Airway Deposition of Extrafine Inhaled Triple Therapy in Patients with COPD: A Model Approach Based on Functional Respiratory Imaging Computer Simulations.

Abstract

Introduction:

There is a clear correlation between small airways dysfunction and poor clinical outcomes in patients with chronic obstructive pulmonary disease (COPD), and it is therefore important that inhalation therapy (both bronchodilator and anti-inflammatory) can deposit in the small airways. Two single-inhaler triple therapy (SITT) combinations are currently approved for the maintenance treatment of COPD: extrafine formulation beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB), and non-extrafine formulation fluticasone furoate/vilanterol/umeclidinium (FluF/VI/UMEC). This study evaluated the lung deposition of the inhaled corticosteroid (ICS), long-acting β2-agonist (LABA), and long-acting muscarinic antagonist (LAMA) components of these two SITTs.

Materials and Methods:

Lung deposition was estimated in-silico using functional respiratory imaging, a validated technique that uses aerosol delivery performance profiles, patients' high-resolution computed tomography (HRCT) lung scans, and patient-derived inhalation profiles to simulate aerosol lung deposition.

Results:

HRCT scan data from 20 patients with COPD were included in these analyses, who had post-bronchodilator forced expiratory volume in 1 second (FEV1) ranging from 19.3% to 66.0% predicted. For intrathoracic deposition (as a percentage of the emitted dose), deposition of the ICS component was higher from BDP/FF/GB than FluF/VI/UMEC; the two triple therapies had similar performance for both the LABA component and the LAMA component. Peripheral deposition of all three components was higher with BDP/FF/GB than FluF/VI/UMEC. Furthermore, the ratios of central to peripheral deposition for all three components of BDP/FF/GB were <1, indicating greater peripheral than central deposition (0.48±0.13, 0.48±0.13 and 0.49±0.13 for BDP, FF and GB, respectively; 1.96±0.84, 0.97±0.34 and 1.20±0.48 for FluF, VI and UMEC, respectively).

Conclusions:

Peripheral (small airways) deposition of all three components (ICS, LABA, and LAMA) was higher from BDP/FF/GB than from FluF/VI/UMEC, based on profiles from patients with moderate to very severe COPD. This is consistent with the extrafine formulation of BDP/FF/GB.

• Authors: Omar S Usmani, Nicola Scichilone, Benjamin Mignot, Dennis Belmans, Cedric Van Holsbeke, Jan De Backer, Roberta De Maria, Erika Cuoghi, Eva Topole, George Georges
• Journal: International journal of chronic obstructive pulmonary disease (Int J Chron Obstruct Pulmon Dis) Vol. 15 Pg. 2433-2440 ( 2020) ISSN: 1178-2005 [Electronic] New Zealand
• PMID: 33116458 (Publication Type: Journal Article)
• Copyright: © 2020 Usmani et al.

Chemical References

• Bronchodilator Agents
• Drug Combinations
• Formoterol Fumarate

Topics

• Administration, Inhalation
• Bronchodilator Agents (adverse effects)
• Computer Simulation
• Drug Combinations
• Formoterol Fumarate (therapeutic use)
• Humans
• Pulmonary Disease, Chronic Obstructive (diagnostic imaging, drug therapy)