LONG TERM EFFECTS OF A LONG-ACTING B2-ADRENORECEPTOR AGONIST, SALMETEROL, ON AIRWAY HYPERRESPONSWENESS IN PATIENTS WITH MILD ASTHMA
Purpose of the Study. To investigate long term effects of long-acting β2 agonist (salmeterol) on bronchodilation and bronchoconstriction caused by methacholine (MCH). Study Population. Twenty-four adult asthmatics (average age 25, range 19-36 yrs) who had not required any regular medication for 6 months. Methods. Parallel double blind study where either salmeterol 50 µg twice daily or placebo was administered during an 8-week trial. A complete dose response curve for MCH was recorded on days 0, 28, 56, and 2 and 4 days after the study ended. The PC20 (concentration required for 20% drop in FEV1) was recorded. Albuterol in an aggregate dose of 400 µg/day was allowed as rescue medication. Findings. Salmeterol caused a significant increase in FEV1 which did not change throughout the study. On the first treatment day salmeterol afforded protection against bronchoconstriction with 10-fold increase in PC20. After 4 and 8 weeks of therapy the change in PC20 returned to baseline after 4 days of washout. Reviewer's Comments. The regular use of long-acting beta agonist leads to tolerance to its protective effect against a bronchoconstrictor stimulus, although bronchodilator properties remain unchanged. Although the mechanism is unknown, this data suggests that long-term monotherapy with beta agonist may not be optimal.