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\begin{document}

\title{The Effect of Combined Septal and Turbinate Injection of Botulinum Toxin
Type A in Allergic Rhinitis}



\author[1]{Mostafa Ismail}%
\author[2]{Alaa Nabil}%
\author[2]{Mostafa Nasr}%
\author[3]{balegh abdel hak}%
\author[1]{Osama Awad}%
\author[1]{khalaf Hamead}%
\affil[1]{Minia University Faculty of Medicine}%
\affil[2]{Minia University}%
\affil[3]{El Minia University hospital}%


\vspace{-1em}



  
  \date{May 18, 2024}


\begingroup
\let\center\flushleft
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\selectlanguage{english}
\begin{abstract}
Objectives: Allergic rhinitis ( AR) has been recently increasing in
prevalence, and traditional treatment strategies sometimes show limited
effectiveness for patients with intractable AR. Botulinum toxin type A
(BTX-A) is among the increasingly used alternative treatment options.
This study was conducted aiming at clinical assessment of the effect of
combined septal and turbinate injection of BTX-A for management of
uncontrolled AR. Design and setting: A single-arm pilot study enrolled
40 patients having moderate to severe uncontrolled AR were recruited in
between October 2018 and August 2019. Each patient received 45 units of
BTX-A injected in 3 fixed points of each side of the nose: inferior
turbinate (15IU), middle turbinate (15IU) and nasal septum (15IU). All
patients were evaluated in terms of nasal hypersecretions, congestion
and sneezing with visual analogue scale prior to treatment and at weeks
1, 2, 4, 8 and 12 during the follow-up period. Results: Throughout the
12 weeks follow-up period, a significant difference in the degree of
nasal hypersecretions could be identified before and after BTX-A
injection. Sneezing differed significantly only in the first 4 weeks
while nasal congestion did not differ significantly, before and after
BTX-A injection. BTX-A was well tolerated by the patients, with no
serious adverse or systemic effects. Conclusion: Combined septal and
turbinate injection of BTX-A, in patients with uncontrolled AR, may be a
long-lasting therapeutic option for the treatment of nasal
hypersecretions, but not as effective as for sneezing and nasal
congestion.%
\end{abstract}%



\sloppy


\textbf{Abstract}

\emph{Objectives:} Allergic rhinitis ( AR) has been recently increasing
in prevalence, and traditional treatment strategies sometimes show
limited effectiveness for patients with intractable AR. Botulinum toxin
type A (BTX-A) is among the increasingly used alternative treatment
options. This study was conducted aiming at clinical assessment of the
effect of combined septal and turbinate injection of BTX-A for
management of uncontrolled AR.

\emph{Design and setting:} A single-arm pilot study enrolled 40 patients
having moderate to severe uncontrolled AR were recruited in between
October 2018 and August 2019. Each patient received 45 units of BTX-A
injected in 3 fixed points of each side of the nose: inferior turbinate
(15IU), middle turbinate (15IU) and nasal septum (15IU). All patients
were evaluated in terms of nasal hypersecretions, congestion and
sneezing with visual analogue scale prior to treatment and at weeks 1,
2, 4, 8 and 12 during the follow-up period.

\emph{Results:} Throughout the 12 weeks follow-up period, a significant
difference in the degree of nasal hypersecretions could be identified
before and after BTX-A injection. Sneezing differed significantly only
in the first 4 weeks while nasal congestion did not differ
significantly, before and after BTX-A injection. BTX-A was well
tolerated by the patients, with no serious adverse or systemic effects.

\emph{Conclusion:} Combined septal and turbinate injection of BTX-A, in
patients with uncontrolled AR, may be a long-lasting therapeutic option
for the treatment of nasal hypersecretions, but not as effective as for
sneezing and nasal congestion.

\textbf{Keywords:} Allergic rhinitis, Botulinum toxin, Nasal
hypersecretions, Sneezing, Nasal congestion, Intranasal injection.

\textbf{Key points}

* Uncontrolled severe allergic rhinitis.

* Intranasal injection of Botulinum toxin type A.

* Combined septal and turbinate injection.

* Nasal hypersecretions.

* Sneezing and nasal congestion.

\textbf{Introduction}

Allergic rhinitis (AR) is a common disease with a high prevalence that
has been increased over last decades (1). Depending on pathogenesis of
AR and patients complaints such as nasal hypersecretions, sneezing and
nasal congestion, several treatment strategies had been conducted (2).
Conventional medications are not able to completely control symptoms in
most of patients with severe AR, other than the possible side effects
and the financial burdens (3).

Botulinum toxin type A (BTX-A) inhibits release of acetylcholine in
presynaptic area of neuromuscular junction and consequently blocks
cholinergic~pathway. Therefore, intranasal administration of BTX-A
through different ways and doses had been reported as a safe and
effective therapeutic option for controlling AR symptoms (4). BTX-A is
expected to suppress nasal hypersecretions by blocking the cholinergic
pathway in the nasal mucosa. However, the effects of BTX-A on sneezing
and nasal congestion remain controversial\textbf{.} Some previous
reports described the beneficial effects of BTX-A on all nasal allergic
symptoms (5),(6),(7),(8), although other reports failed to observe an
effect of BTX-A on sneezing and nasal congestion (3),(9).

The aim of this study was to assess the possible therapeutic effects of
the combined nasal septum, inferior and middle turbinates injection of
BTX-A on AR symptoms over a

period of 12 weeks, and to report any possible side effects.

\textbf{Materials and Methods}

This prospective single-arm pilot study was planned to include 40 adult
patients who received a diagnosis of moderate to severe uncontrolled AR
and were recruited in between December 2018 and October 2019 in a single
institution. The study was approved by the Committee for Medical
Research Ethics in Minia University, Faculty of Medicine, Egypt. All
patients signed a written consent prior being included in the study.

Patients with AR as described in the ARIA guidelines based on history,
clinical findings and positive skin prick test were recruited. Inclusion
criteria included moderate to severe AR, initial mean five-point visual
analogue scale (VAS) score above 3 for all the three cardinal symptoms
of AR (nasal hypersecretions, nasal congestion and sneezing), and
uncontrolled disease (defined as insufficient control of allergic
symptoms with VAS scores for nasal symptoms remained higher to 3 after 4
weeks of regular medical treatment). According to ARIA, intranasal
steroids complemented by antihistamines as add-on treatment are
recommended for treatment of severe persistent AR.

Patients with previous turbinate surgery, marked septal deviation, nasal
polyps or tumors were excluded. Additional exclusion criteria included
pregnancy, lactation, patients receiving treatment with oral
corticosteroids, anticholinergics, drugs affecting hypothyroidism or
hyperthyroidism during the 2 months before the beginning of the study.

Each patient had complete medical history and complete endoscopic
examination. Local anesthesia of nasal mucosa was carried out using a
ribbon gauze soaked with ephedrine: saline (1:1000) + Xylocaine in both
nasal cavities for 15 minutes before the injection. A diluted 100 units
of BTX-A (Medytox inc., South Korea) in normal saline to a final
concentration of 100 units/ml (15 units in 0.15 ml), was slowly injected
using a long needle syringe. Injection was done in 3 fixed points: 1-
Intermediate part of inferior turbinate, 2- Anterior end of middle
turbinate, and 3- Submucoperichondrial at the anterior part of nasal
septum \emph{(Fig.1.A,B,C,D).} Each patient received 45IU in each side
of the nose (90IU, in total) divided as: 15IU in inferior turbinate,
15IU in middle turbinate and 15IU in the nasal septum. After the
application, patients were reminded they should not use additional
allergic therapies.

Subjective symptoms including severity of nasal hypersecretions,
congestion and sneezing were measured by a five-point visual analogue
scale (VAS). The evaluations were made prior to the therapy and at 1, 2,
4, 8 and 12 weeks after the therapy. Each symptom was evaluated
according the scale as follow; (0= no, 1= mild, 2= moderate, 3= moderate
to severe and 4= severe).

Software package SPSS\selectlanguage{ngerman}® version 16.0 (Chicago, U.S.) was used in the
statistical analysis of the data. Wilcoxon signed-rank test for
nonparametric quantitative data was used upon comparing the pre- and
post-injection mean scores. A value of \emph{p \textless{}} 0.05 was
considered to be statistically significant.

\textbf{Results}

Forty patients (22 male, 18 female) were enrolled in the current study.
The mean age overall of participants was 31.7±9.5 years, ranging from 19
to 52 years. None of patients recorded any post injection hemorrhage,
pain or infection as side effects or complications.

\emph{Nasal hypersecretions}

A significant reduction in nasal hypersecretions was observed after
BTX-A injection started by the second week. Upon comparison of the mean
nasal hypersecretions rate before and after injection, the reduction in
nasal hypersecretions was as 27.5\% (p= 0.083) in the first week. The
decrease rate was observed to have increased to 62.5\% (p = 0.001) in
the second week, 57.5\% (p = 0.002) in the fourth week, and 42.5\% (p =
0.025) in the eighth week. The decrease rate was observed to have
regressed to 32.5\% in the twelfth week but still statistically
significant (p = 0.048). Maximum effect was reached in the second and
fourth weeks. Although -A had an eminent effect for 8 weeks, its effect
was continued in a statistically significant level till the twelfth week

\emph{(Table 1 and Figure 2).}

\emph{Sneezing and Nasal congestion}

A significant decrease in the severity of sneezing was detected upon
comparison of the mean scores before and after injection in the first
three follow-up points. It was 37.5\% (p= 0.035) at week 1; 47.5\% (p=
0.016) at week 2; and 40\% (p= 0.031) at week 4. The values before the
therapy were reached at week 8 \emph{(Table.2, Figure.3).} Severity of
nasal congestion decreased after injection in the first three follow-up
points but without significant difference. It was 12.5\% (p= 0.059) at
week 1; 17.5\% (p= 0.071) at week 2; and 7.5\% (p= 0.083) at week 4

\emph{(Table.3, Figure.4).}

\textbf{Discussion}

Various medical protocols for management of allergic rhinitis (AR) have
been formulated in a stepwise manner. The mainstay of all treatments
have been always conservative including antihistamines and intranasal
steroids (10). However, for patients with AR refractory to medication
therapy, a novel form of pharmacological treatment has been attempted,
for controlling allergic symptoms, in form of intranasal injection of
Botulinum toxin type A (BTX-A).

Since it provides a transient and reversible blockage of cholinergic
transmission (11), BTX-A has been used recently in the symptomatic
treatment of nasal hypersecretions (3),(9), that is controlled primarily
by the parasympathetic nervous system (12). However, the effects of
BTX-A on the suppression of sneezing and nasal congestion remain
controversial; as besides the autonomic control of nasal mucosa, some
sensory neuropeptides and sensory branches of the trigeminal nerve are
also responsible for itching, sneezing and nasal congestion in allergic
patients (13),(14).

Kim et al. showed that BTX-A effectively decreased nasal hypersecretions
for 4 weeks, but did not affect nasal congestion and sneezing (3). Sapci
et al. recorded a longer effect on nasal hypersecretions lasting for 8
weeks (9). The overall total nasal symptom score conducted by Zhang et
al. showed greatest effect of BTX-A in subscales of nasal
hypersecretions, followed by sneezing, nasal congestion, and itching,
lasting all for 4 weeks (15). On the other hand, recent reports
demonstrated effectiveness of intranasal BTX-A in improving all cardinal
symptoms of AR including nasal hypersecretions, congestion and sneezing,
with an effect lasting from 4 to 8 weeks (5),(6),(7),(8). Yang et al.
study had the longest effect of BTX-A injection lasting for 20 weeks for
all the allergic symptoms (16).

There is no universally accepted site of administration for the
intranasal BTX-A usage; submucoperichondrial of nasal septum, inferior,
middle turbinate, and posterior lateral nasal wall injections have been
applied for the relief of allergic symptoms in different studies (2).
Although inferior turbinate has been the commonest site for intranasal
injection of BTX-A, some recent reports suggested that intraseptal
injection had prolonged duration of effect. This could return to the
lower blood flow in the submucoperichondrium of nasal septum that may
lead to lesser clearance of BTX-A by bloodstream
(6),(8)\textbf{.}Ineffective infiltration of the area supplied by the
anterior ethmoidal nerve has been postulated to be another reason for
the limited effect in turbinate injections as compared to anterior nasal
septum (9),(17)\textbf{.} On contrary, Abtahi et al. concluded in their
clinical trial that no differences in efficacy were noted between
inferior turbinate and septal injections of BTX-A except a lower
epistaxis rate in septal injections (8). A novel injection technique
into the posterior lateral nasal wall, targeting parasympathetic
innervation at the sphenopalatine ganglion, was described by Zhang et
al. (15), however, the efficacy and safety of this technique require
more investigations.

Although the toxic dose of BTX-A is known to be 2500-3000 units (18),
25--150 U is the range of BTX-A doses used in AR. There is no absolute
agreement on the most suitable and effective dose for the intranasal
injection. The efficacy of intra-turbinate injection of 40 U and 60 U of
BTX-A did not differ significantly in their effectiveness on improving
allergic symptoms, lasting for 8 weeks (5)\textbf{.} Although
Mozafarinia et al. (6) and Hashemi et al. (7) recorded improvement in
allergic symptoms lasting for 4 and 8 weeks, after intraseptal injection
of 80 U and intra-turbinate injection of 150 U of BTX-A, respectively, a
long-lasting effect for 20 weeks had been reached in Yang et al. study
using a lower dose of 50 U injected purely intra-turbinate
(16)\textbf{.} These results indorsed our praise to think that the
effect of BTX-A in the nose is dose independent and it could be site
dependent.

In our study, we proposed a different technique of combined intraseptal
and intra-turbinate injection of BTX-A as; the intermediate part of
inferior turbinate, anterior end of middle turbinate, and
submucoperichondrial at the anterior part of nasal septum. A dose of 90
units was selected, in this study, as an average dose between the
effective doses utilized for AR in the preceding studies. It was safely
below the dose selected by Hashemi et al. (150 U), (7). The reason we
chose this combined injection method was to reduce the parasympathetic
tone to whole nasal mucosa. A recent anatomic study has redefined the
nasal parasympathetic innervation suggesting that two main rami project
from the sphenopalatine ganglion to innervate the nasal mucosa. The
sphenoethmoidal ramus gain access to the nasal cavity via the
sphenopalatine foramen to innervate the posterolateral part of nasal
mucosa, blocked by the intra-turbinate injection and the orbitonasal
ramus gain access to the nasal cavity via the anterior ethmoidal foramen
to innervate the anterosuperior part of nasal mucosa, blocked by the
intraseptal injection (19).

In our study, the combined injection method of BTX-A effectively reduced
nasal hypersecretions in rates ranging from 27.5\% to 62.5\%. The effect
displayed an increase starting from the first week and increased more
reaching the maximum in the second and fourth weeks, which followed a
statistically significant pattern for 12 weeks. These results are in
accordance with those of Ozcan et al. in a clinical study (20), and
Rohrbach et al. on an animal model (21), they have attributed the long
duration of BTX-A effect to the recovery period of the degeneration in
the nasal mucus glands that has been detected as 12 weeks. Another
explanation for the long effect of BTX-A on nasal hypersecretions, in
current study, was attributed to the multiple and different intranasal
injections that enabled extensive distribution of the toxin to nasal
mucosa and nasal glands, resulting in a more reduction of secretomotor
innervation.

Although the combined injection method, in our study, effectively
suppressed nasal hypersecretions, it lacked a similar efficacy on other
allergic symptoms such as sneezing and nasal congestion. The significant
effect of BTX-A on sneezing prominently decreased after the 4th week,
while it was insignificantly different throughout the 12 weeks follow-up
period for nasal congestion. The most likely explanation for these
findings is that BTX-A does not have an essential role in the
histamine-mediated allergic reactions (22)\textbf{.} Minor sensory and
parasympathetic efferent pathways exist in the nasal mucosa that may not
be affected by the injected BTX-A, this may be another reason for the
limited effect of BTX-A on nasal congestion and sneezing (19),(22).

Our study revealed the effect of combined septal and turbinate injection
of BTX-A on the symptoms of AR. The greatest effect was seen in nasal
hypersecretions lasted for 12 weeks, however effect on sneezing lasted
only 4 weeks. The most important limitation of this study; that it was a
subjective analysis after BTX-A injection, so further studies are
required for the objective evaluation of the therapy efficacy. Moreover,
further studies are required, to compare the combined injection
technique with the other techniques reported in previous studies, to
evaluate the effect of repetitive injections of BTX-A in the same
patient, and to evaluate the optimal dose of BTX-A in allergic rhinitis.

\textbf{Conclusion}

In the light of the current results; combined septal and turbinate
injection of BTX-A seems to be a safe and efficient therapeutic choice
for controlling allergic rhinitis symptoms, especially nasal
hypersecretions with a long-lasting effect. Further studies with
extended follow-ups are needed to objectively evaluate the injection
effect, and to determine the efficacy duration and the optimal dose of
BTX-A in allergic rhinitis.

\textbf{References}

1. Dykewicz MS, Hamilos DL. Rhinitis and sinusitis. Journal of Allergy
and Clinical Immunology. 2010;125(2):S103-S15.

2. Ozcan C, Ismi O. Botulinum toxin for rhinitis. Current allergy and
asthma reports. 2016;16(8):58.

3. Kim K-S, Kim S-S, Yoon J-H, Han JW. The effect of botulinum toxin
type A injection for intrinsic rhinitis. The Journal of Laryngology \&
Otology. 1998;112(3):248-51.

4. Rohrbach S, Junghans K, Köhler S, Laskawi R. Minimally invasive
application of botulinum toxin A in patients with idiopathic rhinitis.
Head \& face medicine. 2009;5(1):18.

5. Ünal M, Sevim S, Do\selectlanguage{polish}ğ\selectlanguage{english}u O, Vayiso\selectlanguage{polish}ğ\selectlanguage{english}lu Y, Kanik A. Effect of botulinum
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6. Mozafarinia K, Abna M, Khanjani N. Effect of botulinum neurotoxin a
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idiopathic non-allergic rhinitis and persistent allergic rhinitis.
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7. Hashemi SM, Okhovat A, Amini S, Pourghasemian M. Comparing the
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8. Abtahi SM, Hashemi SM, Abtahi SH, Bastani B. Septal injection in
comparison with inferior turbinates injection of botulinum toxin A in
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9. Sapci T, Yazici S, Evcimik MF, Bozkurt Z, Karavus A, Ugurlu B, et al.
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10. Bro\selectlanguage{polish}ż\selectlanguage{english}ek JL, Bousquet J, Agache I, Agarwal A, Bachert C,
Bosnic-Anticevich S, et al. Allergic Rhinitis and its Impact on Asthma
(ARIA) guidelines---2016 revision. Journal of Allergy and Clinical
Immunology. 2017;140(4):950-8.

11. Moore P, Naumann M. Handbook of botulinum toxin treatment:
Wiley-Blackwell; 2003.

12. Shaari CM, Sanders I, Wu B-L, Biller HF. Rhinorrhea is decreased in
dogs after nasal application of botulinum toxin. Otolaryngology---Head
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13. Widdicombe J. Neuroregulation of the nose and bronchi. Clinical \&
Experimental Allergy. 1996;26:32-5.

14. Tai C-F, Baraniuk JN. A tale of two neurons in the upper airways:
pain versus itch. Current allergy and asthma reports. 2003;3(3):215-20.

15. Zhang EZ, Tan S, Loh I. Botolinum toxin in rhinitis: Literature
review and posterior nasal injection in allergic rhinitis. The
Laryngoscope. 2017;127(11):2447-54.

16. Yang TY, Jung YG, Kim YH, Jang TY. A comparison of the effects of
botulinum toxin A and steroid injection on nasal allergy.
Otolaryngology--Head and Neck Surgery. 2008;139(3):367-71.

17. Braun T, G\selectlanguage{ngerman}ürkov R, Kramer MF, Krause E. Septal injection of
botulinum neurotoxin A for idiopathic rhinitis: a pilot study. American
journal of otolaryngology. 2012;33(1):64-7.

18. Scott AB, Suzuki D. Systemic toxicity of botulinum toxin by
intramuscular injection in the monkey. Movement disorders: official
journal of the Movement Disorder Society. 1988;3(4):333-5.

19. Bleier BS, Schlosser RJ, editors. Endoscopic anatomy of the
postganglionic pterygopalatine innervation of the posterolateral nasal
mucosa. International forum of allergy \& rhinology; 2011: Wiley Online
Library.

20. Özcan C, Vayisoglu Y, Do\selectlanguage{polish}ğ\selectlanguage{english}u O, G\selectlanguage{ngerman}örür K. The effect of intranasal
injection of botulinum toxin A on the symptoms of vasomotor rhinitis.
American journal of otolaryngology. 2006;27(5):314-8.

21. Rohrbach S, Olthoff A, Giefer B, Laskawi R, Götz W. Botulinum toxin
type A induces apoptosis in nasal glands of guinea pigs. Annals of
Otology, Rhinology \& Laryngology. 2001;110(11):1045-50.

22. Nishijima H, Kondo K, Toma-Hirano M, Iwasaki S, Kikuta S, Fujimoto
C, et al. Denervation of nasal mucosa induced by posterior nasal
neurectomy suppresses nasal secretion, not hypersensitivity, in an
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2016;96(9):981-93.

\textbf{Figure legends}

\emph{Fig.1A,B,C,D.} Endoscoic view of Lt nasal cavity showing the
location of -A injection; (B) Intermediate part of inferior turbinate,
(C) Anterior end of middle turbinate, and (D) Submucoperichondrial at
the anterior part of nasal septum.

\emph{Fig.2.} Mean visual analogue score (VAS) for nasal hypersecretions
after BTX-A injection.

\emph{Fig.3.} Mean visual analogue score (VAS) for sneezing after BTX-A
injection.

\emph{Fig.4.} Mean visual analogue score (VAS) for nasal congestion
after BTX-A injection.

Table 1. Effect of BTX-A injection on nasal hypersecretions\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
& \selectlanguage{ngerman}\textbf{(Mean ± SD)} &\tabularnewline
\midrule
\endhead
& 3.7 \selectlanguage{ngerman}± 0.5 & \textbf{Pretreatment}\tabularnewline
& 2.6 \selectlanguage{ngerman}± 0.7 & \textbf{Week 1}\tabularnewline
& 1.2 \selectlanguage{ngerman}± 1.1 & \textbf{Week 2}\tabularnewline
& 1.4 \selectlanguage{ngerman}± 1 & \textbf{Week 4}\tabularnewline
& 2 \selectlanguage{ngerman}± 1.1 & \textbf{Week 8}\tabularnewline
& 2.4 \selectlanguage{ngerman}± 0.5 & \textbf{Week 12}\tabularnewline
\textbf{p-value (pre. vs. post. injection)} & \textbf{p-value (pre. vs.
post. injection)} & \textbf{p-value (pre. vs. post.
injection)}\tabularnewline
0.083 & 0.083 & \textbf{Pre. vs. Week 1}\tabularnewline
0.001* & 0.001* & \textbf{Pre. vs. Week 2}\tabularnewline
0.002* & 0.002* & \textbf{Pre. vs. Week 4}\tabularnewline
0.025* & 0.025* & \textbf{Pre. vs. Week 8}\tabularnewline
0.048* & 0.048* & \textbf{Pre. vs. Week 12}\tabularnewline
\bottomrule
\end{longtable}

Table 2. Effect of BTX-A injection on sneezing\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
& \selectlanguage{ngerman}\textbf{(Mean ± SD)} &\tabularnewline
\midrule
\endhead
& 3.6 \selectlanguage{ngerman}± 0.6 & \textbf{Pretreatment}\tabularnewline
& 2.1 \selectlanguage{ngerman}± 0.7 & \textbf{Week 1}\tabularnewline
& 1.7 \selectlanguage{ngerman}± 0.5 & \textbf{Week 2}\tabularnewline
& 2 \selectlanguage{ngerman}± 0.7 & \textbf{Week 4}\tabularnewline
& 3.6 \selectlanguage{ngerman}± 0.5 & \textbf{Week 8}\tabularnewline
& 3.6 \selectlanguage{ngerman}± 0.6 & \textbf{Week 12}\tabularnewline
\textbf{p-value (pre. vs. post. injection)} & \textbf{p-value (pre. vs.
post. injection)} & \textbf{p-value (pre. vs. post.
injection)}\tabularnewline
0.035* & 0.035* & \textbf{Pre. vs. Week 1}\tabularnewline
0.016* & 0.016* & \textbf{Pre. vs. Week 2}\tabularnewline
0.031* & 0.031* & \textbf{Pre. vs. Week 4}\tabularnewline
1 & 1 & \textbf{Pre. vs. Week 8}\tabularnewline
1 & 1 & \textbf{Pre. vs. Week 12}\tabularnewline
\bottomrule
\end{longtable}

Table 3. Effect of BTX-A injection on nasal congestion\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
& \selectlanguage{ngerman}\textbf{(Mean ± SD)} &\tabularnewline
\midrule
\endhead
& 3.4 \selectlanguage{ngerman}± 0.5 & \textbf{Pretreatment}\tabularnewline
& 2.9 \selectlanguage{ngerman}± 0.7 & \textbf{Week 1}\tabularnewline
& 2.7 \selectlanguage{ngerman}± 1.1 & \textbf{Week 2}\tabularnewline
& 3.1 \selectlanguage{ngerman}± 0.7 & \textbf{Week 4}\tabularnewline
& 3.4 \selectlanguage{ngerman}± 0.5 & \textbf{Week 8}\tabularnewline
& 3.4 \selectlanguage{ngerman}± 0.5 & \textbf{Week 12}\tabularnewline
\textbf{p-value (pre. vs. post. in Group A)} & \textbf{p-value (pre. vs.
post. in Group A)} & \textbf{p-value (pre. vs. post. in Group
A)}\tabularnewline
0.059 & 0.059 & \textbf{Pre. vs. Week 1}\tabularnewline
0.071 & 0.071 & \textbf{Pre. vs. Week 2}\tabularnewline
0.083 & 0.083 & \textbf{Pre. vs. Week 4}\tabularnewline
1 & 1 & \textbf{Pre. vs. Week 8}\tabularnewline
1 & 1 & \textbf{Pre. vs. Week 12}\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fig/Fig}

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

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

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

\end{center}
\end{figure}

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

