Mouth Throat Research Articles

Characterization of pediatric extrathoracic aerosol deposition with air-jet dry powder inhalers

The use of air-jet dry powder inhalers (DPIs) offers a number of advantages for the administration of pharmaceutical aerosols, including the ability to achieve highly efficient and potentially targeted aerosol delivery to the lungs of children using the oral or trans-nasal routes of administration. To better plan targeted lung delivery of pharmaceutical aerosols with these inhalers, more information is needed on the extrathoracic (ET) depositional loss in pediatric subjects when using relatively small (e.g., 0.5–2 μm) particles and including oral or nasal device interfaces. The objective of this study was to implement validated computational fluid dynamics (CFD) models to characterize ET depositional loss during mouth-throat (MT) and nose-throat (NT) aerosol administration to pediatric subjects (2–10 years old) using an air-jet DPI platform across a range of initial small-particle aerosol sizes (0.41–13.65 μm) and inhalation flow rates (8–20 L/min).A new CFD model focused on small-particle aerosol depositional loss in existing pediatric airway models was developed and validated with existing in vitro data. The validated CFD model was then used to characterize depositional loss in the MT and NT regions of children using particle sizes, flow rates and interfaces consistent with air-jet DPIs.Successful validation of the CFD model for small-particle aerosol deposition was achieved through enhanced resolution of the near-wall transport conditions. Existing non-dimensional parameters were used to produce high quality single-curve deposition efficiency correlations with r2 values in the range of 0.95–0.97. A new method for predicting realistic polydisperse aerosol deposition using the developed correlations and an equivalent monodisperse particle diameter was also introduced. In conclusion, the newly developed correlations will be useful in planning the lung delivery of next-generation inhaled medications, where achieving both low ET loss and targeted airway deposition, perhaps with excipient enhanced growth technology, are critical factors.

Adjoint Solver-Based Analysis of Mouth–Tongue Morphologies on Vapor Deposition in the Upper Airway

Even though inhalation dosimetry is determined by three factors (i.e., breathing, aerosols, and the respiratory tract), the first two categories have been more widely studied than the last. Both breathing and aerosols are quantitative variables that can be easily changed, while respiratory airway morphologies are difficult to reconstruct, modify, and quantify. Although several methods are available for model reconstruction and modification, developing an anatomically accurate airway model and morphing it to various physiological conditions remains labor-intensive and technically challenging. The objective of this study is to explore the feasibility of using an adjoint–CFD model to understand airway shape effects on vapor deposition and control vapor flux into the lung. A mouth–throat model was used, with the shape of the mouth and tongue being automatically varied via adjoint morphing and the vapor transport being simulated using ANSYS Fluent coupled with a wall absorption model. Two chemicals with varying adsorption rates, Acetaldehyde and Benzene, were considered, which exhibited large differences in dosimetry sensitivity to airway shapes. For both chemicals, the maximal possible morphing was first identified and then morphology parametric studies were conducted. Results show that changing the mouth–tongue shape can alter the oral filtration by 3.2% for Acetaldehyde and 0.27% for Benzene under a given inhalation condition. The front tongue exerts a significant impact on all cases considered, while the impact of other regions varies among cases. This study demonstrates that the hybrid adjoint–CFD approach can be a practical and efficient method to investigate morphology-associated variability in the dosimetry of vapors and nanomedicines under steady inhalation.

Breathing in danger: Mapping microplastic migration in the human respiratory system

The abundance of air pollutants over the last few years, including the concentration of microplastics, has become an alarming concern across the world. Initially discovered in marine life, these toxic and inflammatory particles have recently been found in human lung tissues. When inhaled, these harmful particles settle down in the lung airways and, over time, lead to respiratory failures. A recent study analyzed the microplastic transport behavior in the mouth–throat airways. However, the knowledge of the microplastic migration in bifurcating tracheobronchial airways is missing in the literature. Therefore, this first-ever study analyzes in detail the transport behavior and settling patterns of microplastic particles of different sizes and shapes at different respiratory intensities in the tracheobronchial lung airways. A numerical technique based on discrete phase modeling is employed to simulate the flow of microplastic particles in a three-dimensional realistic lung geometry. The numerical model results indicate low velocity and turbulence intensity magnitudes with smooth flow in the trachea compared to the airways of left and right lobes, which experience higher velocities and generate secondary vortices. Lower lung lobes are the deposition hotspots for the harmful microplastic particles at a lower flow rate. These hotspots shift to upper lung lobes at a higher flow rate for the same particle size. Moreover, microplastic particle size and shape influence the overall deposition rate in the tracheobronchial lung airways. The results of the current study, including microplastic accumulation regions at different breathing intensities, will contribute to the updated knowledge of pollutant inhalation and facilitate relevant treatment measures.

The effects of aerosol concentration on the evolution, transport, and deposition of hygroscopic droplets in the highly idealized MT model: A numerical study

Inhalation therapy is widely used to treat various respiratory diseases. Nebulizers have been widely adopted due to their ease of operation, high drug delivery efficiency, and low residual volume. Traditional studies on drug delivery in the respiratory tract typically use a one-way coupled method to track drug transport and deposition for non-hygroscopic drug particles. However, neglecting the concentration of nebulized hygroscopic droplet aerosols can lead to significant discrepancies in the deposition efficiency (DE) of nebulized drugs in the airways. To investigate the effect of different nebulization rates on the evolution, transport, and deposition of droplets, a highly idealized mouth-throat (MT) model was selected as a testbed for the in silico trials of drug delivery to the respiratory tract. The interaction between continuous and discrete phases was modeled using a two-way coupled model of highly concentrated droplet aerosol-water vapor interaction, innovated by the particle parcel method. The effects of different coupling methods and boundary conditions on the average droplet diameter and droplet deposition distribution pattern at the outlet of the MT model were compared using a computational fluid dynamics (CFD) method. Simulation results indicate that neglecting the effect of water vapor evaporated from the droplets on the relative humidity (RH) in the oral cavity could lead to a 2.2-fold prediction error of the average droplet diameter at the outlet of the MT model for a conventional nebulization rate of 0.386 g/min. As the nebulization rate increases, the difference in the predicted average droplet diameter at the outlet of the MT model between the one-way coupled method and the two-way coupled method also increases. Increasing the nebulization rate during inhalation therapy could lead to incomplete evaporation of drug droplets, resulting in deposition of larger diameter drug droplets in the oral cavity. In contrast, a lower nebulization rate can reduce the droplet diameter at the outlet of the MT model, allowing it to enter deeper airways.

The impact of actuator nozzle and surroundings condition on drug delivery using pressurized-metered dose inhalers.

The most commonly used method to deliver aerosolized drugs to the lung is with pressurized metered-dose inhalers (pMDIs). The spray actuator is a critical component of pMDI, since it controls the atomization process by forming aerosol plumes and determining droplet size distribution. Through computational fluid dynamics (CFD) simulations, this study investigated the effect of two different nozzle types (single conventional and twin nozzles) on drug deposition in the mouth-throat (MT) region. We also studied the behavior of aerosol plumes in both an open-air environment and the MT geometry. Our study revealed that spray aerosol generated in an unconfined, open-air environment with no airflow behaves distinctly from spray introduced into the MT geometry in the presence of airflow. In addition, the actuator structure significantly impacts the device's efficacy. In the real MTmodel, we found that the twin nozzle increases drug deposition in the MT region, and its higher aerosol velocity negatively affects its efficiency.

Effects of vocal fold adduction on the particle deposition in the glottis: A numerical analysis and in vitro assessment

BackgroundThe efficacy of inhalation therapy depends on the drug deposition in the human respiratory tract. This study investigates the effects of vocal fold adduction on the particle deposition in the glottis. MethodsA realistic mouth-throat (MT) geometry was built based on CT images of a healthy adult (MT-A). Mild (MT-B) and great (MT-C) vocal fold (VF) adduction were incorporated in the original model. Monodisperse particles range in size from 3 to 12 μm were simulated at inspiration flow rates of 15, 30 and 45 L per minute (LPM). The regional deposition of drug aerosols was performed in 3D-printed models and quantified using high-performance liquid chromatography. ResultsBoth the numerical analysis and in vitro experiments show that most particles are deposited in the mouth, pharynx and supraglottis, while few are deposited in the glottis and subglottis. For most cases in MT-A, the particle quantity in glottis is lower than 0.02 N/mm2 at 15 and 30 LPM while they increase dramatically at 45 LPM. It peaked at 0.347 N/mm2 for 5-μm particles at 45 LPM in MT-B and 2.324 N/mm2 for 6-μm particles at 30 LPM in MT-C. The lowest drug mass faction in the glottis in vitro were found at 15 LPM for MT-A and MT-C, and at 30 LPM for MT-B, whereas it peaked at 45 LPM for all MT models, 0.71% in MT-A, 1.16% in MT-B, and 2.53% in MT-C, respectively. ConclusionBased on the results of this study, larger particles are more likely to be deposited in the oral cavity, oropharynx, and supraglottis than in the glottis. However, particle deposition in the glottis generally increases with VF adduction and greater inspiratory flow rates.

Optimization of Vibrating Mesh Nebulizer Air Inlet Structure for Pulmonary Drug Delivery

The vibrating mesh nebulizer (VMN) has gained popularity for its compactness and noiselessness. This study investigates the impact of different air inlet structures on the deposition fraction (DF) of droplets generated by VMNs in an idealized mouth–throat (MT) airway model. Three homemade VMNs with semi-circular inlet, symmetrical four-inlet, and multiple-orifice inlet structures were evaluated through simulations and experiments. The changes in droplet DF of 0.9% w/v concentration of nebulized sodium chloride (NaCl) droplets as a function of inertial parameters were acquired under different inhalation flow conditions. Additionally, flow field distributions in models with different inlet structures were analyzed at a steady inspiratory flow rate of 15 L/min. The results indicate that optimizing the VMN’s air inlet structure significantly enhances droplet delivery efficiency. The multiple–orifice inlet structure outperformed the other designs, directing the airflow from the inlet position to the center of the mouthpiece and then into the oral cavity, achieving a DF of up to 20% at an inhalation flow rate of 15 L/min. The region of high airflow velocity between the mouthpiece and oral cavity proved to be a favorable VMN inlet optimization, reducing direct droplet–wall collisions and improving delivery efficiency. These findings offer insights for VMN design and optimization to enhance pulmonary drug delivery effectiveness and therapeutic outcomes.

Effects of vocal fold lesions on particle deposition in a mouth-throat model: A numerical study

ObjectiveDysphonia is very common worldwide and aerosol drug inhalation is an important treatment for patients with dysphonia. This study aimed to explore the effects of vocal fold (VF) lesions on the particle deposition pattern using computational modeling. MethodsA realistic mouth-throat (MT) model of a healthy adult was constructed based on computed tomography images. Small and large vocal fold lesions were incorporated in the original model. A steady inhalation flowrate of 15 and 30 liter per minute (LPM) was used as the velocity inlet and monodisperse particles with diameters of 5 to 10 µm were simulated. ResultsParticles of larger size are more likely to be deposited in MT models, most of them distributed in oral cavity, oropharynx and supraglottis. The ideal sizes at 30 LPM ranged over 7-10 µm for healthy VFs and 6-8 µm for VF lesions. The best sizes at 15 LPM ranged over 6-8 µm for healthy VFs and 8-9 µm for VF lesions. ConclusionBased on this study, VF lesions influence the deposition pattern in the glottis obviously. The ideal sizes differ at the flow rates of 15 and 30 LPM.

Structural design and mechanics research of a bionic pelican floating object fishing device

In order to meet the needs of surface floating objects fishing operations in small areas such as lakes and rivers, a fishing device is developed that can be used for high-intensity operations and is highly adaptable to the environment. In this paper, a water and land type bionic pelican surface floating object fishing device is developed based on the MeArm robotic arm combined with a three-degree-of-freedom linkage robotic arm using bionic principles. In order to meet the needs of the fishing function, the overall structure of the surface floating object fishing device was bionically designed by combining the large beak and flexible neck of the pelican, The innovative design of the mouth lower beak opening and closing mechanism, the lower beak gear rack lever slide mechanism, the mouth throat pouch bottom release mechanism and the neck structure are mainly carried out.The structural strength of the device under the most dangerous operating conditions was simulated using finite element analysis software for statics and dynamics simulation. The research results show that the structure of this design is reliable, and the experimental test of the prototype model verifies the validity and reliability of this design scheme, which provides the theoretical and experimental basis for the further development of the subsequent products.

The effects of temperature and humidity on the deposition of nebulized droplet in an idealized mouth-throat model

Inhalation therapy is a practical approach to treat respiratory diseases. Vibrating mesh nebulizer (VMN), a device for inhalation therapy, is favored for its advantages, such as portability and noiselessness. The droplet deposition experiment using the VMN was carried out in an idealized mouth-throat (MT) model. This study used the 0.9% w/v concentration of nebulized sodium chloride (NaCl) droplet to measure the deposition fraction (DF). The inhalation flow rates were changed under two different temperature and humidity conditions, and the variation of droplet DFs as a function of inertial parameters was obtained under different inhalation flow rate conditions. The results show that the DF first decreases and then increases with the increasing inertial parameter, which is distinctly different from previous conclusions for dry powder or particle experiments and simulations. It indicates that the droplet evaporation substantially affects the transport and deposition. The results also show that increasing the mass fraction of water vapor in the air increases droplet DF in the airway.

In silico Study on the deposition and distribution of particles in a realistic airway model with Handilaher®

Effective pulmonary drug delivery plays an essential role in the treatment of diseases. Drug aerosolization and inhalers play an essential role in the therapeutic effect of pulmonary diseases. The main objective of this paper is to evaluate the effect of inhalers, inhalation flow rates, and particle properties on the transport and deposition of 1-19 μm particles in a realistic airway model. Computational fluid dynamics coupled with the discrete phrase model (CFD-DPM) was performed to predict the transport and deposition of inhaled particles. Good agreement in deposition mechanisms was observed with the in vivo published data, which proved the effectiveness of the numerical method in pulmonary drug delivery. Airflow structure as well as deposition pattern showed that differences in turbulence, reverse flow, and vortex formulation between the two different models are determined by the existence of inhaler geometry. Enhancing the air flow rate and particle diameter increases the particle inertial as well as the turbulence level, resulting in an uptrend in deposition fraction (DF) of the mouth-throat (MT) region. In conclusion, this in silico method is valuable to help understand the in vitro - in vivo correlation (IVIVC) of pulmonary drug delivery.

Flow Dynamics and Acoustics from Glottal Vibrations at Different Frequencies

Glottal vibration is fundamental to breathing-related disorders and respiratory sound generation. However, responses of the flow and acoustics to glottal vibrations of different frequencies are unclear. The objective of this study is to numerically evaluate the influences of glottal vibration frequencies on inspiratory airflow dynamics and flow-induced sound signals; this is different from normal phonation that is driven by controlled expiratory flows. A computational model was developed that comprised an image-based mouth–throat–lung model and a dynamic glottis expanding/contracting following a sinusoidal waveform. Large Eddy simulations were used to solve the temporal and spatial flow evolutions, and pressure signals were analyzed using different transform algorithms (wavelet, Hilbert, Fourier, etc.). Results show that glottal vibrations significantly altered the flows in the glottis and trachea, especially at high frequencies. With increasing vibration frequencies, the vortices decreased in scale and moved from the main flow to the walls. Phase shifts occurred between the glottis motion and glottal flow rates for all frequencies considered. Due to this phase shift, the pressure forces resisted the glottal motion in the first half of contraction/expansion and assisted the glottal motion in the second half of contraction/expansion. The magnitude of the glottal flow fluctuation was approximately linear with the vibration frequency (~f0), while the normal pressure force increased nonlinearly with the frequency (~f01.85). Instantaneous pressure signals were irregular at low vibration frequencies (10 and 20 Hz) but became more regular with increasing frequencies in the pressure profile, periodicity, and wavelet-transformed parameters. The acoustic characteristics specific to the glottal vibration frequency were explored in temporal and frequency domains, which may be used individually or as a combination in diagnosing vocal fold dysfunction, snoring, sleep apnea, or other breathing-related diseases.

Flow Patterns and Particle Residence Times in the Oral Cavity during Inhaled Drug Delivery.

Pulmonary drug delivery aims to deliver particles deep into the lungs, bypassing the mouth–throat airway geometry. However, micron particles under high flow rates are susceptible to inertial impaction on anatomical sites that serve as a defense system to filter and prevent foreign particles from entering the lungs. The aim of this study was to understand particle aerodynamics and its possible deposition in the mouth–throat airway that inhibits pulmonary drug delivery. In this study, we present an analysis of the aerodynamics of inhaled particles inside a patient-specific mouth–throat model generated from MRI scans. Computational Fluid Dynamics with a Discrete Phase Model for tracking particles was used to characterize the airflow patterns for a constant inhalation flow rate of 30 L/min. Monodisperse particles with diameters of 7 m to 26 m were introduced to the domain within a 3 cm-diameter sphere in front of the oral cavity. The main outcomes of this study showed that the time taken for particle deposition to occur was 0.5 s; a narrow stream of particles (medially and superiorly) were transported by the flow field; larger particles > 20 m deposited onto the oropharnyx, while smaller particles < 12 m were more disperse throughout the oral cavity and navigated the curved geometry and laryngeal jet to escape through the tracheal outlet. It was concluded that at a flow rate of 30 L/min the particle diameters depositing on the larynx and trachea in this specific patient model are likely to be in the range of 7 m to 16 m. Particles larger than 16 m primarily deposited on the oropharynx.

How Nanoparticle Aerosols Transport through Multi-Stenosis Sections of Upper Airways: A CFD-DPM Modelling

Airway stenosis is a global respiratory health problem that is caused by airway injury, endotracheal intubation, malignant tumor, lung aging, or autoimmune diseases. A precise understanding of the airflow dynamics and pharmaceutical aerosol transport through the multi-stenosis airways is vital for targeted drug delivery, and is missing from the literature. The object of this study primarily relates to behaviors and nanoparticle transport through the multi-stenosis sections of the trachea and upper airways. The combination of a CT-based mouth–throat model and Weibel’s model was adopted in the ANSYS FLUENT solver for the numerical simulation of the Euler–Lagrange (E-L) method. Comprehensive grid refinement and validation were performed. The results from this study indicated that, for all flow rates, a higher velocity was usually found in the stenosis section. The maximum velocity was found in the stenosis section having a 75% reduction, followed by the stenosis section having a 50% reduction. Increasing flow rate resulted in higher wall shear stress, especially in stenosis sections. The highest pressure was found in the mouth–throat section for all flow rates. The lowest pressure was usually found in stenosis sections, especially in the third generation. Particle escape rate was dependent on flow rate and inversely dependent on particle size. The overall deposition efficiency was observed to be significantly higher in the mouth–throat and stenosis sections compared to other areas. However, this was proven to be only the case for a particle size of 1 nm. Moreover, smaller nanoparticles were usually trapped in the mouth–throat section, whereas larger nanoparticle sizes escaped through the lower airways from the left side of the lung; this accounted for approximately 50% of the total injected particles, and 36% escaped from the right side. The findings of this study can improve the comprehensive understanding of airflow patterns and nanoparticle deposition. This would be beneficial in work with polydisperse particle deposition for treatment of comprehensive stenosis with specific drugs under various disease conditions.

A CFD Investigation on the Aerosol Drug Delivery in the Mouth–Throat Airway Using a Pressurized Metered-Dose Inhaler Device

Inhalation therapy involving a pressurized metered-dose inhaler (pMDI) is one of the most commonly used and effective treatment methods for patients with asthma. The purpose of this study was to develop a computational fluid dynamics (CFD) model to characterize aerosol flow issued from a pMDI into a simulated mouth–throat geometry. The effects of air flow rate and cone angle were analyzed in detail. The behaviour of the multiphase flow initiated at the inhaler actuation nozzle and extended through the mouth–throat airway was simulated based on the Eulerian-Lagrangian discrete phase model, with the k-ω model applied for turbulency. We validated our model against published experimental measurements and cover the hydrodynamic aspect of the study. The recirculation we observed at the 90° bend inside the mouth–throat airway resulted in the selective retention of larger diameter particles, and the fluid flow patterns were correlated with drug deposition behaviour. Enhancing air flow rates up to three times reduced the aerodynamic particle diameters to 20%. We also observed that, as cone angle increased, mouth deposition increased; an 8° cone angle was the best angle for the lowest mouth–throat deposition.

Numerical study of nano and micro pollutant particle transport and deposition in realistic human lung airways

For respiratory health risk assessment, it is essential to evaluate the transportation and deposition (TD) of pollutant particles in human lung airways, which are responsible for lung diseases. Studies to date improved the knowledge of the particle TD in airways. However, the understanding of the TD of different pollutant particles in realistic airways has not been fully understood. This study investigates TD of three types of pollutant particles: traffic, smoke and dust, with various sizes ranging from nano- to micro-scales in the mouth–throat and tracheobronchial lung airways of a human lung using computational fluid dynamics (CFD). Three different physical activities are considered: sleeping, resting, and intense breathing, corresponding to inhalation flow rates of Qin = 15, 30 and 60 L/min, respectively. Nearly 99.8% of 10-μm traffic particles are deposited in the upper lung airways considered here. However, the TD efficiency of 10-μm dust particles is reduced to 64.28% due to the reduction in particle density. Nanoparticles have a much smaller deposition efficiency than microparticles because impaction effect of microparticles is stronger. Only less than 10% of 5-nm traffic particles are deposited in the airways for all three flow rates, allowing over 90% of particles to reach the deep lung. An important finding is that the effects of density on the particle TD of nanoparticles are much weaker than that of microparticles. At 15 L/min flow rate, the difference between the deposition efficiencies of the heaviest traffic particles and the lightest dust particles is only 3.5%. The effects of particle density on the deposition efficiencies of nano- and micro-particles are different from each other because impaction and diffusion dominate the TD of nano- and micro-particles, respectively. Density only affects impaction significantly but has little effect on diffusion.

Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract Model.

Accurate knowledge of the delivery of locally acting drug products, such as metered-dose inhaler (MDI) formulations, to large and small airways is essential to develop reliable in vitro/in vivo correlations (IVIVCs). However, challenges exist in modeling MDI delivery, due to the highly transient multiscale spray formation, the large variability in actuation–inhalation coordination, and the complex lung networks. The objective of this study was to develop/validate a computational MDI-releasing-delivery model and to evaluate the device actuation effects on the dose distribution with the newly developed model. An integrated MDI–mouth–lung (G9) geometry was developed. An albuterol MDI with the chlorofluorocarbon propellant was simulated with polydisperse aerosol size distribution measured by laser light scatter and aerosol discharge velocity derived from measurements taken while using a phase Doppler anemometry. The highly transient, multiscale airflow and droplet dynamics were simulated by using large eddy simulation (LES) and Lagrangian tracking with sufficiently fine computation mesh. A high-speed camera imaging of the MDI plume formation was conducted and compared with LES predictions. The aerosol discharge velocity at the MDI orifice was reversely determined to be 40 m/s based on the phase Doppler anemometry (PDA) measurements at two different locations from the mouthpiece. The LES-predicted instantaneous vortex structures and corresponding spray clouds resembled each other. There are three phases of the MDI plume evolution (discharging, dispersion, and dispensing), each with distinct features regardless of the actuation time. Good agreement was achieved between the predicted and measured doses in both the device, mouth–throat, and lung. Concerning the device–patient coordination, delayed MDI actuation increased drug deposition in the mouth and reduced drug delivery to the lung. Firing MDI before inhalation was found to increase drug loss in the device; however, it also reduced mouth–throat loss and increased lung doses in both the central and peripheral regions.

LES study on the impact of airway deformation on the airflow structures in the idealized mouth–throat model

To investigate the impacts of upper airway deformation on the airflow structures, the airflow fields in the trachea are simulated using three geometrical models considering three different levels of airway deformations. Structured grids are used to create the high-quality grids. Large eddy simulation with the Smagorinsky sub-grid model is adopted to solve the three-dimensional in-compressible Navier–Stokes equations using the solver pisoFoam in the open-source CFD software OpenFOAM. The numerical results demonstrate that the airway deformation influences the main airflow structures depending on the deformation level. Particularly, it slightly impacts on the laryngeal jet such as the profile and the strength of laryngeal jet. The strength of the laryngeal jet increases slightly for the heavy deformation. In contrast, it impacts on the recirculation zone, secondary vortices, and turbulent kinetic energy more obviously. The increasing airway deformation will produce stronger secondary flow, smaller recirculation zone, and weaker turbulent kinetic energy. The turbulence intensity distribution varies as well. The obviously impacted flow region is mainly within the region of one to six tracheal diameters downstream the glottis.

SYmptom-Based STratification of DiabEtes Mellitus by Renal Function Decline (SYSTEM): A Retrospective Cohort Study and Modeling Assessment.

Background: Previous UK Biobank studies showed that symptoms and physical measurements had excellent prediction on long-term clinical outcomes in general population. Symptoms and signs could intuitively and non-invasively predict and monitor disease progression, especially for telemedicine, but related research is limited in diabetes and renal medicine.Methods: This retrospective cohort study aimed to evaluate the predictive power of a symptom-based stratification framework and individual symptoms for diabetes. Three hundred two adult diabetic patients were consecutively sampled from outpatient clinics in Hong Kong for prospective symptom assessment. Demographics and longitudinal measures of biochemical parameters were retrospectively extracted from linked medical records. The association between estimated glomerular filtration rate (GFR) (independent variable) and biochemistry, epidemiological factors, and individual symptoms was assessed by mixed regression analyses. A symptom-based stratification framework of diabetes using symptom clusters was formulated by Delphi consensus method. Akaike information criterion (AIC) and Bayesian information criterion (BIC) were compared between statistical models with different combinations of biochemical, epidemiological, and symptom variables.Results: In the 4.2-year follow-up period, baseline presentation of edema (−1.8 ml/min/1.73m2, 95%CI: −2.5 to −1.2, p < 0.001), epigastric bloating (−0.8 ml/min/1.73m2, 95%CI: −1.4 to −0.2, p = 0.014) and alternating dry and loose stool (−1.1 ml/min/1.73m2, 95%CI: −1.9 to −0.4, p = 0.004) were independently associated with faster annual GFR decline. Eleven symptom clusters were identified from literature, stratifying diabetes predominantly by gastrointestinal phenotypes. Using symptom clusters synchronized by Delphi consensus as the independent variable in statistical models reduced complexity and improved explanatory power when compared to using individual symptoms. Symptom-biologic-epidemiologic combined model had the lowest AIC (4,478 vs. 5,824 vs. 4,966 vs. 7,926) and BIC (4,597 vs. 5,870 vs. 5,065 vs. 8,026) compared to the symptom, symptom-epidemiologic and biologic-epidemiologic models, respectively. Patients co-presenting with a constellation of fatigue, malaise, dry mouth, and dry throat were independently associated with faster annual GFR decline (−1.1 ml/min/1.73m2, 95%CI: −1.9 to −0.2, p = 0.011).Conclusions: Add-on symptom-based diagnosis improves the predictive power on renal function decline among diabetic patients based on key biochemical and epidemiological factors. Dynamic change of symptoms should be considered in clinical practice and research design.

SARS CoV-2 aerosol: How far it can travel to the lower airways?

The recent outbreak of the SARS CoV-2 virus has had a significant effect on human respiratory health around the world. The contagious disease infected a large proportion of the world population, resulting in long-term health issues and an excessive mortality rate. The SARS CoV-2 virus can spread as small aerosols and enters the respiratory systems through the oral (nose or mouth) airway. The SARS CoV-2 particle transport to the mouth–throat and upper airways is analyzed by the available literature. Due to the tiny size, the virus can travel to the terminal airways of the respiratory system and form a severe health hazard. There is a gap in the understanding of the SARS CoV-2 particle transport to the terminal airways. The present study investigated the SARS CoV-2 virus particle transport and deposition to the terminal airways in a complex 17-generation lung model. This first-ever study demonstrates how far SARS CoV-2 particles can travel in the respiratory system. ANSYS Fluent solver was used to simulate the virus particle transport during sleep and light and heavy activity conditions. Numerical results demonstrate that a higher percentage of the virus particles are trapped at the upper airways when sleeping and in a light activity condition. More virus particles have lung contact in the right lung than the left lung. A comprehensive lobe specific deposition and deposition concentration study was performed. The results of this study provide a precise knowledge of the SARs CoV-2 particle transport to the lower branches and could help the lung health risk assessment system.