Pulmonary haemodynamics in obstructive sleep apnoea

SUMMARY  The time course of right ventricular output (RVO) and transmural pulmonary artery pressure (PAP) changes, detected beat-by-beat, were analysed in a sample of obstructive sleep apnoea (OSA) episodes recorded in six patients with OSA syndrome. RVO showed a trend to a decrease during apnoeas, due to a decrease in heart rate, and decreased further in the immediate post-apnoeic period, due to a decrease in right ventricular stroke volume [post-apnoeic RVO = 82.6 ± 9.3 (SD) % of the value in the immediate pre-apnoeic period; P <0.01]. Both systolic and diastolic transmural PAP showed a progressive increase throughout apnoeas (from 23.7 ± 7.3 to 29 ± 6.9 and from 9.1 ± 4.4 to 14.3 ± 3.3 mmHg, respectively, from early to late apnoeic period; P <0.01), and similarly high values in the late apnoeic and in the immediate post-apnoeic period. Therefore, cardiac output and arterial pressure in the pulmonary circulation undergo simultaneous inverse changes in OSA, similar to what was previously shown in the systemic circulation. Although these data cannot define accurately the behaviour of pulmonary vascular resistance, they suggest that pulmonary vascular resistance could also undergo continuous oscillations in OSA, with recurring peaks detectable between apnoea termination and the immediate post-apnoeic period.     

The value of one hour daytime sleep recording in the diagnosis of the sleep apnoea syndrome

In this study we investigated whether the diagnosis of sleep apnoea syndrome (SAS), based on night-time polysomnography (NPSG), can be predicted or excluded by a one-hour daytime polysomnography (DPSG). The results of 306 NPSGs were compared with DPSGs, which were performed the day before. Treated patients were excluded. In the 89 patients with SAS (Apnoea index (AI)>/=5) 59 showed apnoeas during the DPSG and 30 did not. In the 217 without SAS 25 showed apnoeas daring DPSG and 192 did not. Sensitivity for detecting SAS was 66%, the specificity was 88%, the positive predictive value (PPV) 70% and the negative predictive value (NPV) 86%. For relevant SAS (AI>/=10) the NPV would be 95%. We conclude that the one-hour DPSG is not sufficient for diagnosing or excluding SAS with certainty. It can be used to make the presence of relevant SAS unlikely.     

Effect of upper airway surgery on heart rate variability in patients with obstructive sleep apnoea syndrome

To determine whether surgery influences cardiovascular autonomic modulation in obstructive sleep apnoea syndrome (OSAS), the present study was performed to evaluate the effect of upper airway (UA) surgery on heart rate variability (HRV) using frequency domain analysis for patient groups who have had either successful or unsuccessful surgery. We compared body mass index (BMI), polysomnographic [apnoea index (AI), apnoea-hypopnoea index (AHI), minimum SaO(2)] and HRV [very low frequency (VLF) power, low frequency (LF) power, high frequency (HF) power, HF/LF ratio, LFnu = LF/(LF + HF), HFnu = HF/(LF + HF)] parameters between the unsuccessful (n = 14) and successful (n = 22) surgical groups before and after UA surgery. Significant changes were observed for the successful patient group with respect to mean AI (from 29.1 ± 21.3 to 2.0 ± 3.2 events h(-1), P < 0.001), AHI (from 38.6 ± 20.0 to 5.6 ± 5.1 events h(-1), P < 0.001), minimum SaO(2) (from 73.3 ± 12.7 to 86.3 ± 6.5%, P < 0.001), VLF power (from 25599 ± 12906 to 20014 ± 9839 ms(2), P = 0.013), LF power (from 17293 ± 7278 to 14155 ± 4980 ms(2), P = 0.016), LFnu (from 0.700 ± 0.104 to 0.646 ± 0.128, P = 0.031) and HFnu (from 0.300 ± 0.104 to 0.354 ± 0.128, P = 0.031); however, mean BMI, HF power and LF/HF ratio did not change significantly after UA surgery. No significant changes were observed in the unsuccessful surgical group. Successful UA surgery may improve cardiac sympathetic and parasympathetic modulation in patients with OSAS.     

The severity of obstructive sleep apnoea is associated with insulin resistance

Oral glucose tolerance tests (OGTT) were performed on eighteen patients with suspected obstructive sleep apnoea who also completed a whole-night polygraphic recording with oximetry. Insulin resistance indices (IRI) were calculated as the product of areas under glucose and insulin curves. In the resulting multiple regression analysis the dependent variable was IRI and the independent variables were age, body mass index (BMI) and the number of nocturnal hypoxic episodes with over 4% desaturation per hour (ODI4). ODI4 was between 4.6 and 70 (median 22.3); IRI ranged from 2.20 to 33.55 (median 7.50). In the regression model the coefficient of determination (R2) for IRI was 0.441 (F-ratio = 3.681, P = 0.038). The strongest determinant of IRI was ODI4 and the regression coefficient of BMI was not significantly different from zero even when possible outliers were excluded. It was found that insulin resistance is related to the severity of sleep anoea. This may be due to a hypoxia-induced hormonal stress reaction which decreases tissue insulin sensitivity. Since upper body obesity is associated with both insulin resistance and sleep apnoea, the distribution of fat should be taken into account in future studies.     

Circulating adrenomedullin in obstructive sleep apnoea

Adrenomedullin (AM) is a potent endothelial-derived vasodilator secreted under the influence of various stimuli such as hypoxia, shear stress and cytokines. As all of these stimuli might be active under the conditions of obstructive sleep apnoea (OSA), we hypothesized that vascular AM production is increased in these patients. The study included 41 consecutive OSA patients and 28 control subjects without sleep-disordered breathing who were recruited from a pool of patients hospitalized for other reasons. Both groups were matched for anthropometric and comorbid factors. In all patients, i.e. OSA and controls, peripheral venous blood samples were taken at 07:00 hours after diagnostic polysomnography. In subsets of OSA patients, this was repeated after two nights of continuous positive airway pressure (CPAP) therapy (n = 28) and after several months of constant CPAP use (n = 11). The controls and the untreated OSA patients did not have serial blood sampling. In all blood samples, plasma AM levels were measured by an enzyme immunoassay kit. At baseline, the OSA patients had markedly elevated AM concentrations when compared to the controls. There were no differences between normo- and hypertensive OSA patients. After two nights of CPAP therapy, AM levels significantly decreased. Patients on long-term CPAP treatment showed complete normalization of plasma AM concentrations. In conclusion, this pilot study suggests that circulating AM is increased in untreated OSA irrespective of coexistent arterial hypertension and declines after CPAP therapy. AM upregulation might be considered as an adaptive mechanism to counteract the emergence of OSA-related cardiovascular disease.     

Ischaemic stroke, snoring and obstructive sleep apnoea

SUMMARY  Ischaemic stroke occurs most often during the morning hours before noon. In recent studies the peak time of onset has been between 10.00 and 12.00 hours. Snoring every night or almost every night (habitual snoring) is in relation with ischaemic stroke. Snoring occasionally, on the contrary, is not significantly related with stroke. Habitual snoring is the most typical sign of obstructive sleep apnoea syndrome and it is strongly associated with being overweight. Other possible pathophysiological factors that are in relation with habitual snoring, obstructive sleep apnoea and stroke include arterial hypertension, changes in fibrinolytic activity, adult onset diabetes and smoking. It remains to be seen whether nightly occurring partial upper airway obstruction (habitual snoring) with intrathoracic pressure changes is an independent risk factor of ischaemic stroke. There is recent evidence that everything cannot be explained by other known risk factors.     

Naltrexone improves blood gas patterns in obstructive sleep apnoea syndrome through its influence on sleep

Endogenous opiates have been shown to depress ventilation, and could therefore play a role in sleep apnoea syndrome (SAS). Hence, opiate antagonists have been used to treat SAS. The improvement they seem to give in blood-gas monitoring could derive either from a direct blocking of endorphins that inhibit respiration or else, indirectly, through an influence on sleep patterns. The present study used a double blind cross-over protocol to investigate the relationships between the effects on blood-gas and on sleep patterns of the oral opiate antagonist naltrexone in obstructive SAS. Sleep patterns and transcutaneous blood gas (tcPO2 and tcPCO2) were recorded in parallel. Control recordings, without treatment, were carried out over two nights, followed by two nights of recording after administration either of naltrexone followed by a placebo or of a placebo followed by naltrexone. The number of obstructive apnoea and hypopnoea events per hour of sleep (Apnoea-Hypopnoea Index: AHI), of hypoxic events (defined as a tcPO2 fall of at least 10, 15 or 20 mm Hg) and of hypercapnic events (defined as a tcPCO2 increase of at least 5 mm Hg) were counted. A Metabolic Suffering Index (MSI) was calculated, defined as the product of the number, duration and magnitude of hypoxic and hypercapnic events. Compared to placebo, naltrexone resulted in significant improvements in blood-gas patterns for the duration and MSI of hypoxic events and for the number, duration and MSI of hypercapnic events. Likewise, compared to placebo, naltrexone induced significant decreases in total sleep time, slow-wave sleep and rapid eye movement (REM) sleep, and, on the other hand, significant increases in total wake time and in the number of wakenings per hour of sleep (Nw h-1). Certain naltrexone-linked blood-gas improvements were closely correlated with certain of the sleep pattern changes: the decrease in number and duration of hypoxic events correlated with REM-time decrease and the decrease in number and duration of hypercapnic events correlated with the increase in Nwh-1. These findings suggest that the improvement in blood-gas patterns induced by naltrexone in SAS may be mediated by sleep pattern effects: i.e. a decrease in REM-time and an increase in intra-sleep wakening.     

Prolactin secretion during sleep in obstructive sleep apnoea patients

SUMMARY  Plasma prolactin (PRL) concentration exhibits a sleep-dependent pattern, with highest levels during sleep and lowest levels during the waking period. The syndrome of obstructive sleep apnoea (OSA) is associated with severe hypoxaemia and chronic sleep fragmentation, both of which could affect the sleep-entrained PRL rhythm. Treatment with nasal continuous positive airway pressure (CPAP) immediately restores a normal sleep structure by successful abolition of the apnoeas. In the present study, seven OSA patients underwent two night studies, once when no treatment was given and once during the first night of CPAP treatment. Sleep was recorded polygraphically in all experiments. Plasma PRL was measured at 10 min intervals and secretory rates were calculated by a deconvolution procedure. CPAP treatment greatly reduced hypoxaemia and improved sleep quality. The secretory pulse amplitude and the total amount of PRL secreted during the night remained constant regardless of whether patients were treated or not. The only difference found was a lower pulse frequency in untreated OSA patients as compared to treated patients, which may be attributed either to hypoxaemia or to sleep disturbance or to the combined action of both. Treatment may be considered to normalize PRL release by restoring pulse frequency to values similar to those observed for normal subjects.     

Using tracheal breathing sounds and anthropometric information for screening obstructive sleep apnoea during wakefulness

Obstructive sleep apnoea (OSA) is a common yet underdiagnosed disorder. Undiagnosed OSA significantly increases perioperative morbidity and mortality for OSA patients undergoing surgery, requiring full anaesthesia. Tracheal breathing sounds characteristics during wakefulness have shown a high correlation with the apnoea–hypopnea index (AHI), while they are also affected by the anthropometric parameters, e.g., sex, age, etc. This study investigates the effects of the anthropometric parameters on our new quick objective OSA screening tool during wakefulness. Breathing sounds of 122 individuals (71 with AHI <15 as non-OSA and 51 with AHI?>?15 as OSA) were recorded during wakefulness in the supine position. The spectra and bi-spectra of 81 (47 non-OSA) individuals’ signals, which were randomly selected, were analysed as a training dataset to extract the most significant features with the lowest sensitivity to the anthropometric parameters. Using a support vector machine (SVM) classifier, these features resulted in 72.1, 64.7 and 77.5% testing classification accuracy, sensitivity and specificity, respectively. We also investigated classifying subjects into subgroups related to each anthropometric parameter and incorporating a voting procedure. This routine resulted in 83.6, 74.5 and 90.1% testing classification accuracy, sensitivity and specificity, respectively. In conclusion, it is possible to positively utilise the anthropometric information to enhance the classification accuracy for a reliable OSA screening procedure during wakefulness.     

Practicality of the Sleepstrip in postal screening for obstructive sleep apnoea

The SleepStrip, a disposable screening device for the detection of obstructive sleep apnoea (OSA), which displays an estimated apnoea-hypopnoea index (AHISS) was posted, with instructions, to 48 patients referred for sleep study for suspected OSA. The patients subsequently underwent a cardiorespiratory sleep study from which the AHIE was derived. Thirty patients (63%) returned the SleepStrip, the device displayed an AHISS in 22 patients (73%), of which 17 (57%) was deemed valid by the device. Twelve of the 30 patients who returned the SleepStrip had an AHIE > or = 20 on the detailed sleep study. Of these, the SleepStrip recording was valid in seven of which only two had an AHISS > or = 20. We concluded that the SleepStrip was not suitable for unsupervised postal screening for OSA.     

Mortality risk factors in sleep apnoea: a matched case-control study

Sleep apnoea syndrome was reported to be associated with increased mortality but it is not known if this association is independent of obesity and co-morbidities. The present study investigated predictors of mortality in a large cohort of men with sleep apnoea using a case-control design. The study population consisted of 10,981 men diagnosed during 1991-2000 by whole-night polysomnography with sleep apnoea; 331 men died prior to 1 September 2001, of whom 277 were matched by age, gender, site and time of study to patients who were alive in September 2001. Multivariate analysis revealed that all-cause mortality was associated with chronic obstructive pulmonary disease (COPD) (odds ratio, OR: 7.07, 95% CI 2.75-18.16), chronic heart failure (CHF) (OR: 5.47, 95% CI 1.06-28.31), diabetes mellitus (DM) (OR: 3.30, 95% CI 1.51-7.20) and body mass index (BMI) (increase of 5 kg m(-2), OR: 1.44, 95% CI: 1.04-1.99). Chronic upper airway problems were associated with survival (OR: 0.45, 95% CI 0.23-0.90). There were significant interactions between respiratory disturbance index and BMI and COPD. Mortality of patients younger than the median age (62 years) was associated with COPD, DM and an interaction between BMI and apnoea severity. Predictors of mortality for the older patients were COPD, CHF and DM. We conclude that all-cause mortality in sleep apnoea is associated with co-morbidities and obesity. Severity of sleep apnoea affects mortality by interacting with obesity and lung disease.     

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.     

Respiration in NREM and REM sleep after upper airway surgery for obstructive sleep apnoea

SUMMARY  To verify whether upper airway surgery in obstructive sleep apnoea syndrome affects differently respiration in NREM and REM sleep, 22 patients were studied by polysomnography before and three months after surgical treatment. On the average, treatment improved respiration during both sleep states, but no significant interaction was found between sleep state and effect of surgical treatment. According to the response to treatment, three groups of patients were identified: the first group ( N = 6), with an improvement in apnoea-hypopnoea index (AHI), percentage of sleep time spent in apnoea and hypopnoea (time in AH) and mean oxyhaemoglobin saturation (SaO₂) in both NREM and REM sleep; the second group ( N = 5), with an improvement in AHI only in NREM sleep, associated with improvement in mean SaO₂ in both sleep states; the third group ( N = 11), without any improvement in AHI and time in AH, either associated ( N = 5) or not ( N = 6) with an improvement in mean SaO₂ in both sleep states. An increase in the percentage of hypopnoeas out of the total AHI after treatment could partly account for the apparent discrepancy between AHI and mean SaO₂ behaviour in the subjects of the second group, but not in the patients of the third group who improved their mean SaO₂. Mixed apnoeas occurred before surgery in six subjects; they remained numerous after surgery only in two subjects who did not show any SaO₂ improvement. In conclusion, the degree of improvement in respiration after upper airway surgery was similar in every patient in NREM and REM sleep.     

Oxidative stress and sleep apnoea in clinically healthy infants in the first year of life

Summary Question of the study   Respiratory instability as well as tissue damage by free radicals (oxidative stress) have been hypothesized to play a role in cases of sudden and unexpected infant death in the first year of life. The ratio of the oxidized/reduced form of redox compounds in the circulation could be used as a marker of oxidative stress. Therefore, the sleep apnoea rate and redox status of coenzyme Q10 (CoQ10) (percentage of the oxidized form in total CoQ10) were measured in a population of clinically healthy infants in their first year of life in order to study whether a physiological parameter of respiratory instability is related to a biochemical parameter of oxidative stress. Patients and methods   Between May and December 1999, 323 infants in the first year of life were referred to a paediatric sleep laboratory. Sleep apnoea rate, periodic breathing and parameters of oxygenation (SaO₂ and TcPO₂) were calculated based on polysomnographic recordings. The CoQ10 redox status was calculated based on high-pressure liquid chromatographic (HPLC) analysis. Results   Statistical analysis showed an age-dependent decrease in apnoea rate ( r = – 0.38) and CoQ10 redox status ( r = – 0.40). An increased CoQ10 redox status (median: 16.6 %; range: 7.3 – 29.7 %) was found in infants with high apnoea rates above the 90^th percentile of a reference group in comparison with infants with apnoea rates below the 90^th percentile of a reference group (median: 10.4 %; range: 5.1 – 20.4 %; P = 0.031). Conclusions   These findings may indicate that high apnoea rates are accompanied by increased formation of free radicals in clinically healthy infants in the first year of life.     

Determinants of subjective sleepiness in suspected obstructive sleep apnoea

Although daytime sleepiness is commonly associated with obstructive sleep apnoea (OSA), the relationship between OSA severity and subjective sleepiness has been documented elusive. This study aimed to identify clinical and polysomnographic determinants of subjective sleepiness among patients suspected of having OSA. A sleep clinic-based sample of 915 patients was interviewed with a structured questionnaire and underwent diagnostic overnight polysomnography. Subjective sleepiness was quantified by Epworth Sleepiness Scale (ESS). Excessive daytime sleepiness (defined as ESS score > 10) was present in 38.8% of patients. In multiple linear regression analysis, respiratory disturbance index [RDI; used to define (whenever RDI was >5) and quantify OSA], depression and diabetes were the most important determinants of ESS score accounting for 17%, 11% and 6% of its variability respectively. Chronic obstructive pulmonary disease (COPD), stroke, heart disease, alcohol use and body mass index were less important determinants of ESS score explaining 1-3% of its variability. In conclusion, OSA should not be considered the sole potential cause of increased subjective sleepiness in patients suspected of having OSA. Primarily depression and diabetes, but also COPD, stroke, heart disease, alcohol use and increased body mass index may contribute to increased subjective sleepiness.     

A behavioural test to assess daytime sleepiness in obstructive sleep apnoea

Daytime sleepiness is an important symptom of obstructive sleep apnoea syndrome (OSAS). The standard tests for its objective quantification use EEG recordings, and are time consuming and expensive, which makes them difficult to use for large studies. This study assesses the ability of a simple test of sustained ‘wakefulness’ to discriminate the excessive somnolence of severe symptomatic obstructive sleep apnoea from normality, and compares its results to the traditional EEG based Maintenance of Wakefulness Test (MWT). Ten subjects (7M 3F) with severe sleep apnoea (>4% SaO₂ dip rate median 32.7 (90% central range 9.7–65.6)) and symptoms of daytime sleepiness, (Epworth Sleepiness Score (ESS)17(10–24)) and 10 normal subjects (4M 6F, ESS 3.5(1–8)) were studied. The MWT and the behavioural test (Oxford SLEep Resistance test – OSLER test) were performed on each subject in random order on 2 separate days. The protocol for both tests was the same with 4 × 40 min sleep resistance challenges throughout the day while sound isolated in a darkened room. During the OSLER test subjects were asked to press a switch in response to a light emitting diode (LED), which was lit for 1 s in every three. Both the switch and the light were connected to a computer that stored both the number of times the light was illuminated and whether a correct response was made. The OSLER test discriminated the normal subjects from the sleep apnoea group (mean sleep latency (min) normal group 39.8, OSA group 10.5) as well as the traditional MWT (normal group 38.1, OSA group 7.3) and was much simpler to administer. This test has the advantage that sleep onset is defined objectively and automatically as a failure to respond to the light, rather than from EEG interpretation, which is inevitably partly subjective. This technique may provide a simple and robust method of objectively quantifying daytime sleepiness for large studies.     

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.     

Impairment of daytime cerebrovascular reactivity in patients with obstructive sleep apnoea syndrome

Several studies have demonstrated a clear association between snoring, sleep apnoea and increased risk of stroke. However, the possible role of sleep apnoea in the pathophysiogenetic mechanisms of cerebrovascular disease is still unknown. Our aim in this study was to investigate cerebral haemodynamic changes during the waking state in eight patients with sleep apnoea syndrome (OSAS) by means of transcranial Doppler (TCD). In particular, we studied cerebral vascular reactivity (CVR) to hypercapnia calculated by means of the breath holding index (BHI). The investigation was performed in the early morning, soon after awakening, and in the late afternoon. Data were compared with those of eight healthy subjects matched for age and vascular risk factors. OSAS patients showed significantly lower BHI values with respect to controls both in the morning (0.56 vs. 1.36; P < 0.0001) and in the afternoon (1.12 vs. 1.53; P < 0.0001). In patients, BHI values in the afternoon were significantly higher than in the morning ( P < 0.0001). These data demonstrate a diminished vasodilator reserve in OSAS patients, particularly evident in the morning. This reduction of the possibility of cerebral vessels to adapt functionally in response to stimulation could be linked to hyposensitivity of cerebrovascular chemoreceptors after the continuous stress caused by nocturnal hypercapnia.