Bensch G, Berger WE, Blokhin BM, et al. Ann Allergy Asthma Immunol. 2002;89:180–190
Purpose of the Study.
Previous published studies in adults and children have shown the addition of long-acting β-agonists to low- to medium-dose inhaled corticosteroids provided symptom relief and pulmonary function improvement greater than doubling the dose of inhaled corticosteroids alone. This study investigated the 12-month efficacy and safety of 2 doses of formoterol dry powder capsules for inhalation in children receiving antiinflammatory therapy and still requiring daily administration of short-acting β-agonists for symptom relief.
Five hundred eighteen patients, 5 to 12 years old with persistent asthma. Patients were receiving sodium cromoglycate, nedocromil sodium, and/or inhaled corticosteroids at stable doses for at least 1 month before entry in the study.
After the run-in period, all patients were randomized in a double-blind manner to receive 12 or 24 μg formoterol dry powder capsule or placebo capsule twice daily for 12 months. This was given in addition to their baseline antiinflammatory treatment, which was not changed. The primary study variable was the area under the curve for forced expiratory volume in 1 second (FEV1) measured over 12 hours after the morning dose of study medication.
The area under the curve for FEV1 after the first treatment dose and after 3 and 12 months of treatment was significantly greater in patients receiving formoterol 12 μg and 24 μg than in patients receiving placebo (all P ≤ .0062). Although numerically greater for formoterol 24 μg, there was no statistically significant difference in FEV1 between the 2 active treatment doses. Compared with placebo, both doses of formoterol significantly improved am and pm peak expiratory flow rates. In the group treated with formoterol 24 μg twice daily, median symptom score and median dose of rescue medication at night were lower than during the run-in period, whereas with the 12-μg dose and the placebo group this did not change. Hospitalization for asthma was higher in the 2 formoterol groups than in the placebo group. The number of patients reporting asthma exacerbations during the study was the same for all 3 treatment groups.
In asthmatic children who are still symptomatic despite antiinflammatory therapy, the addition of formoterol 12 or 24 μg improves air flow obstruction, nocturnal symptoms and the use of rescue medication. The regular use of long-acting β-agonists was safe and well-tolerated in this patient population.
Although the overall results are encouraging, the increase in hospitalization in the formoterol-treated patients is concerning. It is possible that this could result from a masking of airway inflammation with potent 12-hour bronchodilatation.