Daytime sleepiness and its determining factors in Chinese obstructive sleep apnea patients

Abstract

The aim of this study was to characterize excessive daytime sleepiness (EDS) in a large cohort of Chinese patients with various severity of obstructive sleep apnea-hypopnea syndrome (OSAHS), and investigate its correlations with clinical/polysomnographic variables.
A total of 1,035 consecutive Chinese patients with snoring (mean age ± SD 45 ± 15 years, BMI 26.6 ± 4.3 kg/m(2)) were examined by overnight polysomnography, and subjective EDS was assessed using the Epworth Sleepiness Scale (ESS).
The 1,035 patients were compared according to severity of sleep-disordered breathing: AHI <5 (primary snoring group or normal overall AHI) (24.1%), AHI 5-20 (mild OSAHS, 21.7%), AHI >20-40 (moderate OSAHS 16.5%), and AHI >40 (severe OSAHS 37.7%). ESS score progressively increased as the severity of OSAHS aggravated among these patients. More severe OSAHS patients were characterized by EDS, nocturnal hypoxemia, and disruption of sleep structure. Progressive worsening of nocturnal hypoxemia was observed from mild to severe OSAHS patients with a strong correlation with ESS score. The stepwise multiple regression analysis performed to evaluate the correlations of individual clinical and polysomnographic variables with the ESS score revealed that the ESS score significantly correlated with the oxygen desaturation index (ODI), apnea-hypopnea index (AHI), and body mass index (BMI), and ODI was the strongest determinant of ESS score.
EDS is correlated with the severity of OSAHS. More severe patients are characterized by higher ESS score, higher BMI, and progressive worsening of nocturnal hypoxemia. Nocturnal hypoxemia is a major determinant of EDS in Chinese OSAHS patients.

Full text

ORIGINAL ARTICLE
Daytime sleepiness and its determining factors in Chinese
obstructive sleep apnea patients
Rui Chen &Kang-ping Xiong &Yi-xin Lian &
Juan-ying Huang &Min-yan Zhao &Jian-xiang Li &
Chun-feng Liu
Received: 22 October 2009 / Revised: 21 January 2010 /Accepted: 27 January 2010 /Published online: 20 February 2010
#Springer-Verlag 2010
Abstract
Objective The aim of this study was to characterize
excessive daytime sleepiness (EDS) in a large cohort of
Chinese patients with various severity of obstructive sleep
apnea–hypopnea syndrome (OSAHS), and investigate its
correlations with clinical/polysomnographic variables.
Materials and methods A total of 1,035 consecutive
Chinese patients with snoring (mean age ± SD 45 ±15 years,
BMI 26.6±4.3 kg/m
2
) were examined by overnight poly-
somnography, and subjective EDS was assessed using the
Epworth Sleepiness Scale (ESS).
Results The 1,035 patients were compared according to
severity of sleep-disordered breathing: AHI <5 (primary
snoring group or normal overall AHI) (24.1%), AHI 5–20
(mild OSAHS, 21.7%), AHI >20–40 (moderate OSAHS
16.5%), and AHI >40 (severe OSAHS 37.7%). ESS score
progressively increased as the severity of OSAHS aggra-
vated among these patients. More severe OSAHS patients
were characterized by EDS, nocturnal hypoxemia, and
disruption of sleep structure. Progressive worsening of
nocturnal hypoxemia was observed from mild to severe
OSAHS patients with a strong correlation with ESS score.
The stepwise multiple regression analysis performed to
evaluate the correlations of individual clinical and poly-
somnographic variables with the ESS score revealed that
the ESS score significantly correlated with the oxygen
desaturation index (ODI), apnea–hypopnea index (AHI),
and body mass index (BMI), and ODI was the strongest
determinant of ESS score.
Conclusion EDS is correlated with the severity of OSAHS.
More severe patients are characterized by higher ESS score,
higher BMI, and progressive worsening of nocturnal
hypoxemia. Nocturnal hypoxemia is a major determinant
of EDS in Chinese OSAHS patients.
Keywords Excessive daytime sleepiness .Nocturnal
hypoxemia .Obstructive sleep apnea–hypopnea syndrome .
Polysomnography
Introduction
Obstructive sleep apnea–hypopnea syndrome (OSAHS) is
characterized by recurrent upper airway collapse during
sleep leading to intermittent nocturnal hypoxemia and sleep
fragmentation [1]. It is often associated with comorbidities
such as hypertension and other cardiovascular and meta-
bolic disorders, neurocognitive dysfunction, etc. [2,3]. The
prominent symptoms of OSAHS are snoring and excessive
daytime sleepiness (EDS), and some of the patients could
have difficulty in concentrating and experience microsleep,
poor memory, and decreased attentional capacity [4]. EDS,
in particular, is known to be a predisposing factor for
accidents, interpersonal problems, and reduced productivity
among OSAHS patients [5,6].
R. Chen :K.-p. Xiong :Y.-x. Lian :J.-y. Huang :M.-y. Zhao :
C.-f. Liu (*)
Sleeping Center,
Second Affiliated Hospital of Soochow University,
1055 Sanxiang Road,
Suzhou, Jiangsu 215004, China
e-mail: liucf20@hotmail.com
R. Chen :K.-p. Xiong :C.-f. Liu
Laboratory of Aging and Nervous Diseases,
Institute of Neuroscience, Soochow University,
Suzhou, Jiangsu 215004, China
J.-x. Li
Department of Toxicology, School of Radiation Medicine and
Public Health, Medical College of Soochow University,
Suzhou, Jiangsu 215007, China
Sleep Breath (2011) 15:129–135
DOI 10.1007/s11325-010-0337-4

The mechanisms underlying EDS observed in the OSAHS
patients remain unclear. It has been postulated to be related to
nocturnal sleep disturbance or to the metabolic and psycho-
logical factors, such as obesity and depression, etc. [7,8].
Likewise, studies investigating a potential relationship be-
tween EDS and several indices of nocturnal oxygenation also
have yielded controversial findings [9–11], some of which
were limited by the small sample size and require further
evaluations in large cohort of patients. In this study, a total of
1,035 consecutive cases of Chinese snoring patients were
examined at our institution by overnight polysomnography,
and subjective EDS was assessed using the Epworth Sleep
Scale (ESS) questionnaire, which is a quick, inexpensive, and
validated tool for the assessment of chronic sleepiness [12,
13]. The aim of the present study was to characterize EDS in
a large cohort of Chinese patients with different degrees of
OSAHS, and evaluate its correlation with various clinical and
polysomnographic variables, including body mass index
(BMI), apnea–hypopnea index (AHI), nocturnal hypoxemia,
and sleep structure, of which the relative importance of their
impact on EDS was also investigated.
Materials and methods
Subjects
We examined a total of 1,180 consecutive patients who
presented snoring problem with clinical suspicion of
OSAHS between April 2004 and December 2008 at our
institution. Of these, a total of 1,035 patients were included
(866 men and 169 women, mean age ± SD 45± 15 years),
and 145 patients were excluded due to (1) patients received
treatment for sleep-related breathing disorders; (2) diagno-
sis of obesity hypoventilation syndrome for patients (N=
26) who has BMI ≥30 kg/m
2
associated with abnormal
daytime blood gas measurement (PaO
2
<70 mm Hg, PaCO
2
>45 mm Hg); (3) concomitant presence of other sleep
disorders, such as central sleep apnea (CSA), restless legs
syndrome, rapid eye movement (REM) sleep behavior
disorders, periodic limb movement disorders, narcoleptic
spectral disorders, etc., and (4) other diseases such as
cancer, severe physical disability, and mental disorders,
including those receiving relevant medications, which
would impact the quality of life, mentality, and sleep
profiles of the patients. The study was approved by the
hospital ethics board and all patients were informed and
consented prior to the study procedures.
EDS evaluation
The medical history, principal symptoms during the day
and sleep at night, and previous and concomitant medi-
cations were collected. A validated Chinese version of the
ESS questionnaire [14] with eight items and four-point
scales (0–3) was completed for each patient on the day of
admission to evaluate the subjective EDS (0 =would never
doze off, 1 =slight chance of dozing off, 2 =moderate
chance of dozing off, and 3= high chance of dozing off,
under the situations of (1) sitting and reading, (2) watching
TV, (3) sitting, inactive in a public place (e.g., theater or a
meeting), (4) as a passenger in a car for an hour without a
break, (5) sitting and talking to someone, (6) sitting quietly
after a lunch without alcohol, (7) while stopped for a few
minutes in traffic in a car, and (8) lying down to rest in the
afternoon when circumstances permit). The ESS score
ranges between 0 and 24 with the normal value ≤10 [12].
EDS was considered present whenever ESS score was >10.
Polysomnographic study
Overnight polysomnographic study (Sandman Elite, Tyco,
Canada) was performed in an attended setting for all patients
on the first night of admission starting from 10 p.m. to 6 a.m.
next morning, and at least 7 h of recording time was
considered a successful monitoring. The polysomnographic
study included the following: airflow by using oronasal
thermistors and nasal pressure transducer, thoracic and
abdominal respiratory movements, arterial oxygen saturation
by pulse oximetry, snoring and body position, electroen-
cephalogram (C3/A2, C4/A1, O1/A2, and O2/A1), electro-
oculogram, chin and leg electromyogram, and
electrocardiogram. The following polysomnographic varia-
bles were obtained: apnea–hypopnea index (AHI), oxygen
desaturation index (ODI, defined as the sum of the numbers
of oxyhemoglobin desaturation of >4% events per hour of
sleep), time of oxygen saturation <90% (Time (SpO
2
<
90%)), minimum pulse oxygen saturation (SpO
2
), total sleep
time (TST), non-rapid eye movement (NREM) sleep phases
1–4, REM sleep, and respiratory arousal index.
All studies were analyzed by trained PSG technicians
and sleep physicians using the criteria of Rechtschaffen and
Kales [15], and in close concordance with scoring updates
given by the American Academy of Sleep Medicine [16].
The traditional Rechtschaffen and Kales terminology for
the five sleep stages (i.e., stages 1, 2, 3, 4, and REM sleep,
with stages 1 and 2 collectively referred to as “light sleep”,
stages 3 and 4 collectively referred to as “deep sleep”or
“Slow wave sleep”) were used in this study. Apneas were
scored when there was a complete cessation of airflow or
≥90% drop in the peak thermal sensor excursion for at least
10 s. Hypopneas were scored when there was a drop in
nasal pressure signal excursion by ≥30% of baseline lasting
at least 10 s with a ≥4% desaturation from pre-event
baseline, or when there was a drop in nasal pressure signal
excursion by ≥50% of baseline lasting at least 10 s with a
130 Sleep Breath (2011) 15:129–135

≥3% desaturation from pre-event baseline and/or the event
associated with arousal. The AHI was defined as the sum of
the numbers of apneas and hypopneas per hour of sleep.
Statistical analysis
Data were presented as mean ± SD, and statistical analysis
was performed by using SPSS 11.0 software: (1) one-way
ANOVA for the comparison of ESS score, clinical and
polysomnographic variables between groups of patients
with different severities of OSAS; (2) linear regression with
calculation of Pearson correlation coefficient (r) to evaluate
the correlations of individual clinical and polysomno-
graphic variables with the ESS score; and (3) stepwise
multiple regression analysis with calculation of standard
partial regression coefficient (β) to examine the relative
importance of major determinants of ESS score. Statistical
significance was defined as p<0.05.
Results
Table 1shows the main demographic and clinical character-
istics of all the subjects studied. This large cohort of
Chinese patients had an average age of 45 years and BMI
of 26.6 kg/m
2
. In addition, BMI ≥30, ≥35, or ≥4 kg/m
2
was
reported in 14.1, 2.2, and 0.4% of patients, respectively,
reflecting an overall non-obese study population. The
cardiovascular and metabolic disorders were relatively
common as history of hypertension, cardiac arrhythmias,
and diabetes was reported in 380 (37%), 79 (8%), and 49
(5%) patients, respectively. Based on the assessments of
AHI according to the OSAHS diagnostic criteria from the
Chinese Medical Association [17], the 1,035 patients were
compared according to severity of sleep-disordered breath-
ing: primary snoring group (AHI <5 events/h, N= 249. This
group did not meet the PSG cut-off criteria for OSA was
categorized as either primary snoring group or normal AHI
group, mild (AHI 5–20 events/h, N=225), moderate (AHI
21–40 events/h, N=171), and severe (AHI >40 events/h,
N=390) OSAHS groups. The majority of patients had
moderate-to-severe OSAHS (54%, N= 561). There was no
significant difference in gender and age among the four
groups, but significantly higher BMI, neck circumference,
and systolic and diastolic blood pressure were reported with
increasing severity of OSAHS (Table 1). In addition to
snoring, patients experienced other common symptoms of
OSAHS such as EDS, poor memory, witnessed apneas,
choking or gasping in sleep, sleep maintenance insomnia,
or unrefreshing sleep and dry mouth, frequent nocturia, etc.
It is of note that more patients reported EDS and poor
memory in moderate/severe OSHAS patients than in
primary snoring and mild OSAHS patients.
As is evident in Fig. 1, the ESS score progressively
increased with the severity of OSAHS. Compared to the
primary snoring (mean ESS score ± SD 8.3±5.0) and mild
Table 1 Demographic and clinical characteristics of primary snoring and mild, moderate, and severe OSAHS patients
Primary snoring Mild OSAHS Moderate OSAHS Severe OSAHS
Number n(%) 249 (24.1) 225 (21.7) 171 (16.5) 390 (37.7)
Age years 40.4± 18.2 45.7 ±14.2 48.8 ±14.2 45.7± 12.6
Gender % of males 63.9 83.1 90.1 92.4
AHI events/h 1.6± 1.4 11.8± 4.2*
,
*** 30.3± 5.6*
,
***
,
***** 66.6± 16.1*
BMI kg/m
2
23.9± 3.7 26.2±3.4*
,
*** 27.5± 3.1*
,
***
,
**** 28.8± 3.9*
Neck circumference cm 37.4± 4.0 39.1± 3.3*
,
*** 40.2± 3.0*
,
***
,
**** 41.8± 3.0*
Morning blood pressure mmHg
Systolic blood pressure 118.20± 12.12 122.76± 15.89*** 122.87±14.92*** 131.83± 16.07*
Diastolic blood pressure 78.13±8.98 81.57± 11.07*** 81.85± 8.86**
,
*** 90.43± 11.86*
Common comorbidities n(%)
Hypertension 45 (18.1) 70 (31.1) 65 (38.0) 200 (51.3)
Cardiac arrhythmias 12 (4.8) 16 (7.1) 15 (8.8) 36 (9.2)
Diabetes 5 (2.0) 8 (3.6) 6 (3.5) 30 (7.7)
Common clinical symptoms n(%)
Daytime sleepiness 95 (38.2) 125 (55.6)**
,
*** 96 (56.1)**
,
*** 295 (75.6)*
Poor memory 83 (33.3) 122 (54.2) 105 (61.4) 252 (64.7)*
Data (age, AHI, BMI, neck circumference, and blood pressure) are presented as mean ± SD
AHI apnea–hypopnea index, BMI body mass index
*p< 0.01 when compared with primary snoring group; **p <0.05 when compared with primary snoring group; ***p<0.01 when compared with
severe OSAHS group; ****p<0.05 when compared with mild OSAHS group; *****p<0.01 when compared with mild OSAHS group
Sleep Breath (2011) 15:129–135 131

OSAHS (9.4±4.6) groups, significantly greater ESS scores
were reported in the moderate OSAHS patients (10.4 ± 4.6,
p<0.01 vs. primary snoring and p<0.05 vs. mild OSAHS),
and reached the highest in the severe OSAHS patients
(13.0±5.0, p< 0.01 vs. moderate OSAHS). In addition,
NREM sleep phase 1/2 and respiratory arousal index
increased whereas slow wave sleep (NREM sleep phase
3/4) decreased significantly from mild to severe OSAHS
suggesting a progressive disruption of sleep structure in the
OSAHS patients (Table 2). However, REM sleep did not
differ among the three OSAHS groups. On the other hand,
the parameters of nocturnal hypoxemia measured by ODI,
Time (SpO
2
<90%), and minimum SpO
2
demonstrated that
nocturnal hypoxemia progressively aggravated among the
four groups of patients. For example, the moderate/severe
OSAHS patients were associated with significantly greater
ODI and Time (SpO
2
<90%), and lower minimum SpO
2
(p<0.01 vs. primary snoring and mild OSAHS groups;
Table 2).
Linear regression analysis was performed to evaluate the
correlations of individual clinical (age, BMI, and neck
circumference) and polysomnographic (AHI, phase 1/2
sleep, slow wave sleep, REM sleep, respiratory arousal
index, ODI, Time (SpO
2
<90%), and Minimum SpO
2
)
variables with the ESS score. All these individual variables
except age and REM sleep significantly correlated with
ESS score. By using the stepwise multiple regression
analysis to further evaluate these correlations and their
relative importance, only three variables, i.e., BMI, AHI,
and ODI, significantly correlated with the ESS score with
the strongest association with ODI (β= 0.258 for ODI vs.
β=0.163 and β=0.05 for BMI and AHI, respectively, all
p<0.05). There was also a trend of correlation between ESS
score and Time (SpO
2
<90%) (p=0.06), but no notable
correlations between ESS score and nocturnal sleep
structure.
Discussion
According to the 2nd edition of International Classification
of Sleep Disorder (ICSD-2) [18], OSAHS ranks the second
in prevalence after insomnia with the prevalence rate of 2–
5% reported in adult population of Caucasian, Asian, and/or
other races [19]. OSAHS negatively impacts multiple organ
systems, impairs cognitive function including memory,
thinking, perception, etc., and an increasing severity of
OSAHS is associated with a greater hazard of all-cause
mortality [20]. Proper treatment has been shown to improve
the neuropsychiatric abnormalities, cardiovascular function,
and quality of life [3,21]. Therefore, the systematic clinical
evaluations of OSAHS with various spectrum of severity
and examination of the correlations between clinical
Fig. 1 ESS score (mean ± SD) in Chinese patients with different
severities of obstructive sleep apnea–hypopnea syndrome
Table 2 ESS score and polysomnographic parameters of primary snoring group and mild, moderate, and severe OSAHS groups
Primary snoring Mild OSAHS Moderate OSAHS Severe OSAHS
ESS score 8.3± 5.0 9.4 ±4.6**
,
*** 10.4± 4.6*
,
***
,
**** 13.0± 5.0*
TST min 401.4± 85.5 400.8± 74.4 405.6± 75.7 428.7 ±76.9
Phases 1+2 % 69.3± 12.8 74.1 ±11.7*** 75.6± 11.3*
,
*** 81.9± 15.7*
Slow wave sleep % 14.0± 12.2 10.5 ±9.1*
,
*** 8.4±7.9*
,
*** 4.6± 7.7*
REM sleep % 16.3± 6.7 15.2±7.2 15.8± 8.2 13.4± 7.6*
Respiratory arousals index events/h 0.4± 0.6 3.0 ±2.5*
,
*** 8.8±4.7*
,
***
,
**** 27.2± 12.2*
Time (SpO
2
<90%) min 0.3± 1.7 4.0 ±14.4*
,
*** 10.0± 19.2*
,
***
,
***** 147.4± 111.5*
Minimum SpO
2
% 83.2 ±23.6 82.5± 9.4*
,
*** 77.3± 8.3*
,
***
,
***** 65.6± 12.7*
ODI events/h 2.3± 2.1 13.1 ±7.2*
,
*** 33.4± 8.8*
,
***
,
***** 66.4± 17.3*
Data are presented as mean ± SD
ESS Epworth Sleepiness Scale, TST total sleep time, REM rapid eye movement, NREM non-rapid eye movement, SpO
2
pulse oxygen saturation,
ODI oxygen desaturation index
*p< 0.01 when compared with primary snoring group; **p <0.05 when compared with primary snoring group; ***p<0.01 when compared with
severe OSAHS group; ****p<0.05 when compared with mild OSAHS group; *****p<0.01 when compared with mild OSAHS group
132 Sleep Breath (2011) 15:129–135

presentations, risk factors, and comorbidities are critical for
the management of patients and disease.
The studies of many aspects of OSAHS in China are at
the beginning from recent years. In our study with a large
cohort of Chinese patients, 561 cases were diagnosed with
either moderate or severe OSAHS (54%) from a total of
1,035 consecutive patients examined at our institution for
snoring problem with clinical suspicion of OSAHS. Hence,
due to the lack of public awareness of OSAHS, a large
proportion of these patients were diagnosed with moderate-
to-severe OSAHS when they first sought medical attention
regarding their symptom of snoring. Consistent with the
literatures in OSAHS patient population, cardiovascular and
metabolic disorders are also relatively common in this large
cohort of Chinese OSAHS patients. Although we did not
perform a quantitative analysis of neurocognitive function
such as memory, attention, and learning ability in this study,
the percentages of patients experiencing poor memory were
higher in the moderate-to-severe OSAHS patients (61–
65%) than the primary snoring (33%) and mild OSAHS
(54%) patients based on the subjective symptom assess-
ment. These findings indicate that cardiovascular diseases
and neurocognitive dysfunction are also the common
comorbidities in Chinese OSAHS patient population.
Obesity is a significant risk factor for OSAHS and
increases the risk of developing symptomatic OSAHS by
∼10-fold, from 2–4% in the general middle-aged adult
population to up to 20–40% in those with a BMI ≥3 kg/m
2
(the cut-off BMI for obesity as defined by WHO) [22]. The
study that compared Asian and white OSAHS patients has
found that Asians are younger with a lower mean BMI
(26.6±3.7 in the Asians vs. 30.7±5.9 in the whites) [23]. In
2000, the WHO convened an expert consultation, which
concluded that there is a substantial proportion of Asian
people who have a high risk of type 2 diabetes and
cardiovascular disease at BMIs lower than the existing
WHO BMI cut-off point for overweight of ≥25 kg/m
2
.
The panel recommended that for some Asians, a BMI of
23 kg/m
2
or higher marks a moderate increase in risk for
these diseases while a BMI of 26 kg/m
2
or more represents
high risk [24]. In Hong Kong Chinese, comparing severity
of sleep-disordered breathing, Asian patients with OSAHS
have been found to have greater severity compared to
Caucasian patients matched for age, gender, and BMI [25].
Data from Lim et al. also found that moderate-to-severe
OSAHS in Singaporean local patients with a BMI of
27.9 kg/m
2
(SD 6.7) has a fair degree of correlation
between AHI and BMI [26]. In our study, lower BMI with
a mean value of 26.6 kg/m
2
(SD 4.3) was reported among
mild to severe Chinese OSAHS patients, and more severe
OSAHS groups indeed had greater BMI values (predomi-
nantly overweight, not obese). In addition, BMI was one of
the three major determinants of the ESS score. These results
underscore the relationship between BMI and OSAHS and
EDS in Chinese OSAHS patients. Our data partially
support the hypothesis of Knorst et al. [27] that factors
such as fragmented sleep, number/duration of respiratory
events, minimum SpO
2
levels, and degree of obesity were
associated with EDS, and obesity has a major effect on the
severity of OSAHS. However, we had excluded those
patients with obesity hypoventilation syndrome, which may
also cause of EDS.
It is well-known that most patients with OSAHS have
subjective EDS which adversely affects their cognitive
function, quality of life, and increases driving accidents
while sleepy [9]. However, EDS is not universally present
in all OSAHS patients. The clinical determinants and
underlying pathology of EDS in OSAHS patients remain
controversial [10,11]. Here we reported that increasingly
higher percentage of patients experienced EDS in more
severe OSAHS patients (76% in severe vs. 56% in mild/
moderate OSAHS), and consistently, the ESS score
progressively increased as the severity of OSAHS aggra-
vated, with a strong positive correlation between the ESS
score and AHI. These findings demonstrate that the degree
of EDS is associated with the severity of OSAHS in
Chinese patients.
In this study, more severe OSAHS patients are charac-
terized by EDS, nocturnal hypoxemia, and disruption of
sleep structure as evidenced by sleep fragmentation,
prolonged light sleep (phase 1/2 sleep), decreased slow
wave sleep, and increased arousals. Progressive worsening
of nocturnal hypoxemia was also observed from mild to
severe OSAHS patients with a strong correlation with ESS
score. The pathogenesis of EDS in OSAHS patients
remains controversial and unclear. Earlier studies have
provided discrepant results regarding the association be-
tween EDS and sleep fragmentation or nocturnal hypox-
emia [7–11]. Bedard et al. [28] evaluated impaired
vigilance in patients with OSAHS and showed that the
severity of nocturnal hypoxia predicted the propensity of
falling asleep and reduction in general intellectual meas-
ures, the ability to perform executive and psychomotor
tasks. In Mediano’s study [11], patients with OSAHS were
dichotomised to those with EDS and those without, and the
two groups were similar in terms of age, BMI, and disease
severity as assessed by AHI. The EDS group was
characterized by shorter sleep latency, improved sleep
efficiency, and worse nocturnal oxygenation than those
without EDS. From these earlier small clinical studies, it
has been postulated that nocturnal hypoxemia may play a
major role in determining EDS in OSAHS. On the other
hand, another study has indicated either no significant
association between EDS and sleep disruption or nocturnal
hypoxemia alternatively [10]. In our study involving a large
cohort of Chinese OSAHS patients, stepwise multiple
Sleep Breath (2011) 15:129–135 133

regression analysis revealed that only three major factors,
i.e., ODI, BMI, and AHI, among a variety of clinical and
polysomnographic variables are significant determinants of
EDS, with the order of relative importance as ODI>BMI>
AHI. These data support that nocturnal hypoxemia is a
more dominant determinant of EDS in OSAHS patients.
Importantly, sleep disruption such as changes in sleep
structure (sleep phase), however, was not found in the
stepwise multiple regression/correlation analysis to be a
significant determinant of EDS.
The findings from animal models of chronic intermittent
hypoxia (CIH) and other relevant pathologies have provid-
ed some insights regarding the underlying mechanisms of
nocturnal hypoxemia contributing to EDS in OSAHS
patients [29–33]. Zhan et al. [30,31] suggested that CIH
during sleep can trigger neural damage of brain regions that
promote and control wakefulness through a convergence of
oxidative and inflammatory events, which ultimately lead
to neuronal cell loss and the manifestation of sleepiness.
Induction of neuronal apoptosis and neurocognitive dys-
function associated with intermittent hypoxia has also been
demonstrated in other animal experiments involving acti-
vation of proinflammatory pathways and excessive forma-
tion of oxidation products [32,33]. Future studies are
warranted to further explore the underlying molecular/
cellular mechanisms.
In conclusion, EDS and sleep disruption are common in
a large cohort of Chinese OSAHS patients. More severe
OSAHS patients are associated with symptoms of EDS,
higher ESS score, higher BMI, worsening of nocturnal
hypoxemia, and profound sleep disruption. Nocturnal
hypoxemia appears to play a major role leading to the
EDS in these patients.
Acknowledgements This study was supported by the Technology-
Development Foundation of Suzhou (No. SS08036).
References
1. Douglas NJ, Polo O (1994) Pathogenesis of obstructive sleep
apnoea/hypopnoea syndrome. Lancet 344:653–655. doi:10.1016/
S0140-6736(94)92088-5
2. Jurkovicova I, Celec P (2004) Sleep apnea syndrome and its
complications. Acta Med Austriaca 31:45–50
3. Banno K, Kryger MH (2007) Sleep apnea: clinical investigations
in humans. Sleep Med 3:400–426. doi:10.1016/j.sleep.2007.
03.003
4. Verstraeten E, Cluydts R, Pevernagie D, Hoffmann G (2004)
Executive function in sleep apnea: controlling for attentional
capacity in assessing executive attention. Sleep 27:685–693
5. Barbé F, Pericás J, Muñoz A, Findley L, Antó JM, Agustí AG
(1998) Automobile accidents in patients with sleep apnea
syndrome. An epidemiological and mechanistic study. Am J
Respir Crit Care Med 158:18–22
6. Gami AS, Howard DE, Olson EJ, Somers VK (2005) Day–night
pattern of sudden death in obstructive sleep apnea. N Engl J Med
352:1206–1214
7. Colt HG, Haas H, Rich GB (1991) Hypoxemia vs sleep
fragmentation as cause of excessive daytime sleepiness in
obstructive sleep apnea. Chest 100:1542–1548. doi:10.1378/
chest.100.6.1542
8. Dixon JB, Dixon ME, Anderson ML, Schachter L, O'brien PE
(2007) Daytime sleepiness in the obese: not as simple as
obstructive sleep apnea. Obesity 15:2504–2511. doi:10.1038/
oby.2007.297
9. Goncalves MA, Paiva T, Ramos E, Guilleminault C (2004)
Obstructive sleep apnea syndrome, sleepiness, and quality of life.
Chest 125:2091–2096. doi:10.1378/chest.125.6.2091
10. Roure N, Gomez S, Mediano O, Duran J, Peña M, Capote F,
Teran J, Masa JF, Alonso ML, Corral J, Sanchez-Armengod A,
Martinez C, Barcelo A, Gozal D, Marin JM, Barbe F (2008)
Daytime sleepiness and polysomnography in obstructive sleep
apnea patients. Sleep Med 9:727–731. doi:10.1016/j.
sleep.2008.02.006
11. Mediano O, Barceló A, de la Peña M, Gozal D, Agustí A, Barbé F
(2007) Daytime sleepiness and polysomnographic variables in
sleep apnoea patients. Eur Respir J 30:110–113. doi:10.1183/
09031936.00009506
12. Johns MW (1991) A new method for measuring daytime
sleepiness: the Epworth Sleepiness Scale. Sleep 14:540–545
13. Chan EY, Ng DK, Chan CH, Kwok KL, Chow PY, Cheung JM,
Leung SY (2009) Modified Epworth Sleepiness Scale in Chinese
children with obstructive sleep apnea: a retrospective study. Sleep
Breath 13:59–63. doi:10.1007/s11325-008-0205-7
14. Chen NH, Johns MW, Li HY, Chu CC, Liang SC, Shu YH,
Chuang ML, Wang PC (2002) Validation of a Chinese version of
the Epworth Sleepiness Scale. Qual Life Res 11:817–821.
doi:10.1023/A:1020818417949
15. Rechtschaffen A, Kales A (1968) Manual of standardized
terminology, techniques and scoring system for the sleep stages
of human subjects, vol. 204. US Government Printing Office,
Washington, DC
16. Iber C, Ancoli-Israel S, Chesson AL, Quan SF (2007) The AASM
manual for the scoring of sleep and associated events: rules,
terminology and technical specifications. American Academy of
Sleep Medicine, Westchester, Illinois (US)
17. Chinese Medical Association, Sleep Breathing Disorders Group
(2002) Diagnostic and therapic manual for obstructive sleep
apnea–hypopnea syndrome. Chin J Tuberc Respir Dis 25:195–198
18. America Academy of Sleep Medicine (2005) International
classification of sleep disorders, 2nd ed.: diagnostic and coding
manual. American Academy of Sleep Medicine, Westchester,
Illinois
19. Young T, Peppard PE, Gottlieb DJ (2002) Epidemiology of
obstructive sleep apnea: a population health perspective. Am J
Respir Crit Care Med 165:1217–1239. doi:10.1164/rccm.2109080
20. Lavie P, Lavie L, Herer P (2005) All-cause mortality in males with
sleep apnoea syndrome: declining mortality rates with age. Eur
Respir J 25:514–520. doi:10.1183/09031936.05.00051504
21. Ferini-Strambi L, Baietto C, Di Gioia MR, Castaldi P, Castronovo
C, Zucconi M, Cappa SF (2003) Cognitive dysfunction in patients
with obstructive sleep apnea (OSA): partial reversibility after
continuous positive airway pressure (CPAP). Brain Res Bull
61:87–92. doi:10.1016/S0361-9230(03)00068-6
22. Kyzer S, Charuzi I (1998) Obstructive sleep apnea in the obese.
World J Surg 22:998–1001
23. Li KK, Powell NB, Kushida C, Riley RW, Adornato B,
Guilleminault C (1999) A comparison of Asian and white patients
with obstructive sleep apnea syndrome. Laryngoscope 109:1937–
1940. doi:10.1007/s002689900506
134 Sleep Breath (2011) 15:129–135

24. WHO Expert Consultation (2004) Appropriate body-mass index
for Asian populations and its implications for policy and
intervention strategies. Lancet 363:157–163. doi:10.1016/S0140-
6736(03)15268-3
25. Ong KC, Clerk AA (1998) Comparison of the severity of sleep-
disordered breathing in Asian and Caucasian patients seen at a
sleep disorders center. Respir Med 92:843–848. doi:10.1016/
S0954-6111(98)90386-9
26. Lim LL, Tham KW, Fook-Chong SM (2008) Obstructive sleep
apnoea in Singapore: polysomnography data from a tertiary sleep
disorders unit. Ann Acad Med Singapore 37:629–636
27. Knorst MM, Souza FJ, Martinez D (2008) Obstructive sleep
apnea–hypopnea syndrome: association with gender, obesity and
sleepiness-related factors. J Bras Pneumol 34:490–496
28. Bedard MA, Montplaisir J, Richer F, Malo J (1991) Nocturnal
hypoxemia as a determinant of vigilance impairment in sleep
apnea syndrome. Chest 100:367–370. doi:10.1378/chest.100.2.
367
29. Gozal D, Kheirandish L (2005) Sleepiness and neurodegeneration
in sleep-disordered breathing: convergence of signalling cascades.
Am J Respir Crit Care Med 171:1325–1327. doi:10.1164/
rccm.2503004
30. Zhan G, Fenik P, Pratico D, Veasey SC (2005) Inducible nitric
oxide synthase in long-term intermittent hypoxia: hypersomno-
lence and brain injury. Am J Respir Crit Care Med 171:1414–
1420. doi:10.1164/rccm.200411-1564OC
31. Zhan G, Serrano F, Fenik P, Hsu R, Kong L, Pratico D, Klann E,
Veasey SC (2005) NADPH oxidase mediates hypersomnolence
and brain oxidative injury in a murine model of sleep apnea. Am J
Respir Crit Care Med 172:921–929. doi:10.1164/rccm.200504-
581OC
32. Row BW, Liu R, Xu W, Kheirandish L, Gozal D (2003)
Intermittent hypoxia is associated with oxidant stress and spatial
learning deficits in the rat. Am J Respir Crit Care Med 167:1548–
1553. doi:10.1164/rccm.200209-1050OC
33. Xu W, Chi L, Row BW, Xu R, Ke Y, Xu B, Luo C, Kheirandish
L, Gozal D, Liu R (2004) Increased oxidative stress is associated
with chronic intermittent hypoxia-mediated brain cortical neuronal
cell apoptosis in a mouse model of sleep apnea. Neuroscience
126:313–323. doi:10.1016/j.neuroscience.2004.03.055
Sleep Breath (2011) 15:129–135 135