ORIGINAL ARTICLE
Impact of chronic rhinosinusitis on sleep: a controlled clinical study
Jeremiah A. Alt, MD, PhD1 , Vijay R. Ramakrishnan, MD2 , Michael P. Platt, MD3 ,
Rodney J. Schlosser, MD4 , Tina Storck, MS4 and Zachary M. Soler, MD, MSc4
Background: Earlier studies have suggested that pa-
tients with chronic rhinosinusitis (CRS) report worse sleep
quality than population norms. What remains unknown is
whether these patients are actually experiencing measur-
able changes in objective sleep parameters. The goal of this
study was to prospectively evaluate objective sleep mea-
sures in a cohort of patients with CRS.
Methods: A prospective, multi-institutional, case-control
study was designed to compare patients with CRS to
nondiseased controls. Sleep quality was measured using
the Pisburgh Sleep Quality Index (PSQI) and the Epworth
Sleepiness Scale (EpSS). Home sleep studies were admin-
istered across all subjects and a baery of objective sleep
measurements were recorded using a portable sleep diag-
nostic device. Regression models were used to control for
any factors that differed across groups.
Results: A total of 108 subjects were enrolled across 4 in-
stitutions, including 52 patients with CRS and 56 controls.
Total PSQI scores were worse in patients with CRS when
compared with controls (10.1 ± 4.3 vs 4.7 ± 2.5; p < 0.001).
Similarly, daytime somnolence, as measured by the EpSS,
was greater in patients with CRS (9.1 ± 5.3 vs 6.5 ± 3.7;
C hronic rhinosinusitis (CRS) impacts 5–10% of the
United States population and is characterized by on-
going mucosal inflammation of the paranasal sinuses that
1 Sinusand Skull Base Surgery Program, Division of
Otolaryngology–Head and Neck Surgery, Department of Surgery,
University of Utah, Salt Lake City, UT; 2 Department of Otolaryngology,
University of Colorado, Aurora, CO; 3 Department of Otolaryngology,
Boston University, Boston, MA; 4 Division of Rhinology and Sinus
Surgery, Department of Otolaryngology–Head & Neck Surgery,
Medical University of South Carolina, Charleston, SC
Correspondence to: Zachary M. Soler, MD, MSc, Division of Rhinology and
Sinus Surgery, Department of Otolaryngology–Head and Neck Surgery,
Medical University of South Carolina, 135 Rutledge Avenue, Charleston, SC
29425; e-mail: solerz@musc.edu
Funding sources for the study: American Academy of Otolaryngic Allergy;
American Rhinologic Society.
Received: 2 August 2018; Revised: 1 September 2018; Accepted:
5 September 2018
DOI: 10.1002/alr.22212
View this article online at wileyonlinelibrary.com.
16 International Forum of Allergy & Rhinology, Vol. 9, No. 1, January 2019
p = 0.006). On home sleep studies, patients with CRS were
found to have an increased number of awakenings during
a night’s sleep (8.6 ± 4.8 vs 6.3 ± 3.0; p = 0.004), lower
average overnight oxygen saturation (93.2 ± 2.6% vs 94.3
± 2.1%; p = 0.042), increased rapid eye movement sleep
(REMS) latency (93.0 ± 67.1 vs 66.7 ± 35.3; p = 0.016), and
spent a greater portion of the night snoring at >40 dB (24.7
± 27.4% vs 14.6 ± 19.7%; p = 0.034). All differences except
mean oxygen saturation remained significant aer control-
ling for baseline differences.
Conclusion: Differences in both patient-reported and ob-
jective sleep measures exist between patients with CRS
and controls. 
C 2018 ARS-AAOA, LLC.
Key Words:
chronic rhinosinusitis; disease severity; patient-reported
outcome measure
How to Cite this Article:
Alt JA, Ramakrishnan VR, Pla MP, et al. Impact of chronic
rhinosinusitis on sleep: a controlled clinical study. Int
Forum Allergy Rhinol. 2019;9:16–22.
persists beyond 3 months.1, 2 The cardinal symptoms of
CRS include nasal congestion, discolored nasal drainage,
facial pain/pressure, and smell loss, but a wide body of
evidence supports impacts that extend beyond just the
nose and sinuses. A number of studies have examined
the impact of CRS on sleep quality.3–7 From a quality-
of-life (QOL) standpoint, sleep dysfunction is a specific
domain of the widely utilized 22-item Sino-Nasal Out-
comes Test (SNOT-22) QOL instrument. Differences in
sleep scores contribute to baseline QOL deficits in pa-
tients with CRS and appear to influence the likelihood
with which those patients choose to undergo sinus surgery.8
A number of studies have explored patient-reported sleep
quality in more detail, often utilizing the Pittsburgh Sleep
Quality Index (PSQI).9 These studies universally found
that patients with CRS report sleep quality to be signif-
icantly worse than population norms, often on par with
other chronic diseases and even sleep-specific disorders such
as obstructive sleep apnea or narcolepsy.6 Furthermore,

patient-reported sleep quality scores have been shown to
improve after both medical and surgical treatment of CRS,
suggesting that the sleep dysfunction experienced by pa-
tients is related to their underlying CRS.3, 6, 7
Although patient-reported sleep quality is clearly worse
in patients with CRS, what remains unknown is whether
these patients are actually experiencing measurable, objec-
tive changes in sleep. From a mechanistic standpoint, it
is certainly plausible that sinonasal inflammation related to
CRS may disturb sleep physiology. Simplistically, this could
be related to nasal airway blockage, altering the balance of
nasal and oral airflow and contributing to snoring and/or
sleep apnea. Alternatively, it remains possible that rhino-
genic symptoms, such as nasal congestion and postnasal
drainage, impact sleep quality by interfering with the sleep
cycle via frequent awakenings. Inflammatory cytokines as-
sociated with CRS could also directly impact sleep via neu-
roimmune signaling.10 Last, it is possible that measurable,
objective changes in sleep are not occurring, despite patient-
reported deficits in sleep quality.
It is important to understand whether CRS patients truly
suffer from objective sleep dysfunction so we may under-
stand the potential for significant psychosocial and health
implications. The goal of this study was to prospectively
evaluate objective sleep measures in a cohort of patients
with CRS, comparing findings with those from a control
population. We hypothesized that patients with CRS would
have alterations in objective measures associated with the
sleep cycle. Secondary goals were to evaluate differences
in subgroups defined by polyp status and control for re-
lated factors more common in CRS patients, which may
confound the analysis.
Patients and methods
This study was implemented as a prospective, multi-
institutional, case-control study. Adults (ࣙ18 years) with
medically refractory CRS were enrolled from tertiary rhi-
nology clinics at 4 academic centers: the Medical Univer-
sity of South Carolina (MUSC; Charleston, SC); the Uni-
versity of Utah (UU; Salt Lake City, Utah); the University
of Colorado (CU; Aurora, Colorado); and Boston Univer-
sity (BU; Boston, Massachusetts). The presence of CRS was
diagnosed using criteria from the the European Position Pa-
per on Rhinosinusitis and Nasal Polyps 2012 (EPOS12).11
Those patients who were considered surgical candidates
were offered the option to undergo ESS after failing ini-
tial attempts at appropriate medical treatment. The ex-
tent of attempted medical treatments varied, but to be in-
cluded all patients must have failed initial medical man-
agement consisting of at least one course of oral steroid,
broad-spectrum, or culture-directed antibiotics for at least
14 days, and a minimum 3 weeks of topical steroid sprays.
To be eligible, patients with CRS must have been off oral
steroids for ࣙ1 month before enrollment.
Control subjects (ࣙ18 years) without any history
of sinusitis were recruited from among individuals
Impact of CRS on sleep
accompanying patients to otolaryngology appointments
at the same institution, such that both cases and controls
derived from the same source population. Theoretically,
this could include bed partners of patients with CRS,
although specific relationships and sleeping arrangements
were not queried. All subjects provided written informed
consent and the study protocol was approved by the
institutional review boards at all contributing sites.
Demographic information and history of comorbidities,
such as asthma, aspirin intolerance, allergies, and depres-
sion, was collected using standardized questionnaires for all
participants. Tobacco and alcohol intake was recorded as
cigarettes/day and drinks/week, respectively. Allergic rhini-
tis was established for those who carried a physician’s di-
agnosis and had confirmation with previous positive ob-
jective testing. Height and weight data were obtained for
each individual and converted into body mass index (BMI).
Current use of antihistamines, antidepressants, anxiolytics,
and antipsychotics was recorded. Any subject with a pre-
viously diagnosed primary sleep disorder (obstructive sleep
apnea, narcolepsy, insomnia) was excluded from the study.
Control subjects were excluded if they reported a history of
CRS or recurrent sinus infections, or met symptoms criteria
for CRS according to EPOS12.11
Measures of CRS
Patients and controls completed the SNOT-22, which re-
quires patients to rate 22 symptom-related items on a scale
ranging from 0 (no problem) to 5 (problem is as bad as
it can be).12 Nasal endoscopy was used to categorize each
patient into CRS with polyps (CRSwNP) and CRS with-
out polyps (CRSsNP) and was also scored using the Lund-
Kennedy (LK) staging system.13 Computed tomography
(CT) scans of patients with CRS were scored using the
Lund-Mackay (LM) scoring method.14
Evaluation of patient-reported sleep quality,
fatigue, daytime somnolence, depression, and pain
All study participants completed the PSQI, a self-reported
questionnaire measuring sleep quality and disturbance over
the preceding 1-month period.9 The PSQI yields 7 compo-
nent or subdomain scores: subjective sleep quality; sleep
latency; sleep duration; sleep efficiency; sleep disturbance;
sleep medication usage; and daytime dysfunction. Subdo-
main component scores (range, 0–3) are assessed using an
openly available scoring algorithm and added to obtain
a total score (range, 0–21), with higher scores indicating
worse sleep quality. The level of fatigue experienced by
the subject was assessed using the Fatigue Severity Scale
(FSS).15, 16 The FSS is a valid, reliable, and internally consis-
tent instrument that measures fatigue over the last 4 weeks
(range, 1–7), with higher scores representing more fatigue.
The Epworth Sleepiness Scale (EpSS) was utilized to mea-
sure a person’s general level of daytime sleepiness, giving
a sleep propensity score ranging from 0 to 24.17 The po-
tential presence of depression was determined using the
International Forum of Allergy & Rhinology, Vol. 9, No. 1, January 2019 17
Alt et al.

Patient Health Questionnaire-2 (PHQ2), which measures TABLE 1. Characteristics of the study population
frequency of depressed mood and anhedonia over the pre-
ceding 2 weeks, with higher scores representing depressed CRS (n = 52) Control (n = 56) p value
mood.18
Demographics
Age 45.6 (14.1) 43.9 (15.1) 0.564
Evaluation of objective sleep measures
All subjects were given a WatchPAT device for home sleep Sex Male 32 (61.5%) 24 (42.9%) 0.052
testing (Itamar Medical, Inc, Franklin, MA). A dedicated Female 20 (38.5%) 32 (57.1%)
study coordinator gave detailed instruction on how to ad-
Race White 42 (80.8%) 48 (85.7%) 0.701
minister the home sleep test and subjects were encour-
aged to choose a night where they follow their typical Black 9 (17.3%) 6 (10.7%)
nightly routine. WatchPAT is a United States Food and Other 1 (1.9%) 2 (3.6%)
Drug Administration–approved, wrist-worn device with 2
BMI 28.9 (6.6) 26.3 (4.9) 0.021
sensors, which attach to the ipsilateral fingers, and an in-
tegrated snoring sensor, which allows measurement of pe- Exposures
ripheral arterial tone (PAT), pulse rate, oxygen saturation, Cigarettes/day 0.3 (1.5) 0.5 (2.9) 0.603
actigraphy, and snoring.19–21 Measurements for Respira-
tory Disturbance Index (RDI) and Apnea-Hypopnea Index Alcoholic drinks/week 2.8 (5.7) 2.3 (3.2) 0.591
(AHI) was done by simultaneously measuring PAT, heart Comorbidities
rate, and oxygen saturation. There have been numerous Asthma No 33 (63.5%) 56 (100.0%) <0.001
direct comparisons to formal in-office polysomnography
(PSG), showing excellent correlation between WatchPAT Yes 19 (36.5%) 0 (0.0%)
RDI/AHI and in-office PSG (r = 0.82-0.89).20–23 Measures Allergic rhinitis No 24 (46.2%) 48 (85.7%) <0.001
of sleep architecture were recorded, including sleep latency,
Yes 28 (53.9%) 8 (14.3%)
total sleep time, and awakenings, as well the percentage of
time in stages of rapid eye movement (REM) and non- Immunodeficiency No 51 (98.1%) 56 (100.0%) 0.481
REM (NREM) sleep. Direct comparisons of WatchPAT to Yes 1 (1.9%) 0 (0.0%)
formal in-office PSG have shown excellent epoch-by-epoch
AERD No 49 (94.2%) 55 (98.2%) 0.350
agreements ranging from 80% to 90%.19, 24, 25 Last, the
percentage of sleep spent snoring at >40 decibels (dB) was Yes 3 (5.8%) 1 (1.8%)
recorded. GERD No 42 (80.8%) 51 (91.1%) 0.122
Yes 10 (19.2%) 5 (8.9%)
Statistical analysis
Depression (MD diagnosis) No 43 (82.7%) 51 (91.1%) 0.195
All data recorded were collected on standardized forms
and entered into a REDCap database using double data- Yes 9 (17.3%) 5 (8.9%)
entry processes to ensure data integrity. Data from each Migraine No 41 (78.9%) 50 (89.3%) 0.137
center were then merged and analysis was performed us-
Yes 11 (21.2%) 6 (10.7%)
ing SPSS version 24.0 (IBM Corporation, Armonk, NY).
Demographic information, comorbidities, patient-reported Pain disorder No 49 (94.2%) 53 (94.6%) 1.000
metrics, and objective sleep parameters were assessed using Yes 3 (5.8%) 3 (5.4%)
descriptive statistics. Continuous variables were compared
between 2 cases and controls using the independent t test Medications
or Mann-Whitney U test. Categorical variables were com- Antihistamines (oral) No 30 (60.0%) 50 (92.6%) <0.001
pared between 2 groups using the Pearson’s chi-square test
Yes 20 (40.0%) 4 (7.4%)
or Fisher’s exact test. Linear, Poisson, and beta-regression
models were created to evaluate for statistical differences Antidepressants No 42 (82.4%) 46 (86.8%) 0.530
while controlling for confounding factors. Resulting regres- Yes 9 (17.7%) 7 (13.2%)
sion coefficients (β) and standard errors (SEs) were used to
Anxiolytics No 50 (98.0%) 53 (98.2%) 1.000
estimate linear changes.
Yes 1 (2.0%) 1 (1.9%)
Antipsychotics No 51 (100.0%) 54 (100.0%) NA
Results
*
Data expressed as mean (standard deviation) or as number (%)
A total of 108 subjects were enrolled across 4 institutions, AERD = aspirin-exacerbated respiratory disease; BMI = body mass index;
including 52 patients with CRS and 56 controls (MUSC GERD = gastroesophageal reflux disease; NA = not applicable.
= 41, UU = 30, CU = 21, BU = 16; Table 1). There
were no differences in age, gender, or race across groups.

18 International Forum of Allergy & Rhinology, Vol. 9, No. 1, January 2019

 Impact of CRS on sleep

TABLE 2. Patient-reported sleep quality, fatigue, TABLE 3. Objective sleep measures from home sleep test
and daytime somnolence
Cohort N Mean (SD) p value
Cohort N Mean (SD) p value
Respiratory disturbance Index CRS 48 19.9 (14.9) 0.516
PSQI Total CRS 50 10.1 (4.3) <0.001
Control 52 18.1 (12.4)
Control 55 4.7 (2.5)
Apnea-Hypopnea Index CRS 48 14.4 (15.2) 0.431
FSS Total CRS 48 3.9 (1.5) <0.001
Control 52 12.2 (13.0)
Control 55 2.5 (1.3)
Average overnight oxygen CRS 48 93.3 (2.6) 0.042a
EpSS Total CRS 49 9.1 (5.3) 0.006 saturation
Control 55 6.5 (3.8) Control 52 94.3 (2.1)
PHQ-2 Total CRS 50 1.8 (1.7) <0.001 Mean pulse rate CRS 50 68.3 (11.0) 0.112
Control 55 0.4 (0.7) Control 52 64.9 (10.3)

SD = standard deviation; PSQI = Pittsburgh Sleep Quality Index; FSS = Fa- Sleep latency (minutes) CRS 51 22.3 (12.9) 0.285
tigue Severity Scale; EpSS = Epworth Sleepiness Scale; PHQ-2 = Patient Health
Questionnaire-2; MPQ-SF = McGill Pain Questionnaire short form. Control 52 19.9 (8.7)
SD = standard deviation.
REM latency (minutes) CRS 50 93.0 (67.1) 0.016a
Control 52 66.7 (35.3)
Patients with CRS had more asthma and allergic rhinitis
Number of wakes CRS 50 8.6 (4.8) 0.004a
compared with controls (p < 0.001). Average BMI was
higher in those with CRS when compared with controls Control 52 6.3 (3.0)
(28.9 ± 6.6 vs 26.3 ± 4.9; p = 0.021). As expected, SNOT- Total sleep time (minutes) CRS 51 367.9 (72.5) 0.786
22 scores were significantly higher in CRS patients than in
controls (54.0 ± 19.8 vs 10.3 ± 9.0; p < 0.001). Patients Control 52 364.0 (72.8)
with CRS were evenly split between CRSwNP (n = 27; Percent of sleep while snoring CRS 51 24.7 (27.4) 0.034a
52%) and CRSsNP (n = 25; 48%), with an average LM at >40 dB
CT score of 12.8 ± 6.0 and LK endoscopy score of 6.5 ± Control 52 14.6 (19.7)
3.3.
Patient-reported outcomes metrics were significantly dif- REM percent CRS 49 25.5 (11.3) 0.936
ferent between cases with CRS and controls (Table 2). As Control 52 25.3 (6.5)
expected, PSQI scores were worse in patients with CRS Light sleep percent CRS 49 56.0 (11.4) 0.798
compared with controls (10.1 ± 4.3 vs 4.7 ± 2.5; p <
0.001). There were also differences in EpSS, with greater Control 52 56.5 (10.2)
daytime somnolence in patients with CRS (9.1 ± 5.3 vs 6.5 Deep sleep percent CRS 49 19.1 (6.1) 0.956
± 3.7; p = 0.006). Fatigue (FSS) and depression (PHQ-
Control 52 19.2 (9.4)
2) scores were also significantly worse in CRS patients
vs controls (p < 0.001 for all). No difference in patient- CRS = chronic rhinosinusitus; REM = rapid eye movement; SD = standard devi-
ation.
reported metrics were seen between CRSsNP and CRSwNP a
Statistically significant (p < 0.05).
subgroups (p > 0.08 for all).
Differences were seen between cases and controls for a
number of objective sleep parameters (Table 3). Patients were seen in objective sleep parameters between CRS
with CRS were found to have an increased number of subgroups.
awakenings during a night’s sleep compared with controls Linear regression was then used to control for factors that
(8.6 ± 4.8 vs 6.3 ± 3.0; p = 0.004), as well as a lower may differentially impact sleep in CRS compared with con-
average overnight oxygen saturation (93.2 ± 2.6% vs 94.3 trols (Tables 4 and 5). In this study, those with CRS were
± 2.1%; p = 0.042). Increased REM sleep latency was also more likely to be male and have higher BMI than controls, 2
seen in patients with CRS when compared with controls factors that could potentially impact sleep in these groups
(93.0 ± 67.1 vs 66.7 ± 35.3; p = 0.016). Last, patients with and confound outcomes. However, PSQI, FSS, and ESS
CRS spent a greater portion of the night snoring at >40 dB remained worse in CRS patients compared with controls
(24.7 ± 27.4% vs 14.6 ± 19.7%; p = 0.034). No differ- in regression models adjusted for gender and BMI. Simi-
ences were seen between groups for total sleep time, AHI, larly, sleep latency and number of awakenings remained
RDI, or percentage of time in discrete sleep stages. When significantly increased after adjusting for gender and BMI,
comparing CRS subgroups, REM latency was increased in whereas average overnight oxygen saturation and percent-
those with CRSsNP when compared with CRSwNP (104.3 age of the night snoring at >40 dB no longer reached
± 48.2 vs 80.7 ± 22.1; p = 0.032). No other differences statistical significance. Last, in patients with CRS, no

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Alt et al.

TABLE 4. Linear regressions of CRS and outcomes adjusting for gendera

Unstandardized coefficients 95% CI for β

Model β SE t p value Lower bound Upper bound

PSQI CRS 5.574 0.682 8.169 <0.001 4.221 6.928

Genderc 1.232 0.682 1.807 0.074 −0.120 2.585
FSS CRS 1.449 0.278 5.211 <0.001 0.897 2.001
Gender 0.130 0.277 0.470 0.639 −0.420 0.681
ESS CRS 2.556 0.907 2.819 0.006 0.758 4.355
Gender −0.093 0.906 −0.102 0.919 −1.890 1.704
PHQ-2 d
CRS 1.511 0.241 e
39.281 (1) <0.001 1.038 1.983
Gender 0.157 0.194 e
0.661 (1) 0.416 −0.222 0.537
Average overnight oxygen saturation CRS −0.814 0.480 −1.695 0.093 −1.766 0.139
Gender 0.820 0.480 1.708 0.091 −0.133 1.772
REM latency CRS 25.574 10.775 2.373 0.020 4.194 46.953
Gender −4.593 10.775 −0.426 0.671 −25.973 16.786
Number of wakes CRS 2.377 0.807 2.947 0.004 0.777 3.977
Gender 0.130 0.807 0.161 0.872 −1.471 1.731
Percent of sleep while CRS 0.372 0.208 1.79 0.076 −0.039 0.784
snoring at >40 dB f
Gender 0.040 0.207 0.200 0.846 −0.370 0.451
a
Significant CRS variables indicate that those with CRS have worse scores than those without for that particular outcome, after adjusting for gender.
b
Statistically significant (p < 0.05).
c
Males are the reference for gender.
d
Poisson regression.
e
Wald chi-square (degrees of freedom).
f
Beta regression.
CI = confidence interval; CRS = chronic rhinosinusitus; EpSS = Epworth Sleepiness Scale; FSS = Fatigue Severity Scale; PHQ-2 = Patient Health Questionnaire-2; PSQI
= Pittsburgh Sleep Quality Index; REM = rapid eye movement.

positive correlation with asthma, allergy, or antihistamine
usage was seen for any of the objective sleep variables that
differed between CRS and controls.
Discussion
Findings from this study support a growing body of evi-
dence showing that patients with CRS have poor subjective
sleep quality compared to similar subjects without CRS.
Furthermore, patients in this study also reported increased
fatigue and daytime somnolence as compared to those with-
out CRS. What has remained unknown is the degree to
which these patient-reported symptoms reflect measurable,
objective sleep changes or are a manifestation of disease
unrelated to actual sleep physiology. Findings from home
sleep tests suggest that discernible changes in objective sleep
are present in patients with CRS as compared with nondis-
eased controls. These data provide further evidence that
the pathophysiologic impacts of CRS extend beyond just
the nose and sinuses and that sleep dysfunction in patients
with CRS is a major consequence of ongoing disease.
The cross-sectional, case-control nature of this study does
not allow for direct insights regarding causality or specific
mechanisms for sleep disturbance in CRS. However, one
can hypothesize mechanisms by which CRS may result in
alterations of sleep parameters. Perhaps the most apparent
is increased snoring, which is likely related to nasal con-
gestion, increased nasal resistance, decreased nasal airflow,
and increased mouth breathing during sleep. The fact that
CRS patients awaken more frequently during the night also
makes intuitive sense and mirrors common patient com-
plaints. Nasal congestion, postnasal drainage, and cough-
ing at night are common in CRS and each could explain
the increased awakenings seen in CRS compared with con-
trols. Furthermore, the high levels of sleep fragmentation,
due to the recurrent awakenings we observed in patients
with CRS may explain why patients with CRS are report-
ing nonrestorative sleep (PSQI, FSS, EpSS), even with ob-
served normal total sleep times. The other consistent finding
in this study was increased REMS latency compared with
controls, but this finding is harder to explain. Depression
can impact REMS latency, but usually this shortens rather
than prolongs latency.26 Primary sleep disorders and psy-
choactive medications can impact REMS latency, but no
difference was seen in AHI/RDI between cases and con-
trols, and subjects with other primary sleep disorders or

20 International Forum of Allergy & Rhinology, Vol. 9, No. 1, January 2019

 Impact of CRS on sleep

TABLE 5. Linear regressions of CRS and outcomes adjusting for BMIa

Unstandardized coefficients 95% CI for β

Model β SE t p value Lower bound Upper bound

PSQI CRS 5.138 0.695 7.389 <0.001b 3.759 6.517

BMI 0.086 0.059 1.469 0.145 −0.030 0.203
FSS CRS 1.411 0.283 4.983 <0.001b 0.849 1.973
BMI 0.007 0.024 0.279 0.781 −0.041 0.054
ESS CRS 2.154 0.902 2.389 0.019b 0.366 3.943
BMI 0.151 0.077 1.962 0.053 −0.002 0.304
PHQ-2 c
CRS 1.422 0.243 10.224 (1) d
<0.001 b
0.946 1.899
BMI 0.019 0.015 1.678 (1)d
0.195 −0.010 0.047
Aveeage overnight oxygen saturation CRS −0.734 0.485 −1.515 0.133 −1.696 0.228
BMI −0.081 0.042 −1.950 0.054 −0.164 0.001
b
REM latency CRS 25.125 11.031 2.278 0.025 3.237 47.014
BMI 0.393 0.945 0.415 0.679 −1.483 2.268
b
Number of wakes CRS 1.579 0.762 2.071 0.041 0.066 3.091
b
BMI 0.259 0.066 3.906 0.000 0.127 0.390
Percent of sleep while snoring at >40 CRS 0.207 0.204 1.01 0.315 −0.200 0.614
dBe
BMI 0.059 0.018 3.33 0.001 0.024 0.094
a
Significant CRS variables indicate that those with CRS have worse scores than those without for that particular outcome, after adjusting for BMI.
b
Statistically significant (p < 0.05).
c
Poisson regression.
d
Wald chi-square (degrees of freedom).
e
Beta regression.
BMI = body mass index; CI =confidence interval; CRS = chronic rhinosinusitus; EpSS = Epworth Sleepiness Scale; FSS = Fatigue Severity Scale; PHQ-2 = Patient Health
Questionnaire-2; PSQI = Pittsburgh Sleep Quality Index; REM = rapid eye movement.

taking medications known to impact sleep were excluded
from the study. Future investigations using the Multiple
Sleep Latency Test (MSLT) could shed further light on this
finding, as the MSLT has been used to distinguish hyper-
somnia, narcolepsy, and behavior-induced inadequate sleep
syndrome.27
Refractory CRS is a disease characterized by chronic in-
flammation and much work has explored local and systemic
inflammatory cytokine profiles.28 On a local level, sinonasal
inflammation results in nasal congestion, drainage, and
coughing, which could impact sleep as hypothesized earlier.
However, circulating inflammatory cytokines could impact
sleep directly, independent of nasal congestion or mucus
production. Studies have shown that fatigue and feelings
of sleepiness can be elicited by injection of exogenous cy-
tokines and thus it remains possible that some degree of
patient-reported sleep quality and fatigue is a direct conse-
quence of the inflammatory, cytokine milieu characteristic
of CRS.10 These same cytokines and downstream media-
tors also appear to play some role in sleep regulation and
maintenance of proper sleep architecture during health and
disease.10, 29, 30 Some studies have also observed alterations
in REM latency related to systemic inflammation.31, 32 Cer-
tainly, the role of any specific inflammatory cytokine in
sleep dysfunction in CRS is speculative and future studies
will need to be specifically designed to explore hypothetical
mechanisms.
The main limitation of this study is its case-control de-
sign. Although patients and controls were enrolled irrespec-
tive of any preconceived notion of sleep quality, one can
never be sure that unintentional selection bias did not occur.
Significant effort was made to assess measures that could
confound the analysis based on preexisting knowledge,
including age, gender, BMI, tobacco/alcohol use, medical
comorbidities, and medication usage. There were major
baseline differences between the CRS and control groups.
Some of these differences were expected, such as increased
asthma and allergic rhinitis in the CRS group. The main
unexpected difference was that patients with CRS had in-
creased BMI compared with controls. It remains unknown
whether increased BMI seen in cases is a real consequence of
CRS, or simply a random association that could confound
outcomes.33 Regardless, differences in patient-reported
(PSQI, FSS, EpSS) and objective (awakenings, REM
latency, snoring) sleep measures persisted when controlling
for BMI, suggesting that differences in BMI could not fully

International Forum of Allergy & Rhinology, Vol. 9, No. 1, January 2019 21

Alt et al.

explain the association between CRS and poor sleep qual-
ity. The difference in average overnight oxygen saturation
was no longer significant when controlling for BMI, sug-
gesting either BMI was confounding this relationship or the
study was not powered to perform this secondary analysis.
Certainly, with a case-control study design, one can never
fully rule out that unmeasured or unknown residual con-
founding was present, and thus confirmatory studies are
needed.
Strengths of the study include its prospective, multi-
institutional design and exploration of both patient-
reported and objective sleep measures. However, the study
took place in tertiary rhinology clinics and included
patients severe enough to consider surgery; thus, it is un-
clear whether these findings are generalizable across all pa-
tients and settings. A logical next step would be to confirm
our findings in a separate, unrelated cohort with a wider
range of disease severity and BMI. In addition, one may ex-
plore whether objective sleep parameters change with dis-
ease exacerbations and therapies, findings that could pro-
vide further evidence of causality.
Conclusion
Patients with CRS report increased sleep dysfunction, fa-
tigue, and daytime somnolence when compared with con-
trol subjects. In addition, subjects with CRS have increased
snoring, more awakenings, and longer REM sleep latency,
even after controlling for confounding factors. Further
study is needed to confirm these findings in additional co-
horts and to determine whether objective measures of sleep
dysfunction improve after treatment.

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