Phase II study comparing nasal pressure monitoring with capnography during invasive endoscopic procedures: a single-center, single-arm trial.

Nasal pressure signal is commonly used to evaluate obstructive sleep apnea. This study aimed to assess its safety for respiratory monitoring during sedation. A total of 45 adult patients undergoing sedation with propofol and fentanyl for invasive endoscopic procedures were enrolled. While both nasal pressure and capnograph signals were continuously recorded, only the nasal pressure signal was displayed. The primary outcome was the incidence of oxygen desaturation below 90%. The secondary outcomes were the ability to predict the desaturation and incidence of harmful events and false alarms, defined as an apnea waveform lasting more than 3 min without desaturation. Of the 45 participants, 43 completed the study. At least one desaturation event occurred in 12 patients (27.9%; 95% confidence interval 15.3-43.7%). In these 12 patients, more than half of the desaturation events were predictable in 9 patients by capnography and 11 patients by nasal pressure monitoring (p = 0.59). In the 43 patients, false alarms were detected in 7 patients with capnography and 11 patients with nasal pressure monitoring (p = 0.427). Harmful events unrelated to nasal pressure monitoring occurred in 2 patients. Nasal pressure monitoring is safe and possibly useful for respiratory monitoring despite false alarms during sedation.

Ertugliflozin and incident obstructive sleep apnea: an analysis from the VERTIS CV trial.

PURPOSE: The sodium-glucose transporter 2 inhibitor (SGLT2i) empagliflozin may reduce the incidence of obstructive sleep apnea (OSA) in patients with type 2 diabetes (T2D) and cardiovascular (CV) disease. This analysis of VERTIS CV, the CV outcome trial for the SGLT2i ertugliflozin conducted in a similar group of patients, explored the effects of ertugliflozin on reported incident OSA. METHODS: In VERTIS CV, patients ≥ 40 years with T2D and atherosclerotic CV disease (ASCVD) were randomized to ertugliflozin 5 or 15 mg or placebo. The primary endpoint was the composite of major adverse CV events. This exploratory analysis evaluated the impact of ertugliflozin (5 and 15 mg pooled) on incident OSA. Patients with prevalent OSA were excluded. Incident OSA events were based on investigator-reported events using the MedDRA SMQ term "sleep apnea syndrome." A multivariable Cox proportional hazards regression model was constructed to assess the association between ertugliflozin and incident OSA. RESULTS: Of 8246 patients enrolled, 7697 (93.3%) were without baseline OSA (placebo, n = 2561; ertugliflozin, n = 5136; mean age 64.4 years; BMI 31.7 kg/m2; HbA1c, 8.2%; 69.2% male; 88.3% White). The OSA incidence rate was 1.44 per 1000 person-years versus 2.61 per 1000 person-years among patients treated with ertugliflozin versus placebo, respectively, corresponding to a 48% relative risk reduction (HR 0.52; 95% CI 0.28-0.96; P = 0.04). CONCLUSIONS: In VERTIS CV, ertugliflozin reduced by nearly half the incidence of OSA in patients with T2D and ASCVD. These data contribute to the literature that SGLT2is may have a significant beneficial impact on OSA. CLINICALTRIALS: gov identifier: NCT01986881.

Incidence, Contributing Factors, and Implications for Clinical Management of Polycythemia in Transmasculine Patients on Testosterone.

Purpose: The goal of this study was to evaluate contributing factors and management strategies for polycythemia in transmasculine patients on testosterone therapy. Methods: A retrospective analysis of medical records was performed for transmasculine patients on testosterone for at least 12 months. Data collected from each patient included age, body mass index (BMI), nicotine dependence, pulmonary disease status, obstructive sleep apnea (OSA) status, oophorectomy status, and testosterone route of administration. For patients who developed polycythemia, polycythemia management strategy data were collected. Results: Five-hundred-eleven patients were evaluated and 113 (22%) experienced an episode of polycythemia. Within the polycythemia group, 77% of patients were younger than age 40, 56% had a BMI >30.0, 44% had current or former nicotine dependence, 12% had a pulmonary disease, 12% had OSA, and 47% had received an oophorectomy. The polycythemia group had a significantly higher average age, BMI, and dose of testosterone, and also had a higher proportion of patients with OSA and an oophorectomy. Conclusion: These results revealed that polycythemia is a common side effect for transmasculine patients on testosterone. Importantly, previous oophorectomy may be associated with polycythemia which appears to be a novel finding. This finding requires further research but provides the potential to be an important screening consideration for transmasculine patients after oophorectomy. Polycythemia will continue to be a major concern for patients on testosterone therapy, and this study provided important information for clinical practice and future research that will lead to improved outcomes.

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.

Incidence and risk factors of chronic opioid use after sleep apnea surgery.

STUDY OBJECTIVES: To assess the incidence and risk factors of chronic opioid use after obstructive sleep apnea surgery. METHODS: Using IBM MarketScan research database, adults (>18 years) who underwent a variety of sleep surgery procedures between 2007 and 2015 were identified. Individuals with 1 year of insurance coverage before and after the surgical procedure were included. Additional anesthesia event(s) in the year following the procedure of interest and those who filled an opioid prescription within the year prior to surgery (not naive) were excluded. Outcomes included rates of persistent opioid use (additional opioid prescriptions filled 90-180 days postoperatively), prolonged use (additional opioid prescriptions filled 181-365 days postoperatively), and inappropriate use (> 100 morphine milligram equivalents). Evaluated variables include demographics, surgical procedures, and comorbidities. RESULTS: A total of 10,766 surgical procedures met the inclusion criteria. There was a trend of increased rates of perioperative opioid prescription. After multivariable logistic regression analysis, perioperative opioid prescription and smoking were independent risk factors for inappropriate opioid use (odds ratio [OR] = 31.51, P < .001; OR = 1.41, P = .016, respectively). Opioid prescription and hypertension were independent risk factors for persistent opioid use (OR = 37.8, P < .001, OR = 1.38, P = .008). Perioperative opioid prescription, previous opioid dependence diagnosis, smoking, and male sex were associated with continuous prolonged opioid use (OR = 73.1, 8.13, 1.95, and 1.55, respectively; P < .001, P = .020, P = .024, and P = .032, respectively). CONCLUSIONS: While efforts by different societies are being implemented to control the opioid crisis, we found that perioperative opioid prescription for airway surgery targeting obstructive sleep apnea is an independent risk factor for persistent, prolonged, and inappropriate opioid use. CITATION: Abdelwahab M, Marques S, Howard J, et al. Incidence and risk factors of chronic opioid use after sleep apnea surgery. J Clin Sleep Med. 2022;18(7):1805-1813.

Preventing Postoperative Opioid-Induced Respiratory Depression Through Implementation of an Enhanced Monitoring Program.

BACKGROUND: Opioid-induced respiratory depression (OIRD) is a serious complication that can lead to negative outcomes. There are known risk factors for OIRD; however, a lack of national guidelines for the prevention and early detection of OIRD exists. METHODS: An evidence-based practice study was conducted to create an enhanced monitoring (EM) program. The EM program consisted of risk stratification of surgical spine patients, including the use of STOP-BANG screening for obstructive sleep apnea, capnography monitoring, use of home positive airway pressure therapy, capnography alarm optimization, hospitalist consultation, nursing education, and patient education. RESULTS: Approximately 17% (N = 937/5,462) of surgical spine patients were enrolled in the EM program. Fifty-six percent of EM patients were monitored with capnography and had out of range end-tidal carbon dioxide levels 17% of the time. The rate of transfers to the intensive care unit (ICU) for OIRD decreased, though not statistically significant (p = .151). CONCLUSIONS: The EM program with risk stratification was found to reduce transfers to the ICU for OIRD. Although not statistically significant, the decreased number of transfers was clinically significant. Engagement of the interprofessional team and capnography alarm parameter optimization helped to reduce nonactionable alarms.

Opioids and obstructive sleep apnea.

Opioids are widely prescribed for pain management, and it is estimated that 40% of adults in the United States use prescription opioids every year. Opioid misuse leads to high mortality, with respiratory depression as the main cause of death. Animal and human studies indicate that opioid use may lead to sleep-disordered breathing. Opioids affect control of breathing and impair upper airway function, causing central apneas, upper airway obstruction, and hypoxemia during sleep. The presence of obstructive sleep apnea (OSA) increases the risk of opioid-induced respiratory depression. However, even if the relationship between opioids and central sleep apnea is firmly established, the question of whether opioids can aggravate OSA remains unanswered. While several reports have shown a high prevalence of OSA and nocturnal hypoxemia in patients receiving a high dose of opioids, other studies did not find a correlation between opioid use and obstructive events. These differences can be attributed to considerable interindividual variability, divergent effects of opioids on different phenotypic traits of OSA, and wide-ranging methodology. This review will discuss mechanistic insights into the effects of opioids on the upper airway and hypoglossal motor activity and the association of opioid use and obstructive sleep apnea. CITATION: Freire C, Sennes LU, Polotsky VY. Opioids and obstructive sleep apnea. J Clin Sleep Med. 2022;18(2):647-652.

The Association between Use of Benzodiazepine Receptor Agonists and the Risk of Obstructive Sleep Apnea: A Nationwide Population-Based Nested Case-Control Study.

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway collapse. Benzodiazepine receptor agonists (BZRAs) are associated with pharyngeal muscle relaxation, increased apnea duration, and hypoxia, which might worsen OSA. This study aimed to examine the association between the use of BZRAs and the risk of OSA. The study was conducted using data from the National Health Insurance Database of Taiwan between 2002 and 2011. We only included new users who were never exposed to any BZRAs and identified 1848 participants with OSA, and 1848 matched controls. A logistic regression model was used to determine the association between the use of BZRAs and the development of OSA. BZRA exposure was divided into usage patterns, dosage, duration, and pharmacokinetic class. We found an increased risk of OSA in current users and recent past users compared with distant past users. Patients with a higher cumulative dose of BZRAs were more likely to develop OSA compared to those with a lower cumulative dose. We found an increased risk of OSA in patients treated with BZRAs, especially for current users and those with higher cumulative doses. A reduced risk of OSA was found in Z-drug users compared with benzodiazepine users.

Dexmedetomidine-induced polysomnography as a diagnostic method in obstructive sleep apnea: a reliable alternative method?

BACKGROUND: Under-diagnosis of obstructive sleep apnea (OSA) is common because of the demanding and time-consuming nature of polysomnography (PSG). Herein, we assessed the utility of a short daytime dexmedetomidine-induced PSG for diagnosis of OSA in adults. METHODS: This was a single-center, prospective, diagnostic trial. We evaluated 86 patients using a full overnight PSG and a short diurnal drug-induced PSG (DIPSG). DIPSG was induced by continuous intravenous dexmedetomidine infusion. Sedation depth was monitored and maintained using the Narcotrend index (50-70). Diagnostic performance for DIPSG with different apnea-hypopnea index (AHI) cut-off values were calculated. Bland-Altman plots used for analysis. Sleep architecture and position were compared. RESULTS: We studied 47 OSA patients and 39 healthy volunteers. Sensitivity and specificity for detection of OSA by DIPSG were 92% and 79%, respectively, for an AHI cut-off value of 5, 90% and 77%, respectively, for an AHI cut-off value of 15, and 95% and 85%, respectively, for an AHI cut-off value of 30. The DIPSG bias was -5 (-25; 15) for AHI and -3 (-13; 7) for minimal oxygen saturation. N2 sleep was increased (32.9% vs. 50.75%, respectively; p < 0.01) and REM sleep was decreased (21.35% vs. 1.24%, respectively; p < 0.01) during DIPSG. Twenty-eight (33%) participants had postural shifts during DIPSG. No significant adverse events were observed during DIPSG. CONCLUSIONS: Dexmedetomidine-induced PSG had a good sensitivity and specificity, and can be used as a screening tool for diagnosis of OSA in adults. CHINESE CLINICAL TRIAL REGISTRATION: ChiCTR1900024044.

Dynamic tongue base thickness measured by drug-induced sleep ultrasonography in patients with obstructive sleep apnea.

BACKGROUND/PURPOSE: The aim of this study was to determine the value of drug-induced sleep ultrasonography (DISU) for evaluating tongue base thickness (TBT) from the awake state to drug-induced sleep, to further understand the impact of dynamic changes in TBT in obstructive sleep apnoea (OSA) patients. METHODS: From May 2017 to May 2018, thirty patients with OSA were prospectively recruited. Sleep was induced with propofol via use of a target-controlled infusion (TCI) system. The depth of sedation was monitored by the bispectral (BIS) index with BIS levels ranging from 50 to 70. The dynamic change in the tongue base from the awake state to drug-induced sleep was recorded. The correlation between TBT in the awake state and in drug-induced sleep with OSA severity was analysed. RESULTS: The mean TBT in drug-induced sleep was significantly greater than that in the awake state (66.2 ± 4.8 mm vs 61.6 ± 4.6 mm, P < 0.001). TBT in drug-induced sleep was more correlated with AHI compared to TBT in the awake state (r = 0.50 vs r = 0.40). This study showed that TBT in drug-induced sleep had the largest AUC (Area Under the Curve) in the ROC (Receiver Operating Characteristics) analysis (0.875), providing a cut-off point of 63.20 mm with 95% sensitivity for diagnosis of moderate versus severe OSA. CONCLUSION: Our findings validate the use of DISU in objectively assessing the tongue base collapse in OSA patients. It provides a convenient and non-invasive way to evaluate the upper airway changes in OSA patients in the future.

Obstructive Sleep Apnea and Testosterone Therapy.

INTRODUCTION: There is persistent speculation that testosterone therapy (TTh) may induce worsening of obstructive sleep apnea (OSA). As both the incidence of OSA and the use of TTh grow more prevalent, it is important to review the current evidence that supports or refutes this relationship. OBJECTIVES: To review the current literature regarding the relationship between TTh and OSA. METHODS: A literature search was conducted to identify relevant studies. Search terms included "obstructive sleep apnea" and "testosterone replacement therapy." Titles and abstracts were reviewed for relevance. References from identified articles were searched and included, if appropriate. RESULTS: The association between TTh and OSA was initially described in a 1978 case report of an individual with worsened nighttime apneas during testosterone administration, a trend seen again in subsequent small case series. In the 1990s, a large retrospective analysis and the first randomized controlled trial on the subject revealed no increased incidence of OSA in individuals on TTh. A randomized controlled trial conducted in 2012 provided a possible explanation to the previously reported discrepancies, describing a time-limited effect, wherein measures of OSA were elevated at seven weeks but were not significantly different at 18 weeks after initiation of TTh. A recent cohort study demonstrated an incidence of OSA in individuals on TTh of 16.5% compared with 12.7% in controls. TTh is thought to affect OSA in several ways. Theories that the anabolic effects of testosterone may decrease airway patency or that testosterone alters sleep architecture have been largely disproven. More likely, testosterone plays a role in altering neural response pathways to hypoxemia. CONCLUSIONS: TTh likely plays a small role in exacerbating or inducing changes in OSA that may be time limited in nature. Clinicians may choose to exercise caution in prescribing TTh to individuals suffering from severe OSA. Payne K, Lipshultz LI, Hotaling JM, et al. Obstructive Sleep Apnea and Testosterone Therapy. J Sex Med 2021;9:296-303.

Opioids and sleep.

PURPOSE OF REVIEW: Summarize the effects of opioids on sleep including sleep architecture, sleep disordered breathing (SDB) and restless legs syndrome. RECENT FINDINGS: Opioids are associated with the development of central sleep apnea (CSA) and ataxic breathing. Recent reports suggest that adaptive servo-ventilation may be an effective treatment for CSA associated with opioids. SUMMARY: Opioids have multiple effects on sleep, sleep architecture and SDB. Although originally described with methadone use, most commonly used opioids have also been shown to affect sleep. In patients on chronic methadone, sleep architecture changes include decreases in N3 and REM sleep. However, in patients with chronic nonmalignant pain, opioids improve sleep quality and sleep time. Opioids, generally at a morphine equivalent dose more than 100 mg/day, are associated with an increased incidence of CSA and ataxic breathing as well as obstructive sleep apnea. Other risk factors may include concomitant use of other medications such as antidepressants, gabapentinoids and benzodiazepines. Opioid-induced CSA can be potentially treated with adaptive servo-ventilation. Finally, opioids are a potential therapeutic option for restless legs syndrome unresponsive to dopamine agonists and other medications. However, use in patients with restless legs syndrome should proceed with caution, taking into account the risk for dependence and development of SDB.

Finasteride Use Is Associated with Higher Odds of Obstructive Sleep Apnea: Results from the US Food and Drug Administration Adverse Events Reporting System.

Finasteride is a 5-α reductase inhibitor indicated for the treatment of androgenetic alopecia and benign prostatic hyperplasia (BPH). Finasteride has been associated with various adverse events, such as erectile dysfunction, fatigue, cognitive impairment, sleep disturbances, including insomnia, depression, and suicidal behavior. These symptoms are sometimes considered features of the "post-finasteride syndrome" (PFS) and are also encountered in obstructive sleep apnea (OSA). The overlapping clinical features of PFS and OSA suggest that OSA could possibly play a mediating role in some of the PFS-related symptoms. There are no reported studies of the association of finasteride use and OSA. The objective of this study was to determine whether finasteride use is associated with a potential safety signal of OSA compared to a baseline potential safety signal for all other drugs in the US Food and Drugs Administration Adverse Event Reporting System (FAERS) database. A case by non-case disproportionality approach was used, whereby a reporting odds ratio (ROR) with 95% confidence interval (CI) was calculated. Cases of finasteride-associated OSA were compared to a reference potential safety signal of OSA with all other drugs in the database. A similar calculation was carried out for finasteride-associated insomnia to confirm previous reports of a greater than expected reporting of insomnia with finasteride use. A significant disproportionality (ROR = 5.65 [95% CI 4.83-6.62, z = 21.56, P < 0.0001]) in reporting of OSA with the use of finasteride was observed. The potential safety signal for OSA with finasteride remained significantly higher when finasteride use for hair loss and BPH was examined separately. Finasteride use was associated with a greater than expected reporting of insomnia (ROR = 1.93 [95% CI 1.77-2.09, z = 15.958, P < 0.0001]). A limitation of this study is that selection bias is inherent in FAERS and adverse events could be underreported. Finasteride use may be associated with a potential safety signal for OSA. Patients complaining of PFS-related symptoms may benefit from a further sleep evaluation to rule out underlying OSA.

Metabolic syndrome and obstructive sleep apnea syndrome among patients with epilepsy on monotherapy.

OBJECTIVES: The study aimed to determine the frequency of metabolic syndrome (MetS) and obstructive sleep apnea syndrome (OSAS) in patients with epilepsy receiving monotherapy and the relationship between these syndromes and antiepileptic drugs (AEDs). METHODS: Two hundred and ninety-seven patients with epilepsy between the ages of 18-65 years receiving monotherapy for at least one year and 50 healthy participants were enrolled. Body mass indices and waist circumferences were measured. Serum fasting glucose levels, high-density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol (TC), triglyceride, and serum AED concentrations were noted. The frequency of MetS in patients with epilepsy was calculated. The snoring, tiredness, observed apnea, high blood pressure, body mass index, age, neck circumference, and male gender (STOP-Bang) questionnaire was used to determine the risk of OSAS. The relationship between these two syndromes and seizure type, disease duration, AED dosage, and treatment duration was analyzed. RESULTS: Metabolic syndrome was more frequent in patients with epilepsy compared with healthy participants (32.6% vs. 12.0%), and it was diagnosed in 37.8% of patients receiving valproic acid (VPA), 36.1% of patients receiving carbamazepine (CBZ), 34.9% of patients receiving oxcarbazepine (OXC), and 30.5% of patients on levetiracetam (LEV). There was a positive correlation between VPA treatment duration and MetS existence (p < 0.05). However, MetS frequency did not change because of seizure type, disease duration, or AED dosages in patients with epilepsy receiving monotherapy. The risk for OSAS was higher in patients with epilepsy compared with healthy participants (24.6% vs. 12%), and it was calculated high in 27.7% of patients receiving CBZ, 32.2% of patients receiving LEV, and 30.2% of patients receiving OXC. The OSAS risk was higher in patients who have focal seizures than generalized seizures (p = 0.044). There was no relationship between OSAS risk and duration of epilepsy, duration of treatment, drug doses, and serum drug levels (p > 0.05). CONCLUSION: Higher frequency of MetS and OSAS risk should be kept in mind on clinical follow-up of patients with epilepsy receiving monotherapy.

Mandibular Advancement Devices Prevent the Adverse Cardiac Effects of Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS).

Although considerable research highlights the interactions between obstructive sleep apnea-hypopnea syndrome (OSAHS) and cardiovascular diseases, the effect of mandibular advancement device (MAD) treatment on cardiovascular complications in OSAHS patients remains unclear. We evaluated the effect of OSAHS treatment with MADs on the myocardium. All methods in this study were in accordance with relevant guidelines and regulations of the medical ethics committee in Hospital of Stomatology, Hebei Medical University approved the work. Thirty New Zealand rabbits were randomized into three groups: the control group, Group OSAHS, and Group MAD. Hydrophilic polyacrylamide gel was injected into the soft palate of the rabbits to induce OSAHS. In Group MAD, a MAD was positioned after OSAHS induction. All animals were induced to sleep in a supine position for 4-6 h/day for 8 weeks. Echocardiography was used to determine the structure and function of the heart. The histological changes were detected by optical microscopy and transmission electron microscopy (TEM). The levels of ET-1(endothelin-1) and Ang II (Angiotensin II) in the plasma were measured by an enzyme-linked immunosorbent assay (ELISA). The expression of ET-1 mRNA in heart tissue was detected by RT-PCR. Histological abnormalities, left ventricular hypertrophy, and left ventricular dysfunctions were demonstrated in Group OSAHS, and the abnormities were rescued with MAD treatment. Higher levels of plasma ET-1 and Ang II and elevated expression of ET-1 mRNA in cardiac tissue were detected in Group OSAHS compared with Group MAD and the control group. The blood oxygen saturation was negatively correlated with the levels of ET-1 and Ang II. OSAHS-induced elevated levels of ET-1 and Ang II may be attributed to myocardial structural abnormalities and dysfunction. Early treatment of MADs may play an important role in preventing myocardial damage in OSAHS rabbit model.

Comparison of upper airway obstruction during zolpidem-induced sleep and propofol-induced sleep in patients with obstructive sleep apnea: a pilot study.

STUDY OBJECTIVES: Drug-induced sleep endoscopy (DISE) using propofol is commonly used to identify the pharyngeal structure involved in collapse among patients with obstructive sleep apnea. DISE has never been compared with zolpidem-induced sleep endoscopy. We hypothesized that propofol at recommended sedation levels does not influence upper airway collapsibility nor the frequency of multilevel pharyngeal collapse as compared with zolpidem-induced sleep. METHODS: Twenty-one patients with obstructive sleep apnea underwent polysomnography and sleep endoscopy during zolpidem-induced sleep and during DISE with propofol. A propofol target-controlled infusion was titrated to achieve a bispectral index between 50 and 70. Airway collapsibility was estimated and compared in both conditions by peak inspiratory flow and the magnitude of negative effort dependence. Respiratory drive was estimated by the difference between end-expiratory and peak-negative inspiratory pharyngeal pressure (driving pressure). Site and configuration of pharyngeal collapse during zolpidem-induced sleep and DISE with propofol were compared. RESULTS: The frequency of multilevel collapse during zolpidem-induced sleep was similar to that observed during DISE with propofol (72% vs 86%, respectively; difference: 14%; 95% confidence interval: -12% to 40%; P = .453). The endoscopic classification of pharyngeal collapse during both conditions were similar. Peak inspiratory flow, respiratory drive (effect size: 0.05 and 0.03, respectively), and negative effort dependence (difference: -6%; 95% confidence interval: -16% to 4%) were also similar in both procedures. CONCLUSIONS: In this pilot study, recommended propofol doses did not significantly increase multilevel pharyngeal collapse or affect upper airway collapsibility and respiratory drive as compared with zolpidem-induced sleep. CLINICAL TRIAL REGISTRATION: Registry: clinicaltrials.gov; Name: Natural and Drug Sleep Endoscopy; URL: https://clinicaltrials.gov/ct2/show/study/NCT03004014; Identifier: NCT03004014.

Lactobacillus rhamnosus GG strain mitigated the development of obstructive sleep apnea-induced hypertension in a high salt diet via regulating TMAO level and CD4+ T cell induced-type I inflammation.

Obstructive sleep apnea (OSA) and high salt content in modern diet has been particularly implicated in systemic hypertension, leading to increased morbidity and mortality. Gut dysbiosis, associated with increased risk of systemic immunological imbalance, plays a causal role in the development of cardiovascular diseases. Here, we investigated the effect of Lactobacillus rhamnosus GG strain (LGG) on the development of hypertension induced by OSA and high salt diet. In this study, hypertension was modeled in rats by feeding a high salt diet (HSD) for 6 wk and exposuring to chronic intermittent hypoxia (CIH) during the sleep cycle. We found that OSA combined with HSD increased the severity of hypertension through increasing level of blood Trimethylamine-Oxide (TMAO), release of Th1-related cytokine (IFN-γ) and inhibition of anti-inflammatory cytokine (TGF-ß1), and affected the gut microbiome in rats, particularly by depleting Lactobacillus. In addition, expression of PERK1/2, PAkt and PmTOR increased in the aorta from rats with a CIH exposure and HSD. Consequently, treatment of model rats with LGG prevented aggravation of hypertension by reducing blood TMAO levels, modulating Th1/Th2 cytokine imbalance and suppressing phosphorylation levels of ERK1/2, Akt and mTOR. In line with these findings, our results connect high salt diet to the gut-immune axis and highlight the gut microbiome as a potential therapeutic target to counteract the development of OSA-induced hypertension basing on a high salt diet.