Objective
Distraction osteogenesis maxillary expansion (DOME) is a reliable method to expand the nasal floor and hard palatal vault in adults with obstructive sleep apnea (OSA). DOME results in a ...reduction in the apnea-hypopnea index (AHI) and subjective report of improved nasal breathing. Using rhinomanometry augmented computational fluid dynamic (CFD) modeling, we propose a mechanism of how DOME reduces upper airway pharyngeal collapse in adults with OSA.
Material and method
A retrospective cohort with 20 subjects and mean age of 29.6 ± 8 years who completed DOME at Stanford University from September 2014 to April 2016. Subjects were included if polysomnography, airway morphology, and rhinomanometry were available for use. From the CBCT data, 3D nasal and pharyngeal airway model were generated. Numeric CFD simulation of the airway models were analyzed under the following conditions: (1) the volume of air was flowing at a velocity of 300 cm
3
/s, (2) the wall surface was not slippery, and (3) the simulations were repeated 1000 times to calculate mean values. Statistical analyses using SPSS v24 software included paired
t
tests, nonparametric Wilcoxon rank test, Friedman test with Bonferroni correction, and Spearman’s correlation coefficients (
p
< 0.05).
Results
Mean AHI improved from 17.8 ± 17.6 to 7.8 ± 7.1 events per hour (
p
< 0.001). Mean lowest oxygen saturation improved from 88.2 ± 7.2 to 90.9 ± 4.2% (
p
< 0.05). Mean airflow velocity within the nasal airway decreased from 15.6 ± 7.3 to 7.4 ± 2.1 m/s (
p
< 0.001) after DOME. Mean negative pressure of the nasal airway, retropalatal airway, oropharyngeal airway, and hypopharyngeal airway is reduced from − 158.4 ± 115.3 to − 48.6 ± 28.7 Pa, from − 174.8 ± 119.9 to − 52.5 ± 31.3 Pa, from − 177.0 ± 118.4 to − 54.9 ± 31.8 Pa and from − 177.9 ± 117.9 to − 56.9 ± 32.1 Pa (
p
< 0.001), respectively. AHI positively correlated with nasal flow velocity (
p
< 0.05) and negatively correlated with pharyngeal airway pressure (
p
< 0.05). ODI was positively correlated with nasal velocity (
p
< 0.05) and negatively correlated with nasal airway pressure (
p
< 0.05), retropalatal airway pressure (
p
< 0.001), oropharyngeal airway pressure (
p
< 0.001), and hypopharyngeal airway pressure (
p
< 0.05).
Conclusion
Anatomic expansion of the nasal floor with widening of the hard palatal vault from DOME is associated with reduction of nasal airflow velocity and downstream reduction of negative pressure in the pharyngeal airway. This dynamic interaction correlates with a reduction in the apnea-hypopnea index (AHI) and Oxygen Desaturation Index (ODI).
A high prevalence of obstructive sleep apnea (OSA) has been reported in Down syndrome (DS) owing to the coexistence of multiple predisposing factors related to its genetic abnormality, posing a ...challenge for the management of OSA. We hypothesized that DS mice recapitulate craniofacial abnormalities and upper airway obstruction of human DS and can serve as an experimental platform for OSA research. This study, thus, aimed to quantitatively characterize the upper airway as well as craniofacial abnormalities in Dp(16)1Yey (Dp16) mice. Dp16 mice demonstrated craniofacial hypoplasia, especially in the ventral part of the skull and the mandible, and rostrally positioned hyoid. These changes were accompanied with a shorter length and smaller cross-sectional area of the upper airway, resulting in a significantly reduced upper airway volume in Dp16 mice. Our non-invasive approach, a combination of computational fluid dynamics and high-resolution micro-CT imaging, revealed a higher negative pressure inside the airway of Dp16 mice compared to wild-type littermates, showing the potential risk of upper airway collapse. Our study indicated that Dp16 mice can be a useful model to examine the pathophysiology of increased upper airway collapsibility of DS and to evaluate the efficacy of therapeutic interventions for breathing and sleep anomalies.
Radiation therapy for head and neck cancers is frequently associated with adverse effects on the surrounding normal tissue. Irreversible damage to radiation-sensitive acinar cells in the salivary ...gland (SG) causes severe radiation-induced xerostomia (RIX). Currently, there are no effective drugs for treating RIX. We investigated the efficacy of treatment with conditioned medium derived from stem cells from human exfoliated deciduous teeth (SHED-CM) in a mouse RIX model. Intravenous administration of SHED-CM, but not fibroblast-CM (Fibro-CM), prevented radiation-induced cutaneous ulcer formation (p < 0.0001) and maintained SG function (p < 0.0001). SHED-CM treatment enhanced the expression of multiple antioxidant genes in mouse RIX and human acinar cells and strongly suppressed radiation-induced oxidative stress. The therapeutic effects of SHED-CM were abolished by the superoxide dismutase inhibitor diethyldithiocarbamate (p < 0.0001). Notably, quantitative liquid chromatography-tandem mass spectrometry shotgun proteomics of SHED-CM and Fibro-CM identified eight proteins activating the endogenous antioxidant system, which were more abundant in SHED-CM than in Fibro-CM (p < 0.0001). Neutralizing antibodies against those activators reduced antioxidant activity of SHED-CM (anti-PDGF-D; p = 0.0001, anti-HGF; p = 0.003). Our results suggest that SHED-CM may provide substantial therapeutic benefits for RIX primarily through the activation of multiple antioxidant enzyme genes in the target tissue.
To assess three rapid maxillary expansion (RME) appliances in nasal ventilation.
Three-arm parallel randomized clinical trial.
Sixty-six growing subjects (10-16 years old) needing RME as part of ...their orthodontic treatment were randomly allocated (1:1:1 ratio) to three groups of 22 patients receiving Hyrax (H), Hybrid-Hyrax (HH), or Keles keyless expander (K). The primary outcome of nasal ventilation (pressure and velocity) and secondary outcomes (skeletal, dental, soft tissue, and nasal obstruction changes) were blindly assessed on the initial (T0) and final (T1, 6 months at appliance removal) cone-beam computed tomography (CBCT) data by applying computational fluid dynamics (CFD) method. Differences across groups were assessed with crude and adjusted for baseline values and confounders (gender, age, skeletal maturation, expansion amount, mucosal/adenoid hypertrophy, nasal septum deviation) regression models with alpha = 5%.
Fifty-four patients were analysed (19H, 21HH, 14K). RME reduced both nasal pressure (H: -45.8%, HH: -75.5%, K: -63.2%) and velocity (H: -30%, HH: -58.5%, K: -35%) accompanied with nasal obstruction resolution (H: 26%, HH: 62%, K: 50%). Regressions accounting for baseline severity indicated HH expander performing better in terms of post-expansion maximum velocity (P = 0.03) and nasal obstruction resolution (P = 0.04), which was robust to confounders. Mucosal/adenoid hypertrophy and nasal septum deviation changes were variable, minimal, and similar across groups. The HH resulted in significantly greater increase in the nasal cross-sectional area (62.3%), anterior (14.6%), and posterior (10.5%) nasal widths. Nasal obstruction resolution was more probable among younger (P = 0.04), skeletally immature (P = 0.03), and male patients (P = 0.02) without pre-treatment mucosal hypertrophy (P = 0.04), while HH was associated with marginal greater probability for obstruction resolution.
RME resulted in improvement of nasal skeletal parameters and simulated ventilation with the former being in favour of the HH and the latter not showing significant differences among the three appliances.
Attrition in the K group due to blocked activation rods possibly leading to limited sample to identify any existing group differences.
Replacement of blocked Keles expanders for finalizing treatment.
The protocol was not published before the trial commencement.
Australian and New Zealand Clinical Trial Registry; ACTRN12617001136392.
Introduction Pharyngeal airway size is increasingly recognized as an important factor in obstructive sleep apnea. However, few studies have examined the changes of pharyngeal airway form after dental ...procedures for treating obstructive sleep apnea during growth. The purpose of this study was to evaluate the effect of the Herbst appliance on the 3-dimensional form of the pharyngeal airway using cone-beam computed tomography. Methods Twenty-four Class II subjects (ANB, ≥5°; 11 boys; mean age, 11.6 years) who required Herbst therapy with edgewise treatment had cone-beam computed tomography images taken before and after Herbst treatment. Twenty Class I control subjects (9 boys; mean age, 11.5 years) received edgewise treatment only. The volume, depth, and width of the pharyngeal airway were compared between the groups using measurements from 3-dimensional cone-beam computed tomography images of the entire pharyngeal airway. Results The increase of the oropharyngeal airway volume in the Herbst group (5000.2 mm3 ) was significantly greater than that of the control group (2451.6 mm3 ). Similarly, the increase of the laryngopharyngeal airway volume in the Herbst group (1941.8 mm3 ) was significantly greater than that of the control group (1060.1 mm3 ). Conclusions The Herbst appliance enlarges the oropharyngeal and laryngopharyngeal airways. These results may provide a useful assessment of obstructive sleep apnea treatment during growth.
Objectives
This study aimed to determine the anteroposterior depth (APD) of the pharyngeal airway (PA) where post‐operative PA obstruction was predicted, using computer fluid dynamics (CFD), in order ...to prevent obstructive sleep apnoea after mandibular setback surgery.
Settings and sample population
Nineteen skeletal Class III patients (8 men; mean age, 26.7 years) who required mandibular setback surgery had computed tomography images taken before and 6 months after surgery.
Methods
The APD of each site of the four cross‐sectional reference planes (retropalatal airway RA, second cervical vertebral airway, oropharyngeal airway and third cervical vertebral airway) were measured. The Maximum negative pressure (Pmax) of the PA was measured at inspiration using CFD, based on a three‐dimensional PA model. Intersite differences were determined using analysis of variance and the Friedman test with Bonferroni correction. The relationship between APD and Pmax was evaluated by Spearman correlation coefficients and non‐linear regression analysis.
Results
The smallest PA site was the RA. Pmax was significantly correlated with the APD of the RA (rs = .628, P < .001). The relationship between Pmax and the APD‐RA was fitted to a curve, which showed an inversely proportional relationship of Pmax to the square of the APD‐RA. Pmax substantially increased even with a slight reduction of the APD‐RA. In particular, when the APD‐RA was 7 mm or less, Pmax increased greatly, suggesting that PA obstruction was more likely to occur.
Conclusions
The results of this study suggest that APD‐RA is a useful predictor of good PA ventilation after surgery.
Abstract Introduction Recent evidence suggests that rapid maxillary expansion (RME) is an effective treatment of obstructive sleep apnea syndrome (OSAS) in children with maxillary constriction. ...Nonetheless, the effect of RME on pharyngeal airway pressure during inspiration is not clear. The purpose of this retrospective study was to evaluate changes induced by the RME in ventilation conditions using computational fluid dynamics. Methods Twenty-five subjects (14 boys, 11 girls; mean age 9.7 years) who required RME had cone-beam computed tomography (CBCT) images taken before and after the RME. The CBCT data were used to reconstruct 3-dimensional shapes of nasal and pharyngeal airways. Measurement of airflow pressure was simulated using computational fluid dynamics for calculating nasal resistance during exhalation. This value was used to assess maximal negative pressure in the pharyngeal airway during inspiration. Results Nasal resistance after RME, 0.137 Pa/(cm3 /s), was significantly lower than that before RME, 0.496 Pa/(cm3 /s), and the maximal negative pressure in the pharyngeal airway during inspiration was smaller after RME (−48.66 Pa) than before (−124.96 Pa). Conclusion Pharyngeal airway pressure during inspiration is decreased with the reduction of nasal resistance by the RME. This mechanism may contribute to the alleviation of OSAS in children.
Intravenous administration of conditioned medium from stem cells of human exfoliated deciduous teeth (SHED-CM) effectively restores mechanically injured osteochondral tissues in mouse ...temporomandibular joint osteoarthritis. However, the underlying therapeutic mechanisms remain elusive. Here, we investigated the direct therapeutic effects of SHED-CM on inflamed primary condylar chondrocytes in vitro. Immunofluorescence staining revealed that interleukin-1β-stimulated chondrocytes showed increased expression of the catabolic marker inducible nitric oxide synthase (iNOS) and reduced expression of the anabolic marker aggrecan (ACAN). We found that SHEDCM treatment, but not conditioned medium from bone marrow mesenchymal stem cells (BMSCCM), effectively suppressed iNOS expression and elevated ACAN levels, indicating that SHEDCM converted the catabolic phenotype of inflamed chondrocytes to an anabolic phenotype. Liquid chromatography with tandem mass spectrometry analysis of SHED-CM and BMSC-CM identified eight proteins enriched in SHED-CM that are related to anti-inflammatory and/or chondrogenic processes. Of these proteins, the Wnt signal inhibitor secreted frizzled-related protein 1 (SFRP1) was the most abundantly enriched in SHED-CM. We found that treatment with the selective SFRP1 inhibitor WAY-316606 abolished the anti-catabolic and pro-anabolic effects of SHED-CM. Collectively, our study suggests that SHED-CM directly suppresses catabolism and promotes anabolic responses of inflamed primary condylar chondrocytes, which partially rely on SFRP1 function in SHED-CM. The direct action of SHED-CM may be useful to treat inflammatory cartilage diseases.
The aim of this study was to analyze the skeletal, dental and airway changes with endoscopically assisted surgical expansion (EASE) to widen the nasomaxillary complex for the treatment of sleep apnea ...in adults.
One hundred and five consecutive patients underwent EASE. Cone beam computed tomography (CBCT) was conducted preoperatively and within four weeks after the completion of the expansion process. Computational fluid dynamic (CFD) analysis was performed on 20 randomly selected patients to assess airway flow changes.
One hundred patients (67 males) with the mean age of 35.0±13.5 years (17-64 years) had completed pre- and post-expansion imaging. Ninety-six patients (96%) had successful expansion defined as separation of the midpalatal suture at least 1 mm from anterior nasal spine (ANS) to posterior nasal spine (PNS). The nasal cavity expansion was 3.12±1.11 mm at ANS, 3.64±1.06 mm at first molar and 2.39±1.15 mm at PNS. The zygoma expansion was 2.17±1.11 mm. The ratio of dental expansion to skeletal expansion was 1.23:1 (3.83 mm:3.12 mm) at canine and 1.31:1 (4.77 mm:3.64 mm) at first molar. CFD airway simulation showed a dynamic change following expansion throughout the airway. The mean negative pressure improved in the nasal airway (from -395.5±721.0 to -32.7±19.2 Pa), nasopharyngal airway (from -394.2±719.4 to -33.6±18.5 Pa), oropharyngeal airway (from -405.9±710.8 to -39.4±19.3 Pa) and hypopharyngeal airway (from -422.6±704.9 to -55.1±33.7 Pa). The mean airflow velocity within the nasal airway decreased from 18.8±15.9 to 7.6±2.0 m/s and the oropharyngeal airway decreased from 4.2±2.9 to 3.2±1.2 m/s. The velocity did not change significantly in the nasopharyngeal and hypopharyngeal regions.
EASE results in expansion of the midpalatal suture from the ANS to PNS with a nearly pure skeletal movement of minimal dental effect. The expansion of the nasomaxillary complex resulted in the widening of the nasal sidewall throughout the nasal cavity. The improved air flow dynamics was demonstrated by CFD simulation.
The regulation of the mesenchymal stem cell (MSC) programming mechanism promises great success in regenerative medicine. Tissue regeneration has been associated not only with the differentiation of ...MSCs, but also with the microenvironment of the stem cell niche that involves various cytokines and immune cells in the tissue regeneration site. In the present study, fibroblast growth factor 2 (FGF2), the principal growth factor for tooth development, dental pulp homeostasis and dentin repair, was reported to affect the expression of cytokines in human dental pulp-derived MSCs. FGF2 significantly inhibited the expression of chemokine C-C motif ligand 11 (CCL11) in a time- and dose-dependent manner in the SDP11 human dental pulp-derived MSC line. This inhibition was diminished following treatment with the AZD4547 FGF receptor (FGFR) inhibitor, indicating that FGF2 negatively regulated the expression of CCL11 in SDP11 cells. Furthermore, FGF2 activated the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinases (JNK) in SDP11 cells. The mechanism of the FGFR-downstream signaling pathway was then studied using the SB203580, U0126 and SP600125 inhibitors for p38 MAPK, ERK1/2, and JNK, respectively. Interestingly, only treatment with SP600125 blocked the FGF2-mediated suppression of CCL11. The present results suggested that FGF2 regulated the expression of cytokines and suppressed the expression of CCL11 via the JNK signaling pathway in human dental pulp-derived MSCs. The present findings could provide important insights into the association of FGF2 and CCL11 in dental tissue regeneration therapy. Key words: dental pulp-derived mesenchymal stem cells, fibroblast growth factor 2, fibroblast growth factor receptor signal, C-C motif ligand 11, c-Jun N-terminal kinase
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