Effects of fluticasone vs. fluticasone/salmeterol on airway calibre and airway hyperresponsiveness in mild persistent asthma
- 9 July 2003
- journal article
- clinical trial
- Published by Wiley in British Journal of Clinical Pharmacology
- Vol. 56 (1) , 11-17
- https://doi.org/10.1046/j.1365-2125.2003.01831.x
Abstract
Inhaled corticosteroids alone or in combination with long acting beta2-agonists are indicated for use in mild persistent asthmatics. We set out to evaluate effects on airway hyperresponsiveness (AHR) and airway calibre using hydrofluoroalkane fluticasone/salmeterol (FP/SM) vs. double the dose of fluticasone alone (FP). Fourteen mild persistent asthmatics completed a randomized double-blind crossover study with 1-week run-in and washout periods prior to treatments. Subjects received 3 weeks of FP 250 microg or FP 125 microg/SM 25 microg as 1 puff twice daily. Methacholine PD20 and lung function were measured after both baseline and treatment periods. There were no significant differences in baseline values prior to randomized treatments. Compared with pooled baseline, FP/SM and FP conferred improvements (P < 0.05) on methacholine PD20: 2.5 (95% confidence interval 1.7, 3.2) and 1.6 (0.8-2.3) doubling dose improvements, respectively; between FP/SM vs. FP there was a 0.9 (0.4, 1.4) doubling dose difference (P < 0.05). For forced expiratory volume in 1 s (FEV1), forced mid-expiratory flow (FEF25-75) and morning peak expiratory flow (PEF), FP/SM but not FP conferred improvements (P < 0.05) compared with pooled baseline, with FP/SM being greater than FP (P < 0.05): differences in FEV1 of 7.2% (3.8, 10.6) predicted, FEF25-75 of 11.2% (6.3, 16.1) predicted, and morning PEF of 17 L x min(-1)(1-32). FP/SM conferred improvements on AHR and airway calibre, while twice the dose of FP improved only AHR in patients with mild asthma. The differential effects of FP/SM and FP suggest separate but complementary actions of the two moieties on airway inflammation and smooth muscle stabilization. This may explain the beneficial effects of combination inhalers on exacerbations.Keywords
This publication has 27 references indexed in Scilit:
- Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis Commentary: Dosage needs systematic and criticalBMJ, 2001
- Dose proportionality of fluticasone propionate from hydrofluoroalkane pressurized metered dose inhalers (pMDIs) and comparability with chlorofluorocarbon pMDIsRespiratory Medicine, 2000
- Airway mast cells and eosinophils correlate with clinical severity and airway hyperresponsiveness in corticosteroid-treated asthmaJournal of Allergy and Clinical Immunology, 2000
- The long‐acting β2‐agonist salmeterol xinafoate: effects on airway inflammation in asthmaEuropean Respiratory Journal, 1999
- Clinical Control and Histopathologic Outcome of Asthma when Using Airway Hyperresponsiveness as an Additional Guide to Long-Term TreatmentAmerican Journal of Respiratory and Critical Care Medicine, 1999
- Effect of Inhaled Formoterol and Budesonide on Exacerbations of AsthmaNew England Journal of Medicine, 1997
- Relationship between the inflammatory infiltrate in bronchial biopsy specimens and clinical severity of asthma in patients treated with inhaled steroids.Thorax, 1996
- Measuring the systemic effects of inhaled beclomethasone: timed morning urine collections compared with 24 hour specimens.Thorax, 1995
- Effect of eight weeks of treatment with salmeterol on bronchoalveolar lavage inflammatory indices in asthmatics.American Journal of Respiratory and Critical Care Medicine, 1994
- Measurement of airway responsiveness to methacholine: relative importance of the precision of drug delivery and the method of assessing response.Thorax, 1993