Obstructive Sleep Apnea Phenotypes Research Articles

Evaluation of daytime sleepiness and insomnia symptoms in OSA patients with a characterization of symptom-defined phenotypes and their involvement in depression comorbidity-a cross-sectional clinical study.

Recent research highlights the significance of insomnia and sleepiness, shifting from obstructive sleep apnea (OSA) severity and sleep structure, in defining OSA phenotypes. This study aimed to characterize insomnia and sleepiness associated with OSA phenotypes and assess their involvement in depression symptoms (DS) in OSA. This cross-sectional, clinical study included 181 participants who underwent polysomnography (PSG) and filled out questionnaires, including the Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and Beck Depression Index (BDI). They were categorized into phenotypes: insomnia-sleepiness (I + S; ESS ≥ 11; ISI ≥ 15; n = 20), sleepiness (S; ESS ≥ 11; ISI < 15; n = 22), insomnia (I; ESS < 11; ISI ≥ 15), and asymptomatic (A; ESS < 11; ISI<15; n=55). A linear regression model for the BDI score (R2=0.357, p < 0.001) included ISI score and subjective-to-objective sleep latency ratio. The ISI score was a predictive factor for mild and moderate DS [OR = 1.23 (95% CI: 1.09-1.38), p < 0.001 and OR = 1.39 (95% CI: 1.13-1.72), p = 0.002]. The I and I + S phenotypes are characterized by higher BDI scores (p < 0.001 and p = 0.02), longer subjective sleep latency (p = 0.008 and p = 0.04), and shorter subjective total sleep time (TST; p = 0.049 and p = 0.006) compared to A. Furthermore, the I and I + S groups had shorter subjective TST than S (p = 0.03 and p = 0.047). The I and I + S had higher BDI scores than A (p < 0.001 and p = 0.02, respectively) and S (p < 0.001 and p = 0.02, respectively). The I phenotype was associated with the risk of mild and moderate DS (OR = 5.61 (95% CI: 1.91-16.53), p < 0.001 and OR = 9.55 (95% CI: 1.81-50.48), p = 0.008 respectively). Moreover, the I + S phenotype presented an even greater risk for mild DS (OR = 10.29 (95% CI: 2.95-35.85), p < 0.001). Using clinical features for OSA phenotyping holds promise for finding OSA individuals with increased risk for DS occurrence.

Beat-to-beat cardiac repolarization lability increases during hypoxemia and arousals in obstructive sleep apnea patients.

Obstructive sleep apnea (OSA) is associated with the progression of cardiovascular diseases, arrhythmias, and sudden cardiac death (SCD). However, the acute impacts of OSA and its consequences on heart function are not yet fully elucidated. We hypothesized that desaturation events acutely destabilize ventricular repolarization, and the presence of accompanying arousals magnifies this destabilization. Ventricular repolarization lability measures, comprising heart rate corrected QT (QTc), short-time-variability of QT (STVQT), and QT variability index (QTVI), were calculated before, during, and after 20,955 desaturations from lead II electrocardiography signals of 492 patients with suspected OSA (52% men). Variations in repolarization parameters were assessed during and after desaturations, both with and without accompanying arousals, and groupwise comparisons were performed based on desaturation duration and depth. Regression analyses were used to investigate the influence of confounding factors, comorbidities, and medications. The standard deviation (SD) of QT, mean QTc, SDQTc, and STVQT increased significantly (P < 0.01), whereas QTVI decreased (P < 0.01) during and after desaturations. The changes in SDQT, mean QTc, SDQTc, and QTVI were significantly amplified (P < 0.01) in the presence of accompanying arousals. Desaturation depth was an independent predictor of increased SDQTc (β = 0.405, P < 0.01), STVQT (β = 0.151, P < 0.01), and QTVI (β = 0.009, P < 0.01) during desaturation. Desaturations cause acute changes in ventricular repolarization, with deeper desaturations and accompanying arousals independently contributing to increased ventricular repolarization lability. This may partially explain the increased risk of arrhythmias and SCD in patients with OSA, especially when the OSA phenotype includes high hypoxic load and fragmented sleep.NEW & NOTEWORTHY Nocturnal desaturations are associated with increased ventricular repolarization lability. Deeper desaturations with accompanying arousals increase the magnitude of alterations, independent of confounding factors, comorbidities, and medications. Changes associated with desaturations can partially explain the increased risk of arrhythmias and sudden cardiac death in patients with OSA, especially in patients with high hypoxic load and fragmented sleep. This highlights the importance of detailed electrocardiogram analytics for patients with OSA.

Achieving Better Understanding of Obstructive Sleep Apnea Treatment Effects on Cardiovascular Disease Outcomes through Machine Learning Approaches: A Narrative Review.

Obstructive sleep apnea (OSA) affects almost a billion people worldwide and is associated with a myriad of adverse health outcomes. Among the most prevalent and morbid are cardiovascular diseases (CVDs). Nonetheless, randomized controlled trials (RCTs) of OSA treatment have failed to show improvements in CVD outcomes. A major limitation in our field is the lack of precision in defining OSA and specifically subgroups with the potential to benefit from therapy. Further, this has called into question the validity of using the time-honored apnea-hypopnea index as the ultimate defining criteria for OSA. Recent applications of advanced statistical methods and machine learning have brought to light a variety of OSA endotypes and phenotypes. These methods also provide an opportunity to understand the interaction between OSA and comorbid diseases for better CVD risk stratification. Lastly, machine learning and specifically heterogeneous treatment effects modeling can help uncover subgroups with differential outcomes after treatment initiation. In an era of data sharing and big data, these techniques will be at the forefront of OSA research. Advanced data science methods, such as machine-learning analyses and artificial intelligence, will improve our ability to determine the unique influence of OSA on CVD outcomes and ultimately allow us to better determine precision medicine approaches in OSA patients for CVD risk reduction. In this narrative review, we will highlight how team science via machine learning and artificial intelligence applied to existing clinical data, polysomnography, proteomics, and imaging can do just that.

Symptom content analysis of OSA questionnaires: time to identify and improve relevance of diversity of OSA symptoms?

Obstructive sleep apnea (OSA) is a heterogeneous condition covering many clinical phenotypes in terms of the diversity of symptoms. Patient-based OSA screening questionnaires used in routine practice contain significantly varying contents that can impact the reliability and validity of the screening. We investigated to what extent common patient-based OSA screening questionnaires differ or overlap in their item content by conducting a rigorous, methodical, and quantified content overlap analysis. We conducted an item content analysis of 11 OSA screening questionnaires validated in adult populations and characterized their overlap using a four-step approach: i) selection of OSA screening questionnaires; ii) item extraction and selection; iii) extraction of symptoms from items; iv) assessment of content overlap with the Jaccard Index (from 0: no overlap to 1: full overlap). We extracted 72 items that provided 25 distinct symptoms from 11 selected OSA questionnaires. The overlap between them was weak (mean Jaccard Index 0.224, ranging from 0.138 to 0.329). All questionnaires contained symptoms of the "OSA symptom" dimension (e.g., snoring or witnessed apneas). The STOP-BANG (0.329) and the Berlin (0.280) questionnaires exhibited the highest overlap content. Ten symptoms (40%) were investigated in only one questionnaire. The heterogeneity of content and the low overlap across these questionnaires reflect the challenges of screening OSA. The different OSA questionnaires potentially capture varying aspects of the disorder, with the risk of biased results in studies. Suggestions are made for better OSA screening and refinement of clinical OSA phenotypes.

A sex-stratified nationwide study on the prevalence and clinical phenotypes of obstructive sleep apnea in Iran

A sex-stratified nationwide study on the prevalence and clinical phenotypes of obstructive sleep apnea in Iran

Prevalence of polysomnographic Low Respiratory Arousal Threshold Obstructive Sleep Apnea phenotype in the general population of São Paulo, Brazil

Prevalence of polysomnographic Low Respiratory Arousal Threshold Obstructive Sleep Apnea phenotype in the general population of São Paulo, Brazil

Heterogeneity of obstructive sleep apnea phenotypes after ischemic stroke: Outcome variation by cluster analysis

IntroductionObstructive sleep apnea (OSA) is common but under-recognized after stroke. The aim of this study was to determine whether post-stroke phenotypic OSA subtypes are associated with stroke outcome in a population-based observational cohort. MethodsIschemic stroke patients (n = 804) diagnosed with OSA (respiratory event index ≥10) soon after ischemic stroke were identified from the Brain Attack Surveillance in Corpus Christi (BASIC) project. Functional, cognitive, and quality of life outcomes were assessed at 90 days post-stroke and long-term stroke recurrence was ascertained. Latent profile analysis was performed based on demographic and clinical features, pre-stroke sleep characteristics, OSA severity, and vascular risk factors. Regression models were used to assess the association between phenotypic clusters and outcomes. ResultsFour distinct phenotypic clusters provided the best fit. Cluster 1 was characterized by more severe stroke; cluster 2 by severe OSA and higher prevalence of medical comorbidities; cluster 3 by mild stroke and mild OSA; and cluster 4 by moderate OSA and mild stroke. Compared to cluster 3 and after adjustment for baseline stroke severity, cluster 1 and cluster 2 had worse 90-day functional outcome and cluster 1 also had worse quality of life. No difference in cognitive outcome or stroke recurrence rate was noted by cluster. ConclusionPost-stroke OSA is a heterogeneous disorder with different clinical phenotypes associated with stroke outcomes, including both daily function and quality of life. The unique presentations of OSA after stroke may have important implications for stroke prognosis and personalized treatment strategies.

Evaluation of clinical and genetic factors in obstructive sleep apnoea.

To evaluate the correlation between several presumed candidate genes for obstructive sleep apnoea (OSA) and clinical OSA phenotypes and propose a predictive comprehensive model for diagnosis of OSA. This case-control study compared polysomnographic patterns, clinical data, morbidities, dental factors and genetic data for polymorphisms in PER3, BDNF, NRXN3, APOE, HCRTR2, MC4R between confirmed OSA cases and ethnically matched clinically unaffected controls. A logistic regression model was developed to predict OSA using the combined data. The cohort consisted of 161 OSA cases and 81 controls. Mean age of cases was 53.5 ± 14.0 years, mostly males (57%) and mean body mass index (BMI) of 27.5 ± 4.3 kg/m2. None of the genotyped markers showed a statistically significant association with OSA after adjusting for age and BMI. A predictive algorithm included the variables gender, age, snoring, hypertension, mouth breathing and number of T alleles of PER3 (rs228729) presenting 76.5% specificity and 71.6% sensitivity. No genetic variant tested showed a statistically significant association with OSA phenotype. Logistic regression analysis resulted in a predictive model for diagnosing OSA that, if validated by larger prospective studies, could be applied clinically to allow risk stratification for OSA.

Anaerobic pathogens associated with OSA may contribute to pathophysiology via amino-acid depletion

The human microbiome is linked to multiple metabolic disorders such as obesity and diabetes. Obstructive sleep apnoea (OSA) is a common sleep disorder with several metabolic risk factors. We investigated the associations between the gut microbiome composition and function, and measures of OSA severity in participants from a prospective community-based cohort study: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Bacterial-Wide Association Analysis (BWAS) of gut microbiome measured via metagenomics with OSA measures was performed adjusting for clinical, lifestyle and co-morbidities. This was followed by functional analysis of the OSA-enriched bacteria. We utilized additional metabolomic and transcriptomic associations to suggest possible mechanisms explaining the microbiome effects on OSA. Several uncommon anaerobic human pathogens were associated with OSA severity. These belong to the Lachnospira, Actinomyces, Kingella and Eubacterium genera. Functional analysis revealed enrichment in 49 processes including many anaerobic-related ones. Severe OSA was associated with the depletion of the amino acids glycine and glutamine in the blood, yet neither diet nor gene expression revealed any changes in the production or consumption of these amino acids. We show anaerobic bacterial communities to be a novel component of OSA pathophysiology. These are established in the oxygen-poor environments characteristic of OSA. We hypothesize that these bacteria deplete certain amino acids required for normal human homeostasis and muscle tone, contributing to OSA phenotypes. Future work should test this hypothesis as well as consider diagnostics via anaerobic bacteria detection and possible interventions via antibiotics and amino-acid supplementation. Described in methods.

The effects of atomoxetine and trazodone combination on obstructive sleep apnea and sleep microstructure: A double-blind randomized clinical trial study

Study objectiveswe aimed to compare the effects of atomoxetine and trazodone (A-T) in combination with placebo in patients with obstructive sleep apnea (OSA). MethodsThis randomized, placebo-controlled, double-blind, crossover trial study was conducted in adults with OSA referred to a Sleep Clinic. Participants with eligibility criteria were recruited. Patients were studied on two separate nights with one-week intervals, once treated with trazodone (50 mg) and atomoxetine (80 mg) combination and then with a placebo and the following polysomnography tests. ResultsA total of 18 patients with OSA completed the study protocol, 9(50%) were male, the mean age was 47.5 years (SD = 9.8) and the mean Body mass index of participants was 28.4 kg/m2 (SD = 3.4). Compared with the placebo, the A-T combination resulted in significant differences in AHI (28.3(A-T) vs. 42.7 (placebo), p = 0.025), duration of the REM stage (1.3%TST (A-T) vs. 13.1%TST (placebo), p = 0.001), and the number of REM cycles (0.8 (A-T) vs. 4.7 (placebo), p = 0.001), number of apneas (38.3 (A-T) vs. 79.3 (placebo), p = 0.011), number of obstructive apneas (37.2 (A-T) vs. 75.2 (placebo), p = 0.011), oxygen desaturation index (29.5 (A-T) vs. 42.3 (placebo), p = 0.022) and number of respiratory arousals (43.2 (A-T) vs. 68.5 (placebo), p = 0.048). This decrement effect did not change among those with a low-arousal phenotype of OSA. ConclusionsThe A-T combination significantly improved respiratory events’ indices compared with placebo in patients with OSA. This combination is recommended to be assessed in a large trial. It could be an alternative for those who do not adhere to the standard available treatments for OSA.

Abstract 19123: Associations Between Multiple Dimensions of Poor Sleep and Life’s Essential 8 Cardiovascular Health Score During the Menopausal Transition: Findings From the AHA Research Goes Red Weight Study

Introduction: The sleep health metric in AHA Life’s Essential 8 (LE8), a measurement of cardiovascular health (CVH), consists only of sleep duration. Associations of other dimensions of sleep health including sleep quality with the LE8 CVH and its individual components have not yet been evaluated. Methods: Participants were 291 women (n=98 pre-, n=94 peri-, n=99 post-menopausal, mean age=50 ± 3.2yr) between 45-55y from the AHA Research Goes Red Weight Study, which utilized Verily’s online platform. Standardized questionnaires included the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Berlin questionnaire for risk of obstructive sleep apnea (OSA), and a 1-wk NIH ASA 24-Hour Dietary Assessment. The LE8 CVH and component scores were computed. Cross-sectional associations between sleep and overall CVH scores and individual metrics were tested using multivariable logistic regression models adjusted for age, race/ethnicity, education, employment, insurance, and menopausal status. Results: Half of women slept &lt;7 hours/night, 79% reported poor sleep quality (PSQI≥5), one-third had high-risk OSA phenotype, 51% reported insomnia symptoms (ISI≥8), and 12% had evening chronotype. Compared to pre-menopausal women (67%), significantly more post-(83%) and peri-menopausal (86%) women reported poor sleep quality (p&lt;0.01). Women with poor sleep quality had 3-fold higher odds of poor overall CVH score (p=.04). Women with high-risk OSA phenotype and evening chronotype also had ~3-fold higher risk of poor overall CVH scores (OR=3.58, CI=1.79-7.18, and OR=3.33, CI=1.45-7.69, respectively). Poor sleep quality was associated with greater odds of low score on the diet component (OR=2.97, CI=1.55-5.69). Insomnia symptoms were associated with poor score on the BMI component (OR=1.92, CI=1.15-3.21). High-risk OSA phenotype was associated with greater odds of poor scores on the blood pressure, blood glucose, and BMI components (OR=2.3, CI=1.2-4.3; OR=3.2, CI=1.5-7.1, and OR=11.6, CI=6.2-21.6). Conclusions: Multiple aspects of sleep other than duration were associated with overall LE8 CVH score, and individual metrics, among women across menopause. Findings support potential incorporation of sleep quality into CVH constructs.

Defining Epiglottic Collapses Patterns in Obstructive Sleep Apnea Patients: Francia-Lugo Classification

Obstructive Sleep Apnea (OSA) is characterized by repetitive collapse of the upper airway during sleep. Drug-Induced Sleep endoscopy (DISE) is used to identify the collapse site. Among the possible sites of collapse, the epiglottis occurs more frequently than previously described. In this study, we reviewed DISE findings and classified different epiglottic collapse patterns. We found 104 patients (16.4%) with epiglottis collapse (primary 12.5% and secondary 3.9%). We described the following patterns of epiglottis collapse: Anterior–Posterior (AP) collapse with rigid component “trapdoor type” (48%); AP collapse with lax component “floppy type” (13.5%); Lateral– Lateral (LL) collapse with omega shape component “book type” (14.5%); and secondary due to lateral pharyngeal wall or tongue base collapse (24%). The identification of the epiglottic collapse pattern is crucial in decision-making when attempting to ameliorate OSA. These findings in OSA phenotyping could influence the type of treatment chosen.

Chronic intermittent hypoxia-induced cardiovascular and renal dysfunction: from adaptation to maladaptation.

Chronic intermittent hypoxia (CIH) is the dominant pathological feature of human obstructive sleep apnoea (OSA), which is highly prevalent and associated with cardiovascular and renal diseases. CIH causes hypertension, centred on sympathetic nervous overactivity, which persists following removal of the CIH stimulus. Molecular mechanisms contributing to CIH-induced hypertension have been carefully delineated. However, there is a dearth of knowledge on the efficacy of interventions to ameliorate high blood pressure in established disease. CIH causes endothelial dysfunction, aberrant structural remodelling of vessels and accelerates atherosclerotic processes. Pro-inflammatory and pro-oxidant pathways converge on disrupted nitric oxide signalling driving vascular dysfunction. In addition, CIH has adverse effects on the myocardium, manifesting atrial fibrillation, and cardiac remodelling progressing to contractile dysfunction. Sympatho-vagal imbalance, oxidative stress, inflammation, dysregulated HIF-1α transcriptional responses and resultant pro-apoptotic ER stress, calcium dysregulation, and mitochondrial dysfunction conspire to drive myocardial injury and failure. CIH elaborates direct and indirect effects in the kidney that initially contribute to the development of hypertension and later to chronic kidney disease. CIH-induced morphological damage of the kidney is dependent on TLR4/NF-κB/NLRP3/caspase-1 inflammasome activation and associated pyroptosis. Emerging potential therapies related to the gut-kidney axis and blockade of aryl hydrocarbon receptors (AhR) are promising. Cardiorenal outcomes in response to intermittent hypoxia present along a continuum from adaptation to maladaptation and are dependent on the intensity and duration of exposure to intermittent hypoxia. This heterogeneity of OSA is relevant to therapeutic treatment options and we argue the need for better stratification of OSA phenotypes.

O008 Refining the Hypoxic Burden Algorithm by Investigating different Methods for Calculating the SpO2 Baseline

Abstract Introduction Intermittent hypoxia is a key mechanism linking Obstructive Sleep Apnoea (OSA) to cardiovascular disease (CVD). Oximetry analysis could enhance understanding of which OSA phenotypes are associated with CVD risk. The hypoxic burden (HB) is a measure calculated from the oximetry signal that shows promise for predicting CVD mortality, but its calculation is complex. With a view to simplifying its calculation, we investigated three different baseline calculation methods and its impact on predicting CVD mortality for the HB algorithm. Methods Data from Sleep Heart Health Study (SHHS) with CVD mortality outcome and complete covariate information was used. We implemented the HB method of Azarbarzin et al 2018 ERJ. The three baseline methods included an event-based baseline (same as Azarbarzin et al 2018 ERJ), a record-based baseline, and a fixed baseline. The performance of each parameter in predicting CVD mortality was assessed using an adjusted Cox proportional hazard ratio (HR) analysis. Results The best performing method was the record-based baseline method which returned a fully adjusted model hazard ratio of 1.83 (95% CI: 1.03-3.27, p&amp;lt;0.05). The results for the event-based and record-based baseline methods were 1.60 (95% CI: 0.86-3.00, p=0.14) and 1.73 (95% CI: 0.93-3.22, p=0.08) respectively. Discussion HB with the record-based baseline was easier to calculate than the original event-based baseline method by Azarbarzin at al. and resulted in improved CVD mortality prediction performance. We believe that this method provides a step towards providing a novel parameter with easy calculation providing early risk stratification in cardiovascular patients.

Cardiovascular diseases across OSA phenotypes: A retrospective cohort study

BackgroundDespite the considerable knowledge of Obstructive Sleep Apnea (OSA) implications for cardiac diseases, the evidence regarding cardiovascular complications across OSA phenotypes including Rapid Eye Movement OSA (REM-OSA) and Positional OSA (POSA) is limited. In this study, we aimed to evaluate the risk of cardiovascular diseases development and progression among patients with REM-OSA and POSA. MethodsBased on a retrospective cohort analysis, we included polysomnography studies done in the sleep lab at the Jordan University Hospital. Regarding cardiovascular diseases, primary outcomes were Heart Failure, and 1-years Major Adverse Cardiac Events while secondary outcomes were atrial fibrillation, pulmonary hypertension, other arrhythmia, metabolic profile, and echocardiographic measurements of the heart. ResultsThe total number of the included patients was 1,026 patients. POSA group had significantly lower percentage of patients with hypertension (P-value = 0.004). Additionally, systolic blood pressure and HbA1c were significantly lower among patients with POSA compared to the NPOSA group (P-value<0.050). Left ventricular end diastolic dimension was significantly higher among patients with POSA while ejection fraction was significantly lower (P-value<0.050). Patients with diabetes and mean HbA1c were significantly lower among patients with REM-OSA compared to patients with NREM-OSA (P-value = 0.015, P-value = 0.046). Multivariate regression analysis revealed that after adjusting for age, gender and preexisting comorbidities, POSA was significantly associated with lower ejection fraction and higher left ventricular diastolic diameter. ConclusionIn conclusion, our findings indicate that POSA might be associated with huge and clinically significant heart strain and poor cardiac functions, yet it might not have a clinically significant atherogenic effect. This study should guide clinicians to identify OSA phenotypes to imply the best treatment plan to reduce its detrimental impact on cardiac muscle.

Evaluation of a custom-made mandibular repositioning device for the treatment of obstructive sleep apnoea syndrome

Obstructive sleep apnoea (OSA) is a common, chronic condition that affects breathing during sleep. The gold standard for treatment is continuous positive airway pressure (CPAP) which is often not well-tolerated. Mandibular repositioning appliances (MRDs) are an alternative that dentists may be requested to provide.The purpose of this audit is to evaluate the effectiveness of an MRD in improving the Oxygen Desaturation Index (ODI) and Epworth Sleepiness Scale (ESS). A total of 52 patients diagnosed with OSA in an NHS hospital respiratory clinic were fitted with an MRD. Analysis of the digitally recorded oximeter signals was recorded among other treatment outcomes before and 6-8 weeks after the fit of the appliance.The meta-analysis of the audit data showed supportive evidence for MRD treatment in OSA patients. There was a statistically significant reduction in ODI and ESS. The audit population consisted of 138 patients (91 men, 47 women; mean age: 49.49 ± 11.93 years). The ODI outcomes improved significantly, from 10.68 to 6.58 (p <0.02). The ESS improved significantly from 9.46 to 6.02 (p <0.01).This audit demonstrates that MRDs are effective and should be considered as an alternative to CPAP in some specific OSA phenotypes.

Obstructive sleep apnea heterogeneity and autonomic function: a role for heart rate variability in therapy selection and efficacy monitoring.

Obstructive sleep apnea is a highly prevalent sleep-related breathing disorder, resulting in a disturbed breathing pattern, changes in blood gases, abnormal autonomic regulation, metabolic fluctuation, poor neurocognitive performance, and increased cardiovascular risk. With broad inter-individual differences recognised in risk factors, clinical symptoms, gene expression, physiological characteristics, and health outcomes, various obstructive sleep apnea subtypes have been identified. Therapeutic efficacy and its impact on outcomes, particularly for cardiovascular consequences, may also vary depending on these features in obstructive sleep apnea. A number of interventions such as positive airway pressure therapies, oral appliance, surgical treatment, and pharmaceutical options are available in clinical practice. Selecting an effective obstructive sleep apnea treatment and therapy is a challenging medical decision due to obstructive sleep apnea heterogeneity and numerous treatment modalities. Thus, an objective marker for clinical evaluation is warranted to estimate the treatment response in patients with obstructive sleep apnea. Currently, while the Apnea-Hypopnea Index is used for severity assessment of obstructive sleep apnea and still considered a major guide to diagnosis and managements of obstructive sleep apnea, the Apnea-Hypopnea Index is not a robust marker of symptoms, function, or outcome improvement. Abnormal cardiac autonomic modulation can provide additional insight to better understand obstructive sleep apnea phenotyping. Heart rate variability is a reliable neurocardiac tool to assess altered autonomic function and can also provide cardiovascular information in obstructive sleep apnea. Beyond the Apnea-Hypopnea Index, this review aims to discuss the role of heart rate variability as an indicator and predictor of therapeutic efficacy to different modalities in order to optimise tailored treatment for obstructive sleep apnea.

Obstructive sleep apnea phenotypes eligible for pharmacological treatment

Obstructive sleep apnea (OSA) is a common disorder. Its prevalence is increasing worldwide, partially due to increasing rates of obesity, and OSA has a well-documented impact on physical health (increased risk of cardiovascular and metabolic disorders) and mental health, as well as major socioeconomic implications. Although continuous positive airway pressure treatment (CPAP) remains the primary therapeutic intervention for moderate to severe OSA, other treatment strategies such as weight loss, positional therapy, mandibular advancement devices (MAD), surgical treatment, myofunctional therapy of upper airways (UA) muscles and hypoglossal nerve stimulation are increasingly used. Recently, several trials have demonstrated the clinical potential for various pharmacological treatments that aim to improve UA muscle dysfunction, loop gain, or excessive daytime sleepiness. In line with the highly heterogeneous clinical picture of OSA, recent identification of different clinical phenotypes has been documented. Comorbidities, incident cardiovascular risk, and response to CPAP may vary significantly among phenotypes. With this in mind, the purpose of this review is to summarize the data on OSA phenotypes that may respond to pharmacological approaches.

Translation of obstructive sleep apnea pathophysiology and phenotypes to personalized treatment: a narrative review.

Obstructive Sleep Apnea (OSA) arises due to periodic blockage of the upper airway (UA) during sleep, as negative pressure generated during inspiration overcomes the force exerted by the UA dilator muscles to maintain patency. This imbalance is primarily seen in individuals with a narrowed UA, attributable to factors such as inherent craniofacial anatomy, neck fat accumulation, and rostral fluid shifts in the supine posture. Sleep-induced attenuation of UA dilating muscle responsiveness, respiratory instability, and high loop gain further exacerbate UA obstruction. The widespread comorbidity profile of OSA, encompassing cardiovascular, metabolic, and neuropsychiatric domains, suggests complex bidirectional relationships with conditions like heart failure, stroke, and metabolic syndrome. Recent advances have delineated distinct OSA phenotypes beyond mere obstruction frequency, showing links with specific symptomatic manifestations. It is vital to bridge the gap between measurable patient characteristics, phenotypes, and underlying pathophysiological traits to enhance our understanding of OSA and its interplay with related outcomes. This knowledge could stimulate the development of tailored therapies targeting specific phenotypic and pathophysiological endotypes. This review aims to elucidate the multifaceted pathophysiology of OSA, focusing on the relationships between UA anatomy, functional traits, clinical manifestations, and comorbidities. The ultimate objective is to pave the way for a more personalized treatment paradigm in OSA, offering alternatives to continuous positive airway pressure therapy for selected patients and thereby optimizing treatment efficacy and adherence. There is an urgent need for personalized treatment strategies in the ever-evolving field of sleep medicine, as we progress from a 'one-size-fits-all' to a 'tailored-therapy' approach.

Comparing the Characteristics of REM and Positional Obstructive Sleep Apnea Phenotypes Among Jordanian Population

Comparing the Characteristics of REM and Positional Obstructive Sleep Apnea Phenotypes Among Jordanian Population