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Randomized controlled trial of triple versus dual inhaler therapy on small airways in smoking asthmatics
Author(s) -
Jabbal Sunny,
Kuo Chris RuiWen,
Lipworth Brian
Publication year - 2020
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.13702
Subject(s) - medicine , spirometry , inhaler , anesthesia , muscarinic antagonist , crossover study , asthma , copd , bronchodilator , randomized controlled trial , gastroenterology , antagonist , receptor , alternative medicine , pathology , placebo
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.