MODERN PHARMACOTHERAPY IN CHRONIC RHINOSINUSITIS

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MODERN PHARMACOTHERAPY IN CHRONIC RHINOSINUSITIS

Abdurakhmonov Ilhomjon Rustamovich

Head of the Department of Clinical Pharmacology, Samarkand State Medical University, PhD

Abduvohidov Shokhrukhmirzo Muzaffar oʻgʻli

Student of the Faculty of Pharmacy, Samarkand State Medical University, group 509

https://doi.org/10.5281/zenodo.14781948

Abstract.

The issues of diagnosis and adequate treatment of MS remain relevant today, as

this disease is one of the most common diseases worldwide [1. ]. Thus, up to 15% of the adult

population suffers from various forms of MS, in children this disease is even more common;

Otorhinolaryngologists and primary care physicians encounter MS every day in their practice. It

should be noted that in many European countries and America, the main role in the treatment of

uncomplicated forms of the disease is played by the general practitioner. It should be noted that

acute and chronic MS leads to a significant decrease in the quality of life index, comparable to

data on heart disease and obstructive pulmonary disease [2-4].

Keywords:

acute MS (ARS) (<3 months); recurrent ARS (2-4 episodes of acute sinusitis

per year); chronic MS (CRS) (>3 months); CRS exacerbation (worsening of existing symptoms

and/or emergence of new symptoms).

Introduction

The EP3OS 2012 guidelines (European Guidelines for the Management of Rhinosinusitis)

have developed a similar classification. Depending on the duration of the disease, the following

are distinguished: ARS (disease duration less than 12 weeks and complete disappearance of

symptoms after recovery), recurrent MS (1 to 4 episodes of acute sinusitis per year, periods

between exacerbations lasting at least 8 weeks, during which there are no symptoms of the disease,

no treatment is carried out) and CRS (presence of symptoms for more than 12 weeks) [6].

In the EP3OS 2012 guidelines, the severity of MS is determined based on a subjective

assessment of the severity of the main symptoms of the disease (nasal congestion, nasal discharge,

facial pain and decreased sense of smell) using a visual analogue scale (VAS). For this, the patient

is asked to mark the intensity of the symptoms on a 10-cm segment, where 0 corresponds to the

absence of complaints and 10 - their maximum severity. In this case, 0-3 points correspond to a

mild course of MS, >3-7 - moderate, >7-10 - severe course of the disease [6].

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Etiology and pathogenesis

Acute MS usually occurs against the background of acute respiratory viral infection

(ARVI). The most common pathogens are rhinoviruses and coronaviruses, as well as influenza,

parainfluenza and adenoviruses. Viral infection leads to pathological changes in the mucous

membrane of the nasal cavity and nasal passages, including its swelling, damage to the ciliary

epithelium, obstruction of the natural sinus ostia, impaired ventilation and secretion evacuation,

etc. All this tends to add bacterial superinfection. The most important pathogens in the etiology of

ARS are Streptococcus pneumoniae and Haemophilus influenzae [7]. In ARS, the maxillary

sinuses and cells of the ethmoid labyrinth are most often affected, and the process can be unilateral

or bilateral. The frontal and sphenoid sinuses can also be affected.

The etiology and pathogenesis of CRS are still not fully understood. The proposed

etiological factors are bacterial and fungal infections; biofilm formation; superantigen stimulation

of the immune system; anatomical abnormalities in the area of the osteometatarsal complex; ciliary

dysfunction; allergy, immunodeficiency and genetic predisposition [1]. Currently, the most

popular theory of the pathogenesis of MS is the rhinogenic theory [2,3], according to which chronic

inflammation of the mucous membrane of the urinary tract is a consequence of impaired aeration

of their aeration [8-10].

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Special forms of CRS include polypous rhinosinusitis (PRS), characterized by the

formation and recurrent growth of polyps, and odontogenic sinusitis. Thus, it can be said that HRS

is a heterogeneous group of conditions. There are banal (neutrophilic) forms of CRS, characterized

by the Th1-polarized nature of the inflammatory process and occurring with an increase in the

content of anti-inflammatory mediators IFN-γ, IL-8 and TGF-β. In PRS, inflammation is Th2-

polarized with a predominance of IL-5, IL-13 and IgE. According to modern concepts, the

pathogenesis of CRS is based on the constant recruitment of neutrophils and other

immunocompetent cells to the mucous membrane of the pulmonary artery, and the immune

response is carried out due to the synthesis of proinflammatory cytokines, the level of their

production. directly affects the activity of the inflammatory process. In widespread forms of CRS,

as in the acute process, the inflammatory cellular infiltrate is represented mainly by neutrophils.

In PRS, the number of eosinophils reaches 50% or more, and in CRS, which is not accompanied

by polyp formation, it is approximately 2% [11].

Research

methods

According to EP3OS 2012, acute viral rhinosinusitis is distinguished, which is almost

always accompanied by a cold. The duration of symptoms is less than 10 days. If the symptoms of

rhinosinusitis worsen after 5 days of illness or persist after 10 days, then we are talking about acute

post-viral rhinosinusitis. Approximately 2% of these patients develop acute bacterial

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rhinosinusitis. Its occurrence can be suspected when the disease worsens after an initial mild stage,

purulent discharge from the nasal cavity (more often on one side), severe facial pain (also usually

unilateral), an increase in div temperature. Above 38º, as well as an increase in ESR and C-

reactive protein in a blood test [6].

When collecting anamnesis, attention is paid to the acute onset of typical complaints

against the background of acute respiratory viral infections. During previous rhinoscopy, swelling

and hyperemia of the nasal mucosa, as well as purulent discharge, usually on one side, are

observed. The absence of discharge from the nasal cavity may indicate obstruction of the natural

anastomosis and impaired drainage of the affected sinus. Examination of the oral cavity and

pharynx allows you to see the flow of secretions along the posterior wall of the pharynx, as well

as to exclude the odontogenic nature of sinusitis. Interestingly, EP3OS 2012 does not recommend

X-ray examination in uncomplicated MS [6]. In our country, it is customary to perform ONP

radiography in the naso-occipital projection if maxillary sinusitis is suspected, and nasofrontal if

frontal sinusitis is suspected. However, it should be understood that during ARVI, a decrease in

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pulmonary artery pneumatization is observed in 90% of cases. Therefore, when prescribing

treatment, it is necessary to be guided, first of all, by the clinic. Along with a subjective assessment

of the severity of the disease using VAS, the doctor should also pay attention to objective signs

and remember that septic complications are possible with ARS. Therefore, when swelling appears

in the periorbital area or in the area of the ONP projection, visual impairment, severe headache,

meningeal signs or focal neurological symptoms, the patient should be urgently hospitalized in an

ENT hospital. .

Chronic MS, like any chronic disease, is characterized by alternating phases of remission

and exacerbation. In previous rhinoscopy and CRS, during endoscopic examination of the nasal

cavity, anatomical anomalies in the area of the ostiomeatal complex are often detected, which

prevent adequate drainage of the OMS and contribute to the stagnation of secretion in them

(bullous middle nasal concha, appendage. anastomosis of the maxillary sinus, spine and ridges of

the nasal septum, etc.). Hyperemia, polypous changes in the mucous membrane of the nasal cavity,

purulent discharges can also be observed. For polypous MS, complaints of difficulty in nasal

breathing are typical, and rhinoscopy reveals polyps that partially or completely block the nasal

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cavity. Odontogenic sinusitis may be caused by oro-antral fistula [12] after extraction of maxillary

teeth or by the presence of a foreign div in the maxillary sinus - a filling material that has fallen

there during the filling of the dental canals.

Principles of therapy

Treatment of mild ARS includes the administration of analgesics, decongestants, and some

herbal remedies, as well as nasal irrigation with isotonic saline. In moderately severe cases,

intranasal glucocorticosteroids (mometasone furoate) may be additionally prescribed. In severe

cases and acute bacterial rhinosinusitis, systemic antibiotics should be prescribed, and if there is

no positive effect within 48 hours, the patient should be referred to an ENT specialist [6].

The main method of treatment of moderate and severe forms of acute rhinosinusitis is

systemic antibiotic therapy based on knowledge of typical pathogens. In outpatient practice, drugs

are prescribed orally, and in inpatient treatment, stepwise therapy is justified: parenteral

administration of the drug for 3-4 days, then switching to oral administration. The drugs of choice

are semi-synthetic penicillins (Amoxicillin or Amoxicillin / clavulanic acid) or 2-3 generation

cephalosporins (Ceftibuten, Cefuroxime). In case of penicillin intolerance, modern macrolides

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(Clarithromycin, Azithromycin) and respiratory fluoroquinolones (Moxifloxacin, Levofloxacin)

are used.

Intranasal glucocorticosteroids and nasal irrigation with isotonic saline have been shown

to be effective in controlling the symptoms of chronic MS. In the case of a persistent course, long

courses of antibacterial therapy are possible [6], in which case, as a rule, 14- and 15-membered

macrolide antibiotics are used (Clarithromycin 250 mg/day; Erythromycin 300 mg/day). Up to 3-

6 months). Chronic MS exacerbations are treated in the same way as acute MS, that is, short

courses of systemic antibiotics are prescribed as indicated. It should be noted that in European

guidelines, a short course of antibiotic therapy is considered to be less than 4 weeks [1]. In the

absence of a positive effect, surgical treatment is indicated, and in the event of complications,

urgent.

Recently, herbal preparations with anti-inflammatory and mucolytic effects have proven

their effectiveness in the treatment of ARS. In this regard, the herbal medicine Sinupret deserves

attention. It contains components of several medicinal plants: gentian root, verbena and sorrel herb,

primrose and elderberry. Sinupret reduces the viscosity of secretions by stimulating the secretory

cells of the bronchial mucosa and bronchial tubes. The pathogenetic feature of this drug is its

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ability to block the exudation phase and reduce the permeability of the vascular wall. Due to this,

the severity of swelling of the nasal mucosa decreases and the evacuation of secretions from the

nasal cavity becomes easier. Sinupret increases the activity of the ciliary epithelium, improves the

rheological properties of exudate and accelerates the evacuation of secretions from the respiratory

tract, that is, it has both mucolytic and mucokinetic effects. Individual components of Sinupret

have antioxidant and antiviral activity [13-15]. In addition to antiviral activity, Sinupret has

immunomodulatory activity (21, 22): it increases the number of phagocytes by 40% and

phagocytosis activity, as well as the concentration of interferons α and γ (22). Under the influence

of the drug Sinupret, local and general factors of the div's immune defense are activated, and the

duration of acute respiratory diseases is reduced (22).

Furthermore, it is recommended not to use Sinupret in combination with antibiotics, as it

may enhance their effects [16, 17].

Sinusitis is one of the most common human diseases. This term refers to inflammation of

the mucous membrane of the paranasal sinuses (PNS). Depending on the lesion of one or another

sinus, maxillary sinusitis or sinusitis, ethmoiditis (inflammation of the ethmoid sinuses), frontal

sinusitis (inflammation of the frontal sinus), sphenoiditis (inflammation of the sphenoid sinus), as

well as a combined lesion of several or all sinuses - polysinusitis and pansinusitis. Since

inflammation in the nasal cavity is always accompanied to varying degrees by pronounced

inflammatory changes in the mucous membrane of the nasal cavity, the term "rhinosinusitis" is

recommended for wider use [3].

Research results:

The epidemiology of rhinosinusitis is constantly and actively studied by leading domestic

and foreign experts. The current understanding of the prevalence of the disease in Russia is based

on the results of the national study CHRONOS 2012. The main foreign sources reflecting the most

up-to-date information on diagnostic criteria, treatment methods, as well as data. The prevalence

of rhinosinusitis is documented in the EPOS document (European Position on Rhinosinusitis and

Nasal Polyps) 2012, IDSA (Infectious Diseases Society of America) 2012 clinical guidelines, CFF

clinical guidelines (Canadian Family Physician Fact Sheet) 2013. The diagnosis of rhinosinusitis

is made on the basis of statistical surveys on the presence of symptoms of the disease, as well as

visits to medical institutions. Based on this, it is known that approximately 15% of the population

in the world suffers from various forms of rhinosinusitis. It is believed that in European countries,

rhinosinusitis occurs in every 7 people every year. In the United States, 31 million cases of

rhinosinusitis are recorded annually, and in Russia - more than 10 million cases per year. The

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number of patients with this pathology increases significantly every year. According to a number

of authors, sinusitis accounts for 15 to 36% of the total number of diseases in ENT hospitals.

Rhinosinusitis is among the ten most common diagnoses in outpatient practice. The incidence of

chronic rhinosinusitis (CRS), which has doubled over the past 10 years, is attracting the attention

of specialists. According to some data, this disease is currently in first place among all chronic

diseases [2, 5, 7].

CRS is an inflammatory disease of the mucous membrane of the nasal cavity and nasal

passages. The diagnosis of "chronic rhinosinusitis" is made by the presence of two main

symptoms: nasal congestion and runny nose, as well as the presence of additional symptoms:

headache with predominant localization in the area of the nasal passages, worsening of pain. sense

of smell. The duration of these symptoms should be more than 12 weeks. The diagnosis should be

confirmed by endoscopic examination (swelling of the mucous membrane and / or swelling of the

mucous membrane in the area of the middle / upper nasal passages) and / or computed tomography

(changes in the mucous membrane. ostiomeatal complex and / or ONP) [8].

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CRS significantly affects the patient's quality of life. Thus, K. McDonald et al. According

to them, in CRS it is the same as in patients with malignant tumors, asthma and arthritis [9]. The

cost of treating CRS in the United States is impressive and amounts to $ 8.6 billion per year [10].

CRS is a complex polyetiological disease that is not yet fully understood. The role of

various predisposing factors and pathogenetic mechanisms in the development of CRS has not yet

been clearly elucidated. It is believed that chronic inflammation in the pulmonary artery develops

against the background of impaired ventilation due to obstruction of the outflow tract. In this

regard, various variants and anomalies of the structure of intranasal structures and the nasal cavity

are of great importance, for example, deviation of the nasal septum, middle nasal concha, Haller's

cell and other variants of the development of the nasal cavity. ethmoid labyrinth. These anatomical

features can be detected, first of all, by performing computed tomography of the NP, which is used

to diagnose the prevalence and nature of the pathological process [1].

The leading role in the pathogenesis of CRS is played by pathological changes in the middle

nasal passage - the ostiomeatal complex. The narrowness and complexity of the anatomy of this

region are important predisposing factors for the development of CRS. Under such conditions,

pathogenic microorganisms have the opportunity to have prolonged contact with the mucous

membrane, as well as a favorable environment for vital activity [4].

In chronic sinusitis, the bacterial spectrum is more represented by microbial associations:

among the pathogens in 48% of cases, obligate (Prevotella - 31%, Fusobacterium - 15%) and

facultative (Streptococcus spp. - 22%). ) anaerobes are distinguished. Aerobes are found in 52%

of patients: various Streptococcus spp. – 21%, Haemophilus influenzae (hemophilus influenzae) –

16%, Pseudomonas aeruginosa (pseudomonas aeruginosa) – 15%, Staphylococcus aureus (golden

staphylococcus) and Moraxella spp. (moraxella) - 10% each. The predominance of anaerobes in

chronic sinusitis can be explained by the changes occurring in the sinuses: first of all, deterioration

of sinus aeration and a decrease in pH, which creates favorable conditions for the development of

microorganisms. Fungal sinusitis caused by Aspergillus, Phycomycetes (Mucor, Rhizopus),

Alternaria, and Candida fungi is a special form of chronic sinusitis and is much less common than

bacterial sinusitis [11].

An important factor in the development of CRS is inadequate antibacterial therapy of the

inflammatory process in the maxillary sinus at the prehospital stage, which leads to long-term

retention of the microbial agent inside the sinus cavity and contributes to persistent morphological

changes in the mucous membrane, mainly of a productive type - metaplasia of the ciliated

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epithelium into stratified squamous epithelium and the development of dysplasia of I-II severity

[12].

Conclusion:

Based on the above information, the goals of CRS treatment are to restore aeration and

reduce the inflammatory process in the ER, as well as to improve the patient's quality of life by

achieving stable remission of the disease. CRS therapy is based on long-term use of intranasal

glucocorticosteroids (ICS). Drugs in this group have anti-inflammatory, anti-edematous effects,

improve the drainage function of the common urinary tract anastomoses and are used in courses

of at least 3 months. At the same time, nasal breathing and sense of smell improve, and the severity

of symptoms of nasal discharge and postnasal drip decrease [13]. Recommendations for the use of

ICS in CRS are based on a high level of evidence similar to irrigation therapy (washing the nasal

cavity with saline) [8, 14].

Currently, there is no consensus on the effectiveness of antimicrobial drugs in CRS. There

is no doubt about the need to use this group of drugs in the acute phase of the disease. In this case,

the approach to the choice of antimicrobial drug is empirical, similar to that for acute bacterial

rhinosinusitis (amino-protected penicillins, modern cephalosporins, macrolides, "respiratory"

fluoroquinolones) [15].

The role of bacterial biofilms in the course of CRS is not fully understood. The formation

of biofilms on the surface of the nasal cavity and ENT mucosa reflects a universal survival strategy

of bacteria (Haemophilus influenzae, Pseudomonas aeruginosa, etc.) in less than optimal

conditions and may serve as a source of recurrent exacerbations. In CRS. Targeting biofilms may

be useful in the treatment of patients with CRS [8].

To determine the nature of the microflora of the urinary tract, it is recommended to perform

a puncture and collect the contents for microbiological examination. As a therapeutic measure,

punctures of the pulmonary artery are used when there are indications for evacuation of

pathological contents and the introduction of locally acting drugs.

When a fungal infection of the urinary tract is detected, especially in the postoperative

period, antimycotics (amphotericin B) are used for local administration. If the presence of an

invasive form of fungal sinusitis is confirmed, systemic antifungal drugs should be used.

The role of mucolytics and herbal medicines in the treatment of CRS is discussed. Given

the low level of evidence [8], these groups of drugs can be used in combination with the main ones

to improve mucus transport and provide additional anti-inflammatory effects.

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Today, conservative treatment of CRS does not always lead to recovery or stable remission

of the disease. If adequate drug therapy is ineffective, the patient is recommended to undergo

functional endoscopic microsurgery, the main goals of which are to eliminate the blockage of the

sinus ostium and restore sinus ventilation. Surgical treatment is also necessary to correct anomalies

in the structure of intranasal structures and remove foreign and fungal bodies of the nasal cavity.

In most cases, minimally invasive surgery, performed according to the indications, allows to

eliminate the inflammatory process and improve the patient's quality of life [16].

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