Effects of adenoid hypertrophy on nasopharyngeal airway ventilation: A computational fluid dynamics study.

OBJECTIVES: Adenoid hypertrophy causes impaired nasopharyngeal airways (NA) ventilation. However, it is difficult to evaluate the ventilatory conditions of NA. Therefore, this study aimed to analyze the nasopharyngeal airway resistance (NARES) based on computational fluid dynamics simulations and the nasopharyngeal airway depth (NAD) and adenoid hypertrophy grade measured on cephalometric cone-beam computed tomography images and determine the relationship between NAD and grade and NARES to ultimately assess using cephalometric measurements whether NA has airway obstruction defects. METHODS: Cephalogram images were generated from cone-beam computed tomography data of 102 children (41 boys; mean age: 9.14 ± 1.43 years) who received orthodontic examinations at an orthodontic clinic from September 2012 to March 2023, and NAD and adenoid grade and NARES values were measured based on computational fluid dynamics analyses using a 3D NA model. Nonlinear regression analyses were used to evaluate the relationship between NARES and NAD and correlation coefficients to evaluate the relationship between grade and NARES. RESULTS: NARES was inversely proportional to the cube of NAD (R2 = 0.786, P < 0.001), indicating a significant relationship between these variables. The resistance NARES increased substantially when the distance NAD was less than 5 mm. However, adenoid Grade 4 (75 % hypertrophy) was widely distributed. CONCLUSIONS: These study findings demonstrate that the ventilatory conditions of NA can be determined based on a simple evaluation of cephalogram images. An NAD of less than 5 mm on cephalometric images results in NA obstruction with substantially increased airflow resistance.

Conditioned Medium From Stem Cells of Human Exfoliated Deciduous Teeth Alleviates Mouse Osteoarthritis by Inducing sFRP1-Expressing M2 Macrophages.

Intravenous administration of conditioned medium from stem cells of human exfoliated deciduous teeth (SHED-CM) regenerates mechanically injured osteochondral tissues in mouse temporomandibular joint osteoarthritis (TMJOA). However, the underlying therapeutic mechanisms remain unclear. Here, we showed that SHED-CM alleviated injured TMJ by inducing anti-inflammatory M2 macrophages in the synovium. Depletion of M2 by Mannosylated Clodrosome abolished the osteochondral repair activities of SHED-CM. Administration of CM from M2-induced by SHED-CM (M2-CM) effectively ameliorated mouse TMJOA by inhibiting chondrocyte inflammation and matrix degradation while enhancing chondrocyte proliferation and matrix formation. Notably, in vitro, M2-CM directly suppressed the catabolic activities while enhancing the anabolic activities of interleukin-1ß-stimulated mouse primary chondrocytes. M2-CM also inhibited receptor activator of nuclear factor NF-κB ligand-induced osteoclastogenesis in RAW264.7 cells. Secretome analysis of M2-CM and M0-CM revealed that 5 proteins related to anti-inflammation and/or osteochondrogenesis were enriched in M2-CM. Of these proteins, the Wnt signal antagonist, secreted frizzled-related protein 1 (sFRP1), was the most abundant and played an essential role in the shift to anabolic chondrocytes, suggesting that M2 ameliorated TMJOA partly through sFRP1. This study suggests that secretome from SHED exerted remarkable osteochondral regeneration activities in TMJOA through the induction of sFRP1-expressing tissue-repair M2 macrophages.

Does rapid maxillary expansion improve nasal airway obstruction? A computer fluid dynamics study in patients with nasal mucosa hypertrophy and obstructive adenoids.

INTRODUCTION: Rapid maxillary expansion (RME) expands the maxillary dentition laterally and improves nasal airway obstruction. However, the incidence of nasal airway obstruction improvement after RME is approximately 60%. This study aimed to clarify the beneficial effects of RME on nasal airway obstruction in specific pathologic nasal airway diseases (nasal mucosa hypertrophy and obstructive adenoids) using computer fluid dynamics. METHODS: Sixty subjects (21 boys; mean age 9.1 years) were divided into 3 groups according to their nasal airway condition (control, nasal mucosa hypertrophy, and obstructive adenoids), and those requiring RME had cone-beam computed tomography images taken before and after RME. These data were used to evaluate the nasal airway ventilation condition (pressure) using computer fluid dynamics and measure the cross-sectional area of the nasal airway. RESULTS: The cross-sectional area of the nasal airway significantly increased after RME in all 3 groups. The pressures in the control and nasal mucosa groups significantly reduced after RME but did not change significantly in the adenoid group. The incidence of improvement in nasal airway obstruction in the control, nasal mucosa, and adenoid groups was 90.0%, 31.6%, and 23.1%, respectively. CONCLUSIONS: The incidence of improvement in nasal airway obstruction after RME depends on the nasal airway condition (nasal mucosa hypertrophy and obstructive adenoids). In patients with nonpathologic nasal airway conditions, the obstruction may be sufficiently improved with RME. Furthermore, to some extent, RME may be effective in treating nasal mucosa hypertrophy. However, because of obstructive adenoids, RME was ineffective in patients with nasal airway obstruction.

Iroquois homeobox 3 regulates odontoblast proliferation and differentiation mediated by Wnt5a expression.

Iroquois homeobox (Irx) genes are TALE-class homeobox genes that are evolutionarily conserved across species and have multiple critical cellular functions in fundamental tissue development processes. Previous studies have shown that Irxs genes are expressed during tooth development. However, the precise roles of genes in teeth remain unclear. Here, we demonstrated for the first time that Irx3 is an essential molecule for the proliferation and differentiation of odontoblasts. Using cDNA synthesized from postnatal day 1 (P1) tooth germs, we examined the expression of all Irx genes (Irx1-Irx6) by RT-PCR and found that all genes except Irx4 were expressed in the tooth tissue. Irx1-Irx3 a were expressed in the dental epithelial cell line M3H1 cells, while Irx3 and Irx5 were expressed in the dental mesenchymal cell line mDP cells. Only Irx3 was expressed in both undifferentiated cell lines. Immunostaining also revealed the presence of IRX3 in the dental epithelial cells and mesenchymal condensation. Inhibition of endogenous Irx3 by siRNA blocks the proliferation and differentiation of mDP cells. Wnt3a, Wnt5a, and Bmp4 are factors involved in odontoblast differentiation and were highly expressed in mDP cells by quantitative PCR analysis. Interestingly, the expression of Wnt5a (but not Wnt3a or Bmp4) was suppressed by Irx3 siRNA. These results suggest that Irx3 plays an essential role in part through the regulation of Wnt5a expression during odontoblast proliferation and differentiation.

Therapeutic benefits of factors derived from stem cells from human exfoliated deciduous teeth for radiation-induced mouse xerostomia.

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.

Nasomaxillary Expansion by Endoscopically-Assisted Surgical Expansion (EASE): An airway centric approach / Expansion nasomaxillaire chirurgicale assistée par endoscopie (EASE) : une approche centrée surles voies respiratoires

Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.

Introduction: L'objectif de cette étude était d'analyser les modifications obtenues au niveau du squelette, des dents et des voies respiratoires lors d'une expansion nasomaxillaire chirurgicale assistée par endoscopie (EASE), visant à élargir le complexe nasomaxillaire pour le traitement de l'apnée du sommeil chez des adultes. Méthodes: Cent cinq patients consécutifs ont subi une EASE. Une tomographie à faisceau conique (CBCT) a été réalisée en préopératoire et dans les quatre semaines suivant la fin du processus d'expansion. Une analyse de la dynamique des fluides computationnelle (DFC) a été réalisée sur vingt patients sélectionnés au hasard pour évaluer les modifications du débit de leurs voies respiratoires. Résultats: Un bilan d'imagerie pré- et post-expansion a été réalisé chez cent patients (dont 67 hommes) d'un âge moyen de 35,0 ± 13,5 ans (17-64 ans). Quatre-vingt-seize patients (96 %) ont bénéficié d'une expansion réussie, définie comme une séparation de la suture médiopalatine d'au moins 1 mm, de l'épine nasale antérieure (ENA) à l'épine nasale postérieure (ENP). L'expansion de la cavité nasale était de 3,12 ± 1,11 mm au niveau de l'ENA, de 3,64 ± 1,06 mm au niveau de la première molaire et de 2,39 ± 1,15 mm au niveau de l'ENP. L'expansion zygomatique était de 2,17 ± 1,11 mm. Le rapport entre l'expansion dentaire et l'expansion squelettique était de 1,23 : 1 (3,83 mm : 3,12 mm) au niveau de la canine et de 1,31 : 1 (4,77 mm : 3,64 mm) au niveau de la première molaire. Après l'expansion, la simulation des voies respiratoires par DFC a montré un changement dynamique au niveau de l'ensemble des voies respiratoires. La pression négative moyenne s'est améliorée dans les voies nasales (de -395,5 ± 721,0 à -32,7 ± 19,2 Pa), les voies nasopharyngiennes (de -394,2 ± 719,4 à -33,6 ± 18,5 Pa), les voies aériennes oropharyngées (de -405,9 ± 710,8 à -39,4 ± 19,3 Pa) et les voies aériennes hypopharyngées (de -422,6 ± 704,9 à -55,1 ± 33,7 Pa). La vitesse moyenne du flux d'air dans les voies nasales a diminué de 18,8 ± 15,9 à 7,6 ± 2,0 m/s et de 4,2 ± 2,9 à 3,2 ± 1,2 m/s dans les voies oropharyngées. La vitesse n'a pas changé de manière significative dans les régions nasopharyngienne et hypopharyngienne. Conclusions: L'EASE entraîne une expansion de la suture médiopalatine, de l'ENA jusqu'à l'ENP avec un mouvement squelettique presque pur et un effet dentaire minimal. L'expansion du complexe nasomaxillaire a entraîné l'écartement des parois nasales latérales dans toute la cavité nasale. L'amélioration de la dynamique du flux d'air a été démontrée par une simulation DFC.

Persistent pediatric obstructive sleep apnea treated with skeletally anchored transpalatal distraction / SAOS pédiatrique persistant traité par distraction transpalatine à ancrage squelettique

Introduction: The aim of this study was to evaluate the impact of nasomaxillary expansion using skeletally anchored transpalatal distraction (TPD) in children without transverse maxillary deficiency that were previously treated by rapid palatal expansion (RPE). Materials and Methods: Twenty-nine consecutive children were treated by TPD. Twenty-five children, aged 10-16 years completed pre- and post-operative clinical evaluations, questionnaires (OSA-18), cone beam computed tomography (CBCT), and polysomnography (PSG). The pre- and post-operative CBCT data were used to reconstruct the 3-dimensional shape of the upper airway. Two measures of airflow function (pressure and velocity) were simulated by using computational fluid dynamics (CFD) at four different airway segments (nasal, nasopharyngeal, oropharyngeal and hypopharyngeal). Results: Twenty-three patients (92%) experienced improvement based on PSG. The apnea hypopnea index (AHI) improved from 6.72 ± 4.34 to 3.59 ± 5.11 (p<0.001) events per hour. Clinical symptoms based on OSA-18 scores were improved in all patients. Twenty-five patients (100%) had successful expansion defined as separation of the midpalatal suture at least 1mm from anterior nasal spine (ANS) to posterior nasal spine (PNS). The nasal sidewall widening was 2.59 ± 1,54 mm at canine, 2.91 ± 1,23 mm at first molar and 2.30 ± 1,29 mm at PNS. The ratio of dental expansion to nasal expansion was 1.12:1 (2.90mm:2.59mm) at canine and 1.37:1 (3.98mm:2.91mm) at first molar. The nasal airflow pressure reduced by 76% (-275.73 to -67.28 Pa) and the nasal airflow velocity reduced by over 50% (18.60 to 8.56 m/s). Conclusions: Nasomaxillary expansion by skeletally anchored TPD improves OSA in children without transverse maxillary deficiency that were previously treated by RPE. A nearly parallel anterior-posterior opening of the mid-palatal suture achieves enlargement of the entire nasal passage with improvement of the airflow characteristics in the nasal and pharyngeal airway. The improved airflow characteristic is significantly correlated with the improved polysomnographic findings, thus demonstrating that nasomaxillary expansion in previously expanded patients is a viable treatment option.

Introduction: L'objectif de cette étude était d'évaluer l'impact de l'expansion nasomaxillaire à l'aide d'une distraction transpalatine (DTP) à ancrage squelettique chez des enfants sans insuffisance maxillaire transversale et qui ont été précédemment traités par expansion palatine rapide (EPR). Matériels et méthodes: Vingt-neuf enfants enrôlés consécutivement ont été traités par DTP. Vingt-cinq enfants, âgés de 10 à 16 ans, ont été soumis à des évaluations cliniques pré- et postopératoires, des questionnaires (OSA-18), une tomographie à faisceau conique (CBCT) et une polysomnographie (PSG). Les données CBCT pré- et postopératoires ont été utilisées pour reconstruire la forme tridimensionnelle des voies aériennes supérieures. Deux mesures des caractéristiques d'écoulement de l'air (pression et vitesse) ont été simulées en utilisant la dynamique des fluides computationnelle (DFC) dans quatre segments différents des voies aériennes (nasal, nasopharyngé, oropharyngé et hypopharyngé). Résultats: Vingt-trois patients (92 %) ont bénéficié d'une rapide amélioration objectivée par la PSG. L'indice d'apnée-hypopnée (IAH) est passé de 6,72 ± 4,34 à 3,59 ± 5,11 (p<0,001) événements par heure. Les symptômes cliniques évalués avec les scores du questionnaire OSA-18 se sont améliorés chez tous les patients. Pour les vingt-cinq patients (100 %), l'expansion a été réussie, selon le critère d'une séparation de la suture médiopalatine d'au moins 1 mm, de l'épine nasale antérieure (ENA) jusqu'à l'épine nasale postérieure (ENP). L'élargissement de la distance entre les parois nasales latérales était de 2,59 ± 1,54 mm au niveau de la canine, de 2,91 ± 1,23 mm au niveau de la première molaire et de 2,30 ± 1,29 mm à l'épine nasale postérieure. Le rapport entre l'expansion dentaire et l'expansion nasale était de 1,12:1 (2,90 mm:2,59 mm) au niveau de la canine et de 1,37:1 (3,98 mm:2,91 mm) au niveau de la première molaire. La pression du flux d'air nasal a diminué de 76 % (-275,73 à -67,28 Pa) et la vitesse du flux d'air nasal a diminué de plus de 50 % (18,60 à 8,56 m/s). Conclusions: L'expansion nasomaxillaire à l'aide d'une distraction transpalatine à ancrage squelettique améliore le SAOS chez les enfants sans déficit maxillaire transverse et qui ont été auparavant traités par EPR. Une ouverture antéro-postérieure et presque parallèle de la suture médiopalatine permet d'élargir l'ensemble du passage nasal et d'améliorer les caractéristiques du flux d'air dans les voies aériennes nasales et pharyngées. L'amélioration des caractéristiques de l'écoulement d'air est significativement corrélée à l'amélioration des résultats polysomnographiques, démontrant ainsi que l'expansion nasomaxillaire chez des patients précédemment traités par EPR est une option thérapeutique viable.

Persistent pediatric obstructive sleep apnea treated with skeletally anchored transpalatal distraction

Introduction: The aim of this study was to evaluate the impact of nasomaxillary expansion using skeletally anchored transpalatal distraction (TPD) in children without transverse maxillary deficiency that were previously treated by rapid palatal expansion (RPE). Materials and Methods: Twenty-nine consecutive children were treated by TPD. Twenty-five children, aged 10-16 years completed pre- and post-operative clinical evaluations, questionnaires (OSA-18), cone beam computed tomography (CBCT), and polysomnography (PSG). The pre- and post-operative CBCT data were used to reconstruct the 3-dimensional shape of the upper airway. Two measures of airflow function (pressure and velocity) were simulated by using computational fluid dynamics (CFD) at four different airway segments (nasal, nasopharyngeal, oropharyngeal and hypopharyngeal). Results: Twenty-three patients (92%) experienced improvement based on PSG. The apnea hypopnea index (AHI) improved from 6.72±4.34 to 3.59±5.11 (p<0.001) events per hour. Clinical symptoms based on OSA-18 scores were improved in all patients. Twenty-five patients (100%) 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 sidewall widening was 2.59±1.54 mm at canine, 2.91±1.23 mm at first molar and 2.30±1.29 mm at PNS. The ratio of dental expansion to nasal expansion was 1.12:1 (2.90 mm:2.59 mm) at canine and 1.37:1 (3.98 mm:2.91 mm) at first molar. The nasal airflow pressure reduced by 76% (-275.73 to -67.28 Pa) and the nasal airflow velocity reduced by over 50% (18.60 to 8.56 m/s). Conclusions: Nasomaxillary expansion by skeletally anchored TPD improves OSA in children without transverse maxillary deficiency that were previously treated by RPE. A nearly parallel anterior-posterior opening of the mid-palatal suture achieves enlargement of the entire nasal passage with improvement of the airflow characteristics in the nasal and pharyngeal airway. The improved airflow characteristic is significantly correlated with the improved polysomnographic findings, thus demonstrating that nasomaxillary expansion in previously expanded patients is a viable treatment option.

Nasomaxillary Expansion by Endoscopically-Assisted Surgical Expansion (EASE): An airway centric approach

Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.

Fibroblast growth factor 2 suppresses the expression of C-C motif chemokine 11 through the c-Jun N-terminal kinase pathway in human dental pulp-derived mesenchymal stem cells.

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.

Nasal ventilation and rapid maxillary expansion (RME): a randomized trial.

OBJECTIVE: To assess three rapid maxillary expansion (RME) appliances in nasal ventilation. TRIAL DESIGN: Three-arm parallel randomized clinical trial. METHODS: 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%. RESULTS: 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. CONCLUSIONS: 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. LIMITATION: Attrition in the K group due to blocked activation rods possibly leading to limited sample to identify any existing group differences. HARMS: Replacement of blocked Keles expanders for finalizing treatment. PROTOCOL: The protocol was not published before the trial commencement. REGISTRATION: Australian and New Zealand Clinical Trial Registry; ACTRN12617001136392.

Evaluation of the effect of oral appliance treatment on upper-airway ventilation conditions in obstructive sleep apnea using computational fluid dynamics.

Objective: To evaluate the effect of oral appliance (OA) treatment on upper-airway ventilation conditions in patients with obstructive sleep apnea (OSA) using computational fluid dynamics (CFD).Methods: Fifteen patients received OA treatment and underwent polysomnography (PSG) and computed tomography (CT). CT data were used to reconstruct three-dimensional models of nasal and pharyngeal airways. Airflow velocity and airway pressure measurements at inspiration were simulated using CFD.Results: The apnea-hypopnea index (AHI) improved from 23.1 to 10.1 events/h after OA treatment. On CFD analysis, airflow velocity decreased at the retropalatal and epiglottis-tip levels, while airway pressure decreased at the retropalatal, uvular- and epiglottis-tip levels. The AHI of patients with OSA before OA treatment was correlated with airway pressure at the epiglottis-tip level.Discussion: Treatment with OA improved the ventilation conditions of the pharyngeal airway and AHI. Results of CFD analysis of airway pressure and airflow velocity helped determine the severity and ventilatory impairment site of OSA, respectively.

Detailed evaluation of the upper airway in the Dp(16)1Yey mouse model of Down syndrome.

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.

Effect of adenoids and tonsil tissue on pediatric obstructive sleep apnea severity determined by computational fluid dynamics.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a respiratory disorder caused by the obstruction of the upper airway during sleep. The most common cause of pediatric OSA is adenotonsillar hypertrophy. Adenotonsillectomy is the first-line treatment for pediatric OSA; however, OSA persists in a significant number of patients due, in part, to the method of evaluating enlarged adenoids and tonsil tissue. The reason for these effects on OSA severity is not clear. This study aimed to establish a method to diagnose the need for adenoidectomy or tonsillectomy. METHODS: Twenty-seven Japanese children (mean age 6.6 years) participated in this study, undergoing polysomnography and computed tomography examination. Pharyngeal airway morphology (adenoids and tonsil tissue size, volume, and cross-sectional area [CSA]) and pressure on the upper airway were evaluated at each site using computational fluid dynamic analysis. RESULTS: Apnea-hypopnea index (AHI) showed a strong linear association with maximum negative pressure (Pmax) (AHI = -0.055* events/h Pmax -1.326, R² = .805). The relationship between minimum CSA (CSAmin) and Pmax was represented by an inversely proportional fitted curve (Pmax = -4797/CSAmin -5.1, R² = .507). The relationship between CSAmin and AHI was also represented by an inversely proportional fitted curve (AHI = 301.6 events/h/CSAmin1.22, R² = .680). Pmax greatly increased if CSAmin became ≤ 30 mm². The negative pressure of each site increased when CSA measured ≤ 50 mm². CONCLUSIONS: In children, when the CSA for each site is ≤ 50 mm², AHI is likely to be elevated, and the patient may require tonsillectomy or adenoidectomy.

Relationship between pharyngeal airway depth and ventilation condition in mandibular setback surgery: A computational fluid dynamics study.

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.

Primary site identification in children with obstructive sleep apnea by computational fluid dynamics analysis of the upper airway.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a respiratory disorder caused by the obstruction of the upper airway during sleep. The identification of the primary site of OSA is essential to determine treatment strategy. This study aimed to establish computational fluid dynamics (CFD) analysis for determining the clinical severity of OSA and the primary site of OSA. METHODS: Twenty children (mean age, 6 years) were divided into OSA and control groups according to their apnea-hypopnea index. Three-dimensional airways were constructed from computed tomography data. The pharyngeal airway morphology and the pressure and velocity of the upper airway were evaluated using CFD analysis. RESULTS: The maximum velocity and negative pressure of the upper airway in the OSA group were significantly correlated with the severity of OSA (rs = .741, P < .001; rs = -.653, P = .002). A velocity higher than 12 m/s indicated the primary site of OSA. In addition, we found that the primary site of OSA is not necessarily the same as the collapsible conduit site. CONCLUSIONS: CFD analysis allows both the evaluation of the disease severity of OSA and the identification of the primary site of OSA in children. The primary site of OSA is not necessarily the same as the collapsible conduit site; therefore, CFD analysis can be used to identify the appropriate intervention for treating OSA.

How does distraction osteogenesis maxillary expansion (DOME) reduce severity of obstructive sleep apnea?

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 cm3/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).

Upper airway in children with unilateral cleft lip and palate evaluated with computational fluid dynamics.

INTRODUCTION: Children with unilateral cleft lip and palate (UCLP) exhibit snoring and mouth breathing. They are also reported to show obstructive sleep apnea syndrome. However, their upper airway ventilation condition is not clearly understood. Therefore, this study was performed to evaluate upper airway ventilation condition in children with UCLP with the use of computational fluid dynamics. METHODS: Twenty-one children (12 boys, 9 girls; mean age 9.1 years) with UCLP and 25 children (13 boys, 12 girls; mean age 9.2 years) without UCLP who required orthodontic treatment underwent cone-beam computed tomography (CBCT). Nasal resistance and upper airway ventilation condition were evaluated with the use of computational fluid dynamics from CBCT data. The groups were compared with the use of Mann-Whitney U tests and Student t tests. RESULTS: Nasal resistance of the UCLP group (0.97 Pa/cm3/s) was significantly higher than that of the control group (0.26 Pa/cm3/s; P < 0.001). Maximal pressure of the upper airway (335.02 Pa) was significantly higher in the UCLP group than in the control group (67.57 Pa; P < 0.001). Pharyngeal airway (from choanae to base of epiglottis) pressure in the UCLP group (140.46 Pa) was significantly higher than in the control group (15.92 Pa; P < 0.02). CONCLUSIONS: Upper airway obstruction in children with UCLP resulted from both nasal and pharyngeal airway effects.

Rapid maxillary expansion effects of nasal airway in children with cleft lip and palate using computational fluid dynamics.

OBJECTIVES: Rapid maxillary expansion (RME) improves nasal airway ventilation in non-cleft palate children. Children with unilateral cleft lip and palate (UCLP) may have nasal obstruction and experience an increased risk of obstructive sleep apnoea. The effect of RME in UCLP children is unclear. This retrospective study evaluated RME-induced changes in ventilation parameters in children with UCLP using computational fluid dynamics. SETTING AND SAMPLE POPULATION: Nineteen patients (10 boys, mean age 10.7 years) who required RME had cone-beam computed tomography images taken before and after RME. Twenty control participants (11 boys, mean age 11.1 years) received regular orthodontic treatment. METHODS: Nasal airway ventilation parameters (air pressure, air velocity and airflow rate) were analysed via computational fluid dynamics, and nasal cross-sectional area (CSA) was measured. RESULTS: Maximum pressure, velocity and nasal resistance were significantly reduced by RME in the UCLP group. Air flow rate and CSA on the cleft side significantly were increased by RME in the UCLP group. CONCLUSIONS: In children with UCLP, increasing the quantity of airflow and CSA on the cleft side by RME substantially improved nasal ventilation.

Relationships among tongue volume, hyoid position, airway volume and maxillofacial form in paediatric patients with Class-I, Class-II and Class-III malocclusions.

OBJECTIVES: To clarify the associations among tongue volume, hyoid position, airway volume and maxillofacial form using cone beam computed tomography (CBCT) data for children with Class-I, Class-II and Class-III malocclusion. SETTING AND SAMPLE POPULATION: Sixty children (mean age, 9.2 years) divided into Class-I, Class-II and Class-III malocclusion groups according to the A-nasion-B angle. MATERIAL AND METHODS: Cone beam computed tomography was used for three-dimensional reconstruction of the maxillofacial region and airway. The hyoid position and the tongue, airway and oral cavity volumes were evaluated. Upper airway ventilation status was calculated using computational fluid dynamics. The groups were compared using analysis of variance and Kruskal-Wallis tests; relationships among the parameters were assessed using Pearson's and Spearman's rank correlation tests. RESULTS: The tongue volume was larger in Class-III patients (50.63 cm3 ) than in Class-I patients (44.24 cm3 ; P < 0.05). The hyoid position was lower (49.44 cm), and anatomical balance (AB; tongue volume/oral cavity volume; 85.06%) was greater in Class-II patients than in Class-I patients (46.06 cm, 80.57%, respectively; P < 0.05 for both). The hyoid height showed a positive correlation with AB (r = 0.614; P < 0.001). CONCLUSIONS: Children with Class-III malocclusion have large tongue volumes and small AB; the reverse is true for children with Class-II malocclusion. The hyoid position is closely associated with AB in children with malocclusion.