The mean baseline FEV1values were very similar on the three test days (2.93 L ± 1.0 SD, 2.99 L ± 1.0 SD, and 3.02 L ± 1.1 SD for placebo, fenoterol 0.4 mg and fenoterol 0.8 mg, respectively). With both fenoterol doses, increases in FEV1 over baseline were (bund before each of the exercise runs, ie, ten minutes, two hours, and four hours alter administration.
Bronchodilation after each dose of fenoterol as measured by mean percentage increases in FEV1 remained at approximately the same level before each of the three exercise periods (Fig 1 and Table 1) and was significantly different from placebo at all test intervals. No significant differences were found between the bronchodilating effects of the two fenoterol doses (Table 1). Changes in FEFt followed the same pattern.
Exercise-induced decreases in FEV1 remained constant throughout the placebo day, averaging 25 percent to 28 percent (Fig 1, Table 2). Pretreatment with both doses of fenoterol resulted in significantly (p <0.001) smaller exercise-induced decreases in FEV1 than with placebo ten minutes and two hours after administration; at four hours, the difference was no longer significant. There was no significant difference at any of the three test intervals between fenoterol 0.4 mg and 0.8 mg in terms of the extent to which they suppressed exercise-induced bronchospasm.
The degrees of protection obtained from 0.4 mg fenoterol was 87 percent, 56 percent, and 23 percent at ten minutes, two hours, and four hours, respectively, while the corresponding figures for the 0.8 mg dose were 88 percent, 54 percent, and 37 percent. At none of the test intervals was the difference between the two doses statistically significant.
The EIA was completely prevented by fenoterol 0.4 mg in nine (75 percent) patients and by fenoterol 0.8 mg in ten (83 percent) patients. Six patients treated with fenoterol 0.4 mg and eight treated with 0.8 mg still had complete protection two hours after medication.
Decreases in FEF after the exercise runs were similarly affected, both doses of fenoterol proving significantly superior to placebo at ten minutes and two hours but not at four hours. There was no significant difference between the protective effects of the two doses of fenoterol at any point.
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Side Effects
One patient complained of nervousness after fenoterol 0.4 mg, and two patients had side effects after fenoterol 0.8 mg (shakiness, weakness). There were no significant changes in pulse rate or blood pressure after administration of the drugs.
Discussion
The results of the present study show that doubling the dose of inhaled fenoterol produced little additional benefit in protecting from EIA, both in terms of the magnitude of the immediate effect or the duration of the effect. There were a few patients who were protected better or longer by 0.8 mg, but in the majority, the usual dose of two whiffs (0.4 mg) was adequate.
Our results agree with those of Anderson and associates who found the duration of the EIA-suppres-sive effect of inhaled fenoterol to be less than four hours. The duration of action of two to four hours compares favorably with that of metaproterenol, which is approximately one to three hours, but is less than the duration of the bronchodilator effect. Eggleston and McMahan observed significant protection from EIA for at least five hours with fenoterol tablets (10 mg), but the effect probably does not set in until about one hour after administration. Moreover, the incidence of side effects tends to be lower when the drug is given by inhalation.
Individuals exercising for many hours should not take a large prophylactic dose of beta-2 agonist since an increased dose, as we have shown, is unlikely to prolong or augment the effect. In case of more prolonged continuous exercise, the bronchodilator may be used again after three hours if the protective effect of the pre-exercise dose has subsided by that time.
Table 1—Percentage BronchodUation in FEV, (Before Exercise)
| Time After administration | 10 Min | 2 Hr | 4 Hr | |
| Fenoterol, 0.8 mg | 32.7±38.1 | 43.3±51.6 | 35.1 ±47.4 | |
| Fenoterol, 0.4 mg | 22.8 ±17.1 | 28.5±24.7 | 23.0±34.4 | |
| Placebo | -3.5 ±10.6 | 5.7 ±27.3 | 3.4±24.1 | |
| 0.8 mg | ||||
| Significance | vs | .005>p>0.0005 | .01>p>.005 | .025>p>.01 |
| placebo | ||||
| of | ||||
| 0.4 mg | ||||
| Differences, | vs | .005>p>.0005 | .005>p>.0005 | .05>p>.025 |
| placebo | ||||
| 0.8 mg | ||||
| vs | ||||
| 0.4 mg | NS | NS | NS | |
Table 2—Exercise-Induced Asthma: Percentage of Fall in FEV
| Run 1 | Run 2 | Run 3 | |
| Fenoterol, | |||
| 0.8 mg | 2.5± 13.0 | 11.1 ±13.3 | 17.6±9.5 |
| Fenoterol | |||
| 0.4 mg | 4.3 ±10.1 | 12.9± 13.3 | 21.0± 15.4 |
| Placebo | 27.8 ±14.9 | 25.0± 18.2 | 25.2± 12.9 |
| Significance | 0.8 mg vs | 0.8 mg vs | 0.8 mg vs |
| placebo p< 0.001 | placebo p< 0.001 | placebo NS | |
| of | 0.4 mg vs | 0.4 mg vs | 0.4 mg vs |
| placebo p< 0.001 | placebo p< 0.001 | placebo NS | |
| Difference | 0.8 mg vs | 0.8 mg vs | 0.8 mg vs |
| 0.4 mg NS | 0.4 mg NS | 0.4 mg NS |