Airway Tree Caliber and Susceptibility to Pollution-associated Emphysema: MESA Air and Lung Studies.

Rationale: Airway tree morphology varies in the general population and may modify the distribution and uptake of inhaled pollutants. Objectives: We hypothesized that smaller airway caliber would be associated with emphysema progression and would increase susceptibility to air pollutant-associated emphysema progression. Methods: MESA (Multi-Ethnic Study of Atherosclerosis) is a general population cohort of adults 45-84 years old from six U.S. communities. Airway tree caliber was quantified as the mean of airway lumen diameters measured from baseline cardiac computed tomography (CT) (2000-2002). Percentage emphysema, defined as percentage of lung pixels below -950 Hounsfield units, was assessed up to five times per participant via cardiac CT scan (2000-2007) and equivalent regions on lung CT scan (2010-2018). Long-term outdoor air pollutant concentrations (particulate matter with an aerodynamic diameter ⩽2.5 µm, oxides of nitrogen, and ozone) were estimated at the residential address with validated spatiotemporal models. Linear mixed models estimated the association between airway tree caliber and emphysema progression; modification of pollutant-associated emphysema progression was assessed using multiplicative interaction terms. Measurements and Main Results: Among 6,793 participants (mean ± SD age, 62 ± 10 yr), baseline airway tree caliber was 3.95 ± 1.1 mm and median (interquartile range) of percentage emphysema was 2.88 (1.21-5.68). In adjusted analyses, 10-year emphysema progression rate was 0.75 percentage points (95% confidence interval, 0.54-0.96%) higher in the smallest compared with largest airway tree caliber quartile. Airway tree caliber also modified air pollutant-associated emphysema progression. Conclusions: Smaller airway tree caliber was associated with accelerated emphysema progression and modified air pollutant-associated emphysema progression. A better understanding of the mechanisms of airway-alveolar homeostasis and air pollutant deposition is needed.

Deep Learning-Based Segmentation of Airway Morphology from Endobronchial Optical Coherence Tomography.

BACKGROUND: Manual measurement of endobronchial optical coherence tomography (EB-OCT) images means a heavy workload in the clinical practice, which can also introduce bias if the subjective opinions of doctors are involved. OBJECTIVE: We aim to develop a convolutional neural network (CNN)-based EB-OCT image analysis algorithm to automatically identify and measure EB-OCT parameters of airway morphology. METHODS: The ResUNet, MultiResUNet, and Siamese network were used for analyzing airway inner area (Ai), airway wall area (Aw), airway wall area percentage (Aw%), and airway bifurcate segmentation obtained from EB-OCT imaging, respectively. The accuracy of the automatic segmentations was verified by comparing with manual measurements. RESULTS: Thirty-three patients who were diagnosed with asthma (n = 13), chronic obstructive pulmonary disease (COPD, n = 13), and normal airway (n = 7) were enrolled. EB-OCT was performed in RB9 segment (lateral basal segment of the right lower lobe), and a total of 17,820 OCT images were collected for CNN training, validation, and testing. After training, the Ai, Aw, and airway bifurcate were readily identified in both normal airway and airways of asthma and COPD. The ResUNet and the MultiResUNet resulted in a mean dice similarity coefficient of 0.97 and 0.95 for Ai and Aw segmentation. The accuracy Siamese network in identifying airway bifurcate was 96.6%. Bland-Altman analysis indicated there was a negligible bias between manual and CNN measurements for Ai (bias = -0.02 to 0.01, 95% CI = -0.12 to 0.14) and Aw% (bias = -0.06 to 0.12, 95% CI = -1.98 to 2.14). CONCLUSION: EB-OCT imaging in conjunction with ResUNet, MultiResUNet, and Siamese network could automatically measure normal and diseased airway structure with an accurate performance.

Comparison of the upper airway morphology between Dutch and Chinese adults with obstructive sleep apnea.

PURPOSE: The pathogenesis of obstructive sleep apnea (OSA) is complex and may vary between different races. It has been suggested that the anatomical balance between skeletal tissues and soft tissues around the upper airway is a key pathophysiologic factor of OSA. Therefore, the aim of this study was to compare the anatomical balance of the upper airway between Dutch and Chinese patients with OSA based on cone beam computed tomography (CBCT) images. METHODS: This was a cross-sectional study performed in two centers and included Dutch and Chinese adults with OSA. CBCT scans in the supine position were obtained for both Dutch and Chinese OSA groups. The primary outcome variable was the anatomical balance of the upper airway, defined as the ratio of the tongue area and the maxillomandibular enclosure area. RESULTS: A total of 28 Dutch adults (mean age ± SD of 46.6 ± 14.1 years, body mass index [BMI] of 26.8 ± 3.5 kg/m2, and apnea-hypopnea index [AHI] of 15.7 ± 7.1 events/h) and 24 Chinese adults (age 41.0 ± 12.4 years, BMI 26.5 ± 3.3 kg/m2, and AHI 16.5 ± 7.8 events/h). There were no significant differences in AHI, age, BMI, and sex between the two groups (P = 0.14-0.76). The Dutch group had a significantly larger tongue area and tongue length compared to the Chinese group (P = 0.01 and P < 0.01). On the other hand, the Chinese group had a smaller maxilla length compared to the Dutch group (P < 0.01). However, the anatomical balance of the upper airway of both groups was not significantly different (P = 0.16). CONCLUSION: Within the limitations of this study, no significant difference was found in the anatomical balance of the upper airway between Dutch and Chinese patients with mild to moderate OSA. TRIAL REGISTRATION: The present study was registered at the ClinicalTrials.gov identifier NCT03463785.

Postintubation Tracheal Stenosis Evaluated by Endobronchial Optical Coherence Tomography: A Canine Model Study.

BACKGROUND: The predictors and airway morphological changes during the development of postintubation tracheal stenosis (PITS) have not been well elucidated. OBJECTIVES: To elucidate the validation of endobronchial optical coherence tomography (EB-OCT) in assessing the airway morphological changes in PITS. METHODS: We performed oral endotracheal intubation in 12 beagles to establish the PITS model. EB-OCT was performed respectively before modeling and on the 1st, 7th, and 12th day after extubation in 9 canines, and was conducted consecutively in 3 canines during the development of PITS. Histological findings and the thickness and gray-scale value of the tracheal wall assessed by EB-OCT measurements were analyzed and compared. RESULTS: The tracheal wall edema, granulation tissue proliferation, cartilage destruction in PITS, and airway wall thickening detected by EB-OCT were in concordance with the histopathological measurements. The consecutive EB-OCT observation of the airway structure demonstrated the tracheal wall thickness significantly increased from 344.41 ± 44.19 µm before modeling to 796.67 ± 49.75 µm on the 9th day after modeling (p < 0.05). The airway wall gray-scale values assessed by EB-OCT decreased from 111.19 ± 14.71 before modeling to 74.96 ± 4.08 on the 9th day after modeling (p < 0.05). The gray-scale value was negatively correlated with the airway wall thickness (r = -0.945, p = 0.001). CONCLUSION: The EB-OCT imaging, in concordance with the histopathological finding, was validated for assessing the airway morphological changes during the development of PITS. The EB-OCT evaluation of cartilage damage and gray-scale value measurement might help predict the development and prognosis of PITS.

Airway Morphological Changes in Pierre Robin Sequence: A Retrospective Study.

OBJECTIVE: To investigate airway morphology changes in patients with Pierre Robin sequence (PRS) pre-/post-mandibular distraction osteogenesis (MDO) and to compare morphologic changes to age-matched controls. DESIGN: Retrospective case-control study. SETTING: Urban, academic, tertiary medical center. PATIENTS, PARTICIPANTS: Fifteen patients with PRS after MDO to relieve upper airway obstruction (UAO) (2008-2018); age-matched controls for post-MDO patients. INTERVENTIONS: Mandibular distraction osteogenesis, curvilinear internal mandibular distractors. MAIN OUTCOME MEASURES: (1) Physiologic improvement after MDO (apnea-hypopnea index; minimum oxygen saturation); (2) airway size (volume, surface area, length, mean/minimum cross-sectional area), shape (lateral:anterior-posterior ratio, cross-sectional area ratios, uniformity, sphericity), and changes with MDO; and (3) post-MDO airway size, shape versus age-matched controls. RESULTS: Airway size increased after MDO (volume, P = .01; surface area, P = .02; length, P = .01), as did cross-sectional area (mean, P = .02; minimum, P = .02; minimum retropalatal, P = .05, mid-retroglossal, P = .02). Post-MDO PRS airways were larger than controls (volume, P < .01; surface area, P < .01; length, P < .01, cross-sectional area, P = .03). Airway shape remained nonuniform and flat post-MDO; control airways were round. Two syndromic patients required repeat MDO and had subphysiologic post-MDO airway cross-sectional area. Post-MDO PRS patients with supraphysiologic cross-sectional area along the entire airway had no UAO recurrence. CONCLUSIONS: In this small, heterogenous patient sample, MDO increases airway size, may preferentially affect the retropalatal airway, and often results in supraphysiologic airway dimensions. These retropalatal changes may be important in relieving severe UAO in patients with PRS. Generalizability of our results is limited by small cohort size and patient heterogeneity.

Changes in craniofacial and airway morphology as well as quality of life after passive myofunctional therapy in children with obstructive sleep apnea: a comparative cohort study.

PURPOSE: To examine the craniofacial and airway morphology as well as the quality of life before and after passive myofunctional therapy (PMFT) for 1 year in children with obstructive sleep apnea (OSA). METHODS: Forty children with OSA wearing an oral device nightly (treatment group) and seventeen without the device (control group) were followed up for 1 year. Lateral cephalometric radiography, polysomnography (without participants wearing the oral device), and quality of life survey (OSA-18) were performed before and after the study period. RESULTS: The apnea-hypopnea index (AHI) during sleep, REM AHI, hypopnea count, and desaturation count in the treatment group dropped significantly, compared with the control group. The craniofacial linear measurements increased significantly in both groups, while the length of mandible (Co-Gn) and anterior facial height (N-Me) became significantly larger in the treatment group. For the airway morphology, the intergroup comparison showed that OPha-Ophp (distance between anterior and posterior sides of oropharynx) increased significantly in the treatment group. For quality of life, the intergroup comparison found statistically significant improvements in the following in the treatment group, based on the OSA-18 survey: loud snoring, dysphagia, mood swings, discipline problems, difficulty awakening, total score for the emotional distress portion, and total survey score. CONCLUSIONS: Preliminary evidence is substantiated for the benefits of 1-year PMFT using an oral device with a built-in tongue bead, including improvements in nasal breathing during sleep, mandible linear growth (Co-Gn and N-Me), airway morphology (OPha-Ophp), and patients' quality of life.

Inflammation-dependent and independent airway remodelling in asthma.

BACKGROUND AND OBJECTIVE: The pathology of asthma is characterized by airway inflammation (granulocytic (GA) or paucigranulocytic (PGA)) and remodelling of airway structures. However, the relationship between inflammatory phenotypes and remodelling is unclear. We hypothesized that some features of airway remodelling are dependent on granulocytic airway inflammation while others are not. METHODS: Post-mortem airway sections from control subjects (n = 48) and cases of asthma with (n = 51) or without (n = 29) granulocytic inflammation in the inner airway wall were studied. The thickness of the airway smooth muscle (ASM) layer, basement membrane and inner and outer airway walls, the size and number of ASM cells, the volume fraction of extracellular matrix within the ASM layer, ASM shortening and luminal mucus were estimated. Airway dimensions were compared between the three subject groups. RESULTS: In cases of PGA, only the thickness of the ASM layer and basement membrane was increased compared with control subjects. In cases of GA, not only the ASM and basement membrane were increased in thickness, but there was also increased inner and outer airway wall thickness and increased narrowing of the airway lumen due to ASM shortening and mucus obstruction, compared with control subjects. Granulocytic inflammation was observed more often in cases of fatal asthma. CONCLUSION: These findings suggest that inner and outer wall thickening coexists with inflammation, whereas thickening of the ASM layer and basement membrane may be present even in the absence of inflammation. Remodelling of the ASM layer and basement membrane may therefore be less susceptible to anti-inflammatory therapy.

Directional preference of airway smooth muscle mass increase in human asthmatic airways.

Airway smooth muscle (ASM) orientation and morphology determine the ability of the muscle to constrict the airway. In asthma, ASM mass is increased, but it is unknown whether ASM orientation and morphology are altered as well or whether the remodeling at the source of the mass increase is ongoing. We dissected human airway trees from asthmatic and control lungs. Stained, intact airway sections were imaged in axial projection to show ASM bundle orientation, whereas cross-sectional histological slides were used to assess ASM area, bundle thickness, and ASM bundle-to-basement membrane distance. We also used these slides to assess cell size, proliferation, and apoptosis. We showed that ASM mass increase in cartilaginous airways is primarily the result of an increase of ASM bundle thickness (as measured radially in an airway cross section) and coincides with an increased distance of the ASM bundles to the airway perimeter. ASM orientation was unchanged in all airways. Apoptosis markers and cell size did not show differences between asthmatics and controls. Our findings show that ASM mass increase likely contributes to the airway-constricting capacity of the muscle. Both the increased bundle thickness and increased thickness of the airway wall inwards of the ASM bundles could further enhance this capacity. Turnover of ASM appears to be the same in airways and biopsies, but the lack of correlation between different markers of proliferation casts doubt on the specificity of markers generally used to assess proliferation.

Dysanapsis is not associated with exertional dyspnoea in healthy male and female never-smokers aged 40 years and older.

In healthy adults, airway-to-lung (i.e., dysanapsis) ratio is lower and dyspnoea during exercise at a given minute ventilation (V̇E) is higher in females than in males. We investigated the relationship between dysanapsis and sex on exertional dyspnoea in healthy adults. We hypothesized that females would have a smaller airway-to-lung ratio than males and that exertional dyspnoea would be associated with airway-to-lung ratio in males and females. We analyzed data from n = 100 healthy never-smokers aged ≥40 years enrolled in the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who underwent pulmonary function testing, a chest computed tomography scan, and cardiopulmonary exercise testing. The luminal area of the trachea, right main bronchus, left main bronchus, right upper lobe, bronchus intermedius, left upper lobe, and left lower lobe were 22%-37% smaller (all p < 0.001) and the airway-to-lung ratio (i.e., average large conducting airway diameter relative to total lung capacity) was lower in females than in males (0.609 ± 0.070 vs. 0.674 ± 0.082; p < 0.001). During exercise, there was a significant effect of V̇E, sex, and their interaction on dyspnoea (all p < 0.05), indicating that dyspnoea increased as a function of V̇E to a greater extent in females than in males. However, after adjusting for age and total lung capacity, there were no significant associations between airway-to-lung ratio and measures of exertional dyspnoea, regardless of sex (all r < 0.34; all p > 0.05). Our findings suggest that sex differences in airway size do not contribute to sex differences in exertional dyspnoea.

3D analysis of upper airway morphology related to obstructive sleep apnea severity.

BACKGROUND: Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder characterized by repetitive collapse of the upper airway during sleep. However, little evidence is available on the differences between the sub-regions of the upper airway morphology and OSA severity. Since orthodontists frequently perform cone beam computed tomography (CBCT) in the neck area, we aimed to investigate the relationship and the differences between upper airway morphology and OSA severity using CBCT. MATERIALS AND METHODS: The medical records, CBCT imaging of 21 OSA patients diagnosed by polysomnography, and the apnea-hypopnea index (AHI) results were included to classify OSA severity as mild, moderate, or severe. The minimum cross-sectional areas (MCA) and volumes of the upper pharyngeal airway boundaries in four sub-regions: nasopharynx, retropalatal, retroglossal, and hypopharynx were measured. Dolphin Imaging software was used for upper airway segmentation. The correlation coefficient (r), one-way ANOVA, and the least significant difference post hoc multiple comparison test were applied to fulfill the objectives. RESULTS: A statistically significant relationship was found between the MCA of the nasopharynx and the AHI (r = -0.473, P < 0.05). Furthermore, a difference was found between mild and moderate and moderate and severe OSA severity in the MCA results of the retroglossal region (P < 0.05). However, no relationship was found between the upper airway volume and OSA severity. CONCLUSIONS: MCA was moderately negatively correlated to AHI only in the nasopharynx subregion. Moderate OSA presented significantly less MCA than mild and severe OSA only in the oropharynx and retroglossal subregions.

Diagnostic value of upper airway morphological data based on CT volume scanning combined with clinical indexes in children with obstructive sleep apnea syndrome.

Background and purpose: Early diagnosis is important for treatment and prognosis of obstructive sleep apnea (OSA)in children. Polysomnography (PSG) is the gold standard for the diagnosis of OSA. However, due to various reasons, such as inconvenient implementation, less equipped in primary medical institutions, etc., it is less used in children, especially in young children. This study aims to establish a new diagnostic method with imaging data of upper airway and clinical signs and symptoms. Methods: In this retrospective study, clinical and imaging data were collected from children ≤10 years old who underwent nasopharynx CT scan(low-dose protocol)from February 2019 to June 2020,including 25 children with OSA and 105 non-OSA. The information of the upper airway (A-line; N-line; nasal gap; upper airway volume; upper and lower diameter, left and right diameter and cross-sectional area of the narrowest part of the upper airway) were measured in transaxial, coronal, and sagittal images. The diagnosis of OSA and adenoid size were given according to the guidelines and consensus of imaging experts. The information of clinical signs, symptoms, and others were obtained from medical records. According to the weight of each index on OSA, the indexes with statistical significance were screened out, then were scored and summed up. ROC analysis was performed with the sum as the test variable and OSA as the status variable to evaluate the diagnostic efficacy on OSA. Results: The AUC of the summed scores (ANMAH score) of upper airway morphology and clinical index for the diagnosis of OSA was 0.984 (95% CI 0.964-1.000). When sum = 7 was used as the threshold (participants with sum>7 were considered to have OSA), the Youden's index reached its maximum at which point the sensitivity was 88.0%, the specificity was 98.1%, and the accuracy was 96.2%. Conclusion: The morphological data of the upper airway based on CT volume scan images combined with clinical indices have high diagnostic value for OSA in children; CT volume scanning plays a great guiding role in the selection of treatment scheme of OSA. It is a convenient, accurate and informative diagnostic method with a great help to improving prognosis. Highlights: - Early diagnosis of OSA in children is very important for the treatment.- However, the traditional diagnostic gold-standard PSG is difficult to implement.- This study aims to explore convenient and reliable diagnostic methods for children.- A new diagnostic model was established combining CT with signs and symptoms.- The diagnostic method in this study is highly effective, informative, and convenient.

Association of age with computed tomography airway tree morphology in male and female never smokers without lung disease history.

BACKGROUND: Sex and aging may affect the airway tree structure in patients with airway diseases and even healthy subjects. Using chest computed tomography (CT), this study sought to determine whether age is associated with airway morphological features differently in healthy males and females. METHODS: This retrospective cross-sectional study consecutively incorporated lung cancer screening CT data of asymptomatic never smokers (n = 431) without lung disease history. Luminal areas were measured at the trachea, main bronchi, bronchus intermedius, segmental and subsegmental bronchus, and the ratio of their geometric mean to total lung volume (airway-to-lung size ratio, ALR) was determined. Airway fractal dimension (AFD) and total airway count (TAC) were calculated for the segmented airway tree resolved on CT. RESULTS: The lumen areas of the trachea, main bronchi, segmental and subsegmental airways, AFD and TAC visible on CT were smaller in females (n = 220) than in males (n = 211) after adjusting for age, height, and body mass index, while ALR or count of the 1st to 5th generation airways did not differ. Furthermore, in males but not in females, older age was associated with larger lumen sizes of the main bronchi, segmental and subsegmental airways, and ALR. In contrast, neither male nor female had any associations between age and AFD or TAC on CT. CONCLUSION: Older age was associated with larger lumen size of the relatively central airways and ALR exclusively in males. Aging may have a more profound effect on airway lumen tree caliber in males than in females.

Correlation analysis of upper airway morphology in patients with obstructive sleep apnea and anatomically small retruded mandibles.

OBJECTIVE: To investigate the relationship between upper airway morphology and the severity of obstructive sleep apnea (OSA) in patients with anatomically small retruded mandibles. METHODS: Fifty-two patients with small retruded mandibles underwent polysomnography and airway computed tomography. The airway morphology parameters and sleep assessment were compared between the patients with or without OSA. RESULTS: Twenty-eight patients diagnosed with OSA, according to polysomnography, had a higher distance between the hyoid bone and mandibular plane (HMP), lateral dimension (LAT)/anteroposterior dimension (AP), but lower minimum cross-sectional area (mCSA), AP, surface area, volume, avgCSA, and airway uniformity (U). The apnea-hypopnea index had negative correlations with mCSA, AP, surface area, volume, avgCSA, and U, and had a positive correlation with HMP and LAT/AP. CONCLUSION: OSA is common among patients with small retruded mandibles and is associated with a more compressed upper airway shape and longer HMP.

Physiological impacts of computed tomography airway dysanapsis, fractal dimension, and branch count in asymptomatic never smokers.

Dysanapsis, a mismatch between airway tree caliber and lung size, contributes to a large variation in lung function on spirometry in healthy subjects. However, it remains unclear whether other morphological features of the airway tree could be associated with the variation in lung function independent of dysanapsis. This study used lung cancer screening chest computed tomography (CT) and spirometry data from asymptomatic never smokers. Dysanapsis and the complexity of airway tree geometry were quantified on CT by measuring airway to lung ratio (ALR) and airway fractal dimension (AFD). Moreover, total airway count (TAC), ratio of airway luminal surface area to volume (SA/V), longitudinal tapering and irregularity of the radius of the internal lumen from the central to peripheral airways (Tapering index and Irregularity index) were quantified. In 431 asymptomatic never smokers without a history of lung diseases, lower ALR was associated with lower forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FEV1/FVC). The associations of ALR with AFD and TAC (r = 0.41 and 0.13) were weaker than the association between TAC and AFD (r = 0.64). In multivariable models adjusted for age, sex, height, and mean lung density, lower AFD and TAC were associated with lower FEV1 and FEV1/FVC independent of ALR, whereas SA/V and Tapering index were not. These results suggest that the smaller airway tree relative to a given lung size and the lower complexity of airway tree shape, including lower branch count, are independently associated with lower lung function in healthy subjects.NEW & NOTEWORTHY This study showed that fractal dimension and total airway count of the airway tree on computed tomography are associated with lung function on spirometry independent of a smaller airway for a given lung size (dysanapsis) in asymptomatic never smokers without a history of lung diseases. In addition to dysanapsis, the morphometric complexity of the airway tree and the airway branch count may cause a substantial variation of lung function in these subjects.

COVID-19 progression in hospitalized patients using follow-up in vivo CT and ex vivo microCT.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease-19 (COVID-19) which can lead to acute respiratory distress syndrome (ARDS) and evolve to pulmonary fibrosis. Computed tomography (CT) is used to study disease progression and describe radiological patterns in COVID-19 patients. This study aimed to assess disease progression regarding lung volume and density over time on follow-up in vivo chest CT and give a unique look at parenchymal and morphological airway changes in "end-stage" COVID-19 lungs using ex vivo microCT. Methods: Volumes and densities of the lung/lobes of three COVID-19 patients were assessed using follow-up in vivo CT and ex vivo whole lung microCT scans. Airways were quantified by airway segmentations on whole lung microCT and small-partition microCT. As controls, three discarded healthy donor lungs were used. Histology was performed in differently affected regions in the COVID-19 lungs. Results: In vivo, COVID-19 lung volumes decreased while density increased over time, mainly in lower lobes as previously shown. Ex vivo COVID-19 lung volumes decreased by 60% and all lobes were smaller compared to controls. Airways were more visible on ex vivo microCT in COVID-19, probably due to fibrosis and increased airway diameter. In addition, small-partition microCT showed more deformation of (small) airway morphology and fibrotic organization in severely affected regions with heterogeneous distributions within the same lung which was confirmed by histology. Conclusions: COVID-19-ARDS and subsequent pulmonary fibrosis alters lung architecture and airway morphology which is described using in vivo CT, ex vivo microCT, and histology.

A Cone Beam CT Study of Upper Airway Morphology in Perimenopausal and Postmenopausal Women.

PURPOSE: Menopause is accompanied by a decline in estrogen and progesterone. Several studies have demonstrated that upper airway patency decreases in women after menopause, while morphology changes are still a lack of evidence. This study aimed to explore upper airway morphology changes in perimenopausal and postmenopausal women. METHODS: This retrospective cross-sectional study included 367 consecutive Chinese female patients over 25 years old who had routinely taken large-field cone beam computed tomography in the imaging library of Peking University School and Hospital of Stomatology from October 2016 to September 2020. A total of 283 males were screened as sex controls according to the same age group. Upper airway morphology, hyoid position and facial pattern were measured. The association between perimenopausal and postmenopausal years and upper airway morphology in both sexes was analyzed. RESULTS: Perimenopausal women (aged 45-54 years) showed a significant decrease in the volume (3172.91mm3, 95% CI = 653.86-5691.96) and minimum cross-sectional area (37.08 mm2, 95% CI = 5.36-68.80), and a significant increase in the length (-1.96mm, 95% CI = -3.62 to -0.29) of upper airway compared to adjacent reproductive years (aged 35-44), while this difference was neither seen in other adjacent two reproductive age groups of females nor in the same age groups of males. In postmenopausal women (55 years and older), hyoid position was significantly lower (-2.74mm, 95% CI = -4.42 to -1.07) than either age group, while no similar changes were seen in men. CONCLUSION: Women had smaller airway volume, reduced upper airway cross-sectional area and longer airway length in perimenopausal years, and a significantly lower hyoid position in postmenopausal years. These changes may be related to menopause itself and independent of the changes associated with aging.

Diagnosis of obstructive sleep apnea with prediction of flow characteristics according to airway morphology automatically extracted from medical images: Computational fluid dynamics and artificial intelligence approach.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is being observed in an increasing number of cases. It can be diagnosed using several methods such as polysomnography. OBJECTIVES: To overcome the challenges of time and cost faced by conventional diagnostic methods, this paper proposes computational fluid dynamics (CFD) and machine-learning approaches that are derived from the upper-airway morphology with automatic segmentation using deep learning. METHOD: We adopted a 3D UNet deep-learning model to perform medical image segmentation. 3D UNet prevents the feature-extraction loss that may occur by concatenating layers and extracts the anteroposterior coordination and width of the airway morphology. To create flow characteristics of the upper airway training data, we analyzed the changes in flow characteristics according to the upper-airway morphology using CFD. A multivariate Gaussian process regression (MVGPR) model was used to train the flow characteristic values. The trained MVGPR enables the prompt prediction of the aerodynamic features of the upper airway without simulation. Unlike conventional regression methods, MVGPR can be trained by considering the correlation between the flow characteristics. As a diagnostic step, a support vector machine (SVM) with predicted aerodynamic and biometric features was used in this study to classify patients as healthy or suffering from moderate OSAS. SVM is beneficial as it is easy to learn even with a small dataset, and it can diagnose various flow characteristics as factors while enhancing the feature via the kernel function. As the patient dataset is small, the Monte Carlo cross-validation was used to validate the trained model. Furthermore, to overcome the imbalanced data problem, the oversampling method was applied. RESULT: The segmented upper-airway results of the high-resolution and low-resolution models present overall average dice coefficients of 0.76±0.041 and 0.74±0.052, respectively. Furthermore, the classification accuracy, sensitivity, specificity, and F1-score of the diagnosis algorithm were 81.5%, 89.3%, 86.2%, and 87.6%, respectively. CONCLUSION: The convenience and accuracy of sleep apnea diagnosis are improved using deep learning and machine learning. Further, the proposed method can aid clinicians in making appropriate decisions to evaluate the possible applications of OSAS.

Association of Craniofacial and Upper Airway Morphology with Cardiovascular Risk in Adults with OSA.

BACKGROUND AND OBJECTIVE: Clinical and population-based studies have demonstrated a strong association between obstructive sleep apnea (OSA) and cardiovascular disease (CVD). Anatomical abnormalities of the craniofacial region and upper airway are important risk factors for OSA. The objective of this study was to investigate the association of craniofacial and upper airway morphology with CVD risk biomarkers. METHODS: One hundred and sixty-nine male patients with OSA underwent in-laboratory polysomnography (PSG) and upper airway computed tomography (CT) scanning. Ten-year Framingham CVD risk score (FRS) was calculated and categorized into low- and moderate-to-high-risk groups. N-terminal pro B-type natriuretic peptide (NT-proBNP) was measured as a biomarker of increased myocardial wall stress. RESULTS: Compared to the low-risk group, total sleep time (TST), the proportion of N3 (N3%) and mean oxygen saturation (SpO2mean) were lower, while the arousal index of non-rapid eye movement (NREM) sleep, apnea index (AI) of NREM sleep, apnea hypopnea index (AHI) of NREM sleep, oxygen desaturation index (ODI) and percentage of total sleep time spent with oxyhemoglobin saturation below 90% (TST90) were higher in the moderate-to-high risk group. The corrected upper airway length (UAL), ANB angle and gonion-gnathion-hyoid angle were larger for subjects in the moderate-to-high risk group than those in the low-risk group. In multiple regression analysis, TST, AINREM and adjusted UAL were independently associated with moderate-to-high CVD risk. Plasma NT-proBNP levels were higher in patients in the moderate- to high-risk group, and among the PSG and CT scan parameters, only SPO2mean was marginally associated with NT-proBNP (r=0.183, P=0.054). CONCLUSION: Craniofacial and upper airway features may contain valid cues about CVD risk, and sleep duration, obstructive event type and occurrence phase may be closely related to CVD risk for patients with OSA.

Airway morphology and inspiratory flow features in the early stages of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is among the leading causes of death worldwide. Inhaled pollutants are the prime risk factor, but the pathogenesis and progression of the diseased is poorly understood. Most studies on the disease onset and trajectory have focused on genetic and molecular biomarkers. Here we investigate the role of the airway anatomy and the consequent respiratory fluid mechanics on the development of COPD. METHODS: We segmented CT scans from a five-year longitudinal study in three groups of smokers (18 subjects each) having: (i) minimal/mild obstruction at baseline with declining lung function at year five; (ii) minimal/mild obstruction at baseline with stable function, and (iii) normal and stable lung function over the five year period. We reconstructed the bronchial trees up to the 7th generation, and for one subject in each group we performed MRI velocimetry in 3D printed models. FINDINGS: The subjects with airflow obstruction at baseline have smaller airway diameters, smaller child-to-parent diameter ratios, larger length-to-diameter ratios, and smaller fractal dimensions. The differences are more significant for subjects that develop severe decline in pulmonary function. The secondary flows that characterize lateral dispersion along the airways are found to be less intense in the subjects with airflow obstruction. INTERPRETATION: These results indicate that morphology of the conducting airways and inspiratory flow features are correlated with the status and progression of COPD already at an early stage of the disease. This suggests that imaging-based biomarkers may allow a pre-symptomatic diagnosis of disease progression.

Three-dimensional analysis of upper airway morphology in skeletal Class III patients with and without mandibular asymmetry.

OBJECTIVE: To compare the three-dimensional (3D) morphology of the upper airway in skeletal Class III patients with and without mandibular asymmetry and to investigate the possible underlying correlations between the morphology of the upper airway and mandibular deviation. MATERIALS AND METHODS: Cone-beam computed tomography images of 54 subjects with skeletal Class III malocclusion (ANB angle ≤ 0.4°, Wits ≤ -5.5°) were taken and 3D upper airway models were reconstructed using Dolphin 3D software. According to the distance (d) from symphysis menti to the sagittal plane, all subjects were divided into a symmetry group (d ≤ 2 mm) and an asymmetry group (d ≥ 4 mm). Based on the severity of mandibular deviation, the asymmetry group was divided into subgroup I (4 mm ≤d <10 mm) and subgroup II (d ≥ 10 mm). Cross-sectional linear distances, areas, and volumetric variables of the upper airway were measured in the 3D airway model. RESULTS: Width of the inferior limit of the glossopharynx (P3W), cross-sectional area of the anterior limit of the nasal airway (P5S), and height of the glossopharynx (GPH) in the asymmetry group were significantly larger than in the symmetry group. As for subjects with severe mandibular deviation in subgroup II (d ≥ 10 mm), volume of the glossopharynx (GPV), total volume of the pharynx (TPV), length of the inferior limit of the velopharynx (P2L), and ratio of length to width of the inferior limit of the velopharynx (P2L/P2W) showed significantly negative correlations with mandibular deviation (r > 0.7, P < .05). CONCLUSIONS: In Class III subjects with severe mandibular asymmetry, the pharyngeal airway showed a tendency toward constriction and presented a more elliptical shape as mandibular deviation became more severe (P < .01).