Asthma is defined as chronic inflammation of the lower small airways, and bronchial hyperreactivity (BHR) is a pathophysiologic feature of asthma. It has been proposed that although there is no direct variable capable of assessing the small airways, a forced expiratory flow of between 25 and 75 percent (FEF_25-75) might be considered a more sensitive early marker of small airway obstruction than the forced expiratory volume in 1 second (FEV₁). Thus, we proposed that the presence and degree of positive responses to bronchial methacholine testing were related to the difference (DFF) and ratio (RFF) between FEV₁ and FEF_25-75 in asthmatic children.

The subjects were 583 symptomatic children, including 324 children with BHR and 259 controls. Pulmonary function tests, methacholine challenge tests, and skin prick tests were performed, and the total eosinophil count, total serum IgE, and serum eosinophil cationic protein level were measured in all subjects. From a concentration-response curve, the methacholine concentration required to produce a decrease of 20% from post-saline FEV₁ was calculated (PC₂₀).

The median DFF and RFF values decreased in controls compared to subjects with bronchial hyperresponsiveness, and this trend was found in groups ranked by its severity. PC₂₀ had a negative correlation with DFF and RFF. Cutoff values of 0.5 for DFF and 1.042 for RFF were identified, and sensitivity and specificity were calculated.

This study revealed that DFF and RFF might be predictive of bronchial hyperresponsiveness in the context of normal FEV₁ in children.