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\begin{document}

\title{Comparison of Sinus Distribution between Nasal irrigation and Nasal
spray Using Fluorescein-labeled in patients with Chronic Rhinosinusitis:
A Randomized Clinical Trial}



\author[1]{yosita muenkaew}%
\author[1]{Navarat Tangbumrungtham}%
\author[1]{Boonsam  Roongpuvapaht}%
\author[1]{Kangsadarn Tanjararak}%
\affil[1]{Mahidol University Faculty of Medicine Ramathibodi Hospital}%


\vspace{-1em}



  
  \date{May 22, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Objective : This study aims to compare the potential sinus distribution
between high-volume nasal irrigation and nasal spray in chronic
rhinosinusitis patients who have not undergone sinus surgery.

Design and Setting : A randomized clinical study was conducted at the
Otolaryngology-Head \& Neck Surgery Department, Ramathibodi Hospital,
Faculty of Medicine, Mahidol University.

Participants : 40 patients undergoing endoscopic sinus surgery for
chronic rhinosinusitis. Thirty-eight patients met the inclusion criteria
and were randomly assigned to receive nasal irrigation or nasal spray
mixed with fluorescein sodium preoperatively.

Main outcome measures : The primary outcome was the mean difference in
the staining score of fluorescein in all sinuses between the two groups.

Results : The total staining score of fluorescein in all sinuses via
nasal irrigation was statistically more significant than the score via
nasal spray, with a mean difference score of 2.90, 95\%CI: 1.22-4.58,
p-value 0.001. The most significantly affected sinuses were specific to
the maxillary and anterior ethmoid sinuses, whereas the frontal and
sphenoid sinuses had the slightest solution distribution from both
techniques.

Conclusion : Nasal irrigation is a potential route to deliver drugs into
the sinus in unoperated CRS patients. However, it is not considered a
superior method to nasal spray at the most challenging anatomical areas,
i.e., the frontal and sphenoid sinuses.

Keywords : Corticosteroid use, Endoscopic sinus surgery, Irrigations,
Topical therapy for chronic rhinosinusitis, Medical therapy for chronic
rhinosinusitis, Nasal polyp, Nasal spray, Chronic rhinosinusitis%
\end{abstract}%



\sloppy


\textbf{Abstract}

\emph{Objective}\textbf{:~} This study aims to compare the potential
sinus distribution between high-volume nasal irrigation and nasal spray
in chronic rhinosinusitis (CRS) patients who have not undergone sinus
surgery.

\emph{Design and Setting}\textbf{:~} A randomized clinical study was
conducted at ``Blinded for review''.

\emph{Participants}\textbf{:} Forty patients undergoing endoscopic sinus
surgery for CRS. Thirty-eight patients met the inclusion criteria and
were randomly assigned to receive nasal irrigation or nasal spray mixed
with fluorescein sodium preoperatively.

Main outcome measures : The primary outcome was the mean difference in
the staining score of fluorescein in all sinuses between the two groups.

\emph{Results}\textbf{:~} The total staining score of fluorescein in all
sinuses via nasal irrigation was statistically more significant than the
score via nasal spray, with a mean difference score of 2.90, 95\%CI:
1.22-4.58,~\emph{p} -value 0.001. The most significantly affected
sinuses were specific to the maxillary and anterior ethmoid sinuses,
whereas the frontal and sphenoid sinuses had the slightest solution
distribution from both techniques.

\emph{Conclusion}\textbf{:~} Nasal irrigation is a potential route to
deliver drugs into the sinus in unoperated CRS patients. However, it is
not considered a superior method to nasal spray at the most challenging
anatomical areas, i.e., the frontal and sphenoid sinuses.

\emph{Keywords}\textbf{:} Corticosteroid use, Endoscopic sinus surgery,
Irrigations, Topical therapy for chronic rhinosinusitis, Medical therapy
for chronic rhinosinusitis, Nasal polyp\textbf{,} Nasal
spray\textbf{,}Chronic rhinosinusitis

\textbf{Key points}

\begin{itemize}
\tightlist
\item
  Most effective topical therapy gives the CRS patients a lower chance
  of invasive intervention in terms of sinus surgery.
\item
  The modification of the delivery system has been developed focusing on
  the distribution method of the drug into the sinus.
\item
  Nasal irrigation is a potential route to administer drugs into the
  sinus in unoperated CRS patients.
\item
  The overall sinus distribution of nasal irrigation had significantly
  more superiority than the nasal spray.
\item
  This intervention brings the advantage of opportunely providing
  anti-inflammatory medications into the sinus using a one-step approach
  for initial CRS treatment.
\end{itemize}

\textbf{Introduction}

While there is a growing trend to use corticosteroid nasal irrigation
instead of spray in

postoperative care after endoscopic sinus surgery (ESS)\textbf{(1-8)} ,
there is some, albeit very limited evidence that supports this
application as an initial treatment before sinus surgery as being the
superior method. A few previous studies investigated the concept of
sinus distribution on pre-surgical sinus cavities with the aim of
determining the most effective methods to deliver the medicine into the
sinus.\textbf{(9-11)} Unfortunately, the results from the studies could
not show any significant benefit of nasal irrigation in sinus
penetration. However, most studies were conducted in either healthy
subjects or cadavers, which could not represent the actual status of
pathological sinus cavities and dynamic physiology while rinsing the
sinus.\textbf{(9, 10)} Furthermore, one study examining sinus
penetration in unoperated chronic rhinosinusitis (CRS) patients used
low-volume nasal irrigation, which could not represent the ideal volume
to enhance sinus penetration even in the post-surgical sinus
status.\textbf{(11)}

Therefore, according to such knowledge gap, this study aims to compare
the sinus distribution of high-volume nasal irrigation and nasal spray
to determine the effective route for drug administration before sinus
surgery in CRS patients.

\textbf{Methods}

\textbf{Study design and setting}

This study was a randomized clinical trial conducted at ``Blinded for
review''. The study was approved by the local ethical committee and was
conducted in accordance with the ethical standards of the Declaration of
Helsinki. The reporting trials have been followed the CONSORT guideline.

\textbf{Participants}

CRS patients over 18 years old who indicated and were scheduled for ESS
between

January 2020-August 2021 were enrolled in this study. The diagnosis of
CRS was based on the criteria according to a European position paper on
rhinosinusitis and nasal polyps.\textbf{(12)~} The exclusion criteria
included patients with underlying diseases that affect mucociliary
function, i.e., cystic fibrosis, ciliary dyskinesia, previous
radiotherapy at head and neck regions, patients who had previous
sinonasal surgery or sinonasal tumors, patients who had evidence of
sinus aplasia or severe deviated nasal septum on computerized tomography
(CT) scan, pregnant women, patients who had allergic to fluorescein and
who refused to participate in the study.

All patients underwent preoperative CT scan of the nose and paranasal
sinuses, and Lund-Mackay (LM) staging system \textbf{(13)} , was
assessed for each nasal cavity separately. Nasal endoscopic exam was
carried out to distinguish phenotype features, CRS with nasal polyp
(CRSwNP) and CRS without nasal polyp (CRSsNP). In addition, the
participants completed the Thai Sinonasal Outcome Test 22 items
(SNOT-22)\textbf{(14)} on the admission date for a baseline assessment.

\textbf{Study interventions}

Patients who met the eligible criteria were then randomized into two
groups by a

computer-generated randomized sequence with a block size of four.
Sequentially numbered sealed opaque envelopes were provided to the
independent investigators

Patients in the nasal irrigation group received a mixture of 250 mL of
normal saline solution and 10\% fluorescein sodium 10 mL, irrigated 125
mL each nostril, using a syringe of 20 mL (contain a volume of 25 mL)
(Terumo, Tokyo, Japan) with a nozzle, 30 minutes before entering the
operating room. Patients in the nasal spray group received a mixture of
corticosteroid suspension and 10\% fluorescein sodium 10 mL, utilizing a
single-use mometasone nasal spray bottle (Sandoz, Ljubljana, Slovenia),
with 2 puffs sprayed into each nostril 30 minutes before entering the
operating room. The trained in-charge nurses supervised and instructed
all the patients to bend their heads forward, 30-45 degrees, to the
vertical plane during irrigation and spray. After receiving the
interventions, the patients were asked to sit upright until they could
lay down in the operating room, preparing for anesthesia.

\textbf{Surgical techniques}

All patients underwent ESS under general anesthesia and video recorded
by either a blinded

rhinologist staff or a fellowship-trained rhinologist supervised by
rhinologist staff. The sinuses were sequentially opened into the common
cavity fashion: uncinectomy and middle meatal antrostomy, anterior and
posterior ethmoidectomy, sphenoidotomy and frontal sinusotomy (Draf
IIa). The blue-light filter system with 0, 45, and 70-degree nasal
endoscopes (Karl Storz, Tuttlingen, Germany) were applied during video
record at each interesting anatomical area, including the OMU, maxillary
sinus, anterior and posterior ethmoid air cells, sphenoid sinus and
frontal sinus, respectively aiming to examine the degree of fluorescein
stain. The normal saline irrigation and the application of cotton
pledget were not allowed to be used during the procedure. Patients with
significant intraoperative bleeding must be excluded from the data
analysis due to fluorescein obscuring.

\textbf{Outcome measurements}

The primary outcome was the mean difference in the fluorescein staining
score under a

blue-light filter system in all interesting areas between the two
groups. The distribution of fluorescein at each interesting area was
graded from the video record independently by two blinded assessors. The
degree of fluorescein stain was graded according to a study by Harvey
RJ. et al.\textbf{(9)} which grade 0 was defined as no staining of
fluorescein on the sinus cavity, grade 1 was partial staining of
fluorescein (present on one wall of the sinus cavity), grade 2 was
staining of fluorescein on two or more walls of the sinus cavity, and
grade 3 was pooling of fluorescein in the sinus cavity.\textbf{(Figure
1)~}

The secondary outcomes included the mean differences in the staining
score of

fluorescein under a blue-light filter system in each area and subgroup
analysis according to the phenotype features, CRSwNP and CRSsNP, and the
severity of the disease by the LM staging system.

\textbf{Statistical analysis}

The sample size of this study was estimated according to a study by
Harvey RJ. et al.\textbf{(9)} , determining the sample size based on two
independent mean formulas using type I error (alpha) of 0.05 and a power
of 0.8. The authors consider the sample size of 70 in total numbers as
the most appropriate to detect a significant difference between groups.
Further, data loss was estimated at 15\%; the final estimation for the
total sample size was 80. Each side of the paranasal sinus system
representing its distinct fluorescein stain; thus, the sample size in
the study was defined as the number by the side of the nostril with
reference to 40 subjects in total.

Baseline characteristics were described using mean and standard
deviation for continuous variables and percentage for categorical
variables. Interrater reliability testing for fluorescein grading scores
by two assessors was determined by the concordance correlation
coefficient. The comparison of outcomes was performed using a linear
mixed-effects model for analysis. All analyses were performed using
Stata version 13.0 (StataCorp, College Station, TX). All test statistics
were reported in terms of magnitude of effect with mean difference and
95\% confident interval (CI), where a \emph{p} -value of less than 0.05
was considered statistically significant.

\textbf{Results}

\textbf{Participant flow and baseline characteristics}

Forty patients were enrolled in the study. However, two patients were
excluded due to a

history of previous sinus surgery. Thirty-eight patients were randomized
to receive nasal irrigation (n=19, 38 sides) or nasal spray (n=19, 38
sides). Five sides of the nasal cavity were excluded for data analysis
due to significant perioperative bleeding. Finally, there were 19
subjects with 36 sides in the nasal irrigation group and 19 subjects
with 35 sides in the nasal spray group for the intention-to-treat
analysis.\textbf{(Figure 2)} ~Of these 38 participants, the baseline
characteristics were balanced between two groups, as shown
in~\textbf{Table 1} .

\textbf{Total staining score of fluorescein in all anatomical areas}

The concordance correlation coefficient to determine the interrater
reliability for the

grading score was 0.98. The total staining score of fluorescein in all
anatomical areas in the nasal irrigation group was statistically more
significant than that of the nasal spray group, with a mean difference
score of 2.90, 95\%CI:1.22-4.58,~\emph{p} -value 0.001.\textbf{(Table
2)}

\textbf{Staining score of fluorescein in each anatomical area}

In the nasal irrigation group, the staining score of fluorescein was
statistically significantly higher at the maxillary sinus (mean
difference=1.38, 95\%CI:0.83-1.93,~\emph{p} -value \textless{}0.001) and
anterior ethmoid sinus (mean difference=0.53, 95\%CI:0.13-0.93,~\emph{p}
-value 0.009). The rest of the sinuses had no significant difference in
fluorescein staining.\textbf{(Table 2)~}

\textbf{Subgroup analysis according to the phenotype features, CRSwNP
and CRSsNP}

For both phenotype features, CRSwNP and CRSsNP, the nasal irrigation had
a better

distribution of fluorescein with statistical significance, however the
effect size was greater in CRSsNP patients (CRSwNP; mean
difference=2.28, 95\%CI:0.33-4.23,~\emph{p} -value 0.02 and CRSsNP; mean
difference=4.36, 95\%CI:1.44-7.27,~\emph{p} -value 0.003).\textbf{(Table
3)}

\textbf{Subgroup analysis according to the severity of the disease by
the LM staging system}

According to the LM staging system, where participants were placed into
three sub-

categories, mild\emph{~} disease~was defined as the LM score of 0-3;
moderate disease was defined with a score of between 4-8, and severe
disease was more than 8. The nasal irrigation had a significantly better
sinus distribution in moderate sinus disease (mean difference=2.61,
95\%CI:0.22-5.00,~\emph{p} -value 0.03) and severe sinus disease (mean
difference=2.96, 95\%CI:0.48-5.44,~\emph{p} -value 0.02).\textbf{(Table
4)}

\textbf{Discussion}

Saline irrigation has been paramount for CRS treatment, with its role
recently being

considered as a vehicle to deliver anti-inflammatory drugs into the
sinus. The sinus ostium is not the sole targeted area for medical
exposure, but the distribution of the drug to the sinus mucosa is also
key to restoring the disease. Thus, the modification of the delivery
system has been developed with a much greater focus on the distribution
method of the drug into the sinus cavity.~There has been a growing
amount of robust evidence on the administration of corticosteroids via
nasal irrigation with respect to technically distributing medication
into the sinus and clinically improving symptoms; however, most studies
to date have been conducted on post-surgical sinus
status.\textbf{(2-5)~} Therefore, corticosteroid nasal irrigation as an
initial treatment before the sinus surgery has not been adopted as a
general practice. Clinically, Jiramongkolchai P. et al.\textbf{(15)}
~recently conducted a randomized controlled trial that showed the
comparable efficacy of corticosteroid irrigation and spray in CRSsNP
patients who have not undergone sinus surgery regarding the improvement
of SNOT-22 scores. In addition, Tait et al.\textbf{(16)} ~carried out
another randomized controlled trial to investigate the efficacy of
large-volume, low-pressure corticosteroid irrigation compared with a
placebo in CRS patients, of which 70\% of patients in the study never
had any sinus surgery. The authors reported that the mean change of
SNOT-22 scores from baseline was greater for the treatment group in the
subgroup of patients who had no prior sinus surgery; however, the
results were not significantly different.

Regarding the technical concept, some publications investigated the
extent of sinus

distribution among the delivery system in the unoperated
sinus.\textbf{(9-11, 17)} ~However, most studies have been done on the
cadavers, and in healthy subjects, which might not sufficiently
represent the actual physiology of diseased sinuses and the natural
mechanisms of oropharyngeal functions during sinus irrigation. Moreover,
the role of the mucociliary function that might impact the sinus
penetration of the solution was one of the biases from previous
studies.~Wormald PJ. et al.\textbf{(10)} ~reported the restriction of
radioactivity via nuclear medicine imaging in unopened sinus cavities on
healthy control subjects. Most radioactivity appeared in the maxillary
sinuses from nasal douching, while there no radioactivity was detected
in any sinus cavity from the spray and nebulizer techniques. Harvey RJ.
et al.\textbf{(9)} ~conducted a study on cadavers and reported a
significant limitation of contrast distribution in unoperated sinuses,
particularly in sphenoid and frontal sinuses, regardless of the delivery
technique. Another study conducted in the pathological sinuses by
Grobler A. et al.\textbf{(17)} found that both unoperated sinuses and
sinuses with a small sinus ostium even after sinus surgery had
unreliable penetration. However, the results of this study were not
compared with the other delivery methods. The following research by
Snidvongs K. et al.\textbf{(11)} utilized a comparative study between
nasal irrigation and nasal spray. Nevertheless, they used low-volume
nasal irrigation and found neither the nasal irrigation nor the nasal
spray could enhance sinus penetration in the unopened sinus.

The present study's advantage was the fact that it was designed to
dynamically evaluate

the potential sinus distribution of different delivery methods in actual
pathological sinuses. In addition, the alternative intervention that was
intended to be investigated has been proven as a gold standard in terms
of high-volume irrigation to deliver drugs into the opened sinus
cavity.\textbf{(6)} ~This study confirmed that the overall sinus
distribution of nasal irrigation had significantly more superiority than
the nasal spray with the conclusive effect size. In addition, the effect
of nasal irrigation could create a greater sinus distribution in each
anatomical site. However, consistent with previous studies, the
maxillary and anterior ethmoid sinuses were the most significantly
affected areas.\textbf{(9,10)} The OMU was the area that could reach the
solution regardless of the delivery method. The rest of the sinuses,
particularly the frontal and sphenoid sinuses, had the least significant
solution distribution from both techniques. These limitations were
explained by their anatomical locations, which sit at the most posterior
and superior parts of the paranasal sinus system. Also, the bony
septation and the sinus pathology under the unoperated sinus were
critical barriers blocking the flow pathway. In the subgroup analysis,
the difference in sinus distribution between the two methods was
significantly greater, and remarkable in the moderate to severe sinus
diseases, in which nasal irrigation had a better result. In the CRSwNP
patients, nasal irrigation, regardless, provided significantly greater
overall sinus distribution than nasal spray but had less significant
effect than the CRSsNP subgroup.

Theoretically, saline irrigation has mechanisms as removing crust and
mucous, reducing

antigen load, enhancing ciliary beat, and response for a vehicle to
deliver the drugs into the sinus. This intervention brings the advantage
of opportunely providing anti-inflammatory medications into the sinus
using a one-step approach, resulting in more satisfactory compliance of
the patients. Furthermore, sufficient therapy duration might help
relieve inflammation at the OMU, maxillary and ethmoid sinuses,
ultimately promoting the distribution of the drug into the most
challenging parts, i.e., the frontal and sphenoid sinuses. Fortunately,
as per the updated evidence, the adverse events of corticosteroid
irrigation showed no serious effects, even in long-term
use.\textbf{(18-20)}

The limitation of this study was that sinus penetration of a solution
can be influenced by

multiple factors, not only the delivery technique, and such factors,
i.e., the head position and the surgical status of the sinus cavity,
were beyond the context of this study. In addition, finding of this
study could not represent the symptomatic outcomes in clinical
applications and could not entirely be used as a substitute for the
standard therapy. Therefore, using corticosteroid irrigation as the
initial treatment for CRS in selected phenotypes, i.e., moderate to high
severity sinus diseases on CT scan or CRSsNP, might potentially benefit
clinical outcomes. Further study on specific phenotypes or even
endotypes might increase the extension of clinical application.

\textbf{Conclusion}

Nasal irrigation is a potential route to administer drugs into the sinus
in unoperated CRS

patients. Patients with phenotyping of moderate to high severity disease
of sinuses and the CRSsNP might benefit from having drugs delivered into
the sinus via nasal irrigation. However, the alternative technique is
not superior to using nasal spray at the most challenging anatomical
areas, i.e., the frontal and sphenoid sinuses.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Steinke JW, Payne SC, Tessier ME, et al. Pilot study of budesonide
  inhalant suspension irrigations for chronic rhinosinusitis. J Allergy
  Clin Immunol 2009;124:1352-54.
\item
  Harvey RJ, Snidvongs K, Kalish LH, et al. Corticosteroid nasal
  irrigations are more effective than simple sprays in a randomized
  double-blinded placebo-controlled trial for chronic rhinosinusitis
  after sinus surgery. Int Forum Allergy Rhinol. 2018;8(4):461--70.
\item
  Kang TW, Chung JH, Cho SH, et al. The effectiveness of budesonide
  nasal irrigation after endoscopic sinus surgery in chronic
  rhinosinusitis with asthma. Clin Exp Otorhinolaryngol 2017;10(1):91-6.
\item
  Kosugi EM, Moussalem GF, Simoes JC, et al. Topical therapy with
  high-volume budesonide nasal irrigations in difficult-to-treat chronic
  rhinosinusitis. Braz J Otorhinolaryngol 2016;82(2):191-7.
\item
  Snidvongs K, Pratt E, Chin D, et al. Corticosteroid nasal irrigations
  after endoscopic sinus surgery in the management of chronic
  rhinosinusitis. Int Forum Allergy Rhinol 2012;2:415--21.
\item
  Succar EF, Turner JH, Chandra R. Nasal saline irrigation: a clinical
  update. Int Forum Allergy Rhinol. 2019;9: S4--S8.
\item
  Orlandi RR, Kingdom TT, Hwang PH, et al. International Consensus
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  Rhinol. 2016;6:S22-S209.
\item
  Thomas WW III, Harvey RJ, Rudmik L, et al. Distribution of topical
  agents to the paranasal sinuses: an evidence-based review with
  recommendations. Int Forum Allergy Rhinol, 2013;3:691--703.
\item
  Harvey RJ, Goddard JC, Wise SK, et al. Effects of endoscopic sinus
  surgery and delivery device on cadaver sinus irrigation. Otolaryngol
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\item
  Wormald P, Cain T, Oates L, et al. A comparative study of three
  methods of nasal irrigation. Laryngoscope 2004;114:2224 --7.
\item
  Snidvongs K, Chaowanapanja P, Aeumjaturapat S, et al. Does nasal
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\item
  Fokkens WJ, Lund VJ, Mullol J, et al. European position paper on
  rhinosinusitis and nasal polyps 2012. Rhinol Suppl 2012;23:1--298.
\item
  Lund VJ, Mackay IS. Staging in rhinosinusitis. Rhinology
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\item
  Numthavaj P, Bhongmakapat T, Roongpuwabaht B, et al. The validity and
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\item
  Jiramongkolchai P, Peterson A, Kallogjeri D, et al. Randomized
  clinical trial to evaluate mometasone lavage vs spray for patients
  with chronic rhinosinusitis without nasal polyps who have not
  undergone sinus surgery. Int Forum Allergy Rhinol. 2020;00:1-8.
\item
  Tait S, Kallogjeri D, Suko J, et al. Effect of budesonide added to
  large-volume, low-pressure saline sinus irrigation forchronic
  rhinosinusitis: a randomized clinical trial. JAMA Otolaryngol Head
  Neck Surg. 2018;144:605-12.
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  Grobler A, Weitzel EK, Buele A, et al. Pre- and postoperative sinus
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  Jiramongkolchai P, Patel S, Schneider JS. Use of Off-Label Nasal
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  2016;6:568-72.
\end{enumerate}

\textbf{Table 1. Baseline characteristics}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Nasal irrigation} (n=19, 36 sides)\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Nasal spray} (n=19, 35 sides)\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\emph{p}\textbf{-value}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Age (mean\emph{+}SD)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
53.74\emph{+}17.09\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
47.58\emph{+}16.89\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.27\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Male (n, \%)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5 (26.32\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
11 (57.89\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.05\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Allergic rhinitis (n, \%)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4 (21.05\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5 (26.32\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.00\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Asthma (n, \%)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
8 (42.11\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4 (21.05\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.16\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Current smoking (n, \%)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1 (5.26\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.00\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Nasal polyp (n, \%)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
14 (73.68\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
14 (73.68\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.00\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{SNOT-22 (mean\emph{+}SD)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
26.95\emph{+}13.63\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
31.74\emph{+}15.64\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.32\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Lund-Mackey CT score (mean\emph{+}SD)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
15.32\emph{+}5.76\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
13.21\emph{+}5.33\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.25\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 2.Fluorescein staining score at all anatomical areas and
each area between groups}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Nasal irrigation} (mean\emph{+}SE)\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Nasal spray} (mean\emph{+}SE)\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Mean difference (95\%CI)}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\emph{p}\textbf{-value}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{All anatomical areas}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6.59\emph{+}0.60\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3.69\emph{+}0.61\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2.90 (1.22, 4.58)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{OMU}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.80\emph{+}0.17\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.41\emph{+}0.17\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.39 (-0.09, 0.87)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.12\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Maxillary sinus}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.90\emph{+}0.20\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.52\emph{+}0.20\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.38 (0.83, 1.93)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Anterior ethmoid sinus}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.24\emph{+}0.14\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.71\emph{+}0.15\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.53 (0.13, 0.93)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0.009}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Posterior ethmoid sinus}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.84\emph{+}0.13\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.51\emph{+}0.13\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.34 (-0.03, 0.70)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.07\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Sphenoid sinus}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.52\emph{+}0.14\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.35\emph{+}0.14\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.16 (-0.23, 0.55)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.41\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Frontal sinus}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.30\emph{+}0.11\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.19\emph{+}0.11\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.11 (-0.21, 0.42)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.51\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 3. Subgroup analysis of fluorescein staining according to
the phenotype features, CRSwNP and CRSsNP}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Nasal irrigation} (mean\emph{+}SE)\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Nasal spray} (mean\emph{+}SE)\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Mean difference (95\%CI)}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\emph{p}\textbf{-value}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{CRSsNP}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
All anatomical areas\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
7.33\emph{+}1.05\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2.97\emph{+}1.05\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4.36 (1.44, 7.27)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0.003}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
OMU\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2.14\emph{+}0.30\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.45\emph{+}0.30\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.69 (-0.13, 1.51)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.98\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Maxillary sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2.16\emph{+}0.34\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.21\emph{+}0.34\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.95 (1.00, 2.89)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Anterior ethmoid sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.34\emph{+}0.25\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.55\emph{+}0.25\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.79 (0.08, 1.49)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0.03}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Posterior ethmoid sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.95\emph{+}0.23\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.37\emph{+}0.23\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.58 (-0.06, 1.21)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.08\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Sphenoid sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.46\emph{+}0.25\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.19\emph{+}0.25\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.27 (-0.42, 0.95)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.45\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Frontal sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.40\emph{+}0.20\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.18\emph{+}0.20\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.21 (-0.33, 0.76)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.44\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{CRSwNP}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
All anatomical areas\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6.28\emph{+}0.70\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4.00\emph{+}0.71\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2.28 (0.33, 4.23)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0.02}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
OMU\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.65\emph{+}0.20\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.39\emph{+}0.20\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.26 (-0.29, 0.81)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.36\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Maxillary sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.79\emph{+}0.23\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.65\emph{+}0.23\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.14 (0.50, 1.77)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Anterior ethmoid sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.20\emph{+}0.17\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.78\emph{+}0.17\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.42 (-0.05, 0.89)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.08\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Posterior ethmoid sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.80\emph{+}0.15\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.57\emph{+}0.15\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.23 (-0.19, 0.66)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.29\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Sphenoid sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.54\emph{+}0.16\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.42\emph{+}0.17\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.12 (-0.34, 0.58)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.61\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Frontal sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.25\emph{+}0.13\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.19\emph{+}0.13\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.06 (-0.31, 0.43)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.75\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 4. Subgroup analysis of fluorescein staining according to
the severity of the disease by the Lund-Mackay (LM) staging system}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Nasal irrigation} (mean\emph{+}SE)\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Nasal spray} (mean\emph{+}SE)\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Mean difference (95\%CI)}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\emph{p}\textbf{-value}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Mild disease (LM 0-3)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
All anatomical areas\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6.90\emph{+}1.98\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2.75\emph{+}1.82\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4.15 (-1.14, 9.43)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.12\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
OMU\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2.39\emph{+}0.53\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.50\emph{+}0.51\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.89 (-0.54, 2.32)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.22\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Maxillary sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2.56\emph{+}0.64\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.00\emph{+}0.56\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2.56 (0.90, 4.22)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0.003}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Anterior ethmoid sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.90\emph{+}0.54\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.50\emph{+}0.40\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.40 (0.08, 2.71)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0.04}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Posterior ethmoid sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
- 0.04\emph{+}0.44\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.25\emph{+}0.39\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.29 (-0.85, 1.44)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.62\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Sphenoid sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.19\emph{+}0.47\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.00 \emph{+}0.41\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.19 (-1.04, 1.42)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.76\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Frontal sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.17\emph{+}0.31\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.50\emph{+}0.33\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.33 (-0.56, 1.23)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.47\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Moderate disease (LM 4-8)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
All anatomical areas\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6.49\emph{+}0.94\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3.88\emph{+}0.77\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2.61 (0.22, 5.00)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0.03}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
OMU\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.78\emph{+}0.26\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.50\emph{+}0.21\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.27 (-0.39, 0.93)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.42\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Maxillary sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.97\emph{+}0.30\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.55\emph{+}0.25\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.42 (0.67, 2.18)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Anterior ethmoid sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.02\emph{+}0.21\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.80\emph{+}0.18\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.22 (-0.33, 0.77)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.43\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Posterior ethmoid sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.84\emph{+}0.20\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.50\emph{+}0.17\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.34 (-0.17, 0.85)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.19\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Sphenoid sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.61\emph{+}0.21\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.37\emph{+}0.18\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.24 (-0.31, 0.78)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.39\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Frontal sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.20\emph{+}0.17\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.15\emph{+}0.14\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.05 (-0.37, 0.48)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.80\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Severe disease (LM 9-12)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
All anatomical areas\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6.63\emph{+}0.80\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3.67\emph{+}0.98\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2.96 (0.48, 5.44)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0.02}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
OMU\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.76\emph{+}0.22\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.22\emph{+}0.27\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.53 (-0.15, 1.21)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.12\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Maxillary sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.79\emph{+}0.25\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.64\emph{+}0.31\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.14 (0.36, 1.93)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0.004}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Anterior ethmoid sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.34\emph{+}0.18\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.63\emph{+}0.24\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.71 (0.13, 1.29)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0.02}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Posterior ethmoid sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.93\emph{+}0.17\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.61\emph{+}0.21\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.32 (-0.21, 0.85)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.23\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Sphenoid sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.48\emph{+}0.18\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.43\emph{+}0.23\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.05 (-0.52, 0.62)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.86\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Frontal sinus\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.37\emph{+}0.14\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.16\emph{+}0.17\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.21 (-0.22, 0.65)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.33\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

