Effect of Obstructive Sleep Apnea on Immunity in Cases of Chronic Rhinosinusitis With Nasal Polyps

Abstract

Objective:
Chronic rhinosinusitis (CRS) with nasal polyp (wNP) is a more severe inflammatory form of CRS that often coexists with obstructive sleep apnea (OSA). However, little is known the relationship between OSA and immunologic profile on patients with CRSwNP. We aimed to investigate the immune profile of patients with CRSwNP according to OSA severity.

Methods:
This study included 63 patients with CRSwNP and nine control subjects. Protein levels of inflammatory mediators were determined using multiplex immunoassay. All patients underwent standard polysomnography.

Results:
We found that, in patients with eosinophilic CRSwNP (ECRSwNP), IL-6 and CXCL-1 (type 1 immune-related markers) were upregulated in cases of moderate-to-severe OSA. Additionally, IL-4, IL-13, CCL-11, CCL-24 (type 2 immune-related markers), and IL-17A (type 3 immune-related marker) were increased in patients with moderate-to-severe OSA. Though there were no significant differences in type 1, 2, or 3 immune-related markers among patients with non-eosinophilic CRSwNP (NECRSwNP) according to the severity of OSA, TGF--β expression was increased in those with moderate-to-severe OSA. Furthermore, in ECRSwNP with moderate-to-severe OSA, associations were detected between serum markers and some upregulated inflammatory markers.

Conclusion:
Our findings revealed that OSA may increase the heterogeneity of immune profiles (types 1, 2, and 3) in patients with ECRSwNP but not in those with NECRSwNP.

Full text

Effect of obstructive sleep apnea on immunity in cases of chronic rhinosinusitis with
nasal polyp
Dong-Kyu Kim, MD, PhD1,2*; Byeong Chan Lee, BS1; Ki Joon Park, MD1; Gil Myeong Son,
MD1
1Department of Otorhinolaryngology-Head and Neck Surgery, Chuncheon Sacred Heart
Hospital, Hallym University College of Medicine, Chuncheon, Republic of Korea
2Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon,
Republic of Korea
Running title: Obstructive sleep apnea and nasal polyp
Conflict of interest: The authors declare that they have no relevant conflicts of interest.
Acknowledgements: This research was supported by a clinical research grant-in-aid from the
Basic Science Research Program through the National Research Foundation of Korea (NRF)
funded by the Ministry of Science, ICT, and Future Planning (NRF-2018R1D1A3B07040862,
and by the Hallym University Research Fund 2019 (HURF-2019-59).
Author contributions:
Conceptualization: DKK. Data curation: DKK, BCL, HJL. Formal analysis: KJP, GMS.
Funding acquisition: DKK. Methodology: BCL, KJP, HJL. Project administration: DKK.
Visualization: GMS. Writing – original draft: DKK. Writing – review & editing: DKK.
Accepted Article

Corresponding author:
Dong-Kyu Kim, MD, PhD
Department of Otorhinolaryngology-Head and Neck Surgery, Chuncheon Sacred Heart
Hospital, Hallym University College of Medicine (24253), 77, Sakju-ro, Chuncheon-si,
Gangwon-do, Republic of Korea
Phone: 82-33-240-5180
Fax: 82-33-241-2909
E-mail: doctordk@naver.com
Dong-Kyu Kim: 0000-0003-4917-0177
Byeong Chan Lee: 0000-0003-0161-260X
Ki Joon Park: 0000-0002-1791-9262
Gil Myeong Son: 0000-0001-7461-9517
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Highlights
 We investigated the immune profile of patients with CRSwNP according to OSA
severity.
 In those with ECRSwNP, IL-6 and CXCL-1 were upregulated with moderate-to-
severe OSA, whereas there were no significant differences in any type 1, 2, or 3
immune-related markers in those with NECRSwNP.
 OSA may increase the heterogeneity of immune profiles in patients with ECRSwNP.
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Objective: Chronic rhinosinusitis (CRS) with nasal polyp (wNP) is a more severe
inflammatory form of CRS that often coexists with obstructive sleep apnea (OSA). However,
little is known the relationship between OSA and immunologic profile on patients with
CRSwNP. We aimed to investigate the immune profile of patients with CRSwNP according to
OSA severity.
Methods: This study included 63 patients with CRSwNP and nine control subjects. Protein
levels of inflammatory mediators were determined using multiplex immunoassay. All patients
underwent standard polysomnography.
Results: We found that, in patients with eosinophilic CRSwNP (ECRSwNP), IL-6 and
CXCL-1 (type 1 immune-related markers) were upregulated in cases of moderate-to-severe
OSA. Additionally, IL-4, IL-13, CCL-11, CCL-24 (type 2 immune-related markers), and IL-
17A (type 3 immune-related marker) were increased in patients with moderate-to-severe OSA.
Though there were no significant differences in type 1, 2, or 3 immune-related markers
among patients with non-eosinophilic CRSwNP (NECRSwNP) according to the severity of
OSA, TGF-β expression was increased in those with moderate-to-severe OSA. Furthermore,
in ECRSwNP with moderate-to-severe OSA, associations were detected between serum
markers and some upregulated inflammatory markers.
Conclusions: Our findings revealed that OSA may increase the heterogeneity of immune
profiles (types 1, 2, and 3) in patients with ECRSwNP but not in those with NECRSwNP.
Keywords: Eosinophils, Nasal polyps, Rhinitis, Sinusitis, Sleep, Sleep apnea syndromes
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Introduction
Chronic rhinosinusitis (CRS) is defined as a chronic inflammatory disorder that involves
nasal and paranasal mucosa and lasts for more than 12 weeks [1]. Its major symptoms include
nasal obstruction, nasal discharge, facial pain, and reduction or loss of smell. However, in
addition to sinonasal symptoms, patients with CRS also suffer from poor sleep quality due to
nasal congestion, upper airway obstruction, and inflammatory status. Previous studies
demonstrated that patients with CRS commonly experience poor sleep quality and have
highly prevalent sleep problems compared to individuals without CRS [2]. Recently, one
study described that incident CRS is associated with impaired sleep quality [3].
Obstructive sleep apnea (OSA) is characterized by repeated cessation of breathing during
sleep that is primarily caused by complete or partial airway obstruction [4,5]. These episodes
of airway obstruction induce nocturnal hypoxemia, hypercapnia, and sleep fragmentation.
OSA can also cause or exacerbate severe major-organ disorders, including cardiovascular
disease, metabolic syndrome, and neurocognitive deterioration. Moreover, a meta-analysis
revealed higher levels of systemic inflammatory markers in patients with OSA compared to
controls [6]. Several studies have also reported that OSA significantly influenced the
sinonasal local immune response, including nitric oxide production, lipid peroxidation,
nuclear factor-kB activation, and neutrophil infiltration [7,8].
CRS is divided into two phenotypes according to the presence of nasal polyps under nasal
endoscopic view: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps
(CRSsNP). Generally, CRSwNP is considered as a more severe inflammatory status of the
sinonasal mucosa, and it also could develop or aggravate of apnea during sleep [9]. Further,
in terms of intermittent hypoxia due to breathing cessation during sleep, OSA could affect the
immunological response of patients with CRSwNP. However, the effect of OSA on the
immune systems of patients with CRSwNP is still poorly understood. Therefore, in the
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present study, we investigated whether OSA influences the immunologic profile of patients
with CRSwNP.
Materials and Methods
Patients and tissue samples
This study was approved by the Institutional Review Board of Hallym Medical University
Chuncheon Sacred Hospital (No. 2018-39), and all participants provided written informed
consent for study participation. NP tissues were obtained from patients with CRSwNP during
routine functional endoscopic sinus surgery. The diagnosis of CRS was based on the
European position paper on rhinosinusitis and nasal polyps guidelines. In this study, we
excluded the subjects as follows: (1) less than 18 years of age, (2) history of prior treatment
with antibiotics, systemic or topical corticosteroids, or other immune-modulating drugs in the
4 weeks before surgery, and (3) presence of unilateral rhinosinusitis, antrochoanal polyp,
allergic fungal sinusitis, cystic fibrosis, or immotile ciliary disease. Control tissue samples
were also obtained from patients without any sinonasal diseases during other types of
rhinologic surgeries. All samples were homogenized with a mechanical homogenizer at 1,000
rpm for 5 minutes on ice. After homogenization, the suspensions were centrifuged at 3,000
rpm for 10 minutes at 4 ºC, and the supernatants were separated and stored at -80 ºC for
further analysis of cytokines and other inflammatory mediators. The atopic status of the
patients was evaluated using the ImmunoCAP® assay (Thermo Scientific Inc., Waltham, MA,
USA), which detected immunoglobulin E (IgE) antibodies against six mixtures of common
aeroallergens (house dust mites; molds; trees; weeds and grass pollen; and animal dander).
Participants were considered atopic if the allergen-specific IgE level was greater than 0.35
KU/L for any one or more of the allergens. A diagnosis of asthma was made by an allergist
based on the medical history and lung function analysis, including the methacholine
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challenge test. In this study, CRSwNP was classified as eosinophilic CRSwNP (ECRSwNP)
if eosinophils comprised more than 10% of the inflammatory cell population or as non-
eosinophilic CRSwNP (NECRSwNP) if eosinophils comprised less than 10% of the
inflammatory cells.
Measurement of inflammatory mediators in tissue homogenates
In the present study, we used multiplex cytokine analysis kits (tumor necrosis factor [TNF]-
ɑ, interferon [IFN]-γ, interleukin [IL]-4, IL-5, IL-10, IL-13, IL-17A, IL-22, IL-23, chemokine
[C-X-C motif] ligand [CXCL]-1, CXCL-8, C-C motif chemokine [CCL]-11, CCL-24,
eosinophil cationic protein [ECP], myeloperoxidase [MPO], and transforming growth factor
[TGF]-β) obtained from R&D systems (Cat. No. LMSAHM; Minneapolis, MN, US). All
assays were run in duplicate according to the manufacturer’s protocol. All protein levels in
tissue homogenates were normalized to the concentration of total protein (mg/mL). Samples
were thawed at room temperature and vortexed to ensure they were well-mixed.
Polysomnography
Standard overnight polysomnography (PSG) was performed preoperatively for all patients
using a computerized polysomnographic device (Nox-A1, Nox Medical Inc. Reykjavik,
Iceland). The sleep stage and respiratory events before and after surgery were scored
according to the guidelines of the American Academy of Sleep Medicine. Briefly, apnea was
scored using an oronasal thermal sensor when the peak signal excursions dropped by ≥ 90%
of the pre-event baseline, lasted for at least two breaths, and were associated with respiratory
effort for the entire period of absent airflow. A respiratory event was scored as a hypopnea if
the peak signal excursions dropped by ≥ 30% of the pre-event baseline using nasal pressure,
lasted for at least two breaths, and were associated with ≥ 3% oxygen desaturation from the
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pre-event baseline or with arousal. The apnea-hypopnea index (AHI) score was the sum of
apnea plus the number of hypopneas per hour of sleep. Based on the AHI, the severity of
OSA was classified as follows: no OSA, AHI < 5 per hour; mild OSA, 5 ≤ AHI < 15 per hour;
moderate OSA, 15 ≤ AHI < 30 per hour; severe OSA, AHI ≥ 30 per hour.
Statistical analysis
Prior to conducting the study, we performed a power calculation and determined the sample
size using G power. R version 3.4.2 software and GraphPad Prism software 7.0 (GraphPad
Software Inc, La Jolla, CA, US) were used for the statistical analyses. A chi-squared test and
two-tailed Mann-Whitney U-test were used for unpaired comparisons between two groups.
For comparisons among more than two groups, the Kruskal–Wallis test was initially used to
identify significant differences. The Bonferroni adjustment was used to adjust the
significance level for each comparison. We also used Pearson’s correlation coefficient to
measure the statistical relationship. The significance level was set at α = 0.05.
Results
Characteristics of the study population
We consecutively enrolled CRSwNP patients during the study period and then, a total of 63
CRSwNP patients underwent PSG before surgery. Of the patients with CRSwNP, ECRSwNP
and NECRSwNP accounted for 20 (31.7%) and 43 (68.3%) patients, respectively. The
demographic and clinical characteristics of the participants enrolled in this study are
presented in Table 1. Additionally, among enrolled patients with CRSwNP, 59 patients
(93.7%) were diagnosed with OSA and 4 CRSwNP patients were considered as non-OSA.
The control subjectss also underwent PSG, but none were diagnosed with OSA. Meanwhile,
the ECRSwNP group consisted of 8 patients with no-to-mild OSA and 12 patients with
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moderate-to-severe OSA, whereas there were 12 patients with no-to-mild OSA and 31
patients with moderate-to-severe OSA in the NECRSwNP group. The demographic and
clinical characteristics, according to the severity of OSA, are presented in Table 2. A
significantly higher body mass index was found in patients with moderate to mild OSA
(P=0.0245). Additionally, we presented the data for sleep quality such as sleep related
questionnaire and sleep parameters from PSG in Table 3.
Expression of inflammatory cytokines and chemokines according to the different endotypes
of CRSwNP
To investigate the immunological profile, we performed ELISA on sinonasal tissues. When
we analyzed type 1 inflammation among the three groups, we found a significant difference
in CXCL-1, CXCL-2, and IL-6 expressions; however, there were no significant differences in
IFN-γ, TNF-ɑ, and MPO expressions among the three groups (Fig. 1A). Additionally, TNF-ɑ
expression was higher in the NECRSwNP group than in the control group. Meanwhile, we
detected significantly higher expression of various type 2 related inflammatory markers,
including IL-4, IL-5, IL-13, CCL-11, and CCL-24 in patients with ECRSwNP (Fig. 1B).
Moreover, in the analysis of type 3 inflammation, IL-22 expression was significantly
increased in the ECRSwNP and NECRSwNP groups when compared to the control group,
whereas there were no significant differences in IL-17A or IL-23 among the three groups (Fig.
1C). TGF-β expression also showed significant downregulation in patients with ECRSwNP
and NECRSwNP.
Effect of obstructive sleep apnea on the expression of inflammatory cytokines and
chemokines according to the different endotypes of CRSwNP
To elucidate the effect of OSA in CRSwNP, we compared the expression of several
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inflammatory markers in NP tissues between patients with no-to-mild OSA and those with
moderate-to-severe OSA. Interestingly, in the patients with ECRSwNP, we found that the
expressions of several type 1 (CXCL-1 and IL-6), type 2 (IL-4, IL-13, CCL-11, and CCL-24),
and type 3 (IL-17A) inflammatory markers were significantly upregulated in patients with
moderate-to-severe OSA compared to those with no-to-mild OSA (Fig. 2). In contrast, there
were no differences between the NECRSwNP patients with no-to-mild OSA and those with
moderate-to-severe OSA in the expression of types 1, 2, or 3 inflammatory markers in the NP
tissues. Moreover, patients with NECRSwNP showed only increased TGF-β expression in
NP tissues in cases of moderate-to-severe OSA compared to cases with no-to-mild OSA (Fig.
3).
Next, to elucidate the relationship between systemic and local immune response in patients
with ECRSwNP and moderate-to-severe OSA, we analyzed the correlation of upregulated
inflammatory mediators with serum markers, such as eosinophil count and c-reactive protein
(CRP) (Fig. 4). Specifically, we found that CRP was significantly associated with IL-6
(r=0.9160, P=0.0014) and CXCL-1 (r=0.7130, P=0.0471), but not IL-17A. Meanwhile, there
was no significant association of serum eosinophil count with type 2 inflammatory markers;
however, we found a nearly significant association between serum eosinophil count and IL-4
(r=0.7024, P=0.0521) and CCL-11 (r=0.6891, P=0.0587).
Discussion
Previously, several studies demonstrated the relationship between CRS and OSA. In
addition, some studies showed improved sleep quality in CRS patients after endoscopic sinus
surgery [10,11]. OSA also may be associated with changes that affect the components and
responses of the immune system, as sleep deprivation impairs host defense mechanisms [12].
Moreover, one recent study of nasal microbiomes showed that the severity of OSA correlated
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with differences in microbiome diversity and composition in the sinonasal cavity [13].
However, to the best of our knowledge, there have been no studies examining the effect of
OSA on the immunologic profile of patients with CRSwNP. In this study, we investigated the
immune profile of patients with CRSwNP according to the severity of OSA. We found that
IL-6 and CXCL-1 (type 1 immune-related markers), IL-4, IL-13, CCL-11, CCL-24 (type 2
immune-related markers), and IL17A (type 3 immune-related marker) levels were
upregulated in cases of moderate-to-severe OSA in ECRSwNP, but not in NECRSwNP.
Therefore, we suggest that OSA may contribute to an increase in immune profile
heterogeneity in patients with ECRSwNP.
ECRSwNP is characterized as a type 2 immune inflammation with increased eosinophil
infiltration, whereas NECRSwNP shows mixed (types 1, 2, and 3) immune inflammation
with predominant neutrophilic infiltration [14, 15]. In accordance with previous reports, our
study sample revealed that ECRSwNP primarily increased type 2 immune inflammation
compared to NECRSwNP, regardless of OSA severity. Interestingly, we showed that, in
patients with ECRSwNP, types 1, 2, and 3-related inflammatory cytokines were upregulated
in moderate-to-severe OSA compared to no-to-mild OSA. However, unlike ECRSwNP,
patients with NECRSwNP had no significant differences in types 1, 2, or 3-related
inflammatory cytokine expressions according to OSA severity. Additionally, we found that,
in ECRSwNP patients with moderate-to-severe OSA, CRP level in serum was significantly
associated with nasal neutrophilic inflammation such as IL-6 and CXCL-1 and serum
eosinophil count showed a linear relation with nasal eosinophilic inflammation such as IL-4
and CCL-11. Collectively, these findings imply that sleep fragmentation and intermittent
hypoxia could contribute to change of immune profile changes in patients with ECRSwNP,
but not in those with NECRSwNP.
To date, multiple studies have consistently reported that undiagnosed or inadequately treated
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OSA adversely affects asthma control, whereas continuous positive airway pressure as a
treatment for OSA could attenuate the risk for worse asthma outcomes; this is partly due to
the effects of intermittent hypoxia on airway inflammation and tissue remodeling [16,17].
Several other human and animal studies showed that OSA could influence the immunologic
profile in asthma from traditional eosinophilic or type 2 inflammation to neutrophilic or type
1 inflammation [16,18,19]. Additionally, real-world datasets revealed that OSA was
associated with poor asthma control [20]. These studies showed that OSA may be a
contributor to increased neutrophil related inflammation in asthma, leading to a more
heterogeneous immune profile and poor disease control. Similar to prior studies, our study
showed an increased type 1 (CXCL-1 and IL-6) and type 3 (IL-17A) immune profile in
patients with ECRSwNP with moderate-to-severe OSA. Consistent with our findings, prior
studies showed that OSA was associated with increased levels of CRP, IL-8, IL-6, and TNF-α
in serum [21-23]. Moreover, several previous studies demonstrated that OSA may be
associated with changes in T-cell activation and proliferation, leading to increased CD4+ and
CD8+ cell counts [24,25]. A recent study reported that OSA affected the immune response by
increasing the proliferative potential of CD4+ and NK cells and decreasing phagocytosis and
NADPH oxidase activity in neutrophils [26]. Similar to those results, we found upregulated
type 2 immune inflammation in patients with ECRSwNP and moderate-to-severe OSA.
Collectively, the increased heterogeneity in immune status may be associated with more
severe disease expression, remodeling, and poor response to corticosteroids in patients with
ECRSwNP and moderate-to-severe OSA.
Generally, NECRSwNP is regarded as an extrinsic CRS, since its inflammation originates
from external stimuli such as bacteria and allergens rather than intrinsic mucosal
abnormalities [27]. Thus, NECRSwNP usually shows enhanced epithelial alterations and
more localized maxillary involvement compared with ECRSwNP [28,29]. For these reasons,
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we assumed that the immune profile of patients with NECRSwNP was relatively affected by
localized immune status (such as sinonasal tissue), while systemic immune status (such as in
asthma) more extensively affected the immune profiles of patients with ECRSwNP. In the
present study, we did not find any significant differences in type 1, 2, and 3-related
inflammatory markers in the NP tissues of patients with NECRSwNP with no-to-mild and
moderate-to-severe OSA. Since OSA should be considered a systemic disease rather than a
local abnormality, we believe the change in immune profile is not definite in patients with
NECRSwNP. However, TGF-β expression was higher in patients with NECRSwNP with
moderate-to-severe OSA than in those with no-to-mild OSA. It has been established that
TGF-β plays an important role in remodeling processes involved in CRS and serves as the
main switch for different remodeling patterns in CRSwNP [30]. Thus, this finding indicates
that OSA severity may partially influence tissue remodeling in patients with NECRSwNP.
As this was a cross-sectional study, it presented some limitations. First, although there was
no significant difference in disease severity as shown by the Lund-Mackay CT score for
CRSwNP and AHI for OSA, whether OSA severity influences the immunologic profile of NP
tissues or if CRSwNP severity contributes to the severity of OSA remains unclear. Therefore,
a longitudinal study is required to investigate the possibility of changes in NP tissue
immunology over time. However, we also found some clues regarding the effect of systemic
immune status on local nasal immunity in ECRSwNP patients with moderate-to-severe OSA.
Interestingly, we observed that an increase in CRP level as a systemic immunologic factor
was associated with an increased expression of nasal neutrophil inflammatory markers, such
as IL-6 and CXCL-1, whereas the association between an increase in serum eosinophil count
as a systemic immunologic factor and increased expression of nasal type 2 inflammatory
markers, such as IL-4 and CCL-11 was nearly significant. These findings imply that sleep
fragmentation and intermittent hypoxia might contribute to change of immune profile
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changes in CRSwNP patients. Secondly, to prove its reliability, an external validation study is
needed.
Conclusion
Our findings suggest that OSA severity influences the immunologic profile of NP tissues of
patients with ECRSwNP. Specifically, a mixed immune response (types 1, 2, and 3) was
upregulated in ECRSwNP, whereas we could not find any significant effect in NECRSwNP
according to OSA severity.
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Table 1. Patient characteristics according to the phenotype of chronic rhinosinusitis with
nasal polyp
Total no. of subjects
Control
NECRSwNP
ECRSwNP
n = 9
n = 43
n = 20
Age (y), mean (SD)
54.9 (10.5)
50.3 (14.9)
49.7 (11.5)
Gender (male), N (%)
8 (88.9)
35 (81.4)
16 (80.0)
Smoking history, N (%)
1(11.1)
18 (41.9)
5 (25.0)
Body mass index
23.7 (1.5)
25.4 (4.5)
24.6 (4.2)
Asthma, N (%)
0 (0)
4 (10.5)
5 (25.0)
Atopy, N (%)
3 (33.3)
17 (39.5)
5 (25.0)
Aspirin sensitivity, N
0
0
0
Serum eosinophil count
(SD)
48.7 (26.8)
159.7 (179.8)
193.9 (70.6)
C-reactive protein (SD)
0.4 (0.3)
0.8 (0.5)
1.4 (0.9)
Lund-Mackay CT score
(SD)
0 (0)
15 (5.1)
14.5 (4.6)
The results reported as n (%) for categorical variables and mean (standard deviation: SD) for
continuous variables.
NECRSwNP, non-eosinophilic chronic rhinosinusitis with nasal polyp
ECRSwNP, eosinophilic chronic rhinosinusitis with nasal polyp
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Table 2. Characteristics of patients with CRSwNP between none to mild and mild to severe
OSA
Total no. of subjects
None to mild OSA
Moderate to severe OSA
n = 24
n = 39
Age (y), mean (SD)
52.0 (12.9)
49.2 (14.4)
Gender (male), N (%)
19 (79.2)
32 (82.1)
Smoking history, N (%)
9 (37.5)
14 (35.9)
Body mass index*
23.3 (3.5)
25.8 (4.5)
Asthma, N (%)
4 (16.7)
5 (12.8)
Atopy, N (%)
11 (45.8)
11 (28.2)
Aspirin sensitivity, N
0
0
Serum eosinophil count
(SD)
190.7 (79.9)
158.1 (185.4)
C-reactive protein (SD)
1.0 (0.8)
0.9 (0.7)
Lund-Mackay CT score
(SD)
14.3 (4.9)
15.5 (4.9)
The results reported as n (%) for categorical variables and mean (standard deviation: SD) for
continuous variables.
Chronic rhinosinusitis with nasal polyp: CRSwNP; Obstructive sleep apnea: OSA
*P<.05
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Table 3 Sleep quality parameters in this study population
Normal to mild OSA
Moderate to severe OSA
Sleep related questionnaire
Epworth sleepiness scale
7.6 (5.5)
16.2 (4.5)
Pitchburg sleep quality
7.4 (3.3)
11.2 (3.1)
Sleep parameters
Total sleep time (min)
381.5 (81.0)
284.3 (99.1)
Sleep efficiency (%)
79.9
68.0
N3 (%)
15 (3.1)
4.3 (6.0)
REM (%)
22 (5.3)
15.3 (5.6)
Mean AHI (event/hr)
7.6 (3.4)
35.1 (28.9)
N3, deep sleep; REM, rapid eye movement; AHI, apnea hypopnea index.
The results reported as mean (standard deviation: SD) for continuous variables.
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Figure Legends
Fig. 1 Expression of inflammatory mediators in nasal tissues according to the phenotype of
chronic rhinosinusitis: (A) type 1 immune-related markers, (B) type 2 immune-related
markers, (C) type 3 immune-related markers (results reported as median and interquartile
range).
ECRSwNP: eosinophilic chronic rhinosinusitis with nasal polyp
NECRSwNP: non-eosinophilic chronic rhinosinusitis with nasal polyp
(*P<.05, **P<.01, and ***P<.001)
Fig. 2 Expression of inflammatory mediators in ECRSwNP patients according to the severity
of OSA: (A) type 1 immune-related markers, (B) type 2 immune-related markers, (C) type 3
immune-related markers (results reported as median and interquartile range).
ECRSwNP: eosinophilic chronic rhinosinusitis with nasal polyp
OSA: obstructive sleep apnea
Fig. 3 Expression of inflammatory mediators in NECRSwNP patients according to the
severity of OSA: (A) type 1 immune-related markers, (B) type 2 immune-related markers, (C)
type 3 immune-related markers (results reported as median and interquartile range).
NECRSwNP: non-eosinophilic chronic rhinosinusitis with nasal polyp
OSA: obstructive sleep
Fig. 4 Correlation of upregulated inflammatory mediators and serum markers in ECRSwNP
patients who have moderate to severe OSA.
(A) Association of C-reactive protein with IL-6, CXCL-1, IL-17A; (B) Association of serum
eosinophil count with IL-4, IL-13, CCL-11. CCL-24.
ECRSwNP: eosinophilic chronic rhinosinusitis with nasal polyp
OSA: obstructive sleep
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figure 1A
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figure 1B
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figure 1C
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figure 2A
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figure 2B
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figure 2C
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figure 3A
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figure 3B
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figure 3C
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figure 4A
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figure 4B
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