Inhaled aerosol dose distribution between proximal bronchi and lung periphery

Verbanck, Sylvia; Biddiscombe, Martyn; Usmani, Omar

doi:10.1016/j.ejpb.2020.04.019

Cited by 12 publications

(5 citation statements)

References 20 publications

(30 reference statements)

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“…Second, inhaled particles that were not trapped in the extrathoracic or central airways were assumed to be deposited in the smaller peripheral airways, rather than being exhaled. (26,27) This assumption is supported by the results from the in vivo extrafine BDP/FF scintigraphy study by De Backer et al, (7) which showed that the exhaled fraction of the extrafine particles was on average only 3.4% of the nominal dose in patients with COPD. (28) The deposition values calculated in this study are consistent with those in available literature on aerosol deposition, which showed similar lung deposition of extrafine drugs (MMAD <2 lm).…”

Section: Discussionmentioning

confidence: 80%

Predicting Lung Deposition of Extrafine Inhaled Corticosteroid-Containing Fixed Combinations in Patients with Chronic Obstructive Pulmonary Disease Using Functional Respiratory Imaging: An In Silico Study

Usmani

Mignot

Kendall

et al. 2021

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Background: Functional respiratory imaging (FRI) is a computational fluid dynamics-based technique using three-dimensional models of human lungs and formulation profiles to simulate aerosol deposition. Methods: FRI was used to evaluate lung deposition of extrafine beclomethasone dipropionate (BDP)/formoterol fumarate (FF)/glycopyrronium bromide (GB) and extrafine BDP/FF delivered through pressurized metered dose inhalers and to compare results with reference gamma scintigraphy data. FRI combined high-resolution computed tomography scans of 20 patients with moderate-to-severe chronic obstructive pulmonary disease (mean forced expiratory volume in 1 second 42% predicted) with in silico computational flow simulations, and incorporated drug delivery parameters to calculate aerosol airway deposition. Inhalation was simulated using profiles obtained from real-life measurements. Results: Total lung deposition (proportion deposited in intrathoracic region) was similarly high for both products, with meanstandard deviation (SD) values of 31.0%-5.7% and 28.1%-5.2% (relative to nominal dose) for BDP/FF/GB and BDP/FF, respectively. Pairwise comparison of the deposition of BDP and FF gave a mean intrathoracic BDP/FF/GB:BDP/FF deposition ratio of 1.10 (p ¼ 0.0405). Mean intrathoracic, central and peripheral deposition ratios for BDP were 1.09 (95% confidence interval [

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Section: Discussionmentioning

confidence: 80%

Predicting Lung Deposition of Extrafine Inhaled Corticosteroid-Containing Fixed Combinations in Patients with Chronic Obstructive Pulmonary Disease Using Functional Respiratory Imaging: An In Silico Study

Usmani

Mignot

Kendall

et al. 2021

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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“… 10 , 11 Additionally, both total lung deposition as well as regional deposition may impact the effectiveness of drug delivery. 12 , 13 Thus, it is important to optimize these characteristics to ensure that patients receive a consistent benefit from their inhaled medications.…”

Section: Introductionmentioning

confidence: 99%

Consistent Pulmonary Drug Delivery with Whole Lung Deposition Using the Aerosphere Inhaler: A Review of the Evidence

Usmani¹,

Roche²,

Jenkins³

et al. 2021

COPD

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Metered dose inhalers (MDIs) are one of the most common device types for delivering inhaled therapies. However, there are several technical challenges in development and drug delivery of these medications. In particular, suspension-based MDIs are susceptible to suspension heterogeneity, in vitro drug-drug interactions, and patient handling errors, which may all affect drug delivery. To overcome these challenges, new formulation approaches are required. The Aerosphere TM inhaler, formulated using cosuspension delivery technology, combines drug crystals with porous phospholipid particles to create stable, homogenous suspensions that dissolve once they reach the airways. Two combination therapies using this technology have been developed for the treatment of COPD: glycopyrrolate/formoterol fumarate (GFF MDI; dual combination) and budesonide/glycopyrrolate/formoterol fumarate (BGF MDI; triple combination). Here, we review the evidence with a focus on studies assessing dose delivery, lung deposition, and effects on airway geometry. In vitro assessments have demonstrated that the Aerosphere inhaler provides consistent dose delivery, even in the presence of simulated patient handling errors. Combination therapies delivered with this technology also show a consistent fine particle fraction (FPF) and an optimal particle size distribution for delivery to the central and peripheral airways even when multiple drugs are delivered via the same inhaler. Studies using gamma scintigraphy and functional respiratory imaging have demonstrated that GFF MDI is effectively deposited in the central and peripheral airways, and provides clinically meaningful benefits on airway volume and resistance throughout the lung. Overall, studies suggest that the Aerosphere inhaler, formulated using co-suspension delivery technology, may offer advantages over traditional formulations, including consistent delivery of multiple components across patient handling conditions, optimal particle size and FPF, and effective delivery to the central and peripheral airways. Future studies may provide additional evidence to further characterize the clinical benefits of these technical improvements in MDI drug delivery.

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“…Principles of aerosol delivery to airways suggest that particles of the order of 1 to 3 μm deposit to the lung periphery, and this is supported by human experimental evidence. 82 , 83 Furthermore, optimal inhalation rate and breath hold also have an impact on total deposition and penetration to the periphery. Treating severe asthma requires optimization of inhaled therapy, and therefore getting high ICS doses reaching the lungs and particularly to the lung periphery, at least for a defined trial period to determine true ICS resistance.…”

Section: The Future: Comprehensive Phenotyping Including Peripheral A...mentioning

confidence: 99%

Improving asthma outcomes: Clinicians’ perspectives on peripheral airways

King,

Chung,

Usmani

et al. 2024

Journal of Allergy and Clinical Immunology: Global

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Inhaled aerosol dose distribution between proximal bronchi and lung periphery

Cited by 12 publications

References 20 publications

Predicting Lung Deposition of Extrafine Inhaled Corticosteroid-Containing Fixed Combinations in Patients with Chronic Obstructive Pulmonary Disease Using Functional Respiratory Imaging: An In Silico Study

Predicting Lung Deposition of Extrafine Inhaled Corticosteroid-Containing Fixed Combinations in Patients with Chronic Obstructive Pulmonary Disease Using Functional Respiratory Imaging: An In Silico Study

Consistent Pulmonary Drug Delivery with Whole Lung Deposition Using the Aerosphere Inhaler: A Review of the Evidence

Improving asthma outcomes: Clinicians’ perspectives on peripheral airways

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