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N.2/2017
ISSN 2531-9299
The Official Journal of the Italian Academy of Rhinology
The Rhinologist The Rhinologist 2-2017
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Table of Contents 3. The Rhinologist 4. Efficacy of intranasal formulation of azelastine hydrochloride/fluticasone propionate in non allergic rhinitis A. Macchi et al. 8. Nasal airflow: fitting experimental data from sinunasal digital manometry by eans of a biophysical model. E. Cantone et al. 14.Role of biofilm scanning through electron microscopy in chronic rhinosinusitis Beltagy YF. Et al 22.Stent in endoscopic choanal atresia repair: a review of literature. Axel Wolf et al 28. Allergic fungal sinusitis in a 5 years old child, case report Raed Sami Aljuboori
EDITORIAL BOARD Journal Editorial Chief: Matteo Castelnuovo Journal Scientific Chief: Matteo Gelardi, Paolo Castelnuovo Administrator and Segretary: PSA&CF srl official Secretariat of IAR Editorial Staff: Stefania Gallo, Paola Terranova, Elena Cantone, Veronica Seccia, Rikki Canevari Editor: PSA&CF srl Via Procaccini, 24
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Registered in the Court of Varese at n. 5/2016 www.therhinologist.com Editor in Varese
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ISSN 2531-9299
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The Rhinologist The Italian Academy of Rhinology (IAR ) was
The Rhinologist, the official Journal of the
founded with the aim to collect those Rhinolo-
Academy, represents the natural evolution of
gy’s various souls that in recent years offered
this journey to improve the research and the
not only professional training opportunities and
study of Rhinology with the scope to give the
contents, but also established themselves at in-
opportunity to share best practices and
ternational level as a valued and constantly
knowledge even with the aim to reach an im-
evolving entities
portant impact factor. Within the journal read-
According to this point the Academy wants to give an active, responsible and significant contribution to the development of the discipline, with the belief of the absolute need to have a unique and shared vision on the nasal field that can represent the totality of the realities which compose the rhinology, including key areas (cytological medical-surgical) and especially the field of endoscopic and reconstructive surgery also with
ers will find the most important dates of courses, conferences and meetings, as well as new job opportunities and facilities. Finally, in order to help the growth of the circulation of this magazine The Rhinologist will be provided for free with the aim to spread as much as possible the values of the publications made by young talents who want to give their contribution to the world of rhinology.
the aesthetic functional-addresses. The objective is to promote the research, education, training and ability to attract young talents in order to make the difference with the aim to grow up the primacy of this specialty, anticipating changes to combine all available forces to implement experiences, willingness and skills.
The Italian Academy of Rhinology encourages
the ambition of its members to be present and competitive on the international scene, through an expertise and a credibility solidly built over the years. Moreover in this way the IAR wants to create conditions for attracting new vital forces that can continue this path of innovation, taken and shared by many colleagues during the years, that allow the academy to be the catalyst of a process that wants to find a new strategic
roadmap to make the world better in terms of medical, technical and surgical approach. The Rhinologist 2-2017
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EFFICACY OF INTRANASAL FORMULATION OF AZELASTINE HYDROCHLORIDE/FLUTICASONE PROPIONATE IN NON ALLERGIC RHINITIS A.Macchi^, A.Periolo°, D.Simoncini*, S. Gallo^, F.Debernardi^, P.Castelnuovo^ ^ENT Clinic, University of Insubria, Varese *Pediatric Unit, ASST-Settelaghi, Varese, DMCS Insubria
University, Varese
°Pediatric Unit, Spedali Civili di Brescia, Brescia
Key Word: NAR, Azelastine Hydrochloride, Fluticasone propionate Received 10.1.2017 Correspondence. Alberto Macchi, Ent Clinic Univesity of Insubria via Guicciardini, 9 21100 Varese, Email:
[email protected]
INTRODUCTION Non allergic rhinitis (NAR) has a huge impact on the quality of life of patients since social life, career and work performances are often severely impaired. Despite the great progress in research into causes, diagnosis and management of rhinitis in the last decades, NAR is inadequately treated. The patients are subjected to multiple rounds of treatment failures that lead to frustration towards seeking medical care and medication use, not to mention that untreated rhinitis is a risk factor for obstructive sleep apnea, fatigue, headache, nasal polyps and asthma. [1] Intranasal corticosteroids have been found to be effective in control of NAR symptoms, however only Fluticasone propionate and beclomethasone are the topical corticosteroids approved by the FDA in USA for the treatment of NAR. Also oral second generation antihistamines are often used but they are usually not sufficient in relieving the symptoms. Among topical antihistamines Azelastine has shown to better improve NAR symptoms. [1, 14] Currently among treatments of allergic rhinitis a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate seems to be a very good therapy because its use result in better compliance, improved efficacy and a faster response together with good levels of tolerability. [10] We investigated if this novel formulation could be useful also in the treatment of NAR, since Fluticasone and Azelastine are normally used as NAR therapy.
MATERIALS AND METHODS The present study was conducted on patients selected out of ENT Department of Varese University Hospital from June 2010 to June 2011. Patients affected by NAR were included. NAR was defined as having symptoms of rhinitis (≥ 2 of the following: sneezing, nasal itch, rhinor-rhea and nasal block) along with a negative skin prick test and negative specific IgE analysis, positive nasal endoscopy, and presence of eosinophils, neutrophils or mastcells at nasal cytology. All subjects were treated with the novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) delivered in a single spray, twice a day for 3 months and underwent a symptoms questionnaire adapted from the TNSS before and after the treatment. [16]
Statistical analysis Student T test was used for statistical processing of data. Significance level was set to the value p = 0,05. RESULTS The efficacy of the mixed formulation have been evaluated in 73 male and 65 female affected by NAR. (Fig 1). Respiratory symptoms such as presence of nasal congestion, sneezing, anosmia, difficult sleep, runny nose, nasal itching, along with rhinocytograms have been investigated before and after the treatment. (Tab 1 and 2). 53 patients were affected by NARES, 40 by NARESMA, 17 by NARNE and 28 by NARMA. (Fig 2) 12 patients reported aftertaste but no other mayor or minor complications have been indicated.
Fig 1 Distribution of male and female in the population studied
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DISCUSSION
Fig 2 Distribution of NAR subtypes
Tab 1 Patients symptoms before and after treatment (the mean value of each symptoms for all the answers given by the patients has been indicated)
Nasal congestion Runny nose Sneezing Nasal itching Difficult sleep Anosmia
The exact prevalence and impact of NAR is most likely grossly underestimated because of a lack of a worldwide definition. By some estimates, NAR affects more than 19 to 20 million patients in the United States, and 50 million Europeans, with a total prevalence of more than 200 million worldwide. Despite the fact that both NAR and AR have a significant economic burden on society and
BEFORE
AFTER
p-value
negative impact on patient quality of life,
3,4 3,42 3,42 3,51 3,40 3,32
1,7 1,65 1,62 1,68 1,63 1,61
0,0025 0,0007 0,0002 0,0003 0,0005 0,0006
Schatz et al. found that patients affected by
Tab 2 Rhinocytograms of patients before and after treatment ( the mean value of the rhinocytograms of all patients has been indicated)
BEFORE
AFTER
p-value
NAR had significantly more health care visits per year for asthma (2-4 times as many), acute sinusitis (6-8 times as many) and all other diagnoses (almost twice as many). They also found that these patients had a higher prevalence of comorbid diseases such as asthma, acute and chronic sinusitis, nasal polyposis, conjunctivitis, acute otitis media, chronic serous otitis media, sleep apnea, and fatigue. [1] The reason of this situation is probably the
NARES p 0,001
damage of inadequately diagnosed and there-
Eosinophils
4
1
Neutrophils
0
0
fore treatment of NAR.
Mastcells
0
0
NAR management is still a problem because of
Bacteria
0
0
the lack of appropriate therapies, and validated guidelines. First of all avoidance of environ-
NARESMA Eosiniphils
4
1
p 0,001
mental triggers such as strong odors, air pollu-
Neutrophils
2
0
N.S
tants, low or high temperatures, wetness, that
Mastcells
4
1
p 0,001
are respiratory irritants is recommended.
Bacteria
Topical and systemic corticosteroids have
NARNE
been found to be effective in non allergic rhinitis, especially in NARES. Nasal lavage with
Eosinophils
0
0
Neutrophils
3
1
Mastcells
0
0
found to be a helpful alone or as an adjuvant
Bacteria
0
0
therapy in these patients.
N.S
NARMA
saline or hypertonic solution has also been
Oral antihistamines might be thought not to
Eosiniphils
0
0
Neutrophils
1
0
Mastcells
4
2
Bacteria
0
0
be so effective in the treatment of NAR, since these diseases aren’t characterized by histap 0,01
mine release. However topical antihistamines have been found to be very effective for the The Rhinologist 2-2017
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overall treatment of NAR, due to their anti-
twice a day, for 3 months.
inflammatory properties. Azelastine in partic-
The compliance was excellent. Despite 12 patient
ular has been shown to be efficacious for non
reported metallic aftertaste, none interrupts the
allergic rhinitis. A multi-center, randomized,
therapy. The metallic aftertaste is due to azelastine
placebo-controlled trial conducted by Banov
and it is dose-dependent and often dissipates over
and Lieberman found a significant improve-
time as shown in other studies [1]. None adverse
ment in NAR symptom scores (TVRSS) in
drug reaction such as nosebleed or infection was re-
those patients receiving azelastine (two
ported.
sprays twice a day, 1.1 mg) versus placebo.
Data collected by using the total nasal symptoms
Another study found that Azelastine has im-
score, indicate a significant statistical improvement
provement in control of NAR symptoms such
in nasal symptoms after the treatments.
as nasal congestion, sneezing and sleeping
At the same time in our study to evaluate the effica-
difficulty. [1] Azelastine has a rapid onset of
cy of this new spray the rhinocytogram of each pa-
action, flexibility of dose and dosage (fix or as
tients before and after the treatment as been ana-
needed). Most of the times antihistamines
lysed. The combination treatment lead to a fall of
are use in combination with intranasal corti-
eosinophils and mast-cells. A reduction also of neu-
costeroids as an adjunctive therapy, because
trophils as been observed but not as stastically im-
the combination has the potential to enhance
portant as the one of the other type of cells.
clinical benefits. [19]
Despite this fact it appear clearly that the new for-
Recently it has been introduced a novel in-
mulation play a big role not only in reducing nasal
tranasal formulation of azelastine hydrochlo-
symptoms but also in decreasing nasal inflammation.
ride (AZE) and fluticasone propionate (FP) de-
Although this encouraging data, a double-blind, pla-
livered in a single spray which seems to pro-
cebo-controlled study is needed to better under-
vide rapid and sustained symptom control in
stand the real efficacy of this therapy in NAR as it
allergic rhinitis. [10, 14]
has been done for allergic rhinitis. [13]
Since Fluticasone and Azelastine are usually used in the treatment of NAR, the current
CONCLUSION
study investigated the efficacy of this novel
The treatment of NAR is a daily challenge for otolar-
intranasal formulation in a group of patients
yngologists. Intranasal corticosteroids, antihista-
affected by NAR.
mines, decongestants aren’t always efficacious in
Thanks to nasal cytology, nasal endoscopy
the improvement of symptoms. However the combi-
and negative prick test, diagnosis of NAR has
nation of steroids and antihistamines seems to be a
been made in all patients evaluated. The
promising option in achieving a better quality of life
different subtypes of NAR have been identi-
in these patients. The novel intranasal formulation
fied by the analysis of the rhinocytogram.
of azelastine hydrochloride (AZE) and fluticasone
The patients evaluated were affected by se-
propionate (FP) delivered in a single spray has
vere symptoms such as nasal congestion,
shown a huge decreased of nasal inflammation and
sneezing, anosmia, difficult sleep, runny nose,
nasal symptoms. Future investigation are need, es-
nasal itching.
pecially to better understand the action of the anti-
Therefore each patient has been treated with
histamine.
the novel intranasal formulation of azelastine and Fluticasone, delivered in a single spray, .
The Rhinologist 2-2017
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