Obstructive sleep apnea (OSA) in children is associated with obesity, insulin resistance, and elevated baseline inflammation as measured by high-sensitivity C-reactive protein (hsCRP). Our goal was to evaluate whether inflammation increases overnight among children suspected of having OSA and to determine whether worsened inflammation is associated with the degree of OSA severity, obesity, and/or insulin resistance.
Twenty-three children with clinical suspicion of OSA underwent a sleep study. Levels of hsCRP were tested the evening before and morning after the sleep study. Fasting insulin and glucose levels were measured from which the homeostasis model of insulin resistance (HOMA-IR) was calculated. Linear correlations were performed to evaluate relationships between hsCRP levels at baseline and change overnight (ΔhsCRP) vs. HOMA-IR, body mass index (BMI) z-score, and sleep study parameters related to O2 saturation and the apnea-hypopnea index (AHI).
Among children with OSA and the entire cohort, hsCRP values were correlated with HOMA-IR and BMI z-scores. HOMA-IR but not BMI z-score correlated with ΔhsCRP overnight in the entire cohort. Sleep study parameters, including AHI mean O2 saturation overnight, REM O2 nadir, and non-REM O2 nadir were not correlated with hsCRP or ΔhsCRP overnight.
Among children being evaluated for OSA, degree of insulin resistance may be an important determinant of increased systemic inflammation overnight. Sleep study markers did not correlate with ΔhsCRP, leaving uncertain the role of OSA in increasing inflammation overnight. Further studies are needed to explore these associations and their potential mechanisms.
Obstructive sleep apnea; Inflammation; hsCRP; Obesity; Insulin resistance; Oxygen desaturation; Adolescents
The aim of our study is to determine the association between the pulsatility index (PI), a surrogate of cerebral small vessel disease and sleep-disordered breathing (SDB).
We conducted a transcranial Doppler ultrasound (TCD) study of 19 consecutive patients free of stroke and cardiovascular disease, referred for the evaluation of SDB. TCD was performed by a certified technologist. Subsequent polysomnography was performed according to the practice parameters of the American Academy of Sleep Medicine. We evaluated the association between the apnea–hypopnea index (AHI), the oxygen nadir, the blood flow velocities, and the Gosling PI, for the middle cerebral artery. We performed Spearman’s rank correlation and nonparametric regression to evaluate the relationship between AHI, oxygen levels, and the PI.
Median age was 48 years (range 37–83), with 52 % male sex (n=10), and median BMI of 29.9 (range 25–40.4). The median AHI was 16.4 (0.2–69). The median PI was 0.97 (0.72–1.89) cm/s. The PI correlated with the AHI (rho=0.44; p=0.004) and with age (rho=0.57; p=0.001). Nonparametric regression adjusting for age showed a positive association between the AHI and the PI (standardized estimate=0.88; p=0.002). There was no relation between the oxygen nadir and the PI.
We observed increased PI in patients with SDB during wakefulness. The PI could potentially be an estimate of cerebral small vessel disease in patients with SDB and hence allow evaluating cerebral hemodynamics during wakefulness with a clinically relevant device.
Transcranial Doppler; Sleep-disordered breathing; Pulsatility index; Stroke; Microvascular disease
Obstructive sleep apnea (OSA) is an increasingly common sleep disorder, especially among obese adults. Early identification of adults at risk for OSA would be of substantial benefit; however the magnitude of the obesity epidemic requires that screening be performed judiciously. The study's aim was to utilize questionnaires that assess OSA risk and symptoms to test the hypothesis that the most insulin-resistant subset of obese individuals is at highest risk for OSA.
Non-diabetic, overweight-to-obese volunteers underwent direct quantification of insulin sensitivity by measuring steady-state plasma glucose concentrations during the insulin suppression test. Insulin-sensitive and insulin-resistant individuals were administered the Berlin and STOP questionnaires to determine OSA risk status, and Epworth Sleepiness Scale (ESS) to evaluate daytime sleepiness. Fasting insulin and lipid/lipoprotein measurements were performed.
Insulin-mediated glucose disposal differed 3-fold (p<0.001) between equally obese, insulin-resistant (n=22) and insulin-sensitive (n=14) individuals, associated with higher fasting insulin and triglyceride and lower high-density lipoprotein cholesterol (HDL-C) concentrations in insulin-resistant individuals. Fourteen (64%) insulin-resistant as compared with 2 (14%) insulin-sensitive individuals were found to be at high risk for OSA by both questionnaires (p<0.01). Whereas half of insulin-resistant individuals met ESS criteria for excessive daytime sleepiness, only 1 insulin-sensitive individual did (p=0.011).
High risk for OSA and excessive daytime sleepiness is prevalent amongst the insulin-resistant subgroup of obese individuals. Surrogate estimates of insulin resistance based on fasting insulin, triglycerides, and/or HDL-C can be used to help identify those obese adults who would benefit most from OSA screening and referral for polysomnography.
obesity; sleep questionnaires; obstructive sleep apnea; daytime sleepiness; insulin-resistant
The effect of sleep quality on asthma control independent from common comorbidities like gastroesophageal reflux disease (GERD) and obstructive sleep apnea (OSA) is unknown. This study examined the association between sleep quality and asthma control and quality of life after accounting for OSA and GERD in non-severe (NSA) and severe (SA) asthma.
Cross-sectional data from 60 normal controls, 143 with NSA, and 79 with SA participating in the Severe Asthma Research Program was examined. Those who reported using positive airway pressure therapy or were at high risk for OSA were excluded.
Both SA and NSA had poorer sleep quality than controls, with SA reporting the worst sleep quality. All asthmatics with GERD and 92% of those without GERD had poor sleep quality (p =.02). The majority (88%–100%) of NSA and SA participants who did not report nighttime asthma disturbances still reported having poor sleep quality. In both NSA and SA, poor sleep quality was associated with worse asthma control and quality of life after controlling for GERD and other covariates.
These results suggest that poor sleep quality is associated with poor asthma control and quality of life among asthmatics and cannot be explained by comorbid GERD and nighttime asthma disturbances.
Asthma control; Gastroesphogeal reflux disease; Sleep
Few studies have evaluated the relationship between sleep architecture and BMI, nutrition, and physical activity in children. This study determined the relationship between sleep architecture and diet and exercise.
319 Caucasian and Hispanic children aged 10 to 17 years participated in the follow up assessment of the Tucson Children’s Assessment of Sleep Apnea (TuCASA) study. The children and parents completed several questionnaires on dietary habits, amount of physical activity, and sleep habits. Subjects also underwent a home polysomnogram (PSG) to characterize their sleep.
Significant bivariate correlations were noted between Stage II sleep percentage and the following: BMI (r=.246, p<.01), estimated total recreational energy expenditure (r=.205, p<.01), vigorous activity (r=.130, p=.009), and total estimated activity (r=.148, p=0.009). In girls, significant correlations were noted between Stage II percentage sleep and BMI score (r=.279, p<.01). Also in girls, significant negative correlation was noted between REM sleep percentage and total fat intake (r=-.168, p=.039). In boys, significant correlations were again seen between Stage II percentage sleep and the following: BMI score (r=.218, p=.005), estimated total recreational energy expenditure (r=.265, p=.001), vigorous activity (r=.209, p=.008), and total estimated activity (r=.206, p=0.010). When controlling for BMI percentile and age, significant bivariate correlation was also noted between REM sleep percentage and total fat intake (r=.176, p=.034) in boys.
BMI and exercise were associated with increases in Stage II sleep. In girls, total fat intake was associated with a reduction in REM sleep, while in boys (after controlling for BMI percentile and age) total fat intake correlated with REM sleep.
Sleep architecture; BMI; exercise; children; nutrition; Stage II sleep
A high level of endogenous erythropoietin (EPO) may be associated with a smaller infarct size determined by the release of necrosis markers. Sleep-disordered breathing (SDB) is a well-known risk factor for cardiovascular diseases. In contrast, protective effects of SDB have also been described. The potential role of increased levels of EPO and vascular endothelial growth factor (VEGF) is suggested in this process. The study aimed to explore the EPO and VEGF serum levels in SDB and non-SDB patients during the acute phase of myocardial infarction.
Thirty-seven patients undergoing successful primary percutaneous coronary intervention in the acute myocardial infarction have been examined for the levels of EPO, VEGF, and troponin I (Tn). In the following, patients had an overnight polysomnography to determine breathing disturbances during sleep.
Both on admission day (day 1) and day 3 of hospitalization, EPO levels showed statistically significant differences in both SDB-positive and SDB-negative patient groups (p = 0.003 and p = 0.018, respectively). There was no statistically significant difference in VEGF levels. No correlation was found between the EPO and Tn levels.
SDB patients tend to have higher levels of EPO during acute myocardial infarction. No statistically significant differences in VEGF levels were observed.
Erythropoietin; Myocardial infarction; Polysomnography; Sleep-disordered breathing
Obstructive sleep apnea (OSA) is independently associated with endothelial dysfunction, which may be perpetuated by alteration in endothelial repair capacity. Our study evaluates changes in endothelial progenitor cell (EPC) profile in relation to OSA and the role of advanced glycation end-products (AGE) in this relationship.
Consecutive Chinese adults undergoing sleep studies, who had no medical illnesses or regular medications, were enrolled. Subjects with morbid obesity or grossly elevated lipoprotein levels were excluded from analysis. Circulating EPC was measured with flow cytometry analysis.
Seventy-two subjects, 64 % with OSA defined by apnea–hypopnea index (AHI) ≥ 5, were analyzed. CD34+ cell counts were positively correlated with oxygen desaturation index (ODI) (r = 0.250, p = 0.041) and duration of oxygen desaturation <90 % (T90) (r = 0.261, p = 0.033) and negatively with minimal oxygen saturation (r = −0.247, p = 0.044) after adjusting for age, glucose, body weight, and smoking status. AGE was positively correlated with indices of OSA severity (AHI, r = 0.249, p = 0.042; ODI, r = 0.244, p = 0.047; T90, r = 0.243, p = 0.047; minimal oxygen saturation, r = −0.251, p = 0.041) and negatively with CD133+ cells (r = −0.281, p = 0.021). On stepwise multiple linear regression analysis, minimal oxygen saturation (p = 0.013) and CD133+ cell counts (p = 0.029) were found to be significant determinants of AGE level (R2 = 0.147).
Nocturnal hypoxemia in OSA subjects was associated with increase in endothelial cells (CD34+) which may promote vascular repair. Accumulation of AGE in OSA may lead to diminution in early EPC (CD133+) and endothelial repair capacity over time, thus contributing to vascular pathogenesis.
Advanced glycation end-products; Endothelial progenitor cells; Intermittent hypoxia
Classically, professional assessment of sleep is done in the sleep laboratory using whole-night polysomnography (PSG). However, given a misbalance between accredited sleep laboratories and the large amount of patients suffering from sleep disorders, only few receive appropriate diagnostic assessment. Recently, some low-cost home sleep scoring systems have been proposed, yet such systems are rarely tested scientifically. The aim of the present study was to evaluate the staging accuracy of the home sleep scoring system Zeo (Newton, MA, USA).
A final sample of 21 nights from ten subjects (aged 23–45) was digitally recorded with PSG as well as with the Zeo system. We compared scorings of Zeo (on an epoch-be-epoch basis) with the Somnolyzer 24 × 7 (an automatic staging algorithm), expert scorers as well as the freeware SleepExplorer.
It was revealed that Zeo shows moderate overall agreement as compared to our study standard Somnolyzer 24 × 7 (κ = 0.56). The most obvious performance difference between Zeo and both other scoring approaches was stage wake (sleep onset latency + wake after sleep onset). While Zeo detected only 40.8 % of the study standard wake epochs, 70.1 % were detected by the expert scorers and 83.4 % by the SleepExplorer, respectively.
Data suggest that the Zeo system produces acceptable sleep scoring for stage REM, light and deep sleep, with a specific weakness in correctly detecting waking periods.
Electronic supplementary material
The online version of this article (doi:10.1007/s11325-012-0757-4) contains supplementary material, which is available to authorized users.
Sleep staging; Wireless headband; EEG; Sleep disturbance
The objective of this study is to assess the risk of sleep-disordered breathing (SDB) in patients with Parkinson’s disease (PD) in a cross-sectional survey of PD subjects and controls in a university-based movement disorders clinic.
One hundred thirty-four consecutive PD subjects and 94 control subjects without prior diagnosis of SDB were assessed. Participants were assessed with clinical history, Unified Parkinson’s Disease Rating Scale, Geriatric Depression Scale, Berlin Questionnaire to classify SDB risk, Epworth Sleepiness Scale, Parkinson’s Disease Sleep Scale, and SF-36 to examine quality of life. The presence of risk for SDB was assessed by the Berlin Questionnaire.
High risk for SDB was apparent in 66 (49.3%) of the PD patients and 32 (34.8%) of the controls. After adjustment for age, gender, and body mass index (BMI), PD subjects in comparison to controls showed higher risk for SBD (odds ratio=2.81; 95% confidence interval, 1.36–5.82). Quality of life (physical component score) was significantly diminished in PD patients at high risk for SDB. PD severity did not correlate well with SDB risk. PD patients at high risk for SDB had higher BMIs and Epworth scores.
PD patients have features suggesting increased risk for SDB. This frequently undiagnosed sleep disorder may have a substantial impact on quality of life of PD patients.
Sleep-disordered breathing; Obstructive sleep apnea; Parkinson’s disease; Berlin questionnaire; Sleepiness; Depression; Quality of life
This prospective clinical study investigates the efficacy of a specific custom-made titratable mandibular advancement device (MAD) for the treatment of obstructive sleep apnea (OSA). This MAD has attachments in the frontal teeth area that allow for progressive titration of the mandible.
Sixty-one adult OSA patients were included (age, 46.7 ± 9.0 years; male/female ratio, 45/16; apnea–hypopnea index (AHI), 23.2 ± 15.4 events/h sleep; body mass index, 27.9 ± 4.1 kg/m²). After an adaptation period, titration started based on a protocol of symptomatic benefit or upon reaching the physiological limits of protrusion. As a primary outcome, treatment response was defined as an objective reduction in AHI following MAD treatment of ≥50 % compared to baseline, and treatment success as a reduction in AHI with MAD to less than 5 and 10 events/h sleep. Compliance failure was defined as an inability to continue treatment.
A statistically significant decrease was observed in AHI, from 23.4 ± 15.7 at baseline to 8.9 ± 8.6 events/h with MAD (p < 0.01). Treatment response was achieved in 42 out of 61 patients (68.8 %), whereas 42.6 % met criteria of AHI < 5 and 63.9 % achieved an AHI < 10 events/h sleep, respectively. Four patients (6.6 %) were considered as “compliance failures.”
The present study has evaluated the efficacy of a specific custom-made titratable MAD in terms of sleep apnea reduction.
Snoring; Sleep-disordered breathing; Daytime sleepiness; Mandibular repositioning appliance
Research during the past 10–20 years shows that positional therapy (PT) has a significant influence on the apnea–hypopnea index. These studies are predominantly performed as case series on a comparably small number of patients. Still, results have not found their way into the daily diagnostic and treatment routine. An average of 56 % of patients with obstructive sleep apnea (OSA) have position-dependent OSA (POSA), commonly defined as a difference of 50 % or more in apnea index between supine and non-supine positions. A great deal could be gained in treating patients with POSA with PT. The aim of this paper was to perform a thorough review of the literature on positional sleep apnea and its therapy.
A broad search strategy was run electronically in the MEDLINE and EMBASE databases using synonyms for position and sleep apnea.
Sixteen studies were found which examined the effect of PT on OSA. In this literature review, we discuss the various techniques, results, and compliance rates.
Long-term compliance for PT remains an issue, and although remarkable results have been shown using innovative treatment concepts for PT, there is room for both technical improvement of the devices and for further research.
Sleep apnea; Obstructive; Review; Sleeping position; Positional therapy
Sleep-disordered breathing (SDB) is associated with increased risk for cardiovascular morbidity and mortality and for sleepiness-related accidents, but >75 % of the patients remain undiagnosed. We sought to determine the diagnostic accuracy of ECG-based detection of SDB when used for population-based screening.
All male workers, mostly truck drivers, of a transport company (n = 165; age, 43 ± 12 years) underwent standard attended overnight polysomnography. Cyclic variation of heart rate (CVHR), a characteristic pattern of heart rate associated with SDB, was detected from single-lead ECG signals during the polysomnography by a newly developed automated algorithm of autocorrelated wave detection with adaptive threshold (ACAT).
Among 165 subjects, the apnea–hypopnea index (AHI) was ≥5 in 62 (38 %), ≥15 in 26 (16 %), and ≥30 in 16 (10 %). The number of CVHR per hour (CVHR index) closely correlated with AHI [r = 0.868 (95 % CI, 0.825–0.901)]. The areas under the receiver operating characteristic curves for detecting subjects with AHI ≥5, ≥15, and ≥30 were 0.796 (95 % CI, 0.727–0.855), 0.974 (0.937–0.993), and 0.997 (0.971–0.999), respectively. With a predetermined criterion of CVHR index ≥15, subjects with AHI ≥15 were identified with 88 % sensitivity and 97 % specificity (likelihood ratios for positive and negative test, 30.7 and 0.12). The classification performance was retained in subgroups of subjects with obesity, hypertension, diabetes mellitus, dyslipidemia, and decreased autonomic function.
The CVHR obtained by the ACAT algorithm may provide a useful marker for screening for moderate-to-severe SDB among apparently healthy male workers.
Apnea–hypopnea index; Cyclic variation of heart rate; Electrocardiogram; Sleep apnea; Sleep-disordered breathing; Population
Sleep-disordered breathing(SDB) may be deleterious to the cardiovascular system and other organs, including the kidney. Although older men are at increased risk for both kidney disease and SDB, it is unknown whether SDB is associated with higher urinary albumin excretion in this population.
We examined 507 community-dwelling men age ≥67 years(mean 76.0±5.3) enrolled in the MrOS Sleep study who underwent overnight polysomnography and gave a spot urine sample. SDB severity was categorized using the respiratory disturbance index and percent total sleep time <90% oxygen saturation(%time O2<90). Urinary albumin excretion was expressed using the albumin-to-creatinine ratio(ACR).
There was a graded association between respiratory disturbance index and ACR (age and race-adjusted mean ACR=9.35 mg/gCr for respiratory disturbance index≥30 versus 6.72 mg/gCr for respiratory disturbance index<5, p=0.007). This association was attenuated after further adjustment for body mass index(BMI), hypertension and diabetes and no longer reached significance(p=0.129). However, even after adjustment for age, race, BMI, hypertension and diabetes, greater %time O2<90 was associated with higher ACR(10.35 mg/gCr for ≥10%time O2<90 versus 7.45 mg/gCr for <1%time O2<90, p=0.046).
SDB, measured by elevated respiratory disturbance index or nocturnal hypoxemia, was associated with higher ACR. The relationship between respiratory disturbance index and ACR was partially explained by higher BMI and greater prevalence of hypertension and diabetes among men with SDB. However, greater nocturnal hypoxemia was independently associated with higher ACR, suggesting that the hypoxia component of SDB may mediate any detrimental effect of SDB on the kidney.
Albuminuria; sleep-disordered breathing; chronic kidney disease; nocturnal hypoxemia
Previous studies have shown that routine heated humidifier (HH) do not provide any benefit during continuous positive airway pressure (CPAP) titration if there are no significant naso-pharyngeal symptoms. In clinical practice, nasal diseases and upper airway symptoms are very common. This study investigates the effects of HH during CPAP titration in subjects with or without naso-pharyngeal symptoms.
Fifty-two patients who received polysomnography with CPAP titration were randomly assigned to HH and non-HH groups. Their nasal cavity, pharynx, and naso-pharynx were evaluated before CPAP titration, and a questionnaire on subjective sensation, including naso-pharyngeal symptoms, willingness to further use CPAP, and sleep improvement, was used. Objective (e.g., leak, apnea–hypopnea index (AHI) reduction, and optimal CPAP pressure level) and subjective data were analyzed between the two groups.
In subjective sensation, the HH group did not have any benefit in further willingness to use CPAP and in sleep improvement, but had improved naso-pharyngeal symptoms (p = 0.043). There were no significant differences in leak, AHI reduction, and optimal CPAP pressure, even in patients with significant naso-pharyngeal symptoms.
Routine use of HH is not necessary during CPAP titration regardless of naso-pharyngeal symptoms.
Continuous positive airway pressure (CPAP) titration; Humidifier; Obstructive sleep apnea–hypopnea syndrome
Despite the efficacy of continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnea (OSA), compliance with therapy remains suboptimal. The aim of this study was to determine whether the use of S9TM increased compliance in established CPAP users.
Subjects with OSA (50) were recruited into the study. When subjects entered the study, 28 days of respective compliance data were downloaded from the patient's usual CPAP device. Subjects trialled the S9 CPAP for 28 days. Subjects then resumed use of their usual CPAP for 28 days. Compliance data from the patient's usual CPAP pre- and post-trialling S9 were compared with data from the S9 CPAP.
Patients were significantly more compliant when using the S9 than their usual CPAP device both pre- and post-S9 based on average daily usage. CPAP pre-S9 = 6.58 ± 1.95 (mean hours ± SD), S9 = 7.08 ± 1.18 h and CPAP post-S9 = 6.71 ± 1.72 h. The difference between CPAP pre-S9 and S9 was 0.5 h (p = 0.003). The difference between S9 and CPAP post-S9 was 0.35 h (p = 0.01). There was no significant difference between CPAP pre-S9 and CPAP post-S9 (p = 0.34). Patients also completed questionnaires comparing the S9 system to their usual device. Subjective feedback showed a strong preference for the S9.
Participants were significantly more compliant when using the S9 than their usual CPAP device both pre- and post-S9 use.
Obstructive sleep apnea; Continuous positive airway pressure; Treatment compliance; Adherence
The aim of this study was to compare the sensitivity and specificity of two questionnaires to identify patients with obstructive sleep apnea (OSA).
Materials and methods
Fifty-three moderate to severe OSA patients [with a respiratory disturbance index (RDI)≥15] and 31 controls (RDI<15) based on ambulatory somnographic assessment were recruited through flyers and mail at USC School of Dentistry. Each patient answered the Berlin and apnea risk evaluation system (ARES) questionnaires. The responses to the questionnaires were scored and compared for significant group differences.
Moderate and severe OSA patients were predominantly male, older, had a larger neck size, and larger body mass index than controls. There were no significant differences in race or ethnicity between the two groups. In this study, subjects having a “high risk” ARES questionnaire were 7.9 times as likely to have OSA as subjects with “low or no risk” score (p=0.0002). The ARES questionnaire had a sensitivity of 90.6%, specificity of 43.2%, a positive predictive value (PPV) of 73.8%, and negative predictive value (NPV) of 73.7% compared to 67.9%, 54.8%, 72%, and 50%, respectively, for the Berlin questionnaire using a cut point of RDI≥15.
In this specific patient group, not uncommon to the regular dental private practice, the ARES questionnaire performed better than the Berlin questionnaire with higher sensitivity, similar PPV, higher NPV, but lower specificity. The lower specificity could be explained in part because the ARES has been tailored to screen patients with an RDI≥5, and our study included mostly mild to severe patients. In conclusion, in this specific group of subjects, the ARES questionnaire is a better choice than the Berlin questionaire; however, the Berlin questionnaire is publicly available and the ARES screener is proprietary.
Obstructive sleep apnea; Screening; Berlin questionnaire; ARES questionnaire
Cells sense oxygen availability using not only the absolute value for cellular oxygen in regard to its energetic and metabolic functions, but also the gradient from the cell surface to the lowest levels in the mitochondria. Signals are used for regulatory purposes locally as well as in the generation of cellular, tissue, and humoral remodeling. Lowered oxygen availability (hypoxia) is theoretically important in the consideration of pharmacology because (1) hypoxia can alter cellular function and thereby the therapeutic effectiveness of the agent, (2) therapeutic agents may potentiate or protect against hypoxia-induced pathology, (3) hypoxic conditions may potentiate or mitigate drug-induced toxicity, (4) hypoxia may alter drug metabolism and thereby therapeutic effectiveness, and (5) therapeutic agents might alter the relative coupling of blood flow and energy metabolism in an organ. The prototypic biochemical effect of hypoxia is related to its known role as a cofactor in a number of enzymatic reactions, e.g., oxidases and oxygenases, which are affected independently from the bioenergetic effect of low oxygen on energetic functions. The cytochrome P-450 family of enzymes is another example. Here, there is a direct effect of oxygen availability on the conformation of the enzyme, thereby altering the metabolism of drug substrates. Indirectly, the NADH/NAD+ ratio is increased with 10% inspired oxygen, leading not only to reduced oxidation of ethanol but also to reduction of azo- and nitro-compounds to amines and disulfides to sulfhydryls. With chronic hypoxia, many of these processes are reversed, suggesting that hypoxia induces the drug-metabolizing systems. Support for this comes from observations that hypoxia can induce the hypoxic inducible factors which in turn alters transcription and function of some but not all cytochrome P-450 isoforms. Hypoxia is identified as a cofactor in cancer expression and metastatic potential. Thus, the effects of hypoxia play an important role in pharmacology, and the signaling pathways that are affected by hypoxia could become new targets for novel therapy or avenues for prevention.
Drug metabolism; Hypoxia; Cytochrome c; Hypoxic response elements; Pharmacology
The narrowest area of the airway between the posterior nasal opening and the epiglottis is usually located in the retro palatal area. Many consider this the most likely site of airway obstruction during an obstructive sleep apnea (OSA) event. The aim of this study was to investigate the differences in soft palate and airway length between OSA and non-OSA patients.
In this study, we analyzed the ratio of the soft palate and the upper airway length in 45 consecutive patients. Twenty-five had an Apnea–Hypoapnea Index of more than five events per hour and were classified in the OSA group (male, 19; female, 6). These patients were compared with 20 normal controls (male, 12; female, 8). Controls who complained of snoring did have sleep studies (n=5). The other fifteen controls were clinically asymptomatic and did not have sleep studies. Medical computed tomography scans were taken to determine the length of the upper airway and the soft palate length measured in the midsagittal image.
Soft palate length was significantly larger in OSA patients compared to controls (p=0.009), and in men compared to women (p=0.002). However, there were no differences in airway length. The soft palate length, as a percent of oropharyngeal airway length, was significantly larger in OSA patients compared to controls (p=<0.0001) and in men compared to women (p=0.02). Soft palate length increases significantly with age by 0.3 mm per year in males (after adjustment for body mass index (BMI) and OSA). Soft palate length as a percent of airway length is larger in OSA patients and increases significantly with BMI in males only after adjusting for age.
In this study, OSA patients had a longer soft palate in proportion to their oropharyngeal airway compared to controls as well as men compared to women. This proportion could be used for identifying patients at risk for OSA in combination with age.
Soft palate length; Oropharyngeal airway; Obstructive sleep apnea; Computerized tomography
Stable severe chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure treated by nocturnal bi-level positive pressure non-invasive ventilation (NIV) may experience severe morning deventilation dyspnea. We hypothesised that in these patients, progressive hyperinflation, resulting from inappropriate ventilator settings, leads to patient–ventilator asynchrony (PVA) with a high rate of unrewarded inspiratory efforts and morning discomfort.
Polysomnography (PSG), diaphragm electromyogram and transcutaneous capnography (PtcCO2) under NIV during two consecutive nights using baseline ventilator settings on the first night, then, during the second night, adjustment of ventilator parameters under PSG with assessment of impact of settings changes on sleep, patient–ventilator synchronisation, morning arterial blood gases and morning dyspnea.
Eight patients (61 ± 8 years, FEV1 30 ± 8% predicted, residual volume 210 ± 30% predicted) were included. In all patients, pressure support was decreased during setting adjustments, as well as tidal volume, while respiratory rate increased without any deleterious effect on nocturnal PtcCO2 or morning PaCO2. PVA index, initially high (40 ± 30%) during the baseline night, decreased significantly after adjusting ventilator settings (p = 0.0009), as well as subjective perception of PVA leaks, and morning dyspnea while quality of sleep improved.
The subgroup of COPD patients treated by home NIV, who present marked deventilation dyspnea and unrewarded efforts may benefit from adjustment of ventilator settings under PSG or polygraphy.
Non-invasive ventilation; COPD; Patient–ventilator asynchrony
Obstructive sleep apnea (OSA) can have adverse effects on cognitive functioning, mood, and cardiovascular functioning. OSA brings with it disturbances in sleep architecture, oxygenation, sympathetic nervous system function, and inflammatory processes. It is not clear which of these mechanisms is linked to the decrease in cognitive functioning. This study examined the effect of inflammatory parameters on cognitive dysfunction.
Materials and methods
Thirty-nine patients with untreated sleep apnea were evaluated by polysomnography and completed a battery of neuropsychological tests. After the first night of evaluation in the sleep laboratory, blood samples were taken for analysis of interleukin 6, tumor necrosis factor-α (TNF-α), and soluble TNF receptor 1 (sTNF-R1).
sTNF-R1 significantly correlated with cognitive dysfunction. In hierarchical linear regression analysis, measures of obstructive sleep apnea severity explained 5.5% of the variance in cognitive dysfunction (n.s.). After including sTNF-R1, percentage of variance explained by the full model increased more than threefold to 19.6% (F= 2.84, df=3, 36, p=0.05). Only sTNF-R1 had a significant individual relationship with cognitive dysfunction (β=0.376 t=2.48, p=0.02).
sTNF-R1 as a marker of chronic inflammation may be associated with diminished neuropsychological functioning in patients with OSA.
Obstructive sleep apnea; Cognitive dysfunction; Cytokine; IL-6; TNF-α; sTNF-R1
The carotid body functions as a chemoreceptor. We hypothesized that head-and-neck paragangliomas (HNP) may disturb the function of these peripheral chemoreceptors and play a role in sleep-disordered breathing.
This is a case–control study.
This study was conducted in a tertiary referral center.
Participants and main outcome measures
We assessed fatigue, sleep, and exercise capacity in 74 HNP patients using three questionnaires (Epworth Sleepiness Scale, St. George Respiratory Questionnaire, and a standard clinical sleep assessment questionnaire). Outcomes were compared to those of age- and sex-matched controls.
Results and conclusions
Activity, disturbance of psychosocial function, and total score were worse compared to controls (15.4 ± 18.5 vs. 7.2 ± 9.9, P = 0.007; 5.3 ± 10.5 vs. 1.2 ± 2.6, P = 0.008; and 10.4 ± 12.9 vs. 5.0 ± 4.8, P = 0.006, respectively). Patients reported more daytime fatigue, concentration difficulties, and depression (51% vs. 24%, P = 0.006; 31% vs. 10%, P = 0.010; and 19% vs. 2%, P = 0.012). Waking up was reported to be less refreshing in HNP patients (53% vs. 73%, P = 0.038). Dysphonia was a predictor of symptoms, activity, disturbance of psychosocial function, and total scores. Remarkably, the presence of a carotid body tumor was an independent predictor of increased daytime sleepiness (β = 0.287, P = 0.029). In conclusion, patients with HNP have remarkable sleep-related complaints. Especially the presence of carotid body tumors appears to be associated with increased daytime somnolence.
Paraganglioma; Glomus tumors; Carotid body tumor; Sleep; SDHD mutation
Medical school surveys of pre-doctoral curriculum hours in the somnology, the study of sleep, and its application in sleep medicine/sleep disorders (SM) show slow progress. Limited information is available regarding dentist training. This study assessed current pre-doctoral dental education in the field of somnology with the hypothesis that increased curriculum hours are being devoted to SM but that competencies are still lacking.
Materials and methods
The 58 US dental schools were surveyed for curriculum offered in SM in the 2008/2009 academic year using an eight-topic, 52-item questionnaire mailed to the deans. Two new dental schools with interim accreditation had not graduated a class and were not included. Responses were received from 49 of 56 (87.5%) of the remaining schools.
Results and Conclusions
Results showed 75.5% of responding US dental schools reported some teaching time in SM in their pre-doctoral dental program with curriculum hours ranging from 0 to 15 h: 12 schools spent 0 h (24.5%), 26 schools 1–3 h, 5 schools 4–6 h, 3 schools 7–10 h, and 3 schools >10 h. The average number of educational hours was 3.92 h for the schools with curriculum time in SM, (2.96 across all 49 responding schools). The most frequently covered topics included sleep-related breathing disorders (32 schools) and sleep bruxism (31 schools). Although 3.92 h is an improvement from the mean 2.5 h last reported, the absolute number of curriculum hours given the epidemic scope of sleep problems still appears insufficient in most schools to achieve any competency in screening for SRBD, or sufficient foundation for future involvement in treatment.
Dental school somnology education; Teaching sleep medicine; Competency; Sleep bruxism; Sleep-related breathing disorder; Oral appliance therapy
Cognitive functions in community-dwelling adults at high risk of obstructive sleep apnea have not been described and nor are associations between cognitive functions and obstructive sleep apnea severity fully understood. The study aimed to describe verbal memory and executive function in community-dwelling adults identified by the Berlin Questionnaire and to investigate associations between these cognitive domains and different obstructive sleep apnea severity indicators.
Among 29,258 age- and gender-stratified persons 30–65 years who received the Berlin Questionnaire by mail, 16,302 (55.7%) responded. From 654 randomly drawn respondents with BQ high risk who were approached for study participation, 290 participants (55.9% males, mean age 48.2 years) were included. Verbal memory was assessed by Rey Auditory Verbal Learning Test and executive function by Stroop test. Obstructive sleep apnea severity indicators were assessed by polysomnography.
Mean (standard deviation) verbal learning score was 42.0 (8.9), mean interference time was 31.1 (12.7), median (25th percentile, 75th percentile) apnea–hypopnea index was 7.7 (2.4–22.2), and mean average oxygen saturation was 94.3 (2.0). Verbal learning score was independently associated with average oxygen saturation (β = 0.721, p = 0.025) in multivariate linear regression models adjusted for putative confounders. Interference time was only related to OSA severity indicators in bivariate analyses.
Verbal memory and executive function impairments were mild in community-dwelling adults at high risk of obstructive sleep apnea. Average oxygen saturation was the indicator of obstructive sleep apnea severity most strongly associated with cognitive function.
Electronic supplementary material
The online version of this article (doi:10.1007/s11325-011-0493-1) contains supplementary material, which is available to authorized users.
Neurobehavioural manifestations; Polysomnography; Epidemiology; Sleep apnea syndromes; Sleep disordered breathing