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Lower Inspiratory Breathing Depth Enhances Pulmonary Delivery Efficiency of ProAir Sprays

Effective pulmonary drug delivery using a metered-dose inhaler (MDI) requires a match between the MDI sprays, the patient’s breathing, and respiratory physiology. Different inhalers generate aerosols with distinct aerosol sizes and speeds, which require specific breathing coordination to achieve opt...

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Autores principales: Talaat, Mohamed, Si, Xiuhua April, Xi, Jinxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227885/
https://www.ncbi.nlm.nih.gov/pubmed/35745624
http://dx.doi.org/10.3390/ph15060706
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author Talaat, Mohamed
Si, Xiuhua April
Xi, Jinxiang
author_facet Talaat, Mohamed
Si, Xiuhua April
Xi, Jinxiang
author_sort Talaat, Mohamed
collection PubMed
description Effective pulmonary drug delivery using a metered-dose inhaler (MDI) requires a match between the MDI sprays, the patient’s breathing, and respiratory physiology. Different inhalers generate aerosols with distinct aerosol sizes and speeds, which require specific breathing coordination to achieve optimized delivery efficiency. Inability to perform the instructed breathing maneuver is one of the frequently reported issues during MDI applications; however, their effects on MDI dosimetry are unclear. The objective of this study is to systemically evaluate the effects of breathing depths on regional deposition in the respiratory tract using a ProAir-HFA inhaler. An integrated inhaler mouth-throat-lung geometry model was developed that extends to the ninth bifurcation (G9). Large-eddy simulation (LES) was used to compute the airflow dynamics due to concurrent inhalation and orifice flows. The discrete-phase Lagrangian model was used to track droplet motions. Experimental measurements of ProAir spray droplet sizes and speeds were used as initial and boundary conditions to develop the computational model for ProAir-pulmonary drug delivery. The time-varying spray plume from a ProAir-HFA inhaler into the open air was visualized using a high-speed imaging system and was further used to validate the computational model. The inhalation dosimetry of ProAir spray droplets in the respiratory tract was compared among five breathing depths on a regional, sub-regional, and local basis. The results show remarkable differences in airflow dynamics within the MDI mouthpiece and the droplet deposition distribution in the oral cavity. The inhalation depth had a positive relationship with the deposition in the mouth and a negative relationship with the deposition in the five lobes beyond G9 (small airways). The highest delivery efficiency to small airways was highest at 15 L/min and declined with an increasing inhalation depth. The drug loss inside the MDI was maximal at 45–60 L/min. Comparisons to previous experimental and numerical studies revealed a high dosimetry sensitivity to the inhaler type and patient breathing condition. Considering the appropriate inhalation waveform, spray actuation time, and spray properties (size and velocity) is essential to accurately predict inhalation dosimetry from MDIs. The results highlight the importance of personalized inhalation therapy to match the patient’s breathing patterns for optimal delivery efficiencies. Further complimentary in vitro or in vivo experiments are needed to validate the enhanced pulmonary delivery at 15 L/min.
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spelling pubmed-92278852022-06-25 Lower Inspiratory Breathing Depth Enhances Pulmonary Delivery Efficiency of ProAir Sprays Talaat, Mohamed Si, Xiuhua April Xi, Jinxiang Pharmaceuticals (Basel) Article Effective pulmonary drug delivery using a metered-dose inhaler (MDI) requires a match between the MDI sprays, the patient’s breathing, and respiratory physiology. Different inhalers generate aerosols with distinct aerosol sizes and speeds, which require specific breathing coordination to achieve optimized delivery efficiency. Inability to perform the instructed breathing maneuver is one of the frequently reported issues during MDI applications; however, their effects on MDI dosimetry are unclear. The objective of this study is to systemically evaluate the effects of breathing depths on regional deposition in the respiratory tract using a ProAir-HFA inhaler. An integrated inhaler mouth-throat-lung geometry model was developed that extends to the ninth bifurcation (G9). Large-eddy simulation (LES) was used to compute the airflow dynamics due to concurrent inhalation and orifice flows. The discrete-phase Lagrangian model was used to track droplet motions. Experimental measurements of ProAir spray droplet sizes and speeds were used as initial and boundary conditions to develop the computational model for ProAir-pulmonary drug delivery. The time-varying spray plume from a ProAir-HFA inhaler into the open air was visualized using a high-speed imaging system and was further used to validate the computational model. The inhalation dosimetry of ProAir spray droplets in the respiratory tract was compared among five breathing depths on a regional, sub-regional, and local basis. The results show remarkable differences in airflow dynamics within the MDI mouthpiece and the droplet deposition distribution in the oral cavity. The inhalation depth had a positive relationship with the deposition in the mouth and a negative relationship with the deposition in the five lobes beyond G9 (small airways). The highest delivery efficiency to small airways was highest at 15 L/min and declined with an increasing inhalation depth. The drug loss inside the MDI was maximal at 45–60 L/min. Comparisons to previous experimental and numerical studies revealed a high dosimetry sensitivity to the inhaler type and patient breathing condition. Considering the appropriate inhalation waveform, spray actuation time, and spray properties (size and velocity) is essential to accurately predict inhalation dosimetry from MDIs. The results highlight the importance of personalized inhalation therapy to match the patient’s breathing patterns for optimal delivery efficiencies. Further complimentary in vitro or in vivo experiments are needed to validate the enhanced pulmonary delivery at 15 L/min. MDPI 2022-06-03 /pmc/articles/PMC9227885/ /pubmed/35745624 http://dx.doi.org/10.3390/ph15060706 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Talaat, Mohamed
Si, Xiuhua April
Xi, Jinxiang
Lower Inspiratory Breathing Depth Enhances Pulmonary Delivery Efficiency of ProAir Sprays
title Lower Inspiratory Breathing Depth Enhances Pulmonary Delivery Efficiency of ProAir Sprays
title_full Lower Inspiratory Breathing Depth Enhances Pulmonary Delivery Efficiency of ProAir Sprays
title_fullStr Lower Inspiratory Breathing Depth Enhances Pulmonary Delivery Efficiency of ProAir Sprays
title_full_unstemmed Lower Inspiratory Breathing Depth Enhances Pulmonary Delivery Efficiency of ProAir Sprays
title_short Lower Inspiratory Breathing Depth Enhances Pulmonary Delivery Efficiency of ProAir Sprays
title_sort lower inspiratory breathing depth enhances pulmonary delivery efficiency of proair sprays
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227885/
https://www.ncbi.nlm.nih.gov/pubmed/35745624
http://dx.doi.org/10.3390/ph15060706
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