Sleep and Breathing

https://doi.org/10.1007/s11325-020-02109-x

SLEEP BREATHING PHYSIOLOGY AND DISORDERS • ORIGINAL ARTICLE

Smoking and sleep apnea duration mediated the sex difference

in daytime sleepiness in OSA patients
Xingjian Wang 1 & Wenyang Li 1 & Jiawei Zhou 1 & Zhijing Wei 1 & Xiaomeng Li 1 &
Jiahuan Xu 2 & Fang Zhang 1 & Wei Wang 1

Received: 16 February 2020 / Revised: 23 April 2020 / Accepted: 15 May 2020

# Springer Nature Switzerland AG 2020

Abstract
Purpose Daytime sleepiness is a common symptom of obstructive sleep apnea (OSA) and is more common in men, but the
underlying mechanism remains unclear. The aim of this study was to assess whether or not sex differences in daytime sleepiness
persisted after controlling for age and OSA severity and to explore the factors contributing to daytime sleepiness in patients with
OSA.
Methods A total of 104 pairs of patients with OSA, matched by age and apnea-hypopnea index (AHI), were enrolled in this
retrospective study. Demographic data were collected; daytime sleepiness was measured by the Epworth Sleepiness Scale (ESS);
and polysomnography (PSG) was performed on each participant. These measurements were compared between sexes, and the
factors affecting daytime sleepiness were explored with correlation and multivariate linear regression analyses.
Results Men had significantly higher ESS scores (p = 0.021) than women. Regarding demographics, BMI, neck/height ratio, and
proportion of habitual smoking and alcohol intake were significantly higher in men. Regarding PSG findings, men had more
rapid eye movement sleep, a longer mean apnea-hypopnea duration, and a longer mean apnea duration (MAD). Regression
analysis showed that two sex-associated variables, habitual smoking (β = 0.189, p = 0.006) and MAD (β = 0.154, p = 0.024), had
the strongest association with ESS scores. Further analysis revealed that MAD was significantly influenced by apnea index (β =
0.306, p < 0.001) and sex (β = − 0.193, p = 0.003).
Conclusion The sex difference in daytime sleepiness persists in patients with OSA, even after matching AHI and age. The
difference is mediated by sex-specific smoking habits and sex differences in apnea duration.

Keywords Obstructive sleep apnea . Daytime sleepiness . Sex . Mean apnea duration

Introduction sleepiness is one of the most common complaints related to

Obstructive sleep apnea (OSA) is a sleep-related breathing
disorder characterized by recurrent collapse of the upper air-
way during sleep, intermittent nocturnal hypoxia, and sleep
fragmentation [1]. In addition to nocturnal manifestations
such as apnea and snoring, OSA is also associated with sub-
stantial daytime symptoms and clinical consequences, which
negatively influence the quality of life of patients [2]. Daytime
* Wei Wang
wwbycmu@126.com
1
Institute of Respiratory and Critical Care Medicine, The First
Hospital of China Medical University, Shenyang, Liaoning, China
2
Department of Respiratory Medicine, Zhejiang Hospital,
Hangzhou, Zhejiang, China
OSA, with considerable impacts on social function, working
performance, and driving safety [2]. The underlying mecha-
nisms of daytime sleepiness in OSA patients may be associ-
ated with fragmented sleep architecture, repetitive arousal,
and intermittent hypoxia during sleep [3]. However, the asso-
ciation between daytime sleepiness and the apnea-hypopnea
index (AHI), the primary measurement of OSA severity, was
not matched in some studies [4, 5], and the predictive effects
of nocturnal hypoxemia parameters were also controversial [4,
6]. Recently, the clinical significance of parameters of respi-
ratory event duration has drawn increasing attention in the
context of OSA evaluation [7, 8]; Zhan et al. [9] further re-
ported that the mean apnea-hypopnea duration (MAHD) pos-
itively correlated with the Epworth Sleepiness Scale (ESS)
score, one of the widely applied daytime sleepiness measure-
ments. Nevertheless, the relationship between other specific

duration markers (such as the mean apnea duration and the
mean hypopnea duration) and daytime sleepiness remains
unclear.
Sex differences in the prevalence, severity, and manifesta-
tions of OSA have also received a large amount of interest. In
the general population, a male predominance in sleep-related
breathing disorders has been widely reported [10, 11]. In the
clinical population, male patients usually have a younger
mean age and a higher prevalence of severe OSA (AHI ≥
30) [12, 13]. Even within the moderate (15 ≤ AHI < 30) and
severe OSA groups, the apnea duration and nocturnal periph-
eral oxygen saturation (SpO2) desaturation area in the males
were found to be longer and larger than those in females,
respectively [14]. The occurrence of daytime sleepiness is also
different between male and female patients with OSA.
Although there were some exceptions [15], accumulating
studies have reported that male patients with OSA were more
likely to experience daytime sleepiness [16–20]. This differ-
ence was attributed by some authors to distinct perceptions of
the symptom [16, 17]. However, the influences of OSA sever-
ity or age differences between sexes as well as the contribu-
tions of other sex-specific polysomnography (PSG) features
and lifestyle habits may also play an important role, which
deserves further research. The aim of this study was to assess
whether the sex difference in daytime sleepiness still existed
in individuals with the same age and OSA severity and to
identify the major factors contributing to daytime sleepiness
in OSA patients.
Methods
Participant selection
Participants suspected of having OSA according to nocturnal
snoring, sleep apnea, or daytime sleepiness reported by them-
selves or their bed partners were referred to the sleep center of
the Department of Respiratory and Critical Care Medicine, the
First Hospital of China Medical University (Shenyang, China)
from January 2018 to June 2019. Of the 1408 participants who
received PSG examination, 946 participants were older than
16 years old and diagnosed with OSA with an AHI ≥ 5 events/
h [21]. Among them, 187 participants were excluded due to
one or more of the following reasons: (1) the medical record
was incomplete or invalid; (2) the participants had potential
comorbidities influencing daytime sleepiness [22] or respira-
tory function such as malignancy, chronic organ failure, cere-
brovascular diseases, neurological or psychiatric disorders,
asthma, or chronic obstructive pulmonary disease; (3) other
sleep conditions such as narcolepsy or restless leg syndrome
were found; (4) the patient had a drug abuse history or used
sedatives or alcohol during the night of examination; (5) the
total sleep time (TST) was less than 180 min; and (6) OSA
Sleep Breath
treatment such as continuous positive airway pressure (CPAP)
therapy, oral appliance therapy, or surgical modification of the
upper airway was received. In the 759 eligible participants
(634 males and 125 females), the males and the females were
matched for both age (within ± 2 years) and AHI (within ± 1 if
5 ≤ AHI < 15, within ± 2 if 15 ≤ AHI < 30, and within ± 3 if
AHI ≥ 30). During the procedure, 530 males and 21 females
were excluded because an age- and AHI-matched partner was
not available, and 104 males and 104 females were ultimately
included in the cohort. The flow chart is shown in Fig. 1. All
the participants received detailed information about the re-
search, and written informed consent was obtained. Ethics
approval was obtained from the Ethics Committee of the
First Hospital of China Medical University, and the study
complied with the principles of the Declaration of Helsinki
(1964).
Collection of demographic data
The height, weight, neck circumference, and waist circumfer-
ence of each participant were measured by a clinician on the
night of the examination. The neck/height ratio (NHtR) and
waist/height ratio (WHtR) were calculated to minimize the
body-size differences between sexes. Clinical data were ob-
tained from a self-reported questionnaire completed by the
participant and his/her sleep partner with information on com-
plaints, sleeping habits, comorbidities, medications, smoking
habits, and alcohol intake history. Habitual smokers referred
to those who smoked two or more packs of cigarettes weekly
for at least 3 years [23], and habitual alcohol consumption was
defined as an estimated weekly alcohol intake of more than
50 g in the past 3 years [24].
Daytime sleepiness evaluation
The subjective daytime sleepiness level was evaluated by ESS
scores. According to the procedure used in other studies [20,
25], the participants were asked to complete a Chinese version
of the ESS questionnaire on the night of examination with the
guidance of an experienced sleep specialist. The ESS ques-
tionnaire consisted of eight questions about the probability of
sleeping or dozing under various situations in ordinary life
[26]. Each question received a score from 0 (never doze) to
3 (high probability of dozing), and the total score ranged from
0 to 24.
PSG measurement
Continuous PSG for at least 7 h during the night was per-
formed on all the patients in the sleep center with the PSG
device Alice 5 (Philips, Netherlands) or SOMNOscreen™
plus (SOMNOmedics, German). The monitoring data for
analysis included the signals of EEG (4 channels: C3/A2,
Sleep Breath

Fig. 1 The flow chart of patient

selection. PSG
polysomnography, AHI apnea-
hypopnea index, TST total sleep
time, OSA obstructive sleep
apnea, COPD chronic obstructive
pulmonary disease, RLS restless
leg syndrome

C4/A1; O1/A2, O2/A1), EOG (2 channels), chin-EMG, leg-
EMG, and ECG recorded by leads; oronasal airflow informa-
tion from a nasal pressure detector and oral thermistor; chest
and abdominal wall movements measured by piezoelectric
sensors; peripheral oxygen saturation detected by a fingertip
photoelectric sensor; snoring recorded by microphone; and
body position information from a position sensor. All the
PSG results were evaluated by experienced sleep specialists
for the identification of respiratory events, according to the
AASM Manual for the Scoring of Sleep and Associated
Events (Version 2.5).
Statistical analysis
The Kolmogorov–Smirnov test was performed to evaluate
whether the demographic parameters, PSG findings, and
ESS scores obeyed a normal distribution. The normally and
abnormally distributed continuous variables are presented as
 Sleep Breath

the mean ± standard deviation (SD) and the median (interquar-
tile range), respectively. The dichotomous results are shown
as numbers (percentages). To compare the differences in con-
tinuous variables between male and female groups, the inde-
pendent Student’s t test for data with a normal distribution or
the Mann–Whitney nonparametric test for data with an abnor-
mal distribution was applied. The differences in dichotomous
categorical variables between sexes were assessed by the chi-
square test. The correlations of ESS sores with the continuous
or dichotomous demographic and PSG parameters were eval-
uated by Pearson’s or Spearman’s correlation analyses, re-
spectively. The variables with statistical significance were
subsequently involved in the stepwise multivariate linear re-
gression analysis. In these analyses, sex was represented as 0
(male) or 1 (female), habitual smoking and habitual alcohol
intake were represented as 0 (no) or 1 (yes), and the comor-
bidity of hypertension or diabetes mellitus was represented as
0 (without) or 1 (with). With a similar method, the potential
contributions of the variables related to the PSG parameter
that was involved in the regression model for explaining
ESS scores were further explored by correlation analyses
and stepwise multivariate linear regression in sequence. All
statistical calculations were completed by SPSS (Version
23.0, IBM Corp., USA). P < 0.05 (two-tailed) was considered
statistically significant.
Results
scores, and PSG findings between both sexes are shown in
Tables 1 and 2. Regarding demographics, male patients were
found to have a significantly higher body mass index (BMI)
(27.7 vs. 25.7, p = 0.003), a higher NHtR (0.25 vs 0.23,
p < 0.001), and a higher proportion of habitual smoking
(33.7% vs. 5.8%, p < 0.001) and alcohol intake (21.1% vs.
1.9%, p < 0.001). In terms of daytime sleepiness, males had
significantly higher ESS scores than females (11.0 vs. 9.0, p =
0.021). PSG monitoring indicated that males had a significant-
ly higher percentage of rapid-eye-movement (REM) sleep
(11.5% vs. 7.6%, p = 0.018), longer MAHD (23.4 vs. 20.9,
p = 0.003), and longer mean apnea duration (MAD) (22.0 vs.
18.0, p < 0.001).
Major factors contributing to ESS scores
The association of the demographic or PSG parameters with
the ESS scores was examined. In the correlation analysis, sex
(r = − 0.16, p = 0.021), habitual smoking (r = 0.204, p =
0.003), AHI (r = 0.162, p = 0.019), apnea index (AI) (r =
0.154, p = 0.026), MAD (r = 0.169, p = 0.015), and ODI
(r = 0.142, p = 0.040) were found to significantly correlate
with the ESS scores (Table 3). To determine the major factors
that contributed to the ESS scores, these variables with statis-
tical significance were further involved in the stepwise multi-
variate linear regression analysis, and only habitual smoking
(β = 0.189, p = 0.006) and MAD (β = 0.154, p = 0.024) were
significant variables in the final regression model (Table 4).

Comparisons of demographic data, ESS scores, and
PSG findings between sexes
A total of 104 pairs of age- and AHI-matched male and female
patients were included in this study. The characteristics of the
study sample and the comparisons of demographic data, ESS
Major factors contributing to MAD
Since MAD was the PSG parameter that remained in the re-
gression model to explain ESS scores, we further explored the
potential factors affecting this parameter. The sleep parame-
ters (TST and REM of TST) and frequency parameters of

Table 1 The comparison of

demographic data and ESS scores Whole population Males (n = 104) Females Pa
between male and female patients (n = 208) (n = 104)
with OSA
Age (year) 54.0 (44.0–59.0) 54.0 (43.3–58.8) 54.0 (44.3–59.8) 0.646
BMI (kg/m2) 26.4 (24.2–29.3) 27.7 (25.1–29.4) 25.7 (23.4–28.7) 0.003
NHtR 0.24 (0.22–0.25) 0.25 (0.23–0.26) 0.23 (0.22–0.25) < 0.001
WHtR 0.59 (0.56–0.63) 0.59 (0.56–0.64) 0.60 (0.55–0.63) 0.984
Habitual smoking, n (%) 41 (19.7%) 35 (33.7%) 6 (5.8%) < 0.001
Habitual alcohol intake n (%) 24 (11.5%) 22 (21.1%) 2 (1.9%) < 0.001
ESS Scores 10.0 (5.0–15.0) 11.0 (6.0–16.8) 9.0 (5.0–13.0) 0.021
Hypertension, n (%) 55 (26.4%) 33 (31.7%) 22 (21.2%) 0.115
Diabetes, n (%) 20 (9.6%) 7 (6.7%) 13 (12.5%) 0.239

Results are presented as mean ± SD, median (25–75% percentiles), or n (%)

BMI body mass index, NHtR neck/height ratio, WHtR waist/height ratio, ESS Epworth sleepiness scale
a
Differences between males and females
Sleep Breath

Table 2 The comparison of PSG

findings between male and female Whole population (n = 208) Males (n = 104) Females (n = 104) Males/Females
patients with OSA P value

TST (min) 427.7 ± 93.1 422.8 ± 90.7 432.6 ± 95.6 0.321

REM of TST (%) 9.1 (5.6–11.4) 11.5 (5.9–17.9) 7.6 (5.0–14.0) 0.018
AHI (events/h) 26.1 (11.8–44.0) 26.4 (12.1–44.6) 25.7 (11.6–43.6) 0.906
AI (events/h) 11.1 (3.6–22.2) 11.1 (3.2–24.3) 10.9 (3.8–22.2) 0.789
HI (events/h) 9.5 (4.1–19.7) 9.3 (4.4–17.1) 10.1 (4.0–20.3) 0.811
MAHD (min) 21.7 (18.2–25.9) 23.4 (19.3–27.3) 20.9 (17.7–24.7) 0.003
MAD (min) 19.8 (16.5–24.8) 22.0 (17.7–26.7) 18.0 (15.6–22.9) < 0.001
MHD (min) 21.9 (17.7–26.2) 22.5 (18.3–28.0) 21.4 (16.7–24.9) 0.061
Mean SpO2 (%) 95.0 (93.5–96.0) 95.0 (93.6–96.0) 95.2 (93.4–96.6) 0.192
Nadir SpO2 (%) 84.0 (73.0, 88.0) 84.5 (73.3, 88.0) 82.8 (72.3, 88.8) 0.504
SIT90 of TST (%) 2.5 (0.1–12.1) 2.8 (0.13–11.6) 2.0 (0.13–13.3) 0.827
ODI (events/h) 23.1 (7.5–46.8) 23.9 (6.7–46.8) 21.6 (7.7–47.3) 0.900

Results are presented as mean ± SD, median (25–75% percentiles), or n (%)

TST total sleep time, REM rapid eye movement, AHI apnea-hypopnea index, AI apnea index, HI hypopnea index,
MAHD mean apnea-hypopnea duration, MAD mean apnea duration, MHD mean hypopnea duration, SpO2
peripheral oxygen saturation, SIT90 saturation impair time below 90%, ODI oxygen desaturation index
* Differences between Males and Females

respiratory events (AHI, AI, and HI) in PSG results and all contribute to (instead of being influenced by) MAD.
demographic data were considered potential factors that may Therefore, we examined the association of only these param-
eters with MAD. In the correlation analysis, sex (r = − 0.273,
p < 0.001), habitual alcohol intake (r = 0.148, p = 0.033), hy-
Table 3 The correlation of demographic and PSG parameters with ESS
pertension (r = 0.136, p = 0.049), total sleep time (TST) (r =
scores 0.192, p = 0.005), AHI (r = 0.428, p < 0.001), and AI (r =
0.504, p < 0.001) were found to significantly correlate with
r P value
MAD (Table 5). After regression analysis, only AI (β =
Demographic parameter 0.306, p < 0.001) and sex (β = − 0.193, p = 0.003) were sig-
Sex − 0.160 0.021 nificant in the final model (Table 4).
Age − 0.049 0.483
BMI 0.111 0.109
NHtR − 0.087 0.212
WHtR − 0.040 0.562
Habitual smoking 0.204 0.003 Discussion
Habitual alcohol intake 0.112 0.107
Hypertension 0.047 0.498 In patients with OSA, sex differences have been widely ad-
Diabetes 0.030 0.671
PSG parameter dressed. However, whether the difference still exists in indi-
TST − 0.006 0.932 viduals with the same OSA severity and its link with demo-
REM of TST 0.125 0.073 graphic or sleep-breathing parameters remains unclear. This
AHI 0.162 0.019
AI 0.154 0.026 study confirmed that the sleepiness level was different be-
HI 0.070 0.315 tween the AHI- and age-matched patients with OSA in both
MAHD 0.124 0.075 sexes. For the first time, we revealed that the difference in
MAD 0.169 0.015
MHD 0.132 0.057
sleepiness level was mediated by the sex-specific smoking
Mean SpO2 − 0.135 0.052 habit and the sex differences in apnea duration. Our results
Nadir SpO2 − 0.080 0.251 suggest the potential value of respiration duration parameters
SIT90 of TST 0.124 0.075
ODI 0.142 0.040
and lifestyle habit data in the evaluation of OSA and the pre-
diction of related clinical consequences.
BMI body mass index, NHtR neck/height ratio, WHtR waist/height ratio, Regarding demographic measurements, male patients with
TST total sleep time‚ REM rapid eye movement, AHI apnea-hypopnea OSA had higher BMI and NHtR than females with the same
index, AI apnea index, HI hypopnea index, MAHD mean apnea-hypopnea
duration, MAD mean apnea duration, MHD mean hypopnea duration,
age and AHI level. Several studies in North America and
SpO2 peripheral oxygen saturation, SIT90 saturation impair time below Europe [27, 28] have reported that male patients with OSA
90%, ODI oxygen desaturation index had a lower BMI than females, while Zhang et al. [20] found
 Sleep Breath

Table 4 The final models of stepwise multivariate linear regression for Similar to our results, the male predominance of daytime
ESS score and MAD
sleepiness in OSA patients was also found in many previous
B Standard error β P studies [13, 16–20]. However, it is difficult to compare our
results with most of the previous results because the male and
Dependent variable: ESS score female patients were matched by age and AHI in our research
Independent variable and were usually randomly selected in the previous studies. In
Constant 7.014 1.333 – < 0.001 a similar case-matched study in Japan [19], a significant dif-
Habitual smoking 2.955 1.063 0.189 0.006 ference in ESS scores was only observed between the age- and
MAD 0.136 0.06 0.154 0.024 BMI-matched groups (male 10.3 ± 5.6 vs. female 9.2 ± 5.6,
Dependent variable: MAD p < 0.01) but not between the age- and AHI-matched groups
Independent variable (male 9.6 ± 5.8 vs. female 9.2 ± 5.6, p > 0.05). However, there
Constant 20.534 0.779 – < 0.001 was no further analysis of the significant difference.
AI 0.114 0.024 0.306 < 0.001 In the correlation analysis, we found that sex, habitual
Sex − 0.728 0.917 − 0.193 0.003 smoking, AHI, AI, MAD, and ODI were significantly corre-
lated with ESS, but after stepwise regression, only two sex-
ESS Epworth sleepiness scale, MAD mean apnea duration, AI apnea index
specific variables, habitual smoking and MAD, remained in
the final model. Regression analyses were also applied in pre-
similar BMI levels between males and females in their vious studies to find the link between sleepiness and other
Chinese OSA cohort. The conflicting results may be associat- factors. Similar to our results, Nigro et al. have shown that
ed with ethnic differences among study populations in both different severities of sleepiness between male and female
anatomical and sociocultural aspects. In the comparison of patients with OSA were actually attributed to the difference
neck and waist sizes, NHtR and WHtR were calculated to in demographics or PSG parameters [13], while in other stud-
standardize the body-size differences between sexes. ies [16, 18], male sex contributed to daytime sleepiness inde-
According to our results, only NHtR was still higher in males pendently even when the confounding factors were controlled.
The contradictory results may be due to different study-cohort
than in females with the same age and AHI level. However,
although the association of NHtR and WHtR with OSA se- characteristics, different study designs, and different variables
verity has been reported in previous studies [29, 30], they did included in the analyses.
The interaction of smoking habits with OSA is complicated.
not show a significant correlation with ESS scores or MAD in
our analyses. Although tobacco may contribute to the pathogenesis of OSA
by inducing epithelial inflammation and increasing upper air-
Table 5 The correlation of demographic and PSG factors with MAD way resistance [31, 32], the association between smoking and
AHI remains controversial [33, 34]. Nevertheless, it is relative-
r P value ly clear that smoking could impair oxygen saturation in patients
with OSA [35] and exacerbate the related cardiovascular and
Demographic Parameter
metabolic complications [36, 37]. The contribution of smoking
Sex − 0.273 < 0.001
to daytime sleepiness has also been reported previously in a
Age 0.029 0.682
large population-based study [38], which is in accordance with
BMI 0.027 0.697
our results. This effect may be related to the disturbed sleep
NHtR 0.010 0.882
architecture and the increased nocturnal arousal because of nic-
WHtR − 0.036 0.605
otine’s intervention on the central nervous system [35].
Habitual smoking 0.123 0.077
MAD was another sex-associated variable to predict ESS
Habitual alcohol intake 0.148 0.033
scores in the final model. Zhan et al. [9] reported the correlation
Hypertension 0.136 0.049
of the integrated duration parameter, MAHD, with daytime
Diabetes − 0.008 0.904
sleepiness, but the authors did not evaluate the detailed duration
PSG Parameter parameters, MAD and MHD. However, in our study, where all
TST 0.180 0.009 three variables were examined, MAD, but not MAHD or
REM of TST − 0.009 0.896 MHD, was associated with sleepiness. Interestingly, we noticed
AHI 0.271 < 0.001 that while AHI, AI, and MAD correlated with ESS scores, HI,
AI 0.311 < 0.001 MAHD, and MHD were not related to ESS in the correlation
HI 0.033 0.634 analysis. This suggests that in addition to the duration of respi-
BMI body mass index, NHtR neck/height ratio, WHtR waist/height ratio,
ratory events, the types of respiratory events may also exert
TST total sleep time, REM rapid eye movement, AHI apnea-hypopnea different physiological influences. As shown in some studies
index, AI apnea index, HI hypopnea index [39, 40], the arousal induced by apnea events was longer than
Sleep Breath
that induced by hypopnea events. Nigro et al. [40] further dem-
onstrated that both the type of apnea (instead of hypopnea) and
the duration of respiratory events > 20 s could predict a higher
probability of arousal > 11 s. Considering that longer arousals are
potentially more relevant to daytime sleepiness [41], we may
ascribe the association between MAD and EDS to the long-
term arousals elicited by long-duration apnea events. In addition
to the disturbance of sleep microstructures such as arousal, longer
respiratory events may also affect the proportion of slow wave
sleep more than shorter events and further influence sleep mac-
rostructure [8, 9], which could be another mechanism through
which MAD is associated with daytime sleepiness.
As MAD was a variable related to ESS scores in the regres-
sion model, we further explored the potential factors affecting
this parameter, and AI as well as sex were finally involved in the
regression model. Similar to our finding that AI was related to
MAD, the correlation of MAHD with AHI was reported in Zhan
et al.’s study [9] and was attributed to the duration requirement in
the diagnostic standard of respiratory events [42]. In addition to
the inclusion of sex in the regression model, the difference in
MAD, as well as MAHD, between sexes was also observed in
our comparison of PSG measurements. This result was consistent
with a previous large-sample (1090 participants) study in which
the apnea events of males were 25.9%, 16.9%, and 19.6% longer
than those of females in mild, moderate, and severe OSA groups,
respectively [14]. Both the distinct mechanical properties of the
upper airway and the different compensatory effectiveness may
account for the sex differences in respiratory events. In Kirkness
et al.’s study [43], the passive pharyngeal critical pressure (Pcrit),
a major indicator of upper airway collapsibility, was significantly
higher in male patients with OSA than in females. Chin et al. [44]
further demonstrated that even under the same passive Pcrit,
female patients with OSA had more effective compensatory re-
actions. This was thought to be mediated by the sex-dependent
genioglossal muscular tone and the different ventilatory re-
sponses to hypoxia or airway obstruction [45, 46] because of
the influence of sex hormones [47]. We speculate that these
mechanisms not only make respiratory events more easily initi-
ated in males, increasing event frequency, but also make the
events more difficult to stop, elongating the duration.
Our study had some limitations. First, the participants with
diabetes mellitus were not excluded. Although diabetes is not
considered a common cause of daytime sleepiness [22], its
potential influence on the symptom has ever been mentioned
in one study [38]. However, sex differences in its morbidity
rate or contribution to daytime sleepiness or MAD were not
shown in our analyses, which suggested that the inclusion of
these participants did not interfere with the results obtained.
Second, the data of NREM sleep stages in the database were
not integrated and therefore were not included in our analysis.
Since the proportion of slow wave sleep may be related to
daytime sleepiness and disturbed by respiratory events [9,
48], future studies are required to reveal its relationship with
the duration of events of each type and to examine the differ-
ences between sexes. Last, information on the menstrual status
of female participants was not available. Given that the pha-
ryngeal dilator muscular tone and the ventilatory response are
affected by sex hormones [47], we may speculate that meno-
pause could influence the duration of respiratory events,
which deserves further exploration.
In conclusion, the sex difference in daytime sleepiness still
exists in patients with OSA with the same AHI and age level,
and such difference is mediated by sex differences in smoking
habits and apnea duration. This increases the awareness that
the different lifestyle habits of patients with OSA will affect
their clinical manifestations and contribute to the sex differ-
ences in the disease. More importantly, our study also sug-
gested that the duration parameters of respiratory events de-
serve more attention since they may better reflect sex-specific
OSA characteristics and be more valuable in predicting some
OSA-related disorders [7]. Future studies are required to re-
veal the underlying mechanisms by which longer respiratory
events induce more detrimental clinical consequences and to
apply the duration parameters in the specific evaluation and
individualized treatment of OSA.
Acknowledgments W-XJ: study design, data collection, statistical anal-
ysis, and initial manuscript drafting. L-WY, Z-JW, and ZF: study design,
data analysis, and critical revision of the manuscript. W-ZJ, L-XM, and
X-JH: participant selection and data collection. WW: study design, result
interpretation, critical revision, and final approval of the manuscript.
Funding information This study was funded by the National Key
Research and Development Program of China (No. 2018YFC1313600),
the National Natural Science Foundation of China (81670085), and the
Construction Project of Translational Medicine Research Center of
Respiratory Disease of Liaoning Province of China (No. 2014225006).
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Ethical approval All procedures performed in studies involving human
participants were in accordance with the ethical standards of the institu-
tional and/or national research committee and with the Declaration of
Helsinki (1964) and its later amendments or comparable ethical
standards.
Informed consent Informed consent was obtained from all individual
participants included in the study.
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