Bronchodilator response to albuterol after regular formoterol and effects of acute corticosteroid administration

Background: There is controversy about the development of bronchodilator subsensitivity after regular administration of long-acting beta(2)-agonists. Objectives: The purpose of the stud, was to evaluate whether regular treatment with formoterol affects the bronchodilator response to repeated puffs of albuterol, and also to assess the effects of acute administration of a bolus dose of IV or inhaled corticosteroid. Materials and methods: Twelve patients (mean [SD] age, 43 [15] years; FEV1, 57[17]% predicted) with stable, moderate to severe persistent asthma who were all taking inhaled corticosteroids were evaluated in a randomized, placebo-controlled, double-blind, double-dummy, crossover study. Patients received treatments each for 2 necks followed by a bolus (IV/inhaled) of corticosteroid or placebo: (1) placebo inhaler bid + bolus placebo: (2) formoterol Turbuhaler 24 mu g metered dosage bid (delivered dosage IS mu g bid) + placebo; (3) formoterol 24 lug bid + bolus IV hydrocortisone, 200 mg; or (4) formoterol 24 mu g bid + bolus inhaled budesonide, I,BOO pg. Bronchodilator response to repeated puffs of albuterol (200 to 1,600 mu g) for > 80 min was measured at 2 h after bolus administration of placebo or corticosteroid. The study. was powered at the 80% level to detect a 20% difference in area under curve between 20 and 80 min (AUC) for FEV1 response to albuterol as change from baseline (primary end point). Results: There was significant subsensitivity (p = 0.01) of the mean albuterol FEV1 response (as AUC, L x s) after formoterol alone (737) as compared to placebo (1,453) along with partial reversal by steroid administration: formoterol + hydrocortisone (1,050), and formoterol + budesonide (942). There was a similar pattern of subsensitivity (p = 0.03) for the mean albuterol forced expiratory flow between 25% and 75% of vital capacity response (as AUC, L): placebo (2,149), formoterol alone (1,002), formoterol + hydrocortisone (1,402), and formoterol + budesonide (1,271). Conclusion: Regular treatment with formoterol produced significant bronchodilator subsensitivity to repeated puffs of albuterol, which was partially reversed by a bolus dose of systemic or inhaled corticosteroid.