Sustained bronchoprotection, bronchodilatation, and symptom control duringregular formoterol use in asthma of moderate or greater severity

Background: Recent studies have raised concern that regular inhalation of b eta(2)-agonists may cause a worsening of asthma control compared with on-de mand dosing regimens. Objective: The objective of this study was to compare the effect of twice d aily formoterol (Foradil), 4 times daily albuterol, and on-demand albuterol on bronchial hyperresponsiveness (BHR), lung function measurements, sympto ms, and other indicators of disease control over 6 months in patients with asthma of moderate or greater severity receiving concomitant inhaled cortic osteroids, We also looked for occurrence of rebound BHR on discontinuation of treatment. Methods: This was a multicenter, parallel-group, double-blind, clinical tri al. Methacholine PC20 was the primary outcome variable. Other outcome varia bles included symptom scores, use of rescue medication, morning peak expira tory flow (PEF), serial FEV1 measurements, and asthma exacerbations, Results: Of the 271 randomized patients, 217 completed the study. Formotero l was significantly superior to on-demand albuterol with regard to methacho line PC20, FEV1, PEF, symptom scores, and use of rescue medication at each measured time point/interval, Regular albuterol was superior to on demand a lbuterol with regard to PC20 and FEV1, but not PEF or various clinical scor es. After a small drop in the magnitude of bronchoprotection and bronchodil atation occurring shortly after randomization, there was no evidence of pro gressive tolerance to either regular treatment for any of the measured vari ables or of rebound increase in BHR 2 days after the end of treatment. The formoterol group had the lowest number of exacerbation days, as defined by high intake of rescue bronchodilator and/or symptom scores, whereas the num ber of exacerbations requiring increased corticosteroid coverage was simila r in the 3 groups. Conclusion: In patients with asthma of moderate or greater severity receivi ng inhaled corticosteroids, formoterol taken twice daily resulted in superi or bronchoprotection, bronchodilatation, and clinical control compared with on-demand albuterol over 6 months. Four times daily albuterol was superior to on-demand albuterol for only some of the end paints, Progressive tolera nce and a rebound increase in BHR on discontinuation of beta-agonists were not found.