1. Art and Diseño

Rapid Eye Movement-Related
Disordered Breathing*
Clinical and Polysomnographic Features
Jose´ Haba-Rubio, MD; Jean-Paul Janssens, MD; Thierry Rochat, MD, PhD; and
Emilia Sforza, MD, PhD
Objective: The existence of a rapid eye movement (REM)-specific sleep-disordered breathing
(SDB) has been suggested based on the finding of an association between sleepiness and
respiratory disturbances confined primarily to REM sleep. The aim of the study was to define the
frequency and the clinical and polysomnographic features of REM SDB in a large clinical
population.
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 ⴝ 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.
(CHEST 2005; 128:3350 –3357)
Key words: polysomnography; rapid eye movement sleep; sleep-disordered breathing; sleepiness
Abbreviations: AHI ⫽ apnea-hypopnea index; AHI-NREM ⫽ apnea-hypopnea index during non-rapid eye movement;
AHI-REM ⫽ apnea-hypopnea index during rapid eye movement; AHI-TST ⫽ apnea-hypopnea index during total sleep
time; BMI ⫽ body mass index; ESS ⫽ Epworth sleepiness scale; MWT ⫽ maintenance wakefulness test;
NREM ⫽ non-rapid eye movement; ODI ⫽ oxygen desaturation index; REM ⫽ rapid eye movement; Sao2 ⫽ arterial
oxygen saturation; SDB ⫽ sleep-disordered breathing; SFI ⫽ sleep fragmentation index; TST ⫽ total sleep time
apid eye movement (REM)-related sleep-disorR dered
breathing (SDB) has been introduced by
sleep researchers to refer to a specific SDB characterized by daytime sleepiness and respiratory distur*From the Sleep Laboratory, Department of Psychiatry (Drs.
Haba-Rubio and Sforza), and Pneumonology Division (Drs.
Janssens and Rochat), University Hospital, Geneva, Switzerland.
Manuscript received January 12, 2005; revision accepted May 27,
2005.
Reproduction of this article is prohibited without written permission
from the American College of Chest Physicians (www.chestjournal.
org/misc/reprints.shtml).
Correspondence to: Emilia Sforza, MD, PhD, Laboratoire de
Sommeil, Service de Psychiatrie Adulte, Hoˆpitaux Universitaires
de Gene`ve, 2 Chemin du Petit Bel Air, 1225 Cheˆne Bourg,
Gene`ve, Switzerland; e-mail: [email protected]
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bances confined to REM sleep in patients with a
global respiratory disturbance index ⬍ 10.1 To the
first hypothesis of a state-specific sleep disorder
expression of sleep fragmentation limited to REM
sleep,1 data have not confirmed a major impact of
REM respiratory events on diurnal impairment,2,3
with REM-related SDB reflecting more a sleep
disorder related to gender4 and severity of the
disease2 than a specific sleep disorder inducing
sleepiness. In the light of these contradictory results,
the aim of the present study was to evaluate the
frequency and the clinical and polysomnographic
aspects of patients presenting with REM-related
SDB. A second aim was to assess whether specific
Clinical Investigations
daytime complaints, clinical aspects, and polysomnographic features differentiate these patients from
those having respiratory disturbances in all sleep
stages.
Materials and Methods
Subjects
From a computerized database of all patients undergoing
polysomnography for suspected SDB at the Geneva University
Hospital sleep laboratory between October 2000 and February
2004, 492 patients were identified. Patients were excluded for the
following: (1) apnea-hypopnea index (AHI) ⬍ 5/h of total sleep
time (TST) (n ⫽ 59); (2) previous treatment for SDB by continuous positive airway pressure therapy, surgery, and/or oral device
(n ⫽ 1); (3) REM sleep ⬍ 15% of TST during nocturnal recording (n ⫽ 54), or if complete clinical data were unavailable
(n ⫽ 23). Of the initial sample, 415 patients fulfilled the inclusion
criteria (mean age, 54.1 ⫾ 12.1 years [mean ⫾ SD]; 73% men);
mean body mass index (BMI) was 31.3 ⫾ 6.3 kg/m2. Globally, the
patient had moderate-to-severe SDB (AHI, 34.1 ⫾ 25.5/h; range,
5.1 to 126.4/h). Patients were informed that some of the collected
data would be used for research purposes, and they gave written
informed consent.
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 AHIREM/AHI-NREM ratio was ⬎ 2, and non-REM SDB if the
AHI-REM/AHI-NREM ratio was ⱕ 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.
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 electrooculograms, 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.6,7
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 ⱖ 50% reduction in
airflow from the baseline value lasting at least 10 s, or a clear
amplitude airflow reduction lasting ⱖ 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
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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.
Results
Parient Characteristics
In the group of patients as a whole, 46.5% were
referred for snoring, 30.3% for witnessed apneas,
and 17.3% for daytime sleepiness. Detailed clinical
interviews revealed a high percentage of patients
presenting with habitual and loud snoring (88.9%),
fatigue (66.3%), excessive daytime sleepiness (52.7%),
nycturia (55.2%), and witnessed apneas (50.6%). A
high proportion of patients had a history of cardiovascular (55.8%), metabolic (47.4%), or psychiatric
illness (32.4%); 24.5% and 17.8% were receiving
antihypertensive or antidepressant drugs, respectively (Table 1).
As a whole, the patients had a mean ESS score
of 9.4 ⫾ 4.9 (Table 2). In the subsample of 228
patients who underwent the MWT, mean sleep
latency was 21.8 ⫾ 12.1 min. In order to ascertain
if these patients were different from those without
an objective sleepiness assessment, we compared
both groups. Patients who performed the MWT
CHEST / 128 / 5 / NOVEMBER, 2005
3351
Table 1—Anthropometric and Clinical Data of the Total SDB Patients, REM SDB Patients, and Non-REM SDB
Patients*
Variables
Total (n ⫽ 415)
REM SDB (n ⫽ 151)
Non-REM SDB (n ⫽ 264)
Patients
Female gender
Age, yr
BMI, kg/m2
Neck circumference, cm
Primary complaint
Snoring
Witnessed apnea
Sleepiness
Medical history
Cardiovascular
Psychiatric
Lung disease
Metabolic
Neurologic
Medications
Antihypertensive
Antidepressant
Benzodiazepine-hypnotic
100
27
54.1 (12.1)
31.3 (6.3)
40.7 (5.7)
36.4
46.4
53 (11.6)
32.2 (6.8)
39.5 (6.6)
63.6
16.5†
55 (12.2)
30.8 (5.9)
41.4 (5)†
46.5
30.3
17.3
52.3
20.5
19.2
43
36.2†
15.4
55.8
32.4
6.8
47.4
3.6
54.2
39
6.5
46.3
4.6
57.9
29
6.3
49
2.8
24.5
17.8
20.6
26.4
17.8
27.7
24
17.5
16.4
*Data are presented as % or mean (SD).
†p ⬍ 0.001, REM SDB vs non-REM SDB.
were of similar age, BMI, and gender distribution,
but they had a more severe SDB with higher
AHI-TST (AHI, 40.2 ⫾ 26.1/h vs 29.2 ⫾ 24.9/h;
p ⬍ 0.001), and complained more frequently of day-
time sleepiness (p ⬍ 0.001), fatigue (p ⬍ 0.001), witnessed apneas (p ⬍ 0.01), snoring (p ⬍ 0.001), and
perspiration (p ⬍ 0.01) when compared with patients
without MWT evaluation.
Table 2—Polysomnographic Data of the Total SDB Patients, REM SDB Patients, and Non-REM SDB Patients*
Variables
Total (n ⫽ 415)
REM SDB (n ⫽ 151)
Non-REM SDB (n ⫽ 264)
TST, min
Wake after sleep onset, min
Stage 1, min
Stage 2, min
Stage 3–4, min
Stage REM, min
Sleep latency, min
Sleep efficiency, %
SFI, No./h
Sleep time in dorsal position, min
Sleep time in lateral position, min
Periodic leg movement index, No./h
AHI, No./h
REM AHI, No./h
Non-REM AHI, No./h
Apnea duration, s
Hypopnea duration, s
Wake Sao2, %
Mean minimal Sao2, %
Minimal Sao2, %
ODI, No./h
MWT, min
ESS score
415.3 (70.2)
98.5 (57.4)
74.5 (31.9)
221 (58.4)
51.8 (40.1)
67.9 (28.8)
10.4 (14.1)
78.1 (10.9)
139.8 (77.2)
183.5 (128.4)
230.8 (130.3)
11.6 (16.2)
34.1 (25.5)
37.9 (23.4)
30.3 (25.1)
18.1 (5.9)
15 (2.6)
93.1 (4.9)
88.4 (3.9)
77.8 (8.6)
21.9 (20.3)
21.8 (12.1)‡
9.4 (4.9)
421.3 (70)
91 (53.4)
61.5 (22.1)
218 (53.1)
66.3 (40)
75.4 (29.1)
10.3 (12.8)
79.3 (10.8)
104.4 (38.3)
186 (131.6)
229.7 (134.9)
9 (12.7)
15.7 (9.2)
40.2 (20.9)
9.6 (7.9)
16.3 (5.7)
14.3 (2.2)
93.1 (7.7)
89.3 (3.2)
79.9 (6.8)
9.7 (7.7)
23.7 (10.7)
9.3 (4.7)
413.1 (69.4)
101.4 (58.7)
81.4 (34)†
223.1 (60.2)
44.5 (38.2)†
64 (27.4)†
10.6 (15.1)
77.5 (10.8)
158.1 (84.6)†
181.3 (126.8)
230.5 (128.3)
13.2 (17.6)
43.3 (25.9)
37.2 (24.5)
40.7 (24.3)†
19.1 (5.8)†
15.4 (2.8)†
93.1 (1.9)
87.9 (4.2)†
76.7 (9)†
27.9 (21.8)†
21.3 (12.5)
9.3 (5)
*Data are presented as mean (SD).
†p ⬍ 0.001, REM SDB vs non-REM SDB.
‡Total patients, n ⫽ 228; REM SDB patients, n ⫽ 67; non-REM SDB patients, n ⫽ 169.
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Clinical Investigations
REM SDB vs non-REM SDB
Table 1 shows the anthropometric and clinical
characteristics of the patient groups. One hundred
fifty-one patients (36.4%) presented with REM
SDB; the remaining 279 patients (63.6%) were
considered as having a SDB nondependent on sleep
stage (ie, non-REM SDB), the AHI-REM/AHINREM ratios being 7.2 ⫾ 7.7 and 1.3 ⫾ 3.6, respectively (p ⬍ 0.001).
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 nonREM 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
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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. Ninetynine 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).
As far as clinical findings are concerned, no differences in initial complaints (snoring, witnessed
apneas, sleepiness) and medical history for cardiovascular, lung, metabolic, neurologic or lung diseases, or drug intake (antihypertensives, antidepressants, benzodiazepines) were noted between REM
SDB and non-REM SDB patients in the different
groups stratified on the basis of disease severity. The
detailed clinical interview also failed to identify any
specific complaint usually associated with SDB, related to one or other group. No significant differences were found in frequency of morning headache,
daytime tiredness or sleepiness, memory or concentration complaints, motor activity during sleep, witnessed apneas, nycturia, snoring, or nocturnal sweating. In all severity groups, neither the ESS nor the
CHEST / 128 / 5 / NOVEMBER, 2005
3353
Table 3—Clinical, Anthropometric, and Polygraphic Findings of REM SDB and Non-REM SDB According to
Severity of Disease*
AHI 5 to 15/h
AHI 15 to 30/h
AHI ⬎ 30/h
Variables
REM SDB
(n ⫽ 87)
Non-REM SDB
(n ⫽ 32)
REM SDB
(n ⫽ 51)
Non-REM SDB
(n ⫽ 57)
REM SDB
(n ⫽ 13)
Non-REM SDB
(n ⫽ 175)
Patients
Female gender
Age, yr
BMI, kg/m2
Neck circumference, cm
TST, min
Wake after sleep onset, min
Stage 1, min
Stage 2, min
Stage 3–4, min
Stage REM, min
Sleep latency, min
Sleep efficiency, %
SFI, No./h
Periodic leg movement index, No./h
Apnea duration, s
Hypopnea duration, s
AHI, No./h
REM AHI, No./h
Non-REM AHI, No./h
Wake Sao2, %
Mean minimal Sao2, %
Minimal Sao2, %
ODI, No./h
MWT, min
ESS score
73.1
48.3
51.6 (12)
32.3 (6.9)
39.5 (5.6)
423.7 (66.2)
89.6 (53.2)
59 (22.6)
215.6 (51.7)
69 (43.1)
79.9 (28.4)
11 (14.9)
79.8 (10.5)
96.1 (33.3)
8.8 (13.8)
15.3 (6.3)
14.1 (2.4)
9.2 (2.9)
27.8 (12.5)
4.8 (2.7)
92.6 (10.2)
89.5 (3.4)
81.2 (6.4)
6.6 (4.7)
24.3 (9.8)
9.6 (4.5)
26.9
9.3†
50.6 (12.4)
26.8 (3.7)†
40.1 (2.6)
426.9 (62.3)
72.3 (55.3)
68.2 (24.6)
217.4 (58.1)
63.6 (29.9)
77.5 (28.1)
8.3 (9.5)
82.7 (9.3)
114.5 (38.5)
9.4 (13.4)
15.5 (4.5)
13.9 (1.5)
10.3 (2.8)
7 (5.3)†
10 (3.1)†
94 (1.4)
90.9 (1.9)
84.6 (3.2)‡
6.2 (5.8)
24.8 (9.7)
9.4 (4.1)
47.2
51
53.8 (10.4)
32.3 (7.2)
39.8 (6.6)
424.2 (70)
89.1 (49)
63.6 (21.1)
224.5 (54.8)
64.3 (33.5)
71.6 (28.6)
9.1 (9.4)
79.3 (10.2)
111.3 (41.2)
9 (11)
17.1 (4.5)
14.6 (1.8)
14.5 (5)
53.3 (15.7)
13.2 (5.5)
93.7 (1.3)
89.1 (2.9)
78.9 (7.1)
11.7 (7.4)
22.1 (10.4)
9.3 (5.1)
52.8
14†
52.2 (11.1)
29.1 (3.9)‡
40.4 (2.9)
408.7 (67.7)
94.2 (50.9)
65.2 (27.3)
213.8 (63.6)
58.3 (27.7)
71.5 (25.4)
7.9 (8.6)
78.3 (10)
118.9 (40.6)
10.9 (15.7)
16.3 (4.1)
14.9 (2.4)
22.1 (4)
17.1 (12.5)†
22.2 (6.8)†
93.4 (1.4)
89.5 (2.4)
82.2 (4.7)‡
12.4 (8.1)
22.7 (9.7)
9.2 (4.8)
6.9
15.4
59 (11.2)
31.4 (4.9)
38.5 (11.8)
394 (92.2)
108 (70.4)
70.1 (21.6)
207.9 (57.2)
56.2 (43)
59.7 (30.2)
10 (8.7)
76.2 (15.4)
133.1 (41.1)
10.6 (11.9)
19 (4.9)
14.3 (2.1)
36.5 (6)
71.5 (20.6)
28 (3.7)
93.5 (1.6)
88.3 (1.9)
75.6 (5.7)
23.5 (7.9)
28.2 (13.8)
8.1 (4.8)
92.1
17.7
56.3 (12.4)
32.1 (6.3)
42 (5.8)
410 (72.5)
111.1 (60.5)
89.9 (35.1)
226.5 (61)
35.1 (39.3)
58.4 (27.1)
11.7 (17)
76 (11.2)
181.8 (94.9)
14.5 (18.9)
20.6 (5.9)
15.8 (3)
58.2 (21)†
48.4 (21)†
54.6 (19.4)†
92.9 (2.1)
86.7 (4.6)
73.3 (9.4)
38.4 (20.8)§
20.2 (13.4)
9.4 (5.2)
*Data are presented as % or mean (SD).
†p ⬍ 0.001, REM SDB vs non-REM SDB inside different severity groups.
‡p ⬍ 0.005, REM SDB vs non-REM SDB inside different severity groups.
§p ⬍ 0.001, REM SDB vs non-REM SDB inside different severity groups.
mean sleep latency on the MWT differed between
REM and non-REM SDB patients.
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).
Discussion
The aim of the current study was to determine
whether clinical and polysomnographic variables dif3354
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ferentiate REM SDB patients in a relatively large
group with different degrees of SDB severity. The
major results of the study are as follows: (1) neither
clinical history nor daytime sleepiness differentiates
patients with and without respiratory disturbances
confined to REM sleep; (2) REM SDB is a sleep
disorder more common in mild and moderate cases,
no sleep stage effect having been found in severe
cases; and (3) the prevalence of REM SDB is
relatively the same in women and men, in contrast to
the strong male predominance generally described
in SDB.11,12 These results suggest that REM SDB is
more a sleep-related breathing disorder linked to
gender and to the severity of the disease, rather than
a specific breathing disorder inducing sleepiness.
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
Clinical Investigations
Figure 1. Percentage of patients with REM SDB and non-REM SDB
in the three groups of patients stratified according to disease severity. A
high incidence of REM SDB is found in mild and moderate cases.
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 AHITST ⬍ 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
ⱖ 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 ⱖ 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
studies2,3 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
Figure 2. Percentage of male and female patients with REM SDB (left panel) and non-REM SDB
(right panel) stratified according to disease severity. The male/female ratio is constant in non-REM
SDB among the different severity groups. In REM SDB, the male/female ratio is approximately 1:1 in
mild and moderate cases.
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CHEST / 128 / 5 / NOVEMBER, 2005
3355
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-tomoderate 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 REMrelated 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,15–17
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 worsen3356
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ing 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.
ACKNOWLEDGMENT: The authors are grateful to B. Adjivon,
E. Claudel, D. Grasset, and A. Lalji for technical assistance.
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