Therapy For Sleep Apnea Research Articles

Physical therapy for sleep apnea: a smartphone application for home-based physical therapy for patients with obstructive sleep apnea.

In this study, we described "PT for Sleep Apnea", a smartphone application for home-based physical therapy of patients with Obstructive Sleep Apnea (OSA). The application was created in a joint program between the University of Medicine and Pharmacy at Ho Chi Minh City (UMP), Vietnam, and National Cheng Kung University (NCKU), Taiwan. Exercises maneuvers were derived from the exercise program previously published by the partner group at National Cheng Kung University. They included exercises for upper airway and respiratory muscle training and general endurance training. The application provides video and in-text tutorials for users to follow at home and a schedule function to assist the user in organizing the training program, which may improve the efficacy of home-based physical therapy in patients with Obstructive Sleep Apnea. In the future, our group plans to conduct a user study and randomized-controlled trials to investigate whether our application can benefit patients with OSA.

Diet Therapy of Obstructive Sleep Apnea Syndrome Treated with Positive Airway Pressure: A Systematic Review of Randomized Controlled Trials

The positive airway pressure (PAP) is a gold standard in therapy for obstructive sleep apnea (OSA) patients, though weight loss is among the most effective supportive therapeutic methods. The aim of the study is to conduct a systematic review of randomized controlled trials (RCTs) of diet therapy interventions for OSA patients treated with PAP. The systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42023398374). The 1436 records were screened and five records were included identified as RCTs available within PubMed and Web of Science databases until 1 February 2023. Two researchers independently conducted identification, screening, inclusion, and evaluation of RCTs, using the revised Cochrane risk-of-bias tool for randomized trials. The studies were conducted in groups with patients treated or intended to be treated with CPAP, while patients with moderate-to-severe or severe OSA were included. Within all included studies, an experimental diet was compared with a control group; however, various interventions were applied, including dietary intervention, which was compared with no intervention, and dietary and physical activity intervention, which was only compared with general advice. The applied intervention included various dietary approaches, such as various energy deficits or dietary health-promoting behaviors. The monitored variables included apnea–hypopnea index (AHI), sleep time, sleep efficiency, sleep latency, oxygen desaturation episodes, oxygen saturation, OSA type, Epworth Sleepiness Scale score, Pittsburgh Sleep Quality Index, and quality of life. For the majority of studies, some concerns were defined for the risk of bias; however, for one study the risk was high. Three studies supported the positive influence of diet therapy, one study somewhat supported it and one study did not support it. It may be stated that for excessive body mass individuals, even if PAP is applied, the diet therapy should be included in order to reduce body mass, reduce the symptoms of OSA, and improve the quality of life. This therapeutic option should be applied, even if no effect on OSA is noted, as body mass reduction have multiple positive effects, which may also influence the quality of life.

Pneumothorax Induced by Automatic Positive Airway Pressure Therapy for Obstructive Sleep Apnea: A Rare Case Report and Review of the Literature

Positive airway pressure (PAP) therapy is known to be an effective treatment for obstructive sleep apnea (OSA) that does not generally have serious complications. However, pneumothorax following lung barotrauma with the use of PAP has rarely been reported. We recently experienced the case of a 72-year old male patient with chronic obstructive pulmonary disease who developed pneumothorax after the use of automatic PAP (APAP). After 4 months of APAP use with a pressure of 4–8 cm H<sub>2</sub>O, he complained of sudden severe dyspnea at midnight. He eventually underwent surgical repair for pneumothorax. After 4 months, continuous PAP with low pressure of 5 cm H<sub>2</sub>O was applied without any complications. In summary, we emphasize the risk of barotrauma when PAP is used by OSA patients with lung disease.

Predictors and consequences of residual apnea during positive airway pressure therapy

Study objectivesDetermine the risk factors for, and consequences of, residual apnea during long-term positive airway pressure (PAP) therapy for obstructive sleep apnea (OSA). MethodsA prospective cohort study of 195 subjects after a split-night polysomnogram. Estimation of residual respiratory events on PAP were done by both automated and manual scoring of data in EncoreAnywhere™. Clinical and polysomnographic predictors of residual apnea were estimated. ResultsThere were 166 and 101 patients still on PAP at the 3 and 12 months, respectively. Seventy four (44.6%) and 46 (45.5%) had a residual scored respiratory event index-flow (sREIFLOW) ≥ 15/hour of use and 46 (45.5%) at the 3rd and 12th month, respectively. Treatment phase central apnea hypopnea index (TCAHI), a surrogate of high loop gain, was the main predictor for residual sREIFLOW (β = 0.345, p: 0.025) at the 3rd and 12th month (β = 0.147, p: 0.020). TCAHI also predicted unstable breathing (U) %. The body mass index (hazard ratio [HR] 1.034, 95% CI 1.008–1.062, p: 0.012) and effective sREIFLOW>15/hour in the first month (HR 2.477, 95% CI 1.510–4.065, p < 0.001) were the key predictors for drop out of PAP use at the 12th month. Effective sREIFLOW>15/hour in the first month was also a predictor for median usage duration >4 h for 70% of the night at both the 3rd month (odds ratio [OR] 0.947, 95% CI 0.909–0.986, p: 0.008) and 12th month (OR 0.973, 95% CI 0.951–0.994, p: 0.014). ConclusionsTreatment-phase CAHI predicts long-term residual apnea on PAP. High residual disease adversely impacts adherence.

Innovations in mandibular advancement splint therapy for obstructive sleep apnoea

Mandibular advancement splint (MAS) therapy emerged as an effective therapy for obstructive sleep apnoea (OSA) in the mid 1990s, and is now the leading treatment alternative for OSA. Since its inception, the field has seen a suite of revisions and advances in relation to design and customisation, fabrication, titration methods, response prediction models and the integration of data collection technology. This paper reviews these current and emerging innovations in MAS therapy and their impact upon sleep apnoea management.

Effect of Continuous Positive Airway Pressure on Glucose and Lipid Profiles in Patients With Obstructive Sleep Apnoea: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background and aimContinuous Positive Airway Pressure (CPAP) is the most effective therapy for symptomatic obstructive sleep apnoea (OSA). However, uncertainty remains about the effectiveness of CPAP in improving OSA-related metabolic dysregulation. This meta-analysis of randomized controlled trials (RCTs) aimed to investigate whether CPAP, compared to other control treatments, could improve glucose or lipid metabolism in OSA patients. MethodsRelevant articles were searched in three different databases (MEDLINE, EMBASE and Web of Science) from inception to 6th Feb 2022 through specific search terms and selection criteria. ResultsFrom a total of 5553 articles, 31 RCTs were included. CPAP modestly improved insulin sensitivity as determined by mean fasting plasma insulin and Homeostasis Model Assessment of Insulin Resistance reduction of 1.33mU/L and 0.287, respectively. In subgroup analyses pre-diabetic/type 2 diabetic patients as well as those with sleepy OSA showed a greater response to CPAP. Regarding lipid metabolism, CPAP was associated with a mean total cholesterol reduction of 0.064mmol/L. In subgroup analyses, the benefit was higher in patients that showed more severe OSA and oxygen desaturations at the baseline sleep study as well as in younger and obese subjects. Neither glycated haemoglobin nor triglycerides, HDL- and LDL-cholesterol were reduced by CPAP. ConclusionCPAP treatment may improve insulin sensitivity and total cholesterol levels in OSA patients but with low effect size. Our results suggest that CPAP does not substantially improve metabolic derangements in an unselected OSA population, but the effect may be higher in specific subgroups of OSA patients.

The effect of head rotation on OSA is associated with disease severity: a cross-sectional study.

Head rotation is an effective positional therapy for obstructive sleep apnea (OSA). However, not all OSA patients benefit from head rotation. This study aimed to explore the clinical phenotype of OSA patients who can benefit from head rotation. We performed a retrospective review of 184 consecutive OSA patients who underwent polysomnography. Head rotation in supine position was determined by high-quality video recording. According to the changes in apnea-hypopnea index (AHI) after head rotation, OSA patients were divided into two groups: patients with response to head rotation(HR) and patients without response to head rotation(NHR). Demographic factors and overnight polysomnography were analyzed. Compared with NHR group, HR group showed significantly lower AHI (51.8 vs 31.5, p < 0.01), time spent with oxygen saturation below 90%(5.3% vs 0.51%, p < 0.01), and higher lowest oxygen saturation(80% vs 86%, p < 0.05). Logistic regression showed that AHI was an independent factor to predict the decrease of AHI in head rotation (OR 0.985, 95% CI 0.970-0.979, p < 0.05). Among mild to moderate group (AHI < 30/h), severe group (30/h ≤ AHI < 60/h), and extremely severe group (AHI ≥ 60/h), the percentage decrease of AHI in head rotation was 18.5%, 9.5%, and 2.6%, respectively. Surprisingly, the percentage decrease of AHI of 6 responders in mild to moderate group was more than 50%. OSA patients who respond well to head rotation have less severe disease, and patients with mild to moderate OSA are more likely to improve and benefit from this position. Our research provides potential strategies and insights into the individual treatment of OSA patients.

Dose-Response Relationship between Obstructive Sleep Apnea Therapy Adherence and Healthcare Utilization.

Rationale: Clear definition of optimal positive airway pressure therapy usage in patients with obstructive sleep apnea is not possible because of scarce data on the relationship between usage hours and major clinical outcomes. Objective: To investigate the dose-response relationship between positive airway pressure usage and healthcare resource utilization and determine the minimum device usage required for benefit. Methods: A linked data set combined deidentified payer-sourced administrative medical/pharmacy claims data from more than 100 U.S. health plans and individual patient positive airway pressure usage data. Eligible adults (age ⩾18 yr) had a new obstructive sleep apnea diagnosis between June 2014 and April 2018. All received positive airway pressure therapy (AirSense 10; ResMed) with claims data for ⩾1 year before, and 2 years after, device setup. Healthcare resource utilization was determined on the basis of the number of all-cause hospitalizations and emergency room visits over 3, 12, and 24 months after positive airway pressure initiation. Results: Data from 179,188 patients showed a clear dose-response relationship between daily positive airway pressure usage and healthcare utilization. Minimum device usage required for benefit was 1-3 hours per night. There was a statistically significant decrease in hospitalizations and emergency room visits at all time points (all Ps < 0.0001) with increasing positive airway pressure usage. Each additional hour of usage per night decreased hospitalizations and emergency room visits by 5-10% and 5-7%, respectively. Conclusions: These data provide compelling evidence for a dose-response relationship between positive airway pressure usage and healthcare utilization, with benefits seen even when usage was as low as 1-2 hours per night.

Changes in tongue morphology predict responses in pharyngeal patency to selective hypoglossal nerve stimulation.

The major goal of the study was to determine whether changes in tongue morphology under selective hypoglossal nerve therapy for obstructive sleep apnea were associated with alterations in airway patency during sleep when specific portions of the hypoglossal nerve were stimulated. This case series was conducted at the Johns Hopkins Sleep Disorders Center at Johns Hopkins Bayview Medical Center. Twelve patients with apnea implanted with a multichannel targeted hypoglossal nerve-stimulating system underwent midsagittal ultrasound tongue imaging during wakefulness. Changes in tongue shape were characterized by measuring the vertical height and polar dimensions between tongue surface and genioglossi origin in the mandible. Changes in patency were characterized by comparing airflow responses between stimulated and adjacent unstimulated breaths during non-rapid eye movement sleep. Two distinct morphologic responses were observed. Anterior tongue base and hyoid-bone movement (5.4 [0.4] to 4.1 [1.0] cm (median and [interquartile range]) with concomitant increases in tongue height (5.0 [0.9] to 5.6 [0.7] cm) were associated with decreases in airflow during stimulation. In contrast, comparable anterior hyoid movement (tongue protrusion from 5.8 [0.5] to 4.5 [0.9] cm) without significant increases in height (5.2 [1.6] to 4.6 [0.8] cm) were associated with marked increases in airflow during sleep. Tongue protrusion with preservation of tongue shape predicted increases in patency, whereas anterior movement with concomitant increases in height were associated with decreased pharyngeal patency. These findings suggest that pharyngeal patency can be best stabilized by stimulating lingual muscles that maintain tongue shape while protruding the tongue, thereby preventing it from prolapsing posteriorly during sleep. Fleury Curado T, Pham L, Otvos T, etal. Changes in tongue morphology predict responses in pharyngeal patency to selective hypoglossal nerve stimulation. J Clin Sleep Med. 2023;19(5):947-955.

Role of craniofacial phenotypes in the response to oral appliance therapy for obstructive sleep apnea.

Mandibular advancement device (MAD) is a good alternative for patients with obstructive sleep apnea (OSA). However, the treatment response varies among individuals. This study aimed to explore the role of craniofacial features in the response to MADs to improve prognostication and patient selection. The retrospective trial contained 42 males aged 41.5±9.0 years, and with an apnea-hypopnea index (AHI) of 21.5±13.8 events/h. According to the mandibular plane angle, participants were divided into three groups: low angle (n=13), average angle (n=14), and high angle (n=15). Under monitor of home sleep testing, adjustable MADs were used to titrate the mandible forward from 0 mm with an increment of 0.5 mm every day. The polysomnography outcomes, mandibular protrusion amounts, changes in upper airway MRI measurements, and nasal resistance were compared among three groups. The normalization rate (AHI < 5 /h) was 92.3%, 57.1%, and 46.7% respectively in the low, average, and high angle groups (p=0.027). The effective protrusion where AHI was reduced by half was 20 (11.3~37.5) %, 31.3 (23.6~50) %, and 50 (36.9~64.9) % of the maximal mandibular protrusion, in the low, average, and high angle groups (p=0.004). Multivariate logistic regression revealed that increased gonion angle (OR=0.878) and baseline AHI(OR=0.868) can reduce the probability of normalization. The high mandibular plane angle might be an unfavorable factor to MAD treatment and more protrusion was needed to achieve a 50% reduction in AHI. Vertical craniofacial pattern (gonion angle) and baseline AHI constituted the model for predicting the effect of MADs.

Fifteen Patients Who Can Be Helped by Medicare: Insurance Policy Changes in the Coverage of CPAP Therapy for Obstructive Sleep Apnea.

Insurance coverage policies define the diagnostic criteria and adherence requirements for patients to qualify for initial and ongoing therapy with continuous positive airway pressure (CPAP) treatment, the most complete therapy for obstructive sleep apnea. Unfortunately, a number of patients who use CPAP and benefit from treatment fail to meet these requirements. We present 15 patients who fail to meet Centers for Medicare and Medicaid Services' (CMS) criteria, highlighting policies that do not support patient care. Finally, we review expert panel recommendations to improve CMS policies, and we suggest ways that physicians can better support CPAP access within the current regulatory restrictions.

Insomnia in Patients Undergoing Hypoglossal Nerve Stimulation Therapy for Obstructive Sleep Apnea.

Hypoglossal nerve stimulation (HGNS) is a treatment for obstructive sleep apnea (OSA) patients with intolerance of positive airway pressure therapy. Comorbid insomnia is quite prevalent in OSA patients. We investigated the impact of insomnia and excessive daytime sleepiness (EDS) on polysomnography metrics after HGNS treatment. Data of 27 consecutive patients (9 female; mean age 55.52 ± 8.6 years) were retrospectively evaluated. Insomnia was assessed using the ISI (insomnia severity index) and EDS using the Epworth sleepiness scale (ESS). The median ISI was reduced significantly 3 months after HGNS activation (preoperative: 19; postoperative: 14; p &lt; 0.01). Significant correlations emerged between preoperative ISI and postoperative AHI (apnea/hypopnea index; Spearman's rho = 0.4, p &lt; 0.05), ∆ AHI (r = -0.51, p &lt; 0.01) and ∆ ODI (oxygen desaturation index; r = -0.48, p &lt; 0.05). ISI correlated strongly with EES both preoperatively (r = 0.46; p &lt; 0.02) and postoperatively (r = 0.79; p &lt; 0.001). Therefore, HGNS therapy is associated with a significant reduction of insomnia-related symptoms, in addition to the improvement in respiratory metrics in OSA. Nonetheless, the preoperative severity of patient-reported insomnia symptoms was inversely correlated with the respiratory PSG-outcomes after HGNS. Insomnia should be considered in studies of EDS in OSA patients, especially those treated with HGNS.

Development and Internal Validation of a Prediction Model for Surgical Success of Maxillomandibular Advancement for the Treatment of Moderate to Severe Obstructive Sleep Apnea.

Background: Maxillomandibular advancement (MMA) has been shown to be the most effective surgical therapy for obstructive sleep apnea (OSA). Despite high success rates, there are patients who are considered as non-responders to MMA. In order to triage and inform these patients on their expected prognosis of MMA before the surgery, this study aimed to develop, internally validate, and calibrate a prediction model for the presence of surgical success for MMA in patients with OSA. Methods: A retrospective cohort study was conducted that included patients that had undergone MMA for moderate to severe OSA. Baseline clinical, polysomnographic, cephalometric, and drug-induced sleep endoscopy findings were recorded as potential predictors. Presence or absence of surgical success was recorded as outcome. Binary logistic regression analyses were conducted to develop the model. Performance and clinical values of the model were analyzed. Results: One hundred patients were included, of which sixty-seven (67%) patients reached surgical success. Anterior lower face height (ALFH) (OR: 0.93 [0.87−1.00], p = 0.05), superior posterior airway space (SPAS) (OR: 0.76 [0.62−0.92], p < 0.05), age (OR: 0.96 [0.91−1.01], p = 0.13), and a central apnea index (CAI) <5 events/hour sleep (OR: 0.16 [0.03−0.91], p < 0.05) were significant independent predictors in the model (significance level set at p = 0.20). The model showed acceptable discrimination with a shrunken area under the curve of 0.74, and acceptable calibration. The added predictive values for ruling in and out of surgical success were 0.21 and 0.32, respectively. Conclusions: Lower age at surgery, CAI < 5 events/hour, lower ALFH, and smaller SPAS were significant predictors for the surgical success of MMA. The discrimination, calibration, and clinical added values of the model were acceptable.

Oral appliance therapy for obstructive sleep apnea: a retrospective study in a psychiatric sleep clinic

We evaluated the continuity and effectiveness of oral appliances (OAs) for treating obstructive sleep apnea (OSA) in a psychiatric sleep clinic, specifically focusing on mild cases and those with psychiatric comorbidity. We retrospectively examined the medical records of 106 OSA patients treated with OA. Survival analysis was performed to assess the discontinuation of OA use. Clinical Global Impression-Improvement (CGI-I) scale were obtained from medical records. The apnea-hypopnea index (AHI), measured by polysomnography (PSG), and Epworth Sleepiness Scale (ESS) were compared between diagnosis and after post-OA treatment if a second PSG for efficacy assessment was conducted. Among all 106 patients, Kaplan-Meier analysis estimated a discontinuation rate of 16.8% at 1 year. This tended to be higher for OSA patients with psychiatric comorbidity (22.7%) than those without (11.6%), though it was not statistically significant (P=0.08). The overall rate of improvement in CGI-I scale was 37.7% and was significantly lower in OSA patients with psychiatric comorbidity (25.0%) than those without (48.3%). Among the 74 patients who underwent a second PSG, AHI and ESS were significantly lower after OA treatment for the entire group and subgroups of OSA severity at diagnosis and psychiatric comorbidity, except for ESS in the moderate OSA severity subgroup. OA continuation was relatively good, and sleepiness was relieved by OA use, even in mild OSA patients and those with psychiatric comorbidity. However, the continuation and subjective improvement of symptoms were slightly lower in OSA patients with psychiatric comorbidity.

Right ventricular responses to CPAP therapy in obstructive sleep apnea: CMR analysis of the MOSAIC randomized trial.

Effects of continuous positive airway pressure (CPAP) on right ventricular (RV) function in patients with untreated mild-to-moderate obstructive sleep apnea (OSA) are unclear. In this exploratory analysis of cardiac magnetic resonance (CMR)-derived indices of RV function in patients with minimally symptomatic OSA from the MOSAIC randomized control trial we found no effect of CPAP on RV CMR parameters. In those with lower RV ejection fraction and higher RV end-diastolic volume (EDV) at baseline, CPAP treatment appeared to improve RV function with a significant reduction in both RV EDV and RV end-systolic volume although between-group effects were not observed. These data suggest potential merit in a larger randomized study of CPAP in patients with mild-to-moderate OSA and a greater breadth of RV dysfunction.

Optimal positive airway pressure requirement and polysomnography indices of obstructive sleep apnea severity in the Saudi population.

Positive airway pressure (PAP) is the first-line therapy for obstructive sleep apnea (OSA). Overnight PAP titration for determining optimal PAP requirements is expensive and often inconvenient. Prediction of optimal PAP requirements from diagnostic polysomnography via mathematical equations is possible but variable across populations. We aimed to (1) determine the optimal PAP requirement, (2) determine differences in optimal PAP requirements across OSA severity groups, (3) determine the relationship between optimal PAP requirement and diagnostic polysomnography measurements of OSA severity, and (4) develop a pilot equation to predict the optimal PAP requirement from diagnostic polysomnography in a sample from the Saudi population. We analyzed records pertaining to adult OSA patients (n = 215; 63% of males) who underwent standardized diagnostic and titration polysomnography in our sleep laboratory between 2015 and 2019. Demographic, anthropometric, and clinical information were also collected for the analysis. Inferential statistics were performed for comparisons between diagnostic and titration studies and between OSA severity groups. Regression analyses were also performed to determine the potential predictors of optimal PAP requirements. Data were presented as the mean (± standard deviation) or median (25th-75th quartiles) according to normality. The median optimal PAP requirement was 13 (9-17) cmH2O. The optimal PAP requirement was significantly greater for male versus female participants (14 [10-17] vs. 12 [8-16] cmH2O) and for participants with severe OSA (16 [12-20] cmH2O, n = 119) versus those with moderate (11 [8-14] cmH2O, n = 63) or mild (9 [7-12] cmH2O, n = 33) OSA. When combined, nadir oxygen saturation, oxygen desaturation index, and arousal index could be used to predict the optimal PAP requirement (R 2= 0.39, F = 34.0, P < 0.001). The optimal PAP requirement in the Saudi population is relatively high and directly correlated with OSA severity. Diagnostic polysomnography measurements of OSA severity predicted the optimal PAP requirement in this sample. Prospective validation is warranted.

Comorbid Insomnia and Sleep Apnea: Assessment and Management Approaches.

Comorbid insomnia and sleep apnea (COMISA) is a highly prevalent and debilitating condition that is more difficult to treat compared with insomnia alone or sleep apnea alone. Approximately 30% to 50% of sleep clinic patients with sleep apnea report comorbid insomnia symptoms. Comorbid insomnia is associated with lower adherence to positive airway pressure therapy for obstructive sleep apnea. Management approaches that include targeted treatments for both insomnia and sleep apnea lead to the best treatment outcomes for patients with COMISA. Therefore, sleep clinics should incorporate insomnia and COMISA management pathways including access to cognitive behavioral therapy for insomnia.

P124 Differences in OSA pathophysiological traits between mandibular advancement therapy responders versus non-responses and the influence of obesity

Abstract Mandibular advancement therapy (MAS) is a recognised second-line therapy for obstructive sleep apnoea (OSA). However, MAS treatment outcomes vary and are difficult to predict. Recent studies have investigated the role of OSA endotypes to predict MAS therapy outcomes. However, whether OSA endotype predictors differ between obese and non-obese people with OSA is unknown. Thus, this study aimed to compare OSA endotypes between responders and non-responders to MAS therapy in obese and non-obese individuals. 90 people with OSA (AHI&amp;gt;10events/h) were studied. OSA was confirmed via in-laboratory polysomnography. A detailed physiology night was subsequently performed prior to MAS therapy. OSA endotypes were estimated from the detailed physiology polysomnography using a custom-designed, validated, semiautomated script. OSA endotypes were compared between responders (residual AHI&amp;lt;10events/h) and non-responders to MAS therapy. Further comparisons were made between obese and non-obese groups. Responders to MAS therapy had a less collapsible upper airway; Vpassive: 93[88,96]vs.85[62,94]%Veupnea,p=0.003); Vactive: 103[95,112]vs.98[16,104] %Veupnea,p=0.008), better pharyngeal muscle compensation Vcomp: 9.8[4.3,19.6]vs.3.3[-19.1,18.6]%Veupnea,p=0.02), lower arousal threshold (114[109,144]vs. 142 [117, 177]%Veupnea,p=0.006) and tended to also have lower loop gain (0.48 ±0.1vs. 0.42±0.1,p=0.05). . These findings were similar in obese versus non-obese individuals although loop gain was significantly lower in responders versus non-responders in the non-obese (p=0.01) but not the obese group (0.97). MAS therapy was most beneficial in people with a less collapsible upper airway, good pharyngeal muscle compensation, lower arousal threshold and loop gain at baseline. Prospective assessment of OSA endotypic traits may therefore help guide treatment decisions and improve MAS therapy outcomes.

O002 A novel, optogenetics based therapy for obstructive sleep apnea

Abstract INTRODUCTION Many obstructive sleep apnea (OSA) patients are sub-optimally treated due to poor tolerance or incomplete response to established therapies. We propose a novel stimulation therapy that sensitises the dilator muscles to light activation (‘optogenetics') and activates the muscles with light during sleep. This study aims to determine feasibility in a rodent model of OSA and identify effective optogenetic constructs. METHODS Rats received intramuscular injections of a viral vector encapsulating the opsin ChR2, driven by either a muscle-specific or non-specific promotor. Three weeks post-injection, opsin expression was quantified via confocal imaging. Light-induced tongue muscle activity afforded by the superior promotor was then measured in an acute model of OSA. The superior promotor was then combined with a novel muscle-targeted viral vector and, light-induced airway dilation was measured with ultrasound imaging. RESULTS With the muscle-specific promotor, opsin expression in the tongue was 470%(p=0.013, RM-ANOVA) greater, and brainstem expression was abolished. In the animals who received this superior promotor, light stimulation facilitated a 56% increase in muscle activity from that recorded during unstimulated breaths in an acute model of OSA(p&amp;lt;0.001, linear mixed model). Ultrasound imaging confirmed that light stimulation of the optogenetic construct with a muscle-specific promotor encapsulated in a muscle-targeted viral vector produced airway dilation in the same OSA model. DISCUSSION The combined muscle-specific promotor and muscle-specific viral vector resulted in a novel and highly effective method of inducing light-sensitivity in upper airway muscles and facilitating light-induced airway dilation. This study provides proof-of-concept for a non-invasive optogenetics-based OSA therapy.

Abstract 13554: Effect of Positive Airway Pressure Therapy for Obstructive Sleep Apnea in Heart Failure Patients With Reduced Ejection Fraction - Implications for Healthcare Resource Utilization

Introduction: Obstructive sleep apnea (OSA) is common in heart failure, although the impact of OSA treatment remains unclear. We assessed the association between adherence to positive airway pressure (PAP) therapy and healthcare resource utilization in patients with OSA and heart failure with reduced ejection fraction (HFrEF). Methods: Administrative insurance claims data linked with objective PAP therapy usage data from patients with OSA and HFrEF were used to measure the association of PAP adherence and a composite clinical outcome of hospitalization and emergency room (ER) visits. US Medicare defines PAP compliance as usage of the device for at least 4 hours/night for 70% of nights in a consecutive 30-day period over 90 days. PAP adherent patients met these criteria for all 4 90-day periods, while PAP non-adherent patients did not meet these criteria for any 90-day period over one year. Propensity score methods were used to create well matched groups with differing PAP adherence levels. Results: The study cohort consisted of 3,182 eligible patients (69.9% male, mean age 59.7 years) of whom 39% were considered adherent to PAP therapy (29% intermediate-adherent, 31% non-adherent). In the year after PAP prescription, after propensity score matching, PAP adherent patients had fewer hospital visits than non-adherent patients, driven by a 24% reduction in ER visits for adherent patients (Table 1a). These results remained consistent with inverse probability weighting and furthermore showed there were no statistically significant differences between intermediate-adherent and non-adherent patients for any outcome (Table 1b). Conclusions: Treating OSA with PAP therapy in patients with HFrEF is associated with a reduction in the composite outcome of hospitalization and ER visits, driven primarily by a reduction in ER visits. Consistent adherence to PAP therapy is required to realize these benefits.