Selective Continuous Positive Airway Pressure Withdrawal With Supplemental Oxygen During Slow-Wave Sleep as a Method of Dissociating Sleep Fragmentation and Intermittent Hypoxemia-Related Sleep Disruption in Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is considered to impair memory processing and increase the expression of amyloid-β (Aβ) and risk for Alzheimer’s disease (AD). Given the evidence that slow-wave sleep (SWS) is important in both memory and Aβ metabolism, a better understanding of the mechanisms by which OSA impacts memory and risk for AD can stem from evaluating the role of disruption of SWS specifically and, when such disruption occurs through OSA, from evaluating the individual contributions of sleep fragmentation (SF) and intermittent hypoxemia (IH). In this study, we used continuous positive airway pressure (CPAP) withdrawal to recapitulate SWS-specific OSA during polysomnography (PSG), creating conditions of both SF and IH in SWS only. During separate PSGs, we created the conditions of SWS fragmentation but used oxygen to attenuate IH. We studied 24 patients (average age of 55 years, 29% female) with moderate-to-severe OSA [Apnea-Hypopnea Index (AHI); AHI4% > 20/h], who were treated and adherent to CPAP. Participants spent three separate nights in the laboratory under three conditions as follows: (1) consolidated sleep with CPAP held at therapeutic pressure (CPAP); (2) CPAP withdrawn exclusively in SWS (OSASWS) breathing room air; and (3) CPAP withdrawn exclusively in SWS with the addition of oxygen during pressure withdrawal (OSASWS + O2). Multiple measures of SF (e.g., arousal index) and IH (e.g., hypoxic burden), during SWS, were compared according to condition. Arousal index in SWS during CPAP withdrawal was significantly greater compared to CPAP but not significantly different with and without oxygen (CPAP = 1.1/h, OSASWS + O2 = 10.7/h, OSASWS = 10.6/h). However, hypoxic burden during SWS was significantly reduced with oxygen compared to without oxygen [OSASWS + O2 = 23 (%min)/h, OSASWS = 37 (%min)/h]. No significant OSA was observed in non-rapid eye movement (REM) stage 1 (NREM 1), non-REM stage 2 (NREM 2), or REM sleep (e.g., non-SWS) in any condition. The SWS-specific CPAP withdrawal induces OSA with SF and IH. The addition of oxygen during CPAP withdrawal results in SF with significantly less severe hypoxemia during the induced respiratory events in SWS. This model of SWS-specific CPAP withdrawal disrupts SWS with a physiologically relevant stimulus and facilitates the differentiation of SF and IH in OSA.

Obstructive sleep apnea and cardiovascular comorbidity: common pathophysiological mechanisms to cardiovascular disease

Obstructive sleep apnea (OSA) is associated with many cardiovascular and metabolic diseases. Sleep apnea causes intermittent hypoxemia, chest pressure fluctuations and a reaction from the cerebral cortex in the form of a short awakening during sleep (EEG-activation). The consequences of pathological pathways are studied in experimental models involving cell cultures, animals, and healthy volunteers. At present, the negative impact of intermittent hypoxemia on a variety of pathophysiological disorders of the heart and blood vessels (vascular tone fluctuations, thickening of the intimamedia complex in the vascular wall, direct damaging effect on the myocardium) has a great evidence base. Two other pathological components of OSA (pressure fluctuations and EEG-activation) can also affect cardiovascular system, mainly affecting the increase in blood pressure and changing cardiac hemodynamics. Although these reactions are considered separately in the review, with the development of sleep apnea they occur sequentially and are closely interrelated. As a result, these pathological pathways trigger further pathophysiological mechanisms acting on the heart and blood vessels. It is known that these include excessive sympathetic activation, inflammation, oxidative stress and metabolic dysregulation. In many respects being links of one process, these mechanisms can trigger damage to the vascular wall, contributing to the formation of atherosclerotic lesions. The accumulated data with varying degrees of reliability confirm the participation of OSA through these processes in the formation of cardiovascular disorders. There are factors limiting direct evidence of this interaction (sleep deprivation, causing similar changes, as well as the inability to share the contribution of other risk factors for cardiovascular diseases, in particular arterial hypertension, obesity, which are often associated with OSA). It is necessary to continue the study of processes that implement the pathological effect of OSA on the cardiovascular system.

Different Associations between Tonsil Microbiome, Chronic Tonsillitis, and Intermittent Hypoxemia among Obstructive Sleep Apnea Children of Different Weight Status: A Pilot Case-Control Study

The tonsil microbiome is associated with chronic tonsillitis and obstructive sleep apnea (OSA) in children, and the gut microbiome is associated with host weight status. In this study, we hypothesized that weight status may be associated with clinical profiles and the tonsil microbiome in children with OSA. We prospectively enrolled 33 non-healthy-weight (cases) and 33 healthy-weight (controls) pediatric OSA patients matched by the proportion of chronic tonsillitis. Differences in the tonsil microbiome between the non-healthy-weight and healthy-weight subgroups and relationships between the tonsil microbiome and clinical variables were investigated. Non-healthy weight was associated with significant intermittent hypoxemia (oxygen desaturation index, mean blood saturation (SpO2), and minimal SpO2) and higher systolic blood pressure percentile, but was not related to the tonsil microbiome. However, chronic tonsillitis was related to Acidobacteria in the non-healthy-weight subgroup, and oxygen desaturation index was associated with Bacteroidetes in the healthy-weight subgroup. In post hoc analysis, the children with mean SpO2 ≤ 97% had reduced α and β diversities and a higher abundance of Bacteroidetes than those with mean SpO2 > 97%. These preliminary findings are novel and provide insights into future research to understand the pathogenesis of the disease and develop personalized treatments for pediatric OSA.

Extubation Readiness in Preterm Infants: Evaluating the Role of Monitoring Intermittent Hypoxemia

Preterm infants with respiratory distress may require mechanical ventilation which is associated with increased pulmonary morbidities. Prompt and successful extubation to noninvasive support is a pressing goal. In this communication, we show original data that increased recurring intermittent hypoxemia (IH, oxygen saturation <80%) may be associated with extubation failure at 72 h in a cohort of neonates <30 weeks gestational age. Current-generation bedside high-resolution pulse oximeters provide saturation profiles that may be of use in identifying extubation readiness and failure. A larger prospective study that utilizes intermittent hypoxemia as an adjunct predictor for extubation readiness is warranted.

Dynamic changes in nocturnal blood glucose levels are associated with sleep-related features in patients with obstructive sleep apnea

Obstructive sleep apnea (OSA) has a bidirectional relationship with insulin resistance conditions; however, the mechanism remains unclear. This study aimed to compare dynamic nocturnal glucose changes among patients with OSA of varying levels of severity and evaluate temporal changes associated with the cardinal features of OSA (sympathetic hyperactivation, intermittent hypoxemia, and sleep fragmentation) in nondiabetic subjects. Nocturnal glucose was measured with a continuous glucose monitoring device every 5 min during polysomnography (PSG). The OSA features were evaluated using heart rate variability (HRV), minimum saturation, and electroencephalography. Eleven subjects with moderate to severe OSA and 12 subjects with no or mild OSA were evaluated. Those with moderate to severe OSA showed an increasing trend in blood glucose levels after sleep onset, whereas those without or with mild OSA showed a decreasing trend (F = 8.933, p < 0.001). Delta band power also showed different trends during sleep between the two groups (F = 2.991, p = 0.009), and minimum saturation remained lower in the moderate to severe OSA group than in the no or mild OSA group. High degrees of coupling between nocturnal glucose levels and each OSA feature were observed. Altered trends in nocturnal glucose in moderate to severe OSA may reflect glucose intolerance and result in metabolic consequences. Managing the features of sleep-related OSA may have implications for metabolic management in the future.