Lung deposition of extrafine vs. non-extrafine tiple therapies in patients with COPD using Functional Respiratory Imaging (FRI)

Introduction: FRI is a validated computational fluid dynamics (CFD)-based technique using aerosol delivery performance profile, patientsʼ high-resolution lung CT scans and patient-derived inhalation profiles to simulate aerosol lung deposition.

Aims and Objectives: To evaluate lung deposition patterns of extrafine beclomethasone dipropionate/formoterol fumarate/glycopyrronium [BDP/FF/G; TRIMBOW^®] pressurized metered dose inhaler (pMDI) and non-extrafine fluticasone furoate/vilanterol/umeclidinium [FluF/VI/UMEC; TRELEGY^® ELLIPTA^®] dry powder inhaler (DPI) in patients with stable COPD and moderate to very severe airflow obstruction.

Methods: Intrathoracic depositions of the inhaled corticosteroid (ICS), long-acting β2 receptor agonist (LABA), and long-acting muscarinic antagonist (LAMA) components were calculated for each inhaler in 20 patients. Inhalation was simulated in silico using a per-patient profile derived from real life measurement.

Results: Pulmonary deposition [% delivered dose] was higher for extrafine BDP than FluF (35.9 ± 6.7% vs. 23.3 ± 4.6%) and comparable between FF and VI and between G and UMEC. Central to peripheral ratios were markedly lower for BDP, FF, and G compared to FluF, VI and UMEC, respectively ([Table 1]).

Table 1 Central to peripheral deposition ratios (all flow rates):

Component	Extrafine BDP/FF/G pMDI	FluF/VI/UMEC DPI
ICS	0.48 ± 0.13	1.96 ± 0.84
LABA	0.48 ± 0.13	0.97 ± 0.34
LAMA	0.49 ± 0.13	1.20 ± 0.48

Conclusions: FRI data indicate a higher peripheral lung (small airways) deposition with extrafine BDP/FF/G than with FluF/VI/UMEC. This may be attributed to the lower Mass Median Aerodynamic Diameter (MMAD) of BDP/FF/G.