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* From the Sleep Laboratory, Department of Psychiatry (Drs. Haba-Rubio and Sforza), and Pneumonology Division (Drs. Janssens and Rochat), University Hospital, Geneva, Switzerland.
Correspondence to: Emilia Sforza, MD, PhD, Laboratoire de Sommeil, Service de Psychiatrie Adulte, Hôpitaux Universitaires de Genève, 2 Chemin du Petit Bel Air, 1225 Chêne Bourg, Genève, Switzerland; e-mail: Emilia.Sforza{at}hcuge.ch
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Abstract |
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Methods: Anthropometric, clinical, and polysomnographic characteristics of 415 patients undergoing polysomnography for SDB were examined. For all patients the apnea-hypopnea index (AHI) during total sleep time, the AHI during REM (AHI-REM), and the AHI during non-REM sleep (AHI-NREM) were calculated. REM SDB was defined as an AHI-REM/AHI-NREM ratio >2. Patients were stratified according to the severity of disease in mild, moderate, and severe cases. Daytime sleepiness was assessed subjectively by the Epworth sleepiness scale (ESS), and objectively, in a subgroup of 228 patients, by the maintenance wakefulness test (MWT).
Results: Of the initial sample, 36.4% of cases (n = 151) fulfilled the REM SDB criteria. No significant differences in subjective complaints, medical history, and drug intake were present between REM and non-REM SDB patients, and no significant differences were found in ESS scores and mean sleep latency of the MWT between groups. A high occurrence of REM SDB was found in mild (73.1%) and moderate cases (47.2%). While in the entire group and in non-REM SDB patients a strong male prevalence was found, the incidence of REM SDB was similar in men and women.
Conclusion: Our results show that neither clinical history nor daytime sleepiness differentiate patients with REM SDB from non-REM SDB patients. The disorder is more common in mild and moderate cases; there is an equal incidence in women and men. These findings may suggest that REM-related SDB is a part of the spectrum of SDB.
Key Words: polysomnography • rapid eye movement sleep • sleep-disordered breathing • sleepiness
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Introduction |
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Materials and Methods |
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Clinical Evaluation
All patients underwent a detailed clinical interview with an experienced sleep specialist concerning the primary complaint motivating the consultation (ie, snoring, reported apneas, and sleepiness) and medical history, with special focus on cardiac and cerebrovascular disease, hypertension, obstructive or restrictive lung disease, metabolic disorders and psychiatric diseases. Actual drug intake including antihypertensives, antiarrythmics, hypolipemiants, hypoglicemiants, antidepressants, benzodiazepines, hypnotics, and neuroleptics was also considered. A semistructured clinical interview for assessing symptoms possibly related with a SDB (morning headache, fatigue, daytime sleepiness, witnessed apneas, snoring, cognitive difficulties, nycturia, disturbed sleep) was performed.
Nocturnal Sleep Studies
Polysomnography included seven EEGs, right and left electro-oculograms, and one electromyogram of chin muscle for conventional sleep staging. Respiratory airflow was monitored with a nasal cannula connected to a pressure transducer (Protech2; Minneapolis, MN), thoracic and abdominal respiratory movements with piezoelectric strain gauges, and tracheal sound by microphone. Arterial oxygen saturation (Sao2) was continuously measured with a finger oximeter.
Sleep was scored using the criteria of Rechtschaffen and Kales5 for epochs of 20 s by a scorer experienced in the use of standard guidelines. As indexes of sleep fragmentation, we considered the number of awakenings and the number of stage shifts combined to calculate a sleep fragmentation index (SFI) per hour of TST.67 Respiratory events were scored using standard criteria.8 Apneas were defined as the absence of airflow on the nasal cannula lasting > 10 s. Hypopneas were defined as a 
50% reduction in airflow from the baseline value lasting at least 10 s, or a clear amplitude airflow reduction lasting 10 s and associated with either an oxygen desaturation of > 3% or an arousal. As indexes of nocturnal hypoxemia, we considered the minimal Sao2, the mean minimal Sao2, and the oxygen desaturation index (ODI). Apnea/hypopnea events were classified as central, obstructive, or mixed according to the absence or presence of breathing efforts.
The AHI was defined as the number of apneas and hypopneas per hour of TST. According to standard recommendations,8 cases were stratified as mild (AHI during TST [AHI-TST] between 5/h and 15/h, n = 119), moderate (AHI-TST >15/h to < 30/h, n = 108), and severe (AHI-TST >30, n = 188). In order to define the presence of respiratory disorders predominantly confined to REM sleep, the AHI was also calculated during REM sleep (AHI-REM) and during non-REM sleep (AHI-NREM), and patients were classified as having REM SDB if the AHI-REM/AHI-NREM ratio was > 2, and non-REM SDB if the AHI-REM/AHI-NREM ratio was 
2, according to a previous report.4
Sleepiness Assessment
Subjective daytime sleepiness was assessed in all patients by the administration of the Epworth sleepiness scale (ESS).9 In patients willing to perform an objective measure of sleepiness, the maintenance wakefulness test (MWT) was performed according to standard criteria (n = 228).10 This was done by asking the patients to sit in a quiet, dark room and to try to stay awake for five sessions scheduled at 9 AM, 11 AM, 1 PM, 3 PM, and 5 PM. All tests were terminated 15 min after sleep onset or after 40 min without sleep, and a mean sleep latency was calculated by averaging the latencies to sleep for the five naps.
Statistical Analysis
Polygraphic and clinical findings in REM-related and non-REM–related SDB were compared using respectively the Mann-Whitney U test and the 
2 test. Statistical significance was determined as p < 0.01 after Bonferroni correction. All statistical analysis were performed with statistical software (SPSS for Windows, version 10.0; SPSS; Chicago, IL). Results are reported as mean ± SD.
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Results |
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REM SDB patients were slightly younger, had higher BMI, and had lower neck circumference; however, differences reaching statistical significance only for neck circumference (p < 0.001). While in the non-REM SDB group a clear male prevalence was present (83.5%), in the REM SDB group, 46.4% of cases were women and 53.6% were men.
Compared to REM SDB, non-REM SDB patients were referred more frequently for witnessed breathing pauses during sleep (p < 0.001). No differences were found between groups as to snoring and daytime sleepiness as chief complaints. Detailed clinical interview did not reveal significant differences between groups as to incidence of morning headache, daytime sleepiness, cognitive difficulties, abnormal motor activity during sleep, nycturia, habitual snoring, or excessive nocturnal sweating. No significant differences were present in medical history for cardiovascular, neurologic, psychiatric, and metabolic disease between non-REM and REM SDB, and no difference was found for habitual drug intake.
Table 2 shows the polysomnographic findings in REM SDB and non-REM SDB patients. The two groups differed significantly in all parameters of sleep continuity and sleep fragmentation, with non-REM SDB patients having lower amounts of slow wave sleep and REM sleep. Since body position could influence the occurrence of respiratory events, we calculated for the two groups the sleep time spent in back and lateral positions, with no significant difference found between groups (p = 0.7 and p = 0.95, respectively). Analysis of respiratory disturbances in the two groups revealed that non-REM patients had higher AHI-TST, more severe nocturnal hypoxemia indexes, and longer apneas and hypopneas. Despite differences in SDB severity, no difference in the EES score (p = 0.8) or in the mean sleep latency at the MWT (p = 0.1) was present between groups.
As shown in Tables 1 and 2, there were no significant differences in the percentage of those receiving different types of medication in REM SDB and in non-REM SDB patients, and the amount of REM sleep was not different between groups. To see whether a possible effect of medication could explain our results, we analyzed data from patients without treatment. Of the total group, 229 patients (55.1%) were completely free of medication, 76 patients (50.3%) in the REM SDB group, and 153 patients (57.3%) in the non-REM SDB group. Two hundred ninety-nine patients did not receive any psychotropic drug that could influence sleep parameters. Ninety-nine patients presented with REM SDB, and 200 patients presented with non-REM SDB. Moreover, analysis of polysomnographic findings between patients with REM and non-REM SDB free of medication or without psychotropic drugs did not reveal significant differences. In particular, there were no differences in subjective sleepiness (p = 0.9) or objective sleepiness (p = 0.3) between REM SDB patients and non-REM SDB patients free of medication.
REM SDB Characteristics in Groups of Varying Severity
In order to assess whether the occurrence of REM SDB was related to the severity of disease, the incidence of REM SDB was assessed in the three groups of patients stratified on the basis of the AHI-TST (Table 3
). A high incidence of REM SDB was found in mild cases (73.1%), with lower incidence in moderate cases (47.2%) and especially in severe cases (6.9%) [Fig 1
]. No significant differences in age, BMI, and neck circumference were seen between REM and non-REM SDB among the different severity groups, except for the BMI that was greater in REM SDB in mild cases (p < 0.001) and moderate cases (p < 0.005). Considering the effect of gender, again the incidence of REM SDB was greater in women, representing, respectively, 48.3% and the 51% of the population in mild and moderate REM SDB cases. This gender difference was not found in severe cases, the male/female ratio being > 4:1 both in REM and non-REM SDB (Table 3, Fig 2
).
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Table 3 reports the polysomnographic findings for REM SDB and non-REM SDB patients according to severity of disease. No significant differences in all analyzed sleep variables were found between groups, including amount of REM sleep.
No significant differences in the AHI-TST and indexes of nocturnal hypoxemia were present between REM SDB and non-REM SDB in mild and moderate cases except for the minimal SaO2 value, which was lower in REM SDB (p < 0.005). In severe cases, the AHI-TST (p < 0.001) and the ODI (p < 0.01) were greater in non-REM SDB patients. As expected, AHI-REM was higher in REM SDB than in non-REM SDB patients in the three severity groups (p < 0.001).
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Discussion |
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The first finding of our study was that despite the fact that REM and non-REM sleep are functionally distinct sleep states, no differences in clinical presentation and sleepiness were found in our patients. Subjective and objective daytime sleepiness were consistently similar between REM and non-REM SDB patients, and complaints of sleepiness did not differentiate REM SDB. These results are partially in contrast with the first description of the disorder,1 in which the AHI during REM predicted the objective and subjective sleepiness of the patients, at least in patients with mild SDB. This could be explained by some differences in criteria applied to define REM SDB and in the assessment of sleepiness. Firstly, we considered patients with a wide range of SDB severity, while Kass et al1 examined only patients with clinically suspected SDB having AHI-TST < 10/h. In order to see if a population sample could explain the above differences, we extracted from our group patients with AHI-TST <10/h, and we applied the criteria of Kass and coworkers1 to compare REM-SDB, ie, patients with AHI-REM 15/h to non-REM SDB patients, ie, those with AHI-REM < 15/h. Sixty-six patients in our sample had AHI-TST <10/h, 53 cases defined as REM SDB and 13 cases defined as non-REM SDB according to criteria of Kass and coworkers.1 Comparison between these subgroups confirmed the greater prevalence of women in the REM SDB group (50.9%), without, however, any differences for anthropometric, clinical, and polygraphic findings. Moreover, patients with AHI-REM 15/h were not more sleepy than patients with AHI-REM < 15/h, with no significant difference found for sleep latency at the MWT (p = 0.16), ESS score (p = 0.4), or the complaints of sleepiness (p = 0.6) or fatigue (p = 0.55). Thus we can conclude that the range of severity and the sample population alone could not explain the differences in the results. Second, while Kass et al1 used the multiple sleep latency test, objective sleepiness was assessed by means of the MWT in our sample. Although the use of a different method to assess sleepiness could affect results, we believe that this is unlikely to be a factor contributing to different results. In fact, in line with our results, two extensive studies23 considering the influence of sleep stage on daytime sleepiness using the multiple sleep latency test have shown that sleep fragmentation limited to REM sleep has no specific impact on diurnal sleepiness. This is also confirmed by experimental data using acoustically induced clustered sleep fragmentation, which reproduces in some ways the sleep alterations found in REM SDB.13 In line with our results, the authors13 did not find any difference in daytime sleepiness, mood, and cognitive functions, suggesting that REM SDB should not be considered a specific sleep-state breathing disorder inducing greater sleepiness.
The second interesting finding is that REM SDB appears to occur more frequently in mild-to-moderate cases with an equal incidence in men and in women, as opposed to a higher prevalence of male subjects with non-REM SDB. This finding replicates the study of O’Connor et al,4 showing a high prevalence of REM SDB in women and in mild-to-moderate cases. The lack of a greater daytime sleepiness in REM SDB and the equal prevalence in women and in men and in mild-to-moderate cases opens discussion as to whether REM SDB really is a distinct clinical entity or whether it reflects the natural progression of the disease. Since neither clinical history, polysomnographic data, nor indexes of daytime sleepiness differentiate REM SDB from non-REM SDB in a sample larger than that firstly described,1 we believe that the existence of the disease as a specific entity could be discarded.
We therefore suggest that occurrence of REM-related SDB may be suspected more frequently in women and in patients in whom clinical and polygraphic findings suggest a mild-to-moderate severity. An attractive hypothesis is that REM SDB may represent the clinical spectrum of the disease, beginning with intermittent apneas predominantly during REM sleep, in stages 0 and 1 of the hypothesis of Lugaresi et al,14 and affecting all sleep stages when the disease progresses. This could also explain why, in untreated patients prospectively examined,151617 the deterioration of the disease is significantly greater in mild-to-moderate cases and in men compared to women.17
There are several limitations to our study that should be keep in mind. First, this is a retrospective study, with all the biases related to such clinical recruitment and referral patterns. However, we think that we can consider our population as clinically representative of the disease, all patients referred for suspected SBD during a specific period being studied. Second, our clinical assessment was based on the medical interview, focusing on subjective complaints such as fatigue and sleepiness, and on nocturnal symptoms. Therefore, we cannot exclude that subtle changes in other diurnal consequences such as cognitive functions could have gone undetected by clinical interview, more specific tests being necessary to allow a better identification of the clinical impact of predominant respiratory events in REM. Third, the criteria we used to define REM SDB (AHI-REM/AHI-NREM ratio > 2) is somewhat arbitrary. However, in the absence of formally established criteria, we applied strictly the criteria previously proposed.4 The use of other cutoff values reduced considerably the size of the REM SDB groups (particularly in the most severe group) without changing the main conclusions of the present study. Fourth, we know that sleep position can influence occurrence of respiratory events, with back position frequently inducing appearance or worsening of respiratory events. Although we did not calculate for non-REM and REM sleep the time spent in each position, we found no significant difference between groups concerning the sleep time spent in both positions, suggesting that sleep position alone did not affect our results. Finally, we did not have an objective assessment of sleepiness in all patients, and patients undergoing the MWT complained more frequently of sleepiness and differed in terms of severity of the disease. Nevertheless, a significant number of patients in the different groups underwent the MWT, allowing us a sufficient comparison between REM SDB and non-REM SDB.
In conclusion, after analyzing the clinical and polysomnographic features of a large group of patients with SDB, we found that REM SDB is frequent in mild-to-moderate cases and its prevalence is similar in women and in men. The occurrence of respiratory disturbances in REM sleep does not seem to affect initial complaints, medical history, and daytime sleepiness, and therefore could not be considered a specific form of SDB. Whether the occurrence of REM SDB reflects only the over-time progression of the disease needs to be confirmed in prospective studies.
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Acknowledgements |
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Footnotes |
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Received for publication January 12, 2005. Accepted for publication May 27, 2005.
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