Acute Relief of Exercise-Induced Bronchoconstriction by Inhaled Formoterol in Children With Persistent Asthma: Discussion


An unexpected result was that the drop in lung function before drug administration on the formot-erol day was statistically significantly smaller than on the placebo day with the drop on the terbutaline day in-between. Baseline antiinflammatory treatment was unchanged, and the analysis revealed no period or carryover effect, so this appears a chance finding and probably reflects the natural variation in severity of bronchial hyperresponsiveness. As a result, the outcome of the analyses of FEV1 and MMEF25-75 depended on the choice of reference point. If using baseline as reference, formoterol would be favored.

If, instead, using the predose value as reference, terbutaline with its larger room for improvement would be favored. The primary analysis used both the baseline and the predose values as covariates. According to this, no statistical difference between formoterol and terbutaline was observed 5 min after dosing. This result of no statistically significant difference between formoterol and terbutaline was also seen when analyzing the response in FEV1 at 5 min in percentage of maximum increase. We applied EIB as a model of a very common clinical situation in which asthmatic children require relief. EIB involves a different pathology from that observed in acute severe attacks of asthma or severe chronic asthma, the mechanism of action being dominated by acute mediator release and short-term effects and less by changes in the underlying chronic inflammatory reaction. Reading here

In addition to FEV1 we also measured MMEF25-75, which is more related to small airway function and may be more sensitive than FEV1. MMEF25-75 showed changes consistent with FEV!. Our findings are in line with previous reports in acute and chronic asthma in both adults and children and with a study of methacholine-induced bronchoconstriction in adults, showing similar onset of action of formoterol and salbutamol. These findings are supported by our previous report of the effect of formoterol and terbutaline in young preschool children using a model of cold-air induced hyperventilation. We chose lung function measurement as the only outcome measure since symptoms are poor predictors of bronchoconstriction after exercise in children. Previous studies have attested to a favorable tolerability of formoterol at high doses in adults and children.