Computational Fluid Dynamics Analysis of Upper Airway Changes after Protraction Headgear and Rapid Maxillary Expansion Treatment

Clinically, it is common for Class III patients with maxillary skeletal deficiency, which may result in a variety of adverse consequences. Protraction headgear and rapid maxillary expansion (PE) is an effective treatment, but its effect on upper airway hydrodynamics has not been reported. The main purpose of this study was to evaluate the changes of the flow in the upper airway after PE by computational fluid dynamics (CFD). The sample includes fifteen patients (6 males, 9 females, age 11.00 ± 1.00) and the paired T-test was used to analyze the differences between the measured data before and after treatment. The maximum flow velocity decreased from 8.42 ± 0.16 m/s to 6.98 ± 0.36 m/s (p < 0.05), and the maximum shear force decreased from 3.72 ± 1.48 Pa to 2.13 ± 0.18 Pa. The maximum negative pressure decreased from −101.78 ± 33.60 Pa to 58.15 ± 9.16 Pa, only the changes of velopharynx and glossopharynx were statistically significant; while the maximum resistance decreased from 140.88 ± 68.68 Pa/mL/s to 45.95 ± 22.96 Pa/mL/s. PE can effectively reduce the airflow resistance of the upper airway and the probability of airway collapse, thus improving the patient’s ventilation function.     

Determination of uric acid in human urine and serum by capillary electrophoresis with chemiluminescence detection

A simple and sensitive method based on capillary electrophoresis (CE) with chemiluminescence (CL) detection has been developed for the determination of uric acid (UA). The sensitive detection was based on the enhancement effect of UA on the CL reaction between luminol and potassium ferricyanide (K₃[Fe(CN)₆]) in alkaline solution. A laboratory-built reaction flow cell and a photon counter were deployed for the CL detection. Experimental conditions for CL detection were studied in detail to achieve a maximum assay sensitivity. Optimal conditions were found to be 1.0 × 10⁻⁴ M luminol added to the CE running buffer and 1.0 × 10⁻⁴ M K₃[Fe(CN)₆] in 0.2 M NaOH solution introduced postcolumn. The proposed CE-CL assay showed good repeatability (relative standard deviation [RSD] = 3.5%, n = 11) and a detection limit of 3.5 × 10⁻⁷ M UA (signal/noise ratio [S/N] = 3). A linear calibration curve ranging from 6.0 × 10⁻⁷ to 3.0 × 10⁻⁵ M UA was obtained. The method was evaluated by quantifying UA in human urine and serum samples with satisfactory assay results.     

Functional imaging using computational fluid dynamics to predict treatment success of mandibular advancement devices in sleep-disordered breathing

Mandibular advancement devices (MADs) have emerged as a popular alternative for the treatment of sleep-disordered breathing. These devices bring the mandibula forward in order to increase upper airway (UA) volume and prevent total UA collapse during sleep. However, the precise mechanism of action appears to be quite complex and is not yet completely understood; this might explain interindividual variation in treatment success. We examined whether an UA model, that combines imaging techniques and computational fluid dynamics (CFD), allows for a prediction of the treatment outcome with MADs. Ten patients that were treated with a custom-made mandibular advancement device (MAD), underwent split-night polysomnography. The morning after the sleep study, a low radiation dose CT scan was scheduled with and without the MAD. The CT examinations allowed for a comparison between the change in UA volume and the anatomical characteristics through the conversion to three-dimensional computer models. Furthermore, the change in UA resistance could be calculated through flow simulations with CFD. Boundary conditions for the model such as mass flow rate and pressure distributions were obtained during the split-night polysomnography. Therefore, the flow modeling was based on a patient specific geometry and patient specific boundary conditions. The results indicated that a decrease in UA resistance and an increase in UA volume correlate with both a clinical and an objective improvement. The results of this pilot study suggest that the outcome of MAD treatment can be predicted using the described UA model.     

Passive movement of human soft palate during respiration: A simulation of 3D fluid/structure interaction

This study reconstructed a three dimensional fluid/structure interaction (FSI) model to investigate the compliance of human soft palate during calm respiration. Magnetic resonance imaging scans of a healthy male subject were obtained for model reconstruction of the upper airway and the soft palate. The fluid domain consists of nasal cavity, nasopharynx and oropharynx. The airflow in upper airway was assumed as laminar and incompressible. The soft palate was assumed as linear elastic. The interface between airway and soft palate was the FSI interface. Sinusoidal variation of velocity magnitude was applied at the oropharynx corresponding to ventilation rate of 7.5L/min. Simulations of fluid model in upper airway, FSI models with palatal Young's modulus of 7539Pa and 3000Pa were carried out for two cycles of respiration. The results showed that the integrated shear forces over the FSI interface were much smaller than integrated pressure forces in all the three directions (axial, coronal and sagittal). The total integrated force in sagittal direction was much smaller than that of coronal and axial directions. The soft palate was almost static during inspiration but moved towards the posterior pharyngeal wall during expiration. In conclusion, the displacement of human soft palate during respiration was mainly driven by air pressure around the surface of the soft palate with minimal contribution of shear stress of the upper airway flow. Despite inspirational negative pressure, expiratory posterior movement of soft palate could be another factor for the induction of airway collapse.     

Numerical investigations of the haemodynamic changes associated with stent malapposition in an idealised coronary artery

The deployment of a coronary stent near complex lesions can sometimes lead to incomplete stent apposition (ISA), an undesirable side effect of coronary stent implantation. Three-dimensional computational fluid dynamics (CFD) calculations are performed on simplified stent models (with either square or circular cross-section struts) inside an idealised coronary artery to analyse the effect of different levels of ISA to the change in haemodynamics inside the artery. The clinical significance of ISA is reported using haemodynamic metrics like wall shear stress (WSS) and wall shear stress gradient (WSSG). A coronary stent with square cross-sectional strut shows different levels of reverse flow for malapposition distance (MD) between 0 mm and 0.12 mm. Chaotic blood flow is usually observed at late diastole and early systole for MD=0 mm and 0.12 mm but are suppressed for MD=0.06 mm. The struts with circular cross section delay the flow chaotic process as compared to square cross-sectional struts at the same MD and also reduce the level of fluctuations found in the flow field. However, further increase in MD can lead to chaotic flow not only at late diastole and early systole, but it also leads to chaotic flow at the end of systole. In all cases, WSS increases above the threshold value (0.5 Pa) as MD increases due to the diminishing reverse flow near the artery wall. Increasing MD also results in an elevated WSSG as flow becomes more chaotic, except for square struts at MD=0.06 mm.     

Pathogenesis of obstructive sleep apnea.

The pathogenesis of obstructive sleep apnea (OSA) has been under investigation for over 25 years, during which a number of factors that contribute to upper airway (UA) collapse during sleep have been identified. Structural/anatomic factors that constrict space for the soft tissues surrounding the pharynx and its lumen are crucial to the development of OSA in many patients. Enlargement of soft tissues enveloping the pharynx, including hypertrophied tonsils, adenoids, and tongue, is also an important factor predisposing to UA collapse, inasmuch as this can impinge on the pharyngeal lumen and narrow it during sleep. Other factors, including impairment of UA mechanoreceptor sensitivity and reflexes that maintain pharyngeal patency and respiratory control system instability, have also been identified as possible mechanisms facilitating UA instability. This suggests that OSA may be a heterogeneous disorder, rather than a single disease entity. Therefore, the extent to which various pathogenic factors contribute to the phenomenon of repetitive collapse of the UA during sleep probably varies from patient to patient. Further elucidation of specific pathogenic mechanisms in individuals with OSA may facilitate the development of new therapies that can be tailored to individual patient needs according to the underlying mechanism(s) of their disease.     

Genetic analysis of candidate SNPs for metabolic syndrome in obstructive sleep apnea (OSA)

Obstructive sleep apnea (OSA) is a common disorder characterized by the reduction or complete cessation in airflow resulting from an obstruction of the upper airway. Several studies have observed an increased risk for cardiovascular morbidity and mortality among OSA patients. Metabolic syndrome (MetS), a cluster of cardiovascular risk factors characterized by the presence of insulin resistance, is often found in patients with OSA, but the complex interplay between these two syndromes is not well understood. In this study, we present the results of a genetic association analysis of 373 candidate SNPs for MetS selected in a previous genome wide association analysis (GWAS). The 384 selected SNPs were genotyped using the Illumina VeraCode Technology in 387 subjects retrospectively assessed at the Internal Medicine Unit of the “Virgen de Valme” University Hospital (Seville, Spain). In order to increase the power of this study and to validate our findings in an independent population, we used data from the Framingham Sleep Study which comprises 368 individuals. Only the rs11211631 polymorphism was associated with OSA in both populations, with an estimated OR = 0.57 (0.42–0.79) in the joint analysis (p = 7.21 × 10^− 4). This SNP was selected in the previous GWAS for MetS components using a digenic approach, but was not significant in the monogenic study. We have also identified two SNPs (rs2687855 and rs4299396) with a protective effect from OSA only in the subpopulation with abdominal obesity. As a whole, our study does not support the idea that OSA and MetS share major genetic determinants, although both syndromes share common epidemiological and clinical features.     

Control mechanism for the upper airway collapse in patients with obstructive sleep apnea syndrome: a finite element study

Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent collapses of the upper airway, which lead to repetitive transient hypoxia, arousals and finally sleep fragmentation. Both anatomical and neuromuscular factors may play key roles in the pathophysiology of OSAS. The purpose of this paper was to study the control mechanism of OSAS from the mechanical point of view. A three-dimensional finite element model was developed, which not only reconstructed the realistic anatomical structure of the human upper airway, but also included surrounding structures such as the skull, neck, hyoid, cartilage and soft tissues. The respiration process during the normal and apnea states was simulated with the fluid-structure interaction method (FSI) and the computational fluid dynamics method (CFD). The airflow and deformation of the upper airway obtained from the FSI and the CFD method were compared and the results obtained under large negative pressure during an apnea episode were analyzed. The simulation results show that the FSI method is more feasible and effective than the CFD method. The concave configuration of the upper airway may accelerate the collapse of the upper airway in a positive feedback mechanism, which supplies meaningful information for clinical treatment and further research of OSAS.     

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.     

Effects of hydrophobic surfactant proteins on collapse of pulmonary surfactant monolayers

To determine if hydrophobic surfactant proteins affect the stability of pulmonary surfactant monolayers at an air/water interface, the studies reported here compared the kinetics of collapse for the complete set of lipids in calf surfactant with and without the proteins. Monomolecular films spread at the surface of captive bubbles were compressed at 37°C to surface pressures above 46 mN/m, at which collapse first occurred. The rate of area-compression required to maintain a constant surface pressure was measured to directly determine the rate of collapse. For films with and without the proteins, higher surface pressures initially produced faster collapse, but the rates then reached a maximum and decreased to values <0.04 min⁻¹ above 53 mN/m. The maximum rate for the lipids with the proteins (1.22 ± 0.28 min⁻¹) was almost twice the value for the lipids alone (0.71 ± 0.15 min⁻¹). Because small increments in surface pressure produced large shifts in the rate close to the fastest collapse, compressions at a series of constant speeds also established the threshold rate required to achieve high surface pressure as an indirect indication of the fastest collapse. Both samples produced a sharply defined threshold that occurred at slightly faster compression with the proteins present, supporting the conclusion of the direct measurements that the proteins produce a faster maximum rate of collapse. Our results indicate that at 47-53 mN/m, the hydrophobic surfactant proteins destabilize the compressed monolayers and tend to limit access to the higher surface pressures at which the lipid films become metastable.     

Flow oscillation-A measure to predict the surgery outcome for obstructed sleep apnea (OSA) subject

Obstructed sleep apnea (OSA) is a common disorder which may need surgery to widen the airway; however the success rate of surgery is limited. Here we report a finding that could be used to predict the outcome of the OSA surgery. We found that inspiratory flow oscillates due to flow separation near the larynx, and the resulting periodic signal (3-5Hz) is an intrinsic property of breathing. This flow oscillating signal may be the afferent stimulus to trigger respiratory events. It is found that the flow oscillation is attenuated for the OSA subjects. The computational fluid dynamics (CFD) simulation reveals that there exists flow separation near larynx and this separation is severely weakened in the OSA upper airway model. It is believed that the flow oscillating signal can serve as the measure to quantify the breathing quality of an OSA subject. This makes it possible to predict the surgery outcome of the OSA subject by applying CFD simulation.     

Effect of the velopharynx on intraluminal pressures in reconstructed pharynges derived from individuals with and without sleep apnea

The most collapsible part of the upper airway in the majority of individuals is the velopharynx which is the segment positioned behind the soft palate. As such it is an important morphological region for consideration in elucidating the pathogenesis of obstructive sleep apnea (OSA). This study compared steady flow properties during inspiration in the pharynges of nine male subjects with OSA and nine body-mass index (BMI)- and age-matched control male subjects without OSA. The k  –ω$\omega$SST turbulence model was used to simulate the flow field in subject-specific pharyngeal geometric models reconstructed from anatomical optical coherence tomography (aOCT) data. While analysis of the geometry of reconstructed pharynges revealed narrowing at velopharyngeal level in subjects with OSA, it was not possible to clearly distinguish them from subjects without OSA on the basis of pharyngeal size and shape alone. By contrast, flow simulations demonstrated that pressure fields within the narrowed airway segments were sensitive to small differences in geometry and could lead to significantly different intraluminal pressure characteristics between subjects. The ratio between velopharyngeal and total pharyngeal pressure drops emerged as a relevant flow-based criterion by which subjects with OSA could be differentiated from those without.     

Determination of nanomolar uric and ascorbic acids using enlarged gold nanoparticles modified electrode

Individual and simultaneous determination of 50 nM uric acid (UA) and ascorbic acid (AA) using enlarged, citrate-stabilized gold nanoparticles (AuNPs) self-assembled to 2,5-dimercapto-1,3,4-thiadiazole (DMT) monolayer modified Au (Au/DMT) electrode by an amperometric method is described for the first time. Self-assembly of AuNPs on the electrode surface was confirmed by atomic force microscopy (AFM), attenuated total reflectance FT-IR and diffuse reflectance spectral measurements. The electron transfer reaction (ETR) of [Fe(CN)₆]^3−/4− was blocked at Au/DMT electrode, whereas it was restored with a peak separation of 200 mV after the attachment of AuNPs on the Au/DMT (Au/DMT/AuNPs) electrode, which was confirmed from the ETR of the [Fe(CN)₆]^3−/4− redox couple. When the self-assembled AuNPs were enlarged by hydroxylamine seeding, the ETR of [Fe(CN)₆]^3−/4− was improved significantly with a peak separation of 100 mV. Tapping mode AFM showed that the average size of the enlarged-AuNPs (E-AuNPs) was 50-70 nm. The E-AuNPs modified electrode catalyzes the oxidation of AA and UA, separates their voltammetric signals by 200 mV, and has excellent sensitivity towards AA and UA with a detection limit of 50 nM. The practical application of the modified electrode was demonstrated by measuring the concentration of UA in blood serum and urine.     

Site of phrenic nerve stimulation-induced upper airway collapse: influence of expiratory time.

Electrical phrenic nerve stimulation (EPNS) applied at end expiration during exclusive nasal breathing can be used to characterize upper airway (UA) dynamics during wakefulness by dissociating phasic activation of UA and respiratory muscles. The UA level responsible for the EPNS-induced increase in UA resistance is unknown. The influence of the twitch expiratory timing (200 ms and 2 s) on UA resistance was studied in nine normal awake subjects by looking at instantaneous flow, esophageal and pharyngeal pressures, and genioglossal electromyogram (EMG) activity during EPNS at baseline and at -10 cmH(2)O. The majority of twitches had a flow-limited pattern. Twitches realized at 200 ms and 2 s did not differ in their maximum inspiratory flows, but esophageal pressure measured at maximum inspiratory flow was significantly less negative with late twitches (-6.6 +/- 2.7 and -5.0 +/- 3.0 cmH(2)O respectively, P = 0.04). Pharyngeal resistance was higher when twitches were realized at 2 s than at 200 ms (6.4 +/- 2.4 and 2.7 +/- 1.1 cmH(2)O x l(-1). s, respectively). EMG activity significant rose at peak esophageal pressure with a greater increase for late twitches. We conclude that twitch-induced UA collapse predominantly occurs at the pharyngeal level and that UA stability assessed by EPNS depends on the expiratory time at which twitches are performed.     

Adverse effect of cake collapse on the functional integrity of freeze-dried bull spermatozoa

Under optimal freeze-drying conditions, solutions exhibit a cake-like porous structure. However, if the solution temperature is higher than the glass transition temperature of the maximally freeze-concentrated phase (T_g′) during drying phase, the glassy matrix undergoes viscous flow, resulting in cake collapse. The purpose of the present study was to investigate the effect of cake collapse on the integrity of freeze-dried bull spermatozoa. In a preliminary experiment, factors affecting the T_g′ of conventional EGTA buffer (consisting of Tris–HCl, EGTA and NaCl) were investigated in order to establish the main experimental protocol because EGTA buffer T_g′ was too low (−45.0 °C) to suppress collapse. Modification of the EGTA buffer composition by complete removal of NaCl and addition of trehalose (mEGTA buffer) resulted in an increase of T_g′ up to −27.7 °C. In the main experiment, blastocyst yields after ooplasmic injection of freeze-dried sperm preserved in collapsed cakes (drying temperature: 0 or −15 °C) were significantly lower than those of sperm preserved in non-collapsed cake (drying temperature: −30 °C). In conclusion, freeze-dried cake collapse may be undesirable for maintaining sperm functions to support embryonic development, and can be inhibited by controlling both T_g′ of freeze-drying buffer and temperature during the drying phase.     

Performance and macrokinetic analysis of biofiltration of toluene and p-xylene mixtures in a conventional biofilter packed with inert material

Interactions of toluene and p-xylene in air treatment biofilters packed with an inert filter media were studied. The effect of the inlet load of toluene, p-xylene and mixtures of both compounds on the biodegradation rate was analyzed in three lab-scale biofilters. A maximum elimination capacity (EC) of 26.5 and 40.3 g C m⁻³ h⁻¹ for an inlet load (IL) of 65.6 and 57.8 g C m⁻³ h⁻¹ was obtained for p-xylene and toluene biofilters, respectively. Inhibition of p-xylene biodegradation by the presence of toluene took place when the mixture was treated, whereas the presence of p-xylene had an enhancing effect on the toluene removal efficiency. Specific growth rates (μ) from 0.019 to 0.068 h⁻¹ were calculated in the mixed biofilter, where the highest values were similar to mixtures with lower p-xylene levels (IL_p-Xyl 8.84 ± 0.29 g C m⁻³ h⁻¹). Michaelis-Menten and Haldane type models were fitted to experimental EC for p-xylene and toluene biofilters, respectively.     

Noninvasive estimation of pharyngeal airway resistance and compliance in children based on volume-gated dynamic MRI and computational fluid dynamics

Computational fluid dynamics (CFD) analysis was used to model the effect of collapsing airway geometry on internal pressure and velocity in the pharyngeal airway of three sedated children with obstructive sleep apnea syndrome (OSAS) and three control subjects. Model geometry was reconstructed from volume-gated magnetic resonance images during normal tidal breathing at 10 increments of tidal volume through the respiratory cycle. Each geometry was meshed with an unstructured grid and solved using a low-Reynolds number k-ω turbulence model driven by flow data averaged over 12 consecutive breathing cycles. Combining gated imaging with CFD modeling created a dynamic three-dimensional view of airway anatomy and mechanics, including the evolution of airway collapse and flow resistance and estimates of the local effective compliance. The upper airways of subjects with OSAS were generally much more compliant during tidal breathing. Compliance curves (pressure vs. cross-section area), derived for different locations along the airway, quantified local differences along the pharynx and between OSAS subjects. In one subject, the distal oropharynx was more compliant than the nasopharynx (1.028 vs. 0.450 mm(2)/Pa) and had a lower theoretical limiting flow rate, confirming the distal oropharynx as the flow-limiting segment of the airway in this subject. Another subject had a more compliant nasopharynx (0.053 mm(2)/Pa) during inspiration and apparent stiffening of the distal oropharynx (C = 0.0058 mm(2)/Pa), and the theoretical limiting flow rate indicated the nasopharynx as the flow-limiting segment. This new method may help to differentiate anatomical and functional factors in airway collapse.     

Pituitary adenylate cyclase-activating polypeptide plays an anti-inflammatory role in endotoxin-induced airway inflammation: in vivo study with gene-deleted mice

The presence of pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors in capsaicin-sensitive peptidergic sensory nerves, inflammatory and immune cells suggest its involvement in inflammation. However, data on its role in different inflammatory processes are contradictory and there is little known about its functions in the airways. Therefore, our aim was to examine intranasal endotoxin-induced subacute airway inflammation in PACAP gene-deficient (PACAP^−/−) and wild-type (PACAP^+/+) mice. Airway responsiveness to inhaled carbachol was determined in unrestrained mice with whole body plethysmography 6 h and 24 h after LPS. Myeloperoxidase (MPO) activity referring to the number of accumulated neutrophils and macrophages was measured with spectrophotometry and interleukin-1β (IL-1β) concentration with ELISA from the lung homogenates. Histological evaluation and semiquantitative scoring were also performed. Bronchial responsiveness, as well as IL-1β concentration and MPO activity markedly increased at both timepoints. Perivascular edema dominated the histological picture at 6 h, while remarkable peribronchial granulocyte accumulation, macrophage infiltration and goblet cell hyperplasia were seen at 24 h. In PACAP^−/− mice, airway hyperreactivity was significantly higher 24 h after LPS and inflammatory histopathological changes were more severe at both timepoints. MPO increase was almost double in PACAP^−/− mice compared to the wild-types at 6 h. In contrast, there was no difference between the IL-1β concentrations of the PACAP^+/+ and PACAP^−/− mice. These results provide evidence for a protective role for PACAP in endotoxin-induced airway inflammation and hyperreactivity.     

Effects of fluid structure interaction in a three dimensional model of the spinal subarachnoid space

It is unknown whether spinal cord motion has a significant effect on cerebrospinal fluid (CSF) pressure and therefore the importance of including fluid structure interaction (FSI) in computational fluid dynamics models (CFD) of the spinal subarachnoid space (SAS) is unclear. This study aims to determine the effects of FSI on CSF pressure and spinal cord motion in a normal and in a stenosis model of the SAS. A three-dimensional patient specific model of the SAS and spinal cord were constructed from MR anatomical images and CSF flow rate measurements obtained from a healthy human being. The area of SAS at spinal level T4 was constricted by 20% to represent the stenosis model. FSI simulations in both models were performed by running ANSYS CFX and ANSYS Mechanical in tandem. Results from this study show that the effect of FSI on CSF pressure is only about 1% in both the normal and stenosis models and therefore show that FSI has a negligible effect on CSF pressure.     

Aerobic granular sludge formation for high strength agro-based wastewater treatment

The present study investigates the formation of aerobic granular sludge in sequencing batch reactor (SBR) fed with palm oil mill effluent (POME). Stable granules were observed in the reactor with diameters between 2.0 and 4.0 mm at a chemical oxygen demand (COD) loading rate of 2.5 kg COD m⁻³ d⁻¹. The biomass concentration was 7600 mg L⁻¹ while the sludge volume index (SVI) was 31.3 mL g SS⁻¹ indicating good biomass accumulation in the reactor and good settling properties of granular sludge, respectively. COD and ammonia removals were achieved at a maximum of 91.1% and 97.6%, respectively while color removal averaged at only 38%. This study provides insights on the development and the capabilities of aerobic granular sludge in POME treatment.