Flow In Airways Research Articles

Bioengineering. Secondary Flow Augmentation during Intermittent Oscillatory Flow in Model Human Central Airways.

The efficiency of axial gas dispersion during ventilation with high-frequency oscillations (HFO) can be improved by manipulating the oscillatory flow waveform such that intermittent oscillatory flow occurs. To clarify the augmentation of axial gas transfer during intermittent oscillatory flow, we measured the axial and secondary velocity profiles during intermittent oscillatory flow through a model human central airway. We used a rigid model of human airways consisting of asymmetrical bifurcations up to third generation. Velocities in the axial and radial directions were measured with two-color laser-Doppler velocimetry. Secondary flow was accelerated at the beginning of the stationary period, particularly in the trachea, which resulted in enhanced gas transport during intermittent oscillatory flow.

913 多分岐管気道モデル内振動流における二次流れの空間・時間的変化

913 多分岐管気道モデル内振動流における二次流れの空間・時間的変化

Spatial and temporal variation of secondary flow during oscillatory flow in model human central airways.

Axial and secondary velocity profiles were measured in a model human central airway to clarify the oscillatory flow structure during high-frequency oscillation. We used a rigid model of human airways consisting of asymmetrical bifurcations up to third generation. Velocities in each branch of the bifurcations were measured by two-color laser-Doppler velocimeter. The secondary velocity magnitudes and the deflection of axial velocity were dependent not only on the branching angle and curvature ratio of each bifurcation, but also strongly depended on the shape of the path generated by the cascade of branches. Secondary flow velocities were higher in the left bronchus than in the right bronchus. This spatial variation of secondary flow was well correlated with differing gas transport rates between the left and right main bronchus.

Use of Heliox-Driven Nebulizer Therapy in the Treatment of Acute Asthma

Study objective: To compare the effectiveness of a helium-oxygen mixture with that of oxygen alone as an aerosolizing gas for β-agonist therapy in patients with mild to moderate exacerbation of asthma. Methods: A prospective, single-blinded study was performed in an urban teaching hospital over a period of 5 months. A convenience sample of 205 patients with mild to moderate exacerbation of asthma were enrolled. The participants were randomly assigned to 1 of 2 groups. The first group received 3 doses of albuterol, 5.0 mg aerosolized in 10 L/min of oxygen, 15 minutes apart. The second group received 3 doses of albuterol, 5.0 mg aerosolized in 10 L/min of a 70:30 helium-oxygen mixture (heliox), 15 minutes apart. Peak expiratory flow rate (PEFR), forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV 1 ) were measured before and after each treatment. Only PEFR and FEV 1 were used in data analysis. Results: Although both the heliox and the oxygen group showed significant improvement in PEFR from baseline after 45 minutes (72% and 70%, respectively), the difference between the 2 groups was clinically and statistically insignificant ( P =.56). Similar findings were observed for FEV 1 . There was no difference in rate of admission or rate of complications between the 2 groups. Conclusion: Despite its ability to decrease the turbulent flow in airways and to reach distal pulmonary tissues, heliox had no clinically significant advantage over standard therapy in the treatment of mild to moderate asthma. Further large-scale studies are necessary to determine the clinical efficacy of heliox in this setting. [Henderson SO, Acharya P, Kilaghbian T, Perez J, Korn CS, Chan LS: Use of heliox-driven nebulizer therapy in the treatment of acute asthma. Ann Emerg Med February 1999;33:141-146.]

REVERSAL OF THE BERNOULLI EFFECT AND CHANNEL FLUTTER

This paper is concerned with the collapse and subsequent self-excited oscillation of compliant tubes conveying fluids. Our model considers a two-dimensional, inviscid, shear flow in a flexible channel of infinite length subject to linear, travelling varicose waves. Analysis of the boundary-value problem leads to two findings which do not seem to have been noticed before, despite the close attention this kind of fluid–structure interaction has attracted on account of its medical significance. The pressure perturbation on the wall has two components, the first is in-phase with the wall displacement and the second with the velocity of the wall motion. For potential flow, the first component is the only one tending to destabilize and is known as the Bernoulli effect. For shear flow, however, the sign of the pressure is reversed as the Bernoulli effect is overcome by the perturbations of the vorticity field. Streamline patterns show that Kelvin's “cats' eyes” are sheltered in the wider channel sections, rendering the effective flow passage smaller where the physical width is larger. The second component produces a wave drag, hence irreversible transfer of energy from the flow to waves. We argue that this is a possible mechanism for the self-excited oscillation observed in experiments. This mechanism is similar to Miles's (1957) mechanism of water wave generation by wind, which is a class B instability according to the Benjamin–Landahl categorization, but the accompanying reversal of the Bernoulli effect is different and depends essentially on the presence of a second boundary. The eigenvalue problem is also considered and it is shown that dynamic instability of long but finite wavelength could be experienced by compliant channels with thick walls, a typical application being the respiratory flow in the upper airways. The critical flow speed is given in terms of the channel properties.

Evaluation of local gas transport rate in oscillatory flow in a model human central airways

Evaluation of local gas transport rate in oscillatory flow in a model human central airways

Effects of endothelins 1, 2 and 3 on mucosal blood flow in the upper airways.

The three endothlins 1, 2 and 3 (ET-1, ET-2 and ET-3) are 21-amino-acid peptides which in a previous study in the rabbit have been shown to increase both mucociliary activity in the maxillary sinus in vivo and ciliary beat frequency (CBF) in sinus and tracheal samples in vitro. We have also demonstrated positive immunohistochemical staining for endothelin in the epithelium of samples from both maxillary sinus and trachea. The aims of the present investigation were to study the effects of the three endothlins on mucosal blood flow in the maxillary sinus of rabbits and the nasal mucosa of humans. ET-1, ET-2 and ET-3 decreased mucosal blood flow in the maxillary sinus of rabbits measured in vivo with laser Doppler flowmetry (LDF). Significant dose-response relationships were established for all endothelins. A comparison of the regression lines of the dose-response relationships for ET-1 and ET-2 did not show any difference, whereas the regression line of the dose-response relationships for ET-3 differed significantly. Maximum effect was seen at 50.0 pmol/kg ET-1, which reduced blood flow by -74.4 +/- 7.0%. Vasoconstriction became evident 30 s after administration of the endothelins, reached its maximum after 1 min and lasted 10 to 20 min. ET-1 induced stronger vasconstriction than ET-2 and ET-3 at equal dosage, except at 100.0 pmol/kg, where ET-2 had the same effect as ET-1. No tachyphylaxis was observed after repeated 10.0 pmol/kg-dose of ET-1. Similarly, there was no tachyphylactic effect on mucociliary activity in vivo in the maxillary sinus of rabbits after repeated challenges with ET-1 at 10.0 pmol/kg. Pretreatment with the cyclooxygenase inhibitors diclofenac had no inhibitory effect on the vasoconstriction induced by ET-1 at 10.0 and 50.0 pmol/kg. In 6 human volunteers the peak blood flow in the nasal septum decreased by -41.8 +/- 11.6% (p < 0.05) and AUC (area under curve) values decreased by -612.0 +/- 322.4% (p < 0.05) after challenge with 0.1 nmol ET-1, delivered in aerosol form into the nose. The effects of the endothelins on the blood flow in the upper airways of rabbit and man indicate that they have a functional role in the regulation of the mucosal vasculature of the upper airways.

Particle diffusion with entrance effects in a smooth-walled cylinder

This work describes convective particle diffusion from developing flows in smooth-walled tubes and presents a closed-form solution for particle deposition efficiencies. The mathematical model is used to simulate inhaled particles in human airways for applicability to aerosol therapy (the treatment of lung diseases) and inhalation toxicology (the risk assessment of air pollutants). Momentum and concentration equations initially written in cylindrical coordinates were simplified by a scaling technique and solved analytically. A general velocity profile within the boundary layer of developing flow was determined based on the reduced momentum equation. A concentration boundary layer equation, different from Ingham's (1991) approach, was solved. Core flow acceleration was allowed in the airway lumen outside the boundary layer. Scale analyses demonstrated that the magnitude of the radial convection term in the particle concentration equation was quite small relative to both the longitudinal convection term and the effect of curvature (i.e., 1 r term where r is tube radius). Therefore, it could be neglected, especially for flow in airways of small dimensions. The effects of core flow acceleration were negligible for particle diffusion studies pertinent to airways of the human lung. Our predictions were between 3% and 75% greater than the corresponding theoretical results of Ingham (1991) for various Schmidt numbers and were, therefore, in better agreement with the experimental results of Cohen and Asgharian (1990). Consideration of the effects of tube curvature contributed significantly to the improved accuracy of our model.

Effects of Substance P and Methacholine on Mucosal Blood Flow in the Upper Airways

The aims of the present investigation were to examine the in vivo effects of substance P (SP) and methacholine on blood flow measured by laser Doppler technique in the maxillary sinus of the rabbit and in the human nasal mucosa. In the rabbit, the test substances were administered by intra-arterial catheter, and the laser Doppler probe was inserted into the maxillary sinus through a trepanation in the anterior wall. In the human nose, the laser Doppler probe was directed toward the nasal septum at the level of the anterior margin of the middle turbinate, and the test substances were administered as aerosols into the ipsilateral nostril. In the rabbit maxillary sinus, both SP and methacholine increased the blood flow, the maximum increases obtained being 13.5 ± 3.1% and 39.0 ± 5.6% after challenges with SP at 0.1 μg/kg and methacholine at 0.5 μg/kg, respectively. The rabbits displayed a decrease in blood flow after challenges at higher dosages of both SP and methacholine, accompanied by a simultaneous fall in systemic blood pressure. Atropine given IV five minutes before methacholine abolished the effects of this compound in the rabbit. The blood flow in the human nose was unaffected by saline controls, whereas it was increased both by SP and by methacholine, the increases being 34.9 ± 6.0% after challenges with SP 1.0 nmol and 119.2 ± 15.1% after challenges with methacholine 5.0 μmol. According to acoustic rhinometry, neither SP nor methacholine had, at the doses used, any effect on human nasal patency. Pretreatment with lidocaine hydrochloride spray into the human nose did not affect the increase in nasal blood flow induced by SP, but abolished the methacholine-evoked blood flow increase. Pretreatment with ipratropium bromide spray into the human nose abolished the increase in blood flow induced by methacholine. The results of the present study indicate that blood flow in the upper airways of humans and rabbits may increase due to release of SP or acetylcholine in vivo, an event that occurs after exposure to airway irritants. The vasodilation in the human nose produced by acetylcholine may be due to a neurogenic reflex, in contrast to the effect of SP.

Gas flow and mixing in the airways.

To survey the current state of scientific knowledge of gas flow and mixing in pulmonary airways, especially at high frequencies. Results from the authors' own laboratory studies and Western bioengineering literature on respiratory fluid mechanics. This survey concentrates on understanding the principal physical mechanisms that underlie the enhancement of airway gas transport in high-frequency oscillation. The results of experimental, computational, and mathematical studies are described. The topic was covered by seven presenters at the Münster Meeting on High Frequency Ventilation, January 31 to February 2, 1993. Six of these presentations are summarized in the six sections of this paper under the following headings: Introductory Survey; Three-Dimensional Numerical Simulation of Inspiratory and Expiratory Flows in Small Airways; Computational and Experimental Models of High-Frequency Oscillation; Unsteady Gas Mixing in Airways; Gas Dispersion From the Lagrangian Viewpoint; and Soluble Gas Mass Transfer in Tubes and Airways. The dominant mechanism for the enhancement of gas transport along airways at high frequency is likely to lie in the coupling of the secondary motions caused by airway curvature with the oscillatory longitudinal flow. However, laboratory experiments and theoretical analyses have led only to an accurate simulation of the phenomena in idealized geometries, not in real lungs.

Maternal Smoking during Pregnancy as a Predictor of Lung Function in Children

Recent studies have suggested that prenatal exposure to environmental tobacco smoke may lead to lower lung function in infants. The authors examined the relation of maternal smoking during pregnancy to persistent deficits in the lung function of older children. Subjects were 8,863 nonsmoking white children aged 8-12 years from 22 North American communities. Information on maternal smoking was provided by the child's mother. Pulmonary function testing of the children was conducted at school in 1988-1991. Children whose mothers smoked during pregnancy, whether or not they still smoked in the year prior to the study, had significantly lower lung function than did children whose mothers did not smoke in either period. On average, forced expiratory flow between 65 and 75 percent of forced vital capacity (FEF65-75%), forced expiratory flow between 25 and 75 percent of forced vital capacity (FEF25-75%), and forced expiratory volume in 3/4 of a second (FEV0.75) were 5.7%, 4.9%, and 1.7% lower, respectively, for children whose mothers smoked during pregnancy. After adjusting for maternal smoking during pregnancy, the authors found that current maternal smoking was not associated with significant differences on any lung function measure. These results show a persistent deficient in lung function associated with maternal smoking during pregnancy that is not explained by current maternal smoking alone. The strongest effects were observed with pulmonary function measures of flow in the small airways. The authors conclude that the effects of exposure to tobacco smoking by the mother during pregnancy and/or environmental tobacco smoke exposure in the first few years of life persist into childhood and may affect the pulmonary function attained throughout the child's life.

A numerical simulation of gas flow during coal/gas outbursts

A model of the gas flow in airways during an instantaneous outburst of coal and gas is formulated and solved numerically using MacCormack's explicit finite-difference scheme. This model is based on the assumption that geological structures, in-situ stresses and high-gas-pressure gradients play important roles in initiating an outburst, with the gas content and gas-pressure gradients being the most dominant factors. The fluid-dynamic processes that occur after an outburst are computed by the numerical integration of the complete time-dependent Navier-Stokes equations. The mixture velocity, the density and the gas-concentration profiles in both time and space domains (immediately after an outburst) are presented. The global results are useful in gaining an improved understanding of gas-flow patterns during coal/gas outbursts and in determining the range of the disturbance so that effective methods of control can be developed.

Tracheal Sound Spectra Depend on Body Height

Tracheal sounds originate from turbulent flow in upper and central airways. Turbulent flow characteristics are influenced by conduit dimensions. Because tracheal dimensions are a function of body height, we hypothesized that there should be a correlation between sound spectra and body length. We recorded tracheal sounds at standardized airflows in 21 healthy children 9.1 +/- 0.6 yr of age (mean +/- SE) and in 24 healthy adults 30.2 +/- 0.8 yr of age. A contact sensor was attached at the suprasternal notch of the sitting subject, and airflow was measured at the mouth with a calibrated pneumotachograph. Tracheal sounds were low-pass-filtered at 2.4 kHz and digitized at 10 kHz. A 2048 point FFT was applied at a successive 100-ms intervals, using a Hanning data window. Resulting spectra were normalized to a reference power of 0.1 (mV)2/5 Hz. We applied a gating algorithm to extract sounds at inspiratory flows of 1 L/s (+/- 10% tolerance), and we computed average power spectra from the collected samples. We calculated the average spectral power (Pavg), the quartile frequencies below which 25% (Q1), 50% (Q2), and 75% (Q3) of the power in the range of 50 to 2,000 Hz was contained, the spectral edge frequency (SE95) below which 95% of the power was found, and the frequency where spectral power rolled off sharply (Fcut).(ABSTRACT TRUNCATED AT 250 WORDS)

NK1 receptors mediate neurogenic inflammatory increase in blood flow in rat airways.

We studied the effect of neurogenic inflammation on airway blood flow in anesthetized F-344 rats. Three successive determinations of blood flow were made by injecting radionuclide-labeled microspheres suspended in 70% dextrose into the left ventricle. A selective agonist of the tachykinin receptor neurokinin 1 (NK1) increased airway blood flow, but NK2- and NK3-selective agonists were without effect. The natural agonist of NK1 receptors, substance P (1 micrograms/kg), increased airway blood flow, an effect that was abolished by the selective NK1 receptor antagonist CP-99,994 [(+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine] but not by the (2R,3R)-enantiomer CP-100,263. Capsaicin (25 micrograms/kg), a drug that releases tachykinins and calcitonin gene-related peptide from sensory nerves, increased airway blood flow, and again this effect was abolished by CP-99,994. We also studied the effect of a selective inhibitor (captopril, 2.5 mg/kg) of the tachykinin-degrading enzyme kininase II [or angiotensin-converting enzyme (ACE)] on substance P-induced airway vasodilation. Captopril potentiated and prolonged the vasodilator effect of substance P. We conclude that neurogenic vasodilation in rat airways is due to the release of substance P, acts via NK1 receptors, and may be modulated by ACE.

Numerical simulation of aerosol particle transport by oscillating flow in respiratory airways.

Particle transport by oscillating flow in a tapered channel or in a tapered tube was computed from the complete equations of motion. These geometries represent a simplified model of the divergent flow field of the mammalian bronchial tree. The computed deformation profile of a line of particles, transported by the oscillatory motion, was compared with prior experimental results and analytical calculations. All three methods agree that there is transport in the divergent direction of the tube by an axial stream of steady drift in the core for moderately high frequency of oscillation (Womersley parameter in the range of 1 to 10). Bidirectional flow is established by an annular stream in the convergent direction, with no net flow on integral cycles of the oscillating fluid. At higher frequency, however, the steady stream transforms to a different shape in the tapered tube, with transport in the divergent direction nearer the walls of the tube, rather than in the core. Transport by the continuing streams with oscillatory ventilation of the respiratory tract should deliver medicinal aerosols of low intrinsic particle mobility to the peripheral regions of the lungs.

Effect of neuropeptides released from sensory nerves on blood flow in the rat airway microcirculation.

Stimulation of sensory nerves in the airway mucosa causes local release of the neuropeptides substance P and calcitonin gene-related peptide (CGRP). In this study we used a modification of the reference-sample microsphere technique to measure changes in regional blood flow and cardiac output distribution produced in the rat by substance P, CGRP, and capsaicin (a drug that releases endogenous neuropeptides from sensory nerves). Three sets of microspheres labeled with different radionuclides were injected into the left ventricle of anesthetized F344 rats before, immediately after, and 5 min after left ventricular injections of capsaicin, substance P, or CGRP. The reference blood sample was withdrawn from the abdominal aorta and was simultaneously replaced with 0.9% NaCl at 37 degrees C. We found that stimulation of sensory nerves with a low dose of capsaicin causes a large and selective increase in microvascular blood flow in the extrapulmonary airways. The effect of capsaicin is mimicked by systemic injection of substance P but not by CGRP, suggesting that substance P is the main agent of neurogenic vasodilation in rat airways.

A longitudinal study of baseline FEV1 and bronchial responsiveness in patients with asthma

The effect of initial airway calibre on the response to bronchial provocation is unclear. Theoretically, geometric relationships within the airways might influence the measurement of responsiveness, particularly since a given change in calibre will produce a disproportionately greater reduction in flow in airways which are already narrowed. We have examined the relationship between serial measurements of prechallenge forced expiratory volume in one second (FEV1) and responsiveness to methacholine (PD20) in 8 children and 12 adults with asthma. Measurements were made every 2-3 wks for 12-18 months and all patients kept a daily record of symptoms and twice daily measurements of peak expiratory flow (PEF). Spearman's rank correlation coefficient (rho) for the relationship PD20 versus pre-challenge FEV1 was derived for each patient and varied widely within the group (range -0.22 to 0.73, mean 0.31); the strength of this correlation was not related to a patient's mean FEV1 % predicted, but was related to the degree to which PD20 and pre-challenge FEV1 themselves reflected concurrent asthma severity (mean morning PEF and mean symptom scores for the three days around each test). This suggests that the observed relationship between pre-challenge FEV1 and PD20 may be due less to the influence of airway geometric factors, which might be expected to be present in all patients, but rather that pre-challenge FEV1 is reflecting the severity of the underlying disease. Larger studies will be needed to test this hypothesis further.

Contribution of large airway to the input impedance of the respiratory system

To evaluate the contribution of the large airway to total respiratory impedance, we develop a one-dimensional model of pressure and flow in these airways by coupling conservation of mass and momentum equations with the geometric information obtained by the acoustic reflection technique. We use this model to calculate the impedance of the respiratory system distal to the carina from impedance data estimated at the airway opening by the forced oscillation technique. Simulations show that the real part of the impedance distal to the carina is uniformly decreased from the impedance at the airway opening, indicating a resistive loss, while the imaginary part is increased as a function of frequency. We estimate parameter values for a six-parameter two-compartment lung model and for a three-parameter reduction of this model before and after the application of the upper airway data to the impedance spectrum. Although compliance terms seem to be minimally affected by the manipulation of the data, resistance and inertance terms are influenced in a fashion that suggests that the resistive contribution of the upper airway to total respiratory impedance is significant. Furthermore it appears that the elastic nature of the walls of the upper airway also impact on estimates of total respiratory impedance at the airway opening.

Management of chronic asthma -a personal view

The word ASTHMA is of Greek origin, meaning "breathless" or "to breathe with open mouth", and was originally applied to breathlessness of any cause. An accurate and comprehensive definition has proved far more elusive than expected, but from a clinician's viewpoint the currently most acceptable is that asthma is a disease characterised by wide variations over short periods of time in resistance to flow in intrapulmonary airways, The definition implies objective measurement and 15-20% variation is a significant level. This vague definition avoids the problem of dividing patients absolutely into categories of asthma and chronic bronchitis and then debating whether patients with chronic bronchitis have reversible airways disease. Even if symptoms suggest bronchitis, the finding of significant variation in resistance to airflow means that asthma co-exists and patients should be regarded as having "chronic bronchitis with asthmatic features."&#x0D; Difficulties with regard to definition make accurate assessment of the prevalence of the disease impossible and there are wide variations in the results of surveys in general practice. However, this is a common disease with a cumulative prevalence of up to about 5% in the United Kingdom.&#x0D; &#x0D;

Mechanism of increased collateral airway resistance during inhomogenous inflation of excised dog lungs

Collateral airway resistance was measured during inflation of an excised lung lobe or a segment within the lobe. Gas blown into the outer lumen of a double lumen cathether (V̇coll) inflated the segment and exited via collateral airways. Pressure at the cathether tip (Pct) was measured through the inner lumen of the catheter, and transpulmonary pressure (Pao) was measured at the lobar bronchus. A pleural capsule measured pressure in the segmental subpleural alveoli (Ps). The segment was inflated with helium (He), air, or sulfurhexafluoride; the lobe was ventilated with air. Collateral airway resistance [ Rcoll=( Pct-Pao)/ V ̇ coll ] , intrasegmental airway resistance [ Rs=( Pct-Ps)/ V ̇ coll ] , and resistance of airways passing through the segment-lobar interface [ Ri= (Ps-Pao)/ V ̇ coll ] were calculated. Rcoll, Rs and Ri were decreased by lobar inflation and increased by segment inflation. The latter increase was due to nonlaminar flow in intrasegmental airways. The major resistance was Ri when V̇coll was laminar or transitional. Moody plots suggested that lobar inflation caused intrasegmental airway dilation whereas segment inflation did not affect segment airway geometry.