26
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(ISSN
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VOLUME
04
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ABSTRACT
Treatment of polyposis rhinosinusitis is currently an urgent problem of modern otorhinolaryngology. A significant
increase in the prevalence of the disease with polypous rhinosinusitis (from 5 to 20%) and a high frequency of relapses
are due to insufficiently studied pathogenetic mechanisms for the development of the polypous process and the lack
of effective methods of treatment. The combination of this disease with bronchial asthma, the asthmatic triad and
the addition of a purulent process significantly complicate the course and treatment of patients with polypous
rhinosinusitis. In accordance with the multifactorial theory, the development of polyposis rhinosinusitis occurs as a
result of mechanical, physical factors, as well as the penetration of microbial, fungal and viral agents on the surface of
the nasal mucosa. This leads to the activation of the mechanisms of local immunity, which is a whole complex of
specific and non-specific reactions that provide the barrier function of the mucous membrane. Long-term exposure
to various agents leads to a decrease in the activity of the protective barrier of the nasal mucosa and stimulates the
development of an infection-dependent allergic process. The latter is accompanied by a violation of immune
homeostasis in the form of secondary immunodeficiency, the formation of persistent immune eosinophilic
inflammation, leading to remodeling of the nasal mucosa and the development of polypous rhinosinusitis.
KEYWORDS
Polyps, nasal cavity, rhinosinusitis, allergy, bronchial asthma.
Research Article
MODERN METHODS OF TREATMENTOF POLYPOID RHINOSINUSITIS
Submission Date:
January 07, 2022,
Accepted Date:
January 17, 2022,
Published Date:
January 27, 2022 |
Crossref doi:
https://doi.org/10.37547/TAJMSPR/Volume04Issue01-04
U.Sharipov
Tashkent State Dental Institute, Uzbekistan
Journal
Website:
https://theamericanjou
rnals.com/index.php/ta
jmspr
Copyright:
Original
content from this work
may be used under the
terms of the creative
commons
attributes
4.0 licence.
27
Volume 04 Issue 01-2022
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VOLUME
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INTRODUCTION
The chronic course of the inflammatory process in the
paranasal sinuses leads to significant changes in the
state of humoral immunity, changes in the
concentration of class A, M, and G immunoglobulins,
suppression of the phagocytic activity of neutrophils
and macrophages [1–4]. The level of immunoglobulin E
in the blood serum is a marker of "preclinical"
registration of allergy in nasal polyposis, which can
serve as a background for changes in the level of
reactivity of the div [10-11]. According to a number of
authors, dysfunction of the mucous membrane of the
nasal cavity and paranasal sinuses is accompanied by
metaplasia, desquamation of the epithelium and, as a
result, a violation of its motor activity [5-9]. However,
to date, the results of objective fundamental studies of
the motor activity of the ciliated epithelium in chronic
polypous rhinosinusitis are not available in the
available
literature.
Over
the
past
decade,
corticosteroid drugs that affect the main links in the
pathogenesis of the polypous process have been the
most effective in the treatment of polypous
rhinosinusitis [12]. The appointment of short courses of
systemic corticosteroid therapy in the treatment of
polypous rhinosinus, combined with bronchial asthma
or the asthmatic triad, accompanied by frequent
relapses of the polyposis process, allows achieving
long-term remission and significantly improving the
quality of life of patients [13-16]. However, due to the
large number of side effects, systemic corticosteroid
therapy is not widely used in clinical practice.
According to the literature, long-term use of these
drugs, due to a pronounced immunosuppressive
effect, weakens the protective immune responses of
the div due to inhibition of production and increased
apoptosis of immature or activated T- and B-
lymphocytes. This leads to a violation of the synthesis
of IgA, IgG, IgM, since the latter are derivatives of B-
lymphocytes [22]. The emerging deficiency of
immunoglobulins becomes an additional factor
stimulating the weakening of the phagocytic activity of
neutrophils, since IgM and IgG direct phagocytes to the
infectious focus, thereby regulating the stages of
phagocytosis. At the same time, against the
background of taking systemic corticosteroids, the
work of the hypothalamic-pituitary-adrenal system is
inhibited, which is accompanied by a progressive
decrease in the synthesis of endogenous cortisol [14].
The concentration of this hormone is important in
maintaining the functional state of the div's immune
system [23,24]. A high level of cortisol is a necessary
condition for a normal response to infection, while a
low level of the hormone can in some way contribute
to the development of autoimmune reactions and lead
to destabilization of the lysosome membrane,
increased capillary permeability, a weakening of the
anti-inflammatory effect of cortisol, and an increase in
the likelihood of a secondary infection [17-21]. In this
regard, the level of cortisol and its correlation with
indicators
of
nonspecific
resistance
and
immunoglobulins M, G and A are a prognostically
important marker of the state of the div's immune
system.
In this regard, the development of principles for
choosing the tactics of treating patients with polypous
rhinosinusitis using corticosteroid drugs based on the
study of the functional state of the nasal mucosa and
monitoring the indirect effect of cortisol concentration
on the state of humoral immunity in patients with
polypous rhinosinusitis is relevant and novel.
28
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MATERIAL AND METHDOS
The work was performed in the multidisciplinary clinic
of the 3rd base of the TMA ENT department. We
examined 128 patients with polypous rhinosinusitis
aged 18 to 50 years, including 83 men and 45 women.
Patients were divided into two groups: main and
comparison. The main group consisted of 98 patients
who were prescribed a course of treatment with
methylprednisolone for 14 days, starting with 40 mg
per day, then for 14 days the dosage was gradually
reduced to a maintenance dose of 4 mg per day and
simultaneously administered the topical steroid
mometasone furoate, 2 inhalations per day. each
nostril 2 times a day for 3 months. The comparison
group included 30 patients who received only the
intranasal corticosteroid mometasone furoate at the
same dosage for 3 months.
Exclusion criteria from the study were: age under 18
years, presence of intolerance to corticosteroids,
breast-feeding, purulent discharge from the nose,
previous treatment with systemic corticosteroids less
than 3 months ago, and a history of severe somatic
diseases and immunodeficiency conditions in patients
that are a contraindication to steroid therapy.
Diagnosis of polyposis rhinosinusitis was carried out on
the basis of patient complaints, history taking,
objective examination data and instrumental methods
of research: anterior active rhinomanometry on the
RINO-SYS apparatus, endoscopy of the nasal cavity and
computed tomography of the paranasal sinuses
according to 4 stages of severity of paranasal sinus
lesions according to G. Z. Piskunov (2002) [16].
The state of mucociliary clearance of the nasal mucosa
was analyzed using television microscopy with
registration of motor activity of cilia on the surface of
the ciliated epithelium and subsequent computer and
mathematical processing of the results [8, 21, 22]. To
assess the state of humoral immunity of the div,
patients underwent laboratory diagnostics of
immunoglobulins A, M, G, determination of the
phagocytic activity of neutrophils and the phagocytic
index. For the purpose of differential diagnosis of
allergic conditions, patients underwent a laboratory
blood test to determine the level of total
immunoglobulin E in the blood serum. The modulating
effect of the hypothalamic-pituitary-adrenal system on
the state of humoral immunity was analyzed by
recording the concentrations of the bound fraction of
cortisol in the blood and the free form of the hormone
in saliva and with simultaneous monitoring of the levels
of specific antibodies and indicators of nonspecific
resistance. Blood and saliva sampling was performed
at 8–9 am, taking into account the peak of the
physiological secretion of the hormone by the adrenal
cortex [18]. To monitor the state of humoral immunity
and the function of the hypothalamic-pituitary-adrenal
system, on the 7th day of taking methylprednisolone
and 2 weeks after the withdrawal of systemic
corticosteroids in patients of the main group and the
comparison group, venous blood and saliva were taken
to determine the level of the bound fraction of cortisol
and the free form of the hormone in saliva. The
obtained parameters of the hormone were analyzed
simultaneously
with
the
concentrations
of
immunoglobulins A, G, E and M. Two weeks after the
start of treatment, simultaneously with the
registration of the levels of specific antibodies in the
systemic circulation, nonspecific resistance indicators
were recorded in both groups: phagocytic activity of
neutrophils and phagocytic index.
The effectiveness of the ongoing pharmacotherapy
was assessed by the dynamics of changes in nasal
symptoms of the disease on the 7th day of treatment,
2 weeks after the start of therapy, after the course of
treatment. As objective criteria for the effectiveness of
29
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the therapy, 3 months after the course of treatment,
the dynamics of data from computed tomography of
the paranasal sinuses and video endoscopic picture of
the nasal cavity were evaluated. Patients with a nasal
septum without perforations and, according to the
results of an endoscopic examination of the nasal
cavity, stage I–III of the prevalence of the polyposis
process according to the classification of G. Z. Piskunov
(2002), a comparative analysis of the main indicators of
anterior active rhinomanometry before treatment and
3 months after it was performed. Research results.
During the examination of patients, it was found that
the incidence of polyposis rhinosinusitis in men is 2
times higher than in women.
The average age of patients is 43.5 years. In 20 (15%)
patients, the polyposis process was combined with
bronchial asthma, and 17 (13%) patients had a complete
asthmatic triad in history. In 23 (18%) of the examined,
the course of the inflammatory process in the nasal
cavity and paranasal sinuses was of a polypous-
purulent nature, however, at the time of the
examination, the patients were in remission. The main
clinical symptoms of polyposis rhinosinusitis in patients
were a pronounced violation of nasal breathing, a
decrease in the sense of smell, up to its complete
absence, and mucous discharge from the nose. The
analysis of humoral immunity parameters in the
subjects of the main group and the comparison group
did not reveal any statistically significant deviations (p
> 0.05) from the physiological norms of specific
antibodies in the blood serum. At the same time, the
concentration of immunoglobulin G was 12.5±3.3 g/l,
immunoglobulin A - 2.28±0.65 g/l, immunoglobulin M -
1.41±0.58 g/l. It should be noted that in patients with
frequent purulent exacerbations of polyposis
rhinosinusitis, a decrease in the level of IgG in the blood
serum from 6.2 to 7.2 g/l was recorded, and the content
of IgA and IgM corresponded to the norm. The results
obtained in this category of patients indicate a
violation of the second line of the immune response,
responsible for the regulation and enhancement of
phagocytosis processes upon repeated encounter with
the same antigen.
Among the indicators of nonspecific resistance in both
groups, there was a decrease in the phagocytic activity
of neutrophils to 43.5±3.7% and a decrease in the
percentage of neutrophils involved in phagocytosis to
2.55±0.65. At the same time, in patients with purulent-
polypous rhinosinusitis, a statistically significant
decrease in phagocytic activity of neutrophils to
32.5±1.5% and a phagocytic index from 0.96 to 1.66
compared to physiological parameters were revealed.
The decrease in the phagocytic index, the phagocytic
activity of neutrophils is primarily due to the long
course of the polyposis process, leading to changes in
the humoral immunity system, which, in turn, is a
predisposing factor in the development of infectious
processes.
The analysis of IgE parameters revealed a statistically
significant (p < 0.05) increase in the values of specific
antibodies up to 208.8±93.4 g/l in patients with a
history of bronchial asthma or Vidal's triad, compared
with patients without concomitant pathology of the
respiratory tract and aggravated allergic history, which
indicates the role of allergy in the development of the
polyposis process. In subjects without a burdened
allergic
anamnesis,
the
concentration
of
immunoglobulins E in the blood serum was 45.6±8.7
g/l. The level of the free fraction of cortisol in saliva at
the peak of secretion in the morning in patients of the
main and control groups had no statistical differences
and amounted to 29.4±5.3 nmol/l, and the
concentration of the bound form of the hormone in the
blood
serum
was
349.2±82.3
nmol/l,
which
corresponds to the norm.
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According to the results of computed tomography of
the paranasal sinuses and the data of endoscopic
sinusoscopy in the main group: stage I lesions of the
paranasal sinuses with a polypous process were
detected in 4 (4.5%) patients, stage II, accompanied by
the presence of single polyps in sinusitis, was
diagnosed in 18 (18%) patients , III stage of polypous
rhinosinusitis with involvement of 2/3 of the volume of
the paranasal sinuses in the polyposis process was
registered in 63 (64.5%) patients, stage IV with a total
lesion of the paranasal sinuses - in 13 (13%) people. In
the comparison group: stage I paranasal sinus
involvement by polyposis was detected in 3 (10%)
patients, stage II - in 15 (50%) patients, stage III
polypous rhinosinusitis - in 11 (36.7%) patients, stage IV
with total paranasal sinuses - in 4 (13.3%) people.
When conducting anterior active rhinomanometry in
patients of the comparison group and the main one,
with stage I of the development of the polyposis
process, before the introduction of vasoconstrictor
drugs, a mild degree of nasal obstruction was
determined, mainly due to swelling of the mucous
membrane of the nasal cavity and paranasal sinuses.
After decongestants in both groups, there was a
decrease in total nasal resistance at a pressure of 150
Pa and an increase in total nasal flow to physiological
values. The dynamics of the main indicators of the
anterior active rhinomanometry at 150 Pa is presented
in the table. In the presence of stages II and III of the
polyposis process, anterior active rhinomanometry
revealed moderate and high degrees of nasal
obstruction in patients of both the main and
comparison groups. At the same time, there were no
significant differences before and after anemization of
the nasal mucosa in terms of total nasal resistance and
total nasal flow.
In the study of mucociliary clearance by television
microscopy with the registration of motor activity of
cilia on the surface of the ciliated epithelium in both
groups of observation, a pronounced motor activity of
cilia was found in the region of the nasal septum, on
the surface of the mucous membrane of the inferior
turbinate and in the polyp zone. The average frequency
of cilia beating was 9, 8 and 8 ± 0.3 Hz, respectively,
which had no significant differences from the healthy
group [22]. Against the background of the treatment,
patients of the main group showed a pronounced
positive trend in terms of a decrease in the main clinical
symptoms compared with the comparison group.
Already on the 7th day of treatment, 57 (58%) patients
noted a significant improvement in nasal breathing,
improved sense of smell and a decrease in nasal
discharge. Almost complete restoration of nasal
breathing and olfactory function of the nose, as well as
the disappearance of nasal discharge in the main group
occurred on the 14th day of therapy in 29 (30.5%)
patients, in 38 (39%) patients - 1 month after the start
of treatment , at the end of the course of treatment -
in 51 (52%) patients.
In the comparison group, the main nasal symptoms
were effectively stopped in 4 (13%) patients after 1
month from the start of therapy and in 6 (20%) patients
- at the end of the course of treatment. Analysis of IgE
parameters after systemic corticosteroid therapy in
the main group showed a pronounced decrease in the
level of this immunoglobulin in the blood serum to 67
± 23 g/l in patients with bronchial asthma, in those
examined without a aggravated allergic history, the
concentration of IgE corresponded to the values
before treatment. In the comparison group, all
patients showed no statistically significant differences
in the content of IgE in the blood (p> 0.05) before and
after therapy. Control over fluctuations in the level of
cortisol in the blood and saliva in the main group
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revealed on the 7th day of taking methylprednisolone
a statistically significant decrease in the concentration
of this hormone (p < 0.05) in the blood serum to 81.5 ±
23.4 nmol/l and a decrease in free fractions of cortisol
in saliva up to 12.5±9.6 nmol/l, which indicates drug
suppression of the activity of the adrenal cortex. In the
comparison group, on the 7th day of therapy and after
2 weeks of treatment, there were no statistically
significant differences in relation to the initial values of
cortisol in the blood and saliva (p > 0.05).
With subsequent registration of cortisol concentration
2 weeks after systemic corticosteroid therapy in the
main group, the restoration of physiological levels of
hormone secretion in the blood to 303±34 nmol/l and
in saliva to 33±11 nmol/l was observed. Against the
background of taking methylprednisolone with a
decrease in the concentration of cortisol in the div on
the 7th day of treatment in the main group, there was
a slight decrease in the phagocytic activity of
neutrophils to 38.5±2.5% and a decrease in the
phagocytic index to 2.4±0.7. In the comparison group,
the indicators of nonspecific resistance were also
below the norm. 2 weeks after the withdrawal of
systemic corticosteroids in the main group, there was
an increase in nonspecific resistance: an increase in
phagocytic activity up to 44.4±7.5% and an increase in
the phagocytic index up to 2.8±0.9, which indicates the
mobilization of the div's protective function. In the
comparison group, these indicators corresponded to
the initial low level before the start of treatment.
Laboratory diagnostics of the levels of specific
antibodies on the 7th day of therapy and 2 weeks after
the start of the course of corticosteroid therapy in both
groups did not reveal statistically significant changes in
the concentration of class A, M, and G
immunoglobulins (p > 0.05).
However, it should be noted that simultaneously with
a decrease in cortisol secretion in the middle of the
course
of
methylprednisolone,
a
statistically
insignificant decrease in nonspecific resistance and a
compensatory increase in the concentration of IgA in
the blood up to 2.7 ± 0.5 g/l, IgM - 1.47 ± 04 were noted
in the main group. g/l, IgG – 15.4±3.5 g/l. With the
subsequent normalization of the hormone level in the
blood and saliva (after the abolition of systemic
corticosteroid therapy) in the main group, a slight
decrease in IgA in the blood to 2.59 ± 0.5 g/l, IgM - 1.04
± 0.4 g/l and IgG - 13.4 ± 3.5 g/l, improvement in non-
specific resistance, which suggests the absence of a
direct inhibitory effect of a short course of systemic
corticosteroid therapy on the humoral immunity
system and the correlation of cortisol levels with non-
specific indicators of the latter.
After treatment, 64 (65%) of the examined patients of
the main group objectively recorded an improvement
in the function of nasal breathing, in the comparison
group, positive dynamics was observed only in 2 (6%)
patients who had stage I lesions of the paranasal
sinuses with a polypous process. At the same time, in
patients of the main group with stage I polyposis,
before and after anemization of the nasal mucosa, the
indicators of total nasal resistance and total nasal flow
corresponded to the norm; cPa/ml and an increase in
the total nasal flow up to 745±32 ml/s both before and
after anemization of the nasal mucosa, in 9 (10%)
patients with stage III, a severe degree of nasal
obstruction remained both before and after the
treatment , which is due to the presence of fibrous
polyps in the nasal cavity, 42 (43%) of the examined
patients showed an improvement in nasal breathing
due to a decrease in the total nasal resistance and an
increase in nasal flow. In patients of the comparison
group who had stages II and III of polyposis
development, there were no significant differences in
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the analysis of the main indicators of anterior active
rhinomanometry before and after the course of
treatment.
3 months after the course of treatment, 61 (62%)
patients of the main group showed positive dynamics
according to computed tomography of the paranasal
sinuses and endoscopy of the nasal cavity. All subjects
of the main group, who had stage I of the polyposis
process according to the classification of G. Z. Piskunov
(2002),
after
treatment,
had
satisfactory
pneumatization of the paranasal sinuses, a significant
reduction in the degree of damage to the paranasal
sinuses by the polyposis process was noted in 12 (12%)
patients with stage II polyposis and in 48 (49%) patients
with stage III lesions of the paranasal sinuses by a
polyposis process, in 9 (9%) patients with stage IV, a
slight positive trend was registered according to CT of
the paranasal sinuses and endoscopy of the nasal
cavity, which made it possible to further reduce the
amount of surgical intervention and reduce nasal
symptoms. In 11 (11%) patients of the main group, the
dynamics against the background of systemic
corticosteroid therapy was not revealed, which is due
to the predominance, according to endoscopy, of the
presence of fibrous polyps. This category of patients
subsequently underwent planned surgical treatment.
In the comparison group, according to the data of
computed tomography of the paranasal sinuses and
endoscopy of the nasal cavity, positive dynamics was
observed in 2 (7%) patients with stage I of the polyposis
process and in 3 (10%) with stage II of the polyposis, in
the rest of the examined patients - without changes.
The follow-up period for patients ranged from 3
months to 2 years. During this time, the recurrence of
the polyposis process in the main group was observed
after 7 months in 8 (8%) patients in connection with the
transferred ARVI, after 1.5 years, the exacerbation of
the polyposis process was detected in 26 patients
(26%). In the comparison group, 19 (63%) had a relapse
of polyposis rhinosinusitis 3 weeks after the end of the
course of treatment.
When conducting television microscopy after a course
of treatment, a high motor activity of the cilia of the
ciliated epithelium was established, which remained in
the region of the nasal septum - up to 9.0 ± 0.2 Hz, the
lower turbinates up to 8.0 ± 0.4 and 9.0 ± 0, 3 Hz on the
surface of polyps in patients of both groups. Thus, the
appointment of systemic corticosteroid therapy in
short courses in polyposis rhinosinusitis objectively
improves the function of nasal breathing, relieves the
main symptoms of the polyposis process, suppresses
allergic reactions, does not have an inhibitory effect on
the secretion of endogenous cortisol and a
pronounced immunosuppressive effect on the
humoral immunity system, but, on the contrary,
contributes to the regulation mechanisms of
nonspecific resistance of the div. In the presence of
stages I and II lesions of the paranasal sinuses with a
polyposis process, this method of conservative
treatment allows you to control the course of the
polyposis process and avoid surgical intervention; in
stages III and IV, systemic corticosteroid therapy is
recommended for preoperative preparation of
patients, as well as anti-relapse therapy after surgery.
CONCLUSION
Polyposis rhinosinusitis is accompanied by violations of
humoral immunity. In chronic polypous rhinosinusitis,
the ciliated epithelium is preserved with pronounced
motor activity on the surface of the polypous tissue. A
short course of systemic corticosteroid therapy in
conjunction with topical intranasal steroids has a high
therapeutic efficacy and safety in the treatment of
nasal polypous sinusitis. Gradual monitoring of
fluctuations in the concentrations of free and bound
fractions of cortisol and the levels of immunoglobulins
33
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A, G and M and indicators of nonspecific resistance is a
necessary condition for the appointment of systemic
corticosteroids for nasal polyposis.
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