Obstructive Sleep Apnea Disease Severity Research Articles

Trends in obstructive sleep apnea disease severity over nearly two decades: update on the VA San Diego experience.

The Sleep Program at the VA San Diego Healthcare System (VASDHS) started a patient database over twenty years ago for its home sleep apnea testing (HSAT) program. An analysis of ten years of diagnostic HSAT data was reported on over 12500 patients in 2014. Over this time period, severe obstructive sleep apnea (OSA) decreased in frequency. In contrast, mild OSA increased in frequency and was the most frequently reported severity in our analysis. In more recent times, the 2021 continuous positive airway pressure (CPAP) crisis created difficulties in dispersing CPAP therapies to individuals including Veterans with OSA, prompting our group to reexamine the HSAT database. A retrospective review was performed of the local clinical database of HSAT diagnostic testing of 8,928 sleep studies from 2018 to 2022. The overall mean apnea-hypopnea index (AHI) decreased from 40.4/hour (2004) to 24.3/hour (2022) (p < .001). The two time periods were examined separately. For 2004-2013, it was found that the mean AHI in 2004 was not significantly different from the mean AHI in 2005, 2006, or 2007 but was significantly different from the mean AHI in each year from 2008 (mean AHI = 30.7/h) to 2013 (mean AHI = 26.1/hour). For 2019-2022, the mean AHI did not significantly differ between the 4 years. These findings have implications for OSA therapies. Additionally, the high prevalence of mild sleep apnea, which is typically associated with lesser adherence to PAP therapy, further highlights the importance of non-PAP alternatives to improve treatment effectiveness.

A Novel Quantitative Arousal-Associated EEG-Metric to Predict Severity of Respiratory Distress in Obstructive Sleep Apnea Patients.

Respiratory arousals (RA) on polysomnography (PSG) are an important predictor of obstructive sleep apnea (OSA) disease severity. Additionally, recent reports suggest that more global indices of desaturation such as the hypoxic burden, namely the area under the curve (AUC) of the oxygen saturation (SaO2) PSG trace may better depict the desaturation burden in OSA. Here we investigated possible associations between a new metric, namely the AUC of the respiratory arousal electroencephalographic (EEG) recording, and already established parameters as the apnea/hypopnea index (AHI), arousal index and hypoxic burden in patients with OSA. In this data-driven study, polysomnographic data from 102 patients with OSAS were assessed (32 female; 70 male; mean value of age: 52 years; mean value of Body-Mass-Index-BMI: 31 kg/m2). The marked arousals from the pooled EEG signal (C3 and C4) were smoothed and the AUC was estimated. We used a support vector regressor (SVR) analysis to predict AHI, arousal index and hypoxic burden as captured by the PSG. The SVR with the arousal-AUC metric could quite reliably predict the AHI with a high correlation coefficient (0,58 in the training set, 0,65 in the testing set and 0,64 overall), as well as the hypoxic burden (0,62 in the training set, 0,58 in the testing set and 0,59 overall) and the arousal index (0,58 in the training set, 0,67 in the testing set and 0,66 overall). This novel arousal-AUC metric may predict AHI, hypoxic burden and arousal index with a quite high correlation coefficient and therefore could be used as an additional quantitative surrogate marker in the description of obstructive sleep apnea disease severity.

Relationship between Sleep Stages and HRV response in Obstructive Sleep Apnea Patients.

Patients suffering from obstructive sleep apnea (OSA) usually present an increased sympathetic activity caused by the intermittent hypoxia effect on autonomic control. This study evaluated the relationship between sleep stages and the apnea duration, frequency, and type, as well as their impact on HRV markers in different groups of disease severity. The hypnogram and R-R interval signals were extracted in 81 OSA patients from night polysomnographic (PSG) recordings. The apnea-hypopnea index (AHI) defined patient classification as mild-moderate (AHI<=30, n=44) or severe (AHI>30, n=37). The normalized power in VLH, LF, and HF bands of RR series were estimated by a time-frequency approach and averaged in 1-min epochs of normal and apnea segments. The autonomic response and the impact of sleep stages were assessed in both segments to compare patient groups. Deeper sleep stages (particularly S2) concentrated the shorter and mild apnea episodes (from 10 to 40 s) compared to light (SWS) and REM sleep. Longer episodes (>50 s) although less frequent, were of similar incidence in all stages. This pattern was more pronounced for the group of severe patients. Moreover, during apnea segments, LFnu was higher (p=0.044) for the severe group, since V LFnu and HFnu presented the greatest changes when compared to normal segments. The non-REM sleep seems to better differentiate OSA patients groups, particularly through VLFnu and HFnu(p<0.001). A significant difference in both sympathetic and vagal modulation between REM and non-REM sleep was only found within the severe group. These results confirm the importance of considering sleep stages for HRV analysis to further assess OSA disease severity, beyond the traditional and clinically limited AHI values.Clinical relevance-Accounting for sleep stages during HRV analysis could better assess disease severity in OSA patients.

A brief report: The National Adult Reading Test (NART) is a stable assessment of premorbid intelligence across disease severity in obstructive sleep apnea (OSA).

Obstructive sleep apnea (OSA) is a widely prevalent disorder that can affect cognitive function. The relationship between cognitive function and OSA is known to be affected by an individual's premorbid cognitive ability. Tools to measure premorbid intelligence across OSA disease severity have not been validated. This brief report aims to establish if the National Adult Reading Test (NART) provides a stable estimate of premorbid intelligence across levels of OSA disease severity. We examined if NART scores varied systematically across levels of untreated OSA severity (defined according to the apnea-hypopnea index [AHI]) and mean oxygen saturation in sleep clinic (n=121) and community samples (n=398) using regression analysis. Simple linear regression was used to predict NART scores based on the AHI. NART-estimated premorbid IQ scores without demographics did not vary systematically with AHI (F<1; β=0.01) or mean SpO2 (F<1; β=0.12). NART-estimated premorbid IQ scores with added demographic information also did not vary systematically with AHI (F<1; β=-0.01) or mean SpO2 (F<1; β=0.15). This preliminary examination shows that the NART provides a stable estimate of premorbid intelligence across untreated OSA disease severity, as demarcated by AHI or mean nocturnal SpO2 .

Quality-of-life improvement after endoscopic sinus surgery in patients with obstructive sleep apnea.

Background:There is preliminary evidence that patients with chronic rhinosinusitis (CRS) and comorbid obstructive sleep apnea (OSA) have reduced quality-of-life (QOL) improvements after functional endoscopic sinus surgery (FESS) compared with patients without OSA. The effect of OSA severity on QOL improvement after FESS is unknown.Objectives:To better characterize the QOL improvement after FESS for patients with comorbid OSA and to assess whether QOL improvement is dependent on OSA severity.Methods:This multi-institution, retrospective cohort study evaluated adult patients with CRS who underwent FESS between 2007 and 2015. Preoperative, 1-month, 3-month, 6-month, and 1-year postoperative 22-Item Sino-Nasal Outcome Test scores were used to evaluate QOL. We compared patients without OSA with patients with stratified OSA based on the preoperative apnea-hypopnea index. A multilevel, mixed-effects linear regression model was used for the analysis.Results:Of 480 participants, 83 (17%) had OSA, and 47 of these patients had polysomnography results available for review. Both patients with OSA and patients without OSA reported significant QOL improvement after surgery (p < 0.0001) relative to baseline. In the unadjusted model, the subjects with OSA demonstrated a statistically worse outcome in 22-Item Sino-Nasal Outcome Test scores at each time point (2.4 points higher per time point, p = 0.006). When controlling for covariates, the adjusted model showed no difference in QOL outcome based on OSA status (p = 0.114). When stratified by OSA disease severity, the adjusted model showed no difference in the QOL outcome.Conclusions:Patients with CRS and comorbid OSA had worse QOL outcomes after FESS; however, when controlling for patient factors, there was no difference in QOL outcome. OSA disease severity did not seem to predict QOL improvement after FESS.

Endothelial function and carotid intima media thickness in obstructive sleep apnea without comorbidity.

The objective of this study was to evaluate endothelial function and carotid intima media thickness (CIMT) in moderate to severe obstructive sleep apnea (OSA) without comorbidities. It is an observational case control study in which endothelial function was assessed using flow-mediated dilatation (FMD) and peripheral arterial tonometry (PAT), and carotid artery ultrasound was used to measure CIMT in study group subjects that included 20 normotensive, non-diabetic, treatment naïve, and moderate to severe OSA patients, and 20 normotensive, non-diabetic, and non-OSA subjects served as a control group. Study was conducted in Polysomnography Laboratory, Department of Internal Medicine, All India Institute of Medical Sciences (AIIMS) Hospital, New Delhi. FMD was significantly lower in the moderate to severe OSA group compared to non-OSA group (mean ± SD, 8.3 ± 2.8 vs. 13.4 ± 4.1%; p = 0.0001). Reactive hyperemia index (RHI) was also significantly lower in the OSA group (1.55 ± 0.27 vs. 2.01 ± 0.48, p = 0.0007). CIMT was observed to be significantly higher in the OSA group compared to the non-OSA group (0.54 ± 0.09 vs. 0.48 ± 0.08mm; p = 0.049). In the OSA group, FMD, RHI, and CIMT did not show a significant correlation with OSA disease severity indices [apnea hypopnea index (AHI), oxygen desaturation index (ODI), and minimum O2 saturation]. Endothelial function in macrovascular and microvascular circulation is significantly impaired in moderate to severe OSA patients without comorbidities. These patients also show evidence of subclinical atherosclerosis, in the form of increased CIMT.

Associations between brain white matter integrity and disease severity in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway blockage, with continued diaphragmatic efforts to breathe during sleep. Brain structural changes in OSA appear in various regions, including white matter sites that mediate autonomic, mood, cognitive, and respiratory control. However, the relationships between brain white matter changes and disease severity in OSA are unclear. This study examines associations between an index of tissue integrity, magnetization transfer (MT) ratio values (which show MT between free and proton pools associated with tissue membranes and macromolecules), and disease severity (apnea-hypopnea index [AHI]) in OSA subjects. We collected whole-brain MT imaging data from 19 newly diagnosed, treatment-naïve OSA subjects (50.4 ± 8.6 years of age, 13 males, AHI 39.7 ± 24.3 events/hr], using a 3.0-Tesla MRI scanner. With these data, whole-brain MT ratio maps were calculated, normalized to common space, smoothed, and correlated with AHI scores by using partial correlation analyses (covariates, age and gender; P < 0.005). Multiple brain sites in OSA subjects, including superior and inferior frontal regions, ventral medial prefrontal cortex and nearby white matter, midfrontal white matter, insula, cingulate and cingulum bundle, internal and external capsules, caudate nuclei and putamen, basal forebrain, hypothalamus, corpus callosum, and temporal regions, showed principally lateralized negative correlations (P < 0.005). These regions showed significant correlations even with correction for multiple comparisons (cluster-level, family-wise error, P < 0.05), except for a few superior frontal areas. Predominantly negative correlations emerged between local MT values and OSA disease severity, indicating potential usefulness of MT imaging for examining the OSA condition. These findings indicate that OSA severity plays a significant role in white matter injury. © 2016 Wiley Periodicals, Inc.

The pathogenesis of obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a major source of cardiovascular morbidity and mortality, and represents an increasing burden on health care resources. Understanding underlying pathogenic mechanisms of OSA will ultimately allow for the development of rational therapeutic strategies. In this article, we review current concepts about the pathogenesis of OSA. Specifically, we consider the evidence that the upper airway plays a primary role in OSA pathogenesis and provide a framework for modelling its biomechanical properties and propensity to collapse during sleep. Anatomical and neuromuscular factors that modulate upper airway obstruction are also discussed. Finally, we consider models of periodic breathing, and elaborate generalizable mechanisms by which upper airway obstruction destabilizes respiratory patterns during sleep. In our model, upper airway obstruction triggers a mismatch between ventilatory supply and demand. In this model, trade-offs between maintaining sleep stability or ventilation can account for a full range of OSA disease severity and expression. Recurrent arousals and transient increases in airway patency may restore ventilation between periods of sleep, while alterations in neuromuscular and arousal responses to upper airway obstruction may improve sleep stability at still suboptimal levels of ventilation.

The effect of increased lung volume in chronic obstructive pulmonary disease on upper airway obstruction during sleep.

Patients with chronic obstructive pulmonary disease (COPD) exhibit increases in lung volume due to expiratory airflow limitation. Increases in lung volumes may affect upper airway patency and compensatory responses to inspiratory flow limitation (IFL) during sleep. We hypothesized that COPD patients have less collapsible airways inversely proportional to their lung volumes, and that the presence of expiratory airflow limitation limits duty cycle responses to defend ventilation in the presence of IFL. We enrolled 18 COPD patients and 18 controls, matched by age, body mass index, sex, and obstructive sleep apnea disease severity. Sleep studies, including quantitative assessment of airflow at various nasal pressure levels, were conducted to determine upper airway mechanical properties [passive critical closing pressure (Pcrit)] and for quantifying respiratory timing responses to experimentally induced IFL. COPD patients had lower passive Pcrit than their matched controls (COPD: -2.8 ± 0.9 cmH2O; controls: -0.5 ± 0.5 cmH2O, P = 0.03), and there was an inverse relationship of subject's functional residual capacity and passive Pcrit (-1.7 cmH2O/l increase in functional residual capacity, r(2) = 0.27, P = 0.002). In response to IFL, inspiratory duty cycle increased more (P = 0.03) in COPD patients (0.40 to 0.54) than in controls (0.41 to 0.51) and led to a marked reduction in expiratory time from 2.5 to 1.5 s (P < 0.01). COPD patients have a less collapsible airway and a greater, not reduced, compensatory timing response during upper airway obstruction. While these timing responses may reduce hypoventilation, it may also increase the risk for developing dynamic hyperinflation due to a marked reduction in expiratory time.

Weight Gain after Adenotonsillectomy Is More Common in Young Children

Adenotonsillectomy (TA), performed for obstructive sleep apnea (OSA) or recurrent tonsillitis (RT), has been associated with weight gain after surgery. The objective of this study was to look at a large population of children undergoing TA and the demographic factors that contribute to postoperative weight gain. Case series with retrospective chart review. Tertiary, urban academic care center. Children undergoing TA at an academic center between 2008 and 2011 were included in this study. Demographic data (age, gender, race), OSA disease severity, preoperative and 3- to 6-month postoperative normalized body mass index (BMI; z-scores), and changes in z-scores were compared. Complete weight data after TA were available for 115 children, 85 of whom underwent surgery for OSA. Mean age (7.2 ± 4.3 vs 7.3 ± 4.4 years, P = .955) and gender distribution (38% female vs 50% male; P = .323) were similar for the OSA and RT groups. However, children with OSA were more likely to be black (60% vs 33%) than RT patients (P = .026). Overall, the preoperative BMI z-score increased from 0.98 ± 1.50 to 1.21 ± 1.25 (P = .0009) with no difference by surgical indication (P = .58). Multiple linear regression analysis demonstrated that only age was significantly, and negatively, associated with changes in BMI z-scores (P = .015). Similar to previous studies, children had weight gain after TA. In this analysis, younger age (≤ 6 years) was a significant predictor of postoperative weight gain. Future research should prospectively evaluate the association between weight gain and demographic factors in children undergoing TA, with special attention to the relationship with age.

Weight Gain Post‐tonsillectomy More Common in Young Children

Objective: Adenotonsillectomy (TA), performed for either obstructive sleep apnea (OSA) or recurrent tonsillitis (RT), has been associated with significant weight gain after surgery. The objective of this study was to look at a large population of children undergoing TA and the demographic factors which may contribute to weight gain. Method: Retrospective chart review of children undergoing TA at an urban tertiary-academic center between 2008 and 2011. Demographic data (including age, gender, and race), OSA disease severity, pre- and 6-month postoperative normalized body mass index (z scores), and changes in were compared. Results: One hundred fifteen children had complete data after TA; 85 of whom underwent surgery for OSA. There were no significant differences between OSA and RT patients in mean age (7.2 ± 4.3 vs 7.3 ± 4.4 years, P = .955) or gender (38% female vs 50%; P = .323). However, the OSA patients were more likely to be black (60% vs 33%) than RT patients ( P = .026). Overall, the preoperative BMI z scores increased from 0.98 ± 1.50 to 1.21 ± 1.25 ( P = .0009) with no significant difference by surgical indication ( P = .58). Multiple linear regression analysis found that only age was significantly, and negatively, associated with changes in BMI z scores ( P = .015). Conclusion: Similar to previous studies, children had significant weight gain after TA. This analysis suggests that younger age is a significant predictor of weight gain after surgery. Further investigation of the relationship between weight gain and demographic factors would benefit from prospective evaluation with special attention to the relationship with age.

Role of leptin as antioxidant in obstructive sleep apnea: an in vitro study using electron paramagnetic resonance method

As in obstructive sleep apnea (OSA), the chronic cycles of hypoxia and reoxygenation are thought to be conducive of oxidative stress (OS) with generation of reactive oxygen species, identifying effective mechanisms of protection against oxidant-mediated tissue damage becomes of outmost importance. Leptin's role had been recently extended into that of participant to OS; while its exact role in this process is yet to be defined, elevated leptin levels correlate significantly with several indices of OSA disease severity such as nocturnal hypoxemia, possibly acting as a counteractive mechanism against the chronic intermittent hypoxia-related OS and serving as a marker of future risk of atherosclerotic disease. We therefore investigated leptin's antioxidant mechanism on superoxide (O (2) (-•) ) anions using spectrophotometry and electron paramagnetic resonance (EPR). The O (2) (-•) was generated by oxidation of xanthine (XAN) by xanthine oxidase (XO) in the presence of spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide with various concentrations of leptin (0.001, 0.01, 0.1, and 1 mg/ml) and without leptin. Signal intensity between 3,440 and 3,540 G was expressed as standard means ± SD. The activity of leptin on XO was determined by monitoring the conversion of XAN to uric acid at 293 nm using a Beckman DU 800 UV-visible spectrophotometer. Leptin added to aqueous solutions at 0.1 and 1 mg/ml concentrations was associated with a statistically significant decrease in the EPR signal due to leptin's direct scavenging activity towards the O (2) (-•) . Leptin is an antioxidant agent of possible use as a marker of OS and future risk of atherosclerotic disease in OSA.

Fatigue in sleep apnea: The role of depressive symptoms and self-reported sleep quality

OBJECTIVES OR BACKGROUND: Obstructive Sleep Apnea (OSA) is characterized by partial or complete cessation of breath during sleep. OSA is associated with increased cardiovascular risk as well as psychosocial complications such as daytime somnolence, depression, and fatigue. The goal of the present study was to better understand fatigue in OSA by examining self-reported sleep quality, depressive symptoms, excessive daytime sleepiness, and OSA severity in a group of newly diagnosed OSA patients. Two hundred and forty newly diagnosed OSA patients enrolled in the study. Participants completed several questionnaires at baseline. Depressive symptoms accounted for 15% of variance in fatigue beyond that of demographics and OSA severity (p<0.001). Self-reported sleep quality accounted for 11% of variance beyond that of depressive symptoms (p<0.001). The total model accounted for 48% of the variance in fatigue. Post hoc analysis found that the total model accounted for only 14% of the variance in sleepiness (as measured by the Epworth Sleepiness Scale). The current study confirms the findings of previous OSA studies, which found depressive symptoms have a greater association with fatigue than OSA disease severity variables. This study extends those findings by showing that self-reported sleep quality is independently associated with fatigue, even after taking into account demographic, comorbid conditions, OSA disease severity, sleepiness, and depressive symptoms. The role of sleep quality as an independent contributor to daytime fatigue in OSA may be under appreciated. Sleep quality should be closely followed in the clinical management of OSA.

Depression, sleepiness, and disease severity in patients with obstructive sleep apnea

To determine if a relationship exists between depression, disease severity, and sleepiness in patients with obstructive sleep apnea (OSA). Case control study. Fifty-three consecutive patients with suspected OSA were evaluated before treatment and compared with controls by using the Beck Depression Inventory (BDI), Epworth Sleepiness Scale (ESS), and polysomnography. OSA was associated with an increased risk of depression in the study group compared to the control group (odds ratio = 6.3, 95% confidence interval: 1.9-20.6, P = .002); depression was seen in 35% of OSA patients and 8% of controls (P < .001). There was a significant correlation between BDI and ESS scores (r = 0.342, P = .012). In addition, ESS was significantly associated (P = .039) with depression in a linear regression model that controlled for race, sex, age, and respiratory disturbance index (RDI). RDI and depression were weakly associated (P = .056) in this model, and there was no correlation found between BDI scores and OSA disease severity (RDI)(r = 0.446). Patients with OSA and daytime sleepiness are more likely to have depressive symptoms as compared with controls. OSA disease severity, as measured with the RDI score, is a weak predictor of BDI score, and no correlation was seen between the severity of OSA and BDI scores after controlling for other factors. However, there was a strong correlation between sleepiness (ESS) and disease severity (BDI). These data suggest that OSA patients with symptoms of excessive sleepiness have the highest risk of associated depressive symptoms and may benefit most from depression screening.

Neural Activation Patterns During Working Memory Tasks and OSA Disease Severity: Preliminary Findings

Obstructive sleep apnea (OSA) is associated with cognitive impairments in working memory (WM). Neuronal activation during WM tasks can be indirectly assessed by blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). The purpose of this study was to describe BOLD-fMRI responses during 2 separate working memory tasks and a finger tapping task in men with OSA. A secondary aim was to explore the possible relation between OSA severity (apnea/hypopnea index) and BOLD-fMRI signal patterns. Nine treatment-naïve men (mean age [+/- SD] of 45.7 [+/- 6.6] years) with OSA underwent BOLD fMRI testing on a research-dedicated university-based MRI scanner. During BOLD-fMRI subjects performed a Paced Auditory Serial Addition task (PASAT), an auditory N-Back task (2-BACK) task, and an alternating finger tapping. PASAT and 2-BACK tasks produced similar patterns of increased bilateral activation in posterior parietal, prefrontal and cerebellar regions. BOLD signal deactivations were observed within posterior cingulate, retrosplenial and inferior frontal regions during PASAT and 2-BACK, but not during tapping. With increased disease severity, BOLD activation patterns were increased in the right parietal lobe, but decreased in the cerebellar vermis. These preliminary findings suggest that the severity of OSA may correlate with neural activation during tasks of working memory, potentially reflecting compensatory neural responses in severe disease.

Quality Adjusted Life Years Added by Treatment of Obstructive Sleep Apnea

We assessed the impact of treatment with nasal continuous positive airway pressure (nCPAP) on the quality of life of 19 patients with obstructive sleep apnea (OSA). We measured the utility for the patients' health states before and with treatment using the standard gamble approach. The study group had an average age of 57 years and had been on treatment for a mean of 9.5 months. For all the patients, the polysomnographic indicators of OSA disease severity improved markedly with treatment. For nine of the 12 symptoms most commonly associated with OSA, the patients reported improvement during treatment. The mean utility and the standard deviation obtained with the standard gamble method were 0.87 +/- 0.17 on treatment and 0.63 +/- 0.29 pretreatment. The difference in utility between treatment and pretreatment health states was combined with the life expectancy of each patient to generate the number of quality adjusted life years (QALYs) considered equivalent to the impact of treatment. This resulted in an average gain of 5.4 QALYs. When we related this impact to the cost of treatment, we obtained a cost-utility ratio between Can $3,397 and Can $9,792 per QALY added. These costs are relatively small when compared to the cost per QALY for many other clinical interventions. Hence, nCPAP clearly offers the prospect for a well-tolerated therapy with a very favorable cost-utility ratio.