Gender differences on polysomnographic findings in Greek subjects with obstructive sleep apnea syndrome.

BACKGROUND AND PURPOSE: Studies from North American clinics have reported that females with obstructive sleep apnea syndrome (OSAS) are about the same age as males but are heavier, have less severe apnea and make up a much smaller proportion of cases. We examined polysomnographic differences between Greek men and women with OSAS in order to study the influence of gender on clinical presentation and laboratory findings. PATIENTS AND METHODS: This retrospective study included a cohort of 1,010 Greek patients (844 males, 166 females) diagnosed with OSAS by overnight polysomnography (PSG), who were referred to the Sleep Disorders Center of Evangelismos Hospital, Athens Medical School, University of Athens. All patients were studied over a period of three consecutive years, during which time clinical and polysomnography (PSG) findings were compared. RESULTS: Body mass index (BMI) was similar in men and women with OSAS (BMI=31.6+/-5.5kg/m(2) in men versus BMI=32.5+/-8.1 (SD) kg/m(2) in women). Female patients were significantly older than male patients (56.9+/-10.6 versus 50.6+/-11.7 year, P=0.001). The mean apnea-hypopnea index (AHI) during total sleep time was higher in men than in women (42.4+/-28.2 versus 33.2+/-27.7 events/h, P<0.001). The AHI in non-rapid eye movement (NREM) sleep was higher in men than in women (42.9+/-28.9 versus 32.6+/-28.7 events/h, P<0.001), but in rapid eye movement (REM) sleep AHI was similar in men and women (36.0+/-23.3 versus 34.9+/-25.4 events/h). Forty percent of men had AHI-REM sleep >AHI-NREM compared to 62% of women, and the difference between REM and NREM-AHI was significantly less in men than in women (14.21+/-11.18 versus 19.76+/-13.43 events/h, P<0.001)). Several aspects of sleep were worse in women versus men: sleep efficiency index was lower (79.4+/-16.1% versus 85.1+/-12.5%, P<0.001); sleep onset latency (27.7+/-27.7 versus 17.9+/-18.1min, P<0.001), and REM onset latency (161.5+/-76.2 versus 145.7+/-71.4min, P<0.018) were longer; wake time after sleep onset (WASO) was also greater in women (42.6+/-46.5 versus 30.7+/-34.9min, P<0.003). CONCLUSIONS: In Greek subjects with OSAS, there was no difference in BMI, and female patients were significantly older than male patients. OSAS was diagnosed in men five times more often than in women. AHI was greater in men than in women, but women are more likely than men to have a higher AHI in REM than NREM. Sleep quality is worse in female than in male patients.

Sleep apnea. From the needles of Dionysius to continuous positive airway pressure.

It is generally believed that the first description of the sleep apnea syndrome was made by Charles Dickens in the Pickwick Papers and that the first medical description was published in 1956. In fact, some of the features of the sleep apnea syndrome were described in antiquity and brief medical reports were published prior to the Pickwick Papers. This article traces the literary and medical contributions to our understanding of sleep apnea.

Diagnosis of sleep breathing disorders in a general hospital. Experience and recommendations.

In the 24 months after a sleep breathing laboratory opened in a general hospital, 48 patients thought to have a primary sleep breathing disorder were referred for study. Evaluation of breathing during sleep was most useful in those having excessive daytime sleepiness or unexplained polycythemia. The sleep apnea syndrome was documented in 19 of 24 patients with excessive daytime sleepiness. Of 15 patients with unexplained polycythemia, ten were found to have severe hypoxemia during sleep. This experience suggests that facilities for evaluation of sleep breathing disorders should be available in larger medical centers.

Irregular breathing during sleep in patients with panic disorder.

OBJECTIVE: The authors examined the nocturnal breathing patterns of patients with panic disorder to determine whether these individuals had respiratory irregularities at a time when anxiety was not manifest. METHOD: Respiratory polysomnography was conducted on 14 medication-free patients with panic disorder and 14 healthy comparison subjects. Semiautomated indices of ventilatory variability were calculated for representative 3-minute, artifact-free sleep samples, and manually scored indices of irregular breathing were rated (blind to diagnosis) for the entire last 2 nights of sleep. RESULTS: Patients with panic disorder had evidence of abnormal sleep breathing as indicated by increased irregularity in tidal volume during REM and an increased rate of microapneas (i.e., brief [5-10-second] pauses in breathing). A subgroup of patients (including some with recent sleep panic attacks) had indices of subtle disorders in breathing during sleep that were above the 95th percentile for the comparison subjects. CONCLUSIONS: These findings extend the observations in the awake state that patients with panic disorder breathe more irregularly than healthy comparison subjects. The irregularities may be attributable to altered brainstem sensitivity to CO2 or to other as yet unexplained factors. A possible relationship between irregular nocturnal breathing and sleep panic attacks is discussed.

Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy.

Seventy-five patients meeting international diagnostic criteria for narcolepsy enrolled in a 6-week, three-period, randomized, crossover, placebo-controlled trial. Patients received placebo, modafinil 200 mg, or modafinil 400 mg in divided doses (morning and noon). Evaluations occurred at baseline and at the end of each 2-week period. Compared with placebo, modafinil 200 and 400 mg significantly increased the mean sleep latency on the Maintenance of Wakefulness Test by 40% and 54%, with no significant difference between the two doses. Modafinil, 200 and 400 mg, also reduced the combined number of daytime sleep episodes and periods of severe sleepiness noted in sleep logs. The likelihood of falling asleep as measured by the Epworth Sleepiness Scale was equally reduced by both modafinil dose levels. There were no effects on nocturnal sleep initiation, maintenance, or architecture, nor were there any effects on sleep apnea or periodic leg movements. Neither dose interfered with the patients' ability to nap voluntarily during the day nor with their quantity or quality of nocturnal sleep. Modafinil produced no changes in blood pressure or heart rate in either normotensive or hypertensive patients. The only significant adverse effects were seen at the 400-mg dose, which was associated with more nausea and more nervousness than either placebo or the 200-mg dose. As little as a 200-mg daily dose of modafinil is therefore an effective and well-tolerated treatment of excessive daytime somnolence in narcoleptic persons.

Diagnosis of obstruction of the upper and central airways.

Patients with obstruction of the upper airways are often treated for long periods of time for other disorders. Correct diagnosis is important since treatment is quite specific. Such patients may present with a characteristic history and findings on physical examination. Certain physiologic tests such as flow-volume loops with and without helium help to prove the diagnosis. Patients with upper airway obstruction may also have sleep apneas and the sleep deprivation syndrome. Methods of diagnosis of upper airway obstruction are presented and three instructive cases are reviewed.

Sleep apnea in acromegaly.

In patients with acromegaly obstruction of the upper airway may develop due to enlargement of the tongue and thickening of the tissues of the larynx. The sleep apnea syndrome may develop in patients with upper airway obstruction from other causes. We studied a somnolent patient with acromegaly in whom we documented the sleep apnea syndrome. Endoscopy, while the patient was sleeping, revealed that periodic obstruction during sleep occurred because the large tongue bulged into the pharynx and obliterated the pharyngeal airway. Tracheostomy was followed by the disappearance of the somnolence. The upper airway obstruction in acromegaly may result in severe hypoxemia and disruption of normal sleep.

Sleep in restrictive lung disease.

Restrictive lung disease patients exhibit a wide range of breathing and oxygenation abnormalities during sleep. The combination of degree of restriction, whether it is intrapulmonary or extrapulmonary, and confounding factors, such as obesity, age, and sex, will ultimately determine the degree of disturbed nocturnal physiology. The sleep literature is still sparse in most restrictive diseases. For patients with interstitial lung disease, the role of nocturnal oxygen in chronic established fibrosis, and also in acute alveolitis (e.g., farmer's lung, bird fancier's lung, etc.), has not been addressed. As fibrotic lung disease progresses, the degree of nocturnal desaturation and breathing dysrhythmias will progress. Changes in sleep architecture are likely related to the progression of the disease, but this is not known with certainty. Long-term evaluation of sleep and breathing in interstitial lung disease will give further insight into whether or not sleep changes are primary or secondary events. For kyphoscoliosis patients, again, we need more information on sleep as the thoracic deformity changes. In addition, the use of drugs (acetazolomide, medroxyprogesterone, and almitrine) and/or nasal CPAP to treat nocturnal desaturation needs to be assessed in a controlled fashion. In neuromuscular disease, the dynamics of gas exchange and sleep structure need to be defined in a larger group of patients. Factors such as degree of muscle weakness, degree of underlying lung diseases, and medications must be taken into consideration. Nocturnal hypoxemia may cause muscle weakness and fatigue, which in time, could cause more nocturnal hypoventilation and further hypoxemia. Supplemental nocturnal oxygen should be evaluated in this population.

Acute effect of nasal CPAP on periodic limb movements associated with breathing disorders during sleep.

Sleep-disordered breathing is commonly associated with periodic limb movements (PLMS). Nasal continuous positive airway pressure (nCPAP) is the most widely used treatment for sleep-disordered breathing. However, it is not clear whether nCPAP treatment of apnea also has a systematic effect on PLMS. We studied 15 patients with sleep-disordered breathing and PLMS in a split-night protocol in order to confirm the acute effects of nCPAP on PLMS. Although the PLMS index (PLMSI) did not change statistically (baseline, 38.7 +/- 20.5; CPAP, 31.3 +/- 17.0; p = ns), the PLMS-related index (PLMS-ArI) decreased significantly on nCPAP (baseline, 17.8 +/- 10.1; CPAP, 9.2 +/- 5.7; p < 0.05). Whether the reduced PLMS-ArI is sustained with chronic nCPAP is unknown and a matter of future investigation.

Nocturnal oximetry: is it a screening tool for sleep disorders?

The objective of this study was to examine the usefulness of home oximetry for the screening of sleep disorders presenting with excessive daytime sleepiness (EDS). This was accomplished by blinded comparison of diagnosis by oximetry alone versus polysomnographic diagnosis carried out at a sleep disorders center at a tertiary referral hospital. This study included three hundred patients who had been referred because of EDS and suspected sleep apnea. A number of measurements were made. The arterial oxygen saturation (SaO2) data were sampled at 2 Hz and stored digitally during polysomnography (PSG). From the SaO2 data recorded onto paper six scorers calculated the number of desaturations > 3% per hour (desaturation index: DI) and then made a diagnosis [normal, DI < 5; mild obstructive sleep apnea (OSA), 5 < DI < 20; moderate OSA, 20 < DI < 40; severe OSA, DI > 40]. Upper airway resistance syndrome (UARS) was diagnosed when DI was < 5 but associated with small fluctuations in SaO2. The diagnosis made by each of six scorers was compared to the clinical diagnosis made independently using PSG. Thirty-one (10.3%) of all the records were rejected by scorers because of inadequate SaO2 signals requiring technologist intervention. Sensitivity of screening for sleep-breathing disorders was 90.0% and specificity was 75.0%. All moderate and severe OSA patients were detected by oximetry. However, among the 66 patients who were classified as normal by oximetry, 1 had mild OSA, 20 had UARS, 9 had periodic limb movements in sleep, 4 had narcolepsy and 2 had a parasomnia. In conclusion, home oximetry may not have sufficient sensitivity and specificity to detect breathing disorders reliably during sleep and is useless for other disorders of sleep.

Nocturnal cluster headache associated with sleep apnea. A case report.

We describe a 49-year-old man with chronic cluster headache unresponsive to all medications. Following investigation in the sleep lab he was found to have obstructive sleep apnea (OSA) with associated oxygen desaturations during rapid eye movement (REM) sleep. He awakened during one of these episodes with a typical headache. Treatment with nasal CPAP abolished his OSA and desaturations, and largely abolished his headaches. He then developed central apneas during REM sleep. Further treatment with BiPAP, with a set backup rate, abolished both the apneas and the headaches. We conclude that there may be a link between nocturnal cluster headaches and sleep apnea.

Oxygenation and breathing pattern during phasic and tonic REM in patients with chronic obstructive pulmonary disease.

Oxygen desaturation in chronic obstructive pulmonary disease (COPD) occurs during sleep and is most marked in REM sleep. REM is not a homogeneous state, consisting of phasic REM (PREM) (REMs, myoclonic twitches) and tonic REM (TREM) (muscle atonia, desynchronized electroencephalogram). In normals, onset of PREM produces transient changes in breathing pattern with a decrease in respiratory amplitude and an increase in frequency, which produce reductions in oxygen saturation (SaO2). Because it is reasonable to expect such breathing pattern changes to cause more desaturation in COPD, and because systematic all-night studies of PREM and TREM have not been reported, we studied 18 patients with severe COPD [Forced expiratory volume in one second (FEV1) = 25.7 +/- 3.5 (SEM) % predicted] during sleep and monitored SaO2 and breathing pattern in PREM and TREM. PREM made up 19.7% of total REM (4.6% total sleep time) but was associated with 81.7% of the total REM desaturations of greater than 5% (57.9% of all sleep desaturations of greater than 5%). With PREM onset, breathing pattern changed 72.5% of the time, most often with a transient decrease in amplitude and increase in frequency. Even though 27.5% of PREM was not associated with changes in breathing pattern and many PREM segments were very short, we were still able to show highly significant SaO2 differences between PREM and TREM. Mean TREM SaO2 was 88.0 +/- 1.2%; mean PREM SaO2 was 86.6 +/- 1.4%, with mean nadir SaO2 for individual PREM segments falling to 84.8 +/- 1.5%. Mean awake SaO2 was 89.7 +/- 0.8%. We conclude that in COPD the transition from TREM to PREM is associated with breathing pattern changes and oxygen desaturation. Differences in breathing pattern with PREM onset may be related to different effects of PREM processes on respiratory neurons and diaphragm motor neurons.

Snoring in normal young adults: prevalence in sleep stages and associated changes in oxygen saturation, heart rate, and breathing pattern.

Six men and three women, asymptomatic light snorers ranging in age from 25-34 years, were studied during sleep to determine the prevalence of snoring in the different sleep stages, the associated changes in oxygen saturation (SaO2), heart rate (HR), and breathing frequency (f), and the associated breathing arrhythmias. Snoring was defined as a 1-minute epoch with more than 80% of the breaths associated with snores. Most of the snoring epochs as well as the apneas and hypopneas occurred during stage 2, mainly because it is the most prolonged sleep stage. The prevalence of snoring, however, normalized for differences in length of sleep stages, was highest in stages 3 and 4 but low in REM, whereas the converse was true for apneas and hypopneas. Snoring caused no change in the mean SaO2, mean HR, or f, as compared with nonsnoring periods in the same sleep stage. Continuous snoring in normal subjects can occur without significant O2 desaturation or breathing arrhythmia. Continuous snoring and breathing arrhythmia tended to occur together in a given subject but were unrelated in time, suggesting a different pathogenesis.

Dynamic in vivo response characteristics of three oximeters: Hewlett-Packard 47201A, Biox III, and Nellcor N-100.

Pulse oximeters (Biox III, Nellcor N-100) and a transmittance oximeter [Hewlett-Packard 47201A (HP)] were compared for SaO2 measurement and responsiveness during dynamic changes in arterial oxygen saturation and heart rate. Five sleep apnea syndrome patients were studied because they had large oscillations in SaO2 and heart rate in sleep. During sleep, each patient exhibited a series of rapid (18.0 +/- 8.3 s, mean +/- SD) oscillations in oxygen saturation (92.1 +/- 2.6% to 74.2 +/- 7.7%). Oxygen saturation measurements were sampled simultaneously from each oximeter by computer (at 2 Hz). Accuracy was assessed by comparing pulse and transmittance oxygen saturation measurements at the peak and trough of each apnea-related oscillation. Oximeter response was defined in terms of the "delay" or absolute time difference between the pulse oximeters and the transmittance oximeter for the determination of the peak and trough saturations. Linear regression analysis was used to establish accuracy and response relationships between pulse oximeter sensors (reusable ear, reusable digit, disposable digit, and disposable nasal sensors) and the transmittance oximeter sensor (reusable ear sensor). Pulse oximeter response delay was highly correlated with heart rate. Pulse oximeter SaO2 measurement and response characteristics varied considerably with sensor type (disposable, reusable) and sensor location (ear, nose, and digit). One must be aware of these differences in clinical and research application.

Sighs during sleep in adult humans.

We analyzed sighs (breaths with a tidal volume at least twice that of baseline breaths) during sleep in 12 normal adults. We found a total of 124 sighs in the group, with an average of 1.66 sighs/h of sleep, but with great intersubject variation (range: 1-25 sighs/night). There were sighs in all sleep stages, but there were more per hour in stage 1. 64.4% of the sighs were associated with an increase in EMG activity or EEG frequency, starting either before or immediately after the sigh. The remainder of the sighs were not associated with any arousal or sleep stage changes. The normal variability of heart rate with breathing is exaggerated during sighs, probably because of the greater inflation and the associated arousal. Sighs have larger mean inspiratory flows (Vt/Ti), expiratory flows (Vt/Te), and a larger fraction of respiratory cycle spent in inspiration (Ti/Ttot) than the previous breaths, all evidence of a change in respiratory control. Sighs during sleep may occasionally be followed by central apneas, hypoventilation, or considerable slowing of respiratory rate. Although it has been shown that a sigh renders the respiratory centers refractory to another sigh, we found that sighs sometimes occur in pairs.

Short technical note: quantification of periodic breathing: preliminary studies.

Although the apnea/hypopnea index is the most widely used measure of breathing pattern abnormality during sleep, this index gives no information about the strength of the oscillation in the breathing pattern, its periodicity or its regularity. Such information may be required in research studies involving breathing patterns and how they are affected by interventions. We are exploring spectral analytic methods to determine two normalized indices, the periodicity index and the modified modulation index, to examine periodic breathing for all-night sleep studies. These methods are automatic and require no user interaction. Data were obtained from 11 heart failure patients who slept for a total of 21 nights in the sleep laboratory. Because individual patients had a marked regularity of their Cheyne-Stokes respiration during sleep, one would expect an extremely high correlation between the traditional measures of breathing pattern abnormality and these spectral analytic techniques. Indeed we found that there was an extremely high correlation between the periodicity index and the modulation index and the traditional measures of apnea/hypopnea index and the proportion of the night with periodic breathing (p less than 0.02 in all cases). When the breathing pattern was irregular but still with many apneas there was a discrepancy between the apnea index and the indices of periodicity. These techniques are still preliminary and future studies will determine their limitations in other patient populations and where the pattern is unstable.

L-DOPA/carbidopa for nocturnal movement disorders in uremia.

Restless legs syndrome (RLS) and periodic limb movements during sleep (PLMS) are sleep disorders that are common and distressing to uremic patients. There are few data regarding effective treatment in this population. Five chronic hemodialysis patients completed a double-blind, placebo-controlled, crossover study using a single bedtime dose of controlled release L-DOPA/carbidopa (100/25 mg) for treatment of RLS and sleep disruption. Leg movements per hour of sleep and percentage of sleep time accompanied by leg movements were decreased with treatment (101.0 +/- 29.1 events/hour on placebo vs. 61.0 +/- 28.3 events per hour on drug, p = 0.006; and 15.1 +/- 4.9% of sleep time with leg movements on placebo vs. 8.6 +/- 4.0% on drug, p = 0.014). In addition, arousals associated with leg movements (mean 209 +/- 49 events on placebo, mean 108 +/- 46 events on drug) and the leg movement arousal index (mean 59 +/- 23 events/hour on placebo, mean 23 +/- 9 events/hour on drug) were decreased by active medication (p = 0.03 and 0.04, respectively). Patients, however, continued to have very disrupted sleep and we could not document consistent subjective or objective improvement in overall sleep except for an increase in slow-wave sleep (SWS) from 9.0% to 22.8% (p = 0.01). The patterns of movements during sleep were not uniform in different patients, and the movements, although often periodic, were much longer than defined for PLMS. Because of this, finding suitable objective parameters to analyze was problematic. Measuring the percentage of sleep time during which there were leg movements was probably the most efficient and reproducible means of quantitating this disorder. Thus, although controlled-release L-DOPA/carbidopa at a dose of 100/25 mg given once nightly reduced leg movements and increased SWS, sleep continued to be disrupted. Whether higher doses or more frequent dosing is effective requires further investigation.

Sleep apnea and body position during sleep.

In patients with obstructive sleep apnea, it is believed that body position influences apnea frequency. Sleeping in the lateral decubitus position often results in significantly fewer apneas, and some have recommended sleeping on the side as the major treatment intervention. Previous studies, although calculating apnea-hypopnea index (AHI) for supine and lateral decubitus positions, have not taken sleep stage into account. To examine the effect of both sleep stage and body position on apnea duration (AD) and frequency, we determined AHI and AD in all spontaneous body positions during rapid eye movement (REM) and non-REM (NREM) sleep by reviewing videotapes and polysomnograms from 11 overnight studies of 7 obese patients with severe sleep apnea. Consistent with previous work, AD was significantly longer in REM then in NREM (32.5 +/- 2.3 s versus 23.5 +/- 1.9 s; p less than 0.05). This difference persisted when adjusting for body position. AHI was greater on the back than on the sides (84.4 +/- 4.9/h versus 73.6 +/- 7.5/h, p less than 0.05), but after accounting for sleep stage, this difference remained only for NREM (103 +/- 4.8/h versus 80.3 +/- 9.2/h, p less than 0.05) and not for REM (83.6 +/- 5.3/h versus 71.1 +/- 4.2/h, p NS). Although reduced, AHI on the sides still remained clinically very high. Body position changed frequently throughout the night, but some patients spent little or no time on their back. We conclude that AD is longer in REM than NREM, regardless of position, and AHI is higher on the back only in NREM. As AHI remains very high on the sides, favoring the lateral decubitus position may not be as beneficial as previously thought in very obese patients. Less obese patients are more likely to benefit by position changes.

Using self-reported questionnaire data to prioritize OSA patients for polysomnography.

Many laboratories have large numbers of patients with suspected obstructive sleep apnea (OSA) waiting to be tested. We assessed the use of simple clinical data to detect those patients with an apnea index <20 (low AI) who could be studied less emergently. Using questionnaires completed by patients prior to evaluation, we collected data on 354 consecutive patients (281 males, 73 females; mean age 48.6 years) referred for OSA and assessed with polysomnography (PSG). The questionnaires included the Epworth sleepiness scale (ESS), height, weight, age, and a history of observed apnea. Analysis of receiver operating characteristics curves revealed that both body mass index (BMI) [area under curve = 0.7258, standard error (SE) = 0.03, p < 0.01] and ESS (area under curve = 0.5581, SE = 0.03, p = 0.03) were significantly better than chance alone in detecting people with AI < 20. ESS < or =12 was found in 37.9% of the subjects but 39.6% of those expected to have a low AI using ESS had an AI > or =20. A BMI < or =28 was found in 24.9% of the subjects; 14.8% of those expected to have a low AI using BMI had an AI > or =20. Combining these variables improved accuracy but resulted in smaller groups; a cut-off of ESS < or =12 and BMI < or =28 resulted in a group of 33 (9.3% of subjects), only two (6%) of whom were falsely called low AI. Adding to this the fact that apnea had not been observed resulted in a group of nine patients (2.5% of subjects), none of whom had an AI > or =20. Thus there is a tradeoff; the more variables used, the greater the accuracy but the smaller the percent of cases selected to have low AI. However, in laboratories with hundreds of patients waiting to be tested, any procedure better than chance to help prioritize patients seems worthwhile.

Utilization of health care services in patients with severe obstructive sleep apnea.

We compared the health care utilization of 97 obese patients diagnosed with obstructive sleep apnea (OSA) and 97 matched control subjects. Over a 2-year period that ended 2 years prior to initial diagnosis, the OSA group had 251 nights in hospital, compared to 90 nights for the control group. During the same 2-year period, total expenditures from physician claims were $82,238 (Canadian dollars) in the OSA patients versus $41,018 in the control group (p < 0.01). Depending upon which assumptions one uses for the calculation of hospital costs, during the same 2-year period, the 97 OSA patients utilized between $100,000 and $200,000 more in services than their control counterparts. We conclude that sleep apnea patients are already heavy consumers of health care services prior to any specific evaluation and treatment for apnea.