Session J07: Respiratory Flows I

Upper Airway Structural Abnormality and the Impact on Air Flow in Chronic Obstructive Pulmonary Disease Patients

While chronic obstructive pulmonary disease (COPD) is a lung disease with lower airway obstruction with declined lung function, there is growing interest in upper airway abnormality in COPD regarding its importance in drug inhalation. We used quantitative computed tomography (QCT) analysis and computational fluid dynamics (CFD) simulations to investigate upper airway structural abnormality in COPD and the associated impact on air flow. From 40 COPD patients and 24 healthy subjects, mouth-throat CT images were acquired during at deep inspiration, with an empty dry power inhaler. From volumetric and length measurements, we found enlarged pharyngeal length and luminal narrowing at the 6th cervical vertebrae (C6). Three representative subjects were selected in each group, and large eddy simulations equipped with passive scale transport were conducted for tidal breathing and deep inhalation cases. We compare regional distributions of velocity, pressure, wall shear stress, temperature, and relative humidity from the mouth entrance to the tracheal entrance. Vortical structures are also compared.

 

    

When fluid mechanics meets virology: revisiting smallpox – a modeling framework for its airborne transmission

Combining virologic data with inhaled particulate dynamics inside respiratory cavities can model the infection onset process for pathogens that are either airborne or are anisotropic with predominantly aerial transmission routes. Here we apply this approach to answer the following questions on smallpox infection: (a) which droplet/aerosol sizes are mainly responsible for ferrying the virions to the infective zones at the oropharynx and in the lower airway; (b) what is its infectious dose, i.e. how many virions can trigger the infection. We have linked LES-based computational tracking of inhaled transport in 3 CT-based anatomic airway geometries – with the virion concentration in respiratory ejecta of a diseased carrier and the droplet/aerosol size distribution that an exposed subject might inhale. The tested droplet/aerosol sizes ranged over 0.1–35 microns and entered the airway through nostrils and mouth for steady-to-moderate breathing rates of 15, 30, 55, and 85 L/min. Viral transmission to the lower airway peaked for droplet diameters 0.1–14 microns; the corresponding range for oropharynx was 7–35 microns. Using literature data on confirmed exposure durations for transmission, this study approximates the smallpox infectious dose at 200–2000, which agrees with known estimates.

    

Effects of endotracheal tube selection on flow behavior to prevent ventilator-associated pneumonia

Ventilator-associated pneumonia (VAP) is a common secondary infection developed from longterm use of mechanical ventilators. The accumulation of mucus around the endotracheal tube (ETT), placed in the upper trachea of an intubated patient, leads to bacterial colonization which is the cause of such secondary infections. Considerable factors affect the mucus pooling along the ETT including the interactions between mucus and airflow, selection of ETT (size and cuff shape), and ventilator cycling. A quantitative understanding of the relationships between these different factors can be obtained from well-resolved simulations of the flow through the upper trachea. The present study focuses on the effect of the ETT on the mucus pooling behavior in an intubated trachea. Large Eddy Simulations of a Weibel-based model are implemented with two different endotracheal cuffs to determine the interaction of the cuff shape with the airflow rates and mucus pathways. This research further employs commonly used ventilator cycles to demonstrate the role of resulting flow patterns in long-term mucus deposition and release. Studying the flow surrounding the ETT will result in a better understanding of the flow behavior of intubated patients to reduce secondary infection.   

Upper Airway Flow Dynamics in Robin Sequence Infants: A 4-D Computed Tomography and Computational Fluid Dynamics Study

Robin Sequence (RS) is a craniofacial condition characterized by undersized jaw, posteriorly displaced tongue, and resultant upper airway obstruction (UAO). It is potentially fatal and requires varying levels of treatment. Accurate assessment of UAO severity is essential for successful management and diagnosis, yet current evaluation has significant limitations and no quantitative measures of breathing resistance exist. In this study we combine 4-D CT and computational fluid dynamics (CFD) to quantify UAO severity and location in RS patients. Dramatic intrapopulation differences are found, with the ratio between most and least severe values of breathing resistance, energy loss, and peak velocity equal to 40:1, 20:1, and 6:1, respectively. The primary UAO is found either at the tongue base or the larynx, with tongue base obstructions causing a more energetic stenotic jet and greater breathing resistance. CFD-derived flow metrics are found to correlate well with the level of clinical respiratory support. Our results highlight the large intrapopulation variability, both in quantitative metrics of UAO severity and in the location and intensity of stenotic jets for RS. These results suggest that computed airflow metrics can provide an evidence-based structure for the management of RS.   

Evaluation of pre- and post-surgery flow within the nasal cavity via 4D magnetic resonance velocimetry

The nasal cavity is the uppermost part of the respiratory system, which acts as a conduit that heats and humidifies inspired air. Understanding the fluid dynamics within this nasal cavity is challenging due to the complex internal flow passages, which make measurement of local velocities difficult. In this study, 4-dimensional magnetic resonance velocimetry (4D MRV) is utilized to measure the complex flow structure within the nasal cavity, before and after turbinoplasty and septoplasty surgeries are performed. 3-dimensional flow fields are obtained at each time phase of the respiration cycle, and large differences are observed before and after surgery. The experimental results are also compared with results from computational fluid dynamics (CFD) and show good agreement. From these findings, the improvement due to surgery can be evaluated. This process may allow 4D MRV to be utilized as the state-of-the-art method for nasal surgery evaluation.   

Exhaled human breath analysis using machine learning

Human exhaled breath is predominantly turbulent. This turbulence can help build algorithms to investigate the uniqueness of the extrathoracic airway. Air, during exhalation, is forced to flow out of the human lung through the trachea and oral cavity. We attempt to validate the hypothesis that turbulent exhaled flow carries a signature of the source of generation, i.e., the geometry of the upstream flow region. 1D velocity time series samples measured using hot-wire anemometer from 94 human volunteers make the dataset. Features from the available time-series data were extracted using MFDFA, a technique widely used for determining the fractal scaling properties and long-range correlations in the time series. The features are attributes of the multifractal spectrum of exhaled velocity data. Tuned random forest models were employed in building subject confirmation algorithms. A subject confirmation algorithm tries to verify whether a human subject is the person who they claim to be. The machine learning-based algorithm was found to achieve a good true confirmation rate. The accuracy in the binary classification of a majority of subject combinations was above 68%, which signifies the existence of some uniqueness in an individual's exhaled breath. Such an algorithm will help us explore the area of personalized medicines. This could be used as a tool to characterize or diagnose the variation in extrathoracic morphology over time. For example, it is possible that the turbulence information can be correlated to occlusion in the extrathoracic passage, which is a major source of deposition of aerosolized therapeutics.   

Transport of Clinical Surfactant in a Three-Dimensional Lung Model of Neonates: A Quantitative Experimental-Computational Study

Neonatal respiratory distress syndrome is mainly treated with the intratracheal delivery of pulmonary surfactants. The success of the therapy depends on the uniformity of distribution and efficiency of the delivery of the instilled surfactant solution to the respiratory zone of the lungs. Direct imaging of the surfactant distribution and quantifying the efficiency of delivery is not feasible in neonates. To address this major limitation, we designed an eight-generation model of neonate lung airway tree using morphometric and geometric data of human lungs and fabricated it using additive manufacturing. Using this model, we performed systematic experimental studies of delivery of a clinical surfactant either at a single aliquot or at two aliquots under different orientations of the airway tree in the gravitational space to mimic rolling a neonate on their side during the procedure. In addition, we developed an efficient computational fluid mechanics algorithm based on the concept of Pore Network Models (PNM) to simulate the delivery of clinical surfactants in complex biological transport networks. The computational algorithm is used to explore the delivery and distribution of clinical agents in lung networks for a wide range of input variables including lung orientations, instillation flow rates, and network morphology.  Our study offers both a novel lung airway model and new insights into the effects of the orientation of the lung airways and the presence of a pre-existing surfactant film on how the instilled surfactant solution distributes in airways.

    

Environmental Exposure, Airway Narrowing, Fibrotic Lung Injury: Multiscale Quantitative CT and CFD Analysis

We investigated a physical mechanism underlying in the association between environmental exposure, airway narrowing, and lung injury. Chest computed tomography (CT) images at full inspiration and full expiration, pulmonary function tests, and exposure information were collected from toxic humidifier disinfectant (HD)-exposed normal-appearing adults (age=50±15, M:F=52:44) as well as normal-appearing adults (age=68±10, M:F=15:51) and idiopathic pulmonary fibrosis (IPF) patients (age=72±7, M:F=43:10) from an air pollution study. About 200 lung structure-function features of static lung and tidal breathing were computed from quantitative CT (QCT) analysis and three-dimensional (3D) and one-dimensional (1D) computational fluid dynamics (CFD) simulations. Lower lobe airway narrowing and associated increase in the workload of breathing were found in both HD-affected patients with normal appearing lungs and IPF patients with relatively high ambient exposure, particularly in the right lower lobe. Common findings in the two groups may suggest that inhalation of toxic environmental agents induces airway narrowing, and airway narrowing increases workload of breathing, even at decreased flow rate.   

Effects of hydrodynamic slip and taenidial structure in insect tracheal flows

Insects have evolved respiratory systems that transport air inside complex microscale tracheal networks in a highly efficient way, as evidenced by the fact that their metabolic range is the highest in the animal kingdom. This exceptional range has been attributed to their unique respiratory systems, which carry oxygen directly to the cells. Insect respiratory flows are characterized by low Reynolds numbers (~0.1), but the Knudsen numbers in insect tracheae span the continuum, slip, and transitional regimes (~0.0001-1). In this work, we investigate the effects of hydrodynamic slip and fine-scale internal tracheal morphology in intratracheal flows in insects in silico. We hypothesize that the helical taenidial structures found on the inner wall of the tracheal tubes determine the structure of the flow field near the wall and play a vital role in transport. We have closely reproduced the internal morphology of the tracheal tubes of the American cockroach, Periplaneta americana, in our computational geometry. To investigate this hypothesis, we performed a series of simulations using the-open source CFD toolbox, OpenFOAM at a Reynolds number of 0.1. We find that the taenidia significantly affect the flow structure and characterize their contribution.

    

Mask deformation and flow leakage during pulsatile expiratory events

It is well established that diseases can be spread by airborne transmission, as small infectious particles are generated during respiratory events such as talking and coughing. One strategy to reduce disease transmission via expiration is the use of face maks. However, gaps between the mask and face result in flow leakage. In this work, the flow leakage around a surgical mask is studied. Using a pulsatile coughing simulator, mask deformations are measured using stereophotogrammetry for single- and double-pulsed (SP,DP) coughs at different cough peak flow rates (CPFR). Using finite element method modelling, these deformations are reproduced using a Kirchoff-Love plate model. Experiments reveal that the mask does not return to its initial position between pulses during a DP cough. This is consistent with previous findings that a DP cough generates greater leakage than a SP event. Furthermore, it is found that the maximum mask displacement does not linearly increase with CPFR. It is suggested that this correlates with observations that the normalized flow leakage out the side of a surgical mask is larger for smaller CPFR single-pulsed coughs.

    

A novel pressure boundary condition based on homothety human factors

A new and novel pressure boundary condition is developed based on the homothety factors of the human airways. The mathematical model, which has the ability to calculate the pressure drop of a number N of airway generations, is validated through CFD simulations for different Reynolds numbers. The boundary condition is implemented in the open source OpenFOAM. Two application cases are developed: the first, a study of airways with an asthma condition using a synthetic model, and the second, a study of airways collapse using a real specific patient model. The results and validations shown a low relative error between the pressure drops obtained with the complete CFD models and the hybrid simulations using CFD with the new boundary condition.

    

Computational Pulmonary Edema

We present a microvascular model of fluid transport in the alveolar septa related to pulmonary edema. It consists of a two-dimensional capillary sheet coursing by several alveoli. The alveolar epithelial membrane runs parallel to the capillary endothelial membrane with an interstitial layer in between, making one long septal tract. A coupled system of equations is derived using lubrication theory for the capillary blood, Darcy flow for the porous media of the interstitium, a passive alveolus, and the Starling equation at both membranes. Case examples include normal physiology, cardiogenic pulmonary edema, noncardiogenic edema ARDS and hypoalbuminemia, and the effects of PEEP. COVID-19 has dramatically increased ARDS in the world population, raising the urgency for such a model to create an analytical framework. Overall, the interstitial pressures are found to be significantly more positive than values used in the traditional physiological literature. That creates a steep gradient near the upstream and downstream ends outlets which drives significant flows towards the distant lymphatics. This may provide a possible explanation to the puzzle, noted since the late 19^th century, of how pulmonary lymphatics can function so far from the alveoli: the interstitium can be self-clearing.