Acute Relief of Exercise-Induced Bronchoconstriction by Inhaled Formoterol in Children With Persistent Asthma: Materials and Methods
The study was performed in accordance with the declaration of Helsinki and approved by the local ethics committee (KF 02-082/00) and the Danish Medicines Agency (2612-1507). Before enrollment, informed consent was obtained from both children and parents/legal guardians.
Patients were recruited from two pediatric outpatient clinics in Copenhagen. Children 7 to 15 years old with a diagnosis of persistent asthma and a fall in FEV1 of at least 15% after exercise at enrollment were eligible for participation. Concurrent use of inhaled corticosteroids (ICS) was unchanged during the month prior to enrollment and was kept constant throughout the study. Children who had an asthma exacerbation necessitating a change in dose of ICS or treatment with systemic steroids within 2 months prior to the study were excluded. Before each visit, long-acting p2-agonists (LABAs) were withheld for 24 h, SABAs were withheld for 6 h, and leukotriene receptor antagonists were withheld for 5 days. read more
The study was of a randomized, double-blind, cross-over design with one screening visit and 3 study days with single-dose administrations of formoterol, 9 |j,g, terbutaline, 0.5 mg, or placebo, all administered as dry powder (Turbuhaler; AstraZeneca; Lund, Sweden). Randomized treatment sequences were generated in balanced blocks containing all six possible combinations by a computer program at AstraZeneca, Lund. Each sequence corresponded to a patient number that was allocated sequentially as the children were eligible for the study. No child was randomized to more than one treatment sequence. After baseline measurements, a standardized exercise test was performed at each visit. All visits were performed at approximately the same time of the day (± 3 h). Study days were separated by washout periods of at least 48 h. The median time of the randomized part of the study was 12 days (range, 4 to 35 days) with the washout periods averaging 6 days rather than the minimum required 2 days, a time period sufficiently eliminating carryover effects in a study with single doses of compounds of at most 24 h in duration.