Human Nasal Cavity Research Articles

Genetic Profiling of Methicillin-resistant Staphylococcus aureus in An African Hospital by Multiplex-PCR

Objectives: Methicillin resistant Staphylococcus aureus (MRSA) nasal carriage often precedes infection. This work aims to genetically profile the MRSA carriage of resistant genes (mecA, blaZ and tetM) and certain virulence genes (nuc, pvl, spa and scn) obtained from human nasal cavity. Methods: Phenotypically confirmed Staphylococcus aureus were Screened for oxacillin resistance and assessed for β-lactamase production. Further confirmation of identity obtained by multiplex PCR of the 16SrRNA, mecA, tetM, pvl, nuc, spa and scn genes. DNA gel fingerprint analysis was carried out and the bands were clustered in a dendrogram. Results: The study analysed 81 Staphylococcus aureus isolates for Methicillin resistance out of which 38 (46.9%) were MRSA. The DNA extraction method was effective for all MRSA isolates evaluated. All phenotypic MRSA isolates (100%) were positive for the S. aureus specific 16SrRNA gene confirming that these isolates were S. aureus strains. The nuc gene was detected in 19/38 (50%) of the MRSA isolates, blaZ gene in 14/38 (36.8%) and tetM in 18/38 (47.4%). Conclusions: The need for improved vigilance to recognize MRSA strains cannot be overemphasized. If MRSA control is not tracked, these strains will increase exponentially. J Microbiol Infect Dis 2020; 10(3):144-153.

The effect of nasal airway obstruction on the dispersion and deposition of inhaled volatile droplets in the human nasal cavity: A numerical study

Nasal airway obstruction (NAO) is one of the main problems in the upper part of the human respiratory system. NAO may considerably affect the airflow and the behavior of droplets in the nasal cavity. In the present study, the effect of septal deviation as a special kind of NAO on the deposition and penetration of initially micron-sized inhaled droplets in the nasal cavities of two patients was numerically investigated. The geometries were constructed using CT scan images, and breathing zones were added to the models to make the inspiratory cycle more physically realistic. The motion of droplets was studied using the Lagrangian trajectory analysis approach, including the drag, Saffman's lift, and Brownian forces, as well as the evaporation process. The results showed that both unhealthy cases with obstruction had less heat transfer than the healthy nasal passage, which results in slower evaporation of droplets. On the other hand, due to the septal deviation, the deposition of droplets increased in the cases with nasal obstruction. Inertial impaction was the primary deposition mechanism, which was more critical than the diffusion in the region in which septal deviations diverted the airflow. The simulation results showed that due to less convoluted turbinate passages and smaller surface area to volume ratio (SAVR) of the nasal cavities with obstruction in comparison with a healthy nose, the size of droplets that escape from the human nasal cavity became smaller. As a result, for patients with septal deviations, small droplets could penetrate deep into the respiratory system and increase the risk of transmission of respiratory diseases.

Nasal disinfection for the prevention and control of COVID-19: A scoping review on potential chemo-preventive agents.

BackgroundNeither pre-exposure nor post-exposure chemo-prophylaxis agents are currently available to prevent COVID-19. On the other hand, high loads of SARS-CoV-2 are shed from the nasal cavity before and after symptoms onset.ObjectiveTo conduct a scoping review on the available evidence on tolerable nasal disinfectants with encouraging health outcomes against SARS-CoV-2, i.e., agents effective against at least two different viruses beyond SARS-CoV-2.MethodsOnline databases were searched to identify papers published during 2010–2020. Publications were selected if they were relevant to the scoping review. The review was narrative, describing for each treatment the mechanism(s) of action, tolerability, in vitro and in vivo evidence of the effects against SARS-CoV-2 and whether the product had been marketed.ResultsEight treatments were scrutinized: hypothiocyanite, lactoferrin, N-chlorotaurine, interferon-alpha, povidone-iodine, quaternary ammonium compounds, alcohol-based nasal antiseptics and hydroxychloroquine. In vitro viricidal effect against SARS-CoV-2 was reported for ethanol, alcohol-based hand sanitizers and povidone-iodine. Inhibition of other coronaviruses was described for lactoferrin, ethanol, hydroxychloroquine and quaternary ammonium compound. No treatment has been tested against SARS-CoV-2 in randomized controlled clinical trials thus far. However, interferon-alpha, lactoferrin and hydroxychloroquine were tested in one-arm open label uncontrolled clinical trial. Oxidant activity (hypothiocyanite, N-chlorotaurine and povidone-iodine), enhancement of endocytic and lysosomal pH (quaternary ammonium compounds and hydroxychloroquine) and destruction of the viral capsid (quaternary ammonium compounds, alcohol-based nasal antiseptics) were the main mechanisms of action. Lactoferrin and interferon-alpha have subtle biological mechanisms. With the exception of N-chlorotaurine, all other products available on the market.ConclusionsEffective and safe chemo-prophylactic drugs against SARS-CoV-2 do not exist yet but most eligible candidates are already in the market. Whilst the human nasal cavity is the port of entry for SARS-CoV-2, the mouth is involved as exit site through emission of respiratory droplets. The well-known hand-to-nose-to-hand cycle of contamination requires appropriate additional strategies for infection control. To narrow down the subsequent laboratory and clinical investigations, a case-control approach could be employed to compare the use of candidate drugs among individuals testing positive and negative to COVID-19 swabs.

An investigation of computational fluid dynamics of human nasal airflow using LS-DYNA®

Understanding the properties of airflow in the nasal cavity is essential in determining the nasal physiology and in diagnosis of various anomalies associated with the nose. This numerical study presents the characteristics of flow features inside a human nasal cavity. A three dimensional nasal cavity model is constructed from computed tomographic images of a healthy adult nose. Pressure inlet of 0 Pa is defined at the left and right nostril inlets representing the atmospheric condition. Negative pressure value is defined at the pharynx outlet to model the airflow suction during inhalation. This study shows the flow charcateristics and distribution in the nasal cavity is dependent on the complex geometry of the nasal airway. This simulation of breathing airflow enables us to visualize the flow features inside the complicated human nasal cavity which is otherwise impossible to be determined by any other method.

Voxel-based simulation of flow and temperature in the human nasal cavity

The nasal airway is an extremely complex structure, therefore grid generation for numerical prediction of airflow in the nasal cavity is time-consuming. This paper describes the development of a voxel-based model with a Cartesian structured grid, which is characterized by robust and automatic grid generation, and the simulation of the airflow and air-conditioning in an individual human nasal airway. Computed tomography images of a healthy adult nose were used to reconstruct a virtual three-dimensional model of the nasal airway. Simulations of quiet restful inspiratory flow were then performed using a Neumann boundary condition for the energy equation to adequately resolve the flow and heat transfer. General agreements of airflow patterns, which were a high-speed jet posterior to the nasal valve and recirculating flow that occupied the anterior part of the upper cavity, and temperature distributions of the airflow and septum wall were confirmed by comparing in-vivo measurements with numerical simulation results.

Olfactory Targeting of Microparticles Through Inhalation and Bi-directional Airflow: Effect of Particle Size and Nasal Anatomy.

Background: Targeting drugs to the olfactory region in the nasal cavity can bypass the restrictive blood-brain barrier and enhance their direct delivery to the brain. However, complex nasal geometry and its demographical variations can pose challenges for targeted drug deposition in the olfactory region. Deposition of particles in the nasal cavity is influenced by particle size, airflow rate, and nasal geometry. Therefore, this study investigated the effect of these parameters on regional microparticle deposition with the view to provide insights into the nose-to-brain delivery of drugs. Methods: In this study, three anatomically accurate human nasal cavities were reconstructed in silico and deposition of microparticles under nebulization and bi-directional airflow conditions was simulated. Microparticle deposition data were analyzed to gain insight into the effect of particle size and nasal geometry. Results: Maximum olfactory deposition was observed with particles in the size range of 8 to 12 μm under nebulization and 14 to 18 μm under bi-directional airflow condition. Geometric differences between subjects were shown to significantly impact overall and regional particle deposition and introduced inter-subject variability. Significant intra-subject variability in microparticle deposition was also observed in the bi-directional delivery cases. Conclusions: The data from this study suggest that tailoring particle size, combined with a delivery protocol, may provide a unique and pragmatic way to target drugs to the olfactory region. Differences in nasal anatomy among humans can cause variability in particle deposition and need to be considered in any future applications.

Deposition characteristics of a novel intranasal formulation of azelastine hydrochloride plus fluticasone propionate in an anatomic model of the human nasal cavity.

Background: Intranasal antihistamines and steroids should be delivered in a volume and with a technique that allow for optimal drug retention within the entire nasal cavity, maximize local absorption by the nasal mucosa, and, subsequently, increase the potential for the most desirable local availability and therapeutic effect. Objective: This in vitro evaluation simulated nasal medication deposition and evaluated the extent of runoff. MP-AzeFlu, a novel intranasal formulation of azelastine hydrochloride (AZE) plus fluticasone propionate (FP), was compared with sequential sprays of available commercial products with the individual medication components. Methods: A model of a normal adult human nasal cavity was used to visualize deposition of nasal spray products. A single spray of MP-AzeFlu (0.137 mL [137 μg of AZE/50 μg of FP]) or single sequential sprays of AZE nasal spray (0.137 mL [137 μg]) followed by brand name or generic FP nasal spray (0.100 mL [50 μg]) were manually actuated into the model. The interior was coated with a water-sensitive dye that changes to magenta when exposed to aqueous-based formulations. A slight vacuum was applied during spray delivery to simulate sniffing. The results were photographed by using anterior and lateral views. Results: Three replicates of MP-AzeFlu showed no dripping from the front of the nostril or backflow from the nasal cavity. However, three replicates of AZE nasal spray, followed by a brand name or generic FP nasal spray, showed significant dripping from the front of the nostril and backflow from the nasal cavity. Conclusion: A single spray of MP-AzeFlu resulted in no runoff compared with sequential dosing of the two other therapeutic products. Product runoff is likely due to the volume exceeding the capacity of the nasal cavity model. Furthermore, the common clinical dosing regimen of two sprays per nostril of each of the individual components would promote even greater increased undesirable flooding and leakage.

Numerical simulation of ellipsoidal particles deposition in the human nasal cavity under cyclic inspiratory flow

In this study, a computational fluid dynamics model of a 53-year-old nonsmoking Caucasian male was used to simulate the deposition of ellipsoidal particles under cyclic inhalation in the nasal cavity. A sinusoidal pattern (frequency: 0.25 Hz, maximum volume flow rate: 20 L/min) was set to simulate the realistic breathing pattern under a rest condition. In order to find the trajectory of inhaled particles, a series of unsteady particle tracking simulations using a Lagrangian approach were performed and ellipsoidal particles between 1 and 20 µm in size and 1–50 in aspect ratio were injected in the fluid domain. Results showed that for small particles (d = 1 µm), the deposition pattern follows the airflow pattern, and it increases/decreases by an increase/decrease in the inlet volume flow rate. Besides, the deposition is highly sensitive to the shape of the particles, and it rises by an increase in the aspect ratio. Interestingly, for particles in the range of 5–20 µm, the deposition is mainly dependent on the diameter. Also, the deposition pattern of particles with a diameter of 20 µm is entirely different from the deposition pattern of smaller particles, and it does not follow the inlet airflow pattern. Moreover, it was seen that the deposition fraction under cyclic breathing pattern in the acceleration and deceleration phases of the inhalation is not equal. Finally, it was shown that the inertial force has more contribution to the deposition of ellipsoidal particles, and as a result, tracking these particles under the equivalent mean airflow rate (Q = 12.7 L/min) causes significant errors in the total deposition fraction.

Numerical simulation of particle deposition in the human nasal cavity

This paper presents the results of numerical simulation of airflow with suspended particles through a human nasal cavity. The stationary and nonstationary problem statements were considered. Within the nonstationary case, two variants were studied: for the first variant, the breath cycle is taken with symmetric inhale/exhale, and for the second variant, we modelled a real asymmetric breath cycle. The solution was based on Navier-Stokes equations for laminar flow of incompressible gas. Particle flow is described using the Lagrangean approach with account for Brownian motion. Numerical simulation results were compared with experimental and simulation data from other authors. Results for different variants of problem statement were compared. Asymmetry of breath cycle should be accounted in calculation of particle deposition efficiency. A simple rule was found that replaces the computation-consuming nonstationary calculation with three stationary flow calculations.

Characterization of the Airflow within an Average Geometry of the Healthy Human Nasal Cavity

This study’s objective was the generation of a standardized geometry of the healthy nasal cavity. An average geometry of the healthy nasal cavity was generated using a statistical shape model based on 25 symptom-free subjects. Airflow within the average geometry and these geometries was calculated using fluid simulations. Integral measures of the nasal resistance, wall shear stresses (WSS) and velocities were calculated as well as cross-sectional areas (CSA). Furthermore, individual WSS and static pressure distributions were mapped onto the average geometry. The average geometry featured an overall more regular shape that resulted in less resistance, reduced WSS and velocities compared to the median of the 25 geometries. Spatial distributions of WSS and pressure of the average geometry agreed well compared to the average distributions of all individual geometries. The minimal CSA of the average geometry was larger than the median of all individual geometries (83.4 vs. 74.7 mm²). The airflow observed within the average geometry of the healthy nasal cavity did not equal the average airflow of the individual geometries. While differences observed for integral measures were notable, the calculated values for the average geometry lay within the distributions of the individual parameters. Spatially resolved parameters differed less prominently.

Qualitative Assessment of the Effect of Continuous Positive Airway Pressure on the Nasal Cavity.

For patients with obstructive sleep apnea (OSA), there is a lack of knowledge regarding the impact of continuous positive airway pressure (CPAP) on the nasal cavity. There is a significant need for evidence-based recommendations regarding the appropriate use of CPAP following endoscopic sinus and skull base surgery. The goal of this study is to translate a previously developed cadaveric model for evaluating CPAP pressures in the sinonasal cavity by showing safety in vivo and quantifying the effect of positive pressurized air flow on the nasal cavity of healthy individuals where physiologic effects are at play. A previously validated cadaveric model using intracranial sensor catheters has proved to be a reliable technique for measuring sinonasal pressures. These sensors were placed in the nasal cavity of 18 healthy individuals. Pressure within the nose was recorded at increasing levels of CPAP. Overall, nasal cavity pressure was on average 85% of delivered CPAP. The amount of pressure delivered to the nasal cavity increased as the CPAP increased. The percentage of CPAP delivered was 77% for 5 cmH2O and increased to 89% at 20 cmH2O. There was a significant difference in mean intranasal pressures between all the levels of CPAP except 5 cmH2O and 8 cmH2O (P < .001). On average, only 85% of the pressure delivered by CPAP is transmitted to the nasal cavity. Higher CPAP pressures delivered a greater percentage of pressurized air to the nasal cavity floor. Our results are comparable to the cadaver model, which demonstrated similar pressure delivery even in the absence of anatomic factors such as lung compliance, nasal secretions, and edema. This study demonstrates the safety of using sensors in the human nasal cavity. This technology can also be utilized to evaluate the resiliency of various repair techniques for endoscopic skull base surgery with CPAP administration.

Deposition fraction of ellipsoidal fibers in the human nasal cavity- Influence of non-creeping formulation of hydrodynamic forces and torques

In this study, the deposition of fibrous particles in a realistic 3D model of the right nasal cavity of a 24-years-old woman was simulated using the non-creeping formulations for hydrodynamic forces and torques. The Lagrangian trajectory analysis approach within the Ansys-Fluent software was used for these simulations. Several user-defined functions (UDFs) for solving the coupled translational and rotational motion of an ellipsoidal fiber and for evaluation of non-creeping forces and torques were developed and were incorporated in the Ansys-Fluent DPM. The passage included the main nasal cavity from the nostril to the beginning of the nasopharynx. Both laminar and turbulent steady inhalation breathing conditions were assumed, and for turbulence modeling, the Realizable k-ε model was employed. It was assumed that the airflow was incompressible. The breathing rates of 2.5, 5.0, 7.5, and 10 lit/min per nostril were considered for laminar airflow corresponding to the rest or light physical activity conditions. For turbulent airflow, the breathing rates of 15, 20, and 30 lit/min were assumed for high physical activities. The transport and deposition of fibers of different sizes and aspect ratios in the nasal cavity under laminar and turbulent airflow regimes were investigated.The simulation results showed that the increase of air flow rate, fiber diameter, and aspect ratio led to the increase of deposition in the human nasal cavity. In addition, the use of forces and torques estimated from the more accurate non-creeping flow estimation led to somewhat lower particle deposition in the nasal cavity compared to those obtained from the simplified creeping flow assumption.

Dual and Triple Epithelial Coculture Model Systems with Donor-Derived Microbiota and THP-1 Macrophages To Mimic Host-Microbe Interactions in the Human Sinonasal Cavities.

The epithelium of the human sinonasal cavities is colonized by a diverse microbial community, modulating epithelial development and immune priming and playing a role in respiratory disease. Here, we present a novel in vitro approach enabling a 3-day coculture of differentiated Calu-3 respiratory epithelial cells with a donor-derived bacterial community, a commensal species (Lactobacillus sakei), or a pathobiont (Staphylococcus aureus). We also assessed how the incorporation of macrophage-like cells could have a steering effect on both epithelial cells and the microbial community. Inoculation of donor-derived microbiota in our experimental setup did not pose cytotoxic stress on the epithelial cell layers, as demonstrated by unaltered cytokine and lactate dehydrogenase release compared to a sterile control. Epithelial integrity of the differentiated Calu-3 cells was maintained as well, with no differences in transepithelial electrical resistance observed between coculture with donor-derived microbiota and a sterile control. Transition of nasal microbiota from in vivo to in vitro conditions maintained phylogenetic richness, and yet a decrease in phylogenetic and phenotypic diversity was noted. Additional inclusion and coculture of THP-1-derived macrophages did not alter phylogenetic diversity, and yet donor-independent shifts toward higher Moraxella and Mycoplasma abundance were observed, while phenotypic diversity was also increased. Our results demonstrate that coculture of differentiated airway epithelial cells with a healthy donor-derived nasal community is a viable strategy to mimic host-microbe interactions in the human upper respiratory tract. Importantly, including an immune component allowed us to study host-microbe interactions in the upper respiratory tract more in depth.IMPORTANCE Despite the relevance of the resident microbiota in sinonasal health and disease and the need for cross talk between immune and epithelial cells in the upper respiratory tract, these parameters have not been combined in a single in vitro model system. We have developed a coculture system of differentiated respiratory epithelium and natural nasal microbiota and incorporated an immune component. As indicated by absence of cytotoxicity and stable cytokine profiles and epithelial integrity, nasal microbiota from human origin appeared to be well tolerated by host cells, while microbial community composition remained representative for that of the human (sino)nasal cavity. Importantly, the introduction of macrophage-like cells enabled us to obtain a differential readout from the epithelial cells dependent on the donor microbial background to which the cells were exposed. We conclude that both model systems offer the means to investigate host-microbe interactions in the upper respiratory tract in a more representative way.

Investigation of Coronavirus Deposition in Realistic Human Nasal Cavity and Impact of Social Distancing to Contain COVID-19: A Computational Fluid Dynamic Approach

The novel coronavirus responsible for COVID-19 has spread to several countries within a considerably short period. The virus gets deposited in the human nasal cavity and moves to the lungs that might be fatal. As per safety guidelines by the World Health Organization (WHO), social distancing has emerged as one of the major factors to avoid the spread of infection. However, different guidelines are being followed across the countries with regards to what should be the safe distance. Thus, the current work is an attempt to understand the virus deposition pattern in the realistic human nasal cavity and also to find the impact of distance that could be termed as a safety measure. This study is performed using Computational Fluid Dynamics as a solution tool to investigate the impact of COVID-19 deposition (i) On a realistic 3D human upper airway model and (ii) 2D social distancing protocol for a distance of 0.6, 1.2, 1.8, and 2.4 m. The results revealed that the regional deposition flux within the nasal cavity was predominantly observed in the external nasal cavity and nasopharyngeal section. Frequent flushing of these regions with saltwater substitutes can limit contamination in healthy individuals. The safe distancing limit estimated with 1 m/s airflow was about 1.8 m. The extensive deposition was observed for distances less than 1.8 m in this study, emphasizing the fact that social distancing advisories are not useful and do not take into account the external dynamics associated with airflow.

Evidence for accessory chemosensory cells in the adult human nasal cavity

The existence of functionally relevant accessory olfactory organs in humans is still a matter of controversy. A vomeronasal organ (VNO) with sensory and non-sensory epithelia exists only in macrosmatic mammals. A similar structure is regularly observed in humans during fetal development. The postnatal persistence of a VNO like epithelial duct has been described in about 10 %. Here we studied tissue samples of nasal mucosa from adults. In all individuals we found epithelial cells in the lower part of the nasal septum which exhibited morphological features of sensory neurons and which showed immunostaining for olfactory marker protein OMP. These cells were interposed by ciliated cells, goblet cells and small intraepithelial capillaries. Only occasionally we found such cells within a morphologically defined epithelial duct. A clear separation of sensory and non-sensory epithelia could not be observed. In most cases we found OMP positive groups of cells either in epithelial cavities or just embedded in respiratory epithelium. With RT-PCR we could confirm the presence of OMP encoding mRNA thus supporting the idea of intrinsic expression of this protein in the nasal mucosa. We conclude that accessory chemosensory structures are regularly conserved in adult humans in the approximate anatomical location of the VNO of microsmatic animals. Their functional importance is yet to be determined.

Influence of airflow dynamics on vortices in the human nasal cavity

Purpose The purpose of this paper is to understand the effect of airflow dynamics on vortices for different flow rates using the human nose three-dimensional model. Design/methodology/approach Olfaction originates with air particles travelling from an external environment to the upper segment of the human nose. This phenomenon is generally understood by using the nasal airflow dynamics, which enhances the olfaction by creating the vortices in the human nose. An anatomical three-dimensional model of the human nasal cavity from computed tomography (CT) scan images using the MIMICS software (Materialise, USA) was developed in this study. Grid independence test was performed through volume flow rate, pressure drop from nostrils and septum and average velocity near the nasal valve region using a four computational mesh model. Computational fluid dynamics (CFD) was used to examine the flow pattern and influence of airflow dynamics on vortices in the nasal cavity. Numerical simulations were conducted for the flow rates of 7.5, 10, 15 and 20 L/min using numerical finite volume methods. Findings At coronal cross-sections, dissimilar nasal airflow patterns were observed for 7.5, 10, 15 and 20 L/min rate of fluid flow in the human nasal cavity. Vortices that are found at the boundaries with minimum velocity creates deceleration zone in the nose vestibule region, which is accompanied by flow segregation. Maximum vortices were observed in the nasal valve region and the posterior end of the turbinate region, which involves mixing and recirculation and is responsible for enhancing the smelling process. Practical implications The proposed analysis is applicable to design the sensor chamber for electronic noses. Originality/value In this paper, the influence of airflow dynamics on vortices in the human nasal cavity is discussed through numerical simulations.

Nasal sprayed particle deposition in a human nasal cavity under different inhalation conditions.

Deposition of polydisperse particles representing nasal spray application in a human nasal cavity was performed under transient breathing profiles of sniffing, constant flow, and breath hold. The LES turbulence model was used to describe the fluid phase. Particles were introduced into the flow field with initial spray conditions, including spray cone angle, insertion angle, and initial velocity. Since nasal spray atomizer design determines the particle conditions, fifteen particle size distributions were used, each defined by a log-normal distribution with a different volume mean diameter (Dv50). Particle deposition in the anterior region was approximately 80% when Dv50 > 50μm, and this decreased to 45% as Dv50 decreased to 10μ m for constant and sniff breathing conditions. The decrease in anterior deposition was countered with increased deposition in the middle and posterior regions. The significance of increased deposition in the middle region for drug delivery shows there is potential for nasal delivered drugs to reach the highly vascularised mucosal walls in the main nasal passages. For multiple targeted deposition sites, an optimisation equation was introduced where deposition results of any two targeted sites could be combined and a weighting between 0 to 1 was applied to each targeted site, representing the relative importance of each deposition site.

Application of a Thermosensitive In Situ Gel of Chitosan-Based Nasal Spray Loaded with Tranexamic Acid for Localised Treatment of Nasal Wounds.

The integrity of the nasal epithelium plays a crucial role in the airway defence mechanism. The nasal epithelium may be injured as a result of a large number of factors leading to nose bleeds, also known as epistaxis. However, local measures commonly used to treat epistaxis and improve wound healing present several side effects and patient discomfort. Hence, this study aims to address some of these drawbacks by developing a new formulation for nasal epithelial wound healing. Chitosan, a biodegradable and biocompatible polymer, was used to develop a thermosensitive nasal formulation for the delivery of tranexamic acid (TXA), one of the most effective pharmacological options to control bleeding with cost and tolerability advantages. The in situ gelation properties of the formulation upon administration in the nasal cavity were investigated in terms of gelation time and temperature. It was found that the developed formulation can undergo rapid liquid-to-gel phase change within approximately 5min at 32°C, which is well within the human nasal cavity temperature range. The spray pattern, deposition and droplet size generated by the nasal spray was also characterised and were found to be suitable for nasal drug delivery. It was also observed that the in situ gelation of the formulation prevent nasal runoff, while the majority of drug deposited mainly in the anterior part of the nose with no lung deposition. The developed formulation was shown to be safe on human nasal epithelium and demonstrated six times faster wound closure compared to the control TXA solution.

Computational investigation of dust mite allergens in a realistic human nasal cavity

Aim: Inhaled allergens from house dust mite (HDM) are a major source of allergic disease such as allergic rhinitis and asthma. It has been a challenge to properly evaluate health risks caused by HDM related allergens including mite bodies, eggs and fecal pellets. This paper presents a numerical study on particle deposition of dust mite allergens in a human nasal cavity.Materials and methods: A realistic nasal cavity model was reconstructed from CT scans and a Computational Fluid Dynamics analysis of steady airflow was simulated. The discrete phase model was used to trace particle trajectories of three dust mite related particles.Results: The flow and particle model were validated by comparing with nasal resistance measurement and previous literature respectively. Aerodynamic characteristics and deposition of dust mite allergens in the nasal cavity were analyzed under different breathing conditions including rest and exercising conditions.Conclusions: The numerical results revealed the roles of different nasal cavity regions in filtering various types of dust mite allergens with consideration of breathing conditions.

Competition among Nasal Bacteria Suggests a Role for Siderophore-Mediated Interactions in Shaping the Human Nasal Microbiota.

Resources available in the human nasal cavity are limited. Therefore, to successfully colonize the nasal cavity, bacteria must compete for scarce nutrients. Competition may occur directly through interference (e.g., antibiotics) or indirectly by nutrient sequestration. To investigate the nature of nasal bacterial competition, we performed coculture inhibition assays between nasal Actinobacteria and Staphylococcus spp. We found that isolates of coagulase-negative staphylococci (CoNS) were sensitive to growth inhibition by Actinobacteria but that Staphylococcus aureus isolates were resistant to inhibition. Among Actinobacteria, we observed that Corynebacterium spp. were variable in their ability to inhibit CoNS. We sequenced the genomes of 10 Corynebacterium species isolates, including 3 Corynebacterium propinquum isolates that strongly inhibited CoNS and 7 other Corynebacterium species isolates that only weakly inhibited CoNS. Using a comparative genomics approach, we found that the C. propinquum genomes were enriched in genes for iron acquisition and harbored a biosynthetic gene cluster (BGC) for siderophore production, absent in the noninhibitory Corynebacterium species genomes. Using a chrome azurol S assay, we confirmed that C. propinquum produced siderophores. We demonstrated that iron supplementation rescued CoNS from inhibition by C. propinquum, suggesting that inhibition was due to iron restriction through siderophore production. Through comparative metabolomics and molecular networking, we identified the siderophore produced by C. propinquum as dehydroxynocardamine. Finally, we confirmed that the dehydroxynocardamine BGC is expressed in vivo by analyzing human nasal metatranscriptomes from the NIH Human Microbiome Project. Together, our results suggest that bacteria produce siderophores to compete for limited available iron in the nasal cavity and improve their fitness.IMPORTANCE Within the nasal cavity, interference competition through antimicrobial production is prevalent. For instance, nasal Staphylococcus species strains can inhibit the growth of other bacteria through the production of nonribosomal peptides and ribosomally synthesized and posttranslationally modified peptides. In contrast, bacteria engaging in exploitation competition modify the external environment to prevent competitors from growing, usually by hindering access to or depleting essential nutrients. As the nasal cavity is a nutrient-limited environment, we hypothesized that exploitation competition occurs in this system. We determined that Corynebacterium propinquum produces an iron-chelating siderophore, and this iron-sequestering molecule correlates with the ability to inhibit the growth of coagulase-negative staphylococci. Furthermore, we found that the genes required for siderophore production are expressed in vivo Thus, although siderophore production by bacteria is often considered a virulence trait, our work indicates that bacteria may produce siderophores to compete for limited iron in the human nasal cavity.