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\begin{document}

\title{Clinical, radiological, and histopathological patterns of allergic
fungal sinusitis: a single center retrospective study}



\author[1]{tao xu}%
\author[1]{xiao-tao guo}%
\author[1]{yi-cui zhou}%
\author[1]{qian zhou}%
\author[1]{Yinfeng Wang}%
\affil[1]{The First Affiliated Hospital of USTC}%


\vspace{-1em}



  
  \date{May 26, 2024}


\begingroup
\let\center\flushleft
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\selectlanguage{english}
\begin{abstract}
Objectives: Allergic fungal rhinosinusitis (AFRS) has unique clinical
symptoms, radiology, and histopathological patterns. It is easy to be
misdiagnosed because of the low detection rate of fungi. The purpose of
this study was to improve the diagnostic rate by analyzing these data of
the clinical, radiology and pathological of AFRS. Methods: The data of
patients with chronic rhinosinusitis (CRS) treated in the Department of
Otolaryngology-Head and neck surgery of the First Affiliated Hospital of
University of Science and technology of China (USTC) from January 2015
to December 2020 were analyzed. The discharged patients diagnosed with
AFRS and the suspected cases in the description of radiology or surgical
records were reviewed, combined with specific immunoglobulin E (IgE)
examination, they were divided into three groups: AFRS, suspected AFRS
and fungal ball sinusitis (FBS). The age, gender, eosinophils and
basophils in peripheral blood, total serum IgE, invasion of sinuses,
bone erosion, computed tomographic (CT) Lund-Mackay score, whether
accompanied with allergic rhinitis, asthma, and olfactory hypothyroidism
were all analyzed. Results: 631 patients with non-invasive fungal
sinusitis were treated in the past 6 years. 29 cases of AFRS, 69 cases
of suspected AFRS and 533 cases of FBS. A total of 98 confirmed and
suspected AFRS cases were identified, with an average age of 34.3 years.
79 cases of multiple paranasal sinus invasion and 55 cases of bilateral
paranasal sinuses. 25 cases with bone erosion. There were no significant
differences in age, eosinophils percentage, basophils percentage, total
serum IgE, CT Lund-Mackay score, combined with allergic rhinitis, asthma
and hypoolfactory between AFRS and suspected AFRS. However, significant
differences were observed in the above indicators between AFRS or
confirmed AFRS and FBS. Conclusion: AFRS may be misdiagnosed due to the
low detection of fungi. Clinical, laboratory, radiology and
histopathological need to focus on improving the detection rate of fungi
in AFRS. In order to reduce the recurrence of the disease, we can
consider the diagnosis of AFRS for patients with clinical, radiology and
immunological characteristics consistent with AFRS but without fungal
etiology%
\end{abstract}%



\sloppy


Clinical, radiological, and histopathological patterns of allergic
fungal sinusitis: a single center retrospective study

\textbf{Abstract}

\textbf{Objectives:}The purpose of this study was to improve the
diagnostic rate by analyzing the data of the clinical, radiology and
pathological of Allergic fungal rhinosinusitis (AFRS).

\textbf{Method:} The data of patients with chronic sinusitis (CRS)
treated in our center from January 2015 to December 2020 were analyzed.
The discharged patients diagnosed with AFRS and the suspected cases in
the description of radiology or surgical records were reviewed, combined
with specific immunoglobulin E (IgE) examination, they were divided into
three groups: AFRS, suspected AFRS and fungal ball sinusitis (FBS). The
participants' demographic, laboratory data and clinical characteristics
were all analyzed.

\textbf{Results:} 631 patients with non-invasive fungal sinusitis were
treated in the past 6 years. 29 cases of AFRS, 69 cases of suspected
AFRS and 533 cases of FBS. A total of 98 confirmed and suspected AFRS
cases were identified, with an average age of 34.3 years, 25 cases with
bone erosion. The significant differences were observed in age,
eosinophils or basophils percentage, total serum IgE, CT Lund-Mackay
score, combined with allergic rhinitis, asthma and hypoolfactory between
AFRS or confirmed AFRS and FBS, but no differences between AFRS and
suspected AFRS.

\textbf{Conclusion:} AFRS may be misdiagnosed due to the low detection
of fungi. In order to reduce the recurrence of the disease, we can
consider the diagnosis of AFRS for patients with clinical, radiology and
immunological characteristics consistent with AFRS but without fungal
etiology.

\textbf{Key points}

* Allergic fungal rhinosinusitis (AFRS) has clinical characteristics
that are obviously different from chronic rhinosinusitis (CRS), with
high recurrence rate and refractory, which is characterized by the
presence of eosinophilic mucin with non-invasive fungal hyphae.

* The low detection rate of fungi leads to misdiagnosis of AFRS,
resulting in non-standard treatment.

* There were more CRS patients with similar clinical manifestations in
AFRS, but they couldn't diagnosed as AFRS because of lack of etiological
evidence.

* AFRS may lead to serious complications, including loss of smell, loss
of vision, blindness, cranial nerve lesions, intracranial abscess or
cavernous sinus syndrome.

* Patients with characteristics of clinical, radiology and immunological
characteristics consistent with AFRS but without fungal etiology, Shall
be treated according to the treatment principles of AFRS.

\textbf{Introduction}

AFRS is non-invasive fungal sinusitis recognized in
1976\textsuperscript{1}, which is a subset of polypoid CRS that is
characterized by the presence of eosinophilic mucin with non-invasive
fungal hyphae within the sinuses and a type I hypersensitivity to fungi.
In 1993, Bent and Kuhn proposed the diagnostic criteria of AFRS based on
the prospective study of 15 patients \textsuperscript{2}. These major
criteria consist of the following: 1. Nasal polyposis; 2. Fungi on
staining; 3. Eosinophilic mucin without fungal invasion into sinus
tissue; 4. Type I hypersensitivity to fungi and; 5. Characteristic
radiology findings with soft tissue differential densities on CT
scanning and unilaterality or anatomically discrete sinus involvement.
The minor criteria include bone erosion, Charcot Leyden Crystals,
unilateral disease, peripheral eosinophilia, positive fungal culture and
the absence of immunodeficiency or diabetes \textsuperscript{3}. The
European position paper on rhinosinusitis and nasal polyps (EPOS) 2020
steering group discussed whether the term `eosinophilic fungal
rhinosinusitis' would be a better umbrella term but it was agreed that
`allergic fungal rhinosinusitis' should be retained as the principal
term due to common usage, recognizing that not all cases have evidence
of an allergic reaction to fungi \textsuperscript{4}.

AFRS has a high recurrence rate. It often requires two or more surgical
treatments, but it is still difficult to achieve a satisfactory
therapeutic effec\textsuperscript{5, 6}. Delays in misdiagnosis may even
lead to serious complications, including loss of smell, loss of vision,
blindness, cranial nerve lesions, intracranial abscess or cavernous
sinus syndrome \textsuperscript{7-12}. In serious cases, fungi may even
turn into an invasive infection, resulting in patient
death\textsuperscript{11}. In order to investigate the incidence and
improve the understanding of AFRS, we reread discharge and operative
records, radiographic imaging, laboratory and pathological reports of
CRS patients treated in our center from January 2015 to December 2020.

\textbf{Materials and methods}

Our research had been reviewed by the ethics committee of our hospital
before initiating this retrospective study; the present work was
produced in conjunction with the STROBE guidelines for reporting on
cohort studies.The medical record information management system was used
to record `sinusitis' as the keyword to search for discharge diagnosis.
All patients treated at our center were collected between January 2015
and December 2020. Read the patient's discharge records and operation
records. When the case was diagnosed as FBS, AFRS or with allergic mucin
described in the operation records, we re-read the data of radiographic
imaging, laboratory, and pathological~section, and re-diagnose according
to Bent-Kuhn diagnostic criteria\textsuperscript{2}. All cases were
divided into three groups: A for AFRS: The patients were diagnosed
according to Bent-Kuhn diagnostic criteria. B for suspect AFRS: The
characteristics of clinical, radiology and allergic mucin were in
accordance with the Bent-Kuhn criteria, and fungal specific IgE was
positive, but no fungal evidence. C for FBS: Fungus ball infection
clinical manifestation, typical radiology, the description of fungus
lump in surgical records, and the fungal examination in
histopathological sections were positive.

The data of three groups were collected, including gender, age, number
of recurrences, side and number of sinus, bone erosion, the peripheral
blood eosinophils and basophils percentage, galactomannan test, serum
total IgE, pathological findings of fungi, and whether conbain with
allergic rhinitis, asthma, or olfactory hypothyroidism. The difference
in the above items between group A and group B, group A and group C, and
group B and group C were compared.

\textbf{Statistical analyses}

Statistical analysis was performed with the Statistical Package for
Social Sciences version 19.0 for Windows (IBM Corp., Armonk, NY). The
prevalence of AFRS was calculated as the percentage of patients
diagnosed and treated as AFRS among all cases of CRS treated in the same
period; the result was presented as a percentage with a 95\% confidence
interval. Categorical variables are presented as frequency and
percentage, while continuous variables are presented as mean \selectlanguage{ngerman}± standard
deviation (SD). The quantitative variables were analyzed by the t-test,
and the data not normally distributed were analyzed by the Kruskal
Wallis.The ratio were tested by the chi square test. The Mann Whitney
test and chi square test were used for multiple comparisons of
quantitative and ratio. The \emph{p} value was corrected by Bonferroni.
A \emph{p} -value of \textless{}0.05 was considered to reject the null
hypothesis.

\textbf{Results}

A total of 2,874 patients underwent endoscopic sinus surgery, including
631 cases of non-invasive fungal sinusitis. 29 patients were
re-diagnosed with AFRS, with a mean age of 33.5 (range, 13-53) years,
and the median age was 35 years. 69 cases were re-diagnosed with suspect
AFRS, with a mean age of 35.4 (range, 12-67) years, and the median age
was 34 years. In addition, 533 cases were re-diagnosed with FBS, with a
mean age of 53.9 (range, 17-85) years, and the median age was 54 years.
There was no significant difference in gender composition among the
three groups (p = 0.316). According to the radiology of all patients,
the lesions in AFRS and suspect AFRS mostly involved bilateral sinuses
and multiple sinuses. The CT Lund Mackay score of the two groups was
significantly higher than that in FBS (\emph{p} \textless{} 0.001).
Furthermore, there was more bone erosion in AFRS and suspect AFRS, and
the proportion of secondary and multiple operations were higher in these
two groups than FBS, in which the maximum number of recurrence was five
(Table 1).

Compared with AFRS and suspect AFRS, there was no significant difference
in age, eosinophils percentage, basophils percentage, galactomannan test
positive rate, serum total IgE, recurrence times, and the proportion of
allergic rhinitis, asthma and olfactory decline (\emph{p} \textgreater{}
0.05). However, significant differences were observed in the above
indexes between group A and group C, and between group B and group C.
Besides age, we also found that there were more cases of blood
eosinophils increase in group A (9, 31.0\%) and group B (28, 40.6\%),
which was significantly higher than that in group C (8, 1.5\%,
\emph{p}\textless{} 0.01). Peripheral basophilic granulocytosis was also
observed in group A (4, 13.8\%) and group B (15, 21.7\%). In addition,
the galactomannan test, serum total IgE, recurrence times, the
proportion of allergic rhinitis or asthma and the proportion of
hypoolfactory in group A and group B were higher than those in group C
(p \textless{} 0.01) (Table 2).

\textbf{Discussion}

AFRS develops in immunocompetent patients, with occurrence influenced by
climate, geography, and several identified host factors.AFRS mostly
occurs in men aged 21-33 years, which is significantly younger than that
of CRSsNP and non-fungal CRSwNP \textsuperscript{13, 14}. It can also
occur in women and children, and AFRS in children is more invasive and
prone to serious complications \textsuperscript{15}. However, there is a
lack of multicenter research on the epidemiology of AFRS in our country.
In this study, the average age of group A was 33.5 years and group B was
35.4 years, which were significantly lower than 53.9 years in group
C(\emph{p} \selectlanguage{english}<0.001).

The confirmed cases of AFRS in our center account for 1\% of CRS, which
is lower than the reported 5\%-10\% prevalence rate \textsuperscript{4,
16, 17}. Based~on~extensive reports, the prevalence of AFRS is greatly
influenced by geographical location and climatic conditions. In the
South American States, the prevalence of AFRS can account for 10\% -23\%
of CRS \textsuperscript{18}. In Japan, the prevalence of AFRS accounts
for 1.4\%-3.9\% of CRS, and the northern region is significantly lower
than the southern \textsuperscript{19}. In Serbia, where the average
temperature is lower, the prevalence of AFRS accounts for 1.3\% of
CRS\textsuperscript{20}. Anhui Province is divided into a north-south
climate by the Huaihe River. The north of the Huaihe River belongs to a
warm temperate semi-humid monsoon climate, and the south belongs to a
subtropical humid monsoon climate, and the average temperature is higher
than that in Japan. Is it possible that this climatic condition may
cause the prevalence of AFRS to be higher than 1\%? In our study,
suspected AFRS accounted for 3.41\% of CRS. We hypothesized whether the
low detection rate of fungi in suspected cases led to the missed
diagnosis of AFRS. This conjecture is worthy of our multicenter system
research.

AFRS is mostly unilateral paranasal sinuses, and 30.8\% of cases are
found to be delayed on the contralateral side \textsuperscript{21}.
However, patients with AFRS are often diagnosed late, at an advanced
disease stage, resulting in the progress of the disease. Salamah
reported that AFRS involved all four sinuses in 69.6\% of patients and
was bilateral in \textgreater{}53.5\% of infected sinuses, of which
maxillary sinus and ethmoid sinus were most involved. CT radiological
imaging showed sinus expansion (35.3\%-51.2\%), remodeling
(20.6\%-37.2\%), and wall thinning (41.2\%-58.1\%) \textsuperscript{22}.
This is similar to our A group cases. In our study, the prevalence of
bilateral sinuses accounted for 58.6\% of all cases in group A, and the
involvement of two or more sinuses was as high as 89.7\%, of which the
patients with maxillary sinus were the most, accounting for 96.6\%,
followed by ethmoid sinus 72.4\%, frontal sinus 51.7.0\% and sphenoid
sinus 48.3\%. Group B and group C also showed the most involvement of
maxillary sinus. However, ethmoid, frontal and sphenoid sinus showed
more involvement in group A and group B (Table 1). Statistical analysis
showed that there was no significant difference in the number of invaded
sinuses and CT Lund-Mackay score between group A and group B (\emph{p}
\textgreater{} 0.1). Besides, we also found bone erosion in the cases,
which were 27.6\% in group A and 24.6\% in group B, but rarely in group
C. Bone erosion in AFRS is a mostly reversible process. Complete bone
regeneration occurred in more than two-thirds of patients within a short
period of time. In addition, the rate of bone regeneration was not
affected by the patients' sex or age, there was no difference in the
rate of bone regeneration between pediatric and adult
patients\textsuperscript{23}. AFRS is a non-invasive fungal sinusitis,
and the process of bone erosion is usually attributed to pressure
atrophy and inflammatory mediators induced by the accumulated fungal
debris. However, paranasal sinus mucosa and periosteum are usually
intact. This may suggest that bone erosion can regenerate after the
compression of allergic mucin and inflammatory stimulation are relieved.
Therefore, for AFRS patients with orbital and skull base bone
resorption, we should pay attention to the mucoperiosteal protection of
bone defect during nasal endoscopic sinus surgery.

AFRS is a type 2 immune response, characterized by antifungal IgE
sensitivity, eosinophil-rich mucus (ie, allergic mucin), and
characteristic CT and magnetic resonance imaging findings in paranasal
sinuses \textsuperscript{24}. Generally, AFRS has a high relapse rate,
often requiring repeated or multiple operations, and is still difficult
to achieve satisfactorily. Younis and Ahmed retrospectively analyzed 117
patients identified over a 5-year period with the diagnosis of AFRS or
EMCRS. Twenty-six of 117 (22\%) of the study patients underwent revision
surgery. Within the 2-year follow-up period, an additional 5 of 26
(19\%) required another revision surgery. Another study included 651
patients with CRSwNP and 45 patients with AFRS, A total of 396 (57\%)
patients with CRSwNPs/AFRS reported having undergone previous endoscopic
nasal polypectomy, of which 182 of the 396 (46\%) reported having
received more than one operation.~Among that, the multiple revision rate
of AFRS patients was as high as 58\%. The mean number of previous
surgeries per patient in the revision group was 3.3 (range
2-30)\textsuperscript{6}. ~In our study, the proportion of two or more
surgical revisions was 34.5\% in group A and 42.0\% in group B, which
was much higher than 6.4\% in group C. This high recurrence rate often
indicates that the disease has not been well controlled. Such patients
often have uncontrollable symptoms of allergic rhinitis or asthma and
may have decreased or even lost sense of smell. We found that 51.7\% of
patients in group A had decreased sense of smell, 55.2\% had allergic
rhinitis, and 13.8\% had obvious asthma symptoms, which was
significantly higher than that in group C (\emph{p} \selectlanguage{english}<0.001). Hence, in
the treatment of AFRS, we still need to pay attention to the control of
complications.

Statistics showed that there were significant differences between AFRS
and FBS in the age, eosinophils and basophils in peripheral blood,
positive rate of galactomannan test, total serum IgE, the number of
relapses, proportion of allergic rhinitis, asthma, or olfactory decline
in our study (\emph{p} \textless{} 0.01). The significant differences
were observed in the above indexes between group B and group C (p
\textless{} 0.01). Another research also pointed out that eosinophils
and basophils in peripheral blood were significantly increased in AFRS,
and statistical analysis found significantly higher blood eosinophils
and basophils levels in AFRS patients who relapsed than in those who did
not\textsuperscript{25}. In addition, no significant difference was
observed between group A and group B (p \textgreater{} 0.05), which may
suggest that there are some similarities between them.
Unfortunately,~according to Bent-Kuhn's diagnostic criteria, 69 cases
could not be diagnosed as AFRS because of no fungal etiological
evidence.

The definition and diagnostic criteria of AFRS are still under debate,
and minor progress has been made in the last two decades to achieve a
consensus. The most widely used is the Bent-Kuhn criteria. According to
each author's clinical experience and the available literature,
different lists of criteria are proposed. These criteria included the
characteristic eosinophilic mucin containing hyphae, along with a
positive fungal strain or culture, in the absence of tissue invasion by
fungi, in addition to other suggestive clinical and biological evidence
of an allergy such as positive atopic history, nasal polyposis, absence
of immunodeficiency, and elevation of total or specific IgE or a
positive skin test to fungal antigens\textsuperscript{3, 22}. However,
these diagnostic criteria were not constantly reported in the
literature. The strict application of the aforementioned criteria may
lead to several AFRS cases going missing diagnosis. In this
single-center, the low prevalence of AFRS leads us to think about two
questions: 1. Is it because of the unqualified pathological specimens or
the limitation of fungal detection methods that affect our diagnosis of
AFRS? 2. Whether the prevalence of AFRS in our center is lower than the
real prevalence in this area due to the low detection rate of fungi.
Hence, we need multi-center research for further discussion.

\textbf{Conclusion}

In conclusion, the low detection rate of fungi often leads to
misdiagnosis of AFRS and non-standard treatment. According to the above
research, we put forward the following two suggestions for clinical
treatment: 1. Improve the detection rate of fungi: including
standardized submission of pathological specimens, secretion fungal
smears (more than 3 times) and culture, strengthen communication with
pathological departments, and fully improve fungal specific examinations
such as hexamine silver or Periodic Acid-Schiff~ staining, microwave
EnVision immunohistochemistry and PCR. 2. When we encounter cases with
clinical, radiology, allergic mucin and fungal specific IgE elevation
that meet the Bent- Kuhn diagnostic criteria, but no fungal etiological
evidence, we can consider treating them according to the principles of
AFRS after excluding eosinophilic mucin sinusitis, so as to reduce the
recurrence rate and reduce the incidence of complications.

\textbf{References}

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\textbf{Table1 Participants' demographic and clinical characteristics}\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
Parameter & Parameter & Category & Category & AFRS & Suspect AFRS &
FBS\tabularnewline
\midrule
\endhead
Gender & & Male (n) & Male (n) & 14 & 36 & 229\tabularnewline
& & Female (n) & Female (n) & 15 & 33 & 304\tabularnewline
Total patients (n) & Total patients (n) & & & 29 & 69 &
533\tabularnewline
Age (year) & Age (year) & Minimum & Minimum & 13 & 12 &
19\tabularnewline
& & Maximum & Maximum & 53 & 67 & 83\tabularnewline
& & Below 18 & Below 18 & 1 & 7 & 0\tabularnewline
& & Mean, SD & Mean, SD & 33.5\selectlanguage{ngerman}±10.6 & 35.4\selectlanguage{ngerman}±13.3 &
53.9\selectlanguage{ngerman}±12.5\tabularnewline
Proportion & Proportion & In non-invasive fungal sinusitis (\%) & In
non-invasive fungal sinusitis (\%) & 4.6 & 10.9 & 84.5\tabularnewline
& & In CRS (\%) & In CRS (\%) & 1.0 & 2.4 & 18.5\tabularnewline
CT radiological imaging & CT radiological imaging & CT radiological
imaging & CT radiological imaging & CT radiological imaging & CT
radiological imaging & CT radiological imaging\tabularnewline
Sinus invasion & Single sinus, n(\%) & Single sinus, n(\%) & Single
sinus, n(\%) & 3 (10.3) & 16 (23.2) & 414 (77.7)\tabularnewline
& Unilateral sinus, n(\%) & Unilateral sinus, n(\%) & Unilateral sinus,
n(\%) & 12 (41.4) & 31 (44.9) & 512 (96.1)\tabularnewline
& Maxillary, n(\%) & Maxillary, n(\%) & Maxillary, n(\%) & 28 (96.6) &
58 (84.1) & 473 (88.7)\tabularnewline
& Ethmoid, n(\%) & Ethmoid, n(\%) & Ethmoid, n(\%) & 21 (72.4) & 52
(75.4) & 113 (21.2)\tabularnewline
& Frontal, n(\%) & Frontal, n(\%) & Frontal, n(\%) & 15 (51.7) & 35
(50.7) & 38 (7.1)\tabularnewline
& Sphenoid, n(\%) & Sphenoid, n(\%) & Sphenoid, n(\%) & 14 (48.3) & 43
(62.3) & 67 (12.6)\tabularnewline
Bone erosion & n (\%) & n (\%) & n (\%) & 8 (27.6) & 17 (24.6) & 10
(1.9)\tabularnewline
CT Lund-Mackay score & CT Lund-Mackay score & CT Lund-Mackay score &
Mean, SD & 6.9\selectlanguage{ngerman}±4.3 & 7.4\selectlanguage{ngerman}±4.8 & 2.6\selectlanguage{ngerman}±1.5\tabularnewline
Endoscopic sinus surgery (ESS) & Endoscopic sinus surgery (ESS) &
Endoscopic sinus surgery (ESS) & Endoscopic sinus surgery (ESS) &
Endoscopic sinus surgery (ESS) & Endoscopic sinus surgery (ESS) &
Endoscopic sinus surgery (ESS)\tabularnewline
First & First & n (\%) & n (\%) & 19 (65.5) & 40 (58.0) & 499
(93.6)\tabularnewline
Second & Second & n (\%) & n (\%) & 5 (17.2) & 10 (21.7) & 32
(6.0)\tabularnewline
Multiple & Multiple & n (\%) & n (\%) & 5 (17.2) & 9 (20.3) & 2
(0.4)\tabularnewline
\bottomrule
\end{longtable}

`Under 18' means the number of patients below 18 years old; `CRS' =
chronic rhinosinusitis; `Single sinus' means the number of patients with
allergic fungal sinusitis involving a single sinus, and the rest were
patients with two or more sinuses involved. `Unilateral sinus' means the
number of patients with allergic fungal sinusitis involving unilateral
sinus, and the others were bilateral sinuses involved. `ESS' =
endoscopic sinus surgery; `First' means patients were treated for the
first time by ESS, ``Multiple'' means patients were treated for the
multiple times by ESS.

\textbf{Table 2 Summary laboratory and clinical data}\selectlanguage{english}
\begin{longtable}[]{@{}llllllll@{}}
\toprule
Parameter & Parameter & Parameter & & AFRS & Suspect AFRS & FBS &
\emph{p}-value\tabularnewline
\midrule
\endhead
Laboratory reports & Laboratory reports & & & & & &\tabularnewline
GM test positive & GM test positive & n, \% & n, \% & 6 (20.7\%)* & 14
(20.3\%)** & 14 (2.6\%) & .000\tabularnewline
Eosinophils & Increased (n, \%) & Increased (n, \%) & Increased (n, \%)
& 9 (31.0)** & 28 (40.6)** & 8 (1.5) &\tabularnewline
& Percentage (Mean,SD) & Percentage (Mean,SD) & Percentage (Mean,SD) &
6.7\selectlanguage{ngerman}±6.0** & 7.0\selectlanguage{ngerman}±5.2** & 2.5\selectlanguage{ngerman}±1.9 & 1.36611E-14\tabularnewline
Basophils & Increased (n, \%) & Increased (n, \%) & Increased (n, \%) &
4 (13.8)* & 15 (21.7)** & 20 (3.8) &\tabularnewline
& Percentage (Mean,SD) & Percentage (Mean,SD) & Percentage (Mean,SD) &
0.8\selectlanguage{ngerman}±1.5* & 0.7\selectlanguage{ngerman}±0.4** & 0.5\selectlanguage{ngerman}±0.4 & 3.76161E-4\tabularnewline
Relapse frequency & Relapse frequency & Maximum & Maximum & 5 & 3 & 2
&\tabularnewline
& & Mean,SD & Mean,SD & 0.5\selectlanguage{ngerman}±0.8* & 0.7\selectlanguage{ngerman}±1.0** & 0.1\selectlanguage{ngerman}±0.3 &
2.965E-7\tabularnewline
Total serum IgE(IU/ml, Mean, SD) & Total serum IgE(IU/ml, Mean, SD)
& Total serum IgE(IU/ml, Mean, SD) & Total serum IgE(IU/ml, Mean,
SD) & 394.6\selectlanguage{ngerman}±167.5** & 346.3\selectlanguage{ngerman}±183.8** & 81.1\selectlanguage{ngerman}±93.6 &
1.30281E-8\tabularnewline
Clinical complication & Clinical complication & Clinical complication &
Clinical complication & Clinical complication & Clinical complication &
Clinical complication & Clinical complication\tabularnewline
Olfactory dysfunction n (\%) & Olfactory dysfunction n (\%) & Olfactory
dysfunction n (\%) & Olfactory dysfunction n (\%) & 15 (51.7)** & 40
(58.0)** & 83 (15.6) & .000\tabularnewline
Asthma & Asthma & n (\%) & n (\%) & 4 (13.8)** & 7 (10.1)** & 3 (0.6) &
.000\tabularnewline
Allergic rhinitis & Allergic rhinitis & n (\%) & n (\%) & 16 (55.2)** &
27 (39.1)** & 33 (6.2) & .000\tabularnewline
\bottomrule
\end{longtable}

\emph{p} -value means the difference between the three groups. `**'
means the difference between AFRS and FBS or between suspect AFRS and
FBS was statistically significant, \emph{p} \textless{} 0.001; `*' means
the difference between AFRS and FBS or between suspect AFRS and FBS was
statistically significant (\emph{p} \textless{} 0.01).

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

