Proton magnetic resonance spectroscopy study of brain metabolism in obstructive sleep apnoea syndrome before and after continuous positive airway pressure treatment

STUDY OBJECTIVES: Obstructive sleep apnoea syndrome (OSAS) causes sleep related oxygen desaturation, excessive daytime sleepiness (EDS), and cognitive impairment. The role of hypoxic brain damage, sleep fragmentation, and the associated comorbidities (hypertension, vascular disorders) in the pathogenesis of cognitive deficits remains controversial. The aim of this study was to evaluate the cerebral metabolism of OSAS patients in vivo before and after CPAP treatment. DESIGN AND PATIENTS: Fourteen OSAS patients without cardiovascular or cerebrovascular impairment underwent the same protocol before and after 6 months of CPAP including: overnight videopolysomnography (VPSG), Multiple Sleep Latency Test (MSLT), and within the next 2 days neuropsychological and 1H-MRS evaluations. Single voxel 1H-MRS was performed in the parietal-occipital cortex, and absolute concentrations of N-acetyl-aspartate (NAA), creatine, and choline were measured, acquiring spectra at multiple echo-times and using water as internal standard. Ten matched controls were also studied. RESULTS: OSAS patients had a mean RDI of 58/hr, a mean arousal index of 57/hr, and a mean nadir SpO2 of 71%. Before CPAP, all patients showed a normal global cognitive functioning, with only a small number of pathological tasks in working memory and attention tests in a minority of patients. CPAP therapy was effective in resolving sleep apnoea and normalizing sleep structure, and improving EDS and neuropsychological alterations. Before CPAP treatment cortical [NAA] in OSAS (11.86 mM +/- 0.80, mean +/- SD) was significantly lower than in controls (12.85 +/- 0.93; P = 0.01) and positively correlated with minimum SpO2 during sleep (r = 0.69; P = 0.006) and MSLT scores (r = 0.62; P = 0.01). Cortical [NAA] reduction persisted after therapy (11.94 +/- 1.33; P = 0.87 versus pre-CPAP). CONCLUSIONS: OSAS patients have cortical metabolic changes consistent with neuronal loss even in the absence of vascular comorbidities. Metabolic changes persisted after CPAP in the absence of EDS, nocturnal arousals, and major cognitive deficits, likely related to hypoxic damage prior to CPAP treatment.     

Cerebrovascular reactivity to hypercapnia is unimpaired in breath-hold divers

Hypercapnic cerebrovascular reactivity is decreased in obstructive sleep apnoea and congestive heart disease perhaps as a result of repeated apnoeas. To test the hypothesis that repeated apnoeas blunt cerebrovascular reactivity to hypercapnia, we studied breath hold divers and determined cerebrovascular reactivity by measuring changes in middle cerebral artery velocity (MCAV, cm s⁻¹) per mmHg change in end-tidal partial pressure of CO₂ (     ) in response to two hyperoxic hypercapnia rebreathing manoeuvres (modified Read protocol) in elite breath-hold divers (BHD, n = 7) and non-divers (ND, n = 7). In addition, ventilation and central (beat-to-beat stroke volume measurement with Modelflow technique) haemodynamics were determined. Ventilatory responses to hypercapnia were blunted in BHD versus ND largely due to lower breathing frequency. Cerebrovascular reactivity did not differ between groups (3.7 ± 1.4 versus 3.4 ± 1.3% mmHg⁻¹     in BHD and ND, respectively; P = 0.90) and the same was found for cerebral vascular resistance and MCAV recovery to baseline after termination of the CO₂ challenge. Cardiovascular parameters were not changed significantly during rebreathing in either group, except for a small increase in mean arterial pressure for both groups. Our findings indicate that the regulation of the cerebral circulation in response to hypercapnia is intact in elite breath-hold divers, potentially as a protective mechanism against the chronic intermittent cerebral hypoxia and/or hypercapnia that occurs during breath-hold diving. These data also suggest that factors other than repeated apnoeas contribute to the blunting of cerebrovascular reactivity in conditions like sleep apnoea.     

Cardiovascular and cerebrovascular responses to acute hypoxia following exposure to intermittent hypoxia in healthy humans

Intermittent hypoxia (IH) is thought to be responsible for many of the long-term cardiovascular consequences associated with obstructive sleep apnoea (OSA). Experimental human models of IH can aid in investigating the pathophysiology of these cardiovascular complications. The purpose of this study was to determine the effects of IH on the cardiovascular and cerebrovascular response to acute hypoxia and hypercapnia in an experimental human model that simulates the hypoxaemia experienced by OSA patients. We exposed 10 healthy, male subjects to IH for 4 consecutive days. The IH profile involved 2 min of hypoxia (nadir     = 45.0 mmHg) alternating with 2 min of normoxia (peak     = 88.0 mmHg) for 6 h. The cerebral blood flow response and the pressor responses to hypoxia and hypercapnia were assessed after 2 days of sham exposure, after each day of IH, and 4 days following the discontinuation of IH. Nitric oxide derivatives were measured at baseline and following the last exposure to IH. After 4 days of IH, mean arterial pressure increased by 4 mmHg ( P < 0.01), nitric oxide derivatives were reduced by 55% ( P < 0.05), the pressor response to acute hypoxia increased ( P < 0.01), and the cerebral vascular resistance response to hypoxia increased ( P < 0.01). IH alters blood pressure and cerebrovascular regulation, which is likely to contribute to the pathogenesis of cardiovascular and cerebrovascular disease in patients with OSA.     

Epidemiology of snoring and obstructive sleep apnoea in a Danish population, age 30-60

SUMMARY  Several epidemiological studies have estimated the prevalence of obstructive sleep apnoea syndrome (OSAS). As many of those suffering from sleep apnoea may be asymptomatic, the occurrence of sleep apnoea may be underestimated. The epidemiology of self-reported snoring, sleep apnoea and OSAS, and their relationships with various symptoms, were evaluated in 1504 randomly selected males and females, aged 30, 40, 50 and 60 years. Nocturnal respiration was determined in 748 participants using inductive plethysmography.
Habitual snoring was reported by 19.1% (9.2–24.2%, age 30–60 years) of the males and 7.9% (3.8–11.7%, age 30–60 years) of the females. Respiratory Distress Index (RDI) was calculated as the number of apnoeas and hypopnoeas per hour lasting longer than 10s. RDI≥5 per hour was found in 10.9% (7.1–18.3%, age 30–60 years) of the males and in 6.3% (5.3–7.6%, age 30–60 years) of the females. Hypersomnia increased with the severity of sleep apnoea ( P < 0.005) and was reported by 15.9% of those with RDI≥5.
The prevalence of OSAS (hypersomnia and RDI ≥5) was 0.9% in the females, 1.9% in the males, and in total 1.4% of all aged 30–60 years. The sensitivity was 70.8% and the specificity was 47.7% for self-reported snoring predicting RDI ≥5.
The following factors were associated with RDI ≥5: age ( P <0.05), gender ( P < 0.0001), BMI ( P < 0.0001), tobacco ( P <0.02) and alcohol ( P <0.05) consumption. Snoring correlated with age ( P <0.02), gender ( P <0.001), BMI ( P <0.0001) and alcohol consumption ( P <0.05).
We conclude that sleep apnoea is common and many of those with sleep apnoea are asymptomatic. Self-reported hypersomnia and snoring are not sensitive enough alone to identify those with sleep apnoea. Sufficient control of the questionnaire is thus essential in studies on snoring and the risk of cardiovascular diseases.     

Executive functions and cognitive subprocesses in patients with obstructive sleep apnoea

In recent years, special interest has been focused on impairments of executive functions in patients with obstructive sleep apnoea syndrome (OSAS). However, the majority of studies have not clearly separated deficits in executive functions from impairments in other cognitive processes involved in task solving. In the present study, working memory (WM) functions of 20 patients with OSAS were compared with those of 10 age-, sex- and education-matched healthy subjects. Cognitive functions were measured four times a day; each of these measurements was accompanied by an assessment of subjective and objective daytime sleepiness. To separate dysfunctions of WM from those of additionally involved processes, n -back tasks were applied embedded in a reaction-time-decomposition approach. Deficits in n -back tasks could be observed in OSAS patients in accuracy and reaction times. However, the slowing could already be observed in simple reaction time tasks. The drop in 1-back accuracy in the morning was related to daytime sleepiness. During the afternoon, accuracy of OSAS patients dropped in 2-back tasks, an effect which correlated neither with sleepiness nor with the extent of sleep apnoea or oxygen desaturation. In conclusion, our data reflect a complex perspective upon cognitive deficits in OSAS. Cross-group differences in processing time on the higher level WM task appeared to be attributable to slowing at a more elementary cognitive processing level. In contrast, reduced accuracy during the WM task in the OSAS group could not be explained by deficits in more elementary cognitive processes.     

Early morning impairment in cerebral autoregulation and cerebrovascular CO2 reactivity in healthy humans: relation to endothelial function

The reduction in cerebrovascular reactivity to CO(2) and/or endothelial function that occurs in the early hours after waking are potential causes for the increased risk for cardiovascular events at this time point. It is unknown whether cerebral autoregulation is reduced in the morning. We tested the hypothesis that early morning reduction in endothelium-dependent vascular reactivity would be linked to changes in cerebrovascular reactivity to CO(2) and cerebral autoregulation (CA). Overnight changes in a dynamic cerebral autoregulation index (ARI) were determined from continuous recordings of blood flow velocity in the middle cerebral artery (MCAv) and arterial blood pressure (BP) during transiently induced hypotension in 20 individuals. Frontal cortical oxygenation (near infrared spectroscopy) and cerebral haemodynamics were also monitored during hypercapnia and before and during 3 min of active standing. Brachial artery flow-mediated endothelium-dependent vasodilatation (FMD) and endothelium-independent dilatation (NFMD) were also monitored. From evening to morning, there was a significant lowering in ARI (5.3 +/- 0.5 versus 4.7 +/- 0.6 a.u.; P < 0.05), cerebrovascular reactivity to CO(2) (5.3 +/- 0.6 versus 4.6 +/- 1.1% mmHg(-1); P < 0.05) and FMD (7.6 +/- 0.9 versus 6.0 +/- 1.4%; P < 0.05). The lowered FMD was related to the decrease in cerebrovascular reactivity to CO(2) (r = 0.76; P < 0.05). Transient reductions in morning MCAv and cortical oxyhaemoglobin concentrations were observed upon resuming a supine-to-upright position (P < 0.05 versus evening). The early morning reduction in cerebral autoregulation may facilitate the onset of cerebrovascular accidents; this may be of particular relevance to at-risk groups, especially upon resuming the upright position.     

Tongue mechanical characteristics and genioglossus muscle EMG in obstructive sleep apnoea patients

The increased genioglossus muscle (GGm) activity seen in obstructive sleep apnoea syndrome (OSAS) may lead to increased fatigability or longer recovery time of the tongue. Maximal force, endurance, and recovery times of the tongue, electromyogram (EMG) absolute value, and EMG spectral analysis of the GGm obtained during submaximal contractions were compared in eight individuals without chronic snoring and eight OSAS patients. Endurance time values were not significantly different between the two groups (P = 0.40). Time to recovery of initial maximal force was significantly greater in the OSAS group (P = 0.01). Final EMG median frequency was significantly higher (P = 0.01) and the final low-frequency EMG component smaller in the OSAS patients (P = 0.02). Patients did not have changes in endurance time or fatigability but had longer recovery times and changes in spectral analysis variations. This functional investigation may be helpful in determining the presence of OSAS and the potential contribution of the tongue to pharyngeal obstruction.     

The nocturnal secretion of cardiac natriuretic peptides during obstructive sleep apnoea and its response to therapy with nasal continuous positive airway pressure

The nocturnal secretion profile of the newly identified natriuretic peptide (NP), brain natriuretic peptide (BNP), was studied in 14 patients with obstructive sleep apnoea syndrome (OSAS) (apnoea hypopnoea index: 60.5±3.4, mean±SE) during two separate nights before and during nasal continuous positive airway pressure (NCPAP) therapy. Plasma levels of NPs (atrial natriuretic peptides; ANP and BNP) were measured at 2-h intervals during sleep. Simultaneously, blood pressure was measured by a non-invasive method (Finapres^®, Ohmeda, Englewood, CO, USA) and urine was collected for determing volume and catecholamine levels. Urinary and serum sodium concentration were determined before and after the study. Eight non-snoring subjects were also studied for the investigation of normal nocturnal profiles of BNP levels. To understand the discrete secretion profiles of the two NPs during sleep, blood was sampled from an additional seven patients every 5 min over a 30-min period around 00.00 and 04.00 hours before NCPAP. In patients with OSAS, plasma BNP levels increased from the beginning of sleep (22:00 h) to the morning (06:00 h) before NCPAP therapy (P< 0.01, anova ). Baseline BNP levels were not significantly correlated with patient's clinical and poly- somnographic parameters. However, in the latter half of the sleep period (02:00–06:00 h), increases in BNP levels during the night before NCPAP therapy were significantly correlated with blood pressure elevations (systolic: r=0.784 P< 0.01, diastolic: r=0.587 P< 0.01) and with apnoea duration (r=0.582 P< 0.01). In normal subjects BP and BNP levels were not changed significantly during sleep. Plasma BNP levels were well correlated with concomitant ANP levels (P< 0.001). NCPAP therapy reduced ANP and BNP levels during sleep and in the morning (P< 0.01). Plasma levels of BNP at 5 min intervals before NCPAP therapy revealed few variations. On the other hand, ANP levels fluctuated over the 30-min period. Changes in BNP levels during sleep in the patients with OSAS may be related to blood pressure variations, but may be too small to play a significant physiological role in regulating diuresis in OSAS. Further work is required to determine the precise role of dual natriuretic system in cardiovascular load and natriuresis in OSAS.     

Obstructive sleep apnea can be provocative for right-to-left shunting through a patent foramen ovale

STUDY OBJECTIVES: Under particular conditions, a patent foramen ovale (PFO) can potentially give rise to ischemic stroke by means of paradoxical embolization, due to right-to-left shunt. Our study aimed to evaluate the presence of right-to-left shunt in patients with obstructive sleep apnea syndrome (OSAS) and diagnosed PFO during sleep. DESIGN AND SETTING: Assessment of provocative-only PFO and concomitant OSAS. Evaluation of right-to-left shunting during sleep by means of transcranial doppler with contrast medium injected in the cubital vein. PARTICIPANTS: 10 consecutive patients affected by PFO detectable only under Valsalva maneuver during wakefulness and affected by OSAS (mean age 52.8 +/- 10.7 years). INTERVENTIONS: Patients underwent transcranial doppler with injection of agitated saline solution mixed with air during normal breathing and during periods of apnea/hypopnea in nocturnal sleep. MEASUREMENTS AND RESULTS: Right-to-left shunt was present in 9 patients out of 10 and appeared during obstructive apneas longer than 17 seconds. In 1 out of 10 patients, only hypopneas occurred and no right-to-left shunt could be shown. The number of microembolic signals detected during periods of nocturnal apnea was positively correlated with the number detected during Valsalva maneuver in wakefulness (p<0.0001). CONCLUSIONS: In the nocturnal sleep period, right-to-left shunt can occur during single obstructive apneas in patients with OSAS and concomitant presence of PFO. This can be a risk factor for cerebrovascular diseases. This risk could probably increase proportionally to the respiratory disturbance index of these patients.     

Cortico-motoneurone excitability in patients with obstructive sleep apnoea

A disordered neuromotor control of pharynx muscles may play a role in the genesis of obstructive sleep apnoea syndrome (OSAS). This raises the possibility of a dysfunction of projections descending from the cortex to segmental nuclei. With single pulse transcranial magnetic stimulation (TMS) we studied the physiology of the corticospinal projection to hand muscles in seven OSAS patients. At first, we compared them with nine age- and sex-matched normal controls in the wake state. The only abnormality was a lengthening of the central silent period (P < 0.001). This supports a steady imbalance of motor cortical interneurone activities towards a state of enhanced inhibition. Then we looked at changes of the motor-evoked potential (MEP) size and latency, according to whether patients were awake, or in a non-rapid eye movement (REM) 2 sleep stage, or during a typical apnoea. During non-REM 2 sleep, the average MEP amplitude was significantly (P < 0.05) smaller than in the awake state. The MEP latency was, in turn, significantly longer (P < 0.05). During apnoeas, the MEP size decreased, and the latency increased further (P < 0.05), indicating an extra depression of the cortico-motoneuronal activity. All TMS changes were detected outside the pharyngeal district, suggesting a widespread dysfunction of the cortico-motoneuronal system in the OSAS, which is more evident during apnoeas.     

Vascular predictors of cognitive decline in patients with mild cognitive impairment

Our aim in this study was to assess the relationship between the state of cerebral vessels and the risk of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). We included 117 MCI patients. They underwent an ultrasonographic assessment of common carotid arteries intima-media thickness (IMT) and carotid plaque index. Cerebrovascular reactivity to hypercapnia in the middle cerebral arteries was calculated with the Breath-Holding Index (BHI). After a 12-month follow-up period, neuropsychological examinations demonstrated a progression to dementia in 21 patients. Pathological values of BHI and IMT significantly increased the risk of conversion (BHI: odds ratio, 5.80; 95% confidence interval, 1.83-18.37, p < 0.05; IMT: odds ratio, 3.08; 95% confidence interval, 1.02-9.33; p < 0.05, multinomial logistic regression analysis). Comparison between patients with all normal values and those with the simultaneous alteration of the 2 vascular indexes showed an increase in the risk of conversion from 9% to 33% (ordinal regression analysis). Our findings show that alterations of cerebral vessel functional and anatomic status increase the risk of conversion from MCI to dementia.     

Early online detection of upper airway obstructions in obstructive sleep apnoea syndrome (OSAS) patients

The obstructive sleep apnoea syndrome (OSAS) is a diagnosis related to snoring and caused by a collapse in the upper airway. OSAS patients suffer from desaturated oxygen levels during sleep as well as daytime sleepiness. In this paper, we propose a system able to identify and detect respiratory disorders online based on monitoring the airflow amplitude from a sleeping OSAS patient. By the use of &#104 2 -analysis and a Haar wavelet transform on signals performed offline, reference templates indicating the specific apnoea pattern for four different patients are constructed and used for similarity matching against online signals. Detection is performed in the early stages of an upcoming airway dysfunction, thus providing an opportunity to alert the patient at sleep. The system-testing results indicate robust performance and flexibility for the patient. Our proposed solution can in turn operate as an alternative to today's OSAS treatment of choice, the continuous positive airway pressure (CPAP).     

Computerized endopharyngeal myotonometry (CEM): a new method to evaluate the tissue tone of the soft palate in patients with obstructive sleep apnoea syndrome

This study compared the tissue tone of the soft palate in nonsnoring subjects and patients with obstructive sleep apnoea syndrome (OSAS) during wakefulness. Here, tissue tone means the biomechanical property of the tissue which can be characterized by two main parameters: stiffness and elasticity. Tissue tone includes both structural and neural components. A new method to evaluate the tissue tone of the soft palate was used - computerized endopharyngeal myotonometry (CEM). This method records and analyses the response of the soft palate tissues to a brief mechanical impact. The method enabled us to evaluate the most important parameters of tissue tone: stiffness, which is expressed as a frequency; and elasticity, expressed as a logarithmic decrement of the damped oscillation. First, a self-reported questionnaire was completed about the medical history of the subjects. Subjects then underwent a physical examination of the oropharynx and polysomnography with overnight pulse oximetry. The results of the CEM method indicated that patients with OSAS show an increased stiffness of the soft palate tissues (20.3, SD 4.7 Hz) compared with nonsnoring subjects (12.2, SD 1.8 Hz). In patients with sleep apnoea, elasticity is not increased in a similar way to stiffness. Thus, the disproportion between tissue stiffness and elasticity of the soft palate is a measure of the pathological changes in patients with sleep apnoea.     

Early online detection of upper airway obstructions in obstructive sleep apnoea syndrome (OSAS) patients

The obstructive sleep apnoea syndrome (OSAS) is a diagnosis related to snoring and caused by a collapse in the upper airway. OSAS patients suffer from desaturated oxygen levels during sleep as well as daytime sleepiness. In this paper, we propose a system able to identify and detect respiratory disorders online based on monitoring the airflow amplitude from a sleeping OSAS patient. By the use of chi(2)-analysis and a Haar wavelet transform on signals performed offline, reference templates indicating the specific apnoea pattern for four different patients are constructed and used for similarity matching against online signals. Detection is performed in the early stages of an upcoming airway dysfunction, thus providing an opportunity to alert the patient at sleep. The system-testing results indicate robust performance and flexibility for the patient. Our proposed solution can in turn operate as an alternative to today's OSAS treatment of choice, the continuous positive airway pressure (CPAP).     

Arousals and sleep stages in patients with obstructive sleep apnoea syndrome: changes under nCPAP treatment

Nocturnal arousals are the essential cause of disturbed sleep structure in patients with obstructive sleep apnoea syndrome (OSAS). The aim of this study was to analyse the relationship between sleep stages, respiratory (type-R) and movement (type-M) related EEG arousals. Furthermore, the value of these arousals as a criterion for the efficiency of nCPAP treatment was estimated. We examined 38 male patients aged between 30 and 71 (49.1±20.9 SD) y. All patients suffered from OSAS. The mean respiratory disturbance index (RDI) was 47.3±27.8 per h. Polysomnographic monitoring was carried out on 4 subsequent nights: baseline night, 2 nights of nCPAP titration and nCPAP control night. Sleep was visually scored and EEG arousals were classified into type R and M, depending on whether changes of respiration or movement caused the arousal. The RDI, the R index (type-R/h), the M index (type-M/h) and the R and M indices in different sleep stages were calculated. During the baseline night a deficit of slow wave sleep (SWS) and REM sleep was found. Furthermore there were more type-R than type-M arousals registered (17.4 h^?1[3.6–43.6] vs. 5.9 h^?1[1.6–11.8]) ( P <0.01). They occurred during stages NREM 1, NREM 2 and REM ( P <0.01). An SWS sleep rebound and a reduction of the SWS and REM latencies were already found during the first CPAP night. The R index was reduced during the first CPAP night in all sleep stages ( P <0.01) and remained approximately the same in the following 2 nights (3. CPAP night: 1.1 h^?1[0.3–5.0]). Type M arousals occurred more in stages 1 and 2 ( P <0.01), and remained unchanged under nCPAP. We concluded that differentiation of nocturnal arousals may provide more detailed information regarding the influence of breathing disturbances on sleep. Respiratory related, not movement related, arousals may be a useful additional tool in judging the efficiency of OSAS.     

Baroreflex-induced sympathetic activation does not alter cerebrovascular CO2 responsiveness in humans

We investigated the effect of baroreflex-induced sympathetic activation, produced by lower body negative pressure (LBNP) at −40 mmHg, on cerebrovascular responsiveness to hyper- and hypocapnia in healthy humans. Transcranial Doppler ultrasound was used to measure blood flow velocity (CFV) in the middle cerebral artery during variations in end-tidal carbon dioxide pressure ( P _ET,CO2) of +10, +5, 0, −5, and −10 mmHg relative to eupnoea. The slopes of the linear relationships between P _ET,CO2 and CFV were computed separately for hyper- and hypocapnia during the LBNP and no-LBNP conditions. LBNP decreased pulse pressure, but did not change mean arterial pressure. LBNP evoked an increase in ventilation that resulted in a 9 ± 2 mmHg decrease in P _ET,CO2, which was corrected by CO₂ supplementation of the inspired air. LBNP did not affect cerebrovascular CO₂ response slopes during steady-state hypercapnia (3.14 ± 0.24 vs. 2.96 ± 0.26 cm s⁻¹ mmHg⁻¹) or hypocapnia (1.31 ± 0.18 vs. 1.32 ± 0.19 cm s⁻¹ mmHg⁻¹), or the CFV responses to voluntary apnoea (+51 ± 19 vs. +50 ± 18 %). Thus, cerebrovascular CO₂ responsiveness was not altered by baroreflex-induced sympathetic activation. Our data challenge the concept that sympathetic activation restrains cerebrovascular responses to alterations in CO₂ pressure.     

Plasma cytokine levels in patients with obstructive sleep apnea syndrome: a preliminary study

The levels of some pro- and anti-inflammatory cytokines [interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-6, IL-10, and transforming growth factor (TGF)-beta], were measured by enzyme-linked immunosorbent assay (ELISA) method in the plasma of patients affected by obstructive sleep apnea syndrome (OSAS) at 22:00 hours before polysomnographic recording and immediately after the first obstructive apnea causing an SaO2 below 85%. Significantly higher levels of TNF-alpha were found in OSAS patients assessed before polysomnography compared with the control group (P < 0.01). A slight but significant increase in the plasma levels of IL-6 was also present (P < 0.05). Conversely, a significant decrease in the plasma levels of IL-10 was evident at baseline in OSAS patients (P < 0.04). No significant difference emerged between the mean values of IL-1alpha and TGF-beta between OSAS patients and controls. The present data support a prevailing activation of the Th1-type cytokine pattern in OSAS patients, which is not associated with the severity and duration of OSAS. This can have important consequences for the outcome of OSAS patients, especially with regard to the increased risk for developing atherosclerosis and cardiovascular and cerebrovascular diseases. Immediately after the first obstructive apnea causing an SaO2 <85%, a significant variation was observed in the plasma levels of TNF-alpha in OSAS patients compared with those measured before the beginning of polysomnographic recording (P < 0.001). The role played by this further increase in TNF-alpha levels after the obstructive apnea in OSAS patients remains to be established in the light of the pathogenic mechanisms of this sleep disorder.     

Changes in upper airway resistance during progressive normocapnic hypoxia in patients with obstructive sleep apnoea syndrome

SUMMARY  The responses of the upper airway to progressive normocapnic hypoxia were studied in 6 healthy men and in 6 patients with obstructive sleep apnoea syndrome (OSAS). The upper airway resistance was calculated by the ratio of the laryngeal pressure (measured using a catheter introduced into oesophagus) to the inspiratory flow. Additionally, genioglossal EMG activity (GG-EMG) was measured and analysed. The changes of all variables were analysed individually for each subject. The OSAS patients showed reduced ventilatory response, GG-reactivity and changes in upper airway resistance during progressive hypoxia. It is concluded that impaired reactivity to hypoxic activation (probably due to the process of adaptation of carotid chemoreceptors to nocturnal hypoxia), might reduce the defence abilities of OSAS patients against episodes of obturation in upper airway and obstructive apnoea events.     

The therapeutic effect of theophylline on sustained attention in patients with obstructive sleep apnea

Summary Question of the Study Patients with obstructive sleep apnea syndrome (OSAS) often suffer from daytime sleepiness and reduced alertness which frequently cannot be normalized despite of nCPAP therapy. Therefore additional treatment options for residual deficits is urgently needed. The objective of this study was to prove the efficacy of Theophylline on a component of attention (tracking) in patients with untreated obstructive sleep apnea syndrome (OSAS). Patients and Methods Theophylline or placebo was given two times in the morning (8:00 and 12:00 a. m.) in randomized order on two consecutive days. During the afternoon, 39 OSAS patients performed a randomised cross-over driving simulation test with the aid of "Carsim", a newly developed driving simulator, prior to undergoing CPAP- therapy. The program "Carsim" simulates a road with curves on a screen, the simulated vehicle should be kept on the right lane by moving the steering wheel. Results Under the effect of Theophylline (the serum level under placebo at the beginning of the measurement was 2.1 µg/ml ± 1.6 µg/ml and under Theopylline 11.2  µg/ml ± 2.8  µg/ml), the duration of track deviations measured by the driving simulator improved significantly from 49.3 ± 99.5 s to 13.6 ± 18.0 s.   Conclusions Theophylline may improve alertness in patients with sleep fragmentation and reduced sustained attention.