A Simplified Geometric Model to Predict Nasal Spray Deposition in Children and Adults

A mathematical approach was developed to estimate spray deposition patterns in the nasal cavity based on the geometric relationships between the emitted spray plume and the anatomical dimensions of the nasal valve region of the nasal cavity. Spray plumes were assumed to be spherical cones and the nasal valve region was approximated as an ellipse. The effect of spray plume angle (15–85°) on the fraction of the spray able to pass through the nasal valve (deposition fraction) was tested for a variety of nasal valve (ellipse) shapes and cross-sectional areas based on measured dimensions from pediatric and adult nasal cavities. The effect of the distances between the tip of the nasal spray device and the nasal valve (0.2–1.9 cm) on the deposition fraction was also tested. Simulation results show that (1) decreasing spray plume angles resulted in higher deposition fractions, (2) deposition fraction was inversely proportional to the spray distance and the nasal valve (ellipse) major/minor axis ratio, and (3) for fixed major/minor axis ratios, improved deposition occurred with larger nasal valve cross-sectional areas. For a typical adult nasal valve, plume angles of less than 40° emitted from a distance of 1 cm resulted depositions greater than 90% within the main nasal cavity, whereas for a 12-year-old child, only the most narrow plume angles (<?20°) administered resulted in significant deposition beyond the nasal valve.     

Effects of Localized Hydrophilic Mannitol and Hydrophobic Nelfinavir Administration Targeted to Olfactory Epithelium on Brain Distribution

Many nasally applied compounds gain access to the brain and the central nervous system (CNS) with varying degree. Direct nose-to-brain access is believed to be achieved through nervous connections which travel from the CNS across the cribriform plate into the olfactory region of the nasal cavity. However, current delivery strategies are not targeted to preferentially deposit drugs to the olfactory at cribriform. Therefore, we have developed a pressurized olfactory delivery (POD) device which consistently and non-invasively deposited a majority of drug to the olfactory region of the nasal cavity in rats. Using both a hydrophobic drug, mannitol (log P = -3.1), and a hydrophobic drug, nelfinavir (log P = 6.0), and POD device, we compared brain and blood levels after nasal deposition primarily on the olfactory region with POD or nose drops which deposited primarily on the respiratory region in rats. POD administration of mannitol in rats provided a 3.6-fold (p < 0.05) increase in cortex-to-blood ratio, compared to respiratory epithelium deposition with nose drop. Administration of nelfinavir provided a 13.6-fold (p < 0.05) advantage in cortex-to-blood ratio with POD administration, compared to nose drops. These results suggest that increasing the fraction of drug deposited on the olfactory region of the nasal cavity will result in increased direct nose-to-brain transport.     

On the removal of air-borne droplets by the human respiratory tract: II. The nasal passages

Theoretical considerations lead to the calculation of the amounts of air-borne materials removed by the various regions of the human nasal passages. These calculations are presented and discussed in the light of available data and lead to the conclusion that impaction due to inertia is the principle factor in the removal of the air-borne particles of diameters greater than one micron. The work described in this paper was done in part under contract between the Medical Division, Chemical Corps, U. S. Army, and The University of Chicago Toxicity Laboratory. Under terms of the contract the Chemical Corps neither restricts nor is responsible for the opinions or conclusions of the author.     

Microdistribution of alpha particles in pathological sections of tissues from thorotrast patients detected by imaging plate autoradiography

Thorotrast is a colloidal suspension of radioactive (232)ThO(2) that naturally emits alpha particles (90%), beta particles and gamma rays (10%). Thorotrast was used as a radiographic contrast agent in the 1930s-1950s; it caused liver cancer several decades after injection because of its life-long deposition and exposure. Determination of the amount and the distribution of radioactive thorium are essential for assessment of radiation risks. We visualized alpha particles on ordinary archival tissue sections using an imaging plate and a BAS5000 image analyzer. Furthermore, we confirmed that the imaging system is sensitive enough to detect alpha particles and accurate in measuring the total amount of thorium deposited in the organ from a single tissue section. This method revealed that the amount of thorium deposited in tumor tissue is correlated to that in non-tumor tissue. Thorotrast deposition was not associated with DNA damage determined by histochemistry. In combination with histological findings, it is suggested that radioactive thorium always migrates within the deposited organs by macrophages, and that the organs are evenly exposed to alpha particles.     

Computational fluid dynamics modeling of the upper airway of children with obstructive sleep apnea syndrome in steady flow

Computational fluid dynamic (CFD) analysis was used to model the effect of airway geometry on internal pressure in the upper airway of three children with obstructive sleep apnea syndrome (OSAS), and three controls. Model geometry was reconstructed from magnetic resonance images obtained during quiet tidal breathing, meshed with an unstructured grid, and solved at normative peak resting flow. The unsteady Reynolds-averaged Navier-Stokes equations were solved with steady flow boundary conditions in inspiration and expiration, using a two-equation low-Reynolds number turbulence model. Model results were validated using an in-vitro scale model, unsteady flow simulation, and reported nasal resistance measurements in children. Pharynx pressure drop strongly correlated to airway area restriction. Inspiratory pressure drop was primarily proportional to the square of flow, consistent with pressure losses due to convective acceleration caused by area restriction. On inspiration, in OSAS pressure drop occurred primarily between the choanae and the region where the adenoids overlap the tonsils (overlap region) due to airway narrowing, rather than in the nasal passages; in controls the majority of pressure drop was in the nasal passages. On expiration, in OSAS the majority of pressure drop occurred between the oropharynx (posterior to the tongue) and overlap region, and local minimum pressure in the overlap region was near atmospheric due to pressure recovery in the anterior nasopharynx. The results suggest that pharyngeal airway shape in children with OSAS significantly affects internal pressure distribution compared to nasal resistance. The model may also help explain regional dynamic airway narrowing during expiration.     

A two-component theory of aerosol deposition in lung airways

The deposition of aerosol particles in the human lung airways is due to two distinct mechanisms. One is by direct deposition resulting from diffusion, sedimentation and impaction as the aerosol moves in and out of the lung. The other is an indirect mechanism by which particles are transported mechanically from the tidal air to the residential air and eventually captured by the airways due to intrinsic particle motion. This last mechanism is not well understood at present. Using a trumpet airway model constructed from Weibel's data, a two-component theory is developed. In this theory, the particle concentrations in the airways and the alveoli at a given airway depth are considered to be quantitatively different. This difference in concentrations will cause a net mixing between the tidal and residential aerosol as the aerosol is breathed in and out. A distribution parameter is then introduced to account for the distribution of ventilation. The effect of intrinsic particle motion on the aerosol mixing is also included. From this theory, total and regional deposition in the lung at the steady mouth breathing without pause is calculated for several different respiratory cycles. The results agree reasonably well with the experimental data.     

Some hydrodynamic aspects of fitter feeding with rectangular-mesh nets

The maximum particle-capture efficiencies of rectangular-mesh nets have been estimated for cases where the net is set up in running water. The pressure drop due to fluid flow through a plane, rectangular network of cylindrical fibres at low Reynolds number was derived from equations published for an array of parallel, equally-spaced cylinders. Expressions were assumed for the pressure drop across a plane, porous disc of finite extent in a high Reynolds-number flow, so as to find the average flow speed through the disc as a function of the flow speed in its absence. This information was used to estimate the speed of water flow through particular examples of Trichoptera larval filter nets, and from this, their efficiencies of particle capture due to direct interception and to diffusional deposition, in terms of the flow approaching the mouth of the filter system from far upstream. The Stokes number, which governs the contribution of inertial impaction to the capture process, was also found for various particle sizes. Diffusional deposition and inertial impaction were estimated to be negligible except for particles smaller than 0·3 μm and larger than 50 μm respectively. It is suggested that coarse-net spinners, Hydropsyche and Arctopsyche, are potentially highly efficient at capturing large particles, whereas Macronema and the philopotamids are better adapted to the capture of particles smaller than 3 μm.     

Mechanisms of Pharmaceutical Aerosol Deposition in the Respiratory Tract

Aerosol delivery is noninvasive and is effective in much lower doses than required for oral administration. Currently, there are several types of therapeutic aerosol delivery systems, including the pressurized metered-dose inhaler, the dry powder inhaler, the medical nebulizer, the solution mist inhaler, and the nasal sprays. Both oral and nasal inhalation routes are used for the delivery of therapeutic aerosols. Following inhalation therapy, only a fraction of the dose reaches the expected target area. Knowledge of the amount of drug actually deposited is essential in designing the delivery system or devices to optimize the delivery efficiency to the targeted region of the respiratory tract. Aerosol deposition mechanisms in the human respiratory tract have been well studied. Prediction of pharmaceutical aerosol deposition using established lung deposition models has limited success primarily because they underestimated oropharyngeal deposition. Recent studies of oropharyngeal deposition of several drug delivery systems identify other factors associated with the delivery system that dominates the transport and deposition of the oropharyngeal region. Computational fluid dynamic simulation of the aerosol transport and deposition in the respiratory tract has provided important insight into these processes. Investigation of nasal spray deposition mechanisms is also discussed.     

Effect of anatomy on human nasal air flow and odorant transport patterns: implications for olfaction

Recent studies that have compared CT or MRI images of an individual's nasal anatomy and measures of their olfactory sensitivity have found a correlation between specific anatomical areas and performance on olfactory assessments. Using computational fluid dynamics (CFD) techniques, we have developed a method to quickly (相似文献   

Computational model of particle deposition in the nasal cavity under steady and dynamic flow

A computational model for flow and particle deposition in a three-dimensional representation of the human nasal cavity is developed. Simulations of steady state and dynamic airflow during inhalation are performed at flow rates of 9–60 l/min. Depositions for particles of size 0.5–20 μm are determined and compared with experimental and simulation results from the literature in terms of deposition efficiencies. The nasal model is validated by comparison with experimental and simulation results from the literature for particle deposition under steady-state flow. The distribution of deposited particles in the nasal cavity is presented in terms of an axial deposition distribution as well as a bivariate axial deposition and particle size distribution. Simulations of dynamic airflow and particle deposition during an inhalation cycle are performed for different nasal cavity outlet pressure variations and different particle injections. The total particle deposition efficiency under dynamic flow is found to depend strongly on the dynamics of airflow as well as the type of particle injection.     

Characterization and Deposition of Respirable Large- and Small-Particle Bioaerosols

The deposition patterns of large-particle microbiological aerosols within the respiratory tract are not well characterized. A novel system (the flow-focusing aerosol generator [FFAG]) which enables the generation of large (>10-μm) aerosol particles containing microorganisms under laboratory conditions was characterized to permit determination of deposition profiles within the murine respiratory tract. Unlike other systems for generating large aerosol particles, the FFAG is compatible with microbiological containment and the inhalational challenge of animals. By use of entrapped Escherichia coli cells, Bacillus atrophaeus spores, or FluoSphere beads, the properties of aerosols generated by the FFAG were compared with the properties of aerosols generated using the commonly available Collison nebulizer, which preferentially generates small (1- to 3-μm) aerosol particles. More entrapped particulates (15.9- to 19.2-fold) were incorporated into 9- to 17-μm particles generated by the FFAG than by the Collison nebulizer. The 1- to 3-μm particles generated by the Collison nebulizer were more likely to contain a particulate than those generated by the FFAG. E. coli cells aerosolized using the FFAG survived better than those aerosolized using the Collison nebulizer. Aerosols generated by the Collison nebulizer and the FFAG preferentially deposited in the lungs and nasal passages of the murine respiratory tract, respectively. However, significant deposition of material also occurred in the gastrointestinal tract after inhalation of both the small (89.7%)- and large (61.5%)-particle aerosols. The aerosols generated by the Collison nebulizer and the FFAG differ with respect to mass distribution, distribution of the entrapped particulates, bacterial survival, and deposition within the murine respiratory tract.     

A computational study of odorant transport and deposition in the canine nasal cavity: implications for olfaction

Olfaction begins when an animal draws odorant-laden air into its nasal cavity by sniffing, thus transporting odorant molecules from the external environment to olfactory receptor neurons (ORNs) in the sensory region of the nose. In the dog and other macrosmatic mammals, ORNs are relegated to a recess in the rear of the nasal cavity that is comprised of a labyrinth of scroll-like airways. Evidence from recent studies suggests that nasal airflow patterns enhance olfactory sensitivity by efficiently delivering odorant molecules to the olfactory recess. Here, we simulate odorant transport and deposition during steady inspiration in an anatomically correct reconstructed model of the canine nasal cavity. Our simulations show that highly soluble odorants are deposited in the front of the olfactory recess along the dorsal meatus and nasal septum, whereas moderately soluble and insoluble odorants are more uniformly deposited throughout the entire olfactory recess. These results demonstrate that odorant deposition patterns correspond with the anatomical organization of ORNs in the olfactory recess. Specifically, ORNs that are sensitive to a particular class of odorants are located in regions where that class of odorants is deposited. The correlation of odorant deposition patterns with the anatomical organization of ORNs may partially explain macrosmia in the dog and other keen-scented species.     

Modelling crystal aggregation and deposition in the catheterised lower urinary tract

Urethral catheters often become encrusted with crystals of magnesium struvite and calcium phosphate. The encrustation can block the catheter, which can cause urine retention in the bladder and reflux into the kidneys. We develop a mathematical model to investigate crystal deposition on the catheter surface, modelling the bladder as a reservoir of fluid and the urethral catheter as a rigid channel. At a constant rate, fluid containing crystal particles of unit size enters the reservoir, and flows from the reservoir through the channel and out of the system. The crystal particles aggregate, which we model using Becker–Döring coagulation theory, and are advected through the channel, where they continue to aggregate and are deposited on the channel’s walls. Inhibitor particles also enter the reservoir, and can bind to the crystals, preventing further aggregation and deposition. The crystal concentrations are spatially homogeneous in the reservoir, whereas the channel concentrations vary spatially as a result of advection, diffusion and deposition. We investigate the effect of inhibitor particles on the amount of deposition. For all parameter values, we find that crystals deposit along the full length of the channel, with maximum deposition close to the channel’s entrance.     

Whole-mount silver staining of Arabidopsis and maize: a new method for staining secondary wall thickenings in tracheary elements

Secondary wall thickenings in tracheary elements were specifically stained by incubation of Arabidopsis and maize in Silver Stain Plus (Bio-Rad) staining solution, after pretreatment with SDS and ethanol solution. Scanning electron microscopic analysis of sections of celery revealed that silver particles were deposited on the secondary wall thickenings, indicating that the staining was due to the deposition of silver through the interaction of the stain with lignin. This method is more sensitive than the acidified phloroglucinol method.     

Surgical treatment of nasal obstruction secondary to craniofacial fibrous dysplasia

Craniofacial fibrous dysplasia, a skeletal disorder most often affecting the mandible or maxilla, can cause a variety of complications. Nasal obstruction secondary to this unusual disorder presents a diagnostic and therapeutic challenge. The nasal obstruction in this case is due to expansion of fibrous lesions in adjacent bones as well as direct involvement of the turbinates with fibrous dysplasia. We describe the surgical correction of nasal obstruction in this unique setting and present a brief update of this intriguing disorder.     

Respiratory deposition model of an inhaled aerosol bolus

The bolus delivery method is designed to deliver a dose to the desired location in the lung, and it has the advantage of fewer side effects and a more efficient way of delivery. Based upon the lung deposition model developed for continuously inhaling aerosols of constant concentration, a mathematical model of aerosol bolus deposition is proposed. The calculated results show that the recovery depends on the bolus penetration depth, flow rate, particle size, breath holding time and bolus volume. Three sets of published experimental data with different controlling factors (particle size, flow rate and breath holding time) are adopted to make the quantitative comparisons with the calculated results. The predictions and data for the low intrinsic motion particles (～1 μm) have good agreement, as do the coarse particles in the shallow airways region. For females, the recovery was found to be consistently lower than that for males.     

Changes in the arrangement of cellulose microfibrils associated with the cessation of cell expansion in tracheids

 The relationship between the cessation of cell expansion and formation of the secondary wall was investigated in the early-wood tracheids of Abies sachalinensis Masters by image analysis and field emission scanning electron microscopy. The area of the lumen and the length of the perimeter of the lumen of differentiating tracheids increased from the cambium towards the xylem. These increases had just ceased in the case of tracheids closest to the cambium in which birefringence was first detected by observations with a polarizing light microscope. Cellulose microfibrils (MFs) deposited on the innermost surfaces of radial walls were not well ordered during the expansion of cells, but well ordered MFs were deposited at the subsequent stage of cell wall formation. The first well ordered MFs were oriented in an S-helix. The well ordered MFs had already been deposited at the tracheids where birefringence was first detected under the polarizing light microscope. These results indicate that the deposition of the well ordered MFs, namely, the formation of the secondary wall, begins before the cessation of cell expansion of tracheids. Therefore, it seems that the expansion of tracheids is restricted by the deposition of the secondary wall because the cell walls become rigid simultaneously with the development of the secondary wall and, therefore, the yield point of cell walls exceeds the turgor pressure of the cell. Received: 3 July 1996 / Accepted: 24 September 1996     

Deposition of Erysiphe graminis Conidia on a Barley Crop

Naturally released Erysiphe graminis conidia were trapped (on horizontal slides, on vertical sticky cylinders and in suction traps) in a barley crop infected with powdery mildew and the numbers of single spores and of clumps of different sizes deposited on the traps were counted. The efficiencies of impaction calculated from deposits and wind speed measurements were higher than expected from mean wind speed measurements. The values were consistent with the hypothesis that spores were removedpredominantly in gusts. More than half the conidia were removed in clumps of two or more spores. The measurements suggest that clumps were more effectively deposited than single spores. The measurements demonstrate that spore release mechanisms can influence spore deposition significantly, especially close to the source.     

Numerical simulation of airflow and microparticle deposition in a synchrotron micro-CT-based pulmonary acinus model

The acinus consists of complex, branched alveolar ducts and numerous surrounding alveoli, and so in this study, we hypothesized that the particle deposition can be much influenced by the complex acinar geometry, and simulated the airflow and particle deposition (density = 1.0 g/cm³, diameter = 1 and 3 μm) numerically in a pulmonary acinar model based on synchrotron micro-CT of the mammalian lung. We assumed that the fluid–structure interaction was neglected and that alveolar flow was induced by the expansion and contraction of the acinar model with the volume changing sinusoidally with time as the moving boundary conditions. The alveolar flow was dominated by radial flows, and a weak recirculating flow was observed at the proximal side of alveoli during the entire respiratory cycle, despite the maximum Reynolds number at the inlet being 0.029. Under zero gravity, the particle deposition rate after single breathing was less than 0.01, although the particles were transported deeply into the acinus after inspiration. Under a gravitational field, the deposition rate and map were influenced strongly by gravity orientation. In the case of a particle diameter of 1 μm, the rate increased dramatically and mostly non-deposited particles remained in the model, indicating that the rate would increase further after repeated breathing. At a particle diameter of 3 μm, the rate was 1.0 and all particles were deposited during single breathing. Our results show that the particle deposition rate in realistic pulmonary acinar model is higher than in an idealized model.     

Respiratory deposition model of an inhaled aerosol bolus

The bolus delivery method is designed to deliver a dose to the desired location in the lung, and it has the advantage of fewer side effects and a more efficient way of delivery. Based upon the lung deposition model developed for continuously inhaling aerosols of constant concentration, a mathematical model of aerosol bolus deposition is proposed. The calculated results show that the recovery depends on the bolus penetration depth, flow rate, particle size, breath holding time and bolus volume. Three sets of published experimental data with different controlling factors (particle size, flow rate and breath holding time) are adopted to make the quantitative comparisons with the calculated results. The predictions and data for the low intrinsic motion particles (～1 μm) have good agreement, as do the coarse particles in the shallow airways region. For females, the recovery was found to be consistently lower than that for males.