Clinical StudiesEffects of Treatment with Formoterol on Bronchoprotection against Methacholine
Section snippets
Patients
We studied patients between the ages of 16 and 65 years who had a diagnosis of asthma with minimum duration of 6 months according to American Thoracic Society criteria (6) and a forced expiratory volume in 1 second (FEV1) equal to or greater than 60% of predicted normal value. In all subjects, the provocative dose of methacholine that caused a 20% fall in FEV1 (PD20) was ≤1000 μg, and there was at least a fourfold increase in PD20 1 hour after inhaling 24 μg of formoterol from a dry powder
Results
A total of 72 subjects were enrolled into the study, of whom 67 completed the full protocol. Characteristics of the subjects who completed the study are summarized in Table 1. The geometric mean baseline unprotected PD20 after the initial run-in, before randomization (at visit 2), was 60 μg.
Discussion
This study of the development of tachyphylaxis with long-acting β2-agonists has three key findings. First, we found that the degree of protection after 14 days was not dependent upon the total daily dose of formoterol, when comparing 6 μg and 24 μg twice daily. Second, the degree of tachyphylaxis occurred to a comparable degree with once-daily and twice-daily administration of formoterol. Third, the residual degree of protection with formoterol was comparable to that observed with terbutaline.
Acknowledgements
The authors wish to acknowledge the technical assistance of C. L. Bromly (Newcastle), Y. Gnosspelius, and P. Larsson (Astra Draco AB, Sweden) for advice on study design and statistical analysis, G. Hamer (Astra Clinical Research Unit, Edinburgh) for monitoring the study, and for the grant support from Astra Draco.
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