Flow distribution through human and canine airways during inhalation and exhalation

Airflow distribution through the tracheobronchial tree is influenced by many factors. In a hollow cast of the central airways, the only factors involved are resistance and inertia of the airflow. Distribution of steady flow during both inhalation and exhalation was measured at different total flow rates in human and canine tracheobronchial casts. The resulting airflow rates in peripheral segments were measured with a sensitive apparatus, which did not disturb the distribution of flow. Inertia of the airflow was found to be small but significant in airways of the human cast and substantially greater in the canine airway cast than in the human cast during inhalation. The influence of airflow inertia during inhalation was largely responsible for the different distributions of flow during inhalation and exhalation through the airway casts. Airflow resistance was found to be considerably greater during exhalation and may have contributed to the redistribution of flow. The forces involved are small but should be considered when modeling the in vivo distribution of airflow.     

Numerical Simulation of Airway Dimension Effects on Airflow Patterns and Odorant Deposition Patterns in the Rat Nasal Cavity

The sense of smell is largely dependent on the airflow and odorant transport in the nasal cavity, which in turn depends on the anatomical structure of the nose. In order to evaluate the effect of airway dimension on rat nasal airflow patterns and odorant deposition patterns, we constructed two 3-dimensional, anatomically accurate models of the left nasal cavity of a Sprague-Dawley rat: one was based on high-resolution MRI images with relatively narrow airways and the other was based on artificially-widening airways of the MRI images by referencing the section images with relatively wide airways. Airflow and odorant transport, in the two models, were determined using the method of computational fluid dynamics with finite volume method. The results demonstrated that an increase of 34 µm in nasal airway dimension significantly decreased the average velocity in the whole nasal cavity by about 10% and in the olfactory region by about 12% and increased the volumetric flow into the olfactory region by about 3%. Odorant deposition was affected to a larger extent, especially in the olfactory region, where the maximum odorant deposition difference reached one order of magnitude. The results suggest that a more accurate nasal cavity model is necessary in order to more precisely study the olfactory function of the nose when using the rat.     

Modeling the bifurcating flow in an asymmetric human lung airway

In a former paper, the inspiratory flow characteristics in a three-generation symmetric bifurcation airway have been numerically investigated using a control volume method to solve the fully three-dimensional laminar Navier-Stokes equations. The present paper extends the work to deal with asymmetric airway extracted from the 5th-11th branches of the model of Weibel (Morphometry of the Human Lung. New York Academic Press, Verlag, 1963) in order to more appropriately model human air passage. Computations are carried out in the Reynolds number range 200-1600, corresponding to mouth-air breathing rates ranging from 0.27 to 2.16l/s, representative for an averaged height man breathing from quiet to vigorous state. Particular attentions are paid to establishing relations between the Reynolds number and the overall flow characteristics, including flow patterns and pressure drop. The study shows that the ratios of airflow rate through the medial branches to that of their mother branches are the same, and this is also true for the ratios of airflow rate through the lateral branches. This partially explains why regular human breathing is not affected by airways of different sizes.     

Flow simulation in the human upper respiratory tract

Computer simulations of airflow patterns within the human upper respiratory tract (URT) are presented. The URT model includes airways of the head (nasal and oral), throat (pharyngeal and laryngeal), and lungs (trachea and main bronchi). The head and throat morphology was based on a cast of a medical school teaching model; tracheobronchial airways were defined mathematically. A body-fitted three-dimensional curvilinear grid system and a multiblock method were employed to graphically represent the surface geometries of the respective airways and to generate the corresponding mesh for computational fluid dynamics simulations. Our results suggest that for a prescribed phase of breath (i.e., inspiration or expiration), convective respiratory airflow patterns are highly dependent on flow rate values. Moreover, velocity profiles were quite different during inhalation and exhalation, both in terms of the sizes, strengths, and locations of localized features such as recirculation zones and air jets. Pressure losses during inhalation were 30-35% higher than for exhalation and were proportional to the square of the flow rate. Because particles are entrained and transported within airstreams, these results may have important applications to the targeted delivery of inhaled drugs.     

Role of aquaporin water channels in airway fluid transport, humidification, and surface liquid hydration

Several aquaporin-type water channels are expressed in mammalian airways and lung: AQP1 in microvascular endothelia, AQP3 in upper airway epithelia, AQP4 in upper and lower airway epithelia, and AQP5 in alveolar epithelia. Novel quantitative methods were developed to compare airway fluid transport-related functions in wild-type mice and knockout mice deficient in these aquaporins. Lower airway humidification, measured from the moisture content of expired air during mechanical ventilation with dry air through a tracheotomy, was 54-56% efficient in wild-type mice, and reduced by only 3-4% in AQP1/AQP5 or AQP3/AQP4 double knockout mice. Upper airway humidification, measured from the moisture gained by dry air passed through the upper airways in mice breathing through a tracheotomy, decreased from 91 to 50% with increasing ventilation from 20 to 220 ml/min, and reduced by 3-5% in AQP3/AQP4 knockout mice. The depth and salt concentration of the airway surface liquid in trachea was measured in vivo using fluorescent probes and confocal and ratio imaging microscopy. Airway surface liquid depth was 45 +/- 5 microm and [Na(+)] was 115 +/- 4 mM in wild-type mice, and not significantly different in AQP3/AQP4 knockout mice. Osmotic water permeability in upper airways, measured by an in vivo instillation/sample method, was reduced by approximately 40% by AQP3/AQP4 deletion. In doing these measurements, we discovered a novel amiloride-sensitive isosmolar fluid absorption process in upper airways (13% in 5 min) that was not affected by aquaporin deletion. These results establish the fluid transporting properties of mouse airways, and indicate that aquaporins play at most a minor role in airway humidification, ASL hydration, and isosmolar fluid absorption.     

Characteristics of airflow in a CT-based ovine lung: a numerical study.

The transient airflow in a rigid, asymmetric monopodial sheep (ovine) tracheobronchial tree of up to 13 generations was investigated numerically. The lung geometry was segmented and reconstructed from computed-tomographic (CT) images. The flow characteristics in the image-based sheep airway were compared with the flow patterns produced by a Weibel-based model at prime locations. Boundary conditions were prescribed 1) a velocity profile from experimental data at the inlet and 2) zero pressure at the bronchial outlets. A mesh convergence study was carried out to establish confidence in the model predictions, and gross left-right ventilation was validated against experimental xenon wash-in-washout data. Detailed flow characteristics were investigated at three points in the breathing cycle: 1) peak inhalation, 2) peak exhalation, and 3) transition. Simulation results revealed fundamental differences between airflow in monopodial and bipodial branching airways. Compared with idealized bipodial flow, the flow in the sheep airway was asymmetric and highly vortical, especially during exhalation and transition. The streak lines during the inhalation phase suggest that the left and right upper lobes are ventilated by airflow in the peripheral region of the trachea. This work may contribute to understanding the interplay between structure and function in the lung.     

Bronchial reactivity in asthmatic adults with normal spirometric values.

A comparison was made between airways obstruction produced by exercise. Hyperventilation of cold air, hyperventilation of room air, and inhalation of ultrasonically nebulised distilled water. Seven asthmatics with no airflow obstruction were studied together with seven normal controls. All four provocations produced comparable mean reductions in forced expired volume in one second in the asthmatic patients, but no reduction was obtained in the controls. Whereas exercise, hyperventilation of cold air, and hyperventilation of room air were associated with heat loss from airways, inhalation of nebulised distilled water was not. Inhalation of ultrasonically nebulised distilled water offers a simple additional diagnostic test for asthma. Changes in the osmolality of airway surface liquid may possibly be the common mechanism by which "fog" and hyperventilation produce bronchoconstruction.     

Modeling the bifurcating flow in a human lung airway

The inspiratory flow characteristics in a three-generation lung airway have been numerically investigated using a control volume method to solve the fully three-dimensional laminar Navier-Stokes equations. The three-generation airway is extracted from the fifth to seventh branches of the model of Weibel (Morphometry of the Human Lung, Academic Press, New York, Springer, Berlin, 1963) with in-plane and 90 degrees off-plane configurations. Computations are carried out in the Reynolds number range of 200-1600, corresponding to mouth-air breathing rates ranging from 0.27 to 2.16l/s, or an averaged height of a man breathing from quiet to vigorous state. Particular attention is paid to establishing relations between the Reynolds number and the overall flow characteristics, including flow patterns and pressure drop. The ratio of airflow rate through the medial branch to that of the lateral branch for an in-plane airway increases as Re(0.227). However, the total pressure drop coefficient varies as Re(-0.497) for an in-plane airway and as Re(-0.464) for an off-plane airway. These pressure drop results are in good agreement with the experimentally measured behavior of Re(-0.5) and are more accurate than the numerically determined behavior of Re(-0.61) assuming the airways to be approximated by two-dimensional channels.     

Effect of airway surface liquid on the forces on the pharyngeal wall: Experimental fluid–structure interaction study

Obstructive sleep apnoea syndrome (OSAS) is a breathing disorder with a multifactorial etiology. The respiratory epithelium is lined with a thin layer of airway surface liquid preventing interactions between the airflow and epithelium. The effect of the liquid lining in OSAS pathogenesis remains poorly understood despite clinical research. Previous studies have shown that the physical properties of the airway surface liquid or altered stimulation of the airway mechanoreceptors could alleviate or intensify OSAS; however, these studies do not provide a clear physical interpretation. To study the forces transmitted from the airflow to the liquid-lined compliant wall and to discuss the effects of the airway surface liquid properties on the stimulation of the mechanoreceptors, a novel and simplified experimental system mimicking the upper airway fundamental characteristics (i.e., liquid-lined compliant wall and complex unsteady airflow features) was constructed. The fluctuating force on the compliant wall was reduced through a damping mechanism when the liquid film thickness and/or the viscosity were increased. Conversely, the liquid film damping was reduced when the surface tension decreased. Based on the experimental data, empirical correlations were developed to predict the damping potential of the liquid film. In the future, this will enable us to extend the existing computational fluid–structure interaction simulations of airflow in the human upper airway by incorporating the airway surface liquid effect without adopting two-phase flow interface tracking methods. Furthermore, the experimental system developed in this study could be used to investigate the fundamental principles of the complex once/twice-coupled physical phenomena.     

Direct visualizations of air flow in the human upper airway using in-vitro models

A better understanding of airflow characteristics in the upper airway(UA) is crucial in investigating obstructive sleep apnea(OSA), particle sedimentation, drug delivery, and many biomedical problems. Direct visualization of air flow patterns in in-vitro models with realistic anatomical structures is a big challenge. In this study, we constructed unique half-side transparent physical models of normal UA based on realistic anatomical structures. A smoke-wire method was developed to visualize the air flow in UA models directly. The results revealed that the airflow through the pharynx was laminar but not turbulent under normal inspiration, which suggested that compared with turbulent models, a laminar model should be more suitable in numerical simulations. The flow predicted numerically using the laminar model was consistent with the observations in the physical models. The comparison of the velocity fields predicted numerically using the half-side and complete models confirmed that it was reasonable to investigate the flow behaviors in UA using the half-side model. Using the laminar model, we simulated the flow and evaluated the effects of UA narrowing caused by rostral fluid shift on pharyngeal resistance. The results suggested that fluid shift could play an important role in the formation of hypopnea or OSA during sleep.     

A threshold lung volume for optimal mechanical effects on upper airway airflow dynamics: studies in an anesthetized rabbit model

Increasing lung volume improves upper airway airflow dynamics via passive mechanisms such as reducing upper airway extraluminal tissue pressures (ETP) and increasing longitudinal tension via tracheal displacement. We hypothesized a threshold lung volume for optimal mechanical effects on upper airway airflow dynamics. Seven supine, anesthetized, spontaneously breathing New Zealand White rabbits were studied. Extrathoracic pressure was altered, and lung volume change, airflow, pharyngeal pressure, ETP laterally (ETPlat) and anteriorly (ETPant), tracheal displacement, and sternohyoid muscle activity (EMG%max) monitored. Airflow dynamics were quantified via peak inspiratory airflow, flow limitation upper airway resistance, and conductance. Every 10-ml lung volume increase resulted in caudal tracheal displacement of 2.1 ± 0.4 mm (mean ± SE), decreased ETPlat by 0.7 ± 0.3 cmH(2)O, increased peak inspiratory airflow of 22.8 ± 2.6% baseline (all P < 0.02), and no significant change in ETPant or EMG%max. Flow limitation was present in most rabbits at baseline, and abolished 15.7 ± 10.5 ml above baseline. Every 10-ml lung volume decrease resulted in cranial tracheal displacement of 2.6 ± 0.4 mm, increased ETPant by 0.9 ± 0.2 cmH(2)O, ETPlat was unchanged, increased EMG%max of 11.1 ± 0.3%, and a reduction in peak inspiratory airflow of 10.8 ± 1.0%baseline (all P < 0.01). Lung volume, resistance, and conductance relationships were described by exponential functions. In conclusion, increasing lung volume displaced the trachea caudally, reduced ETP, abolished flow limitation, but had little effect on resistance or conductance, whereas decreasing lung volume resulted in cranial tracheal displacement, increased ETP and increased resistance, and reduced conductance, and flow limitation persisted despite increased muscle activity. We conclude that there is a threshold for lung volume influences on upper airway airflow dynamics.     

Relationship of tracheal size to maximal expiratory airflow and density dependence

Wave-speed theory predicts that maximal expiratory flow (MEF) at high lung volumes depends strongly on size of central airways. We tested this prediction by correlating MEF and tracheal cross-section area (T-XSA) in 15 (11 males, 4 females) healthy never-smoking volunteers. T-XSA was determined by planimetric analysis of contiguous 1-cm computerized tomographic scans of the intrathoracic trachea. We found a significant correlation between T-XSA at total lung capacity (TLC) and flow at 75% of vital capacity (V75) (r = 0.88, P less than 0.001). This contrasted to the correlation found between lung volume at TLC and V75 (r = 0.60). Density dependence of airflow (percent increase in V75 in air) was 35 +/- 17% and showed a significant inverse relationship to T-XSA (r = 0.70). These results confirm predictions of wave-speed theory and demonstrate the importance of cross-sectional area of central airways in determining MEF at high lung volumes. The large variability of MEF in normal individuals partly represents variations in tracheal size. Poor correlation between lung size and airway size suggests only a loose coupling between airways and lung parenchyma consistent with dysanaptic growth. Our findings indicate that changes in density dependence of airflow are not solely determined by the status of small airways and that differences in tracheal size contribute to its variability.     

Computational model of airflow in upper 17 generations of human respiratory tract

Computational fluid dynamics (CFD) studies of airflow in a digital reference model of the 17-generation airway (bronchial tree) were accomplished using the FLUENT computational code, based on the anatomical model by Schmidt et al. [2004. A digital reference model of the human bronchial tree. Computerized Medical Imaging and Graphics 28, 203-211]. The lung model consists of 6.744 x 10(6) unstructured tetrahedral computational cells. A steady-state airflow rate of 28.3L/min was used to simulate the transient turbulent flow regime using a large eddy simulation (LES) turbulence model. This CFD mesh represents the anatomically realistic asymmetrical branching pattern of the larger airways. It is demonstrated that the nature of the secondary vortical flows, which develop in such asymmetric airways, varies with the specific anatomical characteristics of the branching conduits.     

Effects of Physical Properties of the Lung Parenchyma and Airways on Cough Efficiency

The effects of the physical parameters of the parenchyma and airways on the temporal relationships between the volume flow rate and the linear velocity of airflow in the trachea during coughing were studied using a mathematical model. It was shown that the relationship between the volume flow rate and the duration of the act of conghing can be used for assessment of inertial and viscous properties of the posterior wall of the trachea and for assessment of the parameter characterizing the nonlinearity of the intrapulmonary airway resistance. Computations indicated that the linear air velocity in the trachea and, therefore, the cough efficiency depend weakly on the physical properties of the posterior wall of the trachea and lung parenchyma.     

Comparative analysis of realistic CT-scan and simplified human airway models in airflow simulation

Efforts to model the human upper respiratory system have undergone many phases. Geometrical proximity to the realistic shape has been the subject of many research projects. In this study, three different geometries of the trachea and main bronchus were modelled, which were reconstructed from computed tomography (CT) scan images. The geometrical variations were named realistic, simplified and oversimplified. Realistic refers to the lifelike image taken from digital imaging and communications in medicine format CT scan images, simplified refers to the reconstructed image based on natural images without realistic details pertaining to the rough surfaces, and oversimplified describes the straight wall geometry of the airway. The characteristics of steady state flows with different flow rates were investigated, simulating three varied physical activities and passing through each model. The results agree with previous studies where simplified models are sufficient for providing comparable results for airflow in human airways. This work further suggests that, under most exercise conditions, the idealised oversimplified model is not favourable for simulating either airflow regimes or airflow with particle depositions. However, in terms of immediate analysis for the prediction of abnormalities of various dimensions of human airways, the oversimplified techniques may be used.     

Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure.

To partition the central and peripheral airway resistance in awake humans, a catheter-tipped micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a 3-mm-ID bronchus in 5 normal subjects, 7 patients with chronic bronchitis, 8 patients with emphysema, and 20 patients with bronchial asthma. We simultaneously measured mouth flow, transpulmonary pressure, and intra-airway lateral pressure during quiet tidal breathing. Total pulmonary resistance (RL) was calculated from transpulmonary pressure and mouth flow and central airway resistance (Rc) from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by the subtraction of Rc from RL. The technique permitted identification of the site of airway resistance changes. In normal subjects, RL was 3.2 +/- 0.2 (SE) cmH2O.l-1.s and the ratio of Rp to RL was 0.24 during inspiration. Patients with bronchial asthma without airflow obstruction showed values of Rc and Rp similar to those of normal subjects. Although Rc showed a tendency to increase, only Rp significantly increased in those patients with bronchial asthma with airflow obstruction and patients with chronic bronchitis and emphysema. The ratio of Rp to RL significantly increased in three groups of patients with airflow obstruction (P less than 0.01). These observations suggest that peripheral airways are the predominant site of airflow obstruction, irrespective of the different pathogenesis of chronic airflow obstruction.     

Expiration rate drives human airway design

Analyses of human airway architecture based on calculations of airflow resistance or energy dissipation suggest that the branching pattern is not optimized for minimizing energy loss by flow dissipation during respiration. Airway flow dissipates only a few percent of the total body work during normal breathing, so branching patterns deviate from minimum energy loss to also optimize other physiological needs. Studies of airway performance often record some measure of expiration, such as FEV1 (Forced Expiratory Volume in 1 s), because airway constriction during expiration limits the rate of rapid respiration. We posit that lung structure is optimized for the rate of expiration as well as minimum energy loss. By increasing the daughter-to-parent airway diameter ratio (h) from 0.794 (corresponding to the energy minimum for symmetrically branching airways) to 0.85 (the observed value in humans) luminal pressures at airway generations 4-15 were substantially increased during exercise (a 4.5 and 15 cmH₂O increase during moderate and heavy exercise, respectively). Values of h somewhat larger than 0.794 help airways remain open during expiration by increasing both viscous pressure drop and convective acceleration pressure drop. Asymmetric bifurcations also exhibit higher proximal airway pressures than symmetric ones, but the improvement was not large.