Arousal Threshold Research Articles

Within-night repeatability and long-term consistency of sleep apnea endotypes: the Multi-Ethnic Study of Atherosclerosis and Osteoporotic Fractures in Men Study.

Obstructive sleep apnea (OSA) is characterized by multiple "endotypic traits," including pharyngeal collapsibility, muscle compensation, loop gain, and arousal threshold. Here, we examined (1) within-night repeatability, (2) long-term consistency, and (3) influences of body position and sleep state, of endotypic traits estimated from in-home polysomnography in mild-to-severe OSA (apnea-hypopnea index, AHI > 5 events/h). Within-night repeatability was assessed using Multi-Ethnic Study of Atherosclerosis (MESA): Traits derived separately from "odd" and "even" 30-min periods were correlated and regression (error vs. N windows available) provided a recommended amount of data for acceptable repeatability (Rthreshold = 0.7). Long-term consistency was assessed using the Osteoporotic Fractures in Men Study (MrOS) at two time points 6.5 ± 0.7 years apart, before and after accounting for across-year body position and sleep state differences. Within-night dependence of traits on position and state (MESA plus MrOS data) was estimated using bootstrapping. Within-night repeatability for traits ranged from R = 0.62-0.79 and improved to R = 0.69-0.83 when recommended amounts of data were available (20-35 7-min windows, available in 94%-98% of participants); repeatability was similar for collapsibility, loop gain, and arousal threshold (R = 0.79-0.83), but lower for compensation (R = 0.69). Long-term consistency was modest (R = 0.30-0.61) and improved (R = 0.36-0.63) after accounting for position and state differences. Position/state analysis revealed reduced loop gain in REM and reduced collapsibility in N3. Endotypic traits can be obtained with acceptable repeatability. Long-term consistency was modest but improved after accounting for position and state changes. These data support the use of endotypic assessments in large-scale epidemiological studies. The data used in the manuscript are from observational cohort studies and are not a part of the clinical trial.

Critical evaluation of contrasting evidence on whether male circumcision has adverse psychological effects: A systematic review.

ObjectiveTo conduct the first systematic review critically examining evidence on whether early male circumcision has short‐ and long‐term adverse psychological effects.MethodsWe searched PubMed, EMBASE, SCOPUS, Cochrane Library, and Google Scholar.ResultsTwenty‐four studies with original data met the inclusion criteria. These comprised 11,173 total males, 4340 circumcised in infancy and 6908 uncircumcised. Nineteen were rated 1+, 2++ or 2+, and 5 were rated 2– by SIGN criteria. Neonatal circumcision, particularly without anesthetic, increased vaccination pain response, but had little effect on breastfeeding or cognitive ability. Studies reporting associations with sudden infant death syndrome, autism, alexithymia and impaired sexual function and pleasure had design flaws and were rated 2–. Sexual arousal, touch, pain, and warmth thresholds measured by quantitative sensory testing were not diminished in neonatally circumcised men. Neonatal circumcision was not associated with empathy in men, contradicting the hypothesis that procedural pain causes central nervous system changes. After correcting all associations with socioaffective processing parameters for multiple testing only higher sociosexual desire, dyadic sexual libido/drive, and stress remained significant. The relatively greater sexual activity found in circumcised men might reflect reduced sexual activity in uncircumcised men overall owing to pain and psychological aversion in those with foreskin‐related medical conditions (reverse causality). Most studies employed case‐control designs with limited follow‐up. Studies beyond childhood were prone to confounding.ConclusionThe highest quality evidence suggest that neonatal and later circumcision has limited or no short‐term or long‐term adverse psychological effects.

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)

0742 Characteristics of the Low ArTH phenotype in patients with OSA

Abstract Introduction Obstructive sleep apnea (OSA) is a heterogenous disease with both anatomic and nonanatomic factors contributing to the pathophysiology. Recently low arousal threshold (ArTH) has been described in some patients with sleep apnea and there is early evidence emerging that it could be a clinical phenotype. The aim of this study was to characterize this phenotype in a large cohort of patients with sleep apnea confirmed by overnight polysomnography Methods The setting was a community sleep center. We performed a retrospective review of patient charts. We included patients who underwent full-night diagnostic PSG. OSA was defined as an apnea hypopnea index (AHI) of > 5. Epworth score, body mass index (BMI), neck circumference, and upper airway size using Modified Friedman (MF) were recorded. Low ArTH was calculated using AHI, fraction of hypopneas and O2 nadir.Abnormal airway narrowing was defined by MF >2. Large neck was defined by neck circumference ≥ 17 inches in males or ≥ 16 in females. Obesity was defined by BMI>30 kg/m2. Results 652 patients were included - 421(65%) were male, and 230 (35%) female. 299 (46%) of patients had a low ArTH phenotype. Mean age was similar in both groups 54 +/- 14 vs 55 +/- 13 years. Male % was less pronounced in the low ArTH group (57% of patients with low ArTH male vs 71% of without low ArTH; p<0.05). Patients with a low ArTH had lower percentage of abnormal airway narrowing (53.5 vs 62.6%, p<0.001), large neck circumference ( 64.6 vs 78.8%, p<0.001) and obesity (65.6 vs 77.9%, p<0.001). Average BMI was lower in the low ArTH group (34.8 +/- 8 vs 36.9 +/- 8; p < 0.005), and neck circumference was also lower in low ArTH group (NC 16.5 +/- 1.8 vs 17.4 +/- 1.8 respectively). Epworth sleepiness scale was lower in low ArTh group (10 +/- 8 vs 11 +/- 9; p 0.007) Conclusion We describe the phenotypic characteristics of low ArTH phenotype in a large cohort of patients with OSA. Patients with low ArTH have lower BMI, lower neck circumference, and lower Modified Friedman. Further research studies should focus on whether there are differences in therapeutic responses to this phenotype, and what clinical characteristics might help clinicians more effectively detect this phenotype. Support (If Any) NA

0753 Predictors of Residual sleep apnea in OSA patients on PAP

Abstract Introduction Positive airway pressure (PAP) is the first line therapy for patients with obstructive sleep apnea (OSA). However, clinical OSA may have multiple disease drivers beyond upper airway collapse, such as high loop gain and a low arousal threshold. The burden of residual sleep apnea in patients treated with PAP and it’s predictors remained to be fully defined. Methods Adult patients who were diagnosed with OSA through a split-night polysomnography (PSG) in the AASM accredited sleep center at the Beth Israel Deaconess Medical Center, Harvard Medical School and followed using the EncoreAnywhereTM system were prospectively included. Monthly visual/manual scoring of residual events was done. The ratio of patients with residual sleep apnea (defined as a manually-scored respiratory event index (REI) ≥ 15 times/hour in the 3rd month and 12th month were calculated. A linear regression model was used to explore the predictors of residual sleep apnea on PAP. Results One hundred and ninety five patients were included. In the 3rd month, there were 166 patients still on PAP. There were 74 (44.58%) with a residual AHI ≥ 15 times/h. In the 12th month, there were 93 patients still on PAP and 41 (44.09%) had residual AHI ≥ 15. In the short term, treatment CAHI (β= 0.511, SE=0.123, p=0.001), age (β= 0.123, SE=0.054, p=0.025), and hypertension (β= 3.627, SE=1.536, p=0.019) were the predictors for residual sleep apnea. In the long term, treatment CAHI (β= 0.598, SE=0.163, p=0.001), male gender (β= -5.117, SE=2.005, p=0.013) and baseline mean arousal duration (β= -0.601, SE=0.184, p=0.002) were predictors for residual sleep apnea. Conclusion There was a high percentage of patients with OSA on PAP who have residual sleep apnea. Treatment CAHI is a strong predictor, and may reflect high loop gain effects. Support (If Any) Category-I Strategic Research Award from the AASM Foundation to R. J. Thomas

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)

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).

Association of air pollution exposure with low arousal threshold obstructive sleep apnea: A cross-sectional study in Taipei, Taiwan

Emerging evidence witnesses the association of air pollution exposure with sleep disorders or the risk of obstructive sleep apnea (OSA); however, the results are not consistent. OSA patients with or without a low arousal threshold (LAT) have different pathology and therapeutic schemes. No study has evaluated the potential diverse effects of air pollution on the phenotypes of OSA. The current study aimed to evaluate the associations of short-term and long-term exposure to air pollution with sleep-disordered measures and OSA phenotypes. This cross-sectional study consisted of 4634 participants from a sleep center in Taipei from January 2015 to April 2019. The personal exposure to ambient PM2.5 and NO2 was assessed by a spatial-temporal model. Overnight polysomnography was used to measure the sleep parameters. According to a developed clinical tool, we defined the low arousal threshold (LAT) and identified the OSA patients with or without LAT. We applied a generalized linear model and multinomial logistic regression model to estimate the change of sleep measures and risk of the OSA phenotypes, respectively, associated with an interquartile range (IQR) increment of personal pollution exposure after adjusting for the essential confounders. In the single-pollutant model, we observed the associations of NO2 with sleep-disordered measures by decreasing the total sleep time, sleep efficiency, extending the time of wake after sleep onset, and the association of NO2 with the increased risk of LAT OSA by around 15%. The two-pollutant model with both long-term and short-term exposures confirmed the most robust associations of long-term NO2 exposure with sleep measures. An IQR increment of NO2 averaged over the past year (6.0 ppb) decreased 3.32 min of total sleep time and 0.85% of sleep efficiency. Mitigating exposure to air pollution may improve sleep quality and reduce the risk of LAT OSA.

Loop gain is Increased and the Arousal Threshold is Decreased in Caucasian Compared to African American Males with Obstructive Sleep Apnea

ObjectiveRace and ethnicity may impact the prevalence and treatment of obstructive sleep apnea (OSA). However, only a few studies have made direct comparisons of endotypic characteristics between African Americans and Caucasians. The comparisons completed have focused primarily on differences in anatomical traits (i.e. craniofacial morphology) that may exist between races. The present study was designed to explore if other endotypic traits [(i.e. loop gain (LG) and the arousal threshold (AT)] that influence sleep apnea differ in African American compared to Caucasian males with OSA.Methods26 African Americans [age = 34.9 ± 11.9 years; body mass index = 28.1 ± 4.4 kg/m2; apnea hypopnea index (AHI) = 37.7 ± 21.1 events/hour] and 26 Caucasian male participants (age = 31.2 ± 8.2 years; body mass index = 29.6 ± 3.6 kg/m2; AHI = 41.7 ± 16.5 events/hour) with untreated OSA completed a baseline nocturnal polysomnogram. Thereafter, sleep staging, respiratory events, and arousals were scored according to standard criteria. A MATLAB software program was used to quantify LG and the AT from the ventilatory and sleep measures obtained during non‐rapid eye movement (NREM) sleep throughout the night. LG at the natural frequency (LGn) of obstructive events and at a frequency of 1 cycle/min (LG1, i.e., 60 events/hour) were computed. Data was compared using Student t‐test and is presented as mean ± SD.ResultsAge (p = 0.19), BMI (p = 0.20), and the AHI (p = 0.44) was similar between the two groups. LG was significantly higher in Caucasians compared to African Americans (LGn: 0.44 ± 0.07 vs. 0.40 ± 0.06, p = 0.037; LG1: 0.61 ± 0.12 vs. 0.54 ± 0.12, p = 0.039). In contrast, the AT was significantly lower in Caucasians compared to African Americans (1.22 ± 0.17 vs. 1.38 ± 0.27, p = 0.009). The difference in the AT corresponded to an increased arousal index in Caucasians compared to African Americans (74.99 ± 5.36 vs. 51.13 ± 19.34 arousals/hour, p = 0.029). Furthermore, a subgroup analysis of participants with OSA and co‐existing hypertension also showed that Caucasian males (n = 11) had a higher LG (LGn: 0.45 ± 0.06 vs. 0.39 ± 0.07, p = 0.05; LG1: 0.62 ± 0.12 vs. 0.48 ± 0.09, p = 0.007) and lower AT (1.16 ± 0.12 vs. 1.37 ± 0.27, p = 0.033) than the African American participants (n =10).ConclusionDespite similar anthropometric measures and a similar apnea hypopnea index, loop gain and the arousal threshold were greater in Caucasian compared to African American males with OSA. Our results suggest that these endotypic characteristics may have a more prevalent role in initiating sleep disordered breathing in Caucasians compared to African Americans. Likewise, our findings suggest that Caucasians may be more responsive to therapies that target loop gain and the arousal threshold.

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).

Zebrafish as a Tool in the Study of Sleep and Memory-related Disorders.

Sleep is an evolutionarily conserved phenomenon, being an important biological necessity for the learning process and memory consolidation. The brain displays two types of electrical activity during sleep: slow-wave activity or Non-Rapid Eye Movement (NREM) sleep, and desynchronized brain wave activity or Rapid Eye Movement (REM) sleep. There are many theories regarding "Why we need to sleep?"; one of them is the synaptic homeostasis. This theory suggests the role of sleep in the restoration of synaptic homeostasis, which is destabilized by synaptic strengthening triggered by learning during waking and by synaptogenesis during development. Sleep diminishes the plasticity load on neurons and other cells to normalize synaptic strength whereas it reestablishes neuronal selectivity and the ability to learn, leading to the consolidation and integration of memories. The use of zebrafish as a tool to assess sleep and its disorders is growing, although sleep in this animal is not yet divided, for example, into REM and NREM states. However, zebrafish are known to have a regulated daytime circadian rhythm, and their sleep state is characterized by periods of inactivity accompanied by an increase in arousal threshold, preference for resting place, and the "rebound sleep effect" phenomenon, which causes an increased slow-wave activity after a forced waking period. In addition, drugs known to modulate sleep, such as melatonin, nootropics, and nicotine have been tested in zebrafish. In this review, we discuss the use of zebrafish as a model to investigate sleep mechanisms and their regulation, demonstrating this species as a promising model for sleep research.

A Narrative Review of the Association between Post-Traumatic Stress Disorder and Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) and post-traumatic stress disorder (PTSD) are often co-morbid with implications for disease severity and treatment outcomes. OSA prevalence is higher in PTSD sufferers than in the general population, with a likely bidirectional effect of the two illnesses. There is substantial evidence to support the role that disturbed sleep may play in the pathophysiology of PTSD. Sleep disturbance associated with OSA may interfere with normal rapid eye movement (REM) functioning and thus worsen nightmares and sleep-related movements. Conversely, hyperarousal and hypervigilance symptoms of PTSD may lower the arousal threshold and thus increase the frequency of sleep fragmentation related to obstructive events. Treating OSA not only improves OSA symptoms, but also nightmares and daytime symptoms of PTSD. Evidence suggests that positive airway pressure (PAP) therapy reduces PTSD symptoms in a dose-dependent fashion, but also presents challenges to tolerance in the PTSD population. Alternative OSA treatments may be better tolerated and effective for improving both OSA and PTSD. Further research avenues will be introduced as we seek a better understanding of this complex relationship.

Phenotyping OSAH patients during wakefulness.

Although currently there are simplified methods to measure the pathophysiological traits that stimulate the occurrence and maintenance of obstructive sleep apnea-hypopnea (OSAH), they remain difficult to implement in routine practice. This pilot study aimed to find a simpler daytime approach to obtain a meaningful, similar pathophysiological phenotypic profile in patients with OSAH. After obtaining diagnostic polygraphy from a group of consecutive patients with OSAH, we performed the dial-down CPAP technique during nocturnal polysomnography and used it as reference method. This allowed assessment of upper airway collapsibility, loop gain (LG), arousal threshold (AT), and upper airway muscle gain (UAG). We compared these results with a daytime protocol based on negative expiratory pressure (NEP) technique for evaluating upper airway collapsibility and UAG, on maximal voluntary apnea for LG, and on clinical predictors for AT. Of 15 patients studied, 13 patients with OSAH accurately completed the two procedures. There were strong (all r2 > 0.75) and significant (all p < 0.001) correlations for each phenotypic trait between the measurements obtained through the reference method and those achieved during wakefulness. It is possible to phenotype patients withOSAH from a pathophysiological point of view while they are awake. Using this approach, cutoff values corresponding to those usually adopted using the reference method can be identified to detect abnormal traits, achieving profiles similar to those obtained through the dial-down CPAP technique.

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.

Proposal for determining valence and arousal thresholds: Compromised pleasure threshold, unpleasure threshold, and arousal threshold

AbstractIndividuals' emotions have been studied for nearly half a century, but the literature has not advanced to the point of estimating the intensity of a stimulus capable of influencing valence and arousal. The aim of this study was to elucidate three new thresholds: the valence thresholds, represented by the compromised pleasure threshold (CPT) and unpleasure threshold (UT), and the arousal threshold (AT). Valence and arousal ratings were obtained through the affective slider (AS), and CPT, UT, and AT were determined for images of moldy Brazilian carrot cake. Results showed CPT occurs after 1.9 days of deterioration and the AT is reached after 10.5 days of deterioration. The moldy carrot cake was valenced negatively, in the low‐arousal region. The methodology was shown to be appropriate for measuring emotion thresholds, which highlights its potential to generate deeper understanding of consumers' perceptions of valence and arousal.Practical ApplicationsWhen it comes to emotion‐driven food choices, emotion thresholds methodology can help in the monitoring of unhealthy food choices, because it will be able to provide thresholds corresponding to variables capable of significantly influencing the consumer's mood. Likewise, they may also be useful to industry, public policymakers, and health professionals, in order to facilitate the identification of the intrinsic and extrinsic factors that improve the mood of the consumer. Mitigation efforts can focus on the relationship between eating disorders and negative emotional states, which affect CPT, UT, and AT and, in turn, decision‐making. We propose that identifying the psychophysiological reactions to comforting stimuli allows us to examine differences in food processing cues among individuals with eating disorders (e.g., compulsive eating, anorexia, and bulimia), and how they shape emotion thresholds. This creates opportunities for psychoeducational interventions and improvements in decision‐making.

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.

Opioids and obstructive sleep apnea.

Freire C, Sennes LU, Polotsky VY. Opioids and obstructive sleep apnea. J Clin Sleep Med. 2022;18(2):647-652.