patients with COPD. However, since physicians must always choose a drug that is highly efficacious, well tolerated and inexpensive, the cost-effectiveness analysis in relation to other bronchodilators will determine the proper place of long-acting beta2 agonists in the long term therapy of stable COPD.