Randomised controlled trial of triple versus dual inhaler therapy on small airways in smoking asthmatics

Sunny Jabbal, Chris RuiWen Kuo, Brian Lipworth (Lead / Corresponding author)

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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: 16 current smokers were enrolled: mean age 44 yr, FEV1 84%, FEF25-75 47%, R5 158%, ACQ 1.69, 20 pack yr. Patients were converted to a reference ICS as HFA-BDP during initial run-in at median dose of 800µg. Open label olodaterol 5µg od (OLO) or olodaterol 5µg /tiotropium 5µg od (OLO/TIO) was added to HFA-BDP for median duration of 3 wk in a randomised 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, 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.

The study was registered at clinicaltrials.gov as NCT02682862, and was approved by the East of Scotland Regional Ethics Committee (reference: 15/ES/0032).
Original languageEnglish
Number of pages8
JournalClinical and Experimental Allergy
Early online date7 Jul 2020
Publication statusE-pub ahead of print - 7 Jul 2020


  • asthma
  • pneumology
  • quality-of-life
  • smoking
  • small airways
  • triple therapy

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