Xiuhua A. Si

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.

Electrophoretic Particle Guidance Significantly Enhances Olfactory Drug Delivery: A Feasibility Study

Background Intranasal olfactory drug delivery provides a non-invasive method that bypasses the Blood-Brain-Barrier and directly delivers medication to the brain and spinal cord. However, a device designed specifically for olfactory delivery has not yet been found. Methods In this study, a new delivery method was proposed that utilized electrophoretic forces to guide drug particles to the olfactory region. The feasibility of this method was numerically evaluated in both idealized 2-D and anatomically accurate 3-D nose models. The influence of nasal airflow, electrode strength, and drug release position were also studied on the olfactory delivery efficiency. Findings Results showed that by applying electrophoretic forces, the dosage to the olfactory region was significantly enhanced. In both 2-D and 3-D cases, electrophoretic-guided delivery achieved olfactory dosages nearly two orders of magnitude higher than that without electrophoretic forces. Furthermore, releasing drugs into the upper half of the nostril (i.e., partial release) led to olfactory dosages two times higher than releasing drugs over the entire area of the nostril. By combining the advantages of pointed drug release and appropriate electrophoretic guidance, olfactory dosages of more than 90% were observed as compared to the extremely low olfactory dosage (<1%) with conventional inhaler devices. Conclusion Results of this study have important implications in developing personalized olfactory delivery protocols for the treatment of neurological disorders. Moreover, a high sensitivity of olfactory dosage was observed in relation to different pointed release positions, indicating the importance of precise particle guidance for effective olfactory delivery.

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.

Ultrafine and Fine Aerosol Deposition in the Nasal Airways of a 9-Month-Old Girl, a 5-Year-Old Boy and a 53-Year-Old Male

Exposure to environmental aerosols of submicrometer size may cause significant risks to human health. Submicrometer aerosols include particles in the ultrafine (<100 nm) and fine (100 nm to 1 μm) regimes. Recent studies indicate that aerosols in this size range are biologically more active and potentially more toxic than micrometer particles of the same material (Kreyling et al., 2006; Kreyling et al., 2004; Li et al., 2003; Oberdorster and Utell 2002). Sources of submicrometer aerosols include diesel exhaust (50 to 500 nm) (Kittelson 1998), cigarette smoke (140 to 500 nm) (Bernstein 2004; Keith 1982), and radioactive decay (1 to 200 nm) (ICRP 1994). Submicrometer bioaerosols include respiratory specific viruses such as Avian flu and SARS, which typically range from 20 to 200 nm (Mandell et al., 2004). These aerosols may deposit in the respiratory airways in discrete amounts resulting in local injury and spread of infectious diseases. Considering the extrathoracic nasal airways, which include the nasal passages, pharynx, and larynx, the deposition of submicrometer aerosols is associated with a number of detrimental health effects. The deposition of cigarette smoke particles has been quantitatively linked to the formation of respiratory tract tumors at specific sites (Martonen 1986). Yang et al. (1989) reported that respiratory tract cancers per unit surface area are approximately 3,000 times more likely in the extrathoracic airways including the larynx. Ostiguy et al. (2008) summarized the adverse health effects due to various nanoparticles such as carbon nanotubes, fullerenes, inorganic and organic nanoparticles, and quantum dots. Gurr et al. (2005) studied the effect of ultrafine TiO2 particles on human bronchial epithelial cells and reported that TiO2 particles of 10 and 20 nm triggered oxidative DNA damage and lipid peroxidation, the later of which may also explains the cytotoxicity of water-soluble fullerenes or nC60 (Sayes et al., 2005).

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.

Transport and Absorption of Anesthetic Vapors in a Mouth-Lung Model Extending to G9 Bronchioles

Background: The inhalation of anesthetic vapors into the lungs is a function of both the respiration and inhalant property. Factors which influence the alveolar concentration of anesthetics include breathing activities, airway morphology, anesthetic diffusivity, and wall absorption rate. Administered anesthetic levels could be significantly different from the alveolar level due to wall absorption loss and gas mixing in the airway. Objective: To assess the transport and absorption of inhaled anesthetics in an anatomically accurate respiratory airway geometry. Specifically aims include understanding the transport of inhaled vapors, quantifying the pulmonary dosage of administered anesthetics, and identifying factors that influence airway absorption losses. Methods: The geometry consisted of a CT-based mouth-throat (MT) model and a tracheobronchial (TB) model which extends to G9 bronchioles and consists of 115 outlets. Vapor transport and absorption were simulated using the Chemical Species model coupled with a user-defined vapor-absorption module. Results: Unlike previously assumed developed flows after G6, features of developing flows are still apparent in the G9 bronchioles in this study. Large variations of bronchiolar vapor concentrations were observed among the five lobes. Under quiet breathing conditions, vapor concentrations at the G9 outlets are 15 - 30% of the inhaled concentration level due to gas mixing and wall absorption. The delivered dose to the pulmonary region varies from 48% to 96%, depending on the vapor diffusivity and solubility. Vapor depletion due to wall absorption is significant (52%) for highly soluble anesthetics and is inconsequential for low solubility ones. Conclusion: A computer model was developed that implemented a wall absorption module in a realistic mouth-lung model extending to G9. This model provides the basis for future quantitative studies of the relationship between administered anesthetics and induced anesthetic level.