Acute Relief of Exercise-Induced Bronchoconstriction by Inhaled Formoterol in Children With Persistent Asthma: Patients Enrolled
Carryover effects for predose FEV1 were investigated graphically. The baseline value of the study day and the predose value (5 min after exercise) were both used as covariates in the analysis. Time to recovery (time from drug administration until FEV1 had reached within 5% of baseline FEV1) was compared between active treatments using Wilcoxon signed rank-sum test.
The central tendency of time to recovery is presented by median. All tests were two sided at a 5% significance level. The efficacy analysis included all randomized patients with values from at least 2 study days. The number of patients was based on experience from previous studies with exercise tests in children, indicating that 24 patients would give an 80% chance to detect a difference of 8% (corresponding to approximately 0.2 L) between any two treatments. This assumes a two-sided test at a 5% significance level. However, since the actual design had not previously been used, the study could be considered a pilot study.
One hundred twenty-one children were screened for the study. Thirty-four children fulfilled inclusion criteria, but 4 children declined participation and 4 children were excluded due to poor compliance. Twenty-six children were randomized to a treatment sequence at the second visit. there
Each treatment sequence was applied to four children, and two sequences (formoterol-terbutaline-placebo and placebo-formoterol-terbutaline) were each applied to one additional child. Three randomized children were withdrawn, all due to insufficient drop in FEV1 after exercise; of these, two children only performed one treatment visit and were excluded from the analysis due to lack of data, and one child performed 2 study days (formoterol and terbutaline) and was included in the analysis. Eight children had to reschedule at least one visit due to insufficient drop in FEV1 at the first attempt. Baseline characteristics of the randomized patients are shown in Table 1. Asthma severity ranged from mild-to-moderate persistent asthma according to Global Initiative for Asthma guidelines.
Table 1—Baseline Characteristics of Study Patients
|Randomized patients, No.||26|
|Age (range), yr||12.9 (7-16)|
|Male gender, No. (%)||12 (46)|
|Mean time since asthma diagnosed (range), yr||9(1-15)|
|ICS treatment||23 (89)|
|Mean daily dose of ICS (range), ^g||418 (200-800)|
|Skin-prick test result positive||17 (65)|
|Mean FEVj (range), L||2.61 (1.24-4.24)|
|Mean FEVj % predicted (range), %||91.0(71-121)|
|Mean MMEF25-75 (range), L/s||2.27(1.14-4.90)|
|Mean maximum drop in FEVj (range), %||28.3 (15-65)|
|Mean FeNO (range), parts per billion||37.7 (5-82)|