The role of long-term continuous positive airway pressure in the progression of obstructive sleep apnoea: A longitudinal cohort study.

Recent evidence suggests that short-term obstructive sleep apnea (OSA) treatment could affect OSA pathogenesis such as ventilatory control. The aim of our present study was to identify the impact of long-term treatment on the change in pathogenesis and natural progression of OSA. In a longitudinal analysis of a non-obese cohort study, patients with OSA treated with either continuous positive airway pressure (CPAP) or an oral appliance (OA), interrupted their treatment for 1 week and underwent a polysomnography (PSG) off treatment that was compared with their initial PSG taken 5 years before treatment initiation. In all, 154 consecutive patients with OSA who were treated by CPAP using an auto-titrating continuous positive airway pressure device (CPAP-APAP) (n = 112), or by OA (n = 27) or were untreated (n = 15), PSG was performed twice with a median (range) follow-up of 93 (60-176) months. Multivariate logistic regression showed that reduction of body mass index (BMI) and good treatment adherence to be significant predictors of favourable OSA progression, as represented by an improved or unchanged apnea-hypopnea index (AHI) (odds ratios were 5.14 and 2.89, respectively). Amongst the patients with an unchanged BMI and good CPAP-APAP adherence (n = 55), the improvement in AHI was significantly associated with the decrease in supine non-rapid eye movement-AHI and mixed apnoea index/apnoea index, which are generally recognised to be determinants of ventilator instability. These findings suggest that not only weight but also treatment adherence are determinants in the natural progression of OSA severity.

Machine learning for image-based detection of patients with obstructive sleep apnea: an exploratory study.

PURPOSE: In 2-dimensional lateral cephalometric radiographs, patients with severe obstructive sleep apnea (OSA) exhibit a more crowded oropharynx in comparison with non-OSA. We tested the hypothesis that machine learning, an application of artificial intelligence (AI), could be used to detect patients with severe OSA based on 2-dimensional images. METHODS: A deep convolutional neural network was developed (n = 1258; 90%) and tested (n = 131; 10%) using data from 1389 (100%) lateral cephalometric radiographs obtained from individuals diagnosed with severe OSA (n = 867; apnea hypopnea index > 30 events/h sleep) or non-OSA (n = 522; apnea hypopnea index < 5 events/h sleep) at a single center for sleep disorders. Three kinds of data sets were prepared by changing the area of interest using a single image: the original image without any modification (full image), an image containing a facial profile, upper airway, and craniofacial soft/hard tissues (main region), and an image containing part of the occipital region (head only). A radiologist also performed a conventional manual cephalometric analysis of the full image for comparison. RESULTS: The sensitivity/specificity was 0.87/0.82 for full image, 0.88/0.75 for main region, 0.71/0.63 for head only, and 0.54/0.80 for the manual analysis. The area under the receiver-operating characteristic curve was the highest for main region 0.92, for full image 0.89, for head only 0.70, and for manual cephalometric analysis 0.75. CONCLUSIONS: A deep convolutional neural network identified individuals with severe OSA with high accuracy. Future research on this concept using AI and images can be further encouraged when discussing triage of OSA.

Obstructive sleep apnea phenotypes in men based on characteristics of respiratory events during polysomnography.

PURPOSE: The upper airway (UA) anatomical collapsibility, UA muscle responsiveness, breathing control, and/or arousability are important contributing factors for obstructive sleep apnea (OSA). Differences in clinical manifestations of OSA are believed to reflect interactions among these factors. We aimed to classify OSA patients into subgroups based on polysomnographic (PSG) variables using cluster analysis and assess each subgroup's characteristics. METHODS: Men with moderate or severe OSA and without any concomitant heart or psychosomatic disease were recruited. A hierarchical cluster analysis was performed using variables including fraction of apnea, respiratory event duration, minimum oxygen saturation, arousal rate before termination, and frequency of respiratory events in the supine position. The impact of sleep stages or body position on PSG variables was also evaluated in each cluster. RESULTS: A total of 210 men (mean age, 50.0 years, mean body mass index, 27.4 kg/m2) were studied. The three subgroups that emerged from the analysis were defined as follows: cluster 1 (high fraction of apnea and severe desaturation (20%)), cluster 2 (high fraction of apnea and long event duration (31%)), and cluster 3 (low fraction of apnea (49%)). There were differences in the body mass index and apnea type between the three clusters. Sleep stages and/or body position affected PSG variables in each cluster. CONCLUSIONS: Patients with OSA could be divided into three distinct subgroups based on PSG variables. This clustering may be used for assessing the pathophysiology of OSA to tailor individual treatment other than continuous positive airway pressure therapy.

Is maxillary dental arch constriction common in Japanese male adult patients with obstructive sleep apnoea?

OBJECTIVES Little is known about the contributions of a narrow maxillary dental arch and maxillary skeletal constriction to the development of obstructive sleep apnoea (OSA). Therefore, the purpose of this study was to clarify the relationships between maxillary dental arch width and OSA and between maxillary skeletal constriction and OSA in Japanese male patients.METHODS Study models for 164 Japanese male OSA patients were fabricated for dental arch analyses. We compared the patients' dental arch widths with the standard value for Japanese males. Moreover, the associations between the upper dental arch width and the apnoea-hypopnoea index (AHI), body mass index, skeletal pattern (SNA, SNB, and ANB), cross-sectional area of tongue obtained from an upright lateral cephalogram, lower dental arch width, overjet, and overbite were also examined.RESULTS Although a narrower upper dental arch was associated with severer OSA, the upper dental arch in OSA patients was not significantly narrower than the Japanese standard value. However, the results of a multiple regression analysis revealed that the upper dental arch became narrower as the mandible was positioned more rearward relative to the maxilla.CONCLUSIONS We conclude that dental arch constriction in the maxilla could be associated with the development of OSA but is not a typical feature of our sample of Japanese OSA patients. Moreover, the factor that aggravates OSA is not maxillary skeletal constriction but rather maxillary dental arch constriction related to antero-posterior skeletal discrepancy.

Validity of sheet-type portable monitoring device for screening obstructive sleep apnea syndrome.

PURPOSE: The SD-101 is a non-restrictive sheet-like medical device that measures sleep-disordered breathing using pressure sensors that can detect the gravitational alterations in the body that accompany respiratory movement. One report has described that the screening specificity of the SD-101 for mild to moderate obstructive sleep apnea syndrome (OSAS) is relatively low. The present study examines whether the accuracy of the SD-101 for OSAS screening is improved by simultaneously measuring percutaneous oxygen saturation (SpO2). METHODS: Sixty consecutive individuals with suspected OSAS consented to undergo overnight polysomnography (PSG) together with simultaneous measurements of SD-101 and SpO2 at our laboratory. RESULTS: The apnea-hypopnea index (AHI) determined from PSG and the respiratory disturbance index determined from SD-101 measurements significantly correlated (SD-101 alone: r = 0.871, p < 0.0001; SD-101 with SpO2: r = 0.965, p < 0.0001). Bland-Altman plots showed a smaller dispersion for the SD-101 with SpO2 than for the SD-101 alone. The SD-101 with SpO2 detected an AHI of >15 on PSG with a sensitivity and specificity of 96.9 and 90.5 % compared with 87.5 and of 85.7 %, respectively, of the SD-101 alone. CONCLUSIONS: Simultaneously measuring SpO2 improved the accuracy of the SD-101 for OSAS screening. Furthermore, this modality appears to offer high sensitivity and specificity for detecting even moderately severe OSAS.

Control of Tongue Position in Patients with Obstructive Sleep Apnea: Concept and Protocol for a Randomized Controlled Crossover Trial.

We hypothesize that the control of tongue position using a newly developed tongue position retainer, where the tongue is held in a protruded position (i.e., intervention A) or in its resting position (i.e., intervention B), is effective for maintaining upper airway patency in obstructive sleep apnea (OSA) compared with no control of tongue position. This is a randomized, controlled, non-blinded, crossover, and two-armed trial (i.e., sequence AB/BA) in 26 male participants (i.e., sample size) who are scheduled to undergo a dental operation under intravenous sedation with OSA (10 ≤ respiratory event index < 30/h). Participants will be randomly allocated into either sequence by a permuted block method, stratified by body mass index. Under intravenous sedation, participants will undergo two interventions, separated by a washout period after receiving intervention A or intervention B using a tongue position retainer after baseline evaluation, before each intervention is provided. The primary outcome is the abnormal breathing index of apnea as determined by the frequency of apnea per hour. We expect that, compared with no control of tongue position, both intervention A and intervention B will improve the abnormal breathing events with superior effects achieved by the former, offering a therapeutic option for OSA.

Sleep Apnea Syndrome (SAS) Clinical Practice Guidelines 2020.

The prevalence of sleep disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously believed, with patients having moderate-to-severe OSA accounting for approximately 20% of adult males and 10% of postmenopausal women not only in Western countries but also in Eastern countries, including Japan. Since 1998, when health insurance coverage became available, the number of patients using continuous positive airway pressure (CPAP) therapy for sleep apnea has increased sharply, with the number of patients about to exceed 500,000 in Japan. Although the "Guidelines for Diagnosis and Treatment of Sleep Apnea Syndrome (SAS) in Adults" was published in 2005, a new guideline was prepared in order to indicate the standard medical care based on the latest trends, as supervised by and in cooperation with the Japanese Respiratory Society and the "Survey and Research on Refractory Respiratory Diseases and Pulmonary Hypertension" Group, of Ministry of Health, Labor and Welfare and other related academic societies, including the Japanese Society of Sleep Research, in addition to referring to the previous guidelines. Because sleep apnea is an interdisciplinary field covering many areas, this guideline was prepared including 36 clinical questions (CQs). In the English version, therapies and managements for SAS, which were written from CQ16 to 36, were shown. The Japanese version was published in July 2020 and permitted as well as published as one of the Medical Information Network Distribution Service (Minds) clinical practice guidelines in Japan in July 2021.

Sleep Apnea Syndrome (SAS) Clinical Practice Guidelines 2020.

The prevalence of sleep-disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously believed, with patients having moderate-to-severe OSA accounting for approximately 20% of adult males and 10% of postmenopausal women not only in Western countries but also in Eastern countries, including Japan. Since 1998, when health insurance coverage became available, the number of patients using continuous positive airway pressure (CPAP) therapy for sleep apnea has increased sharply, with the number of patients about to exceed 500,000 in Japan. Although the "Guidelines for Diagnosis and Treatment of Sleep Apnea Syndrome (SAS) in Adults" was published in 2005, a new guideline was prepared to indicate the standard medical care based on the latest trends, as supervised by and in cooperation with the Japanese Respiratory Society and the "Survey and Research on Refractory Respiratory Diseases and Pulmonary Hypertension" Group, of Ministry of Health, Labor and Welfare and other related academic societies, including the Japanese Society of Sleep Research, in addition to referring to the previous guidelines. Since sleep apnea is an interdisciplinary field covering many areas, this guideline was prepared including 36 clinical questions (CQs). In the English version, therapies and managements for SAS, which were written from CQ16 to 36, were shown. The Japanese version was published in July 2020 and permitted as well as published as one of the Medical Information Network Distribution Service (Minds) clinical practice guidelines in Japan in July 2021.

Gradual reduction in the STOP score in patients with obstructive sleep apnea undergoing oral appliance therapy.

Purpose In the treatment of obstructive sleep apnea (OSA), there is not yet a convenient tool for deciding whether a mandibular advancement oral appliance (OA) is adequately adjusted or when to perform post-treatment sleep-testing. We hypothesized that a gradual reduction in the STOP (snoring, tiredness during daytime, observed apnea, high blood pressure) score, i.e., fewer Yes responses in the STOP questionnaire, in patients undergoing OA treatment could be an indicator of better OA adjustment and, thus, the best timing for follow-up polysomnography.Methods The STOP score was recorded at every patient visit when the OA was adjusted ventrally as necessary (i.e., STOP group). We considered that the appropriate timing for follow-up polysomnography was when the STOP score stopped decreasing. A historical control group was established from consecutive patients without a STOP score.Results In the STOP group (n=57), the median (interquartile range) of STOP scores gradually decreased with OA treatment, from 3 (2-3) to 0 (0-1) (p<0.05). While the apnea hypopnea index (AHI) was improved in both the STOP group (19±10 to 5±4 /hr, p<0.01) and the control group (n=61; 19±7 to 8±7 /hr, p<0.01), there was a significant difference in follow-up AHI between the two groups (p<0.05) after controlling for gender (male), age, body mass index, and baseline AHI: a superior treatment outcome in the STOP group.Conclusions The appropriate timing for follow-up sleep-testing in OSA patients undergoing OA therapy is when the STOP score stopped decreasing. This evaluation using the STOP score partly resolves the current "trial-and-error nature" of OA adjustment and facilitates proper post-treatment sleep-testing.

Clinical characteristics of Japanese patients with familial obstructive sleep apnoea syndrome.

BACKGROUND AND OBJECTIVE: Craniofacial structure and body fat are key factors that predispose to upper airway obstruction while asleep, and these phenotypes can be genetically inherited. Neither the clinical characteristics of familial obstructive sleep apnoea syndrome (OSAS) nor the definitive morphological factors responsible for familial occurrence have been well identified. This study compared the clinical and cephalographic characteristics of Japanese patients with familial OSAS, non-familial OSAS and healthy controls, to clarify the mechanisms underlying familial OSAS. METHODS: The study recruited 28 patients with familial OSAS, comprising 14 index cases and 14 first-degree relatives affected with OSAS, and compared these with age- and sex-matched patients with non-familial OSAS (n = 32) and healthy subjects (n = 33). Data on clinical status were collected, including the presence of hypertension, BMI and daytime sleepiness measured on the Epworth sleepiness scale. Respiratory function was evaluated by the AHI, % periods in which SpO(2) fell 90% or below and lowest value of SpO(2) on polysomnograms. Information on the first witnessed age of habitual snoring during sleep was collected via interview with patients and/or their family members. A detailed cephalometric assessment was made of each study subject. RESULTS: Patients with familial OSAS had lower mean BMI than did patients with non-familial OSAS. The first witnessed age of habitual snoring was younger in the familial cases than the non-familial cases. Cephalometric variables showed that the posterior airway space and the distance between the gonion and the gnathion were significantly smaller in the familial group than in the other two groups. CONCLUSIONS: Familial OSAS occurred at a younger age than non-familial OSAS due to minor anomalies of craniofacial morphology.

Elevated risk of motor vehicle accident for male drivers with obstructive sleep apnea syndrome in the Tokyo metropolitan area.

Previous studies have suggested that patients with obstructive sleep apnea syndrome (OSAS) are at an increased risk of motor vehicle accidents (MVAs). This study is the first systematic investigation of MVA risk among Japanese drivers with obstructive sleep apnea syndrome (OSAS). We investigated the rate of MVAs in the preceding 5 years and dozing off at the wheel in Japanese male OSAS drivers (n = 616, mean [S.D.] age: 46.3 [10.1] years old) and age-matched male controls (n = 600), and the characteristics of OSAS patients who experienced multiple MVAs as well as the effectiveness of continuous positive airway pressure (CPAP) treatment in reducing MVA risk. The odds ratio of MVA in the OSAS group compared to a general population was 2.36. Multivariate logistic regression analysis revealed that MVA was significantly associated with either subjective sleepiness beyond normal limits (Epworth sleepiness scale: ESS > or = 11) or serious respiratory disorders (apnea hypopnea index: AHI > or = 40). AHI scores were significantly higher in the group with multiple MVAs than in those with a single MVA, despite the ESS score in the former group being significantly lower. CPAP treatment was effective for reduction of MVA. The MVA rate among OSAS patients in the research area was significantly higher than that among the controls. Subjective excessive daytime sleepiness and severity of OSAS are independently associated with the occurrence of MVA. In conclusion, early diagnosis and treatment of OSAS drivers especially with serious respiratory disorder should be made to prevent multiple MVAs.

Anatomical balance of the upper airway and obstructive sleep apnea.

BACKGROUND: Obesity and craniofacial abnormalities such as small maxilla and mandible are common features of patients with obstructive sleep apnea (OSA). The authors hypothesized that anatomical imbalance between the upper airway soft-tissue volume and the craniofacial size (rather than each alone) may result in pharyngeal airway obstruction during sleep, and therefore development of OSA. METHODS: Blind measurements of tongue cross-sectional area and craniofacial dimensions were performed through lateral cephalograms in 50 adult male patients with OSA and 55 adult male non-OSA subjects with various craniofacial dimensions. RESULTS: Maxillomandibular dimensions were matched between OSA and non-OSA groups. While the tongue was significantly larger in subjects with larger maxillomandible dimensions, OSA patients had a significantly larger tongue for a given maxillomandible size than non-OSA subjects. The hypothesis was also supported in subgroups matched for both body mass index and maxillomandible dimensions. CONCLUSIONS: Upper airway anatomical imbalance is involved in the pathogenesis of OSA.

Effects of mandibular advancement on brain activation during inspiratory loading in healthy subjects: a functional magnetic resonance imaging study.

Oral appliances have been a popular treatment option for subjects with obstructive sleep apnea. However, little information is available on how brain activation induced by respiratory challenge is modulated by mandibular advancement with these appliances. We hypothesized that the brain activation caused by respiratory stress may be alleviated by mandibular advancement. Respiratory stress was induced in 12 healthy subjects by resistive inspiratory loading. The effects of mandibular advancement during resistive inspiratory loading were assessed subjectively by using a visual analog scale. These effects were also evaluated objectively by using blood oxygenation level-dependent functional magnetic resonance imaging. The score for the visual analog scale significantly decreased with mandibular advancement. Cortical deactivation, in association with mandibular advancement, was localized to several specific regions, including the left cingulate gyrus and the bilateral prefrontal cortexes. These regions are known to be involved in respiratory control. Our results suggest that mandibular advancement with an oral appliance appears to be useful for reducing respiratory stress, based on both subjective and neuronal criteria.

Long-term sequellae of oral appliance therapy in obstructive sleep apnea patients: Part 1. Cephalometric analysis.

INTRODUCTION: Oral appliances (OAs) have been widely used to treat snoring and sleep apnea, but their effects on craniofacial structures in patients after 5 years or more of wear have not yet been quantified. METHODS: Seventy-one patients who had worn adjustable mandibular repositioners to treat snoring or sleep apnea were evaluated. Upright lateral cephalometric radiographs in centric occlusion taken before treatment and after a mean of 7.3 +/- 2.1 years of OA use were compared. Baseline sleep studies and patient demographic data were included in the analysis. RESULTS: Cephalometric analyses after long term OA use showed significant (P < .01) changes in many variables, including increases in mandibular plane and ANB angles; decreases in overbite and overjet; retroclined maxillary incisors; proclined mandibular incisors; increased lower facial height; and distally tipped maxillary molars with mesially tipped and erupted mandibular molars. The initial deep overbite group had a significantly greater decrease in overbite. Duration of OA use correlated positively with variables such as decreased overbite and increased mandibular plane angle; changes in the dentition appeared to be progressive over time. CONCLUSIONS: After long-term use, OAs appear to cause changes in tooth positions that also might affect mandibular posture.

Long-term sequellae of oral appliance therapy in obstructive sleep apnea patients: Part 2. Study-model analysis.

INTRODUCTION: Side effects observed in the occlusion and dental arches of patients using an oral appliance (OA) to treat snoring or sleep apnea for more than 5 years have not yet been investigated. METHODS: Stone casts trimmed in centric occlusion before appliance placement and after an average of 7.4 +/- 2.2 years of OA use in 70 patients were compared visually by 5 orthodontists. RESULTS: Of these patients, 14.3% had no occlusal changes, 41.4% had favorable changes, and 44.3% had unfavorable changes. Significant changes in many variables were found. Patients with greater initial overbites and Class II Division 1 and Class II Division 2 malocclusions were more likely to have favorable or no changes. More favorable changes in overbite occurred in subjects with large baseline overbites. A greater baseline overjet and more distal mandibular canine relationship were correlated to favorable changes. A greater initial overjet was correlated to a more favorable change, a decrease in mandibular crowding, a smaller change in anterior crossbite, and a greater change in overjet. CONCLUSIONS: OA wear after a mean of 7.4 years induces clinically relevant changes in the dental arch and the occlusion.

Oropharyngeal Crowding Closely Relates to Aggravation of OSA.

BACKGROUND: Obesity is known to be an important risk factor for OSA; however, OSA can also be seen in nonobese patients with a small maxilla and/or mandible as well as in all obese patients with such features. Thus, we hypothesized that regional factors, oropharyngeal crowding associated with fat deposition, and maxillomandibular enclosure size closely related to the severity of OSA. METHODS: A total of 703 male Japanese subjects were enrolled; theywere classified into obese (BMI ≥ 30 kg/m(2); n = 158) and nonobese (BMI < 30 kg/m(2); n = 545) groups. Using lateral cephalometric analysis, we measured the tongue size (TG), lower face cage (LFC), and TG/LFC ratio (ie, oropharyngeal crowding) to evaluate the state of upper airway crowding. The correlations between these cephalometric measurements and BMI, age, and the apnea-hypopnea index (AHI) were evaluated. RESULTS: In obese subjects, the TG/LFC ratio, BMI, and TG positively correlated with AHI, whereas, in nonobese subjects, age, BMI, and TG/LFC significantly correlated with AHI. Subsequent stepwise multiple linear regression analysis revealed that the variables associated with AHI differed between obese and nonobese OSA subjects, although BMI and TG/LFC were significantly associated with AHI in both groups. In particular, the contribution of TG/LFC to AHI was larger than that of BMI in the obese group. CONCLUSIONS: Oropharyngeal crowding is a local anatomic factor that independently relates to the severity of OSA in both obese and nonobese patients; the more crowded the upper airway, the more severe the OSA.

Mandibular Advancement Device as a Comparable Treatment to Nasal Continuous Positive Airway Pressure for Positional Obstructive Sleep Apnea.

STUDY OBJECTIVES: Positional obstructive sleep apnea (P-OSA) is a clinically common phenotype of OSA, which can be treated effectively with mandibular advancement devices (MADs). We hypothesized that the efficacy of an MAD is comparable to that of nasal continuous positive airway pressure (nCPAP) in P-OSA patients. METHODS: Among patients diagnosed with OSA at a single sleep center from January 2008 to May 2014, male subjects with moderate OSA were recruited and stringently categorized as having P-OSA when the ratio of their lateral apnea-hypopnea index (AHI) to supine AHI was ≤ 0.5, their lateral sleep time was > 60 minutes, and their lateral REM sleep time was longer than 10 minutes. Treatment efficacy was compared between P-OSA subjects with an MAD (n = 34) and those with nCPAP (n = 34) after matching for age, body-mass index, and baseline AHI. RESULTS: There were no significant differences in baseline AHI (MAD: nCPAP = 20.6 ± 3.9/h: 21.3 ± 1.7/h, p = 0.35) or in follow-up AHI (MAD: nCPAP = 4.7 ± 3.5/h: 3.4 ± 3.7/h, p = 0.12) between the 2 treatment groups, and hence MADs lowered the AHI to the same extent as nCPAP. CONCLUSIONS: These findings suggest that an MAD is as efficacious as nCPAP for P-OSA patients. MAD treatment for this specific phenotype may be a promising patient-tailored and first-line approach to OSA. COMMENTARY: A commentary on this article appears in this issue on page 1079.

Obstructive sleep apnea syndrome in a pubescent boy of short stature was improved with an orthodontic mandibular advancement oral appliance: a case report.

ABSTRACT: We report a 16-year-old pubescent pediatric patient with obstructive sleep apnea syndrome (OSAS) and short stature whose apnea hypopnea index (AHI) was significantly reduced following the use of an orthodontic oral appliance that advances the mandible ventrally. The mandible was advanced 64% of the maximal mandibular protrusive position with use of the appliance over a 3-year period. The patient's AHI without the appliance in place decreased from 101.6/h at baseline to 11/h after treatment. Moreover, the patient's height increased 14 cm during treatment, resulting in height close to the average height for his age. Cephalometric analysis revealed an improvement in his retrognathic mandible and proclination of the upper front teeth. In conclusion, an orthodontic mandibular advancement oral appliance played an important role not only in improving the patient's OSAS but also in normalizing his physical growth during puberty.