Differentiation Model for Insomnia Disorder and the Respiratory Arousal Threshold Phenotype in Obstructive Sleep Apnea in the Taiwanese Population Based on Oximetry and Anthropometric Features

Insomnia disorder (ID) and obstructive sleep apnea (OSA) with respiratory arousal threshold (ArTH) phenotypes often coexist in patients, presenting similar symptoms. However, the typical diagnosis examinations (in-laboratory polysomnography (lab-PSG) and other alternatives methods may therefore have limited differentiation capacities. Hence, this study established novel models to assist in the classification of ID and low- and high-ArTH OSA. Participants reporting insomnia as their chief complaint were enrolled. Their sleep parameters and body profile were accessed from the lab-PSG database. Based on the definition of low-ArTH OSA and ID, patients were divided into three groups, namely, the ID, low- and high-ArTH OSA groups. Various machine learning approaches, including logistic regression, k-nearest neighbors, naive Bayes, random forest (RF), and support vector machine, were trained using two types of features (Oximetry model, trained with oximetry parameters only; Combined model, trained with oximetry and anthropometric parameters). In the training stage, RF presented the highest cross-validation accuracy in both models compared with the other approaches. In the testing stage, the RF accuracy was 77.53% and 80.06% for the oximetry and combined models, respectively. The established models can be used to differentiate ID, low- and high-ArTH OSA in the population of Taiwan and those with similar craniofacial features.

Pathophysiology of Obstructive Sleep Apnea in Aging Women

The following review is designed to explore the pathophysiology of sleep apnea in aging women. The review initially introduces four endotypes (i.e., a more collapsible airway, upper airway muscle responsiveness, arousal threshold, and loop gain) that may have a role in the initiation of obstructive sleep apnea. Thereafter, sex differences in the prevalence of sleep apnea are considered along with differences in the prevalence that exist between younger and older women. Following this discussion, we consider how each endotype might contribute to the increase in prevalence of sleep apnea in aging women. Lastly, we address how modifications in one form of respiratory plasticity, long-term facilitation, that might serve to mitigate apneic events in younger women may be modified in aging women with obstructive sleep apnea. Overall, the published literature indicates that the prevalence of sleep apnea is increased in aging women. This increase is linked primarily to a more collapsible airway and possibly to reduced responsiveness of upper airway muscle activity. In contrast, modifications in loop gain or the arousal threshold do not appear to have a role in the increased prevalence of sleep apnea in aging women. Moreover, we suggest that mitigation of long-term facilitation could contribute to the increased prevalence of sleep apnea in aging women.

P019 Obstructive sleep apnoea endotypes in people with multiple sclerosis

Purpose Obstructive sleep apnoea (OSA) is common in people with multiple sclerosis (MS) despite a lack of typical risk factors for OSA in people with MS such as obesity and male predominance. Therefore, underlying factors other than sex and obesity may be particularly important in the pathogenesis of OSA in people with MS. Thus, the primary aim of this study was to determine the relative contributions of OSA endotypes in people with MS and compare this to matched controls with OSA only. Methods Eleven people with MS and OSA (MS-OSA group) (apnoea-hypopnoea index [AHI]>5events/h) and eleven controls matched for OSA severity, age and sex without MS (OSA group) were studied. Participants underwent a detailed overnight polysomnography with an epiglottic pressure catheter and genioglossus intramuscular electrodes to allow for quantification of pathophysiological contributors to OSA. This included the respiratory arousal threshold, genioglossus muscle responsiveness, respiratory loop gain and upper airway collapsibility. Results Measures of the four primary OSA endotypes were not different between the MS-OSA and OSA groups (e.g. NREM respiratory arousal threshold -27±15 vs. -23±8 cmH2O respectively, p=0.24). Within group analysis indicated higher loop gain in non-obese MS-OSA participants compared to obese MS-OSA participants (0.53±0.11 vs. 0.37±0.11, p=0.04). Conclusions Overall, OSA endotypes are similar between MS-OSA participants and matched OSA controls. However, within the MS-OSA group, non-obese participants have higher loop gain (unstable respiratory control) compared to obese participants. Thus, unstable respiratory control may play an important role in OSA pathogenesis in many people with MS.

O013 The pathogenesis of obstructive sleep apnea in individuals with comorbid insomnia and obstructive sleep apnoea (COMISA)

Obstructive sleep apnea (OSA) and Insomnia are prevalent sleep disorders which are highly comorbid. This frequent co-occurrence suggests a shared etiology may exist. OSA is caused by the interaction of four pathophysiological traits: a highly collapsible upper airway, elevated loop gain, a low arousal threshold, and poor muscle compensation. No study has ascertained whether these traits are influenced by insomnia. We aimed to quantify the four traits which contribute to OSA in individuals diagnosed with comorbid insomnia and OSA (COMISA). We non-invasively determined these traits in 52 COMISA patients (Age: 56±14 years) with mild-to-severe OSA (AHI=21.2±10.63 events/h) using polysomnography. Our results indicated that 83% of COMISA patients had a low arousal threshold and only 2% of patients exhibited a highly collapsible airway using previously defined thresholds. Multiple linear regression revealed the arousal threshold (b=0.24, 95%CI[0.11, 0.37], β=0.47, p<0.001) and loop gain (b=23.6, 95%CI[7.02, 40.18], β=0.33, p<0.01) were the strongest predictors of OSA severity in our sample. There was no significant relationship between the arousal threshold and insomnia severity measured by the insomnia severity index (ISI). Further work is being performed to compare these findings with a matched sample of OSA only participants. Our preliminary findings demonstrate OSA in COMISA is characterized by a mildly collapsible airway/low arousal threshold phenotype and is largely driven by non-anatomical factors including a low arousal threshold and high loop gain. OSA treatments which are effective in patients with mild anatomical compromise and raise the arousal threshold may provide therapeutic benefit in COMISA patients.

O023 Impact of weight loss of OSA pathophysiology

Introduction Obesity is a major risk factor for developing obstructive sleep apnoea (OSA), however, the underlying mechanisms are not fully understood. We aimed to assess the impact of weight loss on all OSA endotypes (i.e. upper airway collapsibility, muscle compensation, respiratory arousal threshold, and loop gain). Methods We analysed data from 40 OSA patients (collated from 3 centres) who underwent bariatric surgery. Demographics and clinical polysomnograms (PSG) were performed at baseline and at between 6–18 months post-surgery. OSA endotypes were measured during sleep using non-invasive endotyping methods (derived from clinical PSG). Results Participants lost 28±14 kg and had a post-surgery reduction in the AHI of 19.6 (Interquartile range[IQR] -9.8 to -35.4) events/hr [from baseline 39.9 (24.3 to 65.6) events/hr to 17.0 (9.9 to 33.3) events/hr]. Following surgical weight loss, there was significant improvement in collapsibility (∆6.2 [IQR -1.4 to 13]%Veupnoea, p<0.0001), as well as significant reduction in loop gain and arousal threshold (∆-0.06 [-0.17 to 0.009], p<0.001 and ∆-13.7 [-24.8 to -1.8]%Veupnoea, p<0.001 respectively). There was no significant change in muscle compensation. Conclusion Our findings suggest that weight loss improves upper airway collapsibility and reduces loop gain and the arousal threshold, providing novel insights about the mechanisms by which obesity causes OSA. Further analysis is underway to determine whether knowledge of the baseline OSA endotypes (in isolation and/or in combination) can predict which individuals will have a response to weight loss alone.

Estimated respiratory arousal threshold in patients with rapid eye movement obstructive sleep apnea

Purpose Rapid eye movement (REM) obstructive sleep apnea (OSA) is a prevalent clinical phenotype. However, the literature focusing on the pathophysiology of REM OSA is limited. This study compared the proportion of individuals with a low respiratory arousal threshold between patients with REM and non-REM OSA. Methods REM OSA was defined as having an apnea–hypopnea index (AHI) ≥ 5 and AHI during REM (AHI-REM)/AHI during NREM (AHI-NREM) ≥ 2. REM OSA was sub-divided into REM-predominant OSA and REM-isolated OSA. REM-predominant OSA was defined as satisfying the definition of REM OSA and having an AHI-NREM ≥ 5. REM-isolated OSA was defined as satisfying the definition of REM OSA and having an AHI-NREM < 5. Patients with an AHI-REM/AHI-NREM < 2 were defined as having non-REM OSA. A low respiratory arousal threshold was defined as having 2 or more of the following conditions: AHI < 30 events/h, proportion of hypopnea > 58.3%, and nadir SpO2 > 82.5%. Results The proportions of individuals with low respiratory arousal thresholds among individuals with REM-predominant OSA and REM-isolated OSA were significantly higher (77.2% and 93.7%, respectively) than that of patients with non-REM OSA (48.6%). This was also true when the analysis was performed according to sex. Conclusion These results indicate that a low respiratory arousal threshold might be an important endotype that contributes to the pathogenesis of REM OSA, especially in REM-isolated OSA.

389 The Association between Arousals and Neurochemical Biomarkers Accumulation in Obstructive Sleep Apnea with Low Arousal Threshold

Introduction Previous studies indicated the accumulation of neurodegenerative protein may be caused by higher Obstructive sleep apnea syndrome (OSAS) severity. However, the association between arousal-related parameters induced by OSAS and the amyloid burden remains unclear. The aim of this study is to investigate the association between arousal threshold (ArTH) and neurochemical protein accumulation in OSAS patients. Methods Suspected OSAS participants were performed Mini-mental status examination (MMSE) and full-night polysomnography (PSG) in the sleep center of Taipei Medical University Shuang Ho Hospital, Taiwan. On the same morning, the blood samples were obtained from the participants. The concentrations of total Tau (T-Tau) and amyloid beta peptide 42 (Aβ42) were quantified by ultra-sensitive immunomagnetic reduction assays. An overall of 23 participants were enrolled and classified into Low ArTH group (n=12) and High ArTH group (n=11) based on low ArTH criteria. Regarding the statistical methods, for categorical variables and continuous variables, Fisher’s exact test and Mann-Whitney U test were performed to investigate the differences between groups, respectively. The associations between biomarkers concentrations and PSG parameters were assessed by Spearman’s correlation. Results Regarding the demographic characteristics in two subgroups, significantly lower body-mass index and OSAS severity were noted in Low ArTH group (p&lt;0.05). The MMSE was in normal range in both groups and had no significant differences in subgroups. For PSG parameters, there were significantly lower desaturation index, AHI and higher spontaneous arousals index in each sleep stage in Low ArTH group (p&lt;0.01). Nevertheless, in the plasma neurochemical biomarkers, Aβ42 and Aβ42 X T-Tau were significantly higher in Low ArTH group (p&lt;0.05). Moreover, in Low ArTH group, T-Tau was positively correlated with respiratory arousals index (r=0.61, p&lt;0.05) and all arousals index (r=0.76, p&lt;0.01), respectively. The positive correlations between Aβ42 X T-Tau and respiratory arousals index (r=0.62, p&lt;0.05), all arousals index (r=0.75, p&lt;0.01) could also be observed. There were no significant correlations noted in High ArTH group. Conclusion OSAS patients with low ArTH have higher neurochemical biomarker levels. Also, the significantly positive correlations between arousals and biomarkers were observed in that group. Support (if any):