Citations

Purpose of review Mask choice is among the few modifiable determinants of positive airway pressure (PAP) effectiveness in adults with obstructive sleep apnea OSA), yet selection is often shaped by convention, habit, or local inventory rather than evidence. We review recent literature, emphasizing studies from the past 18 months and incorporating foundational mechanistic and outcomes studies that should influence prescribing choices. Recent findings Population-scale telemonitoring analyses confirm that nasal interfaces outperform oronasal masks on adherence, required pressure, residual apnea–hypopnea index (AHI), and unintentional leak. Switching patients from an oronasal to a nasal mask can increase adherence by up to 77%. Drug-induced sleep endoscopy with PAP, cine MRI, and sealed-compartment physiology suggest three main mechanisms for these observations: oral pressure transmission without oral airflow, posterior tongue and mandibular displacement, and increased pharyngeal collapsibility. Mandibular jaw-movement signals allow leak phenotyping that distinguishes mask-seal failure from mouth opening, supporting targeted intervention rather than reflexive interface change. Summary Current evidence supports a nasal-first prescribing strategy with structured early follow-up using telemonitored adherence, residual AHI, and leak waveform data. Oronasal masks should be reserved for documented and structured nasal-trial failure rather than selected on the basis of self-reported breathing route.

Abstract Introduction Hypoglossal nerve stimulation (HGNS) is an effective therapy for moderate-to-severe obstructive sleep apnea (OSA) in patients intolerant of positive airway pressure. Comorbid insomnia (COMISA) is common and may shape their engagement. Despite reports of improved insomnia symptoms, real-world data suggest reduced adherence and increased support needs. This study evaluated the impact of COMISA on HGNS therapy patterns and outcomes. Methods We conducted a retrospective cohort study of 46 adults with OSA who underwent HGNS implantation at Mayo Clinic Rochester between July 2020 and August 2025. Patients were categorized as OSA alone or COMISA based on pre-implantation data, including documented insomnia diagnosis, insomnia severity index score ≥15, sleep initiation or maintenance complaints, hypnotic or melatonin use, participation in cognitive behavioral therapy for insomnia, or an insomnia care plan within one year prior to activation. We collected HGNS adherence metrics (30-day average nightly use, nightly pauses, percent nights used) at 1, 3, 6, and 12 months; non-visit HGNS-related clinical encounters at 6 and 12 months; and pre- and post-activation AHI from polysomnography or home sleep apnea testing. Longitudinal outcomes were analyzed using mixed-effects models with fixed effects for time and COMISA status and a random intercept for patient. Results The cohort was 54% male and 98% White, with median age 66 years and BMI 31 kg/m2 (24–34). Median pre-implant AHI was 27 (19–40), and 30 patients (65%) had COMISA. Median nightly HGNS use declined from 7.8 to 6.6 hours from 1 to 12 months; mixed-effects modeling confirmed significant decreases over time (p≤0.03). Median nightly therapy pauses increased from 0.1 to 0.5, and median non-visit clinical encounters increased cumulatively from 2.5 at 6 months to 3.0 by 12 months (both p≤0.01). Median AHI reduction was 18.5 (2–27) (p=0.047). There were no statistically significant differences between OSA-alone and COMISA groups in HGNS adherence trajectories, therapy pauses, support needs, or AHI improvement (all p>0.05). Conclusion Although HGNS use declined modestly over time, COMISA was not statistically associated with differences in adherence, clinical support needs, or treatment response. Directional trends suggest greater adaptation challenges among patients with COMISA, warranting evaluation in larger prospective studies. Support (if any)

Abstract Introduction Adherence to continuous positive airway pressure (CPAP) therapy is difficult for many patients with obstructive sleep apnea. Clinical outcomes are improved with CPAP adherence ≥6 hr/night, yet scalable approaches to personalized support are limited. We developed a theory-based, clinic experience–driven conceptual dynamical model for optimizing CPAP use and applied it to a ‘just-in-time’ adaptive version of SleepWell24, a smartphone application integrating near–real-time wearable data, CPAP use, and patient-reported symptoms and CPAP-related problems with evidence-based behavior change interventions. In this feasibility optimization trial, we examined patient acceptability and initial outcomes of the adaptive SleepWell24 platform, and guided by the conceptual model, evaluated a control systems engineering approach to demonstrate, in simulation, improved CPAP adherence. Methods Aim 1: Naïve CPAP users (N=10; M age=61.7, 60% female) participated in this 60-day ongoing trial. Patients were encouraged to interact daily with SleepWell24 to report symptoms, receive personalized troubleshooting recommendations, set goals, and receive feedback on CPAP use (via Wi-Fi-enabled smart plug assessing CPAP ‘on/off state’) and sleep/activity (Fitbit). We assessed SleepWell24 use, post-intervention acceptability, and consistent CPAP use defined as ≥6hr, for ≥6nights/week for ≥2 consecutive weeks. Aim 2: The conceptual model of CPAP adherence produced a dynamical system, informed by Model Predictive Control (MPC) as a decision-making algorithm to optimize CPAP use to ≥6hr/night by tailoring actionable behavioral recommendations using patient data integrated in real-time. Results Aim 1: Across the 60-day trial, average daily SleepWell24 engagement was 72.7%. Median CPAP adherence of ≥6hr/night was 65.8%. All participants (100%) rated SleepWell24 as moderately-to-totally acceptable and would recommend it; perceived helpfulness averaged 7.0 (of 10). Eighty percent achieved consistent CPAP use. Aim 2: In simulation, the MPC framework managed CPAP-associated symptoms (e.g., nasal, anxiety, leak) and adjusted CPAP use goals, improving predicted CPAP adherence and sleep duration and quality. Conclusion SleepWell24 was engaging, acceptable, and helpful, with most users reaching optimal CPAP use. We will next estimate dynamical models using data from trial patients, a necessary step towards full automation of SleepWell24. Support (if any) AASMF #285-SR-22

Abstract Introduction Hypoglossal nerve stimulators (HGNS) are used in patients with moderate-to-severe obstructive sleep apnea (OSA) who are unable to tolerate or do not respond to continuous positive airway pressure (CPAP) therapy. However, a subgroup of patients fail to achieve resolution of OSA with HGNS alone. Previous studies have shown that lower BMI, lower nadir oxygenation, decreased sleep latency, and higher VOTE score on drug-induced sleep endoscopy (DISE) predict better treatment outcome. We hypothesize that baseline diagnostic polysomnography (PSG) may further predict which patients will achieve successful therapeutic outcome with HGNS therapy. Methods We conducted a retrospective analysis of all adult patients who underwent HGNS implantation at Mayo Clinic Arizona between 2019-2025 and had a pre-implantation diagnostic PSG available for review. Treatment success was defined by Sher Criteria: >50% reduction in post-treatment apnea hypopnea index (AHI) to a final AHI of < 20/hr. Responders met Sher criteria and non-responders did not meet Sher criteria. Demographics, sleep questionnaire results, PSG variables, and VOTE score on DISE were collected and analyzed using Spearman’s rank correlation of reduction in AHI. Results Twenty-three patients (11M/12F, median age: 69[IQR:64,75] years) met inclusion criteria. Median baseline AHI was 24[IQR:19,37]/hr. Median post-implant AHI was 8 [IQR:3, 14]/hr. Responders (n=15, 65%) and non-responders (n=8, 35%) demonstrated median post-implant AHI of 4.5[IQR:2.3,7.3]/hr and 15.7[IQR:12.3,28.5]/hr, respectively. Treatment response was associated with less time with SpO2 < 88% (T88%) (21min [IQR:3,64] vs. 73[IQR:36,105mins]; p=0.023) and higher central apnea index (CAI) (1[IQR:0.1,3] vs. 0[IQR:0,1], p=0.03) on pre-implantation PSG. Conclusion In this small cohort of OSA patients, less nocturnal hypoxemia as defined by T88% and higher baseline central apnea index were predictors of better treatment response to HGNS therapy as measured by Sher criteria. We hypothesize that greater nocturnal hypoxemia likely reflects more severe airway obstruction during sleep. Our analysis also showed that responders had higher baseline CAI than non-responders, however we believe this association is not clinically significant and likely driven by one outlier (CAI 13/hr). Further analysis in a larger HGNS cohort is needed to confirm these findings. Data enrichment efforts and more sophisticated analyses are underway. Support (if any)

Abstract Introduction Obstructive sleep apnea is an increasingly common condition seen in sleep medicine with prevalence estimates of up to 1 billion patients globally. Treatment with CPAP machines is the mainstay of therapy for patients with moderate-severe OSA, but is resource intensive due to the need for complex electronic equipment and frequent supply refills. The United States healthcare system is estimated to produce.9 million tons of solid waste annually; however, it has not been determined how sleep medicine clinical practices contribute to this total. The purpose of this study was to estimate the total solid waste produced by the treatment of moderate-severe OSA with CPAP in the U.S. over a 10 year period. Methods We modeled waste generation under a steady-state CPAP-treated population (4.8 or 24 million patients), assuming an annual 15% exit/entry rate. Each new patient was assigned a CPAP machine at initiation; existing users contributed waste from ongoing consumable use. Waste calculations included machine and accessory weight (masks, tubing, filters). We evaluated scenarios by varying mask type distribution, tubing type (heated; non-heated), and machine/supply replacement schedules to create total waste estimates. Results The solid waste associated with treating 4.8 million U.S. patients with moderate-severe OSA over ten years ranged from 88.7 to 104.4 kilotons. Maximum waste occurred with heated tubing use, CMS replacement schedules, 5-year device replacement, regardless of mask mix (104.4-104.5 kilotons). Waste was reduced by 15% using lightweight tubing and extending device life to 7 years, and by 45% using a reduced replacement schedule modeled on French practice (2–4 masks/year, 1 tubing/filter/year, 1 water reservoir/year). Conclusion Treatment with CPAP is a resource intensive therapy that produces a significant amount of plastic and electronic waste annually, likely contributing to ongoing environmental and climate degradation. Extending CPAP machine and supply lifespan and selecting for lighter PAP supplies, such as non-heated tubing, can significantly reduce the waste associated with U.S. CPAP use. Support (if any)

Abstract Introduction Obstructive sleep apnea (OSA) is common but often underdiagnosed and undertreated. Expanding the role of primary care providers (PCPs) may improve timely diagnosis and treatment of OSA, but patients report higher positive airway pressure (PAP) therapy adherence when cared for by specialists at centers accredited by the American Academy of Sleep Medicine. At Mayo Clinic, PCPs are now authorized to order home sleep apnea testing (HSAT) and subsequent therapy; HSAT is reviewed and interpreted by Sleep Medicine specialists (SMSs), but patients receive diagnoses and treatment recommendations through their PCP. This retrospective study evaluates whether patients diagnosed with OSA through primary and specialty care pathways experience comparable timeliness of care, counseling about therapeutic options, and PAP adherence. Methods Fifty-five patients were selected from each of two groups, based on whether their HSAT was ordered and initially managed by a PCP or SMS. Initial sleep metrics, PAP therapy adherence data, and other management details (treatments offered and key dates in the care pathway) were compared across groups. Results Once HSAT had been ordered, provider type was not associated with meaningful discrepancies in diagnosis and treatment timeliness; PCP-managed patients waited just one additional day after the interpretation of their HSAT to be offered treatment (p=0.025). However, consultation with Sleep Medicine introduced upfront delays caused by limited access to specialty care. The total time in the OSA care pathway, between referral to a SMS or pre-HSAT evaluation to the offering of treatment was 113 days for SMS patients versus 28 days for PCP patients (p< 0.001). Additionally, SMSs identified more co-occurring sleep disorders and discussed a broader range of treatment options with their patients, who demonstrated nightly PAP usage of 1.15 hours longer on average. Conclusion Despite differing modes of patient communication, PCPs offer timely OSA testing and diagnosis, allowing patients to bypass lengthy specialty care wait times. However, future efforts are needed to address variations in the counseling provided, and to ensure that all patients are equipped to succeed with PAP therapy. These findings support primary care pathways for uncomplicated OSA while highlighting the need for enhanced education and support to optimize patient outcomes. Support (if any)

Abstract Introduction The remedē System® Therapy Study (reST) is a real world evaluation using transvenous phrenic nerve stimulation (TPNS) to treat adults with moderate-to-severe central sleep apnea (CSA). Based on previous clinical trials, it was expected that most patients with CSA would have heart failure (HF). However, recent CSA prevalence publications demonstrated the opposite. We present the baseline characteristics of patients with CSA treated with TPNS. Methods Adult subjects determined eligible for a commercial TPNS device implant by routine clinical PSGs were consented to participate in the trial. Baseline assessments were performed and medical history collected. Patients will be followed for ≥1 year following therapy activation; follow-up is ongoing. This report describes the baseline characteristics of the patient population. Results Twenty-nine sites enrolled a total of 197 subjects (171 United States & 26 the Netherlands) between July 2019 and March 2025. Median [Q1-Q3] age was 70 [61-76] years, 82% were male, and 97% white race. Body mass index was 28.7 [25.8-31.6] kg/m2, with neck size 41 [28-44] cm. Patients had moderate-to-severe CSA with site-reported apnea-hypopnea index of 46/hour [30-64], including central apnea index of 24/hour [13-38]. Despite a range of comorbidities among patients, HF was documented in just 23%. Other cardiovascular conditions were more prevalent, including hypertension (70%), hyperlipidemia (65%), coronary artery disease (37%), atrial fibrillation (34%), and prior stroke (14%). Non-cardiac issues such as depression (27%), diabetes (26%), and renal disease (18%) were also present. Additionally, 22% of patients used narcotics, and 89% had previously failed another CSA therapy, most often CPAP (79%), Bi-PAP (39%), or ASV (32%). Lastly, almost 20% were from high altitude locations (>5,000 feet). Conclusion Patients implanted with TPNS had significant co-morbidities. However, HF was much less common than anticipated. This finding could be due to CSA being present in clinical practice with a wider range of underlying causes beyond HF, or undiagnosed early-stage HF. Alternatively, it may reflect referral bias for this specific therapy, with patients selected because of prior treatment failures or other comorbidities. These possibilities highlight the importance of recognizing CSA in a diverse patient population and underscore the need for multidisciplinary team management. Support (if any) ZOLL Respicardia, Inc.

Abstract Introduction Klinefelter syndrome (KS) is a chromosomal condition marked by hypogonadism and disturbances in hormonal regulation. The relationship between KS and co-occurring sleep disorders has not been extensively characterized, creating a need for more detailed investigation. Methods We identified individuals with Klinefelter syndrome (KS) evaluated at our institution between January 2000 and December 2025 using ICD-9 and ICD-10-CM codes. Electronic health records were then manually reviewed to confirm KS status and to exclude miscoded entries. For confirmed cases, we extracted data on sleep-related complaints, diagnoses, diagnostic testing (overnight oximetry, polysomnography, home sleep testing), and treatment. Sleep disorders were categorized operationally: obstructive sleep apnea (OSA), central sleep apnea (CSA), insomnia, hypersomnia/narcolepsy, or other according to documented clinician diagnosis or diagnostic test results. When structured Sleep Center data were available, these were included. We summarized cohort characteristics using means (± SD) or medians (interquartile range) as appropriate. For comparison between subgroups (e.g., those with vs without documented sleep-disordered breathing), we applied Welch’s t-test and binomial proportion tests. Analyses were conducted using Python scripts and spreadsheet software. Results Nearly one-third of patients with confirmed KS in this series had either diagnosed or suspected obstructive sleep apnea (OSA), substantially exceeding prevalence estimates in the general population. The frequency of central sleep apnea (CSA) was comparable to that seen in the general population, however its occurrence without usual predisposing factors suggests a predisposition toward idiopathic CSA in KS. Circadian rhythm disorders were rare, occurring in < 1% of the cohort. Notably, nearly 75% of KS patients with documented sleep-related symptoms had never undergone formal evaluation in a Sleep Center. Conclusion The observed rate of presumed idiopathic CSA among individuals with KS suggests the possibility of KS-specific mechanisms affecting ventilatory control stability. Additionally, there appeared to be a larger prevalence of OSA in this patient population. Notably, approximately three-quarters of KS patients who reported sleep-related symptoms had never undergone a formal Sleep Medicine assessment, highlighting a significant gap in structured evaluation that may relate to limited access to specialized care, referral patterns, or other systemic barriers, and warrants additional study. Support (if any) None

ABSTRACT Background and Aims Cellular senescence is a hallmark of several liver diseases, including primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Senescent cholangiocytes exhibit a senescence‐associated secretory phenotype (SASP), characterized by profibroinflammatory mediator release. Current cost‐effective biomarkers predicting disease progression, particularly for PSC, are limited and often lack mechanistic relevance. We sought to define a plasma biomarker signature for PSC and PBC. Methods Plasma from early‐ and late‐stage PSC and PBC, alcoholic liver disease (ALD), inflammatory bowel disease (IBD) patients, and healthy controls was analyzed. Seventy‐one analytes were quantified using Luminex Multiplex Immunoassay or enzyme‐linked immunosorbent assay (ELISA). Principal component analysis (PCA) identified key patterns. Findings from the PSC cohort were then applied to additional cohorts. Results Second principal component (PC2) (17 analytes, 17.1% variability) best separated PSC from controls. ANOVA showed significant differences in PC2 between early PSC vs. controls ( p = 0.0001), late PSC vs. controls ( p < 0.0001), and early vs. late PSC ( p < 0.0001). PC2 analytes also distinguished early PBC vs. controls ( p < 0.0332), late PBC ( p < 0.0001), and ALD ( p < 0.0001), and early vs. late PBC ( p < 0.0001), but not IBD vs. controls ( p = 0.119). Logistic regression using PC2 demonstrated strong discrimination of early‐ and late‐stage PSC (AUC = 0.86) and control vs. early‐stage PSC (AUC = 0.83). Conclusion This is the first study to define a plasma SASP biomarker signature associated with cholestatic liver disease. These analytes track disease stage and represent both mechanistic indicators and potential clinical trial endpoints.

ABSTRACT Obstructive sleep apnea (OSA) is a common, heritable disorder with diverse clinical presentations and etiologies. We conducted a genome-wide association meta-analysis of 492,107 individuals, including 46,028 OSA cases, identifying 14 genome-wide significant loci, eight of which are novel. Analyses adjusting for body mass index (BMI) revealed three loci independent of obesity, implicating alternative biological pathways contributing to disease. Integrative functional analyses, including chromatin interaction mapping, fine-mapping, and eQTL colocalization, prioritized candidate effector genes. Notably, implicated genes in chondrocytes were associated with craniofacial morphology in both mouse and human multivariate genotype-phenotype mapping, supporting a role for craniofacial structure in OSA risk. These findings highlight key genetic pathways (obesity-related, neurological, and craniofacial) underlying the development of OSA, offering new insights into its complex etiology.