Computational fluid dynamics modeling of the upper airway of children with obstructive sleep apnea syndrome in steady flow

Computational fluid dynamic (CFD) analysis was used to model the effect of airway geometry on internal pressure in the upper airway of three children with obstructive sleep apnea syndrome (OSAS), and three controls. Model geometry was reconstructed from magnetic resonance images obtained during quiet tidal breathing, meshed with an unstructured grid, and solved at normative peak resting flow. The unsteady Reynolds-averaged Navier-Stokes equations were solved with steady flow boundary conditions in inspiration and expiration, using a two-equation low-Reynolds number turbulence model. Model results were validated using an in-vitro scale model, unsteady flow simulation, and reported nasal resistance measurements in children. Pharynx pressure drop strongly correlated to airway area restriction. Inspiratory pressure drop was primarily proportional to the square of flow, consistent with pressure losses due to convective acceleration caused by area restriction. On inspiration, in OSAS pressure drop occurred primarily between the choanae and the region where the adenoids overlap the tonsils (overlap region) due to airway narrowing, rather than in the nasal passages; in controls the majority of pressure drop was in the nasal passages. On expiration, in OSAS the majority of pressure drop occurred between the oropharynx (posterior to the tongue) and overlap region, and local minimum pressure in the overlap region was near atmospheric due to pressure recovery in the anterior nasopharynx. The results suggest that pharyngeal airway shape in children with OSAS significantly affects internal pressure distribution compared to nasal resistance. The model may also help explain regional dynamic airway narrowing during expiration.     

Validation of computational fluid dynamics methodology used for human upper airway flow simulations

An anatomically accurate human upper airway model was constructed from multiple magnetic resonance imaging axial scans. This model was used to conduct detailed Computational Fluid Dynamics (CFD) simulations during expiration, to investigate the fluid flow in the airway regions where obstruction could occur. An identical physical model of the same airway was built using stereo lithography. Pressure and velocity measurements were conducted in the physical model. Both simulations and experiments were performed at a peak expiratory flow rate of 200 L/min. Several different numerical approaches within the FLUENT commercial software framework were used in the simulations; unsteady Large Eddy Simulation (LES), steady Reynolds-Averaged Navier-Stokes (RANS) with two-equation turbulence models (i.e. k?ε, standard k?ω, and k?ω Shear Stress Transport (SST)) and with one-equation Spalart–Allmaras model. The CFD predictions of the average wall static pressures at different locations along the airway wall were favorably compared with the experimental data. Among all the approaches, standard k?ω turbulence model resulted in the best agreement with the static pressure measurements, with an average error of ～20% over all ports. The highest positive pressures were observed in the retroglossal regions below the epiglottis, while the lowest negative pressures were recorded in the retropalatal region. The latter is a result of the airflow acceleration in the narrow retropalatal region. The largest pressure drop was observed at the tip of the soft palate. This location has the smallest cross section of the airway. The good agreement between the computations and the experimental results suggest that CFD simulations can be used to accurately compute aerodynamic flow characteristics of the upper airway.     

Interpretation of interrupter resistance after histamine-induced constriction in the dog

The interrupter method for measuring respiratory system resistance involves interrupting flow at the airway opening and measuring the resultant changes in pressure. We have recently shown (J. Appl. Physiol. 65: 408-414, 1988) that in open-chest mongrel dogs, under control conditions, the initial rapid pressure change (delta Pinit) reflects conducting airway resistance and the subsequent gradual pressure change (delta Pdif) reflects stress recovery of the tissues. We questioned whether the same interpretation would apply after induced constriction. Accordingly, we performed interruption experiments on anesthetized, paralyzed, tracheostomized, open-chest mongrel dogs during passive expiration, measuring pressure at the trachea and in three different alveolar regions with alveolar capsules. We recorded measurements before and after the administration of increasing concentrations of histamine aerosol (0.1-30.0 mg/ml). We found a significant increase in the heterogeneity of alveolar pressures during the relaxed expiration with increasing concentrations of histamine. Despite the introduction of significant mechanical heterogeneities, delta Pinit still reflected the pressure drop as the result of the resistance of the conducting airways. delta Pdif, however, reflected a combination of the stress recovery of the tissues and pendelluft.     

Pressure excursions during oscillatory flow in a branching network of tubes

The pressure difference across individual branches of a four-generation network of branching tubes was measured with the objective of obtaining general laws to describe the pressure drop in the airways under conditions of oscillatory flow. Fourier decomposition showed that the pressure signals consisted of a dominant component at the excitation frequency ("fundamental") and a "first harmonic" of smaller magnitude. For values of the ratio Re/alpha less than 200, the fundamental mainly represented fluid acceleration, whereas the first harmonic reflected the effects both of viscous dissipation and the change in total cross-sectional area between parent and daughter generations. For values of Re/alpha greater than 200, the magnitude of the fundamental was considerably larger than that due to fluid acceleration alone, suggesting the possibility of onset of turbulence in the branching network. These pressure measurements were applied to a simple model of the dog lung to predict total airway resistance. The results are found to be in substantial agreement with physiological measurements.     

Inhalation pressure distributions for medical gas mixtures calculated in an infant airway morphology model

A numerical pressure loss model previously used for adult human airways has been modified to simulate the inhalation pressure distribution in a healthy 9-month-old infant lung morphology model. Pressure distributions are calculated for air as well as helium and xenon mixtures with oxygen to investigate the effects of gas density and viscosity variations for this age group. The results indicate that there are significant pressure losses in infant extrathoracic airways due to inertial effects leading to much higher pressures to drive nominal flows in the infant airway model than for an adult airway model. For example, the pressure drop through the nasopharynx model of the infant is much greater than that for the nasopharynx model of the adult; that is, for the adult-versus-child the pressure differences are 0.08 cm H₂O versus 0.4 cm H₂O, 0.16 cm H₂O versus 1.9 cm H₂O and 0.4 cm H₂O versus 7.7 cm H₂O, breathing helium–oxygen (78/22%), nitrogen–oxygen (78/22%) and xenon–oxygen (60/40%), respectively. Within the healthy lung, viscous losses are of the same order for the three gas mixtures, so the differences in pressure distribution are relatively small.     

The influence of straining maneuvers on the pressor response during isometric exercise

Experiments were performed to determine to what extent increments in esophageal and abdominal pressure would have on arterial blood pressure during fatiguing isometric exercise. Arterial blood pressure was measured during handgrip and leg isometric exercise performed with both a free and occluded circulation to active muscles. Handgrip contractions were exerted at 33 and 70% MVC (maximum voluntary contraction) by 4 volunteers in a sitting position and calf muscle contractions at 50 and 70% MVC with the subjects in a kneeling position. Esophageal pressure measured at the peak of inspirations did not change during either handgrip or leg contractions but peak expiratory pressures increased progressively during both handgrip and leg contractions as fatigue occurred. These increments were independent of the tensions of the isometric contractions exerted. Intra-abdominal pressures measured at the peak of either inspiration or expiration did not change during inspiration with handgrip contractions but increased during expiration. During leg exercise, intraabdominal pressures increased during both inspiration and expiration, reaching peak levels at fatigue. The arterial blood pressure also reached peak levels at fatigue, independent of circulatory occlusion and tension exerted, averaging 18.5-20 kPa (140-150 mm Hg) for both handgrip and leg contractions. While blood pressure returned to resting levels following exercise with a free circulation, it declined by only 2.7-3.8 kPa after leg and handgrip exercise, respectively, during circulatory occlusion. These results indicate that straining maneuvers contribute 3.5 to 7.8 kPa to the change in blood pressure depending on body position.     

Respiratory phasic effects of inspiratory loading on left ventricular hemodynamics in vagotomized dogs.

Exaggerated inspiratory swings in intrathoracic pressure have been postulated to increase left ventricular (LV) afterload. These predictions are based on measurements of LV afterload by use of esophageal or lateral pleural pressure. Using direct measurements of pericardial pressure, we reexamined respiratory changes in LV afterload. In 11 anesthetized vagotomized dogs, we measured arterial pressure, LV end-systolic (ES) and end-diastolic transmural (TM) pressures, stroke volume (SV), diastolic left anterior descending blood flow (CBF-D), and coronary resistance. Dogs were studied before and while breathing against an inspiratory threshold load of -20 to -25 cmH2O compared with end expiration. Relative to end expiration, SV and LVES TM pressures decreased during inspiration and increased during early expiration, effects exaggerated during inspiratory loading. In all cases, LV afterload (LVES TM pressure) changed in parallel with SV. LV end-diastolic TM pressure did not change. CBF-D paralleled arterial pressure, and there were no changes in coronary resistance. In two dogs, regional LVES segment length paralleled calculated changes in LVES TM pressure. We conclude that 1) LV afterload decreases during early inspiration and increases during early expiration, changes secondary to those in SV; 2) changes in CBF-D are secondary to changes in perfusion pressure during the respiratory cycle; and 3) the use of esophageal or lateral pleural pressure to estimate LV surface pressure overestimates changes in LV TM pressures during respiration.     

Aerial and underwater carbon metabolism of a Zostera noltii seagrass bed in the Banc d’Arguin, Mauritania

Community respiration and primary production were measured in a dense intertidal Zostera noltii bed on the Banc d’Arguin, Mauritania (West Africa) under aerial and submerged conditions. Metabolism was studied in situ in dark and transparent benthic chambers. CO₂ fluxes in the air were measured over a series of short-term incubations (3 min) using an infrared gas analyzer. Dissolved inorganic carbon fluxes were calculated from concentration changes during one-hour underwater incubations. Air and underwater irradiance levels were measured every minute throughout the experiments. Carbon respiration was lower in the air (2.2 mmol m⁻² h⁻¹) than underwater (5.0 mmol m⁻² h⁻¹); similarly, a production-irradiance model fitted to the data indicated that gross maximal photosynthetic rate was markedly lower during emergence (6.0 mmol C m⁻² h⁻¹) than under water (42.7 mmol C m⁻² h⁻¹). The δ¹³C values observed in shoots indicated a decrease in atmospheric CO₂ contribution, compared to dissolved inorganic carbon, in Z. noltii metabolism along a depth gradient within a single location. As the seagrass bed remains under a thin layer of water at low tide at the studied site, the large difference in primary production can be mainly attributed to photosynthesis inhibition by high pH and oxygen concentration, as well as to the negative feedback of self-shading by seagrass leaves during emersion. The observed differences in respiration can be explained by the oxygen deficit at night during low tide near the sediment surface, a deficit that is consistent with the abundance of anoxia-tolerant species.     

Right atrial pressure affects the interaction between lung mechanics and right ventricular function in spontaneously breathing COPD patients

Introduction

It is generally known that positive pressure ventilation is associated with impaired venous return and decreased right ventricular output, in particular in patients with a low right atrial pressure and relative hypovolaemia. Altered lung mechanics have been suggested to impair right ventricular output in COPD, but this relation has never been firmly established in spontaneously breathing patients at rest or during exercise, nor has it been determined whether these cardiopulmonary interactions are influenced by right atrial pressure.

Methods

Twenty-one patients with COPD underwent simultaneous measurements of intrathoracic, right atrial and pulmonary artery pressures during spontaneous breathing at rest and during exercise. Intrathoracic pressure and right atrial pressure were used to calculate right atrial filling pressure. Dynamic changes in pulmonary artery pulse pressure during expiration were examined to evaluate changes in right ventricular output.

Results

Pulmonary artery pulse pressure decreased up to 40% during expiration reflecting a decrease in stroke volume. The decline in pulse pressure was most prominent in patients with a low right atrial filling pressure. During exercise, a similar decline in pulmonary artery pressure was observed. This could be explained by similar increases in intrathoracic pressure and right atrial pressure during exercise, resulting in an unchanged right atrial filling pressure.

Conclusions

We show that in spontaneously breathing COPD patients the pulmonary artery pulse pressure decreases during expiration and that the magnitude of the decline in pulmonary artery pulse pressure is not just a function of intrathoracic pressure, but also depends on right atrial pressure.     

Hypopharyngeal and neck cross-sectional changes monitored by inductive plethysmography

We present a method to assess cross-sectional area (CSA) changes of the extrathoracic airways (EA) by using an inductive plethysmograph (IP) band placed around the upper part of the neck. Measurements of mouth pressure (Pm) (or flow rate, V) and neck CSA changes during respiratory efforts against a high (or infinite) resistance have shown a highly significant relationship between Pm changes (or V changes, respectively), reflecting CSA changes of the EA and CSA changes of the neck. Simultaneous measurements of CSA of the neck (by IP) and of EA (by computerized tomography) during sustained inspiratory and expiratory efforts against a closed airway showed a high correlation between changes in the former and latter structures. Changes in CSA of the neck were larger with positive than negative transmural pressures, in keeping with the known larger compliance of this airway during expiration. We found this method helpful to assess the behavior of the EA during obstructive apnea episodes, hypopneas, and snoring.     

Reversible and irreversible components of central-airway flow resistance

The flow energy loss (head loss) through a cast of canine central airways is found to be nearly independent of flow direction. By contrast, head loss in geometrically-simpler branching sections at comparable flow conditions is highly irreversible, with inspiratory loss being greater by nearly two units of dynamic pressure (2 X 1/2 rho V2). In these branching sections head loss appears to be independent of important geometric parameters such as the branch length/diameter ratio and the exit/inlet flow-area ratio. An analysis of these observations suggests that kinetic energy factors, not shear stresses, account for most of the energy dissipated in central airways and in simple bifurcating sections. Inspiratory loss in bifurcations is greatly increased by the onset of flow separation: irreversibility is minimal in central airways, where separation either is absent or else is much less pronounced.     

Simulation of turbulent airflow using a CT based upper airway model of a racehorse

Computational model for airflow through the upper airway of a horse was developed. Previous flow models for human airway do not hold true for horses due to significant differences in anatomy and the high Reynolds number of flow in the equine airway. Moreover, models that simulate the entire respiratory cycle and emphasize on pressures inside the airway in relation to various anatomical diseases are lacking. The geometry of the airway was created by reconstructing images obtained from computed tomography scans of a thoroughbred racehorse. Different geometries for inhalation and exhalation were used for the model based on the difference in the nasopharynx size during the two phases of respiration. The Reynolds averaged Navier-Stokes equations were solved for the isothermal flow with the standard k-epsilon model for turbulence. Transient pressure boundary conditions for the entire breathing cycle were obtained from past experimental studies on live horses. The flow equations were solved in a commercial finite volume solver. The flow rates, computed based on the applied pressure conditions, were compared to experimentally measured flow rates for model validation. Detailed analysis of velocity, pressure, and turbulence characteristics of the flow was done. Velocity magnitudes at various slices during inhalation were found to be higher than corresponding velocity magnitudes during exhalation. The front and middle parts of the nasopharynx were found to have minimum intraluminal pressure in the airway during inhalation. During exhalation, the pressures in the soft palate were higher compared to those in the larynx, epiglottis, and nasopharynx. Turbulent kinetic energy was found to be maximum at the entry to the airway and gradually decreased as the flow moved inside the airway. However, turbulent kinetic energy increased in regions of the airway with abrupt change in area. Based on the analysis of pressure distribution at different sections of the airway, it was concluded that the front part of the nasopharynx requires maximum muscular activity to support it during inhalation. During exhalation, the soft palate is susceptible to displacements due to presence of high pressures. These can serve as critical information for diagnosis and treatment planning of diseases known to affect the soft palate and nasopharynx in horses, and can potentially be useful for human beings.     

In Vitro Surfactant and Perfluorocarbon Aerosol Deposition in a Neonatal Physical Model of the Upper Conducting Airways

Objective

Aerosol delivery holds potential to release surfactant or perfluorocarbon (PFC) to the lungs of neonates with respiratory distress syndrome with minimal airway manipulation. Nevertheless, lung deposition in neonates tends to be very low due to extremely low lung volumes, narrow airways and high respiratory rates. In the present study, the feasibility of enhancing lung deposition by intracorporeal delivery of aerosols was investigated using a physical model of neonatal conducting airways.

Methods

The main characteristics of the surfactant and PFC aerosols produced by a nebulization system, including the distal air pressure and air flow rate, liquid flow rate and mass median aerodynamic diameter (MMAD), were measured at different driving pressures (4–7 bar). Then, a three-dimensional model of the upper conducting airways of a neonate was manufactured by rapid prototyping and a deposition study was conducted.

Results

The nebulization system produced relatively large amounts of aerosol ranging between 0.3±0.0 ml/min for surfactant at a driving pressure of 4 bar, and 2.0±0.1 ml/min for distilled water (H₂Od) at 6 bar, with MMADs between 2.61±0.1 µm for PFD at 7 bar and 10.18±0.4 µm for FC-75 at 6 bar. The deposition study showed that for surfactant and H₂Od aerosols, the highest percentage of the aerosolized mass (∼65%) was collected beyond the third generation of branching in the airway model. The use of this delivery system in combination with continuous positive airway pressure set at 5 cmH₂O only increased total airway pressure by 1.59 cmH₂O at the highest driving pressure (7 bar).

Conclusion

This aerosol generating system has the potential to deliver relatively large amounts of surfactant and PFC beyond the third generation of branching in a neonatal airway model with minimal alteration of pre-set respiratory support.     

Respiration and airway reflexes after transversal brain stem lesions in cats

The effect of brain stem transection at different levels of the pons Varolii and the medulla oblongata on respiration and on cough and the aspiration and expiration reflex elicited by mechanical stimulation of the relevant parts of the respiratory tract was studied in experiments on 13 anaesthetized, unparalyzed cats. The results of 142 respiratory reflex elicitation tests showed that: 1. Compared with the control state, transection of the upper and middle part of the pons Varolii and transection at the level of the pontomedullary junction reduced the respiration rate (p less than 0.001), increased the duration of inspiration and expiration (p less than 0.001, transection 10 mm rostrally to the obex) and gave rise to apneustic breathing (8 mm), or to tonic, respiration-modulated activity of the phrenic nerve and diaphragm (6 mm). 2. Successive transection of the pons and the pontomedullary junction region led chiefly to a drop in maximum expiratory pleural pressure values (p less than 0.01-0.001) during cough and the expiration reflex and to a drop in maximum inspiratory pleural pressure values during the aspiration reflex (p less than 0.02-0.001). 3. Transection of the upper part of the medulla oblongata always led to permanent arrest of rhythmic respiration, during which cough and the expiration reflex could not be elicited while the aspiration reflex persisted (though in a weakened form). This state was followed by gasping, during which only a highly elicitable aspiration reflex persisted. 4. It can be assumed from the above findings that the central mechanisms responsible for the development of powerful expiratory efforts in cough and the expiration reflex could be localized in the pons Varolii, while those integrating the aspiration reflex are probably localized mainly in the medulla oblongata.     

Lung parenchymal shear modulus, airway wall remodeling, and bronchial hyperresponsiveness

Lambert, Rodney K., and Peter D. Paré. Lungparenchymal shear modulus, airway wall remodeling, and bronchialhyperresponsiveness. J. Appl. Physiol.83(1): 140-147, 1997.When airways narrow, either through theaction of smooth muscle shortening or during forced expiration, thelung parenchyma is locally distorted and provides an increasedperibronchial stress that resists the narrowing. Although thisinterdependence has been well studied, the quantitative significance ofairway remodeling to interdependence has not been elucidated. We haveused an improved computational model of the bronchial response tosmooth muscle agonists to investigate the relationships between airwaynarrowing (as indicated by airway resistance), parenchymal shearmodulus, adventitial thickening, and inner wall thickening at lungrecoil pressures of 4, 5, and 8 cmH₂O. We have found that, at lowrecoil pressures, decreases in parenchymal shear modulus have asignificant effect that is comparable to that of moderate thickening ofthe airway wall. At higher lung recoil pressures, the effect isnegligible.

     

Effect of immobilization of a bacterial consortium on diuron dissipation and community dynamics

This work intended to study the relationship between diuron herbicide dissipation and the population dynamics of co-cultivated Delftia acidovorans WDL34 (WDL34) and Arthrobacter sp. N4 (N4) for different cell formulations: free cells or immobilization in Ca-alginate beads of one or both strains. GFP-tagged WDL34 and N4 Gram staining allowed analyzing the cell growth and distribution of each strain in both beads and culture medium in the course of the time. Compared to the free cell co-culture of WDL34 and N4, immobilization of WDL34 in Ca-alginate beads co-cultivated with free N4 increased the dissipation rate of diuron by 53% (0.141 mg ml⁻¹ h⁻¹). In that case, immobilization strongly modified the final equilibrium among both strains (highest total N4 to WDL34 ratio). Our results demonstrated that the inoculant formulation played a major role in the cell growth of each cultivated strain possibly increasing diuron dissipation. This optimized cell formulation may allow improving water and soil treatment.     

Inhibitory effects of CO2 on airway defensive reflexes in enflurane-anesthetized humans

We investigated responses of respiration, blood pressure, and heart rate to tracheal mucosa irritation induced by injection of distilled water at three different levels of CO2 ventilatory drive in 11 spontaneously breathing female patients under a constant depth of enflurane anesthesia [1.1 minimum alveolar concentration (MAC)]. The airway irritation at the resting level of spontaneous breathing caused a variety of respiratory responses such as coughing, expiration reflex, apnea, and spasmodic panting, with considerable increases in blood pressure and heart rate. Although the latency of respiratory responses after water injection was much shorter than those of blood pressure and heart rate responses, blood pressure and heart rate responses, once elicited, were prolonged much longer than was the respiratory response. An increase in CO2 ventilatory drive decreased the degree and duration of respiratory, blood pressure, and heart rate responses to the airway irritation, whereas a decrease in CO2 ventilatory drive had the opposite effect on these responses. Our results indicate that changes in CO2 ventilatory drive can modify reflex responses of respiration, blood pressure, and heart rate to airway irritation.     

Influence of upper airway negative pressure reflex on response to airway occlusion in sleeping infants

Artificially produced upper airway suction inhibits the diaphragm in animals and infants; however, the effects of spontaneously generated suction in humans are unknown. We studied nine tracheostomized infants because separation of the upper from the lower airway allowed us to channel suction created by an occluded inspiratory effort to both upper and lower airways (upper + lower airway occlusions) or to the lower airway only (lower airway occlusion). The tracheostomy airway was briefly occluded at end expiration during quiet sleep. In upper + lower airway occlusions, peak airway pressure of the first occluded breath was less negative and rate of pressure decrease slower than that of lower airway occlusions, indicating that upper airway suction inhibits thoracic inspiratory muscles. The threshold for this response was less than or equal to 4 cmH2O suction pressure. The effect on inspiratory time was variable. A decrease in slope of the inspiratory pressure waveform occurring at approximately 0.12 s after inspiration onset was more marked in upper + lower airway occlusions. We conclude that infants have an upper airway reflex response to inspiratory pressure that alters not only the peak and slope but also the shape of the inspiratory pressure waveform.     

Neural control of airway pressures in rabbits

In twenty anaesthetized and spontaneously breathing rabbits airway pressures were measured above and below the larynx during tidal respiration through the larynx. Peak inspiratory and expiratory pressures at both sites were recorded in control conditions and then compared to values obtained in the course of progressive denervation of the airways. The two methods of denervation consisted of (1) bilateral section of superior and recurrent laryngeal nerves and of the midcervical vagotomy (horizontal method); (2) right-sided sections of the three nerves followed by left-sided sections (vertical method). Motor denervation of the larynx due to RLNs neurotomy (horizontal method) produced significant increases in intratracheal pressures in both phases of the respiratory cycle. Less prominent increments in pressures were achieved on RLNs neurotomy in the vertical method. SLNs section and vagotomy had little additional effect on airway pressures. Our results indicate that unilateral laryngeal palsy poses far smaller obstruction to breathing than simultaneous bilateral denervation, and that afferent denervation of the larynx has no effect on airway pressures.