Robust Unidirectional Airflow through Avian Lungs: New Insights from a Piecewise Linear Mathematical Model

Avian lungs are remarkably different from mammalian lungs in that air flows unidirectionally through rigid tubes in which gas exchange occurs. Experimental observations have been able to determine the pattern of gas flow in the respiratory system, but understanding how the flow pattern is generated and determining the factors contributing to the observed dynamics remains elusive. It has been hypothesized that the unidirectional flow is due to aerodynamic valving during inspiration and expiration, resulting from the anatomical structure and the fluid dynamics involved, however, theoretical studies to back up this hypothesis are lacking. We have constructed a novel mathematical model of the airflow in the avian respiratory system that can produce unidirectional flow which is robust to changes in model parameters, breathing frequency and breathing amplitude. The model consists of two piecewise linear ordinary differential equations with lumped parameters and discontinuous, flow-dependent resistances that mimic the experimental observations. Using dynamical systems techniques and numerical analysis, we show that unidirectional flow can be produced by either effective inspiratory or effective expiratory valving, but that both inspiratory and expiratory valving are required to produce the high efficiencies of flows observed in avian lungs. We further show that the efficacy of the inspiratory and expiratory valving depends on airsac compliances and airflow resistances that may not be located in the immediate area of the valving. Our model provides additional novel insights; for example, we show that physiologically realistic resistance values lead to efficiencies that are close to maximum, and that when the relative lumped compliances of the caudal and cranial airsacs vary, it affects the timing of the airflow across the gas exchange area. These and other insights obtained by our study significantly enhance our understanding of the operation of the avian respiratory system.     

O2 cost of inspiratory and expiratory resistive breathing in humans

In six normal male subjects we compared the O2 cost of resistive breathing (VO2 resp) between equivalent external inspiratory (IRL) and expiratory loads (ERL) studied separately. Each subject performed four pairs of runs matched for tidal volume, breathing frequency, flow rates, lung volume, pressure-time product, and work rate. Basal O2 uptake, measured before and after pairs of loaded runs, was subtracted from that measured during resistive breathing to obtain VO2 resp. For an equivalent load, the VO2 resp during ERL (184 +/- 17 ml O2/min) was nearly twice that obtained during IRL (97 +/- 9 ml O2/min). This twofold difference in efficiency between inspiratory and expiratory resistive breathing may reflect the relatively lower mechanical advantage of the expiratory muscles in overcoming respiratory loads. Variable recruitment of expiratory muscles may explain the large variation of results obtained in studies of respiratory muscle efficiency in normal subjects.     

Ventilatory response to inspired CO2 in the lizard, Tupinambis nigropunctatus

Elevating inspired levels of CO2 (1-4%) in Tupinambis nigropunctatus leads to an increase in tidal volume, mean expiratory flow, mean inspiratory flow, duration of the non-ventilatory period, inspiratory duration, expiratory duration and end inspiratory lung volume. Minute ventilation is variable and end expiratory volume decreases. An increase or decrease in CO2 concentration surrounding the head affects the duration of the non-ventilatory period before the altered CO2 concentration is inspired into the lungs. The change in duration of the non-ventilatory period before altered CO2 concentration is inspired into the lungs is probably mediated by CO2 sensitive receptors located in the mouth, nose or on the head surface.     

Defensive reflexes of the respiratory tract in dogs.

Intrapleural pressure, the tracheal air flow and tidal volume were recorded simultaneously in pentobarbital-anaesthetized dogs and changes occurring in them during defensive reflexes elicited by mechanical stimulation of the mucosa of different parts of the respiratory tract were evaluated quantitatively. The results show that, in addition to coughing and sneezing provoked by inserting a nylon fibre into the tracheobronchial region, the larynx and the nose, further respiratory reflexes described in other mammals also appear in these animals. Mechanical stimulation of the epipharynx with a fine polyvinylchloride catheter, for instance, also produces in dogs an aspiration reflex characterized by sniff-like inspiratory efforts without subsequent active expiration. Touching the vocal folds, however, produces an expiration reflex consisting of expiratory efforts without preceding inspiratory effort. The character of all these reflexes is typical and closely resembles their character in cats. Stimulation of the various parts of the respiratory tract sometimes evokes an apnoeic reaction instead of typical respiratory defensive reflexes.     

Respiratory volume perception through the nose and mouth determined noninvasively

The relative importance of the nose vs. the mouth in the perception of respiratory volumes has never been assessed, nor have previous respiratory perception studies been performed noninvasively. Using respiratory inductive plethysmography, we monitored 12 normal subjects noninvasively when breathing either exclusively through the nose or mouth. The sensation of inspired volume mouth breathing was compared with that of nose breathing over a wide range of the inspiratory capacity. The psychophysical techniques of tidal volume duplication, tidal volume doubling, and magnitude estimation were utilized. A just noticeable difference was calculated from the constant error of the tidal volume duplication trials. The exponents for magnitude estimation were 1.06 and 1.07 for nose and mouth breathing, respectively. The other psychophysical techniques also revealed no differences in nose and mouth volume perception. These results suggest that tidal volume changes are perceived equally well through the nose and mouth. Furthermore, the location of the receptors, important in volume perception, is probably at a distal point common to the nose and mouth.     

Mechanical constraints on exercise hyperpnea in endurance athletes.

We determined how close highly trained athletes [n = 8; maximal oxygen consumption (VO2max) = 73 +/- 1 ml.kg-1.min-1] came to their mechanical limits for generating expiratory airflow and inspiratory pleural pressure during maximal short-term exercise. Mechanical limits to expiratory flow were assessed at rest by measuring, over a range of lung volumes, the pleural pressures beyond which no further increases in flow rate are observed (Pmaxe). The capacity to generate inspiratory pressure (Pcapi) was also measured at rest over a range of lung volumes and flow rates. During progressive exercise, tidal pleural pressure-volume loops were measured and plotted relative to Pmaxe and Pcapi at the measured end-expiratory lung volume. During maximal exercise, expiratory flow limitation was reached over 27-76% of tidal volume, peak tidal inspiratory pressure reached an average of 89% of Pcapi, and end-inspiratory lung volume averaged 86% of total lung capacity. Mechanical limits to ventilation (VE) were generally reached coincident with the achievement of VO2max; the greater the ventilatory response, the greater was the degree of mechanical limitation. Mean arterial blood gases measured during maximal exercise showed a moderate hyperventilation (arterial PCO2 = 35.8 Torr, alveolar PO2 = 110 Torr), a widened alveolar-to-arterial gas pressure difference (32 Torr), and variable degrees of hypoxemia (arterial PO2 = 78 Torr, range 65-83 Torr). Increasing the stimulus to breathe during maximal exercise by inducing either hypercapnia (end-tidal PCO2 = 65 Torr) or hypoxemia (saturation = 75%) failed to increase VE, inspiratory pressure, or expiratory pressure. We conclude that during maximal exercise, highly trained individuals often reach the mechanical limits of the lung and respiratory muscle for producing alveolar ventilation. This level of ventilation is achieved at a considerable metabolic cost but with a mechanically optimal pattern of breathing and respiratory muscle recruitment and without sacrifice of a significant alveolar hyperventilation.     

Respiratory effects of transient axial acceleration.

Whereas gravity has an inspiratory effect in upright subjects, transient upward acceleration is reported to have an expiratory effect. To explore the respiratory effects of transient axial accelerations, we measured axial acceleration at the head and transrespiratory pressure or airflow in five subjects as they were dropped or lifted on a platform. For the first 100 ms, upward acceleration caused a decrease in mouth pressure and inspiratory flow, and downward acceleration caused the opposite. We also simulated these experimental observations by using a computational model of a passive respiratory system based on anatomical data and normal respiratory characteristics. After 100 ms, respiratory airflow in our subjects became highly variable, no longer varying with acceleration. Electromyograms of thoracic and abdominal respiratory muscles showed bursts of activity beginning 40-125 ms after acceleration, suggesting reflex responses responsible for subsequent flow variability. We conclude that, in relaxed subjects, transient upward axial acceleration causes inspiratory airflow and downward acceleration causes expiratory airflow, but that after ~100 ms, reflex activation of respiratory musculature largely determines airflow.     

Effect of hyperinflation on inspiratory function of the diaphragm.

The inspiratory efficiency of the diaphragm during unilateral and bilateral phrenic stimulation (UEPS and BEPS) with constant stimulus was studied in seven dogs from FRC to 120% TLC. Alveolar pressures (PAl) were recorded during relaxation, BEPS and UEPS at each lung volume in the closed respiratory system. From the PAl-lung volume curves, tidal volume (VT), and pressure developed by the diaphragm (Pmus) were derived. Results are summarized below. a) Hyperinflation impaired the inspiratory efficiency of the diaphragm which behaved as an expiratory muscle beyond the lung volume of 103.7% TLC (Vinef). b) The diaphragm during UEPS became expiratory at the same Vinef as during (BEPS. C) The VT-lung volume relationship was linear during BEPS, allowing simple quantitation of VT loss with hyperinflation and prediction of Vinef. d) With only one phrenic nerve stimulated, the functional loss is less pronounced in VT than in Pmus, as compared to BEPS, indicating that the respiratory system was more compliant during UEPS than BEPS. This compliance difference from UEPS to BEPS diminished with severe hyperinflation.     

Breath-by-breath alveolar gas exchange

A method is described for breath-by-breath measurement of alveolar gas exchange corrected for changes of lung gas stores. In practice, the subject inspires from a spirometer, and each expired tidal volume is collected into a rubber bag placed inside a rigid box connected to the same spirometer. During the inspiration following any given expiration the bag is emptied by a vacuum pump. A computer monitors inspiratory and expiratory tidal volumes, drives four solenoid valves allowing appropriate operation of the system, and memorizes end-tidal gas fractions as well as mixed expired gas composition analyzed by mass spectrometer. Thus all variables for calculating alveolar gas exchange, based on the theory developed by Auchincloss et al. (J. Appl. Physiol. 21: 810-818, 1966), are obtained on a single-breath basis. Mean resting and steady-state exercise gas exchange data are equal to those obtained by conventional open-circuit measurements. Breathing rates up to 30 X min-1 can be followed. The breath-to-breath variability of O2 uptake at the alveolar level is less (25-35%) than that measured at the mouth as the difference between the inspired and expired volumes, both at rest and during exercise up to 0.7 of maximum O2 consumption.     

Volume of activation of the Hering-Breuer inflation reflex in the newborn infant.

Although the Hering-Breuer inflation reflex (HBIR) is active within tidal breathing range in the neonatal period, there is no information regarding whether a critical volume has to be exceeded before any effect can be observed. To explore this, effects of multiple airway occlusions on inspiratory and expiratory timing were measured throughout tidal breathing range using a face mask and shutter system. In 20 of the 22 healthy infants studied, there was significant shortening of inspiration because the volume at which occlusion occurred rose from functional residual capacity (FRC) to end-inspiratory volume [14.9% reduction in inspiratory time (per ml/kg increase in lung volume at occlusion)]. All infants showed a significant increase in expiratory time [17.1% increase (per ml/kg increase in lung volume at occlusion)]. Polynomial regression analyses revealed a progressive increase in strength of HBIR from FRC to approximately 4 ml/kg above FRC. Eighteen infants showed no further shortening of inspiratory time and 10 infants no further lengthening of expiratory time with increasing occlusion volumes, indicating maximal stimulation of the reflex had been achieved. There was a significant relationship between strength of HBIR and respiratory rate, suggesting that HBIR modifies the breathing pattern in the neonatal period.     

Endothelin involvement in respiratory centre activity.

To evaluate the role of endothelin (ET) in respiratory homeostasis we studied the effects of the ET(A) and ET(B) receptor blocking agent bosentan on respiratory mechanics and control in seven anaesthetised spontaneously breathing pigs, for 180 min after single bolus administration (20 mg/kg i.v.). The results show that the block of ET receptors induced a significant increase in compliance and decrease in resistance of the respiratory system, entailing a significant reduction of diaphragmatic electromyographic activity, without affecting the centroid frequency of the power spectrum. Bosentan administration induced a significant increase in tidal volume (V(T)), accompanied by a significant decrease in respiratory frequency, without any significant change in pulmonary ventilation, CO(2) arterial blood gas pressure or pH. Since the relationship between V(T) and inspiratory time remained substantially constant after bosentan administration, the changes in respiratory pattern appear to be the result of an upward shift in inspiratory off-switch threshold. Both inspiratory and expiratory times during occluded breathing were increased by block of ET receptors, suggesting also a central respiratory neuromodulator effect of ET. In conclusion the present results suggest that the block of ET receptors in spontaneously breathing pigs exerts a role on mechanical properties of the respiratory system as well as on peripheral and central mechanisms of breathing control.     

Blood flow in respiratory muscles during maximal exertion in ponies with laryngeal hemiplegia

The interactive effects of upper airway negative pressure and hypercapnia on the pattern of breathing were assessed in pentobarbital-anesthetized cats. At any given level of pressure in the upper airway, hypercapnia increased respiratory rate, reduced inspiratory time, and augmented tidal volume, inspiratory airflow, and the peak and rate of rise of diaphragm electrical activity. Conversely, at any given level of CO2, upper airway negative pressure decreased respiratory rate, prolonged inspiratory time, and depressed inspiratory airflow and diaphragm electromyogram (EMG) rate of rise. Application of negative pressure to the upper airway shifted the relationship between tidal volume and inspiratory time upward and rightward. The relationship between inspiratory and expiratory times, however, was linearly correlated over a wide range of chemical drives and levels of upper airway pressure. These results suggest that in the anesthetized cat upper airway negative pressure afferent inputs 1) interact in an additive fashion with hypercapnia to alter the pattern of breathing, 2) interact multiplicatively with CO2 to influence mean inspiratory airflow and diaphragm EMG rate of rise, 3) depress the generation of central inspiratory activity, 4) increase the time-dependent volume threshold for inspiratory termination, and 5) affect the ratio between inspiratory and expiratory times in a similar manner as alterations in PCO2.     

Opiate slowing of feline respiratory rhythm and effects on putative medullary phase-regulating neurons

Opiates have effects on respiratory neurons that depress tidal volume and air exchange, reduce chest wall compliance, and slow rhythm. The most dose-sensitive opioid effect is slowing of the respiratory rhythm through mechanisms that have not been thoroughly investigated. An in vivo dose-response analysis was performed on medullary respiratory neurons of adult cats to investigate two untested hypotheses related to mechanisms of opioid-mediated rhythm slowing: 1) Opiates suppress intrinsic conductances that limit discharge duration in medullary inspiratory and expiratory neurons, and 2) opiates delay the onset and lengthen the duration of discharges postsynaptically in phase-regulating postinspiratory and late-inspiratory neurons. In anesthetized and unanesthetized decerebrate cats, a threshold dose (3 microg/kg) of the mu-opioid receptor agonist fentanyl slowed respiratory rhythm by prolonging discharges of inspiratory and expiratory bulbospinal neurons. Additional doses (2-4 microg/kg) of fentanyl also lengthened the interburst silent periods in each type of neuron and delayed the rate of membrane depolarization to firing threshold without altering synaptic drive potential amplitude, input resistance, peak action potential frequency, action potential shape, or afterhyperpolarization. Fentanyl also prolonged discharges of postinspiratory and late-inspiratory neurons in doses that slowed the rhythm of inspiratory and expiratory neurons without altering peak membrane depolarization and hyperpolarization, input resistance, or action potential properties. The temporal changes evoked in the tested neurons can explain the slowing of network respiratory rhythm, but the lack of significant, direct opioid-mediated membrane effects suggests that actions emanating from other types of upstream bulbar respiratory neurons account for rhythm slowing.     

A model of the central and reflex inhibition of inspiration in the cat

An attempt is made to summarize the results obtained in previous work from this and other laboratories on the steady state and transient relationships between the mechanical and neural events in breathing and their precise timing in the breathing cycle at different blood chemical demands for ventilation and at different body temperatures, and to fit these results into a functional and realistic model of the bulbo-pontine inspiratory off-switch mechanisms. The experimentally based requirements for the model are briefly described and listed. After a presentation of the model in qualitative terms its functional properties are considered quantitatively and compared with the performance of the real, biological system. This has been achieved by assuming some simple mathematical approximations for the activities of the introduced physiological parameters and their chemical “drive” dependence. The gaps in our present knowledge are pointed out and some key experiments suggested. The proposed model is consistent with the main conclusions reached in previous work from this laboratory that there are three neural submechanisms which are mainly responsible for the effects of increased CO₂ on ventilation: 1) a rise in the inspiratory off-switch threshold, 2) an increased rate of rise of the centrally generated inspiratory activity that projects to the off-switch mechanism (and to the spinal respiratory motoneurons), and 3) the vagal volume feed-back. Of these 1) and 2) are mainly responsible for the increase in tidal volume, whereas the vagal volume feed-back is mainly responsible for the increase in respiratory rate. The comparison between the model behaviour and experimental data suggest that the slight CO₂ sensitivity of the pulmonary stretch receptors recently reported on, has to be taken into account. The model studies have suggested the increase in respiratory rate with increased temperature may be due either to an increased rate of rise of inspiratory activity or to a decreased off-switch threshold, or both in combination. The mechanism controlling the expiratory durations are briefly discussed.     

Respiratory Function in Healthy Taiwanese Infants: Tidal Breathing Analysis,Passive Mechanics,and Tidal Forced Expiration

Background

Although infant lung function (ILF) testing is widely practiced in developed Western countries it is not typically performed in Eastern countries, and lung measurements are scarce for Asian infants. Therefore, this study aimed to establish normal reference values for Taiwanese infants.

Materials and Methods

Full-term infants without any chronic diseases and major anomalies were enrolled in the Prediction of Allergies in Taiwanese Children (PATCH) cohort study. Detailed medical data, such as body weight and length, birth history, and histories of previous illness and hospitalization were recorded. Lung function measurements such as analysis of tidal breathing, passive respiratory mechanics, and forced tidal expiratory flow-volume curves were obtained through Jaeger Masterscreen BabyBody Paediatrics System. Multiple linear analyses were performed to determine various parameters of the lung function tests.

Results

ILF test parameters were collected from 126 infants, and 189 tests were performed. The results revealed that the ratio of time to peak expiratory flow to total expiratory time, the ratio of volume to peak expiratory flow to total expiratory volume, and the ratio of inspiratory time to total respiratory time remained relatively constant despite differences in age. However, body length is the strongest independent variable influencing tidal volume, respiratory rate, resistance, compliance, and maximal expiratory flow at functional residual capacity.

Conclusion

According to our review of relevant literature, this is the first study to establish a reference data of ILF tests in the Asian population. This study provided reference values and regression equations for several variables of lung function measurements in healthy infants aged less than 2 years. With these race-specific reference data, ILF can more precisely and efficiently diagnose respiratory diseases in infants of Chinese ethnicity.     

Respiratory reactions on microinjections of GABA and baclofen into the Bötzinger complex and the pre-Bötzinger complex in rats

In adult anaesthetized rats the respiratory reactions to microinjections of GABA (10(-5) M) and baclofen (10(-6) M) into Botzinger complex (BC) and pre-Botzinger complex (PBC) were investigated. It was shown, that GABA microinjections into BC shortened inspiratory time and extended expiratory time while respiratory rate was not changed essentially, under this conditions the tidal volume and ventilation were increased. GABA microinjections into PBC significantly inhibited respiratory rhythm due to inspiratory and expiratory time prolongations and reduced tidal volume. The microinjections of baclofen into BC reduced expiration time and ventilation, and increased respiratory frequency whereas microinjections into PBC increased tidal volume without respiratory rate and expiratory time changes. It is suggested that the reactions observed demonstrate the various contribution of GABAergic mechanisms, including GABA(B)-receptors within BC and PBC, in control of respiratory pattern parameters.     

Breathing strategy of the adult horse (Equus caballus) at rest

To investigate the mechanism underlying the polyphasic airflow pattern of the equine species, we recorded airflow, tidal volum, rib cage and abdominal motion, and the sequence of activation of the diaphragm, intercostal, and abdominal muscles during quiet breathing in nine adult horses standing at rest. In addition, esophageal, abdominal, and transdiaphragmatic pressures were simultaneously recorded using balloon-tipped catheters. Analysis of tidal flow-volume loops showed that, unlike humans, the horse at rest breathes around, rather than from, the relaxed volume of the respiratory system (Vrx). Analysis of the pattern of electromyographic activities and changes in generated pressures during the breathing cycle indicate that the first part of expiration is passive, as in humans, with deflation toward Vrx, but subsequent abdominal activity is responsible for a second phase of expiration: active deflation to below Vrx. From this end-expiratory volume, passive inflation occurs toward Vrx, followed by a second phase of inspiration: active inflation to above Vrx, brought about by inspiratory muscle contraction. Under these conditions the abdominal muscles appear to share the principal pumping duties with the diaphragm. Adoption of this breathing strategy by the horse may relate to its peculiar thoracoabdominal anatomic arrangement and to its very low passive chest wall compliance. We conclude that there is a passive and active phase to both inspiration and expiration due to the coordinated action of the respiratory pump muscles responsible for the resting adult horse's biphasic inspiratory and expiratory airflow pattern. This unique breathing pattern perhaps represents a strategy of minimizing the high elastic work of breathing in this species, at least at resting breathing frequencies.     

Pulmonary mechanics during rapid mechanical ventilation in rabbits with saline-lavaged lungs

Infants with respiratory failure are frequently mechanically ventilated at rates exceeding 60 breaths/min. We analyzed the effect of ventilatory rates of 30, 60, and 90 breaths/min (inspiratory times of 0.6, 0.3, and 0.2 s, respectively) on the pressure-flow relationships of the lungs of anesthetized paralyzed rabbits after saline lavage. Tidal volume and functional residual capacity were maintained constant. We computed effective inspiratory and expiratory resistance and compliance of the lungs by dividing changes in transpulmonary pressure into resistive and elastic components with a multiple linear regression. We found that mean pulmonary resistance was lower at higher ventilatory rates, while pulmonary compliance was independent of ventilatory rate. The transpulmonary pressure developed by the ventilator during inspiration approximated a linear ramp. Gas flow became constant and the pressure-volume relationship linear during the last portion of inspiration. Even at a ventilatory rate of 90 breaths/min, 28-56% of the tidal volume was delivered with a constant inspiratory flow. Our findings are consistent with the model of Bates et al. (J. Appl. Physiol. 58: 1840-1848, 1985), wherein the distribution of gas flow within the lungs depends predominantly on resistive factors while inspiratory flow is increasing, and on elastic factors while inspiratory flow is constant. This dynamic behavior of the surfactant-depleted lungs suggests that, even with very short inspiratory times, distribution of gas flow within the lungs is in large part determined by elastic factors. Unless the inspiratory time is further shortened, gas flow may be directed to areas of increased resistance, resulting in hyperinflation and barotrauma.     

Mean airway pressure and mean alveolar pressure during high-frequency jet ventilation in rabbits

Mean airway pressure underestimates mean alveolar pressure during high-frequency oscillatory ventilation. We hypothesized that high inspiratory flows characteristic of high-frequency jet ventilation may generate greater inspiratory than expiratory pressure losses in the airways, thereby causing mean airway pressure to overestimate, rather than underestimate, mean alveolar pressure. To test this hypothesis, we ventilated anesthetized paralyzed rabbits with a jet ventilator at frequencies of 5, 10, and 15 Hz, constant inspiratory-to-expiratory time ratio of 0.5 and mean airway pressures of 5 and 10 cmH2O. We measured mean total airway pressure in the trachea with a modified Pitot probe, and we estimated mean alveolar pressure as the mean pressure corresponding in the static pressure-volume relationship to the mean volume of the respiratory system measured with a jacket plethysmograph. We found that mean airway pressure was similar to mean alveolar pressure at frequencies of 5 and 10 Hz but overestimated it by 1.1 and 1.4 cmH2O at mean airway pressures of 5 and 10 cmH2O, respectively, when frequency was increased to 15 Hz. We attribute this finding primarily to the combined effect of nonlinear pressure frictional losses in the airways and higher inspiratory than expiratory flows. Despite the nonlinearity of the pressure-flow relationship, inspiratory and expiratory net pressure losses decreased with respect to mean inspiratory and expiratory flows at the higher rates, suggesting rate dependence of flow distribution. Redistribution of tidal volume to a shunt airway compliance is thought to occur at high frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of gas properties and waveform asymmetry on gas transport in a branching tube network

Local gas transport coefficients, quantifying longitudinal dispersion through a symmetrical constant-diameter tube network, have been measured during oscillation with both symmetrical and nonsymmetrical waveforms. Experiments were carried out over a range of conditions that would prevail in the central to lower airways during high-frequency ventilation at moderate frequency (5 Hz) and tidal volume (15-80 ml). Gas transport coefficients resulting from oscillation of three different resident-trace gas pairs were measured using a new analytic technique. This technique allowed rapid determination of the transport coefficient distribution along the entire network. Results demonstrate a small but significant influence attributable to changes in gas properties that is similar to that found in a straight tube and indicate that augmented dispersion is an important mechanism of axial transport. Gas transport coefficients were found to be unaffected by changes in flow waveform symmetry, suggesting that previously reported improvements in gas exchange associated with decreasing inspiratory to expiratory time ratios are not due to a change in local conditions such as asymmetry in the velocity profile.