Is there a problem with inhaled long-acting β-adrenergic agonists?

Short-acting β₂-agonists are effective in relieving acute symptoms of asthma and in the short-term prevention of symptoms from stimuli, such as exercise. They are ineffective when used on a regular schedule to improve asthma control. Long-acting β₂-agonists, on the other hand, provide sustained bronchodilation and improve asthma control. Regular use of long-acting β₂-agonists is not associated with significant tolerance to their bronchodilator action, impairment in the response to albuterol, decreased baseline pulmonary function, increased response to methacholine, or increased risk of adverse cardiac events. Case-control studies do not suggest an increased risk for death or intensive care unit admissions with use of long-acting β₂-agonists. In prospective studies in which there has been an increase in asthma deaths or serious asthma exacerbations, this increased risk has not been observed in subjects using inhaled corticosteroids. Where increased deaths have occurred in relation to either short- or long-acting β₂-agonists, the events have not occurred equally throughout the exposed population. This suggests that these outcomes were not a direct toxic effect of the drugs and increases the possibility that they resulted from an interaction between relief of symptoms by β₂-agonists and delay in seeking medical care.

Key words: Short-acting β-agonists, long-acting β-agonists, adverse reactions, asthma mortality, β-adrenergic receptor genotypes

Abbreviations used: ACRN, Asthma Clinical Research Network, BAL, Bronchoalveolar lavage, LABA, Long-acting β₂-adrenergic bronchodilator, OR, Odds ratio, PEF, Peak expiratory flow, RR, Relative risk, SMART, Salmeterol Multicenter Asthma Research Trial