In vivo experiments have shown that nanoparticles depositing in the rat olfactory region can tran... more In vivo experiments have shown that nanoparticles depositing in the rat olfactory region can translocate to the brain via the olfactory nerve. Quantitative predictions of the dose delivered by inhalation to the olfactory region are needed to clarify this route of exposure and to evaluate the dose-response effects of exposure to toxic nanoparticles. Previous in vivo and in vitro studies quantified the percentage of inhaled nanoparticles that deposit in the rat nasal passages, but olfactory dose was not determined. The dose to specific nasal epithelium types is expected to vary with inhalation rate and particle size. The purpose of this investigation, therefore, was to develop estimates of nanoparticle deposition in the nasal and, more specifically, olfactory regions of the rat. A three-dimensional, anatomically accurate, computational fluid dynamics (CFD) model of the rat nasal passages was employed to simulate inhaled airflow and to calculate nasal deposition efficiency. Particle sizes from 1 to 100 nm and airflow rates of 288, 432, and 576 ml/min (1, 1.5, and 2 times the estimated resting minute volume) were simulated. The simulations predicted that olfactory deposition is maximum at 6-9% of inhaled material for 3- to 4-nm particles. The spatial distribution of deposited particles was predicted to change significantly with particle size, with 3-nm particles depositing mostly in the anterior nose, while 30-nm particles were more uniformly distributed throughout the nasal passages.
Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2009
Interindividual variability in nasal filtration is significant due to interindividual differences... more Interindividual variability in nasal filtration is significant due to interindividual differences in nasal anatomy and breathing rate. Two important consequences arise from this variation among humans. First, devices for nasal drug delivery may furnish quite different doses in the nasal passages of different individuals, leading to different responses to therapeutic treatment. Second, people with poor nasal filtration may be more susceptible to adverse health effects when exposed to airborne particulate matter (PM) due to greater lung deposition. Although interindividual variability of nasal filtration has been reported by several authors, a relationship for predicting filtration efficiency from nasal anatomy and ventilation is still lacking. Such a relationship is needed to (1) devise nasal drug delivery systems and (2) define limits of exposure to PM that are effective for the human population at large. Anatomically correct nasal replicas of five adults (four healthy individuals and one atrophic rhinitis patient) were used in aerosol experiments to measure nasal deposition of 1-12-microm particles. The dependence of nasal filtration on nasal anatomy and breathing rate was investigated using various definitions of the Stokes number as well as phenomenological Impaction Parameters proposed in the literature. Interindividual variability among the healthy adults was nearly eliminated when nasal filtration was plotted against a specific definition of the Stokes number or against a pressure-based Impaction Parameter. Nasal filtration in the atrophic rhinitis patient was lower than in the healthy subjects. The new definition of the Stokes number introduced in this study, which is based on a new definition of the characteristic diameter of the nasal passages, nearly eliminated interindividual differences in nasal filtration. Our results suggest that it is possible to estimate nasal filtering efficiency using measurements of transnasal pressure drop.
Septal deviation is an extremely common anatomic variation in healthy adults. However, there are ... more Septal deviation is an extremely common anatomic variation in healthy adults. However, there are no standard criteria to determine when a deviated septum is clinically relevant. Presently, selection of patients for septoplasty is based on mostly clinical examination, which is prone to observer bias and may lead to unsuccessful treatment. The objective of this article is twofold. First, we investigate whether the location of a septal deviation within the nasal passages affects nasal resistance. Second, we test whether computer simulations are consistent with rhinomanometry studies in predicting that anterior septal deviations increase nasal resistance more than posterior deviations. A three-dimensional computational model of a healthy nose was created from computed tomography scans. Geometry-deforming software was used to produce models with septal deviations. Computational fluid dynamics techniques were used to simulate nasal airflow and compute nasal resistance. Our results revealed that the posterior nasal cavity can accommodate significant septal deviations without a substantial increase in airway resistance. In contrast, a deviation in the nasal valve region more than doubled nasal resistance. These findings are in good agreement with the rhinomanometry literature and with the observation that patients with anterior septal deviations benefit the most from septoplasty. In the model, anterior septal deviations increased nasal resistance more than posterior deviations. This suggests, in agreement with the literature, that other causes of nasal obstruction (dysfunction of the nasal valve, allergy, etc.) should be carefully considered in patients with posterior septal deviations because such deviations may not affect nasal resistance. This study illustrates how computational modeling and virtual manipulation of the nasal geometry are useful to investigate nasal physiology.
In vivo experiments have shown that nanoparticles depositing in the rat olfactory region can tran... more In vivo experiments have shown that nanoparticles depositing in the rat olfactory region can translocate to the brain via the olfactory nerve. Quantitative predictions of the dose delivered by inhalation to the olfactory region are needed to clarify this route of exposure and to evaluate the dose-response effects of exposure to toxic nanoparticles. Previous in vivo and in vitro studies quantified the percentage of inhaled nanoparticles that deposit in the rat nasal passages, but olfactory dose was not determined. The dose to specific nasal epithelium types is expected to vary with inhalation rate and particle size. The purpose of this investigation, therefore, was to develop estimates of nanoparticle deposition in the nasal and, more specifically, olfactory regions of the rat. A three-dimensional, anatomically accurate, computational fluid dynamics (CFD) model of the rat nasal passages was employed to simulate inhaled airflow and to calculate nasal deposition efficiency. Particle sizes from 1 to 100 nm and airflow rates of 288, 432, and 576 ml/min (1, 1.5, and 2 times the estimated resting minute volume) were simulated. The simulations predicted that olfactory deposition is maximum at 6-9% of inhaled material for 3- to 4-nm particles. The spatial distribution of deposited particles was predicted to change significantly with particle size, with 3-nm particles depositing mostly in the anterior nose, while 30-nm particles were more uniformly distributed throughout the nasal passages.
Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2009
Interindividual variability in nasal filtration is significant due to interindividual differences... more Interindividual variability in nasal filtration is significant due to interindividual differences in nasal anatomy and breathing rate. Two important consequences arise from this variation among humans. First, devices for nasal drug delivery may furnish quite different doses in the nasal passages of different individuals, leading to different responses to therapeutic treatment. Second, people with poor nasal filtration may be more susceptible to adverse health effects when exposed to airborne particulate matter (PM) due to greater lung deposition. Although interindividual variability of nasal filtration has been reported by several authors, a relationship for predicting filtration efficiency from nasal anatomy and ventilation is still lacking. Such a relationship is needed to (1) devise nasal drug delivery systems and (2) define limits of exposure to PM that are effective for the human population at large. Anatomically correct nasal replicas of five adults (four healthy individuals and one atrophic rhinitis patient) were used in aerosol experiments to measure nasal deposition of 1-12-microm particles. The dependence of nasal filtration on nasal anatomy and breathing rate was investigated using various definitions of the Stokes number as well as phenomenological Impaction Parameters proposed in the literature. Interindividual variability among the healthy adults was nearly eliminated when nasal filtration was plotted against a specific definition of the Stokes number or against a pressure-based Impaction Parameter. Nasal filtration in the atrophic rhinitis patient was lower than in the healthy subjects. The new definition of the Stokes number introduced in this study, which is based on a new definition of the characteristic diameter of the nasal passages, nearly eliminated interindividual differences in nasal filtration. Our results suggest that it is possible to estimate nasal filtering efficiency using measurements of transnasal pressure drop.
Septal deviation is an extremely common anatomic variation in healthy adults. However, there are ... more Septal deviation is an extremely common anatomic variation in healthy adults. However, there are no standard criteria to determine when a deviated septum is clinically relevant. Presently, selection of patients for septoplasty is based on mostly clinical examination, which is prone to observer bias and may lead to unsuccessful treatment. The objective of this article is twofold. First, we investigate whether the location of a septal deviation within the nasal passages affects nasal resistance. Second, we test whether computer simulations are consistent with rhinomanometry studies in predicting that anterior septal deviations increase nasal resistance more than posterior deviations. A three-dimensional computational model of a healthy nose was created from computed tomography scans. Geometry-deforming software was used to produce models with septal deviations. Computational fluid dynamics techniques were used to simulate nasal airflow and compute nasal resistance. Our results revealed that the posterior nasal cavity can accommodate significant septal deviations without a substantial increase in airway resistance. In contrast, a deviation in the nasal valve region more than doubled nasal resistance. These findings are in good agreement with the rhinomanometry literature and with the observation that patients with anterior septal deviations benefit the most from septoplasty. In the model, anterior septal deviations increased nasal resistance more than posterior deviations. This suggests, in agreement with the literature, that other causes of nasal obstruction (dysfunction of the nasal valve, allergy, etc.) should be carefully considered in patients with posterior septal deviations because such deviations may not affect nasal resistance. This study illustrates how computational modeling and virtual manipulation of the nasal geometry are useful to investigate nasal physiology.
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Papers by Guilherme Garcia