Respiratory Arousal Threshold Research Articles

Repeated daily exposure to mild intermittent hypoxia increases the auditory and tactile arousal thresholds in patients with obstructive sleep apnea

Background: Exposure to repeated daily mild intermittent hypoxia (MIH) leads to an increase in upper airway patency coupled to a reduction in continuous positive airway pressure (CPAP) used to treat obstructive sleep apnea (OSA). These modifications are associated with an increase in CPAP adherence. In addition, treatment with MIH might impact other factors that influence adherence, including the arousal threshold. Indeed, we showed that exposure to MIH resulted in an increased respiratory arousal threshold. Objective: The present study was designed to extend these findings to determine if increases in the arousal threshold to auditory or tactile stimuli increase after exposure to MIH. These modifications could be advantageous and contribute to increases in CPAP adherence that were previously observed. Methods: A total of 19 participants with OSA, with an apnea-hypopnea index > 5 (AHI), were recruited and randomly allocated to two groups. One group was exposed to repeated daily MIH, while the other group was exposed to sham MIH. Participants in the MIH group [n = 9; age - 45.22 ± 8.66 years; body mass index - 31.59 ± 5.49 kg/m2; apnea hypopnea index (AHI) - 58.39 ± 17.57 events/hr.] were exposed to twelve 2-minute hypoxic episodes (PETO2 ~ 50 mmHg) separated by 2- minute normoxic intervals (with PETCO2 sustained 2 mmHg above baseline) for 15 days. Participants in the sham group [n = 10; age - 47.1 ± 9.48 years; body mass index - 34.79 ± 4.57 kg/m2; AHI - 70.18 ± 22.42 events/hr.] were exposed to compressed room air. Arousal thresholds were measured objectively during sleep using auditory (ear inserted headphones) (MIH - n = 5; Sham -n = 9) and tactile (digital pressure algometer) (MIH - n = 8; Sham - n = 10) stimulation, while participants were treated with therapeutic levels of CPAP. These measures were obtained during sleep studies completed before exposure to MIH or sham MIH, and 4 days, 4 and 8 weeks after exposure. Results: Body mass index (p = 0.18), age (p = 0.66) and AHI (p = 0.22) were similar between the two groups prior to therapy. A significant increase in the tactile threshold measured on the left side was observed 4 days [1.89 ± 1.08 vs. 2.81 ± 1.23 pound-force (Ibf), p = 0.005] and 4 weeks (1.89 ± vs 1.08 ± 1.48 Ibf, p = 0.024) after therapy in the MIH group. This improvement was not evident after 8 weeks (p = 0.16). No difference in the tactile threshold was evident at any point following exposure to sham MIH (P > 0.128 for all comparisons). There was a significant increase in the auditory threshold immediately after treatment with MIH compared to baseline (54.00 ± 2.24 vs. 67.00 ± 11.51 dB, P = 0.031), which was not evident 4 or 8 weeks after therapy. A significant correlation between the auditory and tactile arousal thresholds was also evident when all time points were included (R = 0.48, P = 0.015). The auditory threshold values were similar at all time points in the Sham MIH group (P > 0.52 for all comparisons). Conclusion: Our results suggest that exposure to repeated daily exposure to mild intermittent hypoxia results in an increase in the auditory and tactile arousal threshold level immediately after exposure to MIH, which was sustained for 4 weeks in the case of the tactile threshold. The increase in the auditory and arousal threshold could contribute to the improved adherence to CPAP that we previously reported was evident after repeated daily exposure to MIH. I01CX000125, IK6CX002287, R01HL142757, R56HL142757. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Association between anthropometric and polysomnographic parameters with respiratory arousal threshold in Obstructive Sleep Apnea

Association between anthropometric and polysomnographic parameters with respiratory arousal threshold in Obstructive Sleep Apnea

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

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

Anatomical Basis of Obstructive Sleep Apnoea: A Review of Randomized Controlled Trials.

Repeated obstruction and closure of the upper airway, sporadic hypoxic episodes, and sympathetic activity are symptoms of obstructive sleep apnea (OSA). Obstructive sleep apnoea is due to a combination of altered upper airway structure and muscular function, a low arousal threshold and increased loop gain.Although recurrent upper airway (UA) collapse during sleep is the most frequent clinical hallmark of OSA, the exact cause of this collapse is unknown. Furthermore, while continuous positive airway pressure aids in the management of OSA, many patients find it intolerable. As a result, a better knowledge of the causes of OSA may result in more effective treatments. We did a review of randomized controlled trials that were done in this regard in the last 10 years and whose full-text version is available on the PubMed database. A total of 20 articles were finalized for review after applying our criteria. The articles have proposed different theories regarding the anatomical basis responsible for obstructive sleep apnoea. The theories proposed by different studies in the last decade include reduced genioglossus and hypoglossal nerve activity, the pharyngeal muscles' failure to keep the airway open or tighten it, tonsils and adenoid hypertrophy, an oversensitive ventilatory control system and low respiratory arousal threshold, mandibular position, pharyngeal muscles' high sympathetic drive, cephalometric alterations such as mandibular and hyoid bone position and the length of the soft palate, obesity, and neck fat and fluid re-distribution in the body, from the lower to the upper parts while reclining. Given the diverse etiological characteristics of OSA patients and to increase our knowledge of the condition, additional study into this group is required. Filling any knowledge gaps that may exist in the anatomical basis of the onset of OSA is the main objective of this review paper.

0479 Prevalence, Clinical Features, and Impact of Low Respiratory Arousal Threshold on Patients with Hypoglossal Nerve Stimulation

Abstract Introduction This study aims to explore the prevalence and clinical features associated with low respiratory arousal threshold (ArTH) amongst patients with hypoglossal nerve stimulation (HNS) for the treatment of obstructive sleep apnea (OSA) and the possible effects it has on HNS adherence and device usage between time of activation and 1-year post-activation. Methods Following institutional review board approval, consecutive patients who underwent HNS system implantation were retrospectively studied, including clinical characteristics, diagnostic polysomnography (PSG) or homes sleep apnea test (HSAT) and HNS post-implant data. Inclusion criteria were patients with ≥1 year of HNS usage who had also completed a post-implant HNS PSG titration study. Results Forty-five patients met inclusion criteria. Low ArTH was present in 44.4% of patients and compared to those with high ArTH, low ArTH had a higher prevalence of restless leg syndrome (RLS) (45% vs 12%, p< 0.05) and depression (60% vs 28%, p< 0.05). Low ArTH exhibited a trend toward shorter diagnostic total sleep time (TST) (295.0 vs 373.3 minutes, 0.05 < p < 0.1). Bivalent logistic regression indicated the odds of having low ArTH is 8.6 times greater in patients with RLS (OR 8.6, CI 1.1 – 68.6, p< 0.05). Across all time points, low ArTH resulted in lower mean percentage of HNS nights used (92% vs 86%, p< 0.001) and a lower HNS amplitude (2.41 V vs 1.96 V, p< 0.001) and demonstrated a trend towards lower percentage of nights used ≥4 hours (72.9% vs 66.1%, 0.05 < p < 0.1). 1-year post activation, low ArTH patients continued to show lower percentage of HNS nights used (89.8% vs 75.6%, p< 0.01) and a lower HNS amplitude (2.3 V vs 1.9 V, p< 0.01). Conclusion Low ArTH was highly prevalent amongst patients with OSA treated with HNS and was more frequently associated in patients with RLS. Patients with a low ArTH demonstrated significantly lower percentage of nights used and lower amplitudes, indicating the importance this particular phenotype may play in patient compliance with HNS. These findings could help better select candidates who will tolerate HNS therapy and develop targeted therapies to improve long-term adherence. Support (if any)

Respiratory arousal threshold among patients with isolated sleep apnea and with comorbid insomnia (COMISA)

Insomnia and obstructive sleep apnea (OSA) are common sleep disorders and frequently coexist (COMISA). Arousals from sleep may be a common link explaining the frequent comorbidity of both disorders. Respiratory arousal threshold (AT) is a physiologic measurement of the level of respiratory effort to trigger an arousal from sleep. The impact of COMISA on AT is not known. We hypothesized that a low AT is more common among COMISA than among patients with OSA without insomnia. Participants referred for OSA diagnosis underwent a type 3 sleep study and answered the insomnia severity index (ISI) questionnaire and the Epworth sleepiness scale. Participants with an ISI score ≥ 15 were defined as having insomnia. Sleep apnea was defined as an apnea hypopnea index (AHI) ≥ 15 events/h. Low AT was determined using a previously validated score based on 3 polysomnography variables (AHI, nadir SpO2 and the frequency of hypopneas). OSA-only (n = 51) and COMISA (n = 52) participants had similar age (61[52–68] vs 60[53–65] years), body-mass index (31.3[27.7–36.2] vs 32.2[29.5–38.3] kg/m2) and OSA severity (40.2[27.5–60] vs 37.55[27.9–65.2] events/h): all p = NS. OSA-only group had significantly more males than the COMISA group (58% vs 33%, p = 0.013. The proportion of participants with a low AT among OSA-only and COMISA groups was similar (29 vs 33%, p = NS). The similar proportion of low AT among COMISA and patients with OSA suggests that the respiratory arousal threshold may not be related to the increased arousability of insomnia.

Shorter respiratory event duration is related to prevalence of type 2 diabetes.

Obstructive sleep apnea (OSA) is a heterogeneous sleep disorder often comorbid with metabolic diseases, and type 2 diabetes (T2DM) is one of them. Although apnea hypopnea index (AHI) is currently the diagnostic criteria for OSA severity, a controversial relationship between AHI and T2DM has been found. On the other hand, the duration of apnea-hypopnea events has been shown to be a useful metric for predicting mortality. This study aimed to test whether average respiratory event duration was associated with prevalence of T2DM. Patients referred to the sleep clinic were recruited in the study. Baseline clinical characteristics and polysomnography parameters including average respiratory event duration were collected. The association of average respiratory event duration with the prevalence of T2DM was evaluated by univariate and multivariate logistic regression analyses. A total of 260 participants were enrolled, and 92 (35.4%) had T2DM. Univariate analysis revealed that age, body mass index (BMI), total sleep time, sleep efficiency, history of hypertension, and shorter average respiratory event duration were associated with T2DM. In multivariate analysis, only age and BMI remained significant. While average respiratory event duration was insignificant in multivariate analysis, subtype event analysis showed that shorter average apnea duration was both significant in univariate (OR, 0.95; 95% CI, 0.92-0.98) and multivariate analyses (OR, 0.95; 95% CI, 0.91-0.99). Neither average hypopnea duration nor AHI was associated with T2DM. Significant association (OR, 1.19; 95% CI, 1.12-1.25) was observed between shorter average apnea duration and lower respiratory arousal threshold after multivariate adjustment. However, causal mediation analysis revealed no mediating effect of arousal threshold on average apnea duration and T2DM. The average apnea duration may be a useful metric in the diagnosis of OSA comorbidity. Shorter average apnea duration indicating poor sleep quality and augmented autonomic nervous system responses might be the potential pathological mechanisms leading to T2DM.

Take an OSA pill and call me in the morning.

Take an OSA pill and call me in the morning.

P086 The insomnia severity index is related to the respiratory arousal threshold in people with Co-Morbid Insomnia and Sleep Apnoea (COMISA)

Abstract Introduction People with co-morbid insomnia and sleep apnoea (COMISA) have worse symptoms and require a tailored therapy approach for their sleep disorders. The relationship between the respiratory arousal threshold, a key OSA non-anatomical contributor and insomnia symptoms is unclear. This study investigated the relationship between insomnia symptoms using the insomnia severity index (ISI) and the respiratory arousal threshold in people with OSA. Methods 46 people with OSA (11 female, age=50±15years, BMI=29±6kgm-2, AHI=33±20events/h) participated in a physiology sleep study to predict response to oral appliance therapy and completed the ISI. Standard polysomnography, an epiglottic airway pressure sensor, bipolar intramuscular electrodes inserted into the genioglossus and a nasal mask with a pneumotachograph to quantify airflow were used. The respiratory arousal threshold was measured as the nadir epiglottic pressure during a respiratory event prior to a cortical arousal. Following this, participants trialled mandibular advancement therapy. Results There was no relationship between ISI (average=12±6) and the arousal threshold (-24±10cmH₂O) in participants with OSA (r=0.1, p=0.42, n=46). However, in the 59% of people with COMISA (ISI ≥11), there was a positive relationship between ISI and arousal threshold, with increasing insomnia severity associated with lower arousal threshold (r=0.5, p=0.017, n=27). People with a BMI<30kgm-2 (n=27), also had a positive linear relationship between ISI and improvement in oral appliance therapy (r=0.49, p<0.01, n=27). Conclusion Greater insomnia symptoms in people with COMISA is associated with a lower respiratory arousal threshold. In non-obese people with OSA, higher ISI values are related to poor response to oral appliance therapy.

O026 Effect of oral appliance therapy on OSA endotypes

Abstract Introduction Long term CPAP therapy alters OSA endotypes (e.g., reduces loop gain and the arousal threshold). However, while oral appliance therapy (OAT) is known to improve upper airway collapsibility, its effects on non-anatomical OSA endotypes are unclear. Methods To investigate the effects of OAT on polysomnographic estimates of OSA endotypes we studied 102 people with OSA (AHI=34±20 events/h) pre vs. post-treatment (following 4-6 weeks OAT acclimatization). AHI and endotypic traits were compared between the diagnostic and OAT study visits. Results OAT reduced the AHI by ~50% (30 [25-39] vs. 15 [12-19], median, 95% confidence interval, p<0.01). Passive pharyngeal collapsibility (94 [92-95] vs. 96 [95-97]% eupnea), active pharyngeal collapsibility (98 [95-100] vs. 102 [101-103]% eupnea) and pharyngeal muscle compensation (3.6 [1.2-5.1] vs 4.9 [3.7-6.5]% eupnea) improved with OAT (all p<0.01). The respiratory arousal threshold (116 [114-122] vs. 109 [106-111]% eupnea, p<0.01) and ventilatory response to arousal (31 [28-35] vs. 23 [20-32]% eupnea, p=0.03) decreased. Loop gain did not systematically change overall (0.43 [0.39-0.47] vs. 0.40 [0.38-0.42], p=0.16). However, loop gain reduced in OAT responders (>50% reduction in AHI) (0.42 [0.39-0.45] vs. 0.38 [0.34-0.4] dimensionless, p<0.01). Conclusions Oral appliance therapy improves upper airway collapsibility and pharyngeal muscle compensation and reduces the ventilatory response to arousal and loop gain in responders. Like CPAP, OAT also decreases the arousal threshold. These findings provide new insight into the mechanisms of improvement in OSA with oral appliance therapy.

0747 Polysomnogram characteristics associated with artificial Intelligence enabled electrocardiogram algorithm predicted probability of atrial fibrillation in patients with obstructive sleep apnea

Abstract Introduction Obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF). Several features of OSA are thought to play role in the development of AF. A recently developed artificial intelligence (AI) enabled electrocardiogram (ECG) algorithm predicts the probability of future development of AF from a single ECG. We sought to examine the relationship between polysomnogram (PSG) and clinical features of patients with OSA and the probability of future AF (P-AF). Methods Consecutive adults (age ≥ 18) with OSA and with an ECG obtained within 2 years of their attended polysomnograms (PSG) were examined. We excluded patients with AF, left ventricular ejection fraction < 50%, implanted pacemaker or cardioverter defibrillator. We recorded demographics, apnea-hypopnea index (AHI), respiratory arousal threshold (RAT), percent sleep time with SpO2 < 89%, arousal index, and a comorbidity score composed of presence of coronary artery disease (CAD), hypertension (HTN), diabetes mellitus (DM), stroke, and chronic lung disease. One and two-way ANOVA was used to examine the relationship of OSA severity (mild, moderate, or severe) with P-AF. Multiple linear regression further characterized associations with P-AF. Results Mean AI determined P- AF was 0.052±0.012 (mean±SE) in mild, 0.064±0.014 in moderate, and 0.105 + 0.014 in severe OSA, demonstrating a significant association of OSA severity with P-AF (p = 0.01). Post-hoc pairwise tests showed a significant difference in P-AF between mild and severe (p = 0.008) but not between moderate and severe OSA (p = 0.083). Multiple linear regression with all the variables listed above showed the association between OSA severity and P-AF remains significant (P = 0.044). Age (p<0.001) and comorbidity score (p<0.001) were the only other variables significantly associated with P-AF. Conclusion OSA severity determined by AHI was significantly associated with P-AF as determined by a novel ECG-based AI algorithm independent of other variables. Given the strength of association with age and the comorbidity score, OSA severity may have been associated as it is known to increase with age and comorbid conditions. Future directions include incorporating AI enabled algorithms to identify individuals with the highest risk of AF in whom the role of OSA treatment in reducing risk of AF may be examined. Support (If Any)

0737 Factors Influencing Arousal Thresholds

Abstract Introduction Obstructive Sleep Apnoea (OSA) is the most common sleep-related breathing disorder with an estimated prevalence of approximately 15-30 percent in males and 10-15 percent in females. A low respiratory arousal threshold (ArTH) is one of several traits involved in OSA pathogenesis. This has been shown to be reliably predicted using an Arousal Score which is calculated using the patients overall Apnoea-Hypopnoea Index (AHI), nadir SpO2 and Hypopnoea:Apnoea ratio where a score of 2 or more predicts a low arousal threshold, and a score of 1 indicates a high arousal threshold. Our objective was to describe factors associated with high arousal thresholds in patients with OSA as determined by the Arousal Score in a metropolitan population. Methods 208 unselected, consecutive, adult, overnight polysomnography with prospectively calculated arousal scores were assessed from 2019 – 2020. Demographic and anthropometric data including Age, Sex, BMI, Epworth Sleepiness Score (ESS), AHI, SpO2 nadir, Hypopnoea:Apnoea ratio and arousal index was recorded. The arousal score was calculated by assigning one point for meeting each of the following requirements: AHI <30; SpO2 nadir > 82.8%; Hypopnoea:Apnoea ratio > 58.3, with a score <2 considered low. Spearmann correlation was performed to determine the factors associated with the Arousal Score. Results 208 patients were included in the study. 35.6% of patients had mild sleep apnoea, 23.1% moderate sleep apnoea, 22.6% severe sleep apnoea with 18.8% of patients with no sleep apnoea. Mean arousal score was 2.47 (Std Dev 0.839). Spearman correlation indicated that disease severity, BMI (rs -.374, p-value < 0.01) and STOP-BANG (r2 -0.419, p-value < 0.01) had a statistically significant relationship with Arousal Score. That is, a higher AHI, BMI and STOP-BANG was associated with a low arousal score. Moreover, Gender and Epworth Sleepiness Score exhibited an insignificant association with arousal score. We found increasing severity of disease was associated with lower arousal score and therefore a higher arousal threshold Conclusion Our study demonstrates that worsening sleep apnoea severity, higher BMI and higher STOP-BANG are associated with a lower arousal score and therefore higher arousal threshold. Gender and ESS do not appear to be significantly associated. Support (If Any)

Examining the impact of multilevel upper airway surgery on the obstructive sleep apnoea endotypes and their utility in predicting surgical outcomes.

Background and objectiveUpper airway surgery for obstructive sleep apnoea (OSA) is an alternative treatment for patients who are intolerant of continuous positive airway pressure (CPAP). However, upper airway surgery has variable treatment efficacy with no reliable predictors of response. While we now know that there are several endotypes contributing to OSA (i.e., upper airway collapsibility, airway muscle response/compensation, respiratory arousal threshold and loop gain), no study to date has examined: (i) how upper airway surgery affects all four OSA endotypes, (ii) whether knowledge of baseline OSA endotypes predicts response to surgery and (iii) whether there are any differences when OSA endotypes are measured using the CPAP dial‐down or clinical polysomnographic (PSG) methods.MethodsWe prospectively studied 23 OSA patients before and ≥3 months after multilevel upper airway surgery. Participants underwent clinical and research PSG to measure OSA severity (apnoea–hypopnoea index [AHI]) and endotypes (measured in supine non‐rapid eye movement [NREM]). Values are presented as mean ± SD or median (interquartile range).ResultsSurgery reduced the AHITotal (38.7 [23.4 to 79.2] vs. 22.0 [13.3 to 53.5] events/h; p = 0.009). There were no significant changes in OSA endotypes, however, large but variable improvements in collapsibility were observed (CPAP dial‐down method: ∆1.9 ± 4.9 L/min, p = 0.09, n = 21; PSG method: ∆3.4 [−2.8 to 49.0]%V eupnoea, p = 0.06, n = 20). Improvement in collapsibility strongly correlated with improvement in AHI (%∆AHISupineNREM vs. ∆collapsibility: p < 0.005; R 2 = 0.46–0.48). None of the baseline OSA endotypes predicted response to surgery.ConclusionSurgery unpredictably alters upper airway collapsibility but does not alter the non‐anatomical endotypes. There are no baseline predictors of response to surgery.

Efficacy of atomoxetine plus oxybutynin in the treatment of obstructive sleep apnea with moderate pharyngeal collapsibility

PurposePreliminary studies have shown a significant decrease in severity of obstructive sleep apnea (OSA) with the use of a combination of atomoxetine and oxybutynin, with patients having moderate pharyngeal collapsibility during sleep more likely to respond. This study evaluated the efficacy and safety of AD036 (atomoxetine 80 mg and oxybutynin 5 mg) in the treatment of OSA.MethodsThis trial was a phase 2, randomized, placebo-controlled crossover study comparing AD036, atomoxetine 80 mg alone, and placebo during three home sleep studies, each separated by about 1 week. The trial included patients with OSA and moderate pharyngeal collapsibility as defined by a higher proportion of hypopneas to apneas and mild oxygen desaturation.ResultsOf 62 patients who were randomized, 60 were included in efficacy analyses. The apnea–hypopnea index (AHI) from a median (interquartile range) of 14.2 (5.4 to 22.3) events/h on placebo to 6.2 (2.8 to 13.6) with AD036 and 4.8 (1.4 to 11.6) with atomoxetine alone (p < .0001). Both drugs also decreased the oxygen desaturation index (ODI) and the hypoxic burden (p < .0001). AD036, but not atomoxetine alone, reduced the respiratory arousal index and improved ventilation at the respiratory arousal threshold (greater Vactive). There was a trend for total sleep time to be decreased more with atomoxetine alone than with AD036. The most common adverse event was insomnia (12% with AD036, 18% with atomoxetine).ConclusionAD036 significantly improved OSA severity in patients with moderate pharyngeal collapsibility. Atomoxetine may account for the majority of improvement in OSA severity, while the addition of oxybutynin may mitigate the disruptive effect of atomoxetine on sleep and further improve ventilation.Trial registrationClinical trial registered with www.clinicaltrials.gov (NCT04445688).

Effect of Zolpidem on nocturnal arousals and susceptibility to central sleep apnea.

Arousals may contribute to the pathogenesis of sleep-disordered breathing (SDB) and central sleep apnea (CSA). We aimed to determine the effect of the nonbenzodiazepine hypnoticzolpidemon the frequency of respiratory-related arousals and central apneain patients withmoderate-to-severe SDB.We hypothesized thatzolpidemdecreasesthe severity of SDB by decreasingthe frequency ofrespiratory-related arousals. Patients with apnea-hypopnea index ≥ 15 events/hour and central apnea-hypopnea index ≥ 5 events/hour underwent a sleep study on zolpidem 5mg and a sleep study with no medication in a randomized order. The respiratory arousal index was compared between the two studies using a randomized crossover design. Sleep, respiratory, and physiologic parameters, including the CO2 reserve and the respiratory arousal threshold, were also compared. Eleven participants completed the study. Compared to no treatment, zolpidem reduced the respiratory arousal index (39.7 ± 7.7 vs. 23.3 ± 4.4 events/h, P = 0.031). Zolpidem also lowered the total apnea-hypopnea index (55.6 ± 8.5 vs. 41.3 ± 7.5 events/hour, P = 0.033) but did not affect other clinical and physiologic parameters. Compared to control, zolpidem did not widen CO2 reserve (- 0.44 ± 1.47 vs. - 0.63 ± 0.86mmHg, P = 0.81). The respiratory arousal threshold did not show a significant change on zolpidem compared to control (- 8.72 ± 2.1 vs. - 8.25 ± 2.81 cmH2O, P = 0.41). Nocturnal arousals and overall SDB severity were reduced with a single dose of zolpidem in patients with moderate-to-severe sleep-disordered breathing with increased susceptibility for central apnea. Zolpidem did not widen the CO2 reserve or increase the arousal threshold. Clinicaltrials.gov. Sleep and Breathing in the General Population - Chemical Stimuli (NCT04720547).

Prevalence, characteristics, and respiratory arousal threshold of positional obstructive sleep apnea in China: a large scale study from Shanghai Sleep Health Study cohort

PurposeTo evaluate the prevalence, characteristics, and respiratory arousal threshold (ArTH) of Chinese patients with positional obstructive sleep apnea (POSA) according to the Cartwright Classification (CC) and Amsterdam Positional Obstructive Sleep Apnea Classification (APOC).MethodsA large-scale cross-sectional study was conducted in our sleep center from 2007 to 2018 to analyze the clinical and polysomnography (PSG) data of Chinese POSA patients. Low ArTH was defined based on PSG indices.ResultsOf 5,748 OSA patients, 36.80% met the CC criteria, and 42.88% the APOC criteria, for POSA. The prevalence of POSA was significantly higher in women than men (40.21% and 46.52% vs. 36.13% and 42.18% for CC and APOC, respectively). Chinese POSA patients had a lower apnea hypopnea index (AHI) and lower oxygen desaturation index, shorter duration of oxygen saturation (SaO2) < 90%, and a higher mean SaO2 and higher lowest SaO2 value compared to subjects with non-positional OSA (NPOSA). More than 40% of the POSA patients had a low ArTH; the proportion was extremely high in the supine-isolated-POSA (si-POSA) group and APOC I group. In multivariate logistic regression analyses, higher mean SaO2 and lower AHI during sleep were positive predictors of POSA.ConclusionsAccording to the CC and APOC criteria, more than 1/3 of our Chinese subjects with OSA had POSA. Chinese POSA patients had less severe OSA and nocturnal hypoxia. Compared to NPOSA patients, significantly more patients with POSA had a low ArTH. A low ArTH may be an important endotype in the pathogenesis of POSA, especially in patients with si-POSA and APOC I. Further studies are necessary to develop personalized management strategies for POSA patients.Trial registration: Chinese Clinical Trial Registry; URL: http://www.chictr.org.cn; No. ChiCTR1900025714 (retrospectively registered).

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.

The Assessment and Clinical Utility of the Respiratory Arousal Threshold in Obstructive Sleep-Disordered Breathing

The Assessment and Clinical Utility of the Respiratory Arousal Threshold in Obstructive Sleep-Disordered Breathing

The negative health effects of having a combination of snoring and insomnia.

Insomnia and snoring are common sleep disorders. The aim was to investigate the association of having a combination of insomnia symptoms and snoring with comorbidity and daytime sleepiness. The study population comprised 25,901 participants (16-75 years, 54.4% women) from 4 Swedish cities, who answered a postal questionnaire that contained questions on snoring, insomnia symptoms (difficulties initiating and/or maintaining sleep and/or early morning awakening), smoking, educational level, and respiratory and nonrespiratory disorders. Snoring was reported by 4,221 (16.2%), while 9,872 (38.1%) reported ≥ 1 insomnia symptom. A total of 2,150 (8.3%) participants reported both insomnia symptoms and snoring. The association with hypertension (adjusted odds ratio [OR], 1.4; 95% confidence interval [CI], 1.2-1.6), chronic obstructive pulmonary disease (adjusted OR, 1.8; 95% CI, 1.3-2.4), asthma (adjusted OR, 1.9; 95% CI, 1.6-2.3), daytime sleepiness (adjusted OR, 7.9; 95% CI, 7.1-8.8), and the use of hypnotics (adjusted OR, 7.5; 95% CI, 6.1-9.1) was highest for the group with both insomnia symptoms and snoring. Participants with both snoring and insomnia run an increased risk of hypertension, chronic obstructive pulmonary disease, asthma, daytime sleepiness, and use of hypnotics. It is important to consider snoring in patients seeking medical assistance for insomnia and, vice versa, in patients with snoring inquiring about insomnia. Hägg SA, Ilieva E, Ljunggren M, etal. The negative health effects of having a combination of snoring and insomnia. J Clin Sleep Med. 2022;18(4):973-981.

O023 Impact of weight loss of OSA pathophysiology

Abstract 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&amp;lt;0.0001), as well as significant reduction in loop gain and arousal threshold (∆-0.06 [-0.17 to 0.009], p&amp;lt;0.001 and ∆-13.7 [-24.8 to -1.8]%Veupnoea, p&amp;lt;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.