Lack of subsensitivity to albuterol after treatment with salmeterol in patients with asthma

The development of tolerance to the bronchodilator effects of beta(2)-agoni sts used in asthma therapy has been the subject of debate. We conducted two placebo-controlled crossover studies to assess the bronchodilator response to a short-acting beta(2)-agonist before and after chronic therapy with sa lmeterol. Patients in one study were corticosteroid-naive; patients in the other study were using inhaled corticosteroids. Changes in FEV1 after cumul ative doubling doses of inhaled albuterol were assessed after a 2-wk beta-a gonist washout period, before administering study medication on Day 1, and again after 28 d of therapy. Ipratropium bromide was provided as rapid-reli ef treatment for asthma, and use of any beta(2)-agonist except the study tr eatment was prohibited. On both assessment days for salmeterol, and during placebo administration periods, significant increases from predose FEV1 val ues were observed beginning with the lowest dose of albuterol and continuin g throughout the dose-response assessment (p less than or equal to 0.001). These increases in FEV1 were maintained for 6 h after the last dose of albu terol (p < 0.05). There were no statistically significant differences in th e albuterol dose response following salmeterol or placebo. These studies in dicate that irrespective of concurrent corticosteroid treatment, chronic th erapy with salmeterol does not result in tolerance to the bronchodilator ef fects of albuterol.