Chronic intermittent hypoxia reveals role of the Postinspiratory Complex in the mediation of normal swallow production.

Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder that results in multiple bouts of intermittent hypoxia. OSA has many neurological and systemic comorbidities, including dysphagia, or disordered swallow, and discoordination with breathing. However, the mechanism in which chronic intermittent hypoxia (CIH) causes dysphagia is unknown. Recently, we showed the postinspiratory complex (PiCo) acts as an interface between the swallow pattern generator (SPG) and the inspiratory rhythm generator, the preBötzinger complex, to regulate proper swallow-breathing coordination (Huff et al., 2023). PiCo is characterized by interneurons co-expressing transporters for glutamate (Vglut2) and acetylcholine (ChAT). Here we show that optogenetic stimulation of ChATcre:Ai32, Vglut2cre:Ai32, and ChATcre:Vglut2FlpO:ChR2 mice exposed to CIH does not alter swallow-breathing coordination, but unexpectedly disrupts swallow behavior via triggering variable swallow motor patterns. This suggests that glutamatergic-cholinergic neurons in PiCo are not only critical for the regulation of swallow-breathing coordination, but also play an important role in the modulation of swallow motor patterning. Our study also suggests that swallow disruption, as seen in OSA, involves central nervous mechanisms interfering with swallow motor patterning and laryngeal activation. These findings are crucial for understanding the mechanisms underlying dysphagia, both in OSA and other breathing and neurological disorders.

Assessment of cephalometric parameters and correlation with the severity of the obstructive sleep apnea syndrome.

BACKGROUND: In individuals diagnosed with obstructive sleep apnea syndrome (OSAS), variations in craniofacial structure have been inconsistently documented, showing differing degrees of alteration between obese and nonobese patients. In addition, sleep disturbance has also been shown to induce disequilibrium in this population of patients. This pilot observational study aimed to assess craniofacial values in obese and nonobese subpopulations of patients with OSAS and their correlation and association with the severity of OSAS. We also assessed whether OSAS patients are characterized by an impaired equilibrium in relation to and associated with the severity of OSAS. METHODS: We included all consecutive adult patients with OSAS. Through cephalometry, we assessed the upper (UPa-UPp) and lower (LPa-LPp) pharynx diameters, superior anterior facial height (Sor-ANS), anterior facial height (ANS-Me), anterior vertical dimension (Sor-Me), posterior facial height (S-Go) and craniovertebral angle (CVA). Furthermore, we analyzed postural equilibrium through a stabilometric examination. RESULTS: Forty consecutive OSAS patients (45% female with a mean age of 56 ± 8.2 years) were included. The subgroup of nonobese patients had a reduced UPa-UPp (p = 0.02). Cephalometric measurements were correlated with the severity of OSAS in nonobese patients, whereas only Sor-ANS was correlated with the severity of OSAS in the obese subpopulation. In the overall population, altered craniofacial values are associated with severe OSAS. Although there are differences in equilibrium between obese and nonobese OSAS patients, the stabilometric measurements were not correlated or associated with OSAS severity. CONCLUSION: Altered craniofacial values and compromised equilibrium in OSAS patients are linked to OSAS severity. Therefore, the management of OSAS should be tailored not only to weight management but also to craniofacial and postural rehabilitation to enhance patient outcomes.

Implications of depressive mood in OSAHS patients: insights from event-related potential.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a chronic breathing disorder characterized by recurrent upper airway obstruction during sleep. Although previous studies have shown a link between OSAHS and depressive mood, the neurobiological mechanisms underlying mood disorders in OSAHS patients remain poorly understood. This study aims to investigate the emotion processing mechanism in OSAHS patients with depressive mood using event-related potentials (ERPs). METHODS: Seventy-four OSAHS patients were divided into the depressive mood and non-depressive mood groups according to their Self-rating Depression Scale (SDS) scores. Patients underwent overnight polysomnography and completed various cognitive and emotional questionnaires. The patients were shown facial images displaying positive, neutral, and negative emotions and tasked to identify the emotion category, while their visual evoked potential was simultaneously recorded. RESULTS: The two groups did not differ significantly in age, BMI, and years of education, but showed significant differences in their slow wave sleep ratio (P = 0.039), ESS (P = 0.006), MMSE (P < 0.001), and MOCA scores (P = 0.043). No significant difference was found in accuracy and response time on emotional face recognition between the two groups. N170 latency in the depressive group was significantly longer than the non-depressive group (P = 0.014 and 0.007) at the bilateral parieto-occipital lobe, while no significant difference in N170 amplitude was found. No significant difference in P300 amplitude or latency between the two groups. Furthermore, N170 amplitude at PO7 was positively correlated with the arousal index and negatively with MOCA scores (both P < 0.01). CONCLUSION: OSAHS patients with depressive mood exhibit increased N170 latency and impaired facial emotion recognition ability. Special attention towards the depressive mood among OSAHS patients is warranted for its implications for patient care.

Risk of Sarcopenia and Osteoporosis in Elderly Male Patients with Obstructive Sleep Apnea Syndrome: A Multicenter Study.

The aim of this study was to assess the risk of sarcopenia and osteoporosis in elderly patients with obstructive sleep apnea syndrome (OSAS). We recruited both OSAS patients and non-OSAS subjects from multiple centers and evaluated their skeletal muscle index (SMI), bone mineral density (BMD), and inflammatory factors. All participants underwent polysomnography (PSG) testing, handgrip strength testing, chest CT, and dual-energy x-ray BMD testing. Based on the PSG diagnosis results, the participants were divided into a control group and an OSAS group. The analysis results revealed a higher incidence of sarcopenia in the OSAS group (χ2 = 22.367; P = 0.000) and osteoporosis (χ2 = 11.730a; P = 0.001). There were statistically significant differences in BMI (P = 0.000), grip strength (P = 0.000), SMI (P = 0.000), bone density (P = 0.000) and vitamin D (P = 0.000). The independent sample t test results showed that there was no statistical difference between IL-6 (P = 0.247) and CRP (P = 0.246). Considering the potential impact of body weight on the observed indicators, we employed covariance analysis to calculate the modified P value for each observation indicator. The findings demonstrated that the grip strength, IL-6, and CRP levels in the OSAS group were significantly higher compared to the control group. Conversely, the SMI, bone density, and Vitamin D levels were found to be significantly lower in the OSAS group than in the control group. These results suggest a higher likelihood of sarcopenia and osteoporosis among OSAS patients. Further studies should be conducted in larger study populations.

Polysomnographic Phenotypes of Obstructive Sleep Apnea in a Real-Life Cohort: A Pathophysiological Approach

Introduction: Obstructive sleep apnea (OSA) is heterogeneous and complex, but its severity is still based on the apnea–hypoapnea index (AHI). The present study explores using cluster analysis (CA), the additional information provided from routine polysomnography (PSG) to optimize OSA categorization. Methods: Cross-sectional study of OSA subjects diagnosed by PSG in a tertiary hospital sleep unit during 2016–2020. PSG, demographical, clinical variables, and comorbidities were recorded. Phenotypes were constructed from PSG variables using CA. Results are shown as median (interquartile range). Results: 981 subjects were studied: 41% females, age 56 years (45–66), overall AHI 23events/h (13–42) and body mass index (BMI) 30kg/m2 (27–34). Three PSG clusters were identified: Cluster 1: “Supine and obstructive apnea predominance” (433 patients, 44%). Cluster 2: “Central, REM and shorter-hypopnea predominance” (374 patients, 38%). Cluster 3: “Severe hypoxemic burden and higher wake after sleep onset” (174 patients, 18%). Based on classical OSA severity classification, subjects are distributed among the PSG clusters as severe OSA patients (AHI≥30events/h): 46% in cluster 1, 17% in cluster 2 and 36% in cluster 3; moderate OSA (15≤AHI<30events/h): 57% in cluster 1, 34% in cluster 2 and 9% in cluster 3; mild OSA (5≤AHI<15events/h): 28% in cluster 1, 68% in cluster 2 and 4% in cluster 3. Conclusions: The CA identifies three specific PSG phenotypes that do not completely agree with classical OSA severity classification. This emphasized that using a simplistic AHI approach, the OSA severity is assessed by an incorrect or incomplete analysis of the heterogeneity of the disorder. (AU)

Targeted Hypoglossal Nerve Stimulation for Patients With Obstructive Sleep Apnea: A Randomized Clinical Trial.

Importance: Evidence is lacking from randomized clinical trials of hypoglossal nerve stimulation in obstructive sleep apnea (OSA). Objective: To evaluate the safety and effectiveness of targeted hypoglossal nerve stimulation (THN) of the proximal hypoglossal nerve in patients with OSA. Design, Setting, and Participants: This randomized clinical trial (THN3) was conducted at 20 centers and included 138 patients with moderate to severe OSA with an apnea-hypopnea index (AHI) of 20 to 65 events per hour and body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or less. The trial was conducted from May 2015 through June 2018. Data were analyzed from January 2022 through January 2023. Intervention: Implant with THN system; randomized 2:1 to activation at month 1 (treatment) or month 4 (control). All received 11 months of THN with follow-up at months 12 and 15, respectively. Main Outcomes and Measures: Primary effectiveness end points comprised AHI and oxygen desaturation index (ODI) responder rates (RRs). Treatment responses at months 4 and 12/15 were defined as a 50% or greater reduction in AHI to 20 or less per hour and an ODI decrease of 25% or greater. Coprimary end points comprised (1) month 4 AHI and ODI RR in the treatment greater than the control group and (2) month 12/15 AHI and ODI RR in the entire cohort exceeding 50%. Secondary end points included sleep apnea severity (AHI and ODI) and patient-reported outcomes (Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale). Results: Among 138 participants, the mean (SD) age was 56 (9) years, and 19 (13.8%) were women. Month 4 THN RRs were substantially greater in those in the treatment vs control group (AHI, 52.3% vs 19.6%; ODI, 62.5% vs 41.3%, respectively) with treatment-control standardized mean differences of 0.725 (95% CI, 0.360-1.163) and 0.434 (95% CI, 0.070-0.843) for AHI and ODI RRs, respectively. Months 12/15 RRs were 42.5% and 60.4% for AHI and ODI, respectively. Improvements in AHI, ODI, Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale scores were all clinically meaningful (medium to large effect size). Two serious adverse events and 100 nonserious related adverse events were observed from the implant procedure or study protocol. Conclusions and Relevance: This randomized clinical trial found that THN demonstrated improvements in sleep apnea, sleepiness, and quality of life in patients with OSAs over an extended AHI and body mass index range without prior knowledge of pharyngeal collapse pattern. Clinically meaningful improvements in AHI and patient-reported responses compared favorably with those of distal hypoglossal nerve stimulation trials, although clinically meaningful differences were not definitive for ODI. Trial Registration: ClinicalTrials.gov Identifier: NCT02263859.

The placebo effect in pharmacological treatment of obstructive sleep apnea, a systematic review and meta-analysis.

OBJECTIVE: New drug treatments are under development in obstructive sleep apnea (OSA). The placebo effect is well recognized in various conditions, but its relevance in OSA is debated. In the current study we determined the influence of a placebo effect in studies of drug therapy in OSA. METHODS: A systematic review and meta-analysis (PROSPERO CRD42021229410) with searches in MEDLINE, Scopus, Web of Science and Cochrane CENTRAL from inception to 2021-01-19. Inclusion criteria were (i) RCTs of adults with OSA, (ii) drug intervention with placebo baseline and follow-up sleep study (iii) outcomes: apnea hypopnea index (AHI), mean oxygen saturation (mSaO2), oxygen desaturation index (ODI) and/or Epworth Sleepiness Scale (ESS). Risk-of-bias was assessed with Cochrane RoB 2. RESULTS: 7436 articles were identified and 29 studies included (n = 413). Studies were generally small (median n = 14), with 78% men, baseline AHI range 9-74 events/h and treatment duration range 1-120 days. Meta-analyses were conducted for main outcomes. Mean change of the primary outcome, AHI, was -0.84 (95% CI -2.98 to 1.30); mSaO2 and ODI estimations were also non-significant. ESS showed a trend towards a reduction of -1 unit. Subgroup analysis did not show significant differences. Risk-of-bias assessment indicated mostly low risk but studies were small with wide confidence intervals. CONCLUSIONS: In this meta-analysis we did not identify systematic placebo effects on the AHI, ODI or mSaO2 while ESS score showed a trend for a small reduction. These results have an impact on the design and interpretation of drug trials in OSA.