No abstract

Hygroscopic growth within the human respiratory tract can be significant, which may notably alter the behavior and fate of the inhaled aerosols. The objective of this study is to evaluate the hygroscopic effects upon the transport and deposition of nasally inhaled fine-regime aerosols in children. A physiologically realistic nasal-laryngeal airway model was developed based on magnetic resonance imaging of a 5-year-old boy. Temperature and relative humidity field were simulated using the low Reynolds number k - ε turbulence model and chemical specie transport model under a spectrum of four thermo-humidity conditions. Particle growth and transport were simulated using a well validated Lagrangian tracking model coupled with a user-defined hygroscopic growth module. The subsequent aerosol depositions for the four inhalation scenarios were evaluated on a multiscale basis such as total, subregional, and cellular-level depositions. Results of this study show that a supersaturated humid environment is possible in the nasal turbinate region and can lead to significant condensation growth (d / d(0) > 10) of nasally inhaled aerosols. Depositions in the nasal airway can also be greatly enhanced by condensation growth with appropriate inhalation temperature and humidity. For subsaturated and mild inhalation conditions, the hygroscopic effects were found to be nonsignificant for total depositions, while exerting a large impact upon localized depositions.

Electrostatic charging occurs in most aerosol generation processes and can significantly influence subsequent particle deposition rates and patterns in the respiratory tract through the image and space forces. The behavior of inhaled aerosols with charge is expected to be most affected in the upper airways, where particles come in close proximity to the narrow turbinate surface, and before charge dissipation occurs as a result of high humidity. The objective of this study was to quantitatively evaluate the deposition of charged aerosols in an MRI-based nasal–laryngeal airway model. Particle sizes of 5 nm–30 µm and charge levels ranging from neutralized to ten times the saturation limit were considered. A well-validated low Reynolds number (LRN) k–ω turbulence model and a discrete Lagrangian tracking approach that accounted for electrostatic image force were employed to simulate the nasal airflow and aerosol dynamics. For ultrafine aerosols, electrostatic charge was observed to exert a discernible but insignificant effect. In contrast, remarkably enhanced depositions were observed for micrometer particles with charge, which could be one order of magnitude larger than no-charge depositions. The deposition hot spots shifted towards the anterior part of the upper airway as the charge level increased. Results of this study have important implications for evaluating nasal drug delivery devices and for assessing doses received from pollutants, which often carry a certain level of electric charges.

Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure variations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treat the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagrangian tracking approach were used to model respiratory airflows and aerosol dynamics. Respirations of tracer aerosols of 1 µm at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug delivery protocol.

Background Although direct nose-to-brain drug delivery has multiple advantages, its application is limited by the extremely low delivery efficiency (<1%) to the olfactory region where drugs can enter the brain. It is crucial to developing new methods that can deliver drug particles more effectively to the olfactory region. Materials and methods We introduced a delivery method that used magnetophoresis to improve olfactory delivery efficiency. The performance of the proposed method was assessed numerically in an image-based human nose model. Influences of the magnet layout, magnet strength, drug-release position, and particle diameter on the olfactory dosage were examined. Results and discussion Results showed that particle diameter was a critical factor in controlling the motion of nasally inhaled ferromagnetic drug particles. The optimal particle size was found to be approximately 15 μm for effective magnetophoretic guidance while avoiding loss of particles to the walls in the anterior nose. Olfactory delivery efficiency was shown to be sensitive to the position and strength of magnets and the release position of drug particles. The results of this study showed that clinically significant olfactory doses (up to 45%) were feasible using the optimal combination of magnet layout, selective drug release, and microsphere-carrier diameter. A 64-fold-higher delivery of dosage was predicted in the magnetized nose compared to the control case, which did not have a magnetic field. However, the sensitivity of olfactory dosage to operating conditions and the unstable nature of magnetophoresis make controlled guidance of nasally inhaled aerosols still highly challenging.