Chronic Intermittent Hypoxemia Research Articles

No impact of a high-fat meal coupled with intermittent hypoxemia on acute kidney injury biomarkers in adults with and without obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxemia, which is associated with progressive loss of kidney function, where postprandial fluctuations in renal physiology may further compromise oxygen supply and kidney function. Therefore, we measured biomarkers of acute kidney injury (AKI) following a high-fat meal with and without intermittent hypoxemia. Eighteen healthy young men (mean age [SD]: 22.7 years [3.1]) and seven middle-aged to older individuals with OSA (54.4 years [6.4]) consumed a high-fat meal during normoxia or intermittent hypoxemia (~15 hypoxic cycles per hour, ~85% oxyhemoglobin saturation) for 6 h. We observed no changes in estimated glomerular filtration rate and plasma concentrations of creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) at any measured time points. In both groups, plasma concentrations of interleukin-18 (IL-18) increased after 6 h during normoxia only (p = 0.033, ηp 2 = 0.122), and plasma concentrations of liver-type fatty acid-binding protein (L-FABP) transiently decreased after 3 h in both conditions (p = 0.008, ηp 2 = 0.152). These findings indicate that AKI biomarkers are not acutely elevated during the postprandial state with or without intermittent hypoxemia, suggesting that other mechanisms may play more important roles in the progression of kidney disease in OSA.

The upper airway in obstructive sleep apnea patients is pathological even when awake

Obstructive sleep apnea (OSA) is characterized by partial or complete obstruction of the pharyngeal airway. Anatomical factors can be distinguished from non-anatomical factors. Age and obesity are the main risk factors for OSA; however, approximately 50% of patients are not obese. In older patients (>60 years), the importance of obesity decreases. There is an increased prevalence of OSA among patients with normal weight. The effects of chronic intermittent hypoxemia, low-grade inflammation, increased sympathetic tone and mechanical stress contribute to a transformation of muscle fibers in the upper airway, resulting in reduced muscle mass and strength. Less frequently encountered non-anatomical factors include decreased muscle tone, increased arousal threshold, and altered sensitivity of CO2 chemoreceptors.

The 3% Oxygen Desaturation Index is an Independent Risk Factor for Hypertension Among Children with Obstructive Sleep Apnea.

BackgroundObstructive sleep apnea (OSA) and obesity are both directional risk factors of hypertension. Chronic intermittent hypoxemia (IH) is a commonly observed pathophysiological mechanism involved in multiple comorbidities of OSA. However, their interactions are not well understood in children. This study aimed to investigate the associations of IH indexes (oxygen desaturation index 3% [ODI3], mean peripheral oxygen saturation [SpO2], least SpO2, and time with SpO2 < 85%), apnea-hypopnea index, and weight status with hypertension in a sample of pediatric OSA patients.MethodsThe medical records of 365 pediatric OSA patients were retrospectively reviewed in this cross-sectional study. Demographics, anthropometrics, standard in-laboratory polysomnography, and nocturnal blood pressure were collected. Multivariate logistic regression with forward selection was used to identify independent predictors of hypertension.ResultsMultivariate logistic regression analysis showed that ODI3 (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 1.01–1.03) and body mass index z-score (OR = 1.34, 95% CI = 1.12–1.60) were independent continuous predictors of pediatric hypertension, whilst severe OSA (OR = 2.62, 95% CI = 1.60–4.29) and overweight/obesity (OR = 2.63, 95% CI = 1.59–4.34) were independent categorical predictors. Traditional risk factors including male sex (OR = 2.33, 95% CI = 1.02–5.33), late childhood/adolescence (OR = 1.98, 95% CI = 1.01–3.88), and overweight/obesity (OR = 2.97, 95% CI = 1.56–5.67) combined with sleep hypoxemia (least SpO2 ≤ 95%) (OR = 2.24, 95% CI = 1.16–4.04) predicted hypertension (R2 = 0.21) in the severe IH subgroup (n = 205), while the no/mild IH subgroup (n = 160) had an entirely different predictor, severe OSA (OR = 3.81, 95% CI = 1.49–9.74) (R2 = 0.07).ConclusionThe close relationships among IH, overweight/obesity, and hypertension highlight the importance of reducing IH and body weight in children with OSA.

PLATYPNEA-ORTHODEOXIA SYNDROME: THE DIAGNOSIS OF UNEXPLAINED HYPOXIA

Platypnea Orthodeoxia Syndrome (POS) is a rare condition defined as hypoxemia and dyspnea that is induced by upright posture that resolves when recumbent. A 52 year old male veteran with obstructive sleep apnea was referred for right heart catheterization (RHC) due to chronic intermittent hypoxemia

Impact of Intermittent Hypoxia on Peripheral Nervous Systems in Obstructive Sleep Apnea Syndrome

Objectives: Intermittent hypoxia resulting in endothelial dysfunction in microvascular circulation constitutes one of the mechanisms underlying complications of obstructive sleep apnea syndrome (OSAS), such as hypertension and atherosclerosis. The role of intermittent hypoxia on peripheral nerves, however, is still debated. Here, we designed a study in patients with OSAS to investigate different levels of the central and peripheral nervous systems, in order to delineate what kind of pathologic substrate was present, if any, and at which level of the neuromuscular pathway. Methods: A total of 20 patients with OSAS and 18 sex- and age-matched healthy controls were enrolled in our study. All participants underwent nerve conduction studies (NCSs) to analyze peripheral nerves, evoked potentials for somatosensory, visual evoked potential (VEP) and brainstem auditory pathways, blink reflex studies to analyze brainstem and subcortical structures, and transcranial magnetic stimulation to analyze the motor cortex and corticospinal pathway. Results: A comparison of NCSs between the two groups showed that the motor amplitudes of the ulnar nerve (P = 0.015) and sensory amplitudes of the sural nerve (P = 0.026) were significantly smaller in the OSAS group than those in the control group. The mean P100 amplitudes of VEP responses were 7.11 ± 2.73 μV in the OSAS group and 9.75 ± 3.52 μV in the control group (P = 0.022). In correlation analysis, the amplitude of P100 responses was positively correlated with the lowest oxygen saturation (P = 0.026). Conclusion: Our results confirmed the presence of generalized axonal involvement in the peripheral nervous system in OSAS, probably secondary to chronic intermittent hypoxemia.

Chronic Intermittent Hypoxemia in Patients with Obstuctive Sleep Apnea Syndrome Causes Reduction of Peripheral Nerve Motor Fibers (Unit Number)

Chronic Intermittent Hypoxemia in Patients with Obstuctive Sleep Apnea Syndrome Causes Reduction of Peripheral Nerve Motor Fibers (Unit Number)

The multi-level impact of chronic intermittent hypoxia on central auditory processing

During hypoxia, the tissues do not obtain adequate oxygen. Chronic hypoxia can lead to many health problems. A relatively common cause of chronic hypoxia is sleep apnea. Sleep apnea is a sleep breathing disorder that affects 3–7% of the population. During sleep, the patient's breathing starts and stops. This can lead to hypertension, attention deficits, and hearing disorders. In this study, we apply an established chronic intermittent hypoxemia (CIH) model of sleep apnea to study its impact on auditory processing. Adult rats were reared for seven days during sleeping hours in a gas chamber with oxygen level cycled between 10% and 21% (normal atmosphere) every 90s. During awake hours, the subjects were housed in standard conditions with normal atmosphere. CIH treatment significantly reduces arterial oxygen partial pressure and oxygen saturation during sleeping hours (relative to controls). After treatment, subjects underwent functional magnetic resonance imaging (fMRI) with broadband sound stimulation. Responses are observed in major auditory centers in all subjects, including the auditory cortex (AC) and auditory midbrain. fMRI signals from the AC are statistically significantly increased after CIH by 0.13% in the contralateral hemisphere and 0.10% in the ipsilateral hemisphere. In contrast, signals from the lateral lemniscus of the midbrain are significantly reduced by 0.39%. Signals from the neighboring inferior colliculus of the midbrain are relatively unaffected. Chronic hypoxia affects multiple levels of the auditory system and these changes are likely related to hearing disorders associated with sleep apnea.

Sleep breathing disorders and cognitive decline in healthy elderly followed for eight years: The PROOF cohort

Sleep breathing disorders (SBD) are the most common sleep disorders frequently under-diagnosed in elderly populations. However, it is it well known that this disorder may contribute to the age-related cognitive decline. In a cohort of healthy elderly subjects, we performed an 8-year longitudinal study to assess whether changes in cognitive function occur in untreated SBD elderly and the nocturnal factors implicated in these changes. A total of 559 participants of the community-based PROOF study aged 67 years at the study entry and free from neurological disorders were examined. SBD was defined by an apnea-hypopnea index (Apnea-Hypopnea Index, AHI) > 15. The raw cognitive data and averaged Z-scores for the attentional, executive and memory functions were collected at the baseline and 8 years later. Estimates of the longitudinal changes were computed for each of the three cognitive abilities by subtracting the averaged scores of last from the first evaluation (delta score, Δ). At baseline, an AHI > 15 was found in 54% of subjects with 18% having a severe form (AHI > 30). At follow-up, the presence of SBD was associated with a slight but significant decline in the attentional domain (P = .01), which was more evident in the subjects with an AHI > 30 (P = .004). The decline of memory score was related to sleep fragmentation (p < .001) without contribution of indices of nocturnal hypoxemia. In healthy elderly subjects, the presence of SBD was associated with a significant decline in attentional and memory function. While the severity of the sleep disorder reflected by the AHI and the severity of sleep fragmentation accounted for the degree of the attentional and memory decline, chronic intermittent hypoxemia had small effect. Interestingly, in some subjects of this population the treatment by positive airway pressure it would be to prevent the long-term cognitive decline (Crowford-Achour & al. 2015). These data stressed the need to make cognitive rehabilitation in elderly and treat the SBD disorder to prevent the long-term cognitive decline. The presence of abnormal respiratory events longitudinally induces a decline in the age-related decline. These pathologies are underdiagnosed in the elderly. These data were essential when it discusses the effect of cognitive rehabilitation in elderly population for which the treatment of SBD coulb be potentiated it.

Tailored treatment strategies for obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by repetitive collapse of the upper airway (UA) during sleep and is associated with chronic intermittent hypoxemia, catecholamine surges, and sleep disrupt. Multiple pathophysiological risk factors have been identified and contribute to OSA, including anatomical abnormalities (elevated UA mechanical load), compromised UA dilators, increased loop gain (unstable respiratory control), and decreased arousal threshold. These factors may contribute to the pathophysiology of sleep apnea in different individuals and recent evidence suggests that treatment may be targeted towards underlying pathophysiological mechanism. In some cases, combination therapy may be required to treat the condition.

Sleep-Disordered Breathing and Cognition in Older Adults

Both sleep-disordered breathing (SDB) and cognitive impairment are common among older adults, yet few studies have examined their relationship within this population to determine whether the effect of SDB on cognition is of a magnitude similar to or greater than that observed in younger and middle-aged adults. Here, we review the extant literature and report that studies are largely supportive of an association between SDB and cognitive impairment in older adults, particularly in the domains of attention/vigilance, executive function, and verbal delayed recall memory. Presence of the APOE4 allele may confer increased vulnerability to SDB-associated cognitive dysfunction among elderly individuals. Although findings are mixed, there is strong evidence to suggest that SDB-related intermittent hypoxemia is the primary mechanism through which SDB exerts its adverse effects on cognition. We propose a microvascular model in which chronic intermittent hypoxemia causes vasculopathy that ultimately is expressed as cognitive impairment in the older adult. However, it remains unclear whether the effects of SDB on cognition are the same regardless of age or whether there is a synergistic interaction between age and SDB.

Resistant hypertension and obstructive sleep apnea in end-stage renal disease

Resistant hypertension and obstructive sleep apnea in end-stage renal disease

Influence of Obstructive Sleep Apnea on Fatty Liver Disease: Role of Chronic Intermittent Hypoxia

Currently the common pathogenetic mechanisms in nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) are gaining increased attention. The aim of this study is to find out the influence of chronic intermittent hypoxemia and OSA related parameters to the severity of NAFLD. We examined the liver functions tests and ultrasonographic data of liver as well as markers of OSA severity (apnea-hypopnea index [AHI], oxygen desaturation index, minimum oxygen saturation, percentage of time spent with S(pO(2)) < 90%) of 106 subjects. Fatty liver disease was diagnosed in 71 subjects (group 1), and the remaining 35 subjects were taken as controls (group 2). The prevalence of OSA was 71.2% versus 35.7% for group 1 and 2, respectively (P < .001). As NAFLD severity increased from mild to severe form, mean AHI and oxygen desaturation index values also increased significantly. Our multivariate analysis showed that AHI, oxygen desaturation index, lowest desaturation values, and percentage of sleep duration with S(pO(2)) < 90% were independent predictors of NAFLD after adjustment for BMI, weight, and insulin resistance. Furthermore, the most correlated parameter for the severity of NAFLD was found as the duration of hypoxia during sleep. The prevalence of NAFLD was higher in patients with severe OSA, suggesting a role for nocturnal hypoxemia in the pathogenesis of fatty liver disease.

Hypoxic damage to pancreatic beta cells – The hidden link between sleep apnea and diabetes

Despite a large body of epidemiologic and clinical evidence suggesting that sleep disordered breathing is an independent risk factor for development of type 2 diabetes (T2DM), the underlying pathogenesis of altered glucose metabolism in sleep apnea remains to be unraveled. While previous studies have proposed some causal pathways linking sleep apnea with T2DM through increased insulin resistance and deterioration in insulin sensitivity, there has been a particular lack of research into sleep apnea-related alterations in pancreatic beta-cell function. Drawing upon our previous observation that sleep apnea is independently associated with an increased basal pancreatic beta-cell function in adults with normal glucose metabolism [1], the idea presented here suggests that sleep apnea imposes an excessive demand for insulin secretion, which may lead to progressive pancreatic beta-cell failure in high-risk individuals. Specifically, we hypothesize that in addition to diabetogenic effects of acute hypoxic activation of the sympathetic nervous system, the chronic intermittent hypoxemia represses the expression of key genes regulating biosynthesis of pancreatic proinsulin convertases with a resultant progressive decrease in their catalytic activity. The long-term hypoxic damage to pancreatic beta-cells may thus contribute to progression of glucose dysregulation in persons with untreated sleep apnea over time. Strategies to prevent and decrease the high prevalence and associated morbidity of T2DM are critically needed. The ideas and hypotheses presented here address the unexplored pathophysiological mechanisms underlying the potential causal link between sleep apnea and T2DM. Future hypotheses-testing will seek to delineate the role of sleep apnea in the development of T2DM, probe the underlying molecular mechanisms for pancreatic beta-cell dysfunction in sleep apnea, and obtain information on clinical, epidemiologic, and other factors responsible for protecting individuals from alterations in insulin-glucose homeostasis. These results could further be utilized in testing genetic susceptibilities and various therapy modalities to prevent pancreatic beta-cell dysfunction and maintain normal glucose status in persons with sleep apnea in the long term.

PO31-FR-08 Chronic intermittent hypoxemia in patients with OSAS leads to the reduction of the number of median nerve fibers

PO31-FR-08 Chronic intermittent hypoxemia in patients with OSAS leads to the reduction of the number of median nerve fibers

Beyond the Fat Boy: the intertwining pathophysiologies of sleep apnea

Over the past 20 years, increasing data have accumulated underscoring the public health importance of sleep apnea with growing evidence of its high prevalence and myriad clinical manifestations. This condition, rarely diagnosed in the past, had been considered to occur predominantly as a