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EFFECT OF SWITCHING FROM MULTI-INHALER NON-EXTRA FINE TO SINGLE-INHALER EXTRA FINE TRIPLE THERAPHY ON REGIONAL BRONCHODILATION AND VENTILATION IN PATIENTS WITH SEVERE COPD

      SESSION TITLE: New Insights into COPD and Its Complications
      SESSION TYPE: Original Investigations
      PRESENTED ON: October 18-21, 2020
      PURPOSE: To identify optimal therapeutics and response parameters for small airways dysfunction evaluation is key in COPD. We explored whether a switch from non-extra fine to extra fine therapeutic particles may result in improved regional bronchodilation and ventilation due to enhanced peripheral drug deposition in patients with severe COPD using functional respiratory imaging (FRI).
      METHODS: This was a multi-center, open-label exploratory trial where patients with symptomatic severe COPD previously on a stable dose non-extra fine multi-inhaler triple therapy (MITT) with inhaled corticosteroid/long-acting β2 agonist (ICS/LABA) plus a long-acting muscarinic antagonist (LAMA) for ≥ 3 months were switched to single-inhaler extra fine triple therapy (SITT) with beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB 100/6/12.5 µg) pressurized metered dose inhaler (pMDI) 2 inhalations bid for 24 weeks. Regional bronchodilation, e.g., changes in image-based specific inner airway volume (siVaw), and resistance (siRaw) were derived from low-dose computed tomography (CT) scans at total lung capacity (TLC) and functional residual capacity (FRC) at week 12 and 24. Regional lung deposition of ICS, LABAs and LAMAs was simulated as a function of age, height, disease severity, aerosol characteristics, and breathing pattern. Percent changes from baseline in FRI parameters, measured on a lobar basis, were assessed post-hoc using a linear mixed-model approach. The correlations between FRI indices and pulmonary function tests were determined using Spearman rank correlation coefficient.
      RESULTS: 21 patients were enrolled, 20 completed the study. Mean age was 63.4 years, FEV1 was 40.5% of predicted normal, 55% were current smokers, 50% were females and 70% showed predominant emphysema on the CT scan. At week 24, overall percent change from baseline was +22.0% (p< 0.001) for siVaw, and -17.6% (p=0.014) for siRaw at TLC. Change from baseline in SGRQ total score was inversely correlated to siVaw (r=-0.470, p=0.042) whereas change from baseline in FEV1 bore no correlation to either siVaw (r=0.299, p=0.214) or siRaw (r=-0.349, p=0.143). Switching from a non-extra fine MITT to extra fine BDP/FF/GB increased the peripheral lung deposition of ICS by 19.8 ± 3.8 %, LABA by 18.8 ± 3.4 % and LAMA by 13.2 ± 7.1 % of delivered dose, respectively.
      CONCLUSIONS: FRI signatures but not FEV1 capture the significant bronchodilation effect occurring after 24 weeks following switch from non-extra fine to extra fine inhaled triple therapy in patients with severe COPD.
      CLINICAL IMPLICATIONS: Switching to extra fine BDP/FF/GB pMDI results in enhanced regional ventilation to the small airways as assessed by CT surrogate ventilation maps
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