Pathogenesis Of Obstructive Sleep Apnea Research Articles

Effect of obesity on sleep apnea pathogenesis differs in women versus men: multiple mediation analyses in the retrospective SNOOzzzE cohort.

There are multiple mechanisms underlying obstructive sleep apnea (OSA) development. However, how classic OSA risk factors such as body mass index (BMI) and sex portend to OSA development has not been fully described. Thus we sought to evaluate how obesity leads to OSA and assess how these mechanisms differ between men and women. The San Diego Multi-Outcome OSA Endophenotype (SNOOzzzE) cohort includes 3,319 consecutive adults who underwent a clinical in-laboratory polysomnography at the University of California, San Diego, sleep clinic between January 2017 and December 2019. Using routine polysomnography signals, we determined OSA endotypes. We then performed mediation analyses stratified by sex to determine how BMI influenced the apnea-hypopnea index (AHI) using OSA pathophysiological traits as mediators, adjusting for age, race, and ethnicity. We included 2,146 patients of whom 919 (43%) were women and 1,227 (57%) were obese [body mass index (BMI) > 30 kg/m2]. BMI was significantly associated with AHI in both women and men. In men, the adjusted effect of BMI on AHI was partially mediated by a reduction in upper airway stiffness (βstandardized = 0.124), a reduction in circulatory delay (βstandardized = 0.063), and an increase in arousal threshold (βstandardized = 0.029; Pboot-strapped,all < 0.05). In women, the adjusted effect of BMI on AHI was partially mediated by a reduction in upper airway stiffness (βstandardized = 0.05) and circulatory delay (βstandardized = 0.037; Pboot-strapped,all < 0.05). BMI-related OSA pathogenesis differs by sex. An increase in upper airway collapsibility is consistent with prior studies. A reduction in circulatory delay may lead to shorter and thus more events per hour (higher AHI), while the relationship between arousal threshold and OSA is likely complex.NEW & NOTEWORTHY Our data provide important insights into obesity-related obstructive sleep apnea (OSA) pathogenesis, thereby validating, and extending, prior research findings. This is the largest sample size study to examine the relationships between obesity and gender on OSA pathogenesis. The influence of obesity on sleep apnea severity is mediated by different mechanistic traits (endotypes).

Association Between Soft Tissue Measures From Computed Tomography and Upper Airway Collapsibility on Drug-Induced Sleep Endoscopy.

Positive airway pressure (PAP) titration during drug-induced sleep endoscopy (DISE) provides objective measures of upper airway collapsibility. While skeletal measurements relate to collapsibility measures on DISE, the influence of soft tissue dimensions on upper airway collapsibility is not known. We analyzed the relationship of measures of upper airway soft tissue volumes, specifically soft palate, pharyngeal lateral walls, and tongue, with metrics of collapsibility. Cross-sectional analysis from a prospective cohort. Academic medical center. Patients seeking PAP alternative therapies for obstructive sleep apnea (OSA) underwent standardized supine computed tomography (CT) acquisition and DISE protocols. The CT analysis primarily focused on soft tissue volumes and, secondarily, on airway and skeletal volumetric measures. DISE with PAP administration (DISE-PAP) enabled the determination of the pressure at which inspiratory airflow first commenced (pharyngeal critical pressure, PcritA) and the pressure at which inspiratory flow limitation was abolished (pharyngeal opening pressure, PhOP). Both unadjusted and adjusted correlation analyses were performed to understand the relationship between upper airway anatomy and either PcritA or PhOP. One hundred thirty-nine subjects completed both CT and DISE-PAP. On average, patients were male (70.5%), white (84.2%), middle-aged (56.6 ± 13.5 years), and overweight (29.6 ± 4.7 kg/m2), with moderate-severe apnea-hypopnea index (29.7 ± 21.3 events/h). Adjusted for age, sex, body mass index, and skeletal volumes, soft palate, and lateral pharyngeal wall volumes were not associated with PhOP or PcritA, but a larger tongue was associated with more positive PhOP (⍴ = 0.20, P = .02), and more positive PcritA (⍴ = 0.16, P = .07). Exploratory analyses revealed smaller minimum cross-sectional retropalatal area and intramandibular volume were also associated with increased collapsibility measures. After controlling for clinical factors and skeletal volume, greater tongue volume was associated with more severe collapsibility during DISE. These results, in concert with previous work, suggest that greater tongue volume in a smaller skeletal dimensions contribute to the severity of airway collapsibility, a key driver of OSA pathogenesis.

A review of obstructive sleep apnea and lung cancer: epidemiology, pathogenesis, and therapeutic options.

Despite undeniable advances in modern medicine, lung cancer still has high morbidity and mortality rates. Lung cancer is preventable and treatable, and it is important to identify new risk factors for lung cancer, especially those that can be treated or reversed. Obstructive sleep apnea (OSA) is a very common sleep-breathing disorder that is grossly underestimated in clinical practice. It can cause, exacerbate, and worsen adverse outcomes, including death and various diseases, but its relationship with lung cancer is unclear. A possible causal relationship between OSA and the onset and progression of lung cancer has been established biologically. The pathophysiological processes associated with OSA, such as sleep fragmentation, intermittent hypoxia, and increased sympathetic nervous excitation, may affect normal neuroendocrine regulation, impair immune function (especially innate and cellular immunity), and ultimately contribute to the occurrence of lung cancer, accelerate progression, and induce treatment resistance. OSA may be a contributor to but a preventable cause of the progression of lung cancer. However, whether this effect exists independently of other risk factors is unclear. Therefore, by reviewing the literature on the epidemiology, pathogenesis, and treatment of lung cancer and OSA, we hope to understand the relationships between the two and promote the interdisciplinary exchange of ideas between basic medicine, clinical medicine, respiratory medicine, sleep medicine, and oncology.

State-Dependent Biomechanical Behavior of Oropharyngeal Structures in Apneic and Control Subjects: A Proof-of-Concept Study.

Rationale: Apneic individuals have reduced airway caliber during sleep. The biomechanical changes in upper airway anatomy contributing to this airway narrowing are largely unknown. Objectives: We sought to investigate the state-dependent (wake vs. sleep) biomechanical behavior of the upper airway soft-tissue and craniofacial structures. Methods: Upper airway magnetic resonance imaging was performed in 15 sleep-deprived control subjects (apnea-hypopnea index, <5; 0.3 ± 0.5 events per hour) and 12 sleep-deprived apneic subjects (apnea-hypopnea index, ⩾5; 35.2 ± 18.1 events per hour) during wake and sleep and analyzed for airway measures and soft-tissue/mandibular movement. Results: In the retropalatal region, control subjects showed sleep-dependent reductions (P ⩽ 0.037) in average cross-sectional airway area (CSA), minimum CSA, and anteroposterior and lateral dimensions. Apneic subjects showed sleep-dependent reductions (P ⩽ 0.002) in average CSA, minimum CSA, and anteroposterior and lateral dimensions. In the retroglossal region, control subjects had no sleep-dependent airway reductions. However, apneic subjects had sleep-dependent reductions in minimal CSA (P = 0.001) and lateral dimensions (P = 0.014). Control subjects only showed sleep-dependent posterior movement of the anterior-inferior tongue octant (P = 0.039), whereas apneic subjects showed posterior movement of the soft palate (P = 0.006) and all tongue octants (P ⩽ 0.012). Sleep-dependent medial movement of the lateral walls was seen at the retropalatal minimum level (P = 0.013) in control subjects and at the retropalatal and retroglossal minimum levels (P ⩽ 0.017) in apneic subjects. There was posterior movement of the mandible in apneic subjects (P ⩽ 0.017). Conclusions: During sleep, control and apneic subjects showed reductions in retropalatal airway caliber, but only the apneic subjects showed retroglossal airway narrowing. Reductions in anteroposterior and lateral airway dimensions were primarily due to posterior soft palate, tongue and mandibular movement and to medial lateral wall movement. These data provide important initial insights into obstructive sleep apnea pathogenesis.

Exploring the link between vitamin D deficiency and obstructive sleep apnea: A comprehensive review.

Despite the high prevalence and significant health burden of obstructive sleep apnea (OSA), its underlying pathophysiology remains incompletely understood. This comprehensive review explores the emerging connection between vitamin D deficiency and OSA, discusses potential mechanisms underlying this association, and explores the therapeutic implications of these findings. Recent research has consistently highlighted the high incidence of vitamin D deficiency among patients with OSA, which often occurs independently of geographical location. This suggests that factors beyond lack of sunlight exposure may be involved. This review also discusses how reduced vitamin D may be associated with more severe manifestations of OSA. In addition, it explores the potentiality of using vitamin D supplements as a therapeutic strategy for OSA, noting that some studies have found improvements in sleep quality and a reduction in OSA severity. Potential mechanisms are proposed, including the role of vitamin D deficiency in promoting inflammation, oxidative stress, hypoxia, impairing immune function, muscle function, and gene polymorphism of vitamin D receptors, all of which could contribute to the pathogenesis of obstructive sleep apnea. The paper underscores the need for future research to validate these observations, to determine optimal vitamin D supplementation dosage and duration, to explore potential side effects and risks, and to investigate potential interactions with other treatments.

Bioinformatics-based identification of key candidate genes and signaling pathways in patients with Parkinson's disease and obstructive sleep apnea.

Existing evidence exhibits that obstructive sleep apnea (OSA) is a potential consequence of Parkinson's disease (PD) or a contributor to PD progression. This investigation aimed to detect potential critical genes and molecular mechanisms underlying interactions between PD and OSA through bioinformatics analyses. The Gene Expression Omnibus (GEO) database was employed to obtain the expression profiles GSE20163 and GSE135917. The identification of common genes connected to PD and OSA was performed utilizing weighted gene co-expression network analysis and the R 4.0.4 program. The Cytoscape program was utilized to generate a network of protein-protein interactions (PPI), and the CytoHubba plugin was utilized to detect hub genes. Subsequently, functional enrichment analyses of the hub genes were conducted. Markers with increased diagnostic values for PD and OSA were confirmed using the GEO datasets GSE8397 and GSE38792. Typically, 57 genes that are common were identified in PD and OSA. Among these common genes, the top 10 hub genes in the PPI network were chosen. The verified datasets confirmed the presence of three important genes: CADPS, CHGA, and SCG3. Functional enrichment analysis revealed that these hub genes mostly participate in GABAergic synapses. Our findings suggest that CADPS, CHGA, and SCG3 are key genes involved in molecular mechanisms underlying interactions between OSA and PD. Functional enrichment of hub genes indicated a link between GABAergic synapses and the shared pathogenesis of PD and OSA. These candidate genes and corresponding pathways offer novel insights regarding biological targets that underlie the transcriptional connection between OSA and PD.

Causal Effects of Blood Metabolites and Obstructive Sleep Apnea: A Mendelian Randomization Study.

Obstructive sleep apnea (OSA) is one of the most common forms of sleep-disordered breathing. Studies have shown that certain changes in metabolism play an important role in the pathophysiology of OSA. However, the causal relationship between these metabolites and OSA remains unclear. We use a mendelian randomization (MR) approach to investigate the causal associations between the genetic liability to metabolites and OSA. We performed a 2-sample inverse-variance weighted mendelian randomization analysis to evaluate the causal effects of genetically determined 486 metabolites on OSA. Multiple sensitivity analyses were performed to assess pleiotropy. We used multivariate mendelian randomization analyses to assess confounding factors and mendelian randomization Bayesian model averaging to rank the significant biomarkers by their genetic evidence. We also conducted a metabolic pathway analysis to identify potential metabolic pathways. We identified 14 known serum metabolites (8 risk factors and 6 protective factors) and 12 unknown serum metabolites associated with OSA. These 14 known metabolites included 8 lipids( 1-arachidonoylglycerophosphoethanolamine, Tetradecanedioate, Epiandrosteronesulfate, Acetylca Glycerol3-phosphate, 3-dehydrocarnitine, Margarate17:0, Docosapentaenoaten3;22:5n3), 3 Aminoacids (Isovalerylcarnitine,3-methyl-2-oxobutyrate,Methionine), 2 Cofactors and vitamins [Bilirubin(E,ZorZ,E),X-11593--O-methylascorbate], 1Carbohydrate(1,6-anhydroglucose). We also identified several metabolic pathways that involved in the pathogenesis of OSA. MR (mendelian randomization) approach was performed to identify 6 protective factors and 12 risk factors for OSA in the present study. 3-Dehydrocarnitine was the most significant risk factors for OSA. Our study also confirmed several significant metabolic pathways that were involved in the pathogenesis of OSA. Valine, leucine and isoleucine biosynthesis metabolic pathways were the most significant metabolic pathways that were involved in the pathogenesis of OSA.

Use of Ultrasound to Verify the Impact of Telemedicine Myofunctional Therapy on Sleep Apnea Syndrome: Study Protocol Proposal.

The anatomy of the upper airways influences the risk of obstructive sleep apnea (OSA). The size of soft tissue structures, such as the tongue, soft palate, and lateral walls of the pharynx, contributes to the pathogenesis of OSA. New lines of treatment for sleep apnea, such as myofunctional therapy (MT), aim to strengthen the oropharyngeal musculature to improve the defining parameters of apnea. The present protocol uses ultrasound imaging to measure the size of the lingual musculature non-invasively and cost-effectively and evaluates the changes in its morphology. Eligible patients include those with OSA who have undergone submental cervical ultrasound and drug-induced sleep endoscopy before starting MT with the AirwayGym app. Follow-up evaluations are conducted at 3 months after beginning treatment. Patients diagnosed with OSA via questionnaires and polysomnography or respiratory polygraphy are evaluated anatomically and functionally using the Iowa Oral Performance Instrument, a tongue digital spoon, somnoscopy, and submental cervical ultrasound to assess their responses to the AirwayGym app. The lingual thickness (mm) and volume (cm3) and the distance between both lingual arteries (mm) are measured. The AirwayGym app helps users and therapists monitor the patient performance of MT. Incorporating submental ultrasound can be a useful non-invasive tool to evaluate OSA and MT.

Analysis of gut target microbiota and species difference in patients with obstructive sleep apnea based on 16S rRNA sequencing

To explore the difference in gut microbiota composition between patients with obstructive sleep apnea (OSA) and healthy individuals and the role of gut microbiota in the pathogenesis of OSA. Thirty-nine patients with OSA admitted to our hospital between May and December, 2022 and 20 healthy individuals were enrolled in this study. Stool samples were collected from all the participants for analysis of microbiome composition using 16S rRNA high- throughput sequencing analysis. The alpha diversity, beta diversity, and species difference were determined between the two groups and marker species analysis and metabolic pathway function prediction analysis were performed. The species diversity (Shannon and Simpson) indexes, richness (observed species) and evenness (Pielou) of gut microbiota were significantly lower in OSA patients than in the healthy individuals (P < 0.05). The OSA patients had also a significantly lowered community diversity (P < 0.05) with different gut microbial communities from those of the healthy individuals shown by increased relative abundance of potentially pathogenic bacteria such as Pseudomonas and Monocytogenes (P < 0.05). LEfSe analysis showed that the abundance of 23 species of gut microbiota differed significantly between the two groups and the OSA patients had significant increases in the abundance of Pseudomonas, Meganomonas, and Fusobacterium (P < 0.05). The differential marker flora affected host homeostasis. Random Forest and ROC curve analyses confirmed that Pseudomonas could be used as important biomarkers for a differential diagnosis. Metabolic pathway function prediction analysis showed that biosynthesis function had the greatest contribution to maintaining gut microbiota homeostasis, and Pseudomonas affected the occurrence and progression of OSA by participating in aromatic bioamine degradation and ketogluconic acid metabolic pathway. OSA patients have obvious gut microbiota disturbances, and Pseudomonas may affect the development of OSA by participating in substance metabolism to serve as the potential target gut bacteria for OSA treatment.

Serum neopterin, YKL-40, IL-6, and TNF-α in patients with obstructive sleep apnea

Objective: Obstructive Sleep Apnea (OSA) is characterized by recurrent episodes of complete or partial upper airway obstruction during sleep. The role of locally increased inflammation in the upper respiratory tract is known in the pathogenesis of OSA. This study aimed to examine the role of some inflammatory markers in OSA. Materials and Methods: Adult patients who underwent diagnostic polysomnography (PSG) for the first time, were evaluated in this prospective study. Serum levels of neopterin, human cartilage glycoprotein 39 (YKL-40), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were examined in the study group. Results: The study included 165 adult patients. Individuals of 56 who were did not have OSA were taken as the control group. Patients diagnosed with OSA (n=109) were included in the study and divided into two groups mild-moderate and severe based on the OSA apnea-hypopnea index (AHI). The study groups were divided into 3 cathegories: AHI &lt;5 (control) Group 1, AHI 5-15 (mild), and AHI 15-30 (moderate) Group 2, AHI&gt;30 (severe) Group 3. Individuals of 165 who completed the study [Group 1 (n=56), Group 2 (n=69), Group 3 (n=40)] were included in the statistical evaluation. There was a significant difference between the groups in terms of neopterin, YKL-40, and IL-6 values (p&lt;0.05). The median value of IL-6 and neopterin measured in the severe group was significantly higher than the value measured in the control and mild-moderate groups (p&lt;0.001). The mean value of YKL-40 measured in the severe group was significantly higher than the value measured in the control group (p=0.012). No significant difference was observed in TNF-α serum levels of groups. Conclusion: Serum levels of neopterin, YKL-40, and IL-6 were found to be elevated in OSA patients (especially in the severe group).

New insights from integrated bioinformatics analysis: the role of circadian rhythm disruption and immune infiltration in obstructive sleep apnea disease.

Circadian rhythm disruption and immune infiltration are both closely associated with the development of Obstructive sleep apnea (OSA) disease and a variety of cardiovascular and neurological complications, but their interactions with OSA disease are not clear. In this study, we used bioinformatics to investigate the roles of circadian rhythm disruption and immune microenvironments in OSA. We analyzed differential genes and their associated functional pathways in the circadian rhythm-associated OSA dataset, then regrouped OSA samples using the differential genes and explored differences in immune cell infiltration between the two different subgroups. Meanwhile, we used two machine learning algorithms to further define circadian rhythm-related signature genes and to explore the relationship between key genes and immune cell infiltration. Finally, we searched for the transcription factors of the key differential gene JUN. We screened 15 circadian rhythm-related differential genes in the OSA-related dataset and further defined 3 signature genes by machine learning algorithms. Immunoassays showed a significant increase in resting mast cell infiltration and a decrease in monocyte infiltration in the OSA group. The results of our animal experiments also confirmed that the expression of these 3 key genes, as well as the immune cell infiltration, showed a trend consistent with the results of the bioinformatics analysis. In conclusion, this study reveals the interaction between circadian rhythm disruption and immune infiltration in OSA, providing new insights into the potential pathogenesis of OSA.

Application value of arousal threshold in obstructive sleep apnea

The pathogenesis of obstructive sleep apnea (OSA) includes anatomical and non-anatomical factors, and the arousal threshold (ArTH) is one of the important non-anatomical factors. At present, the main method is to assess the increased respiratory effort due to arousal to determine the arousal threshold, and invasive epiglottic or esophageal manometry is the gold standard, while the non-invasive continuous positive airway pressure (CPAP) method and polysomnography (PSG) ventilation signal conversion method are also widely used. Arousal threshold is expected to serve as an important evaluation index and potential target for drug therapy in OSA, which is of great importance for realization of precise treatment of OSA. This article focused on the method and clinical significance of OSA arousal threshold.

Analysing the impact of body position shift on sleep architecture and stage transition: A comprehensive multidimensional study using event‐synchronised polysomnography data

SummaryAlthough understanding the physiological mechanisms of obstructive sleep apnea (OSA) is important for treating OSA, limited studies have examined OSA patients’ sleep architecture at the epoch‐by‐epoch level and analysed the impact of sleep position and stage on OSA pathogenesis. The epoch‐labelled polysomnogram was analysed multidimensionally to investigate the effect of sleep position on the sleep architecture and risk factors of apnea in patients with OSA. This retrospective multicentric case–control study reviewed full‐night diagnostic polysomnography of 6983 participants. The difference in the proportion of time spent supine during non‐rapid eye movement (NREM) and REM stages, and the mean duration of respiratory events per body position were evaluated. The frequency of sleep stage transition per body position shift type was computed. Further subgroup analysis was performed based on OSA severity and positional dependency. Supine time in patients with OSA varied across sleep stages, with lower proportions in N3 and REM, and shorter durations with severity. Patients with OSA spent less time in supine positions during N3 and REM, and experienced longer apnea events in both positions compared to the control group. The frequency of all sleep stage transitions increased with OSA severity and was higher among non‐positional OSA than positional OSA and the control group, regardless of body position shift type. The sleep stage transition from N3 and REM to wakefulness was notably heightened during position shift. Understanding the sleep architecture of patients with OSA requires analysing various sleep characteristics including sleep position simultaneously, with future studies focusing on position detection to predict sleep stages and respiratory events.

Urinary metabolite signatures reflect the altered host metabolism in severe obstructive sleep apnea

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder. The onset and progression of OSA are often linked with severe cardiovascular and metabolic comorbidities. At the same time, given the increasing prevalence of OSA, novel methods to screen OSA and its follow-up are needed. Untargeted metabolic profiling of OSA patients and healthy controls was planned to capture a snapshot of urinary metabolites and potential biomarkers using the gas chromatography-mass spectrometry (GC–MS) method.Polysomnography (PSG) confirmed severe OSA patients with AHI index ≥ 30 were considered for urine sample collection. The sample size was constituted of OSA (n = 36) and healthy controls (n = 36). Metabolite extraction and derivatization were performed and metabolomic analysis was performed by using GC–MS.The obtained data set was statistically analyzed using univariate and multivariate analysis. The Orthogonal partial least-squares discriminant analysis (OPLS-DA) was performed to screen differential metabolites between OSA patients and healthy controls.The metabolomic analysis revealed a total of 142 significantly altered metabolites of interest.Biomarker analysis allows for the creation of a list of putative urinary biomarkers including GABA, malic acid, glutamic acid, epichoric acid etc., with an accuracy of 99.8 % to 100 % for OSA screening. Subsequently, pathway analysis revealed that related biochemical pathways like the tricarboxylic acid cycle (TCA), glutamate/glutamine, amino acid and fatty acid metabolism, that are significantly interlinked with these metabolic biomarkers can play a crucial role in the pathogenesis of OSA. This study paves the way to undertake mass screening in a larger population to identify specific and reliable biomarkers.

Sleep Apnea and Dental Implications -A Review

Obstructive sleep apnea (OSA) is an increasingly common, chronic, sleep-related breathing disorder.The prevalence of obstructive sleep apnea (OSA) continues to rise due to change in life patterns.The most common presenting symptom of OSA is excessive sleepiness and is associated with a 2- to 3-fold increased risk of cardiovascular and metabolic disease. The key contributors to OSA pathogenesis include a narrow, crowded, or collapsible upper airway “anatomical compromise” and “non-anatomical” contributors such as ineffective pharyngeal dilator muscle function during sleep, a low threshold for arousal to airway narrowing during sleep, and unstable control of breathing. Effective treatments include weight loss and exercise, positive airway pressure, oral appliances that hold the jaw forward during sleep, and surgical modification of the pharyngeal soft tissues or facial skeleton to enlarge the upper airway. This review summarizes the latest knowledge ondifferent contributors to OSA with a focus on emerging clinical tools.

Cephalometric profile analysis between genders. A study protocol

Background: According to current American Association of Orthodontists guidelines, two-dimensional lateral and posteroanterior cephalometric radiographs are recognized as essential components of diagnostic imaging records in orthodontics. Cephalometry is defined as the discipline that analyzes the craniofacial complex in a segmented way, to study the interrelationships between its structures and understand how the growth or alteration of one of these structures can compromise the whole. Through cephalometry, it is possible to indicate the clinical approach for patients, involving dental therapy with intraoral appliances and physical therapy with continuous positive pressure in the upper airway. Objectives: Investigate possible differences in cephalometric anatomical patterns between genders. Methods: This study protocol follows the STROBE - Strengthening the Reporting of Observational Studies in Epidemiology guidelines. A convenience sample will be used, consisting of teleradiography (cephalograms) of adult patients of both genders, carried out in a private Dental Clinic, located in the city of São José dos Campos (SP), Brazil, by the established inclusion and exclusion criteria. Six angular and nine linear measurements will be used in the analysis of cephalometric measures according to the study protocol. The exams will be distributed into three groups and paired according to the value of the angle formed between point A nasion and point B nasion (ANB). Groups will be formed by exams with class 1 skeletal relationship (0o &lt; ANB angle ≤ 4º), group 2 with class 2 exams (ANB angle &gt; 4°), and group 3 formed by class 3 exams (ANB angle ≤ 0°). Considerations: In some cases, craniofacial changes may predict the risk of sleep-disordered breathing, such as obstructive sleep apnea (OSA). Increased length and thickness of the soft palate and hyoid bone in the mandibular plane and retrognathia are associated with the pathogenesis of OSA. Therefore, the etiology of sleep-disordered breathing may vary in patients according to gender, according to cephalometric analysis.

Association between nasal airway minimal cross-sectional areas and obstructive sleep apnoea.

Patients with obstructive sleep apnoea (OSA) frequently present with some form of upper airway anatomical impairment. Considerable research has been conducted on the role of the structures of the jaw and pharynx in the pathogenesis of OSA; however, the significance of the nose is somewhat unclear. Computed tomography is a widely used imaging modality for assessing the nasal cavity and paranasal sinuses, but only a small amount of the acquired data is used. Our aim was to ascertain whether the size of the cross-sectional areas of the nasal airway, measured from cone beam computed tomography (CBCT) images, is associated with OSA severity. A total of 58 patients with OSA, without any major paranasal sinus inflammatory pathology, were included in this register-based study. Patients had previously undergone ambulatory polysomnography and CBCT. The cross-sectional areas of the nasal cavity were measured in CBCT coronal sections. Statistical analyses were performed to determine any correlation between the cross-sectional area measurements and apnoea-hypopnoea index (AHI) or any significant difference in cross-sectional areas between AHI severity groups. No correlation was found between AHI and the smallest, total, or sum of the anterior cross-sectional areas of the nasal airway. Furthermore, there was no statistically significant difference in the cross-sectional areas between patients with the highest and lowest AHI. The small cross-sectional area of the anterior nasal cavity in patients without any major nasal pathology does not appear to be associated with OSA severity.

Influence of glutamatergic and GABAergic neurotransmission on obstructive sleep apnea.

Glutamate and γ-aminobutyric acid (GABA) are the two main neurotransmitters in the human brain. The balance between their excitatory and inhibitory functions is crucial for maintaining the brain's physiological functions. Disturbance of glutamatergic or GABAergic neurotransmission leads to serious health problems including neurodegeneration, affective and sleep disorders. Both GABA and glutamate are involved in the control of the sleep-wake cycle. The disturbances in their function may cause sleep and sleep-related disorders. Obstructive sleep apnea (OSA) is the most common sleep respiratory disorder and is characterized by repetitive collapse of the upper airway resulting in intermittent hypoxia and sleep fragmentation. The complex pathophysiology of OSA is the basis of the development of numerous comorbid diseases. There is emerging evidence that GABA and glutamate disturbances may be involved in the pathogenesis of OSA, as well as its comorbidities. Additionally, the GABA/glutamate targeted pharmacotherapy may also influence the course of OSA, which is important in the implementation of wildly used drugs including benzodiazepines, anesthetics, and gabapentinoids. In this review, we summarize current knowledge on the influence of disturbances in glutamatergic and GABAergic neurotransmission on obstructive sleep apnea.

Adaptive responses to chronic intermittent hypoxia: contributions from the European Sleep Apnoea Database (ESADA) Cohort.

Obstructive sleep apnoea (OSA) is a common disease in the general population, and is associated with increased cardiovascular risk and several comorbidities. Obesity favours upper airway collapsibility, but other pathophysiological traits have been identified, i.e. upper airway muscle activity, modulation of the respiratory drive, and the arousal threshold. OSA causes chronic intermittent hypoxia, inflammatory activation and autonomic imbalance with diurnal and nocturnal sympathetic hyperactivity. Disentangling so many components to investigate the pathogenesis of OSA's consequences is very hard clinically. However, albeit imperfect, clinical medicine constitutes a major source of inspiration for basic research, and a mutual exchange of information is essential between clinicians and physiologists to improve our understanding of disease states. OSA is no exception, and this narrative review will summarize the results of clinical studies performed over the years by the European Sleep Apnoea Database (ESADA) Study Group, to explore the variables linked to markers of intermittent hypoxia as opposed to the traditional assessment of OSA severity based on the frequency of respiratory events during sleep (the Apnoea Hypopnoea Index). The results of the clinical studies indicate that intermittent hypoxia variables are associated with several comorbidities, although evidence of a cause-effect relationship is still missing in many cases. It is also possible that adaptive rather than maladaptive responses could be evoked by intermittent hypoxia. The intensity, duration and frequency of intermittent hypoxia episodes causing adaptive rather than maladaptive responses, and their clinical implications, deserve further investigation.

Salivary trefoil factor family peptide 3 (TFF3) and flow rate in persons with and without obstructive sleep apnea: A preliminary study.

Obstructive sleep apnea (OSA) is one of the most common chronic diseases. Trefoil factor family 3 (TFF3) peptides are secreted by major and minor salivary glands and may be involved in the pathogenesis of OSA. This study aimed to evaluate salivary TFF3 and flow rate between those with and without OSA. This was a prospective experimental study that enrolled patients with OSA and non-OSA. Total unstimulated saliva was collected, the salivary flow rate was measured, and theTFF3 level was analyzed by using a modified sandwich enzyme-linked immunosorbent assay. Baseline characteristics, TFF3 level, and salivary flow rate were compared between both groups. Factors associated with theTFF3 level and flow rate were computed by using multivariate linear regression analysis. Twenty-eight participants were recruited in the study: 20 patients with OSA (71.42%) and 8 non-OSA as control. The TFF3 and salivary flow rates between both groups of non-OSA versusOSA were comparable (TFF3 non-OSA 61.06 vs.OSA 96.00 ng/mg; p = .276 and flow rate non-OSA0.40 vs. OSA 0.35 mL/min; p = .320). Factors associated with theTFF3 level were neck circumference with a negative coefficient of -16.419 (p = .042). For the salivary flow rate, only age was a significant factor with the coefficient of -0.013 (p = .044). TFF3 and salivary flow rate were comparable between patients with OSA and non-OSA.The factor associated with TFF3 level was neck circumference, while age was negatively associated with the salivary flow rate in patients with OSA.