Easton and coworkers compared the bronchodilating effects of albuterol and IB given by aerosol either alone or in sequence. They administered 120 \Lg of IB and 800 jig of albuterol over a 30-min period. When used alone, both bronchodilators significantly increased airflow and relieved hyperinflation, and there was no significant difference between the two drugs. After the improvement with the initial bronchodilator, the subsequent effect of a second inhaled bronchodilator was not greater than that of placebo. Our results in a group of young patients with chronic lung disease due to CF are similar to the results presented by Easton and coworkers. We did not find any beneficial bronchodilator effect of multidrug therapy when high doses were used. Although the patients did not have side effects with the doses administered, it is possible that in some patients, regular doses of p-adrenergic combined with anticholinergic agents may be a better therapeutic approach to avoid side effects.
There are several limitations to the present study. The first is that it is difficult to know with certainty what is a maximum dose for this group of patients; we chose 80 |tg of IB and 600 |ig of S based on published data and taking into account that most of our patients were younger than 15 years of age. The second is the small sample size and the variability in baseline lung function observed in our subjects. Because this protocol was quite long (more than 8 h each day), we were not able to recruit more patients. We acknowledge that maybe because of the small sample size, we have failed to find an additive effect of high doses of bronchodilators. Thirdly, we did not test the effect of both medications administered at the same time. This, together with the use of a metered dose inhaler, could explain why we did not obtain any additive effect of both bronchodilators in this protocol, which is in contradiction to previously published results in a similar group of young CF patients using more standard doses of drug. In addition, the heterogeneous group in regard to age, lung function tests, and severity of the disease may have had an influence on our results. Finally, we have described only the acute response to bronchodilators and further studies will be needed to assess long-term efficacy and safety.
In conclusion, we have found that in a group of CF patients who had a history of positive response to inhaled bronchodilators, both single and combined therapy with high doses of S and IB had a similar bronchodilator effect (increased FEVi and decreasing Raw). We did not observe any benefit from adding a second drug when high doses of one bronchodilator were previously used. We speculate that adrenergic and muscarinic pathways appear to be equally important in the pathogenesis of expiratory airflow obstruction in some CF patients.