bluuebunny/crossref_metadata_2025 huggingface dataset:
0449 Unbiased Examination of Metabolomic Signatures in Sleep Disordered Breathing and Group 1 PAH in the (PVDOMICS) Cohort
Authors: Ahmad Imama , Grunig Gabriele , Hemnes Anna , Finet Emanuel , Erzurum Serpil , Hill Nicholas , Barnard John , Mehra Reena ,   PVDOMICS Study Group
Published: May 2023

Introduction

Metabolic alterations have been identified as a novel driver of pulmonary arterial hypertension (PAH) pathogenesis. Sleep disordered breathing (SDB), characterized by intermittent hypoxemic episodes, has also been implicated in PAH, particularly when associated with more profound degrees of hypoxia, and metabolic dysfunction. We hypothesize to observe in SDB and PAH in humans a similar pattern of metabolic alterations as previously described in animal models of PAH.

Methods

Pulmonary Vascular Disease Phenomics (PVDOMICS,NCT02980887), a multicenter study, was designed in part to elucidate molecular signatures in PH. We analyzed data from Group 1 PAH participants who underwent home sleep apnea testing with circulating plasma metabolomic measures (Metabolon). We conducted an unbiased analysis of SDB measures: apnea-hypopnea index (AHI, 3% oxygen desaturation hypopnea definition) and % recording time< 90% SpO2 (TRT< 90%), with metabolites (954 after qc filtering) using a flexible and robust semi-parametric proportional hazards model adjusted for age, sex, body mass index (BMI), diabetes mellitus (DM), race and study site. Metabolites with False discovery rate (FDR) adjusted p-values < 0.1 were called significant. Closed-set testing with the Simes method and Metabolon provided annotations (90 sets) was used to test metabolite sets.

Results

The cohort (n=175) was 72% female, 81% White and 16% DM with (1st Quartile/Median/3rd Quartile) Age: 42/54/63 years, BMI: 24.6/29.1/34.1 kg/m2, AHI: 0.9/4.3/12.6 and TRT< 90%: 2.3/37/87.4. 21 metabolites showed significant association with TRT< 90% (8 with positive direction/13 negative) and 0 with AHI. Among metabolite sets, Pregnenolone steroids had the strongest association with TRT< 90% (6 members; adjusted p=0.038; True Discovery Proportion (TDP)=0.33) followed by Fatty Acid Metabolism (Acyl Choline) (7 members; adjusted p-value=0.046; TDP=0.71) and Polyamine Metabolism (7 members; adjusted p-value p=0.054; TDP=0.14).

Conclusion

Three primary metabolite pathways were associated with sleep-related hypoxia in Group 1 PAH. Polyamine metabolism and fatty acid metabolism changes have previously been observed in a rat PAH model, consistent with our findings. Findings specific to metabolic biomarkers in SDB and PAH are novel and may lead to insights that broaden our understanding of PAH pathobiology and potential therapeutic targets.

Support (if any)
0450 Backscattered Ultrasound Imaging of the Tongue Correlates with Severity of Obstructive Sleep Apnea in Adults
Authors: Bosschieter Pien Bosschieter , Kushida Clete , Liu Stanley
Published: May 2023

Introduction

Determination of intervention to manage obstructive sleep apnea (OSA) is dependent on clinical examination, polysomnography results, and imaging analysis. There remains the need of a non-invasive and cost-effective way to correlate relevant upper airway anatomy with severity of obstructive sleep apnea (OSA ) to direct treatment and optimize outcome. We aimed to determine whether ultrasonography with backscattered imaging (BUI) analysis of the tongue correlates with severity of OSA in adults.

Methods

A prospective, single-center, observational study of a consecutive series of patients (aged18 years and older) visiting our sleep clinic. All included patients had a polysomnography (PSG) within 3 years from the moment of BUI analysis. Patients were excluded if their BMI had changed more than 10%. We used and standardized the submental ultrasound scan with a laser alignment tool and applied BUI analysis to the tongue. Outcomes were correlated to the patients’ AHI, BUI results were compared to only echo intensity.

Results

Eighty-nine patients were included between July 2020 and March 2022. Mean age was 38.8±12.7 years, mean BMI was 26.7±5.0 kg/m2, and mean AHI was 17.5±16.8 events/h. Significant differences were found between the subgroups with AHI< 15 and □15 events/h at specific regions of the tongue base using BUI analysis, echo intensity showed no significant differences. BUI values showed a positive correlation with AHI, with Pearson correlation coefficient of 0.42 and 0.37, and Spearman correlation coefficient of 0.43 and 0.43 for the A and B regions of the tongue, respectively. Higher BUI values are associated with more severe AHI, even after correction for covariates (BMI and age).

Conclusion

Standardized ultrasound scanning of the tongue with backscattered imaging analysis yields strong correlation with severity of OSA. With the intrinsic advantages in the use of ultrasonography in outpatient settings, this analysis is pivotal in reducing the gap between anatomy and physiology in clinical decision-making for treating OSA.

Support (if any)

None
0453 3-Year Outcomes of Proximal Hypoglossal Nerve Stimulation in the THN3 Controlled Trial
Authors: Schwartz Alan , Jacobowitz Ofer , Mickelson Samuel , Miller Mitchell , Oliven Arie , Certal Victor , Hopp Martin , Winslow David , Huntley Tod , Nachlas Nathan , Gillespie M , Weeks Brian , Lovett Eric , Malhotra Atul , Maurer Joachim
Published: May 2023

Introduction

The THN3 randomized, controlled trial of moderate to severe obstructive sleep apnea (OSA) showed that proximal (“targeted”) hypoglossal nerve stimulation (HGNS) safely improved sleep-disordered breathing (SDB) and quality of life (QOL) through 11 months of treatment. Outcomes of subjects receiving active proximal HGNS also surpassed those with inactive therapy 4 months post-implant. Herein 3-year outcomes of THN3 are reported and compared to distal HGNS (STAR trial).

Methods

THN3 OSA subjects (Apnea-Hypopnea Index, AHI, 20-65/hr; BMI ≤ 35 kg/m2, no drug-induced sleep endoscopy screening) were followed long-term. Complete data through 3-year follow-up were analyzed. Efficacy measures comprised AHI, Oxygen Desaturation Index (ODI), %sleep time O2 saturation < 90% (T90), Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ) EQ-5D Visual Analog Scale (VAS) and Snore Outcomes Survey (SOS). 36-Month medians were compared against those after 11 months of therapy (Month 12/15) and with STAR. Adverse events (AEs) during Months 12-36 for THN3 and STAR were also compared.

Results

75% of THN3 participants (104/138) attended 3-year follow-up, with complete efficacy records in N≥93 except for SOS (N=67, not administered at all sites). Proximal HGNS produced clinically and statistically significant improvements in SDB and QOL at Month 12/15 that were closely maintained at 36 Months (median paired changes at Month 36 from Baseline/Month 12/15: □AHI:-18.2/-0.1, □ODI:-16.2/0.8, □T90:-1.8/0.2, □FOSQ:3.0/0.0, □ESS:-5.0/0.0, □VAS:5.0/0.0, □SOS:37.5/3.1) and were comparable to STAR at 36 Months (□AHI:-19.4, □ODI:-17.2, □T90:-1.5, □FOSQ: 2.6, □ESS:-4.0). Procedure- and device-related AEs respectively totaled (3 and 27)/(4 and 122) in THN3/STAR over Months 12-36. During this time, 3 severe related-AEs occurred in THN3; the most frequent related AEs involved tongue discomfort (N=8, device-related).

Conclusion

Improvements in sleep apnea and QOL on proximal HGNS at Month 12/15 persisted through at least Month 36. Proximal HGNS long-term efficacy was comparable to distal HGNS. AEs occurred uncommonly during long-term follow-up and were typically mild. Proximal HGNS is a safe, effective, stable, long-term therapy, yielding comparable improvements to distal HGNS in treating moderate to severe OSA. Results of the ongoing, confirmatory OSPREY randomized controlled trial will provide additional insights into therapeutic benefits of proximal HGNS.

Support (if any)

LivaNova
0454 A Specific STOP-BANG Score Cutoff is Not Predictive of Severe Obstructive Sleep Apnea in Bariatric Patients
Authors: Wittine Lara , Corsello Jenalee , Murr Michel
Published: May 2023

Introduction

Obstructive sleep apnea (OSA) is a common sleep disorder with obesity being a significant risk factor. Undiagnosed OSA increases the risk of complications at the time of surgery and those with severe OSA at increased risk of post-operative MI, stroke, arrhythmias, and death as well as readmission and acuity of post-operative care. Because of this, our Bariatric program screens all patients pre-operatively with a STOP-BANG questionnaire. Those with severe OSA (AHI or REI > 29) require pre-treatment with PAP therapy until compliance is reached before the patient is eligible for surgery. This study examines those that screened at high risk for OSA with a STOP-BANG score > 2 to see if there was a specific cutoff that predicts those having severe OSA in order to better expedite sleep testing as recent supply chain issues have greatly impacted the timeliness of care for these patients.

Methods

During the months of January to June 2022, demographic, clinical and sleep data was collected on all new patients being evaluated by the Bariatric Sleep clinic for use in quality assessment. Bariatric patients with BMI < 50 and no significant cardiac or pulmonary disease were tested using HSAT, whereas those who met one or more of the above comorbidities underwent PSG.

Results

There were 143 bariatrics patients who screened as “high risk” for OSA with a STOP-BANG score > 2 during these 6 months and 112 (78%) of them completed sleep testing. There were 25 patients (22%) with severe OSA. The average STOP-BANG score for those with severe OSA was 4.3. Women averaged 4.0 (range 3-6), while men averaged higher at 4.8 (range 4-6) likely reflecting that male gender garners an extra point with the STOP-BANG. STOP-BANG scores increased with age: 20s x=3, 30s x=4.1, 40s x=4.4, 50s x=4.6, 60s x=6.

Conclusion

There was no specific cutoff for the STOP-BANG score that predicted severe OSA in our bariatric patients to help our program triage those most at surgical risk in order to place them in an expedited sleep testing and PAP therapy pathway. Overall, STOP-BANG scores were impacted by gender and age.

Support (if any)
0472 INSOMNIAS IN OSA PATIENTS WITH DIFERENT DEGREES OF SEVERITY: A STEP TOWARDS PHENOTYPING COMISA
Authors: Fonseca Ana , Laranjinha Ana , Cruz Miguel Meira e
Published: May 2023

Introduction

With this pilot study, authors aimed to find how OSA and insomnias (sleep onset and maintenance insomnia) interact.

Methods

Data from PSG-level 1 consecutive Obstructive Sleep Apnea (OSA) patients were retrospectively collected. Insomnia and OSA severity were assessed. Arousals (A), arousal index (AI), wakefulness after sleep onset (WASO), total sleep time (TST) and sleep eficiency (SE) were used to better characterize insomnias. Epworth Sleepiness Sclae (ESS) was used to assess excessive daytime sleepiness (EDS).

Results

From 87 OSA patients, 43 (51.8 %): 53.5 % being females (F), where insomniacs (COMISA). Patients with COMISA where distributed as follows: Mild OSA (5 F: 22%; BMI=26.9±4.0 Kg/m2; Age=50.3±15.8 years old - yo; AHI=15.9±13.3 ev/h; ODI3%=4.0±3.9 ev/h; SaO2mean=96.4±0.98 %; SaO2min=89.5±4.2 %) with a TST of 414.5±70.9 min, SE=79.6±13.6 %, WASO=83.7±57.0 min and 182.7±84.8 arousals (AI=26.6±11.1 ev/h); Moderate OSA (8 F: 35%; BMI=28.7±4.7 Kg/m2; Age=53.5±13.4 yo; AHI=24.4±3.1 ev/h; ODI3%=8.8±5.7 ev/h; SAO2mean=95.3±1.2 %; SaO2min=87.7±3.9 %) with a TTS=385.8±69.2 min, SE=80.7±12.6 %, WASO=81.4±62.3 min and 178.8±69.5 arousals (AI=27.5±8.9 ev/h); Severe OSA (10 F: 43 %; BMI=30±5.2 Kg/m2; Age=58.6±7.8 yo; AHI=48.1± 19.9 ev/h; ODI3%=25.4±25.1 ev/h; SaO2mean=94.5±2.4%; SaO2min=82.6±10%) had a TTS=386.5±64.5 min, SE=77.4±11.4%, WASO=93.3±49.8 min and 274.2±95.3 arousals (AI=42.6±12.9 ev/h). The others 40:48.2 % presented with Isolated OSA: Mild OSA (7 F: 39 %; BMI=27.8±3.9 Kg/m2; Age=48.3±12.1 years old - yo; AHI=8.9±3.2 ev/h; ODI3%=2.5±2.7 ev/h; SaO2mean=96.4±0.8%; SaO2min=90.8±2.6%) had a TST of 423.9±36.7 min, SE=86.4±7.3%, WASO=58.1±27.2 min and 151.6±42.1 arousals (AI=21.6±6.5 ev/h); Moderate OSA (7 F: 39%; BMI=27.1±5.4 Kg/m2; Age=53±13.1 yo; AHI=21.2±3.8 ev/h; ODI3%=6.9±3.8 ev/h; SAO2mean=95.9±0.6%; SaO2min=86.7±4.1%) had a TTS=406.3±86.5 min, SE=79.4±15.2%, WASO=77.2.3±68 min and 196.3.8±60.4 arousals (AI= 29.1±6.6 ev/h); Severe OSA (4 F: 22%; BMI=28.3±4.2 Kg/m2; Age=62±12.5 yo; AHI=51.8± 18.7 ev/h; ODI3%=28.5±21.2 ev/h; SaO2mean=93.9±3.5%; SaO2min=81.4±10.2%) had a TTS=385.9±105.7 min, SE=76.2±20.1%, WASO=92.9±80.1 min and 272.7±115.6 arousals (AI=42.5±14.9 ev/h). ESS was 10.1±7.9, 9±5.4 and 8±5.7 for the Mild, Moderate and Severe OSA in COMISA group, and 14.6±7.3, 10.9±5.2 and 5.9±5.2, for the mild, moderate and severe forms of the isolated OSA group.

Conclusion

Insomnia complaints in OSA patients and PSG correlates seems to indicate clinically relevant COMISA phenotypes that would help to better characterize and manage this condition at different degrees of OSA severity.

Support (if any)
0477 Positive Airway Pressure Therapy and Antidepressant Medication Adherence in Patients with Obstructive Sleep Apnea and Depression
Authors: Sterling Kimberly , Dexter R Benjamin , Pépin Jean-Louis , Cole Kate , Wickwire Emerson
Published: May 2023

Introduction

Previous studies have shown that treatment of obstructive sleep apnea (OSA) with positive airway pressure (PAP) therapy in patients with OSA and comorbid depression may improve response to antidepressant medication therapy. At the same time, scant evidence has examined the impact of medication and PAP adherence in patients with OSA and comorbid depression. Patients that adhere to one therapy may be more likely to adhere to other therapies or healthy behaviors in a so-called “healthy user effect.” This retrospective study investigated the association between antidepressant medication adherence and PAP therapy adherence in patients with newly diagnosed OSA and comorbid depression.

Methods

Our data source was a national sample of administrative claims data linked to objective PAP therapy usage. Included patients either had two healthcare encounters or one hospitalization with a depression ICD-10 diagnosis code the year prior to being diagnosed with OSA and initiated on PAP therapy. Adherence to antidepressant medication was defined as ≥80% of proportion of days covered (PDC), and non-adherence was defined as < 80% PDC within a 180-day exposure window during the year prior to starting PAP therapy. Adherence to PAP therapy was categorized as consistently adherent, intermediately adherent, or not adherent based on objective usage over 2 years.

Results

36,668 patients with OSA and comorbid depression were included. 27% were classified as consistently adherent, 45% intermediately adherent, and 28% non-adherent to PAP therapy. 68.6% of patients used antidepressant medication in the year prior to PAP initiation. 67.7% used a selective serotonin reuptake inhibitor, 43.8% atypical antidepressants, 32.1% serotonin and norepinephrine reuptake inhibitor, 10.7% tricyclic antidepressant, and 0.1% monoamine oxidase inhibitor. Relative to patients not adherent to antidepressant medication (22.2% consistently adherent, 43.8% intermediately adherent, 33.9% not adherent), those adherent to antidepressant medication in the year prior were also more adherent to PAP therapy over 2 years (29.2% consistently adherent, 45.2% intermediately adherent, 25.6% not adherent).

Conclusion

Patients that were adherent to antidepressant medication in the year prior to starting PAP therapy have slightly better adherence to PAP therapy over 2 years. In real-world studies, medication adherence may be an important confounder to adjust for when comparing patient outcomes.

Support (if any)
0478 Pre-test probability of OSA based on subjective questionnaires can indicate who will benefit the most from a Type II study
Authors: Guadagni Veronica , Bender Amy
Published: May 2023

Introduction

Type III home sleep apnea tests have become increasingly popular due to reduced cost and convenience. However, previous research has reported limitations in their diagnostic accuracy. In this study, we assessed which individuals would benefit the most from a Type II home-PSG study when the only information available to clinicians were answers to subjective questionnaires.

Methods

We analyzed responses to a custom sleep survey from 510 participants (age 46.2±12.4; 229 females). We entered 13 outcomes to a principal component analysis (PCA). These included age, body mass index (BMI), Epworth sleepiness scale (ESS) scores, sex, questions about snoring, subjective hours of sleep, satisfaction with own sleep, movement symptoms, problems falling asleep, staying asleep and waking up early. Based on the correlations between the original outcomes, the PCA extracted 3 factors that were interpreted as 3 different phenotypes: I) insomnia (e.g., sleep initiation and maintenance complaints, satisfaction with sleep, lower subjective sleep duration); ii) OSA (e.g., bed partner snoring complaints, snoring self-awareness, sleepiness, respiratory complaints); iii) movement disorder (e.g., movements, female, lower age, higher BMI). We then computed the pre-test probability of OSA (factor 2 scores >80%) and conducted a series of ROC analyses to assess specificity of the AHI in the same patient from both Type II and a simulated Type III (with EEG channels removed), RDI, and ORP metrics.

Results

The AUC values assessing the ability to predict 80% pre-test probability of OSA were: AHI Type II (0.734), AHI Type III (0.672), RDI (0.729), ORPNREM (0.622) and ORPTRT (0.543). The clinically used cut-off of 15 for the AHI Type II correctly classified 83% of patients with 47% probability of false positives, while the same cut-off for Type III correctly classified 43% of patients with 33% probability of false positives.

Conclusion

AHI Type II tests had the highest sensitivity in detecting OSA despite someone having >80% pretest probability. This may be due to the characterization of hypopneas, respiratory effort related arousals, and total sleep time versus total recording time. These analyses indicate the superiority of Type II studies and indices that involve EEG signals to accurately detect OSA in patients with high pretest probability.

Support (if any)
0481 Sex Differences in Moderate-Severe Obstructive Sleep Apnea Diagnosis using Different Sleep Study Modalities
Authors: Junejo Shoaib , Gratton Matt , Shippy Daniel , Stewart Nancy , Stevens Damien , Morris Jonna , Mazzotti Diego
Published: May 2023

Introduction

Male sex is a risk factor for obstructive sleep apnea (OSA). However, because men have been historically described as more vulnerable towards developing OSA, definitions of severity have been based mostly on male-specific pathophysiology. This study aimed to describe sex differences in referral patterns of diagnostic sleep study modalities (in-lab polysomnography [PSG], home sleep apnea tests [HST]) and their results as they related to OSA severity.

Methods

We defined a clinical cohort of individuals that underwent diagnostic sleep testing at the University of Kansas Health System Sleep Disorders Center between 2012-2021. We determined the association between sex and moderate-severe OSA (as compared to no or mild OSA) separately for individuals that underwent HST and PSG, in logistic regression models adjusted for age, body mass index (BMI) and Epworth sleepiness scale (ESS) scores. A complementary analysis stratified by age groups (< 35, 35-50, 50-65, ≥65 years) was also conducted.

Results

A total of 10,357 participants were included in this analysis (5,428 women [52.4%]; 53.0 [14.4] years; BMI=34.0 [16.1] kg/m2). Individuals that underwent HST were younger, more likely to be men, had higher BMI, lower ESS scores, and more severe OSA. Men were more likely to be diagnosed with moderate-severe OSA in both modalities, however higher odds were observed in those diagnosed using HST (ORHST [95%CI] = 2.86 [2.52-3.25]) than in those diagnosed using PSG (ORPSG [95%CI] = 2.48 [2.09-2.95]). Further disparities were observed among those with < 35 years, where men had a 4-fold increase in the odds of a moderate-severe OSA diagnosis than women in a HST (ORHST [95%CI] = 4.10 [2.59-6.50]) and only a 2.5-fold increase in the odds in a PSG (ORPSG [95%CI] = 2.48 [1.13-5.45]).

Conclusion

As expected, men are more likely than women to receive a diagnosis of moderate-severe OSA, however the effects were stronger in those diagnosed with HSTs as compared to PSGs, particularly at younger ages. These results suggest that potential sex inequalities in diagnosis and determination of OSA severity may be influenced by the choice of diagnostic sleep study modality, particular in younger women.

Support (if any)

NCATS (UL1TR002366), AHA (20CDA35310360).
0485 The clinical utility of echocardiography in identifying patients with heart failure at a single academic sleep center
Authors: Patel Salma , Zareba Wojciech , Woosley Raymond , Perez Karolina , Patel Imran , Xia Xiaojuan , Wendel Chris , Miller Jerod , Quan Stuart , Parthasarathy Sairam
Published: May 2023

Introduction

Heart failure and sleep disordered breathing are prevalent in the United States and often co-exist; diagnostic strategy and management for sleep disordered breathing may change based on the presence, absence and type of heart failure. The goal of this study was to evaluate how many additional patients would be identified with either heart failure with reduced (HFrEF) or preserved (HFpEF) ejection fraction through existing echocardiogram results when this diagnosis is not explicitly stated in the medical records for patients evaluated at a single academic sleep center.

Methods

A retrospective chart review was performed for all patients undergoing for a sleep study and/or a PAP device from February 2012 through September 2019 at the University of Arizona. Sleep disordered breathing was identified through either polysomnography (PSG) or home sleep apnea testing (HSAT). Patients were identified with heart failure with reduced ejection fraction if an echocardiogram (TTE) listed ejection fraction

Results

2,817 patients were evaluated (age 57 (±16 years), 53% male and 77% Caucasian). Ninety-nine patients (3.51%) were noted to have HFrEF based on past medical history and an additional 38 patients were identified through TTE. One hundred and fifteen patients (4.08%) were noted to have HFpEF based on past medical history and an additional 265 patients were identified through TTE. Among these, a majority had OSA (77% HFrEF and 83% HFpEF), followed by combined OSA and CSA (7% HFrEF and 5% HFpEF), and primary CSA (5% HFrEF and 3% HFpEF). Of the patients identified after having reviewed TTE results, 6 (16%) with HFrEF and 42 (16%) with HFpEF developed treatment emergent central sleep apnea.

Conclusion

Existing echocardiography data in the electronic medical record can identify additional patients with HFrEF and HFpEF which may impact clinical diagnosis and management of sleep disordered breathing.

Support (if any)

AASM Foundation (203-JF-18), NIH (HL126140, 2L30HL154400-023), University of Arizona (5299903; 5833261; 4258021)
0490 Under-Recognition and Undertreatment of Obesity Hypoventilation Syndrome (OHS) After Hospital Discharge: A Persistent Challenge
Authors: Nowalk Nathan , Neborak Julie , Leonhard Aristotle , Rojas J C , Mokhlesi Babak
Published: May 2023

Introduction

Hospitalization for acute-on-chronic hypercapnic respiratory failure (ACHRF) in OHS is associated with increased short-term mortality. The 2019 American Thoracic Society’s guidelines recommend that hospitalized OHS patients be discharged on nocturnal noninvasive ventilation (NIV). However, this was graded as a weak recommendation given that the data was retrospective and derived from European/Australian studies limiting generalizability to other healthcare systems. We aimed to assess post-discharge therapeutic plans for hospitalized patients with ACHRF and suspected OHS in an urban, tertiary care center in Chicago serving a large minority population.

Methods

We retrospectively queried the electronic health record of University of Chicago from 2008 to 2020 for hospitalized adults with BMI ≥35 kg/m2 admitted from the emergency department, requiring NIV/mechanical ventilation with evidence of respiratory acidosis on first blood gas (pH < 7.35 with PaCO2 ≥ 45 mmHg or PvCO2 ≥ 50mmHg). Subjects were excluded for obstruction on spirometry, greater than 20-pack year smoking history, CT evidence of parenchymal lung disease, acute neurologic process, significant left-sided heart failure and neuromuscular disease.

Results

Of the 797 obese patients requiring NIV/mechanical ventilation, we excluded 672 for lack of acute hypercapnia or low suspicion for OHS. The remaining 125 patients were predominantly Black (n = 116, 93%) and female (n = 94, 75%), mean age of 53±13.9 years, mean BMI of 50.8±12.8 kg/m2, mean first pH of 7.22±0.097, PaCO2 79.9±24.5 mmHg (n = 31) and PvCO2 74.7± 20.2mmHg (n = 94). On admission, 84 patients (67%) did not carry a diagnosis of OHS and 66 patients (53%) were PAP-naïve. 54% were discharged on PAP (43% CPAP, 43% Bilevel, and 14% other). Patients discharged on PAP were more obese (p = 0.001) and more hypercapnic (p = 0.002). Post-discharge polysomnography/sleep clinic referral was planned for 40% of patients. The 1-year mortality rate was 8% with no association recognized between 1-year mortality and PAP on discharge.

Conclusion

In our cohort, the proportion of patients discharged on nocturnal NIV was low. In contrast to the guideline recommendation, we did not find an association between being discharged on PAP therapy and mortality. Larger studies in more diverse populations are needed.

Support (if any)
0493 A new perspective on exploring the predictive factors of blood pressure reduction during CPAP treatment in OSA
Authors: Sun Bo , Shen Jiani , Yang Ting , Meng Zili , Xu Jing
Published: May 2023

Introduction

The predictive factors of BP response to continuous positive airway pressure (CPAP) in obstructive sleep apnea (OSA) are still being explored. We aimed to assess the antihypertensive effect of CPAP considering the obstructive respiratory event-triggered BP surge profiles in 130 subjects with severe OSA and untreated hypertension.

Methods

Nocturnal BP was monitored continuously and synchronized with polysomnography. Event-triggered BP surge profiles were studied: BP surge as the value of event-related systolic BP elevation; BP index as the number of BP surge events of ≥10 mmHg per hour. Patients were then divided into two groups according to the median BP index (high and low BP surge groups) and assigned to 4 weeks of CPAP. Changes in BPs and plasma biomarkers were compared. After the initial evaluation, patients with a better BP response in the high BP surge group were then followed up for the second evaluation at 24 months.

Results

Overall, a modest decrease was observed in both office and asleep BPs at the 4-week follow-up; however, BPs dropped more markedly in patients in high BP surge group than those in low BP surge group, in both office systolic BP (SBP:5.3 mmHg vs.2.2 mmHg, P=.005) and diastolic (DBP:4.0mmHg vs.1.2 mmHg, P=.011), especially the asleep SBP (9.0mmHg vs.2.1 mmHg, P<.001). For 30 cases in the high BP surge group, optimal BP control was achieved in 60.0% of patients and BP < 140/90mmHg reached up to 83.3% after 24 months of CPAP. Linear regression revealed that BP index was significantly associated with BP decrease during CPAP treatment.

Conclusion

Our results suggest that high event-triggered BP surge was a sensitive predictor of BP response to CPAP in patients with severe OSA and hypertension.

Support (if any)
0509 Adverse Event Reports for CPAP, HNS and Oral Devices: An FDA MAUDE Database Analysis
Authors: Liptak Len , Murphy Mark
Published: May 2023

Introduction

This investigation analyzes adverse event reports (AERs) from the FDA MAUDE database for Continuous Positive Airway Pressure (CPAP), Hypoglossal Nerve Stimulation (HNS) and Oral Appliance Therapy (OAT) devices. The FDA defines adverse events as undesirable experiences associated with medical devices that should be reported when the outcome is death, life threatening, hospitalization, disability, required intervention, or serious medical events.

Methods

Publicly available industry reports were utilized to estimate prevalence of AERs.

Results

From January 1, 2022 to September 2022, AERs for CPAP, HNS and OAT were 72,251, 11,867 and 30, respectively. From January 2017 to September 2022, the annual count of AERs for CPAP and HNS increased 245% and 252% respectively. The annual count of AERs for OATs decreased -1.3% over the same period. Device Problems For CPAP, “Degradation” comprised 96.6% of the AERs. For HNS, “Event Without Problem” and “Device Sensing” comprised 78.6% and 11.0% of AERs respectively. For OAT “Event without Identification” and “Breakage” comprised 40.0% and 9.8% of AERs respectively. Patient Problems For CPAP, seven patient problems comprise over 80% of reports: No Clinical Signs/Conditions, 57.3%; Dyspnea, 5.4%; Headache, 5.3%; Sore Throat, 4.3%; Respiratory Tract Infection, 4.1%; Cough, 3.5%; Unspecified Respiratory, 3.0%. For HNS, nine patient problems comprise over 80% of reports: Unspecified Infection, 19%; Pain, 15.2%; No Clinical Conditions, 9.2%; Bacteria Infection, 8.7%; Perforation of Vessels, 7.1%; Erosion, 7.1%; Wound Dehiscence, 4.9%; Swelling/Edema, 4.8%; Hematoma, 4.4%. For OAT, seven patient problems comprise over 80% of reports: Hypersensitivity/Allergic Reaction, 23.5%; Reaction, 19.0%; No Known Impact, 15.9%; Swelling, 8.7%; Pain, 6.2%; Discomfort, 4.5%; Erythema, 3.8%; Rash, 3.5%.

Conclusion

This analysis suggests that healthcare providers may wish to consider the significant differences in the frequencies and the severities of adverse events when prescribing treatment modalities for patients with OSA. Dental side effects, a widely referenced reason for limiting the utilization of OAT devices, do not show up in the top 80% of the most frequently reported types of adverse events.

Support (if any)
0511 An observational retrospective study of the efficacy of oral appliance therapy (OAT) in treating obstructive sleep apnea (OSA)
Authors: Meskill Sarah , Rege Riddhi , Kincheloe Kelly , Meskill Gerard
Published: May 2023

Introduction

Obstructive sleep apnea (OSA) affects approximately 15-30% of males and 10-15% of females in North America. While positive airway pressure (PAP) therapy remains the standard in the treatment of OSA, oral appliance therapy (OAT) has emerged as a viable non-invasive alternative. However, there are limited data on OAT efficacy published, and therefore many sleep clinicians question its efficacy. We conducted a 14-month single-center consecutive chart review to evaluate OAT efficacy.

Methods

A manual chart review was performed for records from 11/1/2020 to 12/10/2022. Potential charts were identified in the electronic health record by searching for prescriptions for OAT and orders for home sleep apnea tests (HSAT). If there was a test performed after the prescription was written, the chart was reviewed manually for previous test results and verified that post-OAT testing was conducted. Extracted information included age, BMI, gender, pre-OAT HSAT apnea-hypopnea index (AHI), and post-OAT HSAT AHI. The 4% desaturation criteria for AHI was used in accordance with current Medicare guidelines. A paired t-test was performed after ensuring there were no outliers and a normal distribution.

Results

There were 10 patients included in the analysis: 6 women, 4 men. The average age was 61.1 years (95% CI 49.9-72.3), and average BMI was 28.9 (95% CI 253-32.4). Prior to intervention, 2 patients had moderate OSA with the rest mild (average pre-OAT AHI 13). After OAT device, 4 patients had mild OSA and the rest did not have residual OSA (average post-OAT AHI 4). The results of the paired t-test showed that the mean AHI was statistically significantly different between the two groups (t=-4.54 with df=9, p=0.0014). The mean difference was -8.1 with 95% confidence interval for the true difference in the population mean AHI of -12.1, -4.06.

Conclusion

The results demonstrate efficacy of OAT in treating OSA. Clinicians should consider OAT as both primary and secondary therapy for mild-to-moderate OSA.

Support (if any)

N/A
0512 Apnea-Hypopnea Index does not correlate with Non-Alcoholic Fatty Liver Disease scores
Authors: Vacheron Albert , Saha Anand , Coughlin Kevin , Freire A X , Theus Sue
Published: May 2023

Introduction

Obstructive Sleep Apnea (OSA) and Nonalcoholic Fatty Liver Disease (NAFLD) are two conditions that have increased in prevalence in the United States. NAFLD is a spectrum of liver disease ranging from steatosis to non-alcoholic steatohepatitis (NASH) to cirrhosis. The purpose of this project is to study the relationship between OSA, measured by apnea-hypopnea index and/or arterial oxygen saturation nadir (O2 nadir) during sleep (independent variable) vs. extent of NAFLD as measured by non-invasive scores such as NAFLD Fibrosis score, aminotransferase to platelet ratio index (APRI), BARD score and FIB-4 score (dependent variable).

Methods

A convenient sample of 91 haphazardly selected veterans with OSA and NAFLD from the Veterans Affairs (VA) Computerized Record System (CPRS) system were included in the study. NAFLD eligibility was determined by abdominal ultrasound, CT scan, MRI, or biopsy. Dependent variables were NAFLD scores of APRI, NAFLD Fibrosis, BARD, and FIB-4. OSA was determined by in-lab polysomnogram or home sleep study. Independent variables were AHI, O2 nadir, age and body mass index (BMI). Patients with a history of alcohol abuse or Hepatitis B or C were excluded from the study. A multiple regression analysis was used to describe the relationship between OSA and NAFLD scores. P< 0.05 was considered statistically significant.

Results

Age correlated with FIB-4 score, BARD score, and NAFLD fibrosis score (p = < 0.001, 0.003, < 0.001, respectively). BMI correlated with NAFLD fibrosis score (p < 0.001). When controlled for age and BMI, AHI and O2 nadir did not correlate with APRI, NAFLD fibrosis, BARD, or FIB-4 scores.

Conclusion

OSA measured by AHI and O2 nadir do not correlate with severity of fatty liver disease as measured by APRI, NAFLD fibrosis, BARD, or FIB-4 scores.

Support (if any)

None
0513 Assessing precision oral appliance efficacy using frequency- and risk-based indices
Authors: Mosca Erin , Grosse Joshua , Jahromi Seyed Abdolali Zareian , Remmers John
Published: May 2023

Introduction

Apnea-hypopnea index (AHI), a frequency-based index commonly used to define the severity of obstructive sleep apnea (OSA), fails to capture the risk related to OSA. Sleep apnea-specific hypoxic burden (SASHB) appears to be more predictive of OSA-related risk than AHI but has only been studied in cohorts of untreated individuals. This is the first assessment of the ability of precision oral appliance therapy (OAT) to reduce SASHB and the use of SASHB, rather than AHI, to define therapeutic efficacy.

Methods

Data previously obtained from a clinical study investigating prediction of response to precision OAT in OSA were analyzed. Study participants with OSA (n = 11 mild, n = 19 moderate, and n = 18 severe) completed two-night level 3 home sleep tests before and after receiving a precision oral appliance (ProSomnus Sleep Technologies, Pleasanton, CA). Apnea-hypopnea index and SASHB were calculated. For SASHB, a cut-off of 53 %min/h was selected based on data suggesting that values above this limit are associated with OSA-related risk; for AHI, cut-offs of < 10 h-1 and < 15 h-1 were selected due to their widespread use in clinical practice.

Results

Precision oral appliance therapy reduced AHI from 31.6 ± 19.2 h-1 to 11.7 ± 15.8 h-1 (p < 0.001) and SASHB from 83.2 ± 63.6 %min/h to 25.2 ± 42.3 %min/h (p < 0.001). Using an AHI-based definition of therapeutic efficacy, 83% (for AHI < 15 h-1) and 71% (for AHI < 10 h-1) of participants achieved efficacy with precision OAT. However, when the risk-based SASHB definition of therapeutic efficacy (SASHB < 53 %min/h) was used, precision OAT efficacy increased to 90%.

Conclusion

In the population studied, precision OAT significantly improved SASHB. The use of AHI, a frequency-based index of OSA, appears to misclassify some individuals as therapeutic non-responders to precision OAT despite their having an SASHB in the low-risk range. Sleep apnea-specific hypoxic burden likely provides a more meaningful assessment of OSA treatment efficacy as it accounts for the risk associated with the disease.

Support (if any)

This work was supported by ProSomnus Sleep Technologies.
0530 Efficacy of obstructive sleep apnea treatment by a unique oral appliance and effect of concurrent myofunctional and CPAP therapy
Authors: Lee-Heidenreich David , Heckman Seth , Kushida Clete
Published: May 2023

Introduction

Current treatment options for obstructive sleep apnea (OSA) include positive airway pressure, oral appliances, and upper airway surgery. The Day and Night Appliance (DNA) is a component of a dentist-guided system (Complete Airway Repositioning and Expansion [CARE], Vivos Therapeutics) that leads to gradual increases in upper airway volume. This study examines the effects of DNA treatment on OSA in patients before and after use of the device; we also examined how DNA treatment was impacted by concurrent myofunctional and CPAP therapy.

Methods

Data from a prospectively-collected clinical database (Vivos Airway Intelligence Service [AIS]) were reviewed, and 94 adult OSA patients who met DNA use criteria and had pre- and post-treatment sleep studies without the device in place were included. We compared the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) pre- and post-treatment using a paired t-test and fit linear regression models with change in AHI and ODI as dependent variables.

Results

Mean patient age was 47.8±14.7 years and 44.7% were men. Pre- and post-treatment sleep studies were conducted 15.2±7.0 months apart. 24.5% of patients were treated with DNA and myofunctional therapy (14.1% exclusively myofunctional, 10.4% myofunctional plus another treatment, e.g., tonsillectomy, frenectomy). 17.0% of patients were treated with CPAP (12.8% exclusively CPAP, 4.2% CPAP plus another treatment). For both pre-treatment and post-treatment, mean AHIs were 22.3±19.4 and 12.7±11.2 respectively (p< 0.0001) and mean ODIs were 11.6±13.7 and 7.8±9.1 respectively (p< 0.0001). Excluding patients who had undergone myofunctional therapy and another treatment modality and adjusting for patient age, BMI, and gender, we found myofunctional therapy was associated with a -10.4 change in AHI (p=0.038). However, myofunctional therapy was not associated with a significant change in ODI (p=0.905). Concurrent CPAP use did not have a significant association with change in either AHI (p=0.47) or ODI (p=0.61).

Conclusion

This study shows that DNA use significantly improved post-treatment OSA severity, and that concurrent myofunctional but not CPAP therapy may result in further OSA improvement. An oral appliance system that provides palatal expansion with consequent improvement in OSA severity but does not require permanent nightly use has advantages over conventional oral appliances; however, further investigation is warranted.

Support (if any)
0538 Mariposa: Oral Therapy AD109 Improves Objective & Patient Reported Outcomes In OSA. Randomized, Placebo Controlled Clinical Trial
Authors: Ojile Joseph , Schweitzer Paula , Thein Stephen , Drake Christopher , Rosenberg Russell , Corser Bruce , Abaluck Brian , Sangal Bart , Maynard James
Published: May 2023

Introduction

Obstructive sleep apnea (OSA) is a common disorder with often poorly tolerated treatment . While there is currently no approved pharmacotherapy for OSA, the combination of noradrenergic and antimuscarinic drugs, counteracting sleep-related upper airway muscle hypotonia, has recently shown encouraging results. AD109 is a combination of the norepinephrine reuptake inhibitor atomoxetine and the antimuscarinic aroxybutynin, the R-enantiomer of oxybutynin which recently showed efficacy over 1-night treatment in mild OSA patients. Safety and efficacy data over longer periods and in more severe OSA patients are needed.

Methods

Mariposa was a 25-center, randomized, controlled, parallel arms clinical trial designed to evaluate efficacy, safety, and tolerability vs placebo of 2 doses of AD109 (75/2.5mg and 75/5mg) and atomoxetine 75mg alone administered for 4 weeks in OSA patients with an apnea-hypopnea index (AHI4, 4% desaturation definition for hypopneas) between 10 and 45. The primary outcome was the change in AHI4, AD109 vs. placebo. Patient reported outcome questionnaires (PROMIS) were studied as exploratory outcomes.

Results

211 patients (41% female) with median (IQR) age 55 (48-60) years and BMI 32.2 (28.0-35.2) kg/m2 were randomized. AHI4 was reduced from 20.5 (12.3-27.2) to 10.8 (5.6-18.5) in the AD109 75/2.5mg dose arm and from 19.4 (13.7-26.4) to 9.5 (6.1-19.3) in the 75/5mg arm (both p< 0.0001 vs placebo). AHI4 was reduced from 19.0 (11.8-28.8) to 11.8 (5.5-21.5) with atomoxetine alone (p< 0.01 vs placebo) and from 20.1 (11.9-25.9) to 16.3 (11.1-28.9) on placebo. Overall, 44% had a reduction from baseline greater than 50% when treated with AD109. On AD109 75/2.5 dose, there was an improvement of PROMIS fatigue scores (p< 0.05 vs placebo and atomoxetine alone). Despite improving AHI4, atomoxetine alone reduced by 20+ minutes total sleep time vs placebo and AD109 (p< 0.05). There were no severe adverse events on AD109 with the most common side effects being dry mouth, insomnia, and nausea.

Conclusion

AD109 objectively and subjectively improved OSA severity in a group of patients with a wide range of AHI4 over 4 weeks of treatment. Results from the Mariposa trial are central for the design of phase 3 trials of AD109 in OSA.

Support (if any)

This study was supported by Apnimed.
0539 OAT Device Designs Are Not the Same When it Comes to FDA Adverse Event Reports
Authors: Murphy Mark , Rohatgi Rose , Liptak Len
Published: May 2023

Introduction

This investigation analyzes whether differences in OAT device designs are associated with different frequencies of adverse event reports (AERs).

Methods

Each AER identifies the OAT device used by the patient. Each OAT device was characterized using public information. Investigators utilized data from public sources, such as Frost & Sullivan, to estimate prevalence.

Results

Most frequently reported events were: allergic, swelling, rash and Pain/Discomfort. Only 2.5% of AERs pertained to dental side effects (tooth movements, bite changes). 98.5% of AERs involved OATs made from Lab Materials (acrylics, thermoformed polymers, nylons). 1.5% of AERs involved OATs made from engineered PMMA or Medical Grade Class VI polymers. OATs with Lab Formed materials were an estimated 22.6 times more likely to have an AER than those with Engineered Materials. Components (Herbsts, clasps, screws) comprised 55.6% of AERs. Elastomeric/Nylon Components (straps, bands, rods) comprised 42.4% of AERs. OATs with Monolithic Structures (no components) accounted for 2.0% of AERs. Compared with monolithic OATs, OATs using Metal Components and OATs using Elastomeric/Nylon components were 18.2 and 13.9 times more likely to have an AER. Anterior Clasps Mechanisms, Push Herbsts, Pull straps, bands, rods, 70-Degree Posts, and 90-Degree Twin Posts accounted for 45%, 42.7%, 6.1%, 5.6% and 0.6% of AERs respectively. Compared with 90-Degree Twin Post Mechanisms, Push mechanisms and OATs with Pull Mechanisms were 154 times and 146 times more likely to have an AER. Lab Formed OATs with Liners, Lab Formed Linerless OATs and Precision Engineered Linerless OAT devices accounted for 77.3%, 21.2% and 1.5% of events reported, respectively. OATs with Liners were an estimated 35.5 times more likely to have an AER than Precision Engineered Linerless OATs.

Conclusion

All OAT device designs are not the same when it comes to AERs. More AERs are associated with reactions. Dental side effects infrequently result in AERs. OAT devices that use Precision Engineered Materials, Monolithic Structures, 90-Degree Twin Posts and Precision Engineered Linerless designs are associated with lower frequencies of AERs. The results of this investigation suggest that medical guidelines and insurance coding should empower therapy providers with the flexibility to prescribe devices that are associated with fewer AERs.

Support (if any)
0542 Obstructive sleep apnea in outpatients with COPD at Can Tho University of Medicine and Pharmacy Hospital – An Observational Study
Authors: Pham Thu Vo
Published: May 2023

Introduction

The concurrence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is generally identified as overlap syndrome.This study evaluated biometric characteristics, sleep disorders, and scores comorbidities on OS and OSA groups in outpatients at the Respiratory Units of Can Tho University of Medicine and Pharmacy Hospital (RU-CTUMP); surveyed respiratory symptom severity, airway obstruction, and aerosol treatment characteristics in OS patients; and determined the correlations between sleep disorder severity and specific patient characteristics.

Methods

A cross-sectional, single-center descriptive study was conducted. We enrolled 48 outpatients at the RU-CTUMP in the study in three months. The patients were divided into two groups with overlapped COPD and OSA (OS, n = 30) vs. OSA-only (n = 18). Patients were asked to complete the demographic questionnaires, Epworth Sleepiness Scale (ESS) scores, STOP-Bang questionnaire, and Snoring Severity Scale (SSS). They were assessed for pulmonary function tests (PFTs) to confirm their COPD diagnosis, overnight respiratory polygraphy (Nox T3x), and Apnea-Hypopnea Index (AHI) to evaluate the severity of OSA, Charlson index to evaluate comorbidities, and their medication history.

Results

In the OS group, 100% of the patients suffered from dyspnea with the mean mMRC scores of 2.83 ± 0.75, mean FEV1 was 60.07 ± 23.09%, and 86% received inhaled medicine. In both groups, all participants suffered from 1 - ≥ 2 comorbidities. Overlapped patients had more comorbidities than OSA-only patients (Charlson scores of 2.33 and 1.17, respectively). There were significant correlations between the AHI value and the body mass index, neck circumferences, STOP-Bang score, the value of the Snoring Severity Scale, and minimum SpO2 (r = 0.45, 0.43, 0.46, 0.44, -0.69, respectively). In addition, COPD was a risk factor for OSA (OR = 1.125).

Conclusion

Home sleep testing in outpatients with COPD in RU-CTUMP revealed an increased prevalence of OSA compared to the OSA-only group. One of the most common comorbidities in individuals with overlap syndrome is hypertension, which is at least as common as in sleep apneic-only patients and may contribute to the disease's overall severity and prognosis.

Support (if any)