The nasopharynx is hidden and the symptoms are not typical at the beginning of the disease, but often manifest as a foreign body sensation and dryness in the nasopharynx. When secretions are attached to the nasopharynx, patients often wish to cough or blow them out by aspiration, so they are often seen for foreign body sensation in the nasopharynx or coughing up sputum after frequent aspiration. With the popularization of nasal endoscopy technology, the clinical diagnosis of nasopharyngitis has become easier, and the treatment of nasopharyngitis has also attracted widespread attention from clinicians. Currently, the use of nasal sprays to locally reduce swelling and promote discharge of secretions is the preferred treatment for nasopharyngitis, but there is no clear test for whether the drugs can effectively act locally on the nasopharynx. In this study, we will analyze the deposition of material particles entering the nasal and nasopharyngeal cavities with the respiratory airflow through numerical computer simulations, with the aim of further investigating the effective deposition mechanism of transnasal drug sprays in the nasopharynx.
Some recent studies have found that lack of exercise is closely associated with the development of a range of chronic diseases, and therefore, some scholars have begun to advocate physical activity on a global scale. However, Ding[2], Sajjadi[3], Andersen[4] and others stated that exercise in polluted environments does not necessarily contribute to physical health. Harmful airborne particles are inhaled by the body and deposited in the nasal cavity, nasopharynx and lungs, causing a series of acute and chronic respiratory diseases. Kuehn[5] pointed out that walking in a clean environment has a significant effect on the improvement of lung function, etc. Healthy individuals would benefit more from exercising in an environment with clean air compared to a polluted atmosphere.The Global Burden of Disease Study 2015 [6] emphasizes the need to quantify various risks to human health in order to avoid various risk factors and improve population health. Therefore, the problem of harmful particle deposition in breathing air will certainly be closely related to healthy and effective exercise.
The fine and complex structure of the respiratory tract makes the study of particle deposition problems more difficult. With the continuous development of computer technology, numerical simulation studies and computational processes have gradually become easier. Many institutions at home and abroad have investigated the particle deposition problem in the airway by means of numerical simulation, etc. Deng[7] et al. established a model by detailed mathematical description of airway bifurcation geometry and contracted the tube diameter to represent different ages of lungs; Yu Shen[8] et al. reconstructed a numerical model of the airway using CT data of patients' airways and explored the characteristics of particle deposition in the airway by numerical simulation. Farnoud et al [9] simulated the diffusion and deposition of nasal aerosol particles at constant inhalation flow rates of 4.78 L/min and 7.5 L/min at different angles and monodisperse particles with particle diameters of 2.4 um and 10 um; Burgos[10] used using computational fluid dynamics (CFD) methods to link nasal and chronic suppurative otitis media, a study that supported the possible association of altered nasal airflow with the etiology of chronic suppurative otitis media. In the current COVID-19 pandemic setting, Mohamadi[11] applied CFD methods to the study of COVID-19 pandemic as an epidemic and investigated the effect of different ventilation conditions on the spread of COVID-19 through CFD modeling, and also studied the effect of social distance and use of face masks on reducing the dispersal of microdroplets containing virus and 19 in different scenarios such as aircraft cabins, small classrooms, supermarkets, hospital operating rooms, and hospital waiting rooms were briefly discussed for CFD application modeling; Gupta et al [12] developed a CFD model to predict respiratory droplet transmission from passengers in aircraft cabins and studied the effects of calm breathing, 100 coughs, and 30 minutes of conversation in a confined cabin under conditions where one passenger Inhalation of exhaled particles from one passenger to another was studied, and it was found that coughing significantly resulted in a previously high number of inhaled particles, so that coughing in an unprotected state could spread a large number of infectious droplets to fellow passengers; the following year, the team [13] again used CFD models to measure the spatial distribution of respiratory particles under influenza outbreak conditions similar to those studied above, and found that the use of N95 respirator masks can significantly reduce the risk of virus transmission; in addition, Abuhegazy et al [14] also used CFD techniques to study the effect of ventilation on the transmission of respiratory droplets to humans in simulated operating rooms and restaurants; Nouri et al [15] applied CFD simulations with Ansys Fluent 2019R3 software to study the effect of air conditioning units on the transmission of infectious particles in elevator cars and aerosol disinfectant combinations, and the results of this experiment provided a more accurate description of the particle airflow generated by natural exhalation, the size and shape of respiratory droplets, and their concentration within the confined environment.
For verification of the authenticity of CFD simulation results, some researchers combined CFD with 3D replica in vitro experiments. Kelly[16], Cheng[17] and Wen[18] used 3D models of the airway to verify particle deposition and found that the 3D models matched the numerically simulated particle deposition data, but the degree of smoothness and accuracy of the 3D models could have some Therefore, the experiments have high requirements on the model preparation process and experimental equipment.In a study by Zhou[19], in vitro experiments and CFD analysis of particle deposition were performed on a nasal replica of a 5-year-old child to evaluate total and regional deposition, and it was found that the total deposition obtained from the in vitro experiments was in good agreement with the CFD predictions. Schroeter[20] also came to the same conclusion that there was good agreement between both CFD predictions and experimental measurements with similar deposition trends.
In this study, namely, a 3D numerical model was established from the acquired CT image data of the upper airway of healthy subjects, and CFD methods were applied to conduct relevant experiments to simulate the real human upper airway environment. During the study, the deposition efficiency [21–23] was compared with the inertial parameter, i.e. da2×Q(µm2cm3/s) [16, 21, 22], where Q and da represent inhalation flow and particle diameter, respectively (Fig. 8), and it was found that the simulation results of the present study were very similar to those of Kelly, Calmet [16, 22] and others at the inertial parameter with very similar results of earlier studies.
DE=\(\frac{\text{N}\text{u}\text{m}\text{b}\text{e}\text{r} \text{o}\text{f} \text{d}\text{e}\text{p}\text{o}\text{s}\text{i}\text{t}\text{e}\text{d} \text{p}\text{a}\text{r}\text{t}\text{i}\text{c}\text{l}\text{e}\text{s}}{\text{N}\text{u}\text{m}\text{b}\text{e}\text{r} \text{o}\text{f} \text{i}\text{n}\text{j}\text{e}\text{c}\text{t}\text{e}\text{d} \text{p}\text{a}\text{r}\text{t}\text{i}\text{c}\text{l}\text{e}\text{s}}\) (1)
It was found that the particle deposition efficiency in this reconstructed model increased continuously as the activity intensity increased, i.e., the respiratory flow rate increased, and particles were also more likely to settle in the anterior segment of the nasal cavity, such as the nasal vestibule and the anterior aspect of the inferior turbinates; more deposition in the nasopharyngeal cavity during calm breathing and more particles escaped from the larynx. For the study of the effect of airflow rate on particle deposition, Koullapis et al [24] found that an increase in airflow rate leads to an increase in inertial collisions, which in turn leads to an increase in particle deposition; Jin[23] found that an increase in peak flow rate due to an increase in respiratory rate led to an increase in particle drag force and enhanced inertial collisions, which increased particle collisions with bronchial walls and deposition; Ahookhosh [25] chose flow rates of 30 L/min, 60 L/min, 90 L/min, and 120 L/min in an experiment to study the effect of different inhalation flow rates on particle deposition and found that particle deposition in the airway increased with increasing inhalation flow rate; Sosnowski[26], on the other hand, verified that under no-flow conditions, due to the inertial effect of droplets, all sprays deposited mainly in the anterior part of the nasal cavity and in the nasal septum, accompanied by further inspiration of the patient, creating a secondary diffusion of the droplets deposited in the nasal cavity, thus allowing the droplets to be delivered deeper into the nasal cavity. Combined with the simulation results of this study, we suggest that short breathing cycles (e.g., vigorous exercise) in dusty air tend to increase the risk of distal lung and bronchial aspiration, indicating that calm breathing is more conducive to nasal spray or nebulized inhalation for the treatment of nasopharyngeal disease and lung lesions.
The particle sizes of 5 µm, 10 µm and 15 µm were chosen for the simulation of this study because it was considered that particles with diameters less than 2.5 µm are easy to be suspended and difficult to be deposited, while particles with too large a particle size are easily partially obscured by nasal hairs in the nasal vestibule and are not easy to be deposited in the nasal cavity. It was found that when the airflow rate and particle density were constant, the deposition efficiency increased with increasing particle size in this reconstructed model. For the nasopharynx, when the particle size is small, particle deposition increases with increasing airflow rate; when the particle size is large, particle deposition decreases with increasing airflow rate instead. We consider that this situation is due to the fact that large diameter particles are more likely to collide with and settle at the nasal threshold and nasal turbinates, and thus the deposition in the nasopharynx is reduced. For the effect of particle size on particle deposition, it has been pointed out by[18] that the factors affecting the deposition of particles of different sizes are different; when the drug diameter is greater than 10 µm, the deposition of particles in the nasal turbinate region will be higher when a smaller tidal volume is given, and for drug particles less than 5 µm in diameter, a higher tidal volume will result in higher deposition of particles in the turbinate region; Kiaee[27] found that nasal spray particles passing through the nasal cavity and pharynx, it is relatively insensitive to the release rate but highly sensitive to particle size, thus suggesting that the focus should be on particle size distribution when designing nasal drug delivery devices; Calmet[22] et al. in their study of the relationship between three respiratory flow rates, sniffing, constant flow and breath holding, and nasal spray drug delivery, found that different respiratory flow rates affect particles of different particle sizes to different degrees, the particle size affected drug particles to a greater extent compared to the respiratory flow rate, thus suggesting that the selection of an appropriate particle size is crucial for drug distribution when choosing a transnasal drug delivery strategy. These further suggest that the effect of particle size and airflow rate on particle deposition should not be a single relationship, and the degree of influence is dominated by particle size. The present study also came to the consistent conclusion that particle size, airflow rate, and particle density all have an effect on particle deposition, with particle size having the greatest effect on particle deposition, followed by airflow rate, and particle density having an insignificant effect on particle deposition.
XI[28] simulated multi-regional airflow and particle transport in the nasolaryngeal airway at different ages to assess ultrafine particle deposition characteristics under different breathing conditions from sedentary to vigorous activity, and found that the nasolaryngeal airway at different ages had no significant effect on the total deposition fraction or maximum local deposition enhancement of ultrafine particles, although there were significant differences in morphology and dimensionality. This study mainly focused on the effects of airflow rate, particle diameter, and particle density on particle deposition, and lacked the investigation of the effects of airway structure on particle deposition in different age groups, and this part needs to be further improved in the follow-up study.