Forced Expiratory Flow (FEF25–75%) as a Clinical Endpoint in Children and Adolescents with Symptomatic Asthma Receiving Tiotropium: A Post Hoc Analysis
Tóm tắt
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. 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. 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). 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.
Tài liệu tham khảo
Spahn JD, Cherniack R, Paull K, Gelfand EW. Is forced expiratory volume in one second the best measure of severity in childhood asthma? Am J Respir Crit Care Med. 2004;169(7):784–6.
Simon MR, Chinchilli VM, Phillips BR, et al. Forced expiratory flow between 25% and 75% of vital capacity and FEV1/forced vital capacity ratio in relation to clinical and physiological parameters in asthmatic children with normal FEV1 values. J Allergy Clin Immunol. 2010;126(3):527–34.e1-8.
Rao DR, Gaffin JM, Baxi SN, Sheehan WJ, Hoffman EB, Phipatanakul W. The utility of forced expiratory flow between 25% and 75% of vital capacity in predicting childhood asthma morbidity and severity. J Asthma. 2012;49(6):586–92.
Vilozni D, Hakim F, Livnat G, Ofek M, Bar-Yoseph R, Bentur L. Assessment of airway bronchodilation by spirometry compared to airway obstruction in young children with asthma. Can Respir J. 2016;2016:6.
Ciprandi G, Capasso M, Tosca M, et al. A forced expiratory flow at 25–75% value <65% of predicted should be considered abnormal: a real-world, cross-sectional study. Allergy Asthma Proc. 2012;33(1):e5–e8.
Hamelmann E, Bernstein JA, Vandewalker M, et al. A randomised controlled trial of tiotropium in adolescents with severe symptomatic asthma. Eur Respir J. 2017;49:1601100.
Szefler SJ, Murphy K, Harper T, et al. A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma. J Allergy Clin Immunol. 2017;140:1277–87.
Vogelberg C, Engel M, Laki I, et al. Tiotropium add-on therapy improves lung function in children with symptomatic moderate asthma. J Allergy Clin Immunol. 2018;6(6):2160–2.e9.
Hamelmann E, Bateman ED, Vogelberg C, et al. Tiotropium add-on therapy in adolescents with moderate asthma: a 1-year randomized controlled trial. J Allergy Clin Immunol. 2016;138(2):441–50.e8.
Graham BL, Steenbruggen I, Miller MR, et al. Standardization of spirometry 2019 update: An official American Thoracic Society and European Respiratory Society technical statement. Am J Respir Crit Care Med. 2019;200(8):e70–e88.
Sposato B, Scalese M, Migliorini MG, Di Tomassi M, Scala R. Small airway impairment and bronchial hyperresponsiveness in asthma onset. Allergy Asthma Immunol Res. 2014;6(3):242–51.
Stanojevic S, Wade A, Stocks J, et al. Reference ranges for spirometry across all ages: a new approach. Am J Respir Crit Care Med. 2008;177(3):253–60.
Quanjer PH, Weiner DJ, Pretto JJ, Brazzale DJ, Boros PW. Measurement of FEF25-75% and FEF75% does not contribute to clinical decision making. Eur Respir J. 2014;43(4):1051–8.
Gibb E, Kaplan D, Thyne SM, Ly NP. Fef 25–75 as a predictor of asthma severity in children. Am J Respir Crit Care Med. 2012;185:A6801.