Forced Expiratory Flow (FEF25–75%) as a Clinical Endpoint in Children and Adolescents with Symptomatic Asthma Receiving Tiotropium: A Post Hoc Analysis

Abstract

Introduction 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 (FEF25–75%) is a potentially more sensitive parameter for assessing peripheral airway function. This post hoc analysis compared FEF25–75% with FEV1 as an endpoint to assess bronchodilator responsiveness in children with asthma. Methods Change from baseline in trough FEF25–75% 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 FEF25–75% and FEV1 were calculated and analyzed. Results A total of 1590 patients were included in the analysis. Tiotropium Respimat® consistently improved FEF25–75% and FEV1 versus placebo, although in adolescents with severe asthma, the observed improvements were not statistically significant. Improvements in FEF25–75% response with tiotropium versus placebo were largely more pronounced than improvements in FEV1. Statistical assessment of the correlation of FEV1 and FEF25–75% showed moderate-to-high correlations (Pearson’s correlation coefficients 0.73–0.80). Conclusions In pediatric patients, FEF25–75% 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.

Effect of Vitamin C Supplementation for Pregnant Smokers on Offspring Airway Function and Wheeze at Age 5 Years

“…23 In children with asthma, FEF 25-75 was previously reported to be better than FEV 1 in assessing treatment effects. 24 We demonstrated that FEF 25-75 in the offspring of vitamin C-supplemented pregnant smokers was improved by 17.2% over the placebo group (mean [SE] 1.45 [0.04] vs 1.24 [0.04] L/s; adjusted mean difference, 0.21 [95% CI, 0.13-0.30]) and, importantly, was associated with a significant 40.0% decrease (P = .003) in the occurrence of wheeze. Both groups had a high occurrence of wheeze (28.3% vs 47.2% in the vitamin C vs placebo group; 37.7% overall), which highlights the high respiratory morbidity associated with in utero smoke exposure.…”

Impulse oscillometry system for assessing small airway dysfunction in pediatric bronchiolitis obliterans; association with conventional pulmonary function tests

“…We used a cutoff for FEV1 < 75% based on the criteria for the definition of BO from the National Institutes of Health (NIH) consensus, 2014 [ 20 ]. FEF25-75% is a potentially sensitive parameter for evaluating small airway function in pediatrics [ 21 ]. There are no guidelines regarding normal values in children, and previous studies have suggested thresholds of 60% or 65% in children to define peripheral airflow obstruction [ 22 , 23 ].…”

Tiotropium as an add‑on treatment to inhaled corticosteroids in children with severe and mild symptomatic asthma: Multi‑center observational study for efficacy and safety analysis

“…The efficacy and safety parameters of ICS + tiotropium in contrast to ICS + LABA are available in other studies (14,18). In a randomized trial (14) on adult patients with moderate asthma, tiotropium showed comparable efficacy and tolerability to LABA (salmeterol).…”