1175053

letter2021
EARXXX10.1177/01455613211044224Ear, Nose & Throat JournalIsraeli et al

Original Research
Ear, Nose & Throat Journal

Clinical Efficacy of Topical Nasal

2024, Vol. 103(3) NP148­–NP157
© The Author(s) 2021
Article reuse guidelines:
Pomegranate Fruit Extract for Chronic sagepub.com/journals-permissions
DOI: 10.1177/01455613211044224
https://doi.org/10.1177/01455613211044224

Rhinitis and Chronic Rhinosinusitis journals.sagepub.com/home/ear

Asaf Israeli, BSc1, Golda Grinblat, MD1,2 , Isaac Shochat, MD1,2 ,

Miri Sarid, PhD3, Mickey Dudkiewicz, MD2,4, and Itzhak Braverman, MD1,2

Abstract
Objective: To evaluate the clinical efficacy of topical nasal Pomegranate Fruit Extract (PFE) for Chronic Rhinitis (CR), Chronic
Rhinosinusitis with Nasal Polyposis (CRSwNP), and Chronic Rhinosinusitis without Nasal Polyposis (CRSsNP). Methods:
Prospective, double-blinded, randomized study including 111 consecutive patients, between April 2012 and January 2017,
afflicted by CRSwNP, CRSsNP, and CR. Patients from each group were randomly assigned to either PFE treatment or placebo
twice daily for 30 days. Therapeutic efficacy was assessed by Ear Nose and Throat, blood and tomographic examinations, and the
SNOT-20 questionnaire. Results: CR patients treated with PFE suffered significantly less from thick nasal discharge, difficulty
falling asleep, reduced productivity, reduced concentration, and sadness (P = .004, P = .02, P = .03, P = .007 and P = .02,
respectively). Conclusions: Topical nasal PFE was found to have some benefits for CR patients, however, not for CRS with or
without Nasal Polyposis.

Keywords
Chronic Rhinitis, extract, pomegranate, Chronic Rhinosinusitis, nasal polyposis

Introduction may penetrate a bacterial biofilm.12 Topical antifungals rep-

Chronic Rhinosinusitis (CRS) and Chronic Rhinitis (CR) are
highly prevalent conditions in adults, affecting roughly 10%
of the general population,1 that have significant impacts on
morbidity and quality of life (QoL), constituting major con-
sequences for patients, their families, and society altogether.
To add insult to injury, the prevalence is increasing annually
throughout the world.2-6
One of the main mechanisms suggested for CRS devel-
opment is a formation of biofilm in the nasal and sinus
cavities.7,8 The EPOS 2020 steering group has emphasized
doubt regarding the use of systemic antibiotics in CRS patients
due to a rise of bacterial resistance occurring worldwide,
which in turn compromises the efficacy of antibiotics. Con-
sequently, this recommendation led to the emergence of other
treatment possibilities,9-11 one of which suggests topical an-
tibiotics as an alternative for systemic treatment. It has been
proposed that this method allows deliverance of high con-
centrations of antibiotics onto the sinus surfaces where they
resent another appealing alternative for similar reasons, also
due to the observation that CRS may result from an exag-
gerated allergic response to fungi in nasal mucus.13 Never-
theless, distribution of topical treatments to a non-operated
sinus was found to be rather limited, accounting for less than
1
Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of
Technology, Haifa, Israel
2
Department of Otorhinolaryngology, Head and Neck Surgery, Hillel Yaffe
Medical Center, Hadera, Israel
3
Head of Learning Disabilities Department, Western Galilee College, Acco,
Israel
4
Directory of Hillel Yaffe Medical Center, Hadera, Israel
Received: May 10, 2021; revised: August 14, 2021; accepted: August 18,
2021
Corresponding Author:
Golda Grinblat, MD, Ororhinology Head and Neck Surgery, Hillel Yaffe
Medical Center, Uriel Ofek 10, Herzliya 38100, Israel.
Email: goldagrinblatmd@gmail.com

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons
Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use,
reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE
and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
2 Ear, Nose & Throat Journal 0(0)
Israeli et al
2–3% of the total irrigation volume or nebulized solution
attaining sinus penetration in the setting of CRS with mucosal
edema.14,15
Pomegranates have a long history of antibacterial use
dating back to biblical times. Punica granatum L. (Punica-
ceae) is a shrub native to Asia and Mediterranean Europe,
popularly referred to in English as pomegranate. According to
Ebers Papyrus, one of the oldest medical writings, circa 1500
BC, the plant was used by Egyptians as a treatment for
tapeworm and other parasitic infestations.16
Several studies investigated the bactericidal effects of
pomegranates on a number of highly pathogenic and drug-
resistant strains, determining bactericidal potency of different
pomegranate plant extracts against a range of different bacteria
by utilizing disc diffusion assays or minimum inhibitory
concentration.17,18
Pomegranate extract was found to have antibacterial ac-
tivity against S. aureus S. epidermidis, L. acidophilus, S.
mutans, and S. salivarius.19 Moreover, it has also been shown
to inhibit the formation of biofilms as well as to disrupt
preformed biofilms.20 In one study, ethanolic extracts of
pomegranate were effective at inhibiting 35 hospital isolates of
MRSA, and scanning electron microscopy of the bacteria
showed that the pomegranate extract caused alterations in the
bacterial cell walls after 2 hours of treatment.21
Figure 1. Study design.
NP149
Several other studies have been conducted regarding an-
tiviral activities associated with pomegranate and its extracts.
The fruit’s antiviral effects have been reported against clini-
cally relevant viruses: influenza virus, herpes virus, poxvi-
ruses, human immunodeficiency (HIV-1) virus, FCV-F9,
MNV-1, and bacteriophage MS2.22-27
Pomegranate, with its dual contribution, both as an anti-
biofilm and an antimicrobial agent, has directed us to evaluate
its clinical efficacy utilizing topical nasal Pomegranate Fruit
Extract (PFE) in patients with Chronic Rhinitis, Chronic
Rhinosinusitis with Nasal Polyposis (CRSwNP), and Chronic
Rhinosinusitis without Nasal Polyposis (CRSsNP) in the
setting of a double-blinded randomized study.
Materials and Methods
Study Participants and Data Collection
Data was prospectively collected on 111 consecutive patients
afflicted by CRS and CR during the study period of April
2012-January 2017 at the Department of Otorhinolaryngol-
ogy, Head and Neck Surgery, Hillel Yaffe Medical Center,
Hadera, Israel.
Cooperative healthy non-smoker subjects aged ≥18 years
were enrolled in the study as per inclusion criteria. Patients
NP150
Israeli et al.

Table 1. Male to Female Ratio and Mean Age among Study Groups, (n = 111).

CR (n = 49) CRsP (n = 35) CRwP (n = 27) Total

n (%) M (%) Age ± SD n (%) M (%) Age ± SD n (%) M (%) Age ± SD n (%) M (%) Age ± SD

PFE 25 (51%) 8 (38%) 45.08 ± 14.5 17 (51%) 8 (47%) 43.88 ± 21.1 16 (59%) 9 (56%) 46.69 ± 15.1 58 (52%) 25 (43%) 45.17 ± 16.6
Placebo 24 (49%) 6 (25%) 42.33 ± 14.2 18 (51%) 10 (56%) 36.94 ± 16.4 11 (41%) 7 (64%) 46.73 ± 17.6 53 (48%) 23 (43%) 41.42 ± 15.8
Abbreviations: n, number of patients; M, male; PFE, Pomegranate Fruit Extraction; SD, standard deviation.
3
4 Ear, Nose & Throat Journal 0(0)
Israeli et al NP151

under 18 years of age, history of prior sinonasal surgeries or
chemoradiation, concurrent medical conditions, allergy to
pomegranates/yeast were excluded from the study. Corre-
sponding to the pathology, subjects were divided into 3
groups: CR, CRSwNP, and CRSsNP. Chronic Rhinitis patients
were diagnosed according to the World Health Organization
and the Allergic Rhinitis and its Impact on Asthma (ARIA)
Classification and were distinguished from CRS patients who
were diagnosed based on the 2012 European position paper on
rhinosinusitis and nasal polyps28 using major and minor
criteria, for patients suffering symptoms for more than
12 weeks, backed by endoscopic test showing purulent
discharge or nasal polyposis, or by CT findings of presence/
absence of sinonasal polyposis. Since allergic and non-allergic
patients were not distinguished separately and were allocated
to their group based on symptomatology alone, the presence of
aeroallergy was not considered as mandatory. Above-
mentioned 3 groups were further randomly assigned into
either PFE treatment or Placebo groups. The study design is
displayed in Figure 1.
Detailed documentation of the relevant parameters before
and 1 month after the treatment was made. Inferior turbinate
hypertrophy, discharge from inferior and middle meatus, and
nasal polyposis were appreciated by anterior rhinoscopy and

Table 2. Pre-, Post-Treatment SNOT-20 Score and Improvement among the Different Groups.

Diagnosis Group SNOT-20 Post SNOT-20 Post SNOT-20 Improvement

Mean CRSsP PFE 42.4 28.5 15.2

Placebo 53.0 41.9 13.9
CR PFE 37.4 23.7 7.4
Placebo 34.9 31.5 2.3
CRSwP PFE 26.0 27.5 5.2
Placebo 45.6 35.6 4.6
Standard deviation CRSsP PFE 18.0 19.2 19.1
Placebo 17.1 20.3 13.7
CR PFE 15.7 14.1 11.3
Placebo 17.4 20.5 15.0
CRSwP PFE 12.0 26.2 13.3
Placebo 30.6 27.2 8.8
Abbreviations: PFE, Pomegranate Fruit Extraction; CR, Chronic Rhinitis.

Figure 2. SNOT-20 mean improvement among the different groups.

Israeli et al.
NP152
fiberoptic exam. Otoscopy was done using otologic micro-
scope. In addition, Lund-Mackay scores, eosinophilic counts,
and C-Reactive Protein values were recorded along with Sino-
Nasal Outcome Test-20 (SNOT-20) questionnaire responses.
Treatment Protocol
Each group received either PFE or Placebo spray twice daily
for 30 days. The solutions were packaged in 2 amber glass
bottles, each containing 15 mL. Each bottle was sealed with a
nasal spray device, made of polypropylene (PP), Polyoxy-
methylene (POM), and Ethylene-vinyl acetate (EVA), capable
of delivering .15 ± .01 mL per dose (ie, a total of 200 doses).
Statistical Analysis
Data was analyzed using SPSS software. To assess the dif-
ference of improvement between each of the study groups
with the placebo group, before and after the treatment, the
paired t-test was applied for continuous variables and chi-
square test categorical variables. Eta squared was applied to
measure association, as appropriate. A two-sided P-value of
≤.05 was considered statistically significant. Mean values are
presented with their standard deviations.
Ethical Issues
The current prospective, double-blinded, randomized study
followed the tenets of the Declaration of Helsinki and was
approved by the institutional ethical committee (Hillel Yaffe
Medical Center Committee, No. 0089-11-HYMC). Informed
consent was obtained from all participating patients.
Results
A total of 111 patients comprised the current study group. The
study population’s mean age was 43.4 ± 16.3 years (range
Figure 3. Comparison of mean values for thick nasal discharge, difficulty falling asleep, decreased productivity, decreased concentration, and
sadness.
5
Ear, Nose & Throat Journal 103(3)
18–81 years), and 56.8% were men. No significant difference
was found in the mean age nor male/female ratio of experi-
mental vs placebo groups in the CR, CRSwNP, and CRSsNP
groups. (Table 1).
The initial and post-treatment mean SNOT-20 scores
among the PFE and Placebo groups are depicted in Table 2.
The SNOT-20 improvement among the different groups is
displayed in Figure 2.
To compare pre-and post-treatment signs and symptoms
between the PFE and Placebo groups, paired t-tests were
employed, exhibiting no significant difference between groups
regarding physical exam, laboratory values, and Lund-
Mackay score. To capture the culprit of discrepancies in the
SNOT-20 questionnaire, its separate components were further
analyzed using estimate independent mean difference. The
questions pertaining to thick nasal discharge, difficulty falling
asleep, reduced productivity, reduced concentration, and sad-
ness variated significantly among disease groups as follows.
Regarding thick nasal discharge, both CRSwNP and
CRSsNP cases showed a decrease within PFE and Placebo
groups. However, it was found to be significant only among
CRSsNP cases (P = .001 and P = .001, respectively), and
utilizing estimate independent mean difference showed no
superiority to either group. Conversely, within the CR group,
PFE exhibited superiority over placebo, with a significant
decline of thick nasal discharge after treatment (P = .005).
Similarly, superiority was demonstrated amongst the CR
group for difficulty falling asleep (P = .04), reduced pro-
ductivity (P = .04), and sadness (P = .04). Regarding Reduced
productivity, a decrement was observed also in the CRSsNP
group (P = .02), but no superiority over the placebo group was
observed.
In CR patients, solely the PFE group showed Improved
concentration (P = .007), while no significant differences
within CRSwNP and CRSsNP patients were observed. Ad-
ditional analysis showed tendency to favor the CR group, but
6 Ear, Nose & Throat Journal 0(0)
Israeli et al NP153

no significant superiority was demonstrated using estimated
means difference (P = .06).
Figure 3 demonstrates a comparison of means for the
aforementioned SNOT-20 questions in all disease types for
PFE and Placebo, before and after treatment; Figure 4 displays
estimate independent mean difference for the discussed
questions.
Broadly, CRSwNP and CRSsNP patients did not show
noteworthy differences between PFE and Placebo groups.
However, within CR patients, significant recovery in symp-
toms according to the SNOT-20 questionnaire in PFE vs the
Placebo group was observed, (Figure 5, bolded), exhibiting
improvement regarding thick nasal discharge, difficulty fall-
ing asleep, reduced productivity, reduced concentration, and
sadness (P = .004, P = .02, P = .03, P = .007, and P = .02,
respectively). Table 3 displays the changes in the CR group.
Discussion
In the present prospective, double-blinded, randomized study,
we assessed and analyzed the clinical efficacy of topical nasal
Pomegranate Fruit Extract for Chronic Rhinitis, Chronic
Rhinosinusitis with Nasal Polyposis, and Chronic Rhinosi-
nusitis without Nasal Polyposis.
Both CRS and CR constitute a significant impact on the
healthcare system. In the United States, Allergic Rhinitis (AR)
alone results in 3.5 million lost workdays and 2 million lost
school days annually.29 Most patients with CRS and CR seek

Figure 4. Estimate independent mean difference within CR patients for selected SNOT-20 questions.
Israeli et al. 7
NP154 Ear, Nose & Throat Journal 103(3)

medical treatment only when they experience significant QoL
impairments. Thus, improvements in the SNOT-20 ques-
tionnaire, corresponding to QoL in these conditions, can
reasonably serve as reliable indicators for treatment success.30
Whether it stems from allergic (AR) or non-allergic (NAR)
origin, Chronic Rhinitis has a variety of proposed treatments.
One option is intranasal steroids; however, safety of long-term
use is questionable31,32 as they may result in adverse effects
such as mucosal atrophy,33 hypothalamic-pituitary-adrenal
axis suppression, and other systemic effects.34 Prior studies
have shown superior results with the addition of azelastine
Figure 5. SNOT-20 Questionnaire. Red colored are symptoms
relieved in CR patients with Topical Nasal PFE treatment. PFE,
Pomegranate Fruit Extract; CR, Chronic Rhinitis.
hydrochloride to intranasal steroids over solely intranasal
steroids use,35 while others have shown significant QoL
improvement with anti-histaminergic therapy.36 Last, surgical
treatment with radiofrequency turbinoplasty or immunother-
apy may be suggested for patients who failed to respond to
conservative lines of treatment.37
Likewise, topical intranasal and systemic oral corticoste-
roids constitute the first line of therapy in treating CRS.
However, they must be given with caution in particular
populations such as children, pregnant women, and elderly
patients and especially in those with comorbid conditions such
as asthma, due to possible high steroid intake.38
Presence of bacterial biofilm species has been demon-
strated in several in vitro trials for CRS patients,8,39 though
according to the International Consensus Statement on Al-
lergy and Rhinology: Rhinosinusitis Executive Summary,
there is insufficient clinical evidence to determine their role.40
Topical antimicrobial agents might be preferable due to
their ability to localize delivery to the sino-nasal mucosa and
minimize systemic effects found with oral agents. This could
play an important role in treating biofilms, where higher
concentrations of antibiotics usually required. However, until
now, topical antibiotics have not shown consistent results for
CRS treatment. While mupirocin reduced S. aureus biofilm
mass and topical macrolides showed significant improvement
in CRS patients, topical ciprofloxacin and vancomycin were
both largely ineffective in reducing biofilms.41,42 Overall,
several randomized control trials and systemic reviews have
been performed on this topic.40 While the antibiotic mecha-
nism of delivery (standard vs non-standard delivery, ie, sprays
and drops vs irrigation and nebulizers, respectively) and pa-
tients’ selection (CRSwNP vs CRSsNP) varied significantly,
these studies and reviews have failed to show additional
benefit of topical antibiotics.40

Table 3. Chronic Rhinitis SNOT-20 Symptoms, Before and After Treatment with Pomegranate Fruit Extract and Placebo.

Before treatment After treatment Change P value

Thick nasal discharge P = .004

PFE 3.43 1.75 1.68
Placebo 2.27 1.60 .67
Difficulty falling asleep P = .02
PFE 2.00 1.36 .63
Placebo .81 .81 0
Reduced productivity P = .03
PFE 1.81 0.8 1.00
Placebo 1.21 1.4 0.2
Reduced concentration P = .007
PFE 1.29 .41 .88
Placebo 2.18 2.27 .09
Sadness P = .02
PFE 2.06 1.06 1
Placebo 1.40 1.90 .50

Abbreviations: PFE, Pomegranate Fruit Extraction.

8 Ear, Nose & Throat Journal 0(0)
Israeli et al
Previous studies described a significant improvement in
SNOT-22 results for CRS patients using intranasal chemical
surfactants as agents to disrupt biofilm integrity,43 while others
demonstrated destabilization of P. aeruginosa with the use of
topical furosemide under in vitro experiment.44
In addition to being proven to be a safe therapeutic option,45
Pomegranate Fruit Extract and its biologically active com-
pounds have been studied extensively.46 Many studies have
shown its various pathophysiologic anti-inflammatory effects,
including inhibition of PMACI-induced proinflammatory cy-
tokines assembly by inhibiting gene expression through the
blockage of JNK and ERK-MAPK and NF-κB activation in
human KU812 cells,47 a reduction of Prostaglandin E2 (PGE2)
levels in colonic mucosa by downregulating overexpressed
COX-2 and Prostaglandin E synthase (PTGES) level through
the action of ellagic acid,48 inhibition of numerous single
transduction pathways and downstream pathogenic cellular
response,49 and disrupting biofilms,20 possibly through alter-
ations in bacterial cell walls by ethanolic extracts.21 Interest-
ingly, PFE may have a therapeutic role in other disease states. A
randomized controlled trial50 demonstrated that daily oral
pomegranate consumption may lead to enhanced protection
from UV photodamage, possibly through abundance of skin
bacteria containing pigments absorbing UV irradiation that
might contribute to UVB skin protection.
The current analysis shows that topical nasal PFE impacts
QoL in patients with CR, being effective in reducing thick
nasal discharge, difficulty falling asleep, reduced productivity,
reduced concentration, and sadness. Despite this, in the
present study, PFE did not prove effective for the treatment of
CRS. Nonetheless, we believe that it cannot yet be concluded
that PFE is not an applicable antimicrobial and anti-biofilm
agent, as, in this study, we used a standard irrigation method in
the form of nasal spray. Thus, further research and devel-
opment of different delivery methods, enabling higher con-
centration levels of PFE into the nasal sinuses, may yield more
favorable outcomes. Moreover, it is possible that PFE will be
effective for patients who have undergone ESS, as it has been
shown to enhance the delivery of nasal solutions into the
sinuses.51-54
This study has several limitations. First, albeit a relatively
large sample size, the sub-divided groups are more modest.
Second, CR was treated without division into sub-groups and
separate etiologies, which might obscure the results. Third,
our study was conducted prior to the publication of the new
EPOS 2020; therefore, data regarding the proportion of pa-
tients with type 2 and non-type 2 CRS is lacking, which may
have influenced contemporary interpretation. Future studies
integrating this division are required and may shed a brighter
light on the topic.
Conclusion
The current study showed that topical nasal PFE could offer
some clinical benefits for treating patients affected by Chronic
NP155
Rhinitis, specifically for thick nasal discharge, difficulty
falling asleep, reduced productivity, reduced concentration,
and sadness. However, in patients afflicted by CRSwNP or
CRSsNP, this substance presently displayed no significant
treatment role, possibly due to inability to reach the sinus
mucosa. Future studies are required concerning development
of an optimal delivery device that may ameliorate some of the
abovementioned results.
Author’s note
The authors take responsibility for all aspects of the reliability and
freedom from bias of the data presented and their discussed
interpretation.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, au-
thorship, and/or publication of this article.
ORCID iDs
Golda Grinblat  https://orcid.org/0000-0002-0229-8715
Isaac Shochat  https://orcid.org/0000-0003-0153-8956
References
1. Bachert C, Zhang L, Gevaert P. Current and future treatment
options for adult chronic rhinosinusitis: focus on nasal poly-
posis. J Allergy Clin Immunol. 2015;136(6):1431-1440. doi:10.
1016/j.jaci.2015.10.010.
2. Rudmik L, Smith TL. Quality of life in patients with chronic
rhinosinusitis. Curr Allergy Asthma Rep. 2011;11(3):247-252.
doi:10.1007/s11882-010-0175-2.
3. Meltzer EO. Allergic rhinitis: burden of illness, quality of life,
comorbidities, and control. Immunol Allergy Clin. 2016;36(2):
235-248. doi:10.1016/j.iac.2015.12.002.
4. Hellgren J, Cervin A, Nordling S, Bergman A, Cardell LO.
Allergic rhinitis and the common cold - high cost to society.
Allergy. 2010;65(6):776-783. doi:10.1111/j.1398-9995.2009.
02269.x.
5. Vuurman EF, van Veggel LM, Uiterwijk MM, Leutner D,
O’Hanlon JF. Seasonal allergic rhinitis and antihistamine effects
on children’s learning. Ann Allergy. 1993;71(2):121-126.
6. Crans Yoon AM, Chiu V, Rana JS, Sheikh J. Association of
allergic rhinitis, coronary heart disease, cerebrovascular disease,
and all-cause mortality. Ann Allergy Asthma Immunol. 2016;
117(4):359-364.e1. doi:10.1016/j.anai.2016.08.021.
7. Boase S, Foreman A, Cleland E, et al. The microbiome of
chronic rhinosinusitis: culture, molecular diagnostics and bio-
film detection. BMC Infect Dis. 2013;13:210. doi:10.1186/1471-
2334-13-210.
Israeli et al.
NP156
8. Al-Mutairi D, Kilty SJ. Bacterial biofilms and the pathophysi-
ology of chronic rhinosinusitis. Curr Opin Allergy Clin Immunol.
2011;11(1):18-23. doi:10.1097/ACI.0b013e3283423376.
9. Fokkens WJ, Lund VJ, Mullol J, et al. EPOS 2012: European
position paper on rhinosinusitis and nasal polyps 2012. A
summary for otorhinolaryngologists. Rhinology. 2020;50(suppl
S29):1-12. doi:10.4193/Rhin20.600.
10. Bachert C, Zinreich SJ, Hellings PW, et al. Dupilumab reduces
opacification across all sinuses and related symptoms in patients
with CRSwNP. Rhinology. 2020;58(1):10-17. doi:10.4193/
Rhin18.282.
11. Bachert C, Hellings PW, Mullol J, et al. Dupilumab improves
health-related quality of life in patients with chronic rhinosi-
nusitis with nasal polyposis. Allergy. 2020;75(1):148-157. doi:
10.1111/all.13984.
12. Varshney R, Lee JT. Current trends in topical therapies for
chronic rhinosinusitis: update and literature review. Expert Opin
Drug Deliv. 2017;14(2):257-271. doi:10.1080/17425247.2016.
1214563.
13. Hamilos DL. Allergic fungal rhinitis and rhinosinusitis. Proc Am
Thorac Soc. 2010;7(3):245-252. doi:10.1513/pats.200909-
098AL.
14. Barshak MB, Durand ML. The role of infection and antibiotics
in chronic rhinosinusitis. Laryngoscope Investig Otolaryngol.
2017;2(1):36-42. doi:10.1002/lio2.61.
15. Lal D, Cain D. Update on the management of chronic rhino-
sinusitis. Infect Drug Resist. 2013;6:1-14. doi:10.2147/IDR.
S26134.
16. Bedigian D. Pomegranates. Ancient roots to modern medicine.
Medicinal and aromatic plants—industrial profiles 43. Econ Bot.
2007;61(1):107-108. doi:10.1663/0013-0001(2007)61[107b:
PARTMM]2.0.CO;2. Navindra P. Seeram, Risa N. Schulman,
David. Heber., eds. 2006 CRC Press, Taylor & Francis Group.
6000 Broken Sound Parkway NW, Suite 300, Boca Raton, FL
33487–2742. xii +. 244 (hardcover). US$ 129.95, £ 74.99.
ISBN: 0-8493-9812-6.
17. Prashanth D, Asha MK, Amit A. Antibacterial activity of Punica
granatum. Fitoterapia. 2001;72(2):171-173. doi:10.1016/
S0367-326X(00)00270-7.
18. Naz S, Siddiqi R, Ahmad S, Rasool SA, Sayeed SA. Anti-
bacterial activity directed isolation of compounds from Punica
granatum. J Food Sci. 2007;72(9):M341-M345. doi:10.1111/j.
1750-3841.2007.00533.x.
19. Abdollahzadeh Sh, Mashouf R, Mortazavi H, Moghaddam M,
Roozbahani N, Vahedi M. Antibacterial and antifungal activities
of punica granatum peel extracts against oral pathogens. J Dent.
2011;8(1):1-6.
20. Bakkiyaraj D, Nandhini JR, Malathy B, Pandian SK. The anti-
biofilm potential of pomegranate (Punica granatumL.) extract
against human bacterial and fungal pathogens. Biofouling. 2013;
29(8):929-937. doi:10.1080/08927014.2013.820825.
21. Howell AB, D’Souza DH. The pomegranate: effects on bacteria
and viruses that influence human health. Evid Based Comple-
ment Alternat Med. 2013;2013:606212. doi:10.1155/2013/
606212.
9
Ear, Nose & Throat Journal 103(3)
22. Haidari M, Ali M, Ward Casscells S, Madjid M. Pomegranate
(Punica granatum) purified polyphenol extract inhibits influenza
virus and has a synergistic effect with oseltamivir. Phytome-
dicine. 2009;16(12):1127-1136. doi:10.1016/j.phymed.2009.
06.002.
23. Neurath AR, Strick N, Li YY, Debnath AK. Punica granatum
(pomegranate) juice provides an HIV-1 entry inhibitor and
candidate topical microbicide. Ann N Y Acad Sci. 2005;1056:
311-327. doi:10.1196/annals.1352.015.
24. Kotwal GJ. Genetic diversity-independent neutralization of
pandemic viruses (e.g. HIV), potentially pandemic (e.g. H5N1
strain of influenza) and carcinogenic (e.g. HBV and HCV) vi-
ruses and possible agents of bioterrorism (variola) by enveloped
virus neutralizing compounds (EVNCs). Vaccine. 2008;26(24):
3055-3058. doi:10.1016/j.vaccine.2007.12.008.
25. Steinmann J. Surrogate viruses for testing virucidal efficacy of
chemical disinfectants. J Hosp Infect. 2004;56(suppl 2):49-54.
doi:10.1016/j.jhin.2003.12.030.
26. Dawson DJ, Paish A, Staffell LM, Seymour IJ, Appleton H.
Survival of viruses on fresh produce, using MS2 as a surrogate
for norovirus. J Appl Microbiol. 2005;98(1):203-209. doi:10.
1111/j.1365-2672.2004.02439.x.
27. Wobus CE, Thackray LB, Virgin HW. Murine norovirus: a
model system to study norovirus biology and pathogenesis. J
Virol. 2006;80(11):5104-5112. doi:10.1128/JVI.02346-05.
28. Fokkens WJ, Lund VJ, Mullol J, et al. EPOS 2012: European
position paper on rhinosinusitis and nasal polyps 2012. A
summary for otorhinolaryngologists. Rhinology. 2012;50(1):
1-12. doi:10.4193/Rhino12.000.
29. Nathan RA. The burden of allergic rhinitis. Allergy Asthma
Proc. 2007;28(1):3-9. doi:10.2500/aap.2007.28.2934.
30. Piccirillo JF, Merritt MG, Richards ML. Psychometric and
clinimetric validity of the 20-item Sino-Nasal outcome test
(SNOT-20). Otolaryngol Head Neck Surg. 2002;126(1):41-47.
doi:10.1067/mhn.2002.121022.
31. Vasar M, Houle P-A, Douglass JA, et al. Fluticasone furoate
nasal spray: effective monotherapy for symptoms of perennial
allergic rhinitis in adults/adolescents. Allergy Asthma Proc.
2008;29(3):313-321. doi:10.2500/aap.2008.29.3126.
32. Nathan RA, Berger W, Yang W, et al. Effect of once-daily
fluticasone furoate nasal spray on nasal symptoms in adults and
adolescents with perennial allergic rhinitis. Ann Allergy Asthma
Immunol. 2008;100(5):497-505. doi:10.1016/S1081-1206(10)
60477-2.
33. Verkerk MM, Bhatia D, Rimmer J, Earls P, Sacks R, Harvey RJ.
Intranasal steroids and the myth of mucosal atrophy: a sys-
tematic review of original histological assessments. Am J Rhinol
Allergy. 2015;29(1):3-18. doi:10.2500/ajra.2015.29.4111.
34. Allen DB. Systemic effects of intranasal steroids: an endocri-
nologist’s perspective. J Allergy Clin Immunol. 2000;106(4
suppl l):S179-S190. doi:10.1067/mai.2000.110038.
35. Price D, Bousquet J, Hellings P, et al. Short and long-term safety
of MP29-02*: a new therapy for the treatment of allergic rhinitis.
Clin Transl Allergy. 2013;3(suppl 2):O15. doi:10.1186/2045-
7022-3-S2-O15.
10
Israeli et al
36. Lam HCK, Tong MCF, Hasselt CAV. Rhinitis symptoms and
quality of life in patients with chronic perennial rhinitis treated
with desloratadine. J Laryngol Otol. 2007;121(12):1151-1155.
doi:10.1017/S0022215107000059.
37. Thongngarm T, Assanasen P, Pradubpongsa P, Tantilipikorn P.
The effectiveness of oxymetazoline plus intranasal steroid in the
treatment of chronic rhinitis: a randomised controlled trial. Asian
Pac J Allergy Immunol. 2016;34(1):30-37. doi:10.12932/
AP0649.34.1.2016.
38. Mullol J, Obando A, Pujols L, Alobid I. Corticosteroid treatment
in chronic rhinosinusitis: the possibilities and the limits. Im-
munol Allergy Clin. 2009;29(4):657-668. doi:10.1016/j.iac.
2009.07.001.
39. Karunasagar A, Garag SS, Appannavar SB, Kulkarni RD, Naik
AS. Bacterial biofilms in chronic rhinosinusitis and their im-
plications for clinical management. Indian J Otolaryngol. 2018;
70(1):43-48. doi:10.1007/s12070-017-1208-0.
40. Orlandi RR, Kingdom TT, Hwang PH. International consensus
statement on allergy and rhinology: rhinosinusitis executive
summary. Int Forum Allergy Rhinol. 2016;6(suppl 1):S3-S21.
doi:10.1002/alr.21694.
41. Desrosiers M, Bendouah Z, Barbeau J. Effectiveness of topical
antibiotics on Staphylococcus aureus biofilm in vitro. Am J
Rhinol. 2007;21(2):149-153. doi:10.2500/ajr.2007.21.3007.
42. Wallwork B, Coman W, Mackay-Sim A, Greiff L, Cervin A. A
double-blind, randomized, placebo-controlled trial of macrolide
in the treatment of chronic rhinosinusitis. Laryngoscope. 2006;
116(2):189-193. doi:10.1097/01.mlg.0000191560.53555.08.
43. Chiu AG, Palmer JN, Woodworth BA, et al. Baby shampoo
nasal irrigations for the symptomatic post-functional endoscopic
sinus surgery patient. Am J Rhinol. 2008;22(1):34-37. doi:10.
2500/ajr.2008.22.3122.
44. Cross JL, Ramadan HH, Thomas JG. The impact of a cation
channel blocker (Furosemide) on pseudomonas aeruginosa
PA01 biofilm architecture. Otolaryngol Head Neck Surg. 2007;
137(1):21-26. doi:10.1016/j.otohns.2007.02.022.
45. Patel C, Dadhaniya P, Hingorani L, Soni MG. Safety assessment
of pomegranate fruit extract: acute and subchronic toxicity
studies. Food Chem Toxicol. 2008;46(8):2728-2735. doi:10.
1016/j.fct.2008.04.035.
Ear, Nose & Throat Journal 0(0)
NP157
46. Sreekumar S, Sithul H, Muraleedharan P, Azeez JM, Sreehar-
shan S. Pomegranate fruit as a rich source of biologically active
compounds. Biomed Res Int. 2014;2014:686921. doi:10.1155/
2014/686921.
47. Rasheed Z, Akhtar N, Anbazhagan AN, Ramamurthy S, Shukla
M, Haqqi TM. Polyphenol-rich pomegranate fruit extract
(POMx) suppresses PMACI-induced expression of pro-
inflammatory cytokines by inhibiting the activation of MAP
Kinases and NF-κB in human KU812 cells. J Inflamm (Lond).
2009;6:1. doi:10.1186/1476-9255-6-1.
48. Larrosa M, González-Sarrı́as A, Yáñez-Gascón MJ, et al. Anti-
inflammatory properties of a pomegranate extract and its me-
tabolite urolithin-A in a colitis rat model and the effect of colon
inflammation on phenolic metabolism. J Nutr Biochem. 2010;
21(8):717-725. doi:10.1016/j.jnutbio.2009.04.012.
49. Shukla M, Gupta K, Rasheed Z, Khan KA, Haqqi TM. Con-
sumption of hydrolyzable tannins-rich pomegranate extract
suppresses inflammation and joint damage in rheumatoid ar-
thritis. Nutrition. 2008;24(7-8):733-743. doi:10.1016/j.nut.
2008.03.013.
50. Henning SM, Yang J, Lee R-P, et al. Pomegranate juice and
extract consumption increases the resistance to UVB-induced
erythema and changes the skin microbiome in healthy women: a
randomized controlled trial. Sci Rep. 2019;9(1):14528. doi:10.
1038/s41598-019-50926-2.
51. Grobler A, Weitzel EK, Buele A, et al. Pre- and postoperative
sinus penetration of nasal irrigation. Laryngoscope. 2008;
118(11):2078-2081. doi:10.1097/MLG.0b013e31818208c1.
52. Harvey RJ, Goddard JC, Wise SK, Schlosser RJ. Effects of
endoscopic sinus surgery and delivery device on cadaver sinus
irrigation. Otolaryngol Head Neck Surg. 2008;139(1):137-142.
doi:10.1016/j.otohns.2008.04.020.
53. Miller TR, Muntz HR, Gilbert ME, Orlandi RR. Comparison of
topical medication delivery systems after sinus surgery. La-
ryngoscope. 2004;114(2):201-204. doi:10.1097/00005537-
200402000-00004.
54. Orlandi RR, Kingdom TT, Smith TL, et al. International con-
sensus statement on allergy and rhinology: rhinosinusitis 2021.
Int Forum Allergy Rhinol. 2021;11(3):213-739. doi:10.1002/alr.
22741.