Efficacy of a novel invisible mandibular advancement device in patients with mild to moderate obstructive sleep apnea: a preliminary study

Efficacy of a novel invisible mandibular advancement device in patients with mild to moderate obstructive sleep apnea: a preliminary study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Efficacy of a novel invisible mandibular advancement device in patients with mild to moderate obstructive sleep apnea: a preliminary study Xi Wang, Ruijie Ju, Jianwei Liu, Naiyuan Zheng, Kaan Orhan, Xieqi Shi, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8989379/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objectives To investigate the efficacy and working mechanism of a novel invisible mandibular advancement devices (iMAD) on respiratory parameters and upper airway in obstructive sleep apnea (OSA) patients. Materials and Methods Patients with mild to moderate OSA were recruited and each OSA patient underwent two home sleep apnea test (HSAT), and two cone beam computed tomography (CBCT) scans in supine position: one at baseline and one after 3 months with the iMAD in situ . The primary outcome variables were the obstructive apnea index (OAI), the minimal cross-sectional area (CSAmin) of the upper airway, and airway resistance derived from computational fluid dynamics (CFD). Results A total of 48 patients were recruited, and 27 patients with a mean (± SD) age of 42.44 (±7.64) years and a mean OAI of 15.59 (±6.86) /h completed the study. HSAT results showed that there was significant decrease in the OAI with iMAD in situ (p < 0.001). Nearly half of the patients (48.1%) met the responder criterion (≥ 50% reduction in OAI). CBCT showed that there was significant increase in the CSAmin of the upper airway with iMAD in situ (p < 0.001). CFD analysis showed that the maximum velocity of the mid-sagittal plane was significantly reduced with iMAD in situ (p < 0.05). Conclusions Within the limitations of this study, we conclude that iMAD could improve the respiratory parameters, increase upper airway dimensions, and reduce airflow velocity in mild to moderate OSA patients. Clinical Relevance: iMAD may offer an esthetic, comfortable alternative to conventional MAD for mild to moderate OSA. Trial registration: chictr.org.cn (ChiCTR2400092896) obstructive sleep apnea mandibular advancement device invisible 3D printing cone beam computed tomography upper airway dimensions computational fluid dynamics Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1. Introduction Obstructive sleep apnea (OSA) is characterized by recurrent obstructions of the upper airway, often resulting in oxygen desaturations and arousals from sleep [ 1 ]. The gold standard for the diagnosis of OSA is full-night polysomnography (PSG). Based on PSG recording, OSA severity for adults is classified as mild (5 ≤ apnea-hypopnea index (AHI) 30 events/hour) [ 1 ]. Mandibular advancement device (MAD) therapy is recommended as a primary treatment option in patients with mild and moderate OSA [ 2 ]. There is a large variety of commercially available customized MADs. MADs can be broadly classified into customized (titratable/nontitratable) and non-customized (titratable/nontitratable) devices [ 3 ]. Most currently available MADs are bulky and externally visible, which may compromise comfort, speech, and aesthetics, thereby limiting patient acceptance and long-term compliance [ 4 ]. To address limitations associated with conventional MADs, we developed a novel invisible mandibular advancement device (iMAD) characterised by a transparent, less bulky design that minimises intraoral volume and improves wearing comfort. By leveraging three-dimensional (3D) printing technology, the iMAD can be manufactured at a substantially lower cost than conventional MADs, thereby reducing the financial burden for patients. Owing to its reduced bulk and improved affordability, the iMAD is expected to enhance patient compliance. Therefore, before broad clinical application, it is essential to investigate the clinical feasibility and therapeutic efficacy of this newly introduced iMAD. The primary aim is to investigate the effect of iMAD on the sleep variables of the OSA patients. Over the last few decades, cone beam computed tomography (CBCT) has been used to analyze the volumetric dimensions of the upper airway in patients with OSA [ 5 ]. Furthermore, computational fluid dynamics (CFD) has been used to simulate airflow within the upper airway in OSA research [ 6 – 8 ]. CFD enables functional assessment of aerodynamic characteristics such as airflow velocity, thereby transforming static airway morphology into dynamic measures of respiratory function [ 9 ]. Previous studies suggested that the working mechanism of MAD is related to the improvement of the upper airway [ 10 ]. In this study, we will also focus on the upper airway and investigate the working mechanism of iMAD based on CBCT images and CFD analysis. The secondary aim is to investigate the effect of iMAD on the upper airway dimension and airflow characteristics of the OSA patients. 2. Material and methods 2.1 Overview This study was a prospective pilot study, in which the effects of a novel iMAD on respiratory parameters and upper airway were assessed. The Medical Research Ethics Committee of School of stomatology, Shandong University approved this study (NO.20240306). The study was registered at chictr.org.cn (ChiCTR2400092896). Written informed consent was obtained from all participants. 2.2 Participants Patients that fit the following inclusion/exclusion criteria were recruited from Department of Orthodontics, School of stomatology, Shandong University, China. The inclusion criteria were as follows: (1) age ≥ 18 years; (2) diagnosed with symptomatic mild or moderate OSA. The exclusion criteria were as follows: (1) medication use related to sleeping disorders; (2) evidence of respiratory and/or sleep disorders other than OSA (e.g., central sleep apnea syndrome); (3) systemic disorders (based on medical history and clinical examination, e.g., rheumatoid arthritis); (4) medical history of known daytime fatigue or severe sleep disturbance (e.g., insomnia, PLMS, narcolepsy); (5) known medical history of mental retardation, memory impairment, or psychiatric disorders; (6) reversible morphological upper airway abnormalities (viz., indication for upper airway surgery); (7) syndromes with craniofacial abnormalities (e.g., Pierre Robin sequence and Down syndrome). 2.3 Invisible MAD (iMAD) A novel iMAD (Smartee, Shanghai, China) was used in this study ( Fig.1 ). After adequate assessment of the central relation and maximum protrusion/retrusion using the George Gauge system (Great Lakes Orthodontics, Tonawanda, NY), iMADs were initially set at 75% of the maximal mandibular protrusion. Necessary titration adjustments were performed at follow-up visits at 4, 8, and 12 weeks, based on the patients’ perceived treatment outcomes and the self-reported side effects [11]. The self-reported side effects were recorded at each clinical visit, including the following: 1. sensitive teeth in the morning; 2. temporomandibular joint complaints; 3. changed occlusion in the morning. At each consecutive visit, the iMADs were evaluated and advanced 15% if subjective improvement (e.g., perceived reduction of snoring or excessive daytime sleepiness) of OSA was not reached. On the other hand, if side effects were not acceptable for the patient (e.g., tooth pain or signs of temporomandibular disorders), the advancement was adjusted backwards 15%. No adjustments were made when the patient reported sufficient efficacy without side effects. For every adjustment, new iMAD was made by 3D printing technique using photopolymer 3D printer (Ruifeng Technique company, Shenzhen, China) and dental pressure thermoforming machine (Scheu, Germany). After 3 months, adherence information was obtained via an online survey using the following measures: (1) the proportion of total sleep time during which the iMAD was used and (2) the proportion of days per week with iMAD use. 2.4 Home sleep apnea test (HSAT) All participants included in this study underwent an overnight level 3 PSG recording (Alice 6, Phillips Respironics, USA) for the diagnosis of OSA. Every patient underwent a baseline home sleep apnea test (HSAT) and a 3-month follow-up HSAT with iMAD in situ. HSAT included the following variables: pulse oximetry, body position, neck microphone, nasal cannula pressure transducer, and inductive plethysmography by means of thoracic band. The respiratory events index (REI) is the number of respiratory events per hour. The obstructive apnea index (OAI) is the number of obstructive apneas per hour. The central apnea index (CAI) is the number of central apneas per hour. Lowest Desat is the lowest blood oxygen level that lasted at least 2 seconds. 2.5 Cone beam computed tomography (CBCT) The CBCT datasets of Chinese patients were obtained using NewTom 5G CBCT systems (QR systems, Verona, Italy), according to an examination protocol developed in a previous study [12]. All patients underwent two CBCT scans (NewTom 5G, QR systems, Italy) at the Department of Oral Radiology, School of Dentistry, Shandong University: a baseline scan and a follow-up scan with the iMAD in situ (in the same protrusion position as during the follow-up PSG recording). The exposure settings were 110 kV, 4 mA, 0.3 mm voxel size, 3.6-s exposure time (pulsed radiation), and 18-36-s scanning time, depending on the size of the patient [13]. At baseline, patients were instructed to maintain maximum intercuspation, while at the follow-up scan, patients were instructed to relax their masticatory muscles with the iMAD in situ. During CBCT acquisition, patients were in supine position, and their head were positioned with the Frankfort horizontal plane, defined by the porion (Po) and orbitale (Or), perpendicular to the floor. To standardized the measurements, the acquired CBCT images were further reconstructed by adjusting the palatal plane (the plane crossing anterior nasal spine (ANS)-posterior nasal spine (PNS)) being parallel to the global horizontal plane in the sagittal view, and perpendicular to the global horizontal plane in the axial view [14]. For further analysis, the images were exported and stored in DICOM files. All images were presented to the observers in a room with dimmed light. 2.6 Minimum cross-sectional area of the upper airway Using Amira ® software (v4.1, Visage Imaging Inc., Carlsbad, CA, USA), upper airway segmentation was performed by defining the superior and inferior boundaries of the upper airway. The superior boundary of the upper airway was the palatal plane, and the inferior boundary was the horizontal plane across the anterior-inferior point of the fourth cervical vertebra (parallel to the palatal plane) ( Fig. 2A ). After upper airway segmentation, the upper airway volume (V) and the cross-sectional area (CSA) of each slice were calculated automatically in the software. Based on the results of CSA, the minimum CSA(CSAmin) could be identified and located ( Fig. 2B ). On the cross-sectional slice of CSAmin, the anterior-posterior dimension (A-P) and lateral dimension (La) of CSAmin were measured by the observer, using the linear measuring tool integrated in the software ( Fig. 2C ). The length of upper airway (L) was calculated by multiplying the slice numbers of the upper airway with 0.3mm (the thickness of every slice) [12]. As a small CSAmin is the most relevant anatomical characteristic of the upper airway related to the pathogenesis of OSA [15], the CSAmin was selected as the primary outcome variable of upper airway dimensions. All of the upper airway variables were measured by an experienced examiner. To test the intra-rater reliability of the assessment of the upper airway, 10 CBCT scans were randomly selected and re-measured after a 1-month interval of the original measurements. 2.7 Computational fluid dynamics (CFD) analysis The procedure of CFD analysis was described in detail in our previous studies [16, 17]. The upper airway was segmented based on the aforementioned superior and inferior boundary (Appendix 1). By surface triangulation, the segmented models were subsequently converted into 3D standard tessellation language (STL) models. The segmented STL models of the upper airway were exported into ANSYS ICEM CFD 17.0 (ANSYS, Inc., Canonsburg, Pennsylvania) for CFD analysis. The upper boundary was set at the coronal plane through PNS point, and the lower boundary was set at the horizontal plane across the base of the fourth cervical vertebra. The boundary condition consisted of axial velocity at the inlet plane, and no-slip boundary conditions for the upper airway wall. An inlet volume flow rate of 166 mL/s (10 L/min) was used in the flow simulation, as per previous studies [18, 19]. The aerodynamic characteristics, e.g., velocity, wall shear stress, and wall static pressure, were calculated in the upper airway model of each OSA patient during both inspiration and expiration. The inspiration phase was simulated by setting the inlet plane at the coronal plane across the PNS point and the outlet plane at the base of epiglottis. Conversely, the expiration phase was simulated by setting the inlet plane at the base of epiglottis and the outlet plane at the coronal plane across the PNS point [16]. Based on CFD calculations, airway resistance R was determined using the following formulation: R=∆P/Q, where ∆P is the total pressure drop between the inlet and outlet boundaries of the upper airway; Q is the volume flow rate within the upper airway. The aerodynamic characteristics, viz., velocity and static pressure of the mid-sagittal plane of the upper airway model were also calculated during both inspiration and expiration [16]. 2.8 Overbite and overjet analysis Based on baseline and follow-up CBCT images, the vertical opening with the iMAD in situ was determined in two steps. Firstly, the overbite was measured based on baseline CBCT images ( Fig. 3A ). Secondly, the vertical distance between the tip of upper and lower incisors with the iMAD in situ was measured based on follow-up CBCT images ( Fig. 3B ). All vertical distances were measured as the perpendicular distance to palatal plane. By adding these two values, the mandibular vertical opening with iMAD in situ was determined. 2.8 Statistical analysis A priori power analysis was performed for a paired-samples t test using GPower. Based on data from previous study on conventional MAD (mean difference = 6.0, pooled SD = 8.12), [20] the estimated effect size (Cohen’s d) was 0.74. With a two-sided α of 0.05 and 80% power, a minimum sample size of 18 subjects was required to detect a statistically significant pre-post treatment difference. Normality of continuous data was tested by Shapiro-Wilk test. Paired t-test (for normally distributed variables), Wilcoxon signed-rank test (for non-normally distributed variables), and Chi-squared test or Fisher's exact test (for nominal variables) were used to compare the respiratory parameters and upper airway dimensions before and after iMAD therapy. The intra-rater reliability for the upper airway variables was assessed. Reliability was defined as poor (ICC 0.9). Statistical analyses were performed using IBM® SPSS® Statistics for Macintosh, Version 26 (IBM Corp., Armonk, NY, USA). 3. Results 3.1 Participants The flow-chart of OSA who were recruited for this study is shown in Fig. 5 . In total, 48 patients were recruited consequently. Of those patients, 11 patients are snorers, 2 patients are severe OSA patients, 4 patients lost contact, 4 patients refused the second HSAT. Finally, 27 patients completed the entire study and were included in this trial. The baseline characteristics of the OSA patients are shown in Table 1 . By sub-group analysis, there was no significant between male and female in their BMI, neck circumference, and blood pressure. On average, the advancement is 70.5% of the maximal mandibular protrusion. The patients report high adherence with wear hour per sleep time (100%) and wearing days per week (87±5%). As for the side effects, five patients reported sensitive teeth in the morning, six patients reported TMD symptoms, and one patient reported changed occlusion in the morning. Those side effects could be related with the change of the mandible position of the OSA patients with iMAD in situ. Table 1 Demographic characteristics of the OSA patients Variable (N = 27) Mean Standard deviation (SD) Age (Year) 42.44 7.64 Gender (F/M) 5F/22M Height (cm) 172.30 7.66 Weight (kg) 82.17 18.27 Body mass index (BMI) 27.43 4.61 Neck circumference (cm) 40.69 4.80 Blood pressure (systolic) (Pa) 123.13 15.63 Blood pressure (diastolic) (Pa) 78.87 10.96 3.2 Comparison of the respiratory variables of OSA patients at baseline and with iMAD in situ The respiratory variables without and with iMAD in situ of the OSA patients were shown in Table 2 . There was significant difference in OAI between baseline and with iMAD in situ in OSA patients (P < 0.001). 10 OSA patients end up with OAI < 5/h with iMAD in situ. Responder to iMAD was defined as at least 50% reduction in OAI, and it was estimated that 48.1% of the OSA patients were responders to iMAD. Table 2 The variables of the respiratory variables of OSA patients at baseline and with iMAD in situ Variables At baseline With iMAD in situ Standardized Test Statistic P REI 38.5 (20.25, 43.35) 17.5 (8.8, 37.0) -4.457 < 0.001 OAI 13.7 (10.2, 21.5) 5.8 (2.7, 13.1) -4.373 < 0.001 CAI 2.6 (1.275, 515) 2.3 (0.7, 5.6) 0.28 0.78 minSpO 2 77 (68, 83) 81 (70, 89) 2.094 0.036 Non-normally distributed data are shown as median (25th percentile, 75th percentile); Standardized Test Statistic: Wilcoxon signed-rank test. 3.3 Comparison of the anatomic characteristics of the upper airway of OSA patients at baseline and with iMAD in situ The intra-rater reliability for the upper airway assessment was excellent, with ICC = 1.000 for the CSAmin and ICC = 0.998 to 1.000 for the other outcome variables. The upper airway variables without and with iMAD in situ of the OSA patients were shown in Table 3 . There was significant difference in CSAmin between baseline and with iMAD in situ in OSA patients (P < 0.001). Table 3 The variables of the anatomic characteristics of the upper airway of OSA patients at baseline and with iMAD in situ Variables At baseline With iMAD in situ T/Standardized Test Statistic P Volume(mm 3 ) 13065.65±3960.95 14985.65±4008.71 -3.021 0.006 Length(mm) 75.6±6.71 75.87±6.87 -0.673 0.507 CSAmin (mm 2 ) 36.36 (26.55, 65.34) 65.43 (30.42, 93.87) 3.292 < 0.001 Lateral dimension of CSAmin(mm) 11.62±5.11 13.72±5.95 -3.430 0.002 AP dimension of CSAmin(mm) 4.38±1.94 5.57±2.20 -3.190 0.004 Normally distributed data are shown as mean ± standard deviation (SD); non-normally distributed data are shown as median (25th percentile, 75th percentile); T: paired t-test; Standardized Test Statistic: Wilcoxon signed-rank test. 3.4 Comparison of the aerodynamic characteristics of the upper airway of OSA patients at baseline and with iMAD in situ The aerodynamic characteristics of the upper airway without and with iMAD in situ of the OSA patients were shown in Table 4 . There was significant difference in the aerodynamic characteristics of the upper airway such as maximum velocity of mid-sagittal plane during respiration between baseline and with iMAD in situ in OSA patients (P < 0.001). Table 4 The variables of the aerodynamic characteristics of the upper airway of OSA patients at baseline and with iMAD in situ Variables At baseline With iMAD in situ Standardized Test Statistic P Inspiration Maximum velocity (m/s) 6.71(4.61, 8.56) 5.07(3.79, 6.98) 1.64 0.10 Maximum wall shear stress (Pa) 0.95(0.70, 1.28) 0.92(0.58, 1.27) 0.075 0.94 Minimum wall static pressure (Pa) -15.68(-39.24, -6.74) -8.59(-18.90, -2.57) 2.165 0.03 Airway resistance 2.10(0.86, 2.77) 0.98(0.49, 2.03) 1.381 0.167 Mean velocity (m/s) 1.05(0.74, 1.34) 0.85(0.72, 1.25) 1.12 0.263 Mean wall static pressure (Pa) 6.75(3.82, 17.15) 4.57(2.67, 11.16) 1.195 0.232 Maximum wall static pressure (Pa) 24.31(11.42, 40.75) 18.74(12.26, 31.29) 0.411 0.681 Mean velocity of mid-sagittal plane (m/s) 1.72(1.19, 2.20) 1.39(1.01, 1.95) 1.811 0.07 Maximum velocity of mid-sagittal plane (m/s) 6.17(4.27, 7.54) 4.47(2.98, 6.68) 2.50 0.012 Minimum pressure of mid-sagittal plane (Pa) -7.68(-16.09, -4.35) -6.66(-13.67, -2.18) 1.46 0.145 Mean pressure of mid-sagittal plane (Pa) 7.28(3.52, 12.48) 4.41(2.21, 10.8) 1.20 0.232 Maximum pressure of mid-sagittal plane (Pa) 21.01(7.98, 29.41) 10.83(4.86, 20.03) 1.38 0.167 Expiration Maximum velocity (m/s) 6.37(4.42, 8.86) 4.83(2.81, 7.38) 2.68 0.007 Maximum wall shear stress (Pa) 1.06(0.7, 1.79) 0.65(0.38, 1.15) 2.00 0.045 Minimum wall static pressure (Pa) -14.53(-45.09, -6.93) -10.84(-27.33, -2.42) 1.13 0.257 Airway resistance 1.96(0.62, 2.64) 0.94(0.39, 1.97) 1.83 0.067 Mean velocity (m/s) 1.09(0.95, 1.42) 0.85(0.69, 1.22) 2.46 0.014 Mean wall static pressure (Pa) 7.62(3.22, 17.26) 4.04(1.40, 10.62) 2.42 0.016 Maximum wall static pressure (Pa) 21.45(8.61, 28.17) 11.49(7.45, 21.01) 1.33 0.184 Mean velocity of mid-sagittal plane (m/s) 1.69(1.14, 2.44) 1.34(0.94, 1.64) 2.92 0.004 Maximum velocity of mid-sagittal plane (m/s) 6.15(3.72, 7.78) 4.26(2.65, 5.90) 2.98 0.003 Minimum pressure of mid-sagittal plane (Pa) -8.42(-25.90, -4.08) -4.53(-11.65, -0.80)) 2.199 0.028 Mean pressure of mid-sagittal plane (Pa) 7.26(2.93, 13.99) 4.27(1.47, 9.75) 1.59 0.112 Maximum pressure of mid-sagittal plane (Pa) 19.2(8.28, 27.01) 10.79(3.83, 20.22) 1.81 0.071 Non-normally distributed data are shown as median (25th percentile, 75th percentile). 3.5 Comparison of the overjet and overbite of OSA patients at baseline and with iMAD in situ With iMAD in situ, the change of the overbite for the OSA patients is 7.07±1.71mm; the change of the overjet for the OSA patients is 2.92±2.20mm (Table 5 ). Table 5 The variables of overjet and overbite of OSA patients at baseline and with iMAD in situ Variables At baseline (mean ± SD) With MAD in situ (mean ± SD) Change (mean ± SD) Overbite (mm) 3.69±2.53 -3.24±1.99 7.07±1.71(overbite change) Overjet (mm) 4.10±1.74 1.22±2.17 2.92±2.20 (overjet change) 4. Discussion The aim is to investigate the efficacy of a novel iMAD on respiratory parameters and upper airway dimensions in patients with mild to moderate OSA. The results showed that there was significant decrease in the OAI with iMAD in situ. CBCT images showed that there was significant increase in the CSAmin of the upper airway with iMAD in situ. Besides, there was significant decrease in the maximum velocity of the mid-sagittal plane of the upper airway with iMAD in situ based on CFD analysis. 4.1 Overall iMAD effects Conventional MADs are effective in reducing apnea events and improving airway patency in patients with mild to moderate OSA. However, they are often bulky, visible, and associated with various side effects, which can affect long-term compliance [ 4 ]. In this study, the novel iMAD was designed to overcome these challenges by offering a more compact and aesthetically acceptable alternative [ 21 ]. Our results indicate that iMAD is effective in significantly reducing both REI and OAI. This finding is consistent with previous literature demonstrating the efficacy of conventional MAD in alleviating upper airway obstruction during sleep [ 22 – 24 ]. With iMAD in situ, patients exhibited improved minimum oxygen saturation levels. However, regardless of whether conventional MAD or iMAD is used, although MADs can improve sleep quality in patients with OSA, both responders and non-responders are observed. Using a definition of responders as at least a 50% reduction in the obstructive apnea index (OAI), it was estimated that 48.1% of patients with OSA responded to iMAD, a rate comparable to that reported for conventional MAD therapy [ 25 ].These findings highlight the need for future studies to phenotype non-responders and to optimize treatment for those non-responders to MADs through multidisciplinary, personalized therapeutic strategies. 4.2 Working mechanism of iMAD The mechanism of MADs in treating OSA involves anterior displacement of the mandible, which enlarges the upper airway and reduces its collapsibility during sleep [ 26 ]. In our study, CBCT imaging showed significant increases not only in CSAmin but also in the lateral and anterior-posterior dimensions of the CSAmin. This suggests that iMAD effectively expands the upper airway in both lateral and anterior-posterior directions. Our findings align with previous studies, which reported that MAD could improve airway patency and increase airway dimensions, especially at the oropharyngeal level [ 27 , 28 ]. These findings support the hypothesis that mandibular protrusion contributes to airway patency by enlarging the upper airway [ 29 , 30 ]. CFD analysis provides a vivid visualization of airflow characteristics within the upper airway. Our findings indicated that iMAD can greatly improve the airflow characteristics of OSA patients. Based on the CFD results, the maximum airflow velocity was significantly reduced with iMAD in situ. It is hypothesized that high-velocity airflow may impose excessive shear stress on the airway wall, thereby contributing to mucosal injury and inflammation [ 31 ]. With iMAD in situ, it could significantly reduce the velocity of the airflow, and thereby reduce the damage to the airway wall. 4.3 Vertical distance of the incisors with MADs in situ To further explore the working mechanism of iMAD, the change in the vertical distance between the upper and lower incisors of the patients were evaluated. As iMAD is thinner than conventional MADs, the influence of the iMAD on the vertical distance between incisors is much less than conventional MAD. Our previous study showed that with conventional MAD in situ, the vertical distance between incisors is about 11 mm [ 20 ]. Comparatively, in this study, vertical opening with iMAD in situ (7.07±1.71mm) reduced significantly, which may greatly improve the patient tolerance and compliance. This could be a reason that in this trial, patients reported fewer side effects such as jaw discomfort, tooth sensitivity [ 20 ]. Besides, it is suggested that the increase in the vertical dimension between incisors could also make the mandible rotate posteriorly and place the mandible in a more retrusive position, which is not beneficial for the OSA patients [ 32 ]. Therefore, it is recommended that to reduce side effects, the change vertical dimension of the mandible caused by MAD therapy should be limited as much as possible [ 33 ]. 4.4 Limitations and strengths This study has several limitations. First, the relatively small sample size (n = 27) may limit the generalizability of our findings, although statistically significant differences were observed. Second, the follow-up duration was limited to three months, and longer-term outcomes, including device durability and patient compliance, remain to be assessed. Third, HSAT, while practical, does not capture sleep architecture or arousal indices, which may underestimate treatment effects compared with in-lab PSG. Despite these limitations, this study presents several strengths. It is one of the few studies to combine polysomnographic outcomes with detailed 3D morphological and functional analysis of the upper airway using CBCT. The design and fabrication of iMAD using 3D printing also highlight the potential for customized, cost-effective therapeutic options for OSA patients. 5. Conclusions Within the limitations of this study, we conclude that iMAD has the potential to improve the respiratory parameters and increase upper airway dimensions in patients with mild to moderate OSA, supporting its potential as a comfortable and effective alternative to conventional MADs. Declarations Author Contributions Statement H.C. and X.W. designed the experiment; X.W. and RJ.J. recruited the patients, JW.L. and NY.ZH. collected the data of the patients; RJ.J. analyzed the image, PGS data; H.C. did the statistical analysis; RJ.J. and NY.Zh. prepared the tables and figures. All authors prepared and reviewed the manuscript. The data that support the findings of this study are available from the corresponding author upon request. Funding The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Young Elite Sponsorship Program of Shandong Provincial Medical Association (2024-GJ-0057) Author Contribution H.C. and X.W. designed the experiment; X.W. and RJ.J. recruited the patients, JW.L. and NY.ZH. collected the data of the patients; RJ.J. analyzed the image, PGS data; H.C. did the statistical analysis; RJ.J. and NY.Zh. prepared the tables and figures. All authors prepared and reviewed the manuscript. The data that support the findings of this study are available from the corresponding author upon request. Data Availability The data that support the findings of this study are available from the corresponding author upon request. References Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research (1999) The Report of an American Academy of Sleep Medicine Task Force. Sleep 22(5):667–689 Randerath W, Verbraecken J, de Raaff CAL, Hedner J, Herkenrath S, Hohenhorst W et al (2021) European Respiratory Society guideline on non-CPAP therapies for obstructive sleep apnoea. Eur Respir Rev 30(162). https://doi.org/10.1183/16000617.0200-2021 Johal A, Hamoda MM, Almeida FR, Marklund M, Tallamraju H (2023) The role of oral appliance therapy in obstructive sleep apnoea. Eur Respir Rev 32(168):220257. https://doi.org/10.1183/16000617.0257-2022 Uniken Venema JAM, Rosenmöller B, de Vries N, de Lange J, Aarab G, Lobbezoo F et al (2021) Mandibular advancement device design: A systematic review on outcomes in obstructive sleep apnea treatment. Sleep Med Rev 60:101557. https://doi.org/10.1016/j.smrv.2021.101557 Taha YM, Abu El Sadat SM, Gaber RM, Farid MM (2025) Ability of upper airway metrics to predict obstructive sleep apnea severity: a systematic review. Dentomaxillofac Radiol 54(4):245–255. https://doi.org/10.1093/dmfr/twaf010 Powell NB, Mihaescu M, Mylavarapu G, Weaver EM, Guilleminault C, Gutmark E (2011) Patterns in pharyngeal airflow associated with sleep-disordered breathing. Sleep Med 12(10):966–974. https://doi.org/10.1016/j.sleep.2011.08.004 Xiao Q, Bates A (2025) Quantifying Neuromuscular and Pressure Force Dynamics in Obstructive Sleep Apnea: A Novel Computational Fluid Dynamics Approach Using Airway Wall Acceleration. J Biomech Eng 147(10). https://doi.org/10.1115/1.4069664 Xiao Q, Ignatiuk D, Gunatilaka C, McConnell K, Schuler C, Romaker A et al (2025) Effects of Hypoglossal Nerve Stimulation on Upper Airway Structure and Function Using Moving Wall Computational Fluid Dynamics Simulations: A Pilot Study. J Sleep Res 34(5):e70040. https://doi.org/10.1111/jsr.70040 Van den Bossche K, Op de Beeck S, Dieltjens M, Verbruggen AE, Vroegop AV, Verbraecken JA et al (2022) Multimodal phenotypic labelling using drug-induced sleep endoscopy, awake nasendoscopy and computational fluid dynamics for the prediction of mandibular advancement device treatment outcome: a prospective study. J Sleep Res 31(6):e13673. https://doi.org/10.1111/jsr.13673 Tsuiki S, Lowe AA, Almeida FR, Kawahata N, Fleetham JA (2004) Effects of mandibular advancement on airway curvature and obstructive sleep apnoea severity. Eur Respir J 23(2):263–268. https://doi.org/10.1183/09031936.04.00094304 de Ruiter MHT, Aarab G, de Vries N, Lobbezoo F, de Lange J (2020) A stepwise titration protocol for oral appliance therapy in positional obstructive sleep apnea patients: proof of concept. Sleep Breath 24(3):1229–1236. https://doi.org/10.1007/s11325-020-02045-w Chen H, Aarab G, Parsa A, de Lange J, van der Stelt PF, Lobbezoo F (2016) Reliability of three-dimensional measurements of the upper airway on cone beam computed tomography images. Oral Surg Oral Med Oral Pathol Oral Radiol 122(1):104–110. https://doi.org/10.1016/j.oooo.2016.04.005 Shi X, Chen H, Lobbezoo F, de Lange J, van der Stelt P, Berkhout E et al (2023) Comparison of the upper airway morphology between Dutch and Chinese adults with obstructive sleep apnea. Sleep Breath 27(6):2223–2230. https://doi.org/10.1007/s11325-023-02834-z Weissheimer A, Menezes LM, Sameshima GT, Enciso R, Pham J, Grauer D (2012) Imaging software accuracy for 3-dimensional analysis of the upper airway. Am J Orthod Dentofac Orthop 142(6):801–813. https://doi.org/10.1016/j.ajodo.2012.07.015 Chen H, Aarab G, de Ruiter MH, de Lange J, Lobbezoo F, van der Stelt PF (2016) Three-dimensional imaging of the upper airway anatomy in obstructive sleep apnea: a systematic review. Sleep Med 21:19–27. https://doi.org/10.1016/j.sleep.2016.01.022 Chen H, Li Y, Reiber JH, de Lange J, Tu S, van der Stelt P et al (2018) Analyses of aerodynamic characteristics of the oropharynx applying CBCT: obstructive sleep apnea patients versus control subjects. Dentomaxillofac Radiol 47(2):20170238. https://doi.org/10.1259/dmfr.20170238 Chen H, Elham E, Li Y, Ge S, Schmittbuhl M, Lavigne G et al (2022) Comparison of anatomic and aerodynamic characteristics of the upper airway among edentulous mild, moderate, and severe obstructive sleep apnea in older adults. J Clin Sleep Med 18(3):759–768. https://doi.org/10.5664/jcsm.9716 Mylavarapu G, Murugappan S, Mihaescu M, Kalra M, Khosla S, Gutmark E (2009) Validation of computational fluid dynamics methodology used for human upper airway flow simulations. J Biomech 42(10):1553–1559. https://doi.org/10.1016/j.jbiomech.2009.03.035 Zhao M, Barber T, Cistulli P, Sutherland K, Rosengarten G (2013) Computational fluid dynamics for the assessment of upper airway response to oral appliance treatment in obstructive sleep apnea. J Biomech 46(1):142–150. https://doi.org/10.1016/j.jbiomech.2012.10.033 Shi X, Lobbezoo F, Chen H, Rosenmöller B, Berkhout E, de Lange J et al (2023) Comparisons of the effects of two types of titratable mandibular advancement devices on respiratory parameters and upper airway dimensions in patients with obstructive sleep apnea: a randomized controlled trial. Clin Oral Investig 27(5):2013–2025. https://doi.org/10.1007/s00784-023-04945-z Putrino A, Barbato E, Galluccio G (2021) Clear Aligners: Between Evolution and Efficiency-A Scoping Review. Int J Environ Res Public Health 18(6). https://doi.org/10.3390/ijerph18062870 Gurgel M, Cevidanes L, Costa F, Pereira R, Cunali P, Bittencourt L et al (2023) Three-dimensional comparison between the effects of mandibular advancement device and maxillomandibular advancement surgery on upper airway. BMC Oral Health 23(1):436. https://doi.org/10.1186/s12903-023-03125-5 Verbraecken J, Dieltjens M, Op de Beeck S, Vroegop A, Braem M, Vanderveken O et al (2022) Non-CPAP therapy for obstructive sleep apnoea. Breathe (Sheff) 18(3):220164. https://doi.org/10.1183/20734735.0164-2022 Verma A, Jain S (2023) Efficacy of Mandibular Advancement Device in the Treatment of Obstructive Sleep Apnoea by Evaluating Upper Airway Space Volume Using CBCT. J Coll Physicians Surg Pak 33(10):1194–1197. https://doi.org/10.29271/jcpsp.2023.10.1194 Shi X, Lobbezoo F, Chen H, Rosenmöller B, Berkhout E, de Lange J et al (2023) Effects of mandibular advancement devices on upper airway dimensions in obstructive sleep apnea: responders versus non-responders. Clin Oral Investig 27(9):5649–5660. https://doi.org/10.1007/s00784-023-05186-w Pahkala R, Seppä J, Myllykangas R, Tervaniemi J, Vartiainen VM, Suominen AL et al (2020) The impact of oral appliance therapy with moderate mandibular advancement on obstructive sleep apnea and upper airway volume. Sleep Breath 24(3):865–873. https://doi.org/10.1007/s11325-019-01914-3 Marco-Pitarch R, García-Selva M, Plaza-Espín A, Puertas-Cuesta J, Agustín-Panadero R, Fernández-Julián E et al (2021) Dimensional analysis of the upper airway in obstructive sleep apnoea syndrome patients treated with mandibular advancement device: A bi- and three-dimensional evaluation. J Oral Rehabil 48(8):927–936. https://doi.org/10.1111/joor.13176 Shete CS, Bhad WA (2017) Three-dimensional upper airway changes with mandibular advancement device in patients with obstructive sleep apnea. Am J Orthod Dentofac Orthop 151(5):941–948. https://doi.org/10.1016/j.ajodo.2016.09.025 Camañes-Gonzalvo S, Marco-Pitarch R, Plaza-Espín A, Puertas-Cuesta J, Agustín-Panadero R, Fons-Font A et al (2021) Correlation between Polysomnographic Parameters and Tridimensional Changes in the Upper Airway of Obstructive Sleep Apnea Patients Treated with Mandibular Advancement Devices. J Clin Med 10(22). https://doi.org/10.3390/jcm10225255 Pereira A, Gurgel M, Pereira R, Fabbro CD, de Barros Silva P, Costa F et al (2024) Evaluation of condylar and mandibular movements on the upper airway during the use of mandibular advancement device for obstructive sleep apnea treatment. Clin Oral Investig 28(2):122. https://doi.org/10.1007/s00784-024-05513-9 Chen H, Aarab G, Liu JW, Yu YL, Guo J, van der Stelt PF et al (2017) A novel imaging technique to evaluate airflow characteristics in the upper airway of an obstructive sleep apnea patient. Clin Case Rep 5(7):1084–1087. https://doi.org/10.1002/ccr3.716 Mayoral P, Lagravere MO, Miguez-Contreras M, Garcia M (2019) Antero-posterior mandibular position at different vertical levels for mandibular advancing device design. BMC Oral Health 19(1):85. https://doi.org/https://dx.doi.org/10.1186/s12903-019-0783-8 Barbero M, Flores-Mir C, Blanco JC, Nuño VC, Casellas JB, Girado JLC et al (2020) Tridimensional upper airway assessment in male patients with OSA using oral advancement devices modifying their vertical dimension. J Clin Sleep Med 16(10):1721–1729. https://doi.org/10.5664/jcsm.8666 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8989379","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":602598761,"identity":"c7a385b9-00f9-4c72-b016-3875fe280519","order_by":0,"name":"Xi Wang","email":"","orcid":"","institution":"Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Xi","middleName":"","lastName":"Wang","suffix":""},{"id":602598762,"identity":"430ca6b4-df60-45aa-b4cc-b0b90a8b99f7","order_by":1,"name":"Ruijie Ju","email":"","orcid":"","institution":"Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Ruijie","middleName":"","lastName":"Ju","suffix":""},{"id":602598763,"identity":"6c7ae8c5-8e00-49c8-84bc-12e0d62686fb","order_by":2,"name":"Jianwei Liu","email":"","orcid":"","institution":"Jinan Stomatologic Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jianwei","middleName":"","lastName":"Liu","suffix":""},{"id":602598764,"identity":"441bc443-f15b-4f1a-83b3-9e23a78e3be5","order_by":3,"name":"Naiyuan Zheng","email":"","orcid":"","institution":"Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Naiyuan","middleName":"","lastName":"Zheng","suffix":""},{"id":602598765,"identity":"425cbf38-0a06-4475-aa4c-c4779e54ddb8","order_by":4,"name":"Kaan Orhan","email":"","orcid":"","institution":"Ankara University","correspondingAuthor":false,"prefix":"","firstName":"Kaan","middleName":"","lastName":"Orhan","suffix":""},{"id":602598766,"identity":"fd0080aa-1f19-4b3b-9052-f53b61d52cb6","order_by":5,"name":"Xieqi Shi","email":"","orcid":"","institution":"University of Bergen","correspondingAuthor":false,"prefix":"","firstName":"Xieqi","middleName":"","lastName":"Shi","suffix":""},{"id":602598767,"identity":"3ac1d33e-4668-45c8-a853-cdf953128c98","order_by":6,"name":"Nelly huynh","email":"","orcid":"","institution":"Universite de Montreal","correspondingAuthor":false,"prefix":"","firstName":"Nelly","middleName":"","lastName":"huynh","suffix":""},{"id":602598768,"identity":"02f9d91e-4758-4dca-b07f-8eb452f79d80","order_by":7,"name":"Shaohua Ge","email":"","orcid":"","institution":"Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Shaohua","middleName":"","lastName":"Ge","suffix":""},{"id":602598769,"identity":"86bfe7f9-2dfb-4b3f-9671-0ff4d74ee672","order_by":8,"name":"Hui Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuklEQVRIiWNgGAWjYBACAwYGNiBlw8BwAEjxkKAljXQth0nQYs7A/OzBxx3n7fluJDA+eNvGIG9OSItlA5u54cwztxNn3khgNpzbxmC4s4GQww7wsEnztt1OMLiRAGIwJBgcIEbL37Zz9kAt7L+J18LYdoBxA9AWZuK0HGYzk+xtS06ceeZhs+SccxKGGwhqOd78TOJnm5093/Hkgx/elNnIE7SFgRnOYmwAEhKE1I+CUTAKRsEoIAYAAGScPcECjkNtAAAAAElFTkSuQmCC","orcid":"","institution":"Shandong University","correspondingAuthor":true,"prefix":"","firstName":"Hui","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2026-02-27 14:54:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8989379/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8989379/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104781305,"identity":"18ab16a3-8e3e-407d-ad6b-949487cbdf30","added_by":"auto","created_at":"2026-03-17 07:55:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":465230,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA. \u003c/strong\u003eiMAD and\u003cstrong\u003e \u003c/strong\u003ePatient with iMAD in situ; \u003cstrong\u003eB.\u003c/strong\u003e Normal occlusion; \u003cstrong\u003eC.\u003c/strong\u003e Protrusion position.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8989379/v1/026f49ed3014c05a8c1ac84d.png"},{"id":104781455,"identity":"3e86fad6-d83f-4c40-9dd0-061fc773e338","added_by":"auto","created_at":"2026-03-17 07:55:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":340878,"visible":true,"origin":"","legend":"\u003cp\u003eMeasurements of the upper airway dimensions using cone beam computed tomography (CBCT) imaging. \u003cstrong\u003eA. \u003c/strong\u003eThe boundaries of the upper airway from the hard palate (a) to the anterior-inferior point of the fourth cervical vertebra (b) in the sagittal plane. \u003cstrong\u003eB.\u003c/strong\u003e The location of the minimal cross-sectional area of the upper airway (CSAmin) in the axial plane. \u003cstrong\u003eC.\u003c/strong\u003e The measurements of the anterior-posterior dimension (A-P) and lateral dimension (La) of the CSAmin.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8989379/v1/31bbafb168ba668d7ad388f2.png"},{"id":104781502,"identity":"ec00f99c-bded-4308-8def-cd3732ee555d","added_by":"auto","created_at":"2026-03-17 07:55:48","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":130468,"visible":true,"origin":"","legend":"\u003cp\u003eMeasurements of mandibular vertical opening using CBCT imaging. \u003cstrong\u003eA.\u003c/strong\u003eMeasurement of overbite at baseline (4.7mm in this example). \u003cstrong\u003eB. \u003c/strong\u003eMeasurement of the vertical distance between the tip of upper and lower incisors with iMAD \u003cem\u003ein situ \u003c/em\u003e(3.4mm in this example). In this case, the vertical opening with iMAD \u003cem\u003ein situ\u003c/em\u003eis 8.1mm (viz., sum of the 4.7mm and 3.4mm)\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8989379/v1/b27e868fbd886826bb25d3e1.png"},{"id":104546844,"identity":"080aca20-905c-428f-b301-c06d56eb0bc2","added_by":"auto","created_at":"2026-03-13 07:29:55","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":135259,"visible":true,"origin":"","legend":"\u003cp\u003eMeasurements of change of overjet with and without iMAD using CBCT imaging. \u003cstrong\u003eA.\u003c/strong\u003e Measurement of overjet at baseline (5.7mm in this example). \u003cstrong\u003eB. \u003c/strong\u003eMeasurement of overjet with iMAD \u003cem\u003ein situ \u003c/em\u003e0.3mm in this example). In this case, the mandibular advancement with iMAD \u003cem\u003ein situ\u003c/em\u003e is 5.4mm (viz., the difference between 5.7mm and 0.3mm)\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8989379/v1/98819912015031a1099ca528.png"},{"id":104546842,"identity":"93025496-b9f1-48b6-ad01-91afc8d118f9","added_by":"auto","created_at":"2026-03-13 07:29:55","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":62420,"visible":true,"origin":"","legend":"\u003cp\u003eThe flow-chart of patients recruited. OSA: obstructive sleep apnea; iMAD: invisible mandibular advancement devices.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-8989379/v1/5d369bef2b299d36573afbcb.png"},{"id":108944455,"identity":"a9a13eda-2f12-422e-9958-498092f1a0f7","added_by":"auto","created_at":"2026-05-11 05:59:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1745049,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8989379/v1/0fd08a7e-5dc2-4646-8155-df8a445c4ea4.pdf"},{"id":104546848,"identity":"fc3c0ae0-6e70-4484-89f3-3f9978602e1b","added_by":"auto","created_at":"2026-03-13 07:29:56","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":303569,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix.docx","url":"https://assets-eu.researchsquare.com/files/rs-8989379/v1/e1d02ee63e67a9745532d25e.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy of a novel invisible mandibular advancement device in patients with mild to moderate obstructive sleep apnea: a preliminary study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eObstructive sleep apnea (OSA) is characterized by recurrent obstructions of the upper airway, often resulting in oxygen desaturations and arousals from sleep [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The gold standard for the diagnosis of OSA is full-night polysomnography (PSG). Based on PSG recording, OSA severity for adults is classified as mild (5\u0026thinsp;\u0026le;\u0026thinsp;apnea-hypopnea index (AHI)\u0026thinsp;\u0026lt;\u0026thinsp;15 events/hour), moderate (15\u0026thinsp;\u0026le;\u0026thinsp;AHI\u0026thinsp;\u0026le;\u0026thinsp;30 events/hour), or severe (AHI\u0026thinsp;\u0026gt;\u0026thinsp;30 events/hour) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMandibular advancement device (MAD) therapy is recommended as a primary treatment option in patients with mild and moderate OSA [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. There is a large variety of commercially available customized MADs. MADs can be broadly classified into customized (titratable/nontitratable) and non-customized (titratable/nontitratable) devices [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Most currently available MADs are bulky and externally visible, which may compromise comfort, speech, and aesthetics, thereby limiting patient acceptance and long-term compliance [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. To address limitations associated with conventional MADs, we developed a novel invisible mandibular advancement device (iMAD) characterised by a transparent, less bulky design that minimises intraoral volume and improves wearing comfort. By leveraging three-dimensional (3D) printing technology, the iMAD can be manufactured at a substantially lower cost than conventional MADs, thereby reducing the financial burden for patients. Owing to its reduced bulk and improved affordability, the iMAD is expected to enhance patient compliance. Therefore, before broad clinical application, it is essential to investigate the clinical feasibility and therapeutic efficacy of this newly introduced iMAD. The primary aim is to investigate the effect of iMAD on the sleep variables of the OSA patients.\u003c/p\u003e \u003cp\u003eOver the last few decades, cone beam computed tomography (CBCT) has been used to analyze the volumetric dimensions of the upper airway in patients with OSA [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Furthermore, computational fluid dynamics (CFD) has been used to simulate airflow within the upper airway in OSA research [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. CFD enables functional assessment of aerodynamic characteristics such as airflow velocity, thereby transforming static airway morphology into dynamic measures of respiratory function [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Previous studies suggested that the working mechanism of MAD is related to the improvement of the upper airway [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In this study, we will also focus on the upper airway and investigate the working mechanism of iMAD based on CBCT images and CFD analysis. The secondary aim is to investigate the effect of iMAD on the upper airway dimension and airflow characteristics of the OSA patients.\u003c/p\u003e"},{"header":"2. Material and methods","content":"\u003cp\u003e\u003cstrong\u003e2.1 Overview\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was a prospective pilot study, in which the effects of a novel iMAD on respiratory parameters and upper airway were assessed. The Medical Research Ethics Committee of School of stomatology, Shandong University approved this study (NO.20240306). The study was registered at chictr.org.cn (ChiCTR2400092896). Written informed consent was obtained from all participants.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2 Participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients that fit the following inclusion/exclusion criteria were recruited from Department of Orthodontics, School of stomatology, Shandong University, China. The inclusion criteria were as follows: (1) age ≥ 18 years; (2) diagnosed with symptomatic mild or moderate OSA. The exclusion criteria were as follows: (1) medication use related to sleeping disorders; (2) evidence of respiratory and/or sleep disorders other than OSA (e.g., central sleep apnea syndrome); (3) systemic disorders (based on medical history and clinical examination, e.g., rheumatoid arthritis); (4) medical history of known daytime fatigue or severe sleep disturbance (e.g., insomnia, PLMS, narcolepsy); (5) known medical history of mental retardation, memory impairment, or psychiatric disorders; (6) reversible morphological upper airway abnormalities (viz., indication for upper airway surgery); (7) syndromes with craniofacial abnormalities (e.g., Pierre Robin sequence and Down syndrome).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3 Invisible\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eMAD (iMAD)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA novel iMAD (Smartee, Shanghai, China) was used in this study (\u003cstrong\u003eFig.1\u003c/strong\u003e). After adequate assessment of the central relation and maximum protrusion/retrusion using the George Gauge system (Great Lakes Orthodontics, Tonawanda, NY), iMADs were initially set at 75% of the maximal mandibular protrusion.\u0026nbsp;Necessary titration adjustments were performed at follow-up visits at 4, 8, and 12 weeks, based on the patients’ perceived treatment outcomes and the self-reported side effects [11].\u003c/p\u003e\n\u003cp\u003eThe self-reported side effects were recorded at each clinical visit, including the following: 1. sensitive teeth in the morning; 2. temporomandibular joint complaints; 3. changed occlusion in the morning.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt each consecutive visit, the iMADs were evaluated and advanced 15% if subjective improvement (e.g., perceived reduction of snoring or excessive daytime sleepiness) of OSA was not reached. On the other hand, if side effects were not acceptable for the patient (e.g., tooth pain or signs of temporomandibular disorders), the advancement was adjusted backwards 15%. No adjustments were made when the patient reported sufficient efficacy without side effects. For every adjustment, new iMAD was made by 3D printing technique using photopolymer 3D printer (Ruifeng Technique company, Shenzhen, China) and dental pressure thermoforming machine (Scheu, Germany).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter 3 months, adherence information was obtained via an online survey using the following measures: (1) the proportion of total sleep time during which the iMAD was used and (2) the proportion of days per week with iMAD use.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.4 Home sleep apnea test (HSAT)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants included in this study underwent an overnight level 3 PSG recording (Alice 6, Phillips Respironics, USA) for the diagnosis of OSA. Every patient underwent a baseline home sleep apnea test (HSAT) and a 3-month follow-up HSAT with iMAD \u003cem\u003ein situ.\u003c/em\u003e HSAT included the following variables: pulse oximetry, body position, neck microphone, nasal cannula pressure transducer, and inductive plethysmography by means of thoracic band. The respiratory events index (REI) is the number of respiratory events per hour. The obstructive apnea index (OAI) is the number of obstructive apneas per hour. The central apnea index (CAI) is the number of central apneas per hour. Lowest Desat is the lowest blood oxygen level that lasted at least 2 seconds.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.5 Cone beam computed tomography (CBCT)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe CBCT datasets of Chinese patients were obtained using NewTom 5G CBCT systems (QR systems, Verona, Italy), according to an examination protocol developed in a previous study [12].\u003c/p\u003e\n\u003cp\u003eAll patients underwent two CBCT scans (NewTom 5G, QR systems, Italy) at the Department of Oral Radiology, School of Dentistry, Shandong University: a baseline scan and a follow-up scan with the iMAD in situ (in the same protrusion position as during the follow-up PSG recording). The exposure settings were 110 kV, 4 mA, 0.3 mm voxel size, 3.6-s exposure time (pulsed radiation), and 18-36-s scanning time, depending on the size of the patient [13]. At baseline, patients were instructed to maintain maximum intercuspation,\u0026nbsp;while at the follow-up scan, patients were instructed to relax their masticatory muscles with the iMAD in situ. During CBCT acquisition, patients were in supine position, and their head were positioned with the Frankfort horizontal plane, defined by the porion (Po) and orbitale (Or), perpendicular to the floor.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo standardized the measurements, the acquired CBCT images were further reconstructed by adjusting the palatal plane (the plane crossing anterior nasal spine (ANS)-posterior nasal spine (PNS)) being parallel to the global horizontal plane in the sagittal view, and perpendicular to the global horizontal plane in the axial view [14]. For further analysis, the images were exported and stored in DICOM files. All images were presented to the observers in a room with dimmed light.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.6 Minimum cross-sectional area of the upper airway\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUsing Amira\u003csup\u003e®\u0026nbsp;\u003c/sup\u003esoftware (v4.1, Visage Imaging Inc., Carlsbad, CA, USA), upper airway segmentation was performed by defining the superior and inferior boundaries of the upper airway. The superior boundary of the upper airway was the palatal plane, and the inferior boundary was the horizontal plane across the anterior-inferior point of the fourth cervical vertebra (parallel to the palatal plane) (\u003cstrong\u003eFig. 2A\u003c/strong\u003e). After upper airway segmentation, the upper airway volume (V) and the cross-sectional area (CSA) of each slice were calculated automatically in the software. Based on the results of CSA, the minimum CSA(CSAmin) could be identified and located (\u003cstrong\u003eFig. 2B\u003c/strong\u003e). On the cross-sectional slice of CSAmin, the anterior-posterior dimension (A-P) and lateral dimension (La) of CSAmin were measured by the observer, using the linear measuring tool integrated in the software (\u003cstrong\u003eFig. 2C\u003c/strong\u003e). The length of upper airway (L) was calculated by multiplying the slice numbers of the upper airway with 0.3mm (the thickness of every slice) [12]. As a small CSAmin is the most relevant anatomical characteristic of the upper airway related to the pathogenesis of OSA [15], the CSAmin was selected as the primary outcome variable of upper airway dimensions. All of the upper airway variables were measured by an experienced examiner. To test the intra-rater reliability of the assessment of the upper airway, 10 CBCT scans were randomly selected and re-measured after a 1-month interval of the original measurements.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.7 Computational fluid dynamics (CFD) analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe procedure of CFD analysis was described in detail in our previous studies [16, 17]. The upper airway was segmented based on the aforementioned superior and inferior boundary (Appendix 1). By surface triangulation, the segmented models were subsequently converted into 3D standard tessellation language (STL) models. The segmented STL models of the upper airway were exported into ANSYS ICEM CFD 17.0 (ANSYS, Inc., Canonsburg, Pennsylvania) for CFD analysis. The upper boundary was set at the coronal plane through PNS point, and the lower boundary was set at the horizontal plane across the base of the fourth cervical vertebra. The boundary condition consisted of axial velocity at the inlet plane, and no-slip boundary conditions for the upper airway wall. An inlet volume flow rate of 166 mL/s (10 L/min) was used in the flow simulation, as per previous studies [18, 19].\u003c/p\u003e\n\u003cp\u003eThe aerodynamic characteristics, e.g., velocity, wall shear stress, and wall static pressure, were calculated in the upper airway model of each OSA patient during both inspiration and expiration. The inspiration phase was simulated by setting the inlet plane at the coronal plane across the PNS point and the outlet plane at the base of epiglottis. Conversely, the expiration phase was simulated by setting the inlet plane at the base of epiglottis and the outlet plane at the coronal plane across the PNS point [16].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBased on CFD calculations, airway resistance R was determined using the following formulation: R=∆P/Q, where ∆P is the total pressure drop between the inlet and outlet boundaries of the upper airway; Q is the volume flow rate within the upper airway. The aerodynamic characteristics, viz., velocity and static pressure of the mid-sagittal plane of the upper airway model were also calculated during both inspiration and expiration [16].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.8 Overbite and overjet analysis\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBased on baseline and follow-up CBCT images, the vertical opening with the iMAD\u003cem\u003e\u0026nbsp;in situ\u003c/em\u003e was determined in two steps. Firstly, the overbite was measured based on baseline CBCT images (\u003cstrong\u003eFig. 3A\u003c/strong\u003e). Secondly, the vertical distance between the tip of upper and lower incisors with the iMAD \u003cem\u003ein situ\u003c/em\u003e was measured based on follow-up CBCT images (\u003cstrong\u003eFig. 3B\u003c/strong\u003e). All vertical distances were measured as the perpendicular distance to palatal plane. By adding these two values, the mandibular vertical opening with iMAD\u003cem\u003e\u0026nbsp;in situ\u0026nbsp;\u003c/em\u003ewas determined.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.8 Statistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA priori power analysis was performed for a paired-samples t test using GPower. Based on data from previous study on conventional MAD (mean difference = 6.0, pooled SD = 8.12), [20]\u0026nbsp; the estimated effect size (Cohen’s d) was 0.74. With a two-sided α of 0.05 and 80% power, a minimum sample size of 18 subjects was required to detect a statistically significant pre-post treatment difference.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNormality of continuous data was tested by Shapiro-Wilk test. Paired t-test (for normally distributed variables), Wilcoxon signed-rank test (for non-normally distributed variables), and Chi-squared test or Fisher's exact test (for nominal variables) were used to compare the respiratory parameters and upper airway dimensions before and after iMAD therapy.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe intra-rater reliability for the upper airway variables was assessed. Reliability was defined as poor (ICC \u0026lt; 0.5), moderate (ICC = 0.5-0.75), good (ICC = 0.75-0.9), or excellent (ICC \u0026gt; 0.9). Statistical analyses were performed using IBM® SPSS® Statistics for Macintosh, Version 26 (IBM Corp., Armonk, NY, USA).\u0026nbsp;\u003c/p\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Participants\u003c/h2\u003e \u003cp\u003eThe flow-chart of OSA who were recruited for this study is shown in \u003cb\u003eFig.\u0026nbsp;5\u003c/b\u003e. In total, 48 patients were recruited consequently. Of those patients, 11 patients are snorers, 2 patients are severe OSA patients, 4 patients lost contact, 4 patients refused the second HSAT. Finally, 27 patients completed the entire study and were included in this trial. The baseline characteristics of the OSA patients are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. By sub-group analysis, there was no significant between male and female in their BMI, neck circumference, and blood pressure.\u003c/p\u003e \u003cp\u003eOn average, the advancement is 70.5% of the maximal mandibular protrusion. The patients report high adherence with wear hour per sleep time (100%) and wearing days per week (87\u0026plusmn;5%). As for the side effects, five patients reported sensitive teeth in the morning, six patients reported TMD symptoms, and one patient reported changed occlusion in the morning. Those side effects could be related with the change of the mandible position of the OSA patients with iMAD in situ.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic characteristics of the OSA patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable (N\u0026thinsp;=\u0026thinsp;27)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStandard deviation (SD)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (Year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (F/M)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5F/22M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e172.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7.66\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18.27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index (BMI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeck circumference (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood pressure (systolic) (Pa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e123.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood pressure (diastolic) (Pa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Comparison of the respiratory variables of OSA patients at baseline and with iMAD in situ\u003c/h2\u003e \u003cp\u003eThe respiratory variables without and with iMAD in situ of the OSA patients were shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. There was significant difference in OAI between baseline and with iMAD in situ in OSA patients (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). 10 OSA patients end up with OAI\u0026thinsp;\u0026lt;\u0026thinsp;5/h with iMAD in situ. Responder to iMAD was defined as at least 50% reduction in OAI, and it was estimated that 48.1% of the OSA patients were responders to iMAD.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe variables of the respiratory variables of OSA patients at baseline and with iMAD in situ\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAt baseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWith iMAD in situ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStandardized Test Statistic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eREI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.5 (20.25, 43.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.5 (8.8, 37.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-4.457\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOAI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.7 (10.2, 21.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.8 (2.7, 13.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-4.373\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.6 (1.275, 515)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.3 (0.7, 5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eminSpO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77 (68, 83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81 (70, 89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.094\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNon-normally distributed data are shown as median (25th percentile, 75th percentile); Standardized Test Statistic: Wilcoxon signed-rank test.\u003c/p\u003e \u003cp\u003e \u003cb\u003e3.3 Comparison of the anatomic characteristics of the upper airway of OSA patients at baseline and with iMAD in situ\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe intra-rater reliability for the upper airway assessment was excellent, with ICC\u0026thinsp;=\u0026thinsp;1.000 for the CSAmin and ICC\u0026thinsp;=\u0026thinsp;0.998 to 1.000 for the other outcome variables. The upper airway variables without and with iMAD in situ of the OSA patients were shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. There was significant difference in CSAmin between baseline and with iMAD in situ in OSA patients (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe variables of the anatomic characteristics of the upper airway of OSA patients at baseline and with iMAD in situ\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAt baseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWith iMAD in situ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT/Standardized Test Statistic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume(mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13065.65\u0026plusmn;3960.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14985.65\u0026plusmn;4008.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-3.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75.6\u0026plusmn;6.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75.87\u0026plusmn;6.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.673\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.507\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCSAmin (mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.36 (26.55, 65.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65.43 (30.42, 93.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.292\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLateral dimension of CSAmin(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.62\u0026plusmn;5.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.72\u0026plusmn;5.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-3.430\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAP dimension of CSAmin(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.38\u0026plusmn;1.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.57\u0026plusmn;2.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-3.190\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNormally distributed data are shown as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD); non-normally distributed data are shown as median (25th percentile, 75th percentile); T: paired t-test; Standardized Test Statistic: Wilcoxon signed-rank test.\u003c/p\u003e \u003cp\u003e \u003cb\u003e3.4 Comparison of the aerodynamic characteristics of the upper airway of OSA patients at baseline and with iMAD in situ\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe aerodynamic characteristics of the upper airway without and with iMAD in situ of the OSA patients were shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. There was significant difference in the aerodynamic characteristics of the upper airway such as maximum velocity of mid-sagittal plane during respiration between baseline and with iMAD in situ in OSA patients (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe variables of the aerodynamic characteristics of the upper airway of OSA patients at baseline and with iMAD in situ\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAt baseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWith iMAD in situ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStandardized Test Statistic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInspiration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum velocity (m/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.71(4.61, 8.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.07(3.79, 6.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum wall shear stress (Pa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.95(0.70, 1.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.92(0.58, 1.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.075\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinimum wall static pressure (Pa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-15.68(-39.24, -6.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-8.59(-18.90, -2.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAirway resistance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.10(0.86, 2.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.98(0.49, 2.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.381\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.167\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean velocity (m/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.05(0.74, 1.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.85(0.72, 1.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.263\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean wall static pressure (Pa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.75(3.82, 17.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.57(2.67, 11.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.195\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum wall static pressure (Pa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24.31(11.42, 40.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18.74(12.26, 31.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.411\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.681\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean velocity of mid-sagittal plane (m/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.72(1.19, 2.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.39(1.01, 1.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.811\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum velocity of mid-sagittal plane (m/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.17(4.27, 7.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.47(2.98, 6.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinimum pressure of mid-sagittal plane (Pa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-7.68(-16.09, -4.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-6.66(-13.67, -2.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.145\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean pressure of mid-sagittal plane (Pa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.28(3.52, 12.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.41(2.21, 10.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum pressure of mid-sagittal plane (Pa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21.01(7.98, 29.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.83(4.86, 20.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.167\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExpiration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum velocity (m/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.37(4.42, 8.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.83(2.81, 7.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum wall shear stress (Pa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.06(0.7, 1.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.65(0.38, 1.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinimum wall static pressure (Pa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-14.53(-45.09, -6.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-10.84(-27.33, -2.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.257\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAirway resistance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.96(0.62, 2.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.94(0.39, 1.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.067\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean velocity (m/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.09(0.95, 1.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.85(0.69, 1.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean wall static pressure (Pa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.62(3.22, 17.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.04(1.40, 10.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum wall static pressure (Pa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21.45(8.61, 28.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11.49(7.45, 21.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.184\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean velocity of mid-sagittal plane (m/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.69(1.14, 2.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.34(0.94, 1.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum velocity of mid-sagittal plane (m/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.15(3.72, 7.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.26(2.65, 5.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinimum pressure of mid-sagittal plane (Pa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-8.42(-25.90, -4.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-4.53(-11.65, -0.80))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.199\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.028\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean pressure of mid-sagittal plane (Pa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.26(2.93, 13.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.27(1.47, 9.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.112\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum pressure of mid-sagittal plane (Pa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19.2(8.28, 27.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.79(3.83, 20.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.071\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNon-normally distributed data are shown as median (25th percentile, 75th percentile).\u003c/p\u003e \u003cp\u003e \u003cb\u003e3.5 Comparison of the overjet and overbite of OSA patients at baseline and with iMAD in situ\u003c/b\u003e \u003c/p\u003e \u003cp\u003eWith iMAD in situ, the change of the overbite for the OSA patients is 7.07\u0026plusmn;1.71mm; the change of the overjet for the OSA patients is 2.92\u0026plusmn;2.20mm (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe variables of overjet and overbite of OSA patients at baseline and with iMAD in situ\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAt baseline\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWith MAD in situ\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChange\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverbite (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.69\u0026plusmn;2.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e-3.24\u0026plusmn;1.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.07\u0026plusmn;1.71(overbite change)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverjet (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e4.10\u0026plusmn;1.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.22\u0026plusmn;2.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.92\u0026plusmn;2.20 (overjet change)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe aim is to investigate the efficacy of a novel iMAD on respiratory parameters and upper airway dimensions in patients with mild to moderate OSA. The results showed that there was significant decrease in the OAI with iMAD in situ. CBCT images showed that there was significant increase in the CSAmin of the upper airway with iMAD in situ. Besides, there was significant decrease in the maximum velocity of the mid-sagittal plane of the upper airway with iMAD in situ based on CFD analysis.\u003c/p\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e4.1 Overall iMAD effects\u003c/h2\u003e \u003cp\u003eConventional MADs are effective in reducing apnea events and improving airway patency in patients with mild to moderate OSA. However, they are often bulky, visible, and associated with various side effects, which can affect long-term compliance [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In this study, the novel iMAD was designed to overcome these challenges by offering a more compact and aesthetically acceptable alternative [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Our results indicate that iMAD is effective in significantly reducing both REI and OAI. This finding is consistent with previous literature demonstrating the efficacy of conventional MAD in alleviating upper airway obstruction during sleep [\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. With iMAD in situ, patients exhibited improved minimum oxygen saturation levels. However, regardless of whether conventional MAD or iMAD is used, although MADs can improve sleep quality in patients with OSA, both responders and non-responders are observed. Using a definition of responders as at least a 50% reduction in the obstructive apnea index (OAI), it was estimated that 48.1% of patients with OSA responded to iMAD, a rate comparable to that reported for conventional MAD therapy [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].These findings highlight the need for future studies to phenotype non-responders and to optimize treatment for those non-responders to MADs through multidisciplinary, personalized therapeutic strategies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e4.2 Working mechanism of iMAD\u003c/h2\u003e \u003cp\u003eThe mechanism of MADs in treating OSA involves anterior displacement of the mandible, which enlarges the upper airway and reduces its collapsibility during sleep [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In our study, CBCT imaging showed significant increases not only in CSAmin but also in the lateral and anterior-posterior dimensions of the CSAmin. This suggests that iMAD effectively expands the upper airway in both lateral and anterior-posterior directions. Our findings align with previous studies, which reported that MAD could improve airway patency and increase airway dimensions, especially at the oropharyngeal level [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. These findings support the hypothesis that mandibular protrusion contributes to airway patency by enlarging the upper airway [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCFD analysis provides a vivid visualization of airflow characteristics within the upper airway. Our findings indicated that iMAD can greatly improve the airflow characteristics of OSA patients. Based on the CFD results, the maximum airflow velocity was significantly reduced with iMAD in situ. It is hypothesized that high-velocity airflow may impose excessive shear stress on the airway wall, thereby contributing to mucosal injury and inflammation [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. With iMAD in situ, it could significantly reduce the velocity of the airflow, and thereby reduce the damage to the airway wall.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e4.3 Vertical distance of the incisors with MADs in situ\u003c/h2\u003e \u003cp\u003eTo further explore the working mechanism of iMAD, the change in the vertical distance between the upper and lower incisors of the patients were evaluated. As iMAD is thinner than conventional MADs, the influence of the iMAD on the vertical distance between incisors is much less than conventional MAD. Our previous study showed that with conventional MAD in situ, the vertical distance between incisors is about 11 mm [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Comparatively, in this study, vertical opening with iMAD in situ (7.07\u0026plusmn;1.71mm) reduced significantly, which may greatly improve the patient tolerance and compliance. This could be a reason that in this trial, patients reported fewer side effects such as jaw discomfort, tooth sensitivity [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Besides, it is suggested that the increase in the vertical dimension between incisors could also make the mandible rotate posteriorly and place the mandible in a more retrusive position, which is not beneficial for the OSA patients [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Therefore, it is recommended that to reduce side effects, the change vertical dimension of the mandible caused by MAD therapy should be limited as much as possible [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003e4.4 Limitations and strengths\u003c/h2\u003e \u003cp\u003eThis study has several limitations. First, the relatively small sample size (n\u0026thinsp;=\u0026thinsp;27) may limit the generalizability of our findings, although statistically significant differences were observed. Second, the follow-up duration was limited to three months, and longer-term outcomes, including device durability and patient compliance, remain to be assessed. Third, HSAT, while practical, does not capture sleep architecture or arousal indices, which may underestimate treatment effects compared with in-lab PSG.\u003c/p\u003e \u003cp\u003eDespite these limitations, this study presents several strengths. It is one of the few studies to combine polysomnographic outcomes with detailed 3D morphological and functional analysis of the upper airway using CBCT. The design and fabrication of iMAD using 3D printing also highlight the potential for customized, cost-effective therapeutic options for OSA patients.\u003c/p\u003e \u003c/div\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eWithin the limitations of this study, we conclude that iMAD has the potential to improve the respiratory parameters and increase upper airway dimensions in patients with mild to moderate OSA, supporting its potential as a comfortable and effective alternative to conventional MADs.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eAuthor Contributions Statement\u003c/h2\u003e \u003cp\u003eH.C. and X.W. designed the experiment; X.W. and RJ.J. recruited the patients, JW.L. and NY.ZH. collected the data of the patients; RJ.J. analyzed the image, PGS data; H.C. did the statistical analysis; RJ.J. and NY.Zh. prepared the tables and figures. All authors prepared and reviewed the manuscript. The data that support the findings of this study are available from the corresponding author upon request.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Young Elite Sponsorship Program of Shandong Provincial Medical Association (2024-GJ-0057)\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eH.C. and X.W. designed the experiment; X.W. and RJ.J. recruited the patients, JW.L. and NY.ZH. collected the data of the patients; RJ.J. analyzed the image, PGS data; H.C. did the statistical analysis; RJ.J. and NY.Zh. prepared the tables and figures. All authors prepared and reviewed the manuscript. The data that support the findings of this study are available from the corresponding author upon request.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research (1999) The Report of an American Academy of Sleep Medicine Task Force. Sleep 22(5):667\u0026ndash;689\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRanderath W, Verbraecken J, de Raaff CAL, Hedner J, Herkenrath S, Hohenhorst W et al (2021) European Respiratory Society guideline on non-CPAP therapies for obstructive sleep apnoea. Eur Respir Rev 30(162). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1183/16000617.0200-2021\u003c/span\u003e\u003cspan address=\"10.1183/16000617.0200-2021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJohal A, Hamoda MM, Almeida FR, Marklund M, Tallamraju H (2023) The role of oral appliance therapy in obstructive sleep apnoea. Eur Respir Rev 32(168):220257. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1183/16000617.0257-2022\u003c/span\u003e\u003cspan address=\"10.1183/16000617.0257-2022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUniken Venema JAM, Rosenm\u0026ouml;ller B, de Vries N, de Lange J, Aarab G, Lobbezoo F et al (2021) Mandibular advancement device design: A systematic review on outcomes in obstructive sleep apnea treatment. Sleep Med Rev 60:101557. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.smrv.2021.101557\u003c/span\u003e\u003cspan address=\"10.1016/j.smrv.2021.101557\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaha YM, Abu El Sadat SM, Gaber RM, Farid MM (2025) Ability of upper airway metrics to predict obstructive sleep apnea severity: a systematic review. Dentomaxillofac Radiol 54(4):245\u0026ndash;255. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/dmfr/twaf010\u003c/span\u003e\u003cspan address=\"10.1093/dmfr/twaf010\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePowell NB, Mihaescu M, Mylavarapu G, Weaver EM, Guilleminault C, Gutmark E (2011) Patterns in pharyngeal airflow associated with sleep-disordered breathing. Sleep Med 12(10):966\u0026ndash;974. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.sleep.2011.08.004\u003c/span\u003e\u003cspan address=\"10.1016/j.sleep.2011.08.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXiao Q, Bates A (2025) Quantifying Neuromuscular and Pressure Force Dynamics in Obstructive Sleep Apnea: A Novel Computational Fluid Dynamics Approach Using Airway Wall Acceleration. J Biomech Eng 147(10). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1115/1.4069664\u003c/span\u003e\u003cspan address=\"10.1115/1.4069664\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXiao Q, Ignatiuk D, Gunatilaka C, McConnell K, Schuler C, Romaker A et al (2025) Effects of Hypoglossal Nerve Stimulation on Upper Airway Structure and Function Using Moving Wall Computational Fluid Dynamics Simulations: A Pilot Study. J Sleep Res 34(5):e70040. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/jsr.70040\u003c/span\u003e\u003cspan address=\"10.1111/jsr.70040\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan den Bossche K, Op de Beeck S, Dieltjens M, Verbruggen AE, Vroegop AV, Verbraecken JA et al (2022) Multimodal phenotypic labelling using drug-induced sleep endoscopy, awake nasendoscopy and computational fluid dynamics for the prediction of mandibular advancement device treatment outcome: a prospective study. J Sleep Res 31(6):e13673. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/jsr.13673\u003c/span\u003e\u003cspan address=\"10.1111/jsr.13673\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsuiki S, Lowe AA, Almeida FR, Kawahata N, Fleetham JA (2004) Effects of mandibular advancement on airway curvature and obstructive sleep apnoea severity. Eur Respir J 23(2):263\u0026ndash;268. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1183/09031936.04.00094304\u003c/span\u003e\u003cspan address=\"10.1183/09031936.04.00094304\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Ruiter MHT, Aarab G, de Vries N, Lobbezoo F, de Lange J (2020) A stepwise titration protocol for oral appliance therapy in positional obstructive sleep apnea patients: proof of concept. Sleep Breath 24(3):1229\u0026ndash;1236. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s11325-020-02045-w\u003c/span\u003e\u003cspan address=\"10.1007/s11325-020-02045-w\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen H, Aarab G, Parsa A, de Lange J, van der Stelt PF, Lobbezoo F (2016) Reliability of three-dimensional measurements of the upper airway on cone beam computed tomography images. Oral Surg Oral Med Oral Pathol Oral Radiol 122(1):104\u0026ndash;110. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.oooo.2016.04.005\u003c/span\u003e\u003cspan address=\"10.1016/j.oooo.2016.04.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShi X, Chen H, Lobbezoo F, de Lange J, van der Stelt P, Berkhout E et al (2023) Comparison of the upper airway morphology between Dutch and Chinese adults with obstructive sleep apnea. Sleep Breath 27(6):2223\u0026ndash;2230. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s11325-023-02834-z\u003c/span\u003e\u003cspan address=\"10.1007/s11325-023-02834-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWeissheimer A, Menezes LM, Sameshima GT, Enciso R, Pham J, Grauer D (2012) Imaging software accuracy for 3-dimensional analysis of the upper airway. Am J Orthod Dentofac Orthop 142(6):801\u0026ndash;813. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ajodo.2012.07.015\u003c/span\u003e\u003cspan address=\"10.1016/j.ajodo.2012.07.015\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen H, Aarab G, de Ruiter MH, de Lange J, Lobbezoo F, van der Stelt PF (2016) Three-dimensional imaging of the upper airway anatomy in obstructive sleep apnea: a systematic review. Sleep Med 21:19\u0026ndash;27. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.sleep.2016.01.022\u003c/span\u003e\u003cspan address=\"10.1016/j.sleep.2016.01.022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen H, Li Y, Reiber JH, de Lange J, Tu S, van der Stelt P et al (2018) Analyses of aerodynamic characteristics of the oropharynx applying CBCT: obstructive sleep apnea patients versus control subjects. Dentomaxillofac Radiol 47(2):20170238. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1259/dmfr.20170238\u003c/span\u003e\u003cspan address=\"10.1259/dmfr.20170238\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen H, Elham E, Li Y, Ge S, Schmittbuhl M, Lavigne G et al (2022) Comparison of anatomic and aerodynamic characteristics of the upper airway among edentulous mild, moderate, and severe obstructive sleep apnea in older adults. J Clin Sleep Med 18(3):759\u0026ndash;768. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5664/jcsm.9716\u003c/span\u003e\u003cspan address=\"10.5664/jcsm.9716\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMylavarapu G, Murugappan S, Mihaescu M, Kalra M, Khosla S, Gutmark E (2009) Validation of computational fluid dynamics methodology used for human upper airway flow simulations. J Biomech 42(10):1553\u0026ndash;1559. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jbiomech.2009.03.035\u003c/span\u003e\u003cspan address=\"10.1016/j.jbiomech.2009.03.035\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao M, Barber T, Cistulli P, Sutherland K, Rosengarten G (2013) Computational fluid dynamics for the assessment of upper airway response to oral appliance treatment in obstructive sleep apnea. J Biomech 46(1):142\u0026ndash;150. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jbiomech.2012.10.033\u003c/span\u003e\u003cspan address=\"10.1016/j.jbiomech.2012.10.033\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShi X, Lobbezoo F, Chen H, Rosenm\u0026ouml;ller B, Berkhout E, de Lange J et al (2023) Comparisons of the effects of two types of titratable mandibular advancement devices on respiratory parameters and upper airway dimensions in patients with obstructive sleep apnea: a randomized controlled trial. Clin Oral Investig 27(5):2013\u0026ndash;2025. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00784-023-04945-z\u003c/span\u003e\u003cspan address=\"10.1007/s00784-023-04945-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePutrino A, Barbato E, Galluccio G (2021) Clear Aligners: Between Evolution and Efficiency-A Scoping Review. Int J Environ Res Public Health 18(6). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/ijerph18062870\u003c/span\u003e\u003cspan address=\"10.3390/ijerph18062870\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGurgel M, Cevidanes L, Costa F, Pereira R, Cunali P, Bittencourt L et al (2023) Three-dimensional comparison between the effects of mandibular advancement device and maxillomandibular advancement surgery on upper airway. BMC Oral Health 23(1):436. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12903-023-03125-5\u003c/span\u003e\u003cspan address=\"10.1186/s12903-023-03125-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVerbraecken J, Dieltjens M, Op de Beeck S, Vroegop A, Braem M, Vanderveken O et al (2022) Non-CPAP therapy for obstructive sleep apnoea. Breathe (Sheff) 18(3):220164. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1183/20734735.0164-2022\u003c/span\u003e\u003cspan address=\"10.1183/20734735.0164-2022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVerma A, Jain S (2023) Efficacy of Mandibular Advancement Device in the Treatment of Obstructive Sleep Apnoea by Evaluating Upper Airway Space Volume Using CBCT. J Coll Physicians Surg Pak 33(10):1194\u0026ndash;1197. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.29271/jcpsp.2023.10.1194\u003c/span\u003e\u003cspan address=\"10.29271/jcpsp.2023.10.1194\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShi X, Lobbezoo F, Chen H, Rosenm\u0026ouml;ller B, Berkhout E, de Lange J et al (2023) Effects of mandibular advancement devices on upper airway dimensions in obstructive sleep apnea: responders versus non-responders. Clin Oral Investig 27(9):5649\u0026ndash;5660. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00784-023-05186-w\u003c/span\u003e\u003cspan address=\"10.1007/s00784-023-05186-w\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePahkala R, Sepp\u0026auml; J, Myllykangas R, Tervaniemi J, Vartiainen VM, Suominen AL et al (2020) The impact of oral appliance therapy with moderate mandibular advancement on obstructive sleep apnea and upper airway volume. Sleep Breath 24(3):865\u0026ndash;873. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s11325-019-01914-3\u003c/span\u003e\u003cspan address=\"10.1007/s11325-019-01914-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarco-Pitarch R, Garc\u0026iacute;a-Selva M, Plaza-Esp\u0026iacute;n A, Puertas-Cuesta J, Agust\u0026iacute;n-Panadero R, Fern\u0026aacute;ndez-Juli\u0026aacute;n E et al (2021) Dimensional analysis of the upper airway in obstructive sleep apnoea syndrome patients treated with mandibular advancement device: A bi- and three-dimensional evaluation. J Oral Rehabil 48(8):927\u0026ndash;936. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/joor.13176\u003c/span\u003e\u003cspan address=\"10.1111/joor.13176\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShete CS, Bhad WA (2017) Three-dimensional upper airway changes with mandibular advancement device in patients with obstructive sleep apnea. Am J Orthod Dentofac Orthop 151(5):941\u0026ndash;948. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ajodo.2016.09.025\u003c/span\u003e\u003cspan address=\"10.1016/j.ajodo.2016.09.025\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCama\u0026ntilde;es-Gonzalvo S, Marco-Pitarch R, Plaza-Esp\u0026iacute;n A, Puertas-Cuesta J, Agust\u0026iacute;n-Panadero R, Fons-Font A et al (2021) Correlation between Polysomnographic Parameters and Tridimensional Changes in the Upper Airway of Obstructive Sleep Apnea Patients Treated with Mandibular Advancement Devices. J Clin Med 10(22). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/jcm10225255\u003c/span\u003e\u003cspan address=\"10.3390/jcm10225255\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePereira A, Gurgel M, Pereira R, Fabbro CD, de Barros Silva P, Costa F et al (2024) Evaluation of condylar and mandibular movements on the upper airway during the use of mandibular advancement device for obstructive sleep apnea treatment. Clin Oral Investig 28(2):122. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00784-024-05513-9\u003c/span\u003e\u003cspan address=\"10.1007/s00784-024-05513-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen H, Aarab G, Liu JW, Yu YL, Guo J, van der Stelt PF et al (2017) A novel imaging technique to evaluate airflow characteristics in the upper airway of an obstructive sleep apnea patient. Clin Case Rep 5(7):1084\u0026ndash;1087. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/ccr3.716\u003c/span\u003e\u003cspan address=\"10.1002/ccr3.716\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMayoral P, Lagravere MO, Miguez-Contreras M, Garcia M (2019) Antero-posterior mandibular position at different vertical levels for mandibular advancing device design. BMC Oral Health 19(1):85. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/https://dx.doi.org/10.1186/s12903-019-0783-8\u003c/span\u003e\u003cspan address=\"10.1186/s12903-019-0783-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarbero M, Flores-Mir C, Blanco JC, Nu\u0026ntilde;o VC, Casellas JB, Girado JLC et al (2020) Tridimensional upper airway assessment in male patients with OSA using oral advancement devices modifying their vertical dimension. J Clin Sleep Med 16(10):1721\u0026ndash;1729. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5664/jcsm.8666\u003c/span\u003e\u003cspan address=\"10.5664/jcsm.8666\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"obstructive sleep apnea, mandibular advancement device, invisible, 3D printing, cone beam computed tomography, upper airway dimensions, computational fluid dynamics","lastPublishedDoi":"10.21203/rs.3.rs-8989379/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8989379/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eTo investigate the efficacy and working mechanism of a novel invisible mandibular advancement devices (iMAD) on respiratory parameters and upper airway in obstructive sleep apnea (OSA) patients.\u003c/p\u003e\u003ch2\u003eMaterials and Methods\u003c/h2\u003e \u003cp\u003ePatients with mild to moderate OSA were recruited and each OSA patient underwent two home sleep apnea test (HSAT), and two cone beam computed tomography (CBCT) scans in supine position: one at baseline and one after 3 months with the iMAD \u003cem\u003ein situ\u003c/em\u003e. The primary outcome variables were the obstructive apnea index (OAI), the minimal cross-sectional area (CSAmin) of the upper airway, and airway resistance derived from computational fluid dynamics (CFD).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 48 patients were recruited, and 27 patients with a mean (\u0026plusmn;\u0026thinsp;SD) age of 42.44 (\u0026plusmn;7.64) years and a mean OAI of 15.59 (\u0026plusmn;6.86) /h completed the study. HSAT results showed that there was significant decrease in the OAI with iMAD in situ (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Nearly half of the patients (48.1%) met the responder criterion (\u0026ge;\u0026thinsp;50% reduction in OAI). CBCT showed that there was significant increase in the CSAmin of the upper airway with iMAD in situ (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). CFD analysis showed that the maximum velocity of the mid-sagittal plane was significantly reduced with iMAD in situ (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eWithin the limitations of this study, we conclude that iMAD could improve the respiratory parameters, increase upper airway dimensions, and reduce airflow velocity in mild to moderate OSA patients.\u003c/p\u003e\u003ch2\u003eClinical Relevance:\u003c/h2\u003e \u003cp\u003eiMAD may offer an esthetic, comfortable alternative to conventional MAD for mild to moderate OSA.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e \u003cp\u003echictr.org.cn (ChiCTR2400092896)\u003c/p\u003e","manuscriptTitle":"Efficacy of a novel invisible mandibular advancement device in patients with mild to moderate obstructive sleep apnea: a preliminary study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-13 07:29:51","doi":"10.21203/rs.3.rs-8989379/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7c203600-4f08-407f-881d-03be62c583d9","owner":[],"postedDate":"March 13th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Rejected","date":"2026-05-11T05:50:33+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T12:16:05+00:00","index":63,"fulltext":""},{"type":"reviewerAgreed","content":"82935246320012526282062910662809881642","date":"2026-05-04T17:55:38+00:00","index":61,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-11T05:57:55+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-13 07:29:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8989379","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8989379","identity":"rs-8989379","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}