Forced Expiratory Flow (FEF_25-75%) as a Clinical Endpoint in Children and Adolescents with Symptomatic Asthma...

In pediatric patients with asthma, measurements of forced expiratory volume in 1 s (FEV₁) may be normal or may not correlate with symptom severity. Forced expiratory flow at 25-75% of the vital capacity (FEF_25-75%) is a potentially more sensitive parameter for assessing peripheral airway function. This post hoc analysis compared FEF_25-75% with FEV₁ as an endpoint to assess bronchodilator responsiveness in children with asthma.

Change from baseline in trough FEF_25-75% and trough FEV₁ following treatment with either tiotropium (5 µg or 2.5 µg) or placebo Respimat^® was analyzed in four phase III trials in children (aged 6-11 years) and adolescents (aged 12-17 years) with symptomatic moderate (VivaTinA-asthma^® and PensieTinA-asthma^®) and mild (CanoTinA-asthma^® and RubaTinA-asthma^®) asthma. Data from all treatment arms were pooled and correlations between FEF_25-75% and FEV₁ were calculated and analyzed.

A total of 1590 patients were included in the analysis. Tiotropium Respimat^® consistently improved FEF_25-75% and FEV₁ versus placebo, although in adolescents with severe asthma, the observed improvements were not statistically significant. Improvements in FEF_25-75% response with tiotropium versus placebo were largely more pronounced than improvements in FEV₁. Statistical assessment of the correlation of FEV₁ and FEF_25-75% showed moderate-to-high correlations (Pearson's correlation coefficients 0.73-0.80).

In pediatric patients, FEF_25-75% may be a more sensitive measure to detect treatment response, certainly to tiotropium, than FEV₁ and should be evaluated as an additional lung function measurement.