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In-silico quantification of intersubject variability on aerosol deposition in the oral airway

Journal Article · · Pharmaceutics

The extrathoracic oral airway I s not only a major mechanical barrier for pharmaceutical aerosols to reach the lung but also a major source of variability in lung deposition. Using computational fluid dynamics, deposition of 1-30 µm particles was predicted in 11 CT-based models of the oral airways of adults (7 healthy subjects and 4 patients with chronic obstructive pulmonary disease). Simulations were performed for mouth breathing during both inspiration and expiration at two steady-state flow rates representative of resting/light activity (18 L/min) and of that typically used during aerosol inhalation from a dry powder inhaler (45 L/min). For each subject, oral deposition increased with increasing particle size and flow rate. When averaged over all subjects, there was no significant difference in oral deposition efficiency between inspiration and expiration, unlike subregional deposition that show significantly different patterns between the two breathing phases. Consistent with previous in-vitro inspiratory studies, our data showed a large intersubject variability in oral deposition. These results highlight the need for incorporating morphological variation of the upper airway in predictive models of aerosol deposition for accurate predictions of particle dosimetry in the intrathoracic region of the lung.

Research Organization:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
AC05-76RL01830
OSTI ID:
1910049
Report Number(s):
PNNL-SA-180130
Journal Information:
Pharmaceutics, Vol. 15, Issue 1
Country of Publication:
United States
Language:
English

References (50)

An in silico inter-subject variability study of extra-thoracic morphology effects on inhaled particle transport and deposition journal September 2018
Degree of Throat Deposition Can Explain the Variability in Lung Deposition of Inhaled Drugs journal December 2006
In Vivo–In VitroCorrelations: Predicting Pulmonary Drug Deposition from Pharmaceutical Aerosols journal December 2010
A case series on lung deposition analysis of inhaled medication using functional imaging based computational fluid dynamics in asthmatic patients: effect of upper airway morphology and comparison with in vivo data journal January 2012
In silico models of aerosol delivery to the respiratory tract — Development and applications journal March 2012
Aerosol Deposition in the Extrathoracic Region journal August 2003
In vitro intersubject and intrasubject deposition measurements in realistic mouth–throat geometries journal August 2004
An In vitro Study on the Deposition of Micrometer-Sized Particles in the Extrathoracic Airways of Adults During Tidal Oral Breathing journal January 2013
Particle Deposition in a Cast of Human Oral Airways journal October 1999
Measurements of Airway Dimensions and Calculation of Mass Transfer Characteristics of the Human Oral Passage journal November 1997
Inhaled Corticosteroids: Hazardous Effects on Voice—An Update journal January 2007
Steroid Inhaler Laryngitis journal June 2002
Visualization of local deposition of nebulized aerosols in a human upper respiratory tract model journal November 2017
Tutorial: Understanding the transport, deposition, and translocation of particles in human respiratory systems using Computational Fluid-Particle Dynamics and Physiologically Based Toxicokinetic models journal January 2021
Can CFD establish a connection to a milder COVID-19 disease in younger people? Aerosol deposition in lungs of different age groups based on Lagrangian particle tracking in turbulent flow journal March 2021
Development of a stochastic individual path (SIP) model for predicting the tracheobronchial deposition of pharmaceutical aerosols: Effects of transient inhalation and sampling the airways journal November 2011
Micro-particle transport and deposition in a human oral airway model journal December 2002
Effects of surface smoothness on inertial particle deposition in human nasal models journal January 2011
Total and regional deposition of inhaled aerosols in supine healthy subjects and subjects with mild-to-moderate COPD journal September 2016
Impact of endoscopic craniofacial resection on simulated nasal airflow and heat transport journal March 2019
Normative ranges of nasal airflow variables in healthy adults journal July 2019
On predicting particle-laden turbulent flows journal June 1994
Influence of Mesh Density on Airflow and Particle Deposition in Sinonasal Airway Modeling journal February 2016
Computational modeling and validation of human nasal airflow under various breathing conditions journal November 2017
Detailed flow patterns in the nasal cavity journal July 2000
Two-equation eddy-viscosity turbulence models for engineering applications journal August 1994
Orally Inhaled Drug Particle Transport in Computerized Models of Laryngotracheal Stenosis journal October 2020
Comparison of Inhaled Drug Delivery in Patients With One‐ and Two‐level Laryngotracheal Stenosis journal May 2022
Influence of alveolar mixing and multiple breaths of aerosol intake on particle deposition in the human lungs journal November 2022
Intercomparison of Experimental Regional Aerosol Deposition Data journal January 1989
Transport and Deposition of Micro-Aerosols in Realistic and Simplified Models of the Oral Airway journal January 2007
Effect of Respiratory Tract Disease on Particle Deposition journal September 2021
Aerosol Deposition in Health and Disease journal June 2012
Experimental measurements and empirical modelling of the regional deposition of inhaled particles in humans journal June 1980
Regional deposition of 2.5–7.5 μm diameter inhaled particles in healthy male non-smokers journal January 1978
Measurements of the total and regional deposition of inhaled particles in the human respiratory tract journal January 1982
New regional deposition data of the human respiratory tract journal January 1983
Experimental determination of the regional deposition of aerosol particles in the human respiratory tract journal June 1980
Biological variability of regional deposition of aerosol particles in the human respiratory tract journal May 1981
In silico assessment of mouth-throat effects on regional deposition in the upper tracheobronchial airways journal March 2018
Inspiratory and expiratory aerosol deposition in the upper airway journal February 2011
What the pulmonary specialist should know about the new inhalation therapies journal February 2011
Annexe D. deposition of inhaled particles journal September 1994
Proper Use of Aerosol Corticosteroids To Control Asthma journal February 1989
Frequency of voice problems and cough in patients using pressurized aerosol inhaled steroid preparations journal April 1995
Dynamic imaging of the upper airway during respiration in normal subjects journal April 1993
Upper airway dynamic imaging during tidal breathing in awake and asleep subjects with obstructive sleep apnea and healthy controls journal May 2018
A comparison of posterior pharyngeal wall areas between different tongue positions during inhalation journal February 2019
Determination of the preferred tongue position for optimal inhaler use journal May 2018
An investigation of the relationship between the flow field and regional deposition in realistic extra-thoracic airways journal August 2004