The language of sleepiness in obstructive sleep apnea beyond the Epworth.

PURPOSE: Obstructive sleep apnea (OSA) is underdiagnosed, partially from variable clinical presentations. Emphasis is often placed on Epworth Sleepiness Scale (ESS), a subjective measure of sleepiness, but variable in OSA. We hypothesized that daytime complaints measured with Language of Sleepiness Questionnaire (LOS) in OSA are not being captured by ESS. METHODS: Adults referred to a tertiary sleep clinic undergoing sleep studies completed ESS and LOS questionnaires (20 items with various patient-reported descriptors). LOS was examined in patients who had or did not have OSA without sleepiness based on ESS < 10. Cluster analysis was performed to assess whether or not groups of individuals differed based on classification with or without OSA and with or without ESS-based sleepiness. RESULTS: Approximately half the study population (n = 185 completed) had OSA. ESS score (mean ± SD) was 9.0 ± 5.4. There was no significant difference in ESS between patients with and without OSA (9.0 ± 5.1 vs 9.1 ± 5.7, p = 0.969). In patients with OSA, females, older patients and white patients were significantly less likely to have an ESS ≥ 10 when compared to patients with an ESS < 10. In patients with an ESS < 10, there were no significant differences in descriptors of sleepiness between patients with and without OSA with the most common descriptors selected being "I lack energy," "I wake up sleepy," "I keep waking up," and "I don't sleep enough." CONCLUSIONS: The ESS failed to discriminate patients with OSA from those without OSA. Despite an ESS < 10, both daytime and sleep complaints using the LOS questionnaire were present in patients with OSA. Asymptomatic OSA may be less common than previously reported.

Isovolemic hemodilution in chronic mountain sickness acutely worsens nocturnal oxygenation and sleep apnea severity.

STUDY OBJECTIVES: Chronic mountain sickness (CMS) is commonly observed among Andean and other highland populations. Sleep-disordered breathing (SDB) is highly prevalent at high altitude, and SDB and nocturnal hypoxemia have been observed in CMS. Phlebotomy is commonly performed to treat CMS, but it is unknown whether reducing hematocrit improves SDB. We hypothesized that isovolemic hemodilution (IVHD) in CMS would reduce SBD severity and improve sleep efficiency. METHODS: Six participants with CMS and 8 without CMS, all residents of Cerro de Pasco, Peru (altitude 4340 m), completed baseline nocturnal sleep studies. CMS participants then underwent IVHD, and nocturnal sleep studies were repeated 24-48 hours after IVHD. We analyzed sleep apnea severity, nocturnal oxygenation, and sleep quality in those with CMS relative to those without CMS, and the effects of IVHD in CMS participants. RESULTS: Participants with CMS did not have altered sleep architecture, sleep apnea severity, or nocturnal oxygenation relative to non-CMS participants. However, IVHD in CMS increased apnea-hypopnea index (40.9 ± 6.9 events/h to 61.5 ± 7.7 events/h, P = .009). IVHD increased oxyhemoglobin desaturation index (P = .008) and the percentage of sleep time spent with oxyhemoglobin saturation at or below 80% (P = .012). There was no effect of IVHD on sleep efficiency, arousal index, or sleep staging. CONCLUSIONS: In this cohort, CMS was not associated with worsened SDB or changes in sleep architecture. IVHD, a putative therapeutic option for participants with CMS, appears to worsen nocturnal oxygenation and SDB within 48 hours post-IVHD. CITATION: Sanchez-Azofra A, Villafuerte FC, DeYoung PN, et al. Isovolemic hemodilution in chronic mountain sickness acutely worsens nocturnal oxygenation and sleep apnea severity. J Clin Sleep Med. 2022;18(10):2423-2432.

The impact of daytime transoral neuromuscular stimulation on upper airway physiology - A mechanistic clinical investigation.

There is a need for alternatives to positive airway pressure for the treatment of obstructive sleep apnea and snoring. Improving upper airway dilator function might alleviate upper airway obstruction. We hypothesized that transoral neuromuscular stimulation would reduce upper airway collapse in concert with improvement in genioglossal muscle function. Subjects with simple snoring and mild OSA (AHI < 15/h on screening) underwent in-laboratory polysomnography with concurrent genioglossal electromyography (EMGgg) before and after 4-6 weeks of twice-daily transoral neuromuscular stimulation. Twenty patients completed the study: Sixteen males, mean ± SD age 40 ± 13 years, and BMI 26.3 ± 3.8 kg/m2 . Although there was no change in non-rapid eye movement EMGgg phasic (p = 0.66) or tonic activity (p = 0.83), and no decrease in snoring or flow limitation, treatment was associated with improvements in tongue endurance, sleep quality, and sleep efficiency. In this protocol, transoral neurostimulation did not result in changes in genioglossal activity or upper airway collapse, but other beneficial effects were noted suggesting a need for additional mechanistic investigation.

Diagnostic performance of screening tools for the detection of obstructive sleep apnea in people living with HIV.

STUDY OBJECTIVES: Many people living with human immunodeficiency virus (PLWH) have undiagnosed obstructive sleep apnea (OSA), which may contribute to commonly reported fatigue and the high cardiovascular disease burden in this population. Our objective was to assess the utility of traditional OSA screening tools (STOP-BANG, Berlin Questionnaire, and Epworth Sleepiness Scale) for detecting OSA in PLWH. METHODS: Adult PLWH were recruited from sleep/ human immunodeficiency virus clinics and the community into a larger clinical trial that included completion of these questionnaires before in-laboratory polysomnography. Discriminatory performance of these screening tools was assessed using area under receiver operating characteristic curves (AUC). The reference standard for the primary analysis was OSA based on an apnea-hypopnea index ≥ 5 events/h using recommended "1A"-criteria (hypopnea with 3% desaturation and/or arousal). Secondary analyses explored acceptable "1B"-criteria (hypopnea with 4% desaturation) and/or higher apnea-hypopnea index cut-offs (≥ 15 events/h). RESULTS: 120 PLWH were included (mean age: 50 ± 11 years; body mass index: 27 ± 4 kg/m2, 84% male) and OSA was diagnosed in 75% using 1A-criteria. In the primary analysis, the discriminatory performance of the 3 screening tools was low (AUCs 0.58 to 0.70) and similar across the tools (P ≥ .14). In secondary analyses, STOP-BANG showed moderate-high discriminatory ability (AUCs 0.77-0.80) and performed significantly better (P ≤ .008) than the Berlin Questionnaire or Epworth Sleepiness Scale (AUCs 0.53-0.62). CONCLUSIONS: OSA was highly prevalent in our cohort of PLWH. Although STOP-BANG could reasonably identify moderate-severe OSA, the tools were not reliable for mild disease. Specifically, the questionnaires perform poorly for PLWH with mild OSA manifesting with arousals, yet such people may be at risk of fatigue/sleepiness and impaired memory consolidation. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Obstructive Sleep Apnea Endotypes and Impact on Phenotypes of People Living with HIV (PLWH/OSA); Identifier: NCT03575143; URL: https://clinicaltrials.gov/ct2/show/NCT03575143. CITATION: Schmickl CN, Bosompra N-O, DeYoung PN, et al. Diagnostic performance of screening tools for the detection of obstructive sleep apnea in people living with HIV. J Clin Sleep Med. 2022;18(7):1797-1804.

A Pilot Randomized Controlled Trial of Effect of Genioglossus Muscle Strengthening on Obstructive Sleep Apnea Outcomes.

The genioglossus is a major upper airway dilator muscle. Our goal was to assess the efficacy of upper airway muscle training on Obstructive Sleep Apnea (OSA) as an adjunct treatment. Sixty-eight participants with OSA (AHI > 10/h) were recruited from our clinic. They fall into the following categories: (a) Treated with Automatic Positive Airway Pressure (APAP), (n = 21), (b) Previously failed APAP therapy (Untreated), (n = 25), (c) Treated with Mandibular Advancement Splint (MAS), (n = 22). All subjects were given a custom-made tongue strengthening device. We conducted a prospective, randomized, controlled study examining the effect of upper airway muscle training. In each subgroup, subjects were randomized to muscle training (volitional protrusion against resistance) or sham group (negligible resistance), with a 1:1 ratio over 3 months of treatment. In the baseline and the final visit, subjects completed home sleep apnea testing, Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), SF-36 (36-Item Short Form Survey), and Psychomotor Vigilance Test (PVT). Intervention (muscle training) did not affect the AHI (Apnea-Hypopnea Index), (p-values > 0.05). Based on PSQI, ESS, SF-36 scores, and PVT parameters, the changes between the intervention and sham groups were not significant, and the changes were not associated with the type of treatment (p-value > 0.05). The effectiveness of upper airway muscle training exercise as an adjunct treatment requires further study.

Impact of obstructive sleep apnea on cardiopulmonary performance, endothelial dysfunction, and pulmonary hypertension during exercise.

RATIONALE: OSA has been associated with reduced exercise capacity. Endothelial dysfunction and exercise-induced pulmonary hypertension (ePH) may be mediators of this impairment. We hypothesized that OSA severity would be associated with impaired exercise performance, endothelial dysfunction, and ePH. METHODS: Subjects with untreated OSA were recruited. Subjects underwent endothelial function, and cardiopulmonary exercise testing with an echocardiogram immediately before and following exercise. RESULTS: 22 subjects were recruited with mean age 56 ± 8 years, 74 % male, BMI 29 ± 3 kg/m2, and AHI 22 ± 12 events/hr. Peak V˙O2 did not differ from normal (99.7 ± 17.3 % predicted; p = 0.93). There was no significant association between OSA severity (as AHI, ODI) and exercise capacity, endothelial function, or pulmonary artery pressure. However, ODI, marker of RV diastolic dysfunction, and BMI together explained 59.3 % of the variability of exercise performance (p < 0.001) via our exploratory analyses. CONCLUSIONS: Exercise capacity was not impaired in this OSA cohort. Further work is needed to elucidate mechanisms linking sleep apnea, obesity, endothelial dysfunction and exercise impairment.

Relationships Between Chemoreflex Responses, Sleep Quality, and Hematocrit in Andean Men and Women.

Andean highlanders are challenged by chronic hypoxia and many exhibit elevated hematocrit (Hct) and blunted ventilation compared to other high-altitude populations. While many Andeans develop Chronic Mountain Sickness (CMS) and excessive erythrocytosis, Hct varies markedly within Andean men and women and may be driven by individual differences in ventilatory control and/or sleep events which exacerbate hypoxemia. To test this hypothesis, we quantified relationships between resting ventilation and ventilatory chemoreflexes, sleep desaturation, breathing disturbance, and Hct in Andean men and women. Ventilatory measures were made in 109 individuals (n = 63 men; n = 46 women), and sleep measures in 45 of these participants (n = 22 men; n = 23 women). In both men and women, high Hct was associated with low daytime SpO2 (p < 0.001 and p < 0.002, respectively) and decreased sleep SpO2 (mean, nadir, and time <80%; all p < 0.02). In men, high Hct was also associated with increased end-tidal PCO2 (p < 0.009). While ventilatory responses to hypoxia and hypercapnia did not predict Hct, decreased hypoxic ventilatory responses were associated with lower daytime SpO2 in men (p < 0.01) and women (p < 0.009) and with lower nadir sleep SpO2 in women (p < 0.02). Decreased ventilatory responses to CO2 were associated with more time below 80% SpO2 during sleep in men (p < 0.05). The obstructive apnea index and apnea-hypopnea index also predicted Hct and CMS scores in men after accounting for age, BMI, and SpO2 during sleep. Finally, heart rate response to hypoxia was lower in men with higher Hct (p < 0.0001). These data support the idea that hypoventilation and decreased ventilatory sensitivity to hypoxia are associated with decreased day time and nighttime SpO2 levels that may exacerbate the stimulus for erythropoiesis in Andean men and women. However, interventional and longitudinal studies are required to establish the causal relationships between these associations.

Cognitive function and mood at high altitude following acclimatization and use of supplemental oxygen and adaptive servoventilation sleep treatments.

Impairments in cognitive function, mood, and sleep quality occur following ascent to high altitude. Low oxygen (hypoxia) and poor sleep quality are both linked to impaired cognitive performance, but their independent contributions at high altitude remain unknown. Adaptive servoventilation (ASV) improves sleep quality by stabilizing breathing and preventing central apneas without supplemental oxygen. We compared the efficacy of ASV and supplemental oxygen sleep treatments for improving daytime cognitive function and mood in high-altitude visitors (N = 18) during acclimatization to 3,800 m. Each night, subjects were randomly provided with ASV, supplemental oxygen (SpO2 > 95%), or no treatment. Each morning subjects completed a series of cognitive function tests and questionnaires to assess mood and multiple aspects of cognitive performance. We found that both ASV and supplemental oxygen (O2) improved daytime feelings of confusion (ASV: p < 0.01; O2: p < 0.05) and fatigue (ASV: p < 0.01; O2: p < 0.01) but did not improve other measures of cognitive performance at high altitude. However, performance improved on the trail making tests (TMT) A and B (p < 0.001), the balloon analog risk test (p < 0.0001), and the psychomotor vigilance test (p < 0.01) over the course of three days at altitude after controlling for effects of sleep treatments. Compared to sea level, subjects reported higher levels of confusion (p < 0.01) and performed worse on the TMT A (p < 0.05) and the emotion recognition test (p < 0.05) on nights when they received no treatment at high altitude. These results suggest that stabilizing breathing (ASV) or increasing oxygenation (supplemental oxygen) during sleep can reduce feelings of fatigue and confusion, but that daytime hypoxia may play a larger role in other cognitive impairments reported at high altitude. Furthermore, this study provides evidence that some aspects of cognition (executive control, risk inhibition, sustained attention) improve with acclimatization.

Adaptive Servoventilation as Treatment for Central Sleep Apnea Due to High-Altitude Periodic Breathing in Nonacclimatized Healthy Individuals.

Orr, Jeremy E., Erica C. Heinrich, Matea Djokic, Dillon Gilbertson, Pamela N. Deyoung, Cecilia Anza-Ramirez, Francisco C. Villafuerte, Frank L. Powell, Atul Malhotra, and Tatum Simonson. Adaptive servoventilation as treatment for central sleep apnea due to high-altitude periodic breathing in nonacclimatized healthy individuals. High Alt Med Biol. 19:178-184, 2018. AIMS: Central sleep apnea (CSA) is common at high altitude, leading to desaturation and sleep disruption. We hypothesized that noninvasive ventilation using adaptive servoventilation (ASV) would be effective at stabilizing CSA at altitude. Supplemental oxygen was evaluated for comparison. METHODS: Healthy subjects were brought from sea level to 3800 m and underwent polysomnography on three consecutive nights. Subjects underwent each condition-No treatment, ASV, and supplemental oxygen-in random order. The primary outcome was the effect of ASV on oxygen desaturation index (ODI). Secondary outcomes included oxygen saturation, arousals, symptoms, and comparison to supplemental oxygen. RESULTS: Eighteen subjects underwent at least two treatment conditions. There was a significant difference in ODI across the three treatments. There was no statistical difference in ODI between no treatment and ASV (17.1 ± 4.2 vs. 10.7 ± 2.9 events/hour; p > 0.17) and no difference in saturation or arousal index. Compared with no treatment, oxygen improved the ODI (16.5 ± 4.5 events/hour vs. 0.5 ± 0.2 events/hour; p < 0.003), in addition to saturation and arousal index. CONCLUSIONS: We found that ASV was not clearly efficacious at controlling CSA in persons traveling to 3800 m, whereas supplemental oxygen resolved CSA. Adjustment in the ASV algorithm may improve efficacy. ASV may have utility in acclimatized persons or at more modest altitudes.