A protocol for performing reproducible methacholine inhalation tests in children with moderate to severe asthma

Reproducibility of methacoline inhalation tests (MIT) over a 2-wk period has been established in adult populations, but similar studies demonstrating reproducibility in children are lacking. We set out to establish the reproducibility of MIT in children as a prerequisite for a study of the natural history of airway hyperreactivity in asthmatic children. Most inhalation testing is done in persons with mild asthma because the recommended time interval for the withholding of medications prior to bronchial challenge is poorly tolerated by more labile asthmatics. In order to evaluate asthmatic with more severe disease, we modified a standardized method of methacholine inhalation to include a three-tier pretest medication regimen and investigated the reproducibility of this MIT protocol in 11 children as young as 6 yr of age. The three tiers were designed to keep baseline FEV₁ ≥ 70% predicted since diminished baseline airway caliber may affect MIT results. Eight of the 11 children were bronchodilator-dependent, and two of the eight also required inhaled steroids. Eleven children (6 to 13 yr of age) underwent MIT, between December and March, 1 day, 1 wk, and 1 month after an initial test. The PD₂₀FEV₁ using cumulative breath units (BU) were compared. The range of PD₂₀FEV₁ in the 11 children was 0.27 to 14.4 BU, with nine subjects classified as severe (PD₂₀FEV₁ < 2.5 BU). We found a high degree of reproducibility of MIT. The interest correlation coefficient (r) was 0.98 after 1 day, 0.95 after 1 wk, and 0.96 after 1 month. We conclude that our three-tier pretest medication regimen allows children as young as 6 yr of age, with moderate to severe asthma, to undergo successive MIT. This protocol should prove useful in allowing serial studies of airway hyperreactivity in asthmatic children.