JongWon Kim

Dynamic growth and deposition of hygroscopic aerosols in the nasal airway of a 5‐year‐old child

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.

Growth of Nasal and Laryngeal Airways in Children: Implications in Breathing and Inhaled Aerosol Dynamics

BACKGROUND: The human respiratory airway undergoes dramatic growth during infancy and childhood, which induces substantial variability in air flow pattern and particle deposition. However, deposition studies have typically focused on adult subjects, the results of which cannot be readily extrapolated to children. We developed models to quantify the growth of human nasal-laryngeal airways at early ages, and to evaluate the impact of that growth on breathing resistance and aerosol deposition. METHODS: Four image-based nasal-laryngeal models were developed from 4 children, ages 10 days, 7 months, 3 years, and 5 years, and were compared to a nasal-laryngeal model of a 53-year-old adult. The airway dimensions were quantified in terms of different parameters (volume, cross-section area, and hydraulic diameter) and of different anatomies (nose, pharynx, and larynx). Breathing resistance and aerosol deposition were computed using a high-fidelity fluid-particle transport model, and were validated against the measurements made with the 3-dimensional models fabricated from the same airway computed tomography images. RESULTS: Significant differences in nasal morphology were observed among the 5 subjects, in both morphology and dimension. The turbinate region appeared to experience the most noticeable growth during the first 5 years of life. The nasal airway volume ratios of the 10-day, 7-month, 3-year, and 5-year-old subjects were 6.4%, 18.8%, 24.2%, and 40.3% that of the adult, respectively. Remarkable inter-group variability was observed in air flow, pressure drop, deposition fraction, and particle accumulation. The computational fluid dynamics predicted pressure drops and deposition fractions were in close agreement with in vitro measurements. CONCLUSIONS: Age effects are significant in both breathing resistance and micrometer particle deposition. The image/computational-fluid-dynamics coupled method provides an efficient and effective approach in understanding patient-specific air flows and particle deposition, which have important implications in pediatric inhalation drug delivery and respiratory disorder diagnosis.

Modeling the pharyngeal anatomical effects on breathing resistance and aerodynamically generated sound

The objective of this study was to systematically assess the effects of pharyngeal anatomical details on breathing resistance and acoustic characteristics by means of computational modeling. A physiologically realistic nose-throat airway was reconstructed from medical images. Individual airway anatomy such as the uvula, pharynx, and larynx was then isolated for examination by gradually simplifying this image-based model geometry. Large eddy simulations with the FW-H acoustics model were used to simulate airflows and acoustic sound generation with constant flow inhalations in rigid-walled airway geometries. Results showed that pharyngeal anatomical details exerted a significant impact on breathing resistance and energy distribution of acoustic sound. The uvula constriction induced considerably increased levels of pressure drop and acoustic power in the pharynx, which could start and worsen snoring symptoms. Each source anatomy was observed to generate a unique spectrum with signature peak frequencies and energy distribution. Moreover, severe pharyngeal airway narrowing led to an upward shift of sound energy in the high-frequency range. Results indicated that computational aeroacoustic modeling appeared to be a practical tool to study breathing-related disorders. Specifically, high-frequency acoustic signals might disclose additional clues to the mechanism of apneic snoring and should be included in future acoustic studies.

Hygroscopic aerosol deposition in the human upper respiratory tract under various thermo-humidity conditions

The deposition of hygroscopic aerosols is highly complex in nature, which results from a cumulative effect of dynamic particle growth and the real-time size-specific deposition mechanisms. The objective of this study is to evaluate hygroscopic effects on the particle growth, transport, and deposition of nasally inhaled aerosols across a range of 0.2–2.5 μm in an adult image-based nose-throat model. Temperature and relative humidity fields were simulated using the LRN k-ω turbulence model and species transport model under a spectrum of thermo-humidity conditions. Particle growth and transport were simulated using a well validated Lagrangian tracking model coupled with a user-defined hygroscopic growth module. Results of this study indicate that the saturation level and initial particle size are the two major factors that determine the particle growth rate (d/d0), while the effect of inhalation flow rate is found to be not significant. An empirical correlation of condensation growth of nasally inhaled hygroscopic aerosols in adults has been developed based on a variety of thermo-humidity inhalation conditions. Significant elevated nasal depositions of hygroscopic aerosols could be induced by condensation growth for both sub-micrometer and small micrometer particulates. In particular, the deposition of initially 2.5 μm hygroscopic aerosols was observed to be 5–8 times that of inert particles under warm to hot saturated conditions. Results of this study have important implications in exposure assessment in hot humid environments, where much higher risks may be expected compared to normal conditions.

Exhaled aerosol pattern discloses lung structural abnormality: a sensitivity study using computational modeling and fractal analysis.

Background Exhaled aerosol patterns, also called aerosol fingerprints, provide clues to the health of the lung and can be used to detect disease-modified airway structures. The key is how to decode the exhaled aerosol fingerprints and retrieve the lung structural information for a non-invasive identification of respiratory diseases. Objective and Methods In this study, a CFD-fractal analysis method was developed to quantify exhaled aerosol fingerprints and applied it to one benign and three malign conditions: a tracheal carina tumor, a bronchial tumor, and asthma. Respirations of tracer aerosols of 1 µm at a flow rate of 30 L/min were simulated, with exhaled distributions recorded at the mouth. Large eddy simulations and a Lagrangian tracking approach were used to simulate respiratory airflows and aerosol dynamics. Aerosol morphometric measures such as concentration disparity, spatial distributions, and fractal analysis were applied to distinguish various exhaled aerosol patterns. Findings Utilizing physiology-based modeling, we demonstrated substantial differences in exhaled aerosol distributions among normal and pathological airways, which were suggestive of the disease location and extent. With fractal analysis, we also demonstrated that exhaled aerosol patterns exhibited fractal behavior in both the entire image and selected regions of interest. Each exhaled aerosol fingerprint exhibited distinct pattern parameters such as spatial probability, fractal dimension, lacunarity, and multifractal spectrum. Furthermore, a correlation of the diseased location and exhaled aerosol spatial distribution was established for asthma. Conclusion Aerosol-fingerprint-based breath tests disclose clues about the site and severity of lung diseases and appear to be sensitive enough to be a practical tool for diagnosis and prognosis of respiratory diseases with structural abnormalities.

CFD modeling and image analysis of exhaled aerosols due to a growing bronchial tumor: Towards non-invasive diagnosis and treatment of respiratory obstructive diseases

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.

Effects of the facial interface on inhalation and deposition of micrometer particles in calm air in a child airway model

Abstract Context: How the facial interface affects particle inhalability and depositions within the airway is not well understood. Previous studies of inhalation dosimetry are limited to either inhalability or deposition, rather than the two studied in a systematic way. Objective: To systematically evaluate the effects of the facial interface on aerosol inhalability, nasal deposition and thoracic dose in a 5-year-old child airway model using a coupled imaging-computational fluid dynamics approach. Methods: A face–nose–throat model was developed from magnetic resonance imaging scans of a 5-year-old boy. Respiration airflows and particle transport were simulated with the low Reynolds number k-ω turbulence model and the Lagrangian tracking approach. Particles ranging from 1 to 70 µm were considered in a calm air. Results: Retaining the facial interface in the computational model induced substantial variations in flow dynamics, aerosol inhalability and thoracic doses. The nasal and thoracic deposition fractions were much lower with the facial interface due to the low inhalability into downward-facing nostrils and facial deposition losses. For a given inhalation rate of 10 L/min, including the facial interface reduced the thoracic dose by 5% for 2.5-µm particles and by 50% for 10 µm particles in the child model. Considering localized conditions, facial interface substantially increased depositions at the turbinate region and dorsal pharynx. Conclusion: This study highlighted the need to include facial interface in future numerical and in vitro studies. Findings of this study have practical implications in the design of aerosol samplers and interpretation of deposition data from studies without facial interfaces.

Characterizing Respiratory Airflow and Aerosol Condensational Growth in Children and Adults Using an Imaging-CFD Approach

The dynamic growth of water-soluble aerosols within human respiratory tracts can be significant and may notably alter the transport and deposition of such inhaled aerosols. Moreover, considerable structural changes occur in human respiratory tracts during early ages, leading to further variations in respiratory airflow pattern and aerosol dynamics. This chapter will review some of the latest advances in modeling and simulations of the psychrometric phenomena in human upper airways, examine hygroscopic factors that influence the growth and deposition of inhaled particles, discuss their implications in health assessments of environmental exposure, and demonstrate the applications of aerosol hygroscopic properties to improve inhalation drug delivery efficiency. Characterization of respiratory anatomical variation at different ages based on CT/MRI imaging will be presented. Specifically, psychrometric behaviors of inhaled airflow and hygroscopic aerosols will be examined in three physiological-realistic geometries, which include an adult nose-throat model, a child nose-throat model, and an adult mouth-lung airway model. Results reported in this chapter highlight the particle condensation growth as a potentially significant mechanism in the deposition of fine aerosol particles under saturated inhalation conditions. Furthermore, particle condensation growth possesses a promising implication to improve delivery efficiency targeting either the nasal olfactory region or the lungs. These results are intended to provide guidance in making appropriate exposure risk assessment of environmental pollutants, dose-response predictions of inhaled medications, and in designing targeted respiratory drug delivery systems.