P225 Comparison of ICS containing open triple and dual therapy on small airways function in the smoking asthma phenotype

Background Patients with asthma who smoke are difficult to manage and are usually excluded from clinical trials. Smoking not only worsens underlying asthma inflammation and airway hyper-responsiveness but also induces resistance to inhaled corticosteroids (ICS). Small airways dysfunction measured by impulse oscillometry (IOS) is associated with worse control. We therefore investigated for the first time the effects on small airways of adding LABA or LABA/LAMA to ICS in asthmatic smokers. Patients and methods 16 current smokers were enrolled: mean age 44 yr, FEV184%, FEF25–7547%, R5 158%, ACQ 1.69, 20 pack yr. Patients were converted to a reference ICS as HFA-BDP pMDI (Clenil Modulite) during initial run-in at a median dose of 800µg. Open label olodaterol 5µg od (OLO) or olodaterol 5µg/tiotropium 5µg od (OLO/TIO) was added to HFA-BDP for 2–4 weeks (am dosing) in a randomised cross over design, along with 2–4 weeks run-in and washout periods on HFA-BDP. IOS and spirometry were measured at peak/trough after each treatment (BDP/OLO/TIO or BDP/OLO) and at baseline after run-in and washout (BDP). Results IOS outcomes after chronic dosing at trough were all improved with BDP/OLO/TIO compared to BDP/OLO (Fig). For the primary end point of total airway resistance (as R5) the mean difference was: 0.06 (95% CI 0.015–0.098) kPa/l/s, peripheral airways resistance (as R5–20): 0.03 (0.003–0.06) kPa/l/s, peripheral lung reactance (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 BDP/OLO/TIO vs BDP/OLO: 0.93 (0.86 – 0.95) l/s while FEV1 was not different. There was no difference in peak IOS values between treatments. Mean change from baseline in ACQ with BDP/OLO/TIO (0.60) but not BDP/OLO (0.34) exceeded MCID of 0.5. Conclusions Open triple therapy with ICS/LABA/LAMA was superior to dual therapy with ICS/LABA on trough small airway outcomes in asthma patients who smoke. Further studies are warranted in this phenotype to evaluate if such effects on small airways translate into reduced exacerbations when using single triple inhalers.