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Clinical Study
Role of α-Tocopherol Acetate on Nasal
Respiratory Functions: Mucociliary
Clearance and Rhinomanometric
Evaluations in Primary Atrophic Rhinitis
Domenico Testa, MD, PhD
1
, Giuseppina Marcuccio, MD, PhD
1
,
Nicola Lombardo, MD
2
, Salvatore Giuseppe Cocuzza, MD, PhD
3
,
Germano Guerra, MD, PhD
4
, and Gaetano Motta, MD, PhD
1
Abstract
Primary atrophic rhinitis is a disease of the nose and of paranasalsinuses characterized by a progressive loss of function of nasal and
paranasal mucosa caused by a gradual destruction of ciliary mucosalepithelium with atrophy of serous–mucous glands and loss of
bonestructures.The aim of this study was to evaluate the therapeutic effects of topic a-tochopherol acetate (vitamin E) in patients
with primary atrophicrhinitis based on subjective and objective data.We analyzed 44 patients with dry nose sensation and
endoscopic evidence of atrophic nasal mucosa. We analyzed endoscopic mucosascore, anterior rhinomanometry, and nasal
mucociliary clearance before and after 6 months of topic treatment with a-tochopherol acetate. For statistical analysis, we used
paired samples ttest (95% confidence interval [CI], P< .05) for rhinomanometric and muciliary transit time evaluations and
analysis of variance 1-way test (95% CI, P< .05) for endoscopic evaluation. All patients showed an improvement in ‘‘dry nose’’
sensation and inperception of nasal airflow. Rhinomanometric examination showed increase of nasal airflow at follow-up (P< .05);
nasal mucociliaryclearance showed a reduction in mean transit time (P< .05); and endoscopic evaluation showed significative
improvement of hydration of nasalmucosa and significative decreasing nasal crusts and mucusaccumulation (P< .05). Medical
treatment for primary atrophic rhinitis is not clearly documented in the literature; in this research, it was demonstrated that a-
ochopherol acetate could be a possible treatment for atrophic rhinitis.
Keywords
primary atrophic rhinitis, rhinomanometry, nasal mucociliary clearance, a-tochopherol acetate, dry nose, rhinitis
Introduction
The definition of dry nose involves several clinical conditions
such as the anterior dry rhinitis, primary atrophic rhinitis (PAR)
and secondary atrophic rhinitis (SAR), and their complications
like ozena and empty nose syndrome.
1
Atrophic rhinitis (AR) is
a disease of the nose and paranasal sinuses of considerable clin-
ical interest in otolaryngology. Fraenkel described it for the first
time in 1876, but its etiopathogenesis is still debated nowadays.
1-
2
According to its etiology, it is classified into PAR and SAR and
it is characterized by a progressive loss of function of nasal and
paranasal mucosa caused by the gradual destruction of the ciliary
mucosal epithelium or respiratory epithelium, by the atrophy of
exocrine serous-mucous glands, and by the loss of underlying
bone structures.
1
Moreover, the disease involves the metaplastic
replacement of the squamous epithelium and subsequent loss of
1
Department of General and Specialistic Surgery—Head and Neck Unit,
University of Campania ‘‘L Vanvitelli,’’ Napoli, Italy
2
Department of Surgical and Medical Science, Otolaryngology, ‘Magna Grecia’
University, Catanzaro, Italy
3
Department of Surgical and Medical Science and Advanced Technologies
‘‘G.F. Ingrassia,’’ Otolaryngology, University of Catania, Catania, Italy
4
Department of Medicine and Health Sciences ‘‘V Tiberio,’’ University of
Molise, Campobasso, Italy
Received: July 02, 2019; accepted: July 26, 2019
Corresponding Author:
Giuseppina Marcuccio, MD, PhD, Department of General and Specialistic
Surgery—Head and Neck Unit, University of Campania ‘‘L Vanvitelli,’’ via
Sergio Pansini, Ed. 17, Napoli, Italy.
Email: giuseppina_marcuccio@hotmail.it
Ear, Nose & Throat Journal
2021, Vol. 100(6) NP290–NP295
ªThe Author(s) 2019
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mucociliary clearance.
1
This morphostructural damage of nasal
mucosa leads to clinical manifestations such as nasal congestion
and paradoxal nasal respiratory obstruction, despite an increase
in nasal spaces (paradox stuffy nose) and persistence of secre-
tions; these conditions are mainly determined by the loss of the
nasal nerve sensitivity due to submucosal atrophy.
1-2
The diagnosis is clinical based on the subjective and objec-
tive findings: increased mucociliary clearance transit time,
alteration in rhinomanometric values, nasal symptoms (conges-
tion, dry nose, nasal respiratory obstruction, nasal crusts,
mucus secretion, and hypo/anosmia), and epistaxis.
1-2
Several authors have investigated the role of a-tocopherol
acetate for its anti-inflammatory, immune, and antioxidant
functions have been widely documented in the literature with
restoration of epithelium in skin, in oral and vulvovaginal
mucosa, and in gastric mucosa and nasal mucosa.
3-14
Vitamin E acts as a cofactor for the binding of different
enzymes for oxidative cascade reaction: it prevents oxidation
and destruction of membrane lipids; it interacts with different
cellular proteins that regulate the transcription and the expres-
sion of genes that code for cytokines and chemokines.
3,9,13
The aim of this study was to evaluate the effects of the
therapeutic protocol with a-tocopherol acetate in patients with
PAR without infection, based on the subjective and objective
measures.
Patients and Methods
From October 2017 to September 2018, we enrolled 44 patients
(29 female and 15 male) aged between 34 and 70 years, mean age
57.2 years old, with clinical history and objective findings of PAR.
Most of the patients referred hyposmia/anosmia associated with
the sensation of dry nose. Informed consent was obtained from all
individual participants included in the study. The research proto-
col was approved by University Control Group; this study was
conducted according to the World Medical Association Declara-
tion of Helsinki. This is a retrospective observational research.
Theinclusioncriteriawereclinical evidence of paradox
nasal stuffiness sensation, hyposmia/anosmia, sensation of
‘‘dry nose,’’ and endoscopic and computed tomography (CT)
scan evidence of mucosal epithelium atrophy with abnormal
expansion of paranasal sinuses and nasal spaces. Patients with
the history of previous nasal surgery, allergic chronic vasomo-
tor rhinitis, chronic granulomatous disease, use of topical nasal
drugs, diagnosis of Sjogren syndrome, prior radiotherapy of the
head and neck, and complications of the disease such as septal
perforation and crusts infections were excluded. Patients
underwent, after general ear, nose and throat examination, a
CT scan of the nose and paranasal sinuses, endoscopic rhino-
logic evaluation, rhinomanometry, and nasal mucociliary clear-
ance (NMC) test with charcoal and saccharine powder.
At endoscopic rhinologic evaluation, using a quantitative
scale, we analyzed:
– State of hydration of nasal mucosa (0, dry mucosa; 1, par-
tially wet mucosa; and 2, wet mucosa);
– presence of nasal crusts (1, 2, and 3 for poor, moderate,
and severe crusting; 0 for absence of crusting);
– presence of mucus accumulation (1, 2, and 3 for poor,
moderate, and severe mucus accumulation; 0 for absence
of mucus accumulation).
The endoscopic evaluation was performed always by the
same specialist since this score was a subjective data.
Bilateral anterior rhinomanometry (evaluated at 150 Pascal
drop pressure) was conducted in basal condition and 5 minutes
after nasal decongestion with naphazoline 0.1%nasal spray
(1 puff each nostril) in order to analyze nasal flow rates (cm
3
/s)
and nasal resistances (Pa/cm
3
/s) using ATMOS1Rhino 31
(anterior measurements using olive measuring probe). We
obtained 8 groups of results before and after topic treatment with
a-tocopherol acetate:
– Nasal airflow basal before topic treatment (AFbasalT0);
– nasal airflow basal after topic treatment (AFbasalT1);
– nasal resistance basal before topic treatment (RbasalT0);
– nasal resistance basal after topic treatment (RbasalT1);
– nasal airflow after decongestant before topic treatment
(AFdecongT0);
– nasal airflow after decongestant after topic treatment
(AFdecongT1);
– nasal resistance after decongestant before topic treatment
(RdecongT0);
– nasal resistance after decongestant after topic treatment
(RdecongT1).
The NMC test was performed 2 hours before rhinomanome-
try using a mixture of charcoal and 3%of saccharine powder, at
1to3PM in order to eliminate the influence of circadian nasal
rhythms.
15
Patients waited in a chair 15 to 30 minutes to get
acclimated with room temperature and humidity and to control
for effects of mucosal decongestion due to exercise. The end-
point of this examination was detected by the perception of
sweet taste and appearance of the dye at the pharyngeal inspec-
tion (subjective and objective methods).
The treatment scheme used for this study was the nasal
administration of pure a-tocopherol acetate 2 puffs in each
nostril, 3 times a day, for 6 months, so the follow-up was
performed at the end of medical treatment.
For statistical analysis, we used descriptive data, means, and
standard deviations of each group of results at both rhinomano-
metric and NMC transit time values before and after topic
treatment; and then we compared means between different
groups by means of paired samples ttest (95%confidence
interval (95%CI), P< .05). For endoscopic scores, we used
analysis of variance 1-way test (95%CI, P< .05).
Results
In all patients selected for treatment, we analyzed endoscopic
evaluation, nasal airflow, and nasal resistances rates at basal
and after decongestant rhinomanometry and NMC transit time
(Tables 1 -3).
Testa et al NP291
We observed at endoscopic examination a greater hydration
of the nasal mucosa than before topic treatment and a decrease
of crusts and mucus accumulation (P< .05; Table 1). Before
topic treatment with a-tocopherol acetate, we observed dry
mucosa with severe crusting and moderate mucus accumula-
tion; after topic treatment, mucosa was wet with poor of
absent crusting and mucus accumulation (Figures 1 and 2).
At rhinomanometric examination, the analysis of nasal air-
flows before and after medical treatment, both at basal and
after decongestant evaluation, demonstrated increased airflows
at follow-up with statistical significance (P< .05); while nasal
resistances did not have significative differences before and after
topic treatment with a-tocopherol acetate (P> .05; Table 4).
The NMC test before topic nasal treatment showed a severe
prolonged time (mean 31.52 minutes) instead after medical
topic treatment with a-tocopherol acetate, the mean transit time
was 21.55 minutes (prolonged transit time) with statistical sig-
nificance (P< .05; Table 5).
All patients showed an improvement in ‘‘dry nose’’ sensa-
tion and in the perception of nasal airflow (apparent remission
of paradoxical stuffy nose sensation) with an improvement of
hyposmia/anosmia.
Discussion
Nasal-sinusoidal walls are lined by nasal mucosa providing to
several functions like heating up, humidifying and purifying
inspired air, and nonspecific and specific acting against envi-
ronmental pathogens and others. Nasal mucosa functions are
regulated by several factors like nervous system and sex hor-
mones acting in different manner during life.
16
Dysregulation or dysfunction of these mechanisms leads to
several clinical conditions characterized by dry nose such as
PAR, SAR, and their complications.
1,2
Primary chronic AR is a clinical condition with a higher
prevalence in women after puberty, associated with hereditary
factors, endocrine imbalances, racial factors, nutritional defi-
ciencies such as lack of vitamin A or D, iron, and autoimmune
disorders.
16
The diagnosis was clinical while CT scan was indicated
when signs of chronic rhinosinusitis are found or to obtain
adjunctive evidence of PAR.
1,2
Treatment for PAR is not well defined, and it is often empiri-
cal.
17-18
The saline washes must be considered as the first choice
for several authors to promote the cleaning of the nasal cavity
and to remove secretions and crusts, which could provoke sec-
ondary infections.
17-18
Other therapeutic approaches propose the
use of bicarbonate antiseptic solutions in which the diborated
sodium acts as an antiseptic and antibacterial substance; bicar-
bonate sodium helps to dissolve the crusts; and the chloride
sodium makes the solution isotonic.
17-18
Glycerin drops or spray
associated with glucose can be used because they allow the
lubrification of the nasal mucosa.
17-18
The glucose fermentation
acidifies the pH and hinders bacterial growth.
17-18
Bacterial superinfections are treated with specific antibio-
tics such as rifampicin 600 mg daily for 12 weeks; ciproflox-
acin 500 to 750 mg for 8 weeks.
19
Surgical treatments, instead, provides for the partial or com-
plete closure of the nostrils with autologous or synthetic
implants.
19
Other alternative treatments described in the litera-
ture propose the use of liposucked with autologous platelet-
reached plasma, subcutaneous fat, cancellous bone, autologous
bone marrow grafts, grafts of placenta, or adipose tissue.
20
Table 1. Hydration of Nasal Mucosa, Nasal Crusts and Mucus Accu-
mulation Mean Scores at Endoscopic Evaluation Before and After
Topic Treatment With a-Tocopherol Acetate.
a
Hydration of
Nasal Mucosa,
Mean Values
Presence of
Nasal Crusts,
Mean Values
Mucus
Accumulation,
Mean Values
Before topic
treatment with a-
tocopherol acetate
0.06 +025 2.88 +0.32 1.91 +0.74
After topic treatment
with a-tocopherol
acetate
2.36 +0.65 0.47 +0.5 0.48 +0. 5
Pvalues, ANOVA 1-
way paired variable
<.00001 <.00001 <.00001
Abbreviation: ANOVA, analysis of variance.
a
State of hydration of nasal mucosa (0, dry mucosa; 1, partially wet mucosa;
2, wet mucosa); presence of nasal crusts (1, 2, and 3 for poor, moderate, and
severe crusting; 0 for absence of crusting); presence of nasal mucus (1, 2, and
3 for poor, moderate, and severe mucus accumulation; 0 for absence of
mucus accumulation).
Table 2. Rhinomanometric Medical Treatment.
a
Variable Mean Std Dev Minimum Maximum
AFbasalT0 521.89 131.26 183.00 691.00
AFbasalT1 671.70 105.07 379.00 757.00
RbasalT0 0.56 0.02 0.54 0.60
RbasalT1 0.42 0.02 0.38 0.46
AFdecongT0 533.07 129.37 191.00 706.00
AFdecongT1 672.93 102.91 381.00 765.00
RdecongT0 0.52 0.02 0.47 0.54
RdecongT1 0.40 0.03 0.33 0.43
Abbreviations: AFbasalT0, nasal airflow basal before topic treatment; AFba-
salT1, nasal airflow basal after topic treatment; AFdecongT0, nasal airflow after
decongestant before topic treatment; AFdecongT1, nasal airflow after decon-
gestant after topic treatment; RdecongT0, nasal resistance after decongestant
before topic treatment; RdecongT1, nasal resistance after decongestant after
topic treatment; RbasalT0, nasal resistance basal before topic treatment; Rba-
salT1, nasal resistance basal after topic treatment; std dev, standard deviation.
a
Evaluation at 150 Pa; AF in cm
3
/s; R in Pa/cm
3
/s.
Table 3. NMC (Transit Time) Results Expressed in Minutes.
a
Variable Mean Std Dev Minimum Maximum
NMCT0 31.52 2.05 28.00 36.00
NMCT1 21.55 1.97 18.00 27.00
Abbreviations: NMC, nasal mucociliary clearance; std dev, standard deviation;
T0, before medical treatment; T1, after medical treatment.
a
Valid cases ¼44, cases with missing value(s) ¼0.
NP292 Ear, Nose & Throat Journal 100(6)
In our previous study, we found a decreased healing time in
elderly patients affected by chronic rhinosinusitis after endo-
scopic sinus surgery treated with topic nasal a-tocopherol acet-
ate for 3 months.
14
In consideration of our previous research,
14
the treatment
scheme used for the present study was the nasal administration
of a-tocopherol acetate 2 puffs in each nostril 3 times a day, for
6 months. The follow-up was performed after 6 months of
medical treatment and consists of the endoscopic rhinologic
examination, basal and after decongestant rhinomanometry,
and NMC transit time test.
All patients showed an improvement in nasal respiratory
function for increased nasal airflow; the patients had a better
response to rhinomanometric tests after treatment (increased
nasal airflow). Nasal resistances, according to the literature,
did not have significative differences before and after medical
treatment proposed in this research, neither after decongestant:
maybe due to a vascular depletion in AR and to the duration of
treatment.
18
Furthermore, the NMC test, after treatment, showed a reduc-
tion of the mean transit time near the normal transit time (up to
20 minutes but less than 31 minutes). The duration of NMC in
normal individuals is up to 20 minutes, it is prolonged if it is 21
to 31 minutes; it is considered severely or grossly prolonged if
it is 31 to 60 minutes or up to 60 minutes.
21
The results obtained suggest the use of a-tocopherol acet-
ate in PAR; this study investigated an aspect scientifically
poorly explored: What is the most correct strategy in the
pharmacological treatment of PAR? Moreover, we also want
to give an impulse for scientific studies on the effect of vita-
min E, and specifically of a-tocopherol acetate, in the nasal
tropism.
PAR and ozena are often used to indicate the same clin-
ical condition, even if it is important to distinguish them
because of in the second one, we find bacterial infection.
Medical treatment for PAR is not clearly documented in the
literature in terms of follow-up and clinical evaluation with
subjective (symptoms) and objective methods (endoscopic
evaluation, rhinomanometry, and NMC transit time) and
medical treatment. In the present study, we showed relevant
results in nasal functions after medical topic treatment with
a-tocopherol acetate (vitamin E), and these results lay the
foundation for further application of this molecule in sino-
nasal pathology.
Figure 1. Endoscopic view of nasal mucosa (inferior turbinate) in primary atrophic rhinitis before medical treatment: (A) medial face;
(B-D) head.
Testa et al NP293
Figure 2. Endoscopic view of nasal mucosa (inferior turbinate) in primary atrophic rhinitis after medical treatment: (A) inferior face; (B-D) head.
Table 5. Paired Samples t-Test for Nasal Mucociliary Clearance Transit Time Values.
Paired Differences
Mean Standard Deviation Standard Error of the Mean
95% Confidence Interval
of the Difference tdfSig (2-Tailed)
NMCT0-NMCT1 9.98 0.79 0.12 9.74-10.22 83.56 43 <.001
Abbreviations: NMC, nasal mucociliary clearance; T0, before medical treatment; T1, after medical treatment.
Table 4. Paired Samples tTest For Rhinomanometric Values.
a
Mean Standard Error of Difference 95% Confidence Interval of the Difference tdfSig (2-Tailed)
AF basal T0-AFbasalT1 149.81 25.34 200.2 to 99.42 5.91 86 <.0001
b
Rbasal T0-RbasalT1 0.06 0.27 0.48 to 0.6 0.22 86 <.8275
AFdecongT0-AFdecongT1 1139.86 24.92 189.4 to 90.32 5.61 86 <.0001
b
RdecongT0-RdecongT1 0.06 0.28 0.5 to 0.62 0.21 86 <.315
Abbreviations: AFbasalT0, nasal airflow basal before topic treatment; AFbasalT1, nasal airflow basal after topic treatment; AFdecongT0, nasal airflow after
decongestant before topic treatment; AFdecongT1, nasal airflow after decongestant after topic treatment; RdecongT0, nasal resistance after decongestant before
topic treatment; RdecongT1, nasal resistance after decongestant after topic treatment; RbasalT0, nasal resistance basal before topic treatment; RbasalT1, nasal
resistance basal after topic treatment; sig, significance.
a
AF in cm
2
/s; R in Pa/cm
2
/s.
b
p< 0.05.
NP294 Ear, Nose & Throat Journal 100(6)
Authors’ Note
Giuseppina Marcuccio and Domenico Testa contributed equally to
this work.
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest
with respect to the research, authorship, and/or publication of this
article: All participants in peer-review and publishing have no con-
flicts of interest since they have no financial or personal relationship
that might bias or be seen bias their work.
Funding
The author(s) received no financial support for the research, author-
ship, and/or publication of this article.
ORCID iD
Giuseppina Marcuccio https://orcid.org/0000-0001-9211-5523
Gaetano Motta https://orcid.org/0000-0001-7899-5691
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