1. Randomized controlled trial of triple versus dual inhaler therapy on small airways in smoking asthmatics.
- Author
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Jabbal S, Kuo CR, and Lipworth B
- Subjects
- Administration, Inhalation, Adrenal Cortex Hormones adverse effects, Adrenergic beta-2 Receptor Agonists adverse effects, Adult, Anti-Asthmatic Agents adverse effects, Asthma diagnosis, Asthma physiopathology, Benzoxazines adverse effects, Cross-Over Studies, Drug Combinations, Female, Humans, Lung physiopathology, Male, Muscarinic Antagonists adverse effects, Nebulizers and Vaporizers, Recovery of Function, Scotland, Smoking physiopathology, Time Factors, Tiotropium Bromide adverse effects, Treatment Outcome, Adrenal Cortex Hormones administration & dosage, Adrenergic beta-2 Receptor Agonists administration & dosage, Anti-Asthmatic Agents administration & dosage, Asthma drug therapy, Benzoxazines administration & dosage, Lung drug effects, Muscarinic Antagonists administration & dosage, Smokers, Smoking adverse effects, Tiotropium Bromide administration & dosage
- Abstract
Background: Smoking worsens underlying asthma inflammation and also induces resistance to inhaled corticosteroids (ICS). Small airways dysfunction measured by impulse oscillometry (IOS) is associated with worse control., Objectives: We investigated the effects on small airways of adding long-acting beta-agonist (LABA) alone or with long-acting muscarinic antagonist (LAMA) to ICS in asthmatic smokers., Methods: Sixteen current smokers were enrolled: mean age 44 year, FEV1 84%, FEF25-75 47%, R5 158%, ACQ 1.69, 20 pack year . Patients were converted to a reference ICS as HFA-BDP during initial run-in at median dose of 800 µg/day. Open label olodaterol 5 µg od (OLO) or olodaterol 5 µg/tiotropium 5 µg od (OLO/TIO) was added to HFA-BDP for median duration of 3 weeks in a randomized cross over design, including run-in and washout periods on HFA-BDP. IOS and spirometry were measured after each treatment (BDP/OLO/TIO or BDP/OLO) and at baseline after run-in and washout (BDP)., Results: After chronic dosing, IOS outcomes at trough except for R20 were all significantly improved with OLO/TIO compared to OLO. For the primary end-point of total airway resistance (as R5), the mean difference (95%CI) at trough was 0.06 (0.015-0.10) kPa/l/s, peripheral airways resistance (as R5-R20) 0.03 (0.003-0.06) kPa/l/s, peripheral lung reactance area (as AX) 0.38 (0.08-0.68) kPa/l and resonant frequency (as RF) 2.28 (0.45-4.12) Hz. FEF25-75 at trough was also better with OLO/TIO vs TIO: 0.93 (0.86 - 0.95) l/s while FEV1 was not different., Conclusions: ICS/LABA/LAMA was superior to ICS/LABA on trough small airway outcomes in asthma patients who smoke., (© 2020 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)
- Published
- 2020
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