The role of a leukotriene receptor blocker in restoring nasal breathing in patients with polypous rhinosinusitis

Despite the large number of studies devoted to the treatment of polypous rhinosinusitis (PRS), one of the most complex and controversial issues of this problem remains the search for the most effective methods for eliminating nasal obstruction, allowing for the longest possible preservation of the adequacy of nasal breathing, due to the violation of which the human body develops as an organ , and tissue hypoxia.

Experience shows that surgical treatment of polyposis is symptomatic, standardly eliminating the “final” result of the pathological process - impaired nasal breathing, does not interrupt the development of polyposis, and therefore has virtually no effect on the duration of remission. The number of postoperative relapses remains high and often reaches 40-50% with a recurrence rate of 2-3 or more times a year [1-3].

Drug treatment of PRS, unlike surgical treatment, is pathogenetic in nature, since it has the opportunity to influence various stages of the development of the disease [4-7].

Research in recent decades has established that in the formation of the polyposis process, allergy and inflammation play an important role, during which the synthesis and release of a number of mediators occurs, including leukotrienes, characteristic of the late (chronic) phase of allergic inflammation. Leukotrienes mediate their action through receptors on the surface of respiratory epithelial cells and are an ideal target for therapeutic blockade of allergic reactions in both the upper and lower respiratory tract. It is this link in the pathogenesis of polyposis that remains poorly understood and almost inaccessible to drug intervention [8, 9].

The modern concept of “single airways”, according to which PRS is considered as one of the components of systemic pathology of the respiratory tract, served as the basis for the use of anti-leukotriene drugs for PRS, created and recommended for the treatment and prevention of bronchial asthma, allergic rhinitis and the asthmatic triad [10-13] .

Patients and methods

In accordance with the goal, based on endoscopic, clinical, laboratory and morphological indicators, the effectiveness of pharmacological control of nasal obstruction using a leukotriene receptor blocker was studied in 87 patients with PRS, aged from 22 to 76 years, whose main complaint was impaired nasal breathing.

Patients with chronic purulent-polyposis forms of sinusitis of both rhinogenic and odontogenic origin were excluded from the study.

The age of 53% of patients did not exceed 50 years. There were slightly more women - 54%, men - 46%.

Primary polyposis was diagnosed in 65.5% of patients, recurrent polyposis was diagnosed in 34.5%, with a recurrence rate of 3 or more times a year.

Among the subjects, 25.3% suffered from bronchial asthma and received treatment in accordance with federal clinical guidelines for the diagnosis and treatment of this pathology without the use of preventive therapy with leukotriene receptor antagonists. The rest were diagnosed with allergic rhinitis.

34.5% of patients were operated on repeatedly for PRS.

The control group consisted of 20 practically healthy people aged 21-26 years without impaired nasal breathing and signs of allergies.

For an objective assessment and systematization of rhinoscopic data, I.B.’s classification was used. Soldatova et al. [14], in which the prevalence of the polyposis process has 4 stages. According to this classification, in the vast majority of patients (70.1%), the volume of polypous tissue in the nasal cavity corresponded to stage III-IV.

Characterizing the prevalence of polyposis in the paranasal sinuses according to the classification of S.Z. Piskunov and G.Z. Piskunova [15], in which the authors also distinguish 4 stages, we found that in 75.8% of patients, the prevalence of polyposis in the paranasal sinuses according to computed tomography (CT) corresponded to stages I-II, i.e. did not correlate with endoscopy data and did not significantly affect nasal breathing.

An objective assessment of nasal obstruction and the processes occurring in the body of patients with PRS was carried out on the basis of data from anterior active rhinomanometry, the acid-base state of the blood and the dynamics of the concentration of leukotriene C4 (LTC4) in the blood serum. LTC4 causes swelling of the airways, mucus formation and does not directly affect bronchoconstriction, but is involved in inflammation, vascular permeability and the development of tissue fibrosis, which is the morphological basis of polyposis.

It is these properties of this mediator that determined the choice of LTC4 as a marker of allergic inflammation and the effectiveness of a leukotriene receptor antagonist in the treatment of nasal obstruction in patients with PRS.

An objective assessment of the dynamics of nasal breathing was carried out using a domestically produced serial pressotachospirograph PTS-14P-01.

The normative values of the total flow of inhaled air according to the control group were 700 ml/s, the total resistance was 0.14 Pa/cm3/s.

To characterize the level of hypoxia, the partial pressure of oxygen (pO2) and carbon dioxide (pCO2) in the blood was studied using an automatic analyzer of gases, electrolytes and CO-oxometry parameters of the cartridge type PapidLab 1200.

The normative value of blood CO2 tension according to the control group was 38.5 mmol/l, the normative value of O2 tension was 39 mmol/l.

To objectively assess the dynamics of allergic inflammation in patients with PRS, the concentration of LTC4 in the blood serum was determined using the ELISA method in biological fluids, cat. No. 406410, version D 406410−09/17−07.

The statistical package Statistica 10 was used for data analysis. Descriptive statistics methods were used to determine mean, mode, standard deviation, skewness, kurtosis, and coefficient of variation.

To assess the significance of differences between average sample values, taking into account the sample size and the nature of their distribution, nonparametric methods were used: Wilcoxon-Mann-Whitney, Kruskal-Wallis tests and Pearson's χ2 test as methods that are the most adequate from a mathematical point of view [16].

As criterion statistics, the upper 5% region of the Wilcoxon, Kruskal-Wallis and χ2 distributions was used as more stringent compared to t

-distribution to ensure greater accuracy of estimates.

Despite the abundance of scientific works devoted to the role of leukotrienes in the development of many diseases (bronchial asthma, allergic rhinitis, atopic dermatitis, ulcerative colitis, etc.), in the literature available to us, we have not found reports on quantitative indicators of the concentration of leukotrienes in the blood serum, not normal , nor in pathology. The absence of such data indicates that these diseases, according to L.A. Goryachkina et al. [17], are not static states. In this regard, to determine the “comparison point” in our study, we used the average value of leukotriene C4 concentration in 20 practically healthy people without signs of allergies and nasal breathing disorders (control group).

Aspirin-induced bronchial asthma and leukotriene antagonists

Bronchial asthma

(BA) is a chronic inflammatory disease of the respiratory tract, in which many cells participate: mast cells, eosinophils, T-lymphocytes. In susceptible individuals, this inflammation leads to recurrent episodes of wheezing, shortness of breath, chest tightness and cough, especially at night and/or in the early morning. These symptoms are usually accompanied by widespread but variable obstruction of the bronchial tree, which is partially or completely reversible spontaneously or with treatment.

The term “ aspirin asthma”

” (
AA
) is used to designate a clinical-pathogenetic variant, when one of the bronchoconstrictor factors in the patient is
non-steroidal anti-inflammatory drugs (NSAIDs)
, including acetylsalicylic acid. Aspirin-induced asthma usually consists of a triad of symptoms: polypous rhinosinusitis, asthma attacks and intolerance to NSAIDs. Often aspirin-induced asthma is combined with atopic asthma, but it can also be observed as an isolated form of the disease.

Epidemiology

There is no convincing evidence of a hereditary predisposition to AA. However, research in this area is being carried out because There is evidence of several families with a combination of asthma and aspirin intolerance. AA occurs between the ages of 30 and 50, and women are more often affected. The frequency of occurrence among all patients with asthma is 9-22%, according to the latest data - up to 40%.

Background

Aspirin was introduced into clinical practice in 1899 as an analgesic and antipyretic drug, and already in 1903 Franke (Germany) described an allergic reaction in the form of laryngospasm and shock to taking aspirin. In 1905, Barnett reported 2 cases of difficulty breathing while taking aspirin. In 1919, Francis identified a relationship between polyposis rhinitis and hypersensitivity to aspirin. In 1922, Widal first established the relationship between aspirin intolerance, polyposis rhinitis and bronchial asthma. In 1968, Samter and Beers again described this symptom complex, which they called the “aspirin triad.” Since that time, we have learned a lot about the epidemiology, clinical manifestations and pathophysiology of intolerance to aspirin and other NSAIDs in patients with asthma. The key question is: why are only some patients with asthma intolerant to NSAIDs? The discovery of cystenyl-leukotrienes and their participation in the pathogenesis of bronchial asthma largely explains the pathogenesis of the aspirin triad.

Clinical picture

Aspirin asthma is often characterized by a severe, persistent course. Patients with AA quite often end up in intensive care units, according to some authors, more often than patients with other clinical and pathogenetic variants of bronchial asthma. Of particular note is the course of rhinosinusitis in patients with AA. Most often, AA debuts with prolonged rhinitis, which in 20-25% of patients gradually turns into polypous rhinosinusopathy. Manifestations of aspirin-induced rhinosinusopathy:

rhinorrhea, nasal congestion, lack of smell perception, pain in the projection of the paranasal sinuses, headaches. About half of patients with polypous rhinosinusitis eventually begin to react with suffocation to taking NSAIDs. Often, the first attacks of suffocation in this category of patients occur after surgical interventions, for example, polypectomies, radical operations on the paranasal sinuses, etc. In some cases, polyposis also affects other mucous membranes - the stomach, the genitourinary system. Sometimes the first attack of suffocation is preceded by years of continuously recurrent chronic rhinitis, in which exoallergens cannot be detected. As a rule, nasal symptoms are severe and difficult to treat. Topical and sometimes systemic glucocorticosteroids are usually used. But their therapy is often not effective enough, and patients regularly undergo surgical treatment.

AA patients cannot tolerate aspirin and other NSAIDs. This intolerance manifests itself in the form of facial redness, attacks of suffocation, cough, rhinitis and conjunctivitis, urticarial rashes, Quincke's edema, fever, diarrhea, abdominal pain, accompanied by nausea and vomiting. The most severe manifestations of a reaction to aspirin and other NSAIDs are status asthmaticus, respiratory arrest, loss of consciousness and shock. It should be noted that the tolerability of various NSAIDs varies, which depends on the anticyclooxygenase activity of the drug and its dose, as well as on the sensitivity of the patient. Drugs with high cyclooxygenase activity include salicylates (acetylsalicylic acid - aspirin, salicylic acid), polycyclic acids (indomethacin, tolmetin), unsaturated fatty acids (diclofenac, ibuprofen, ketoprofen, tiaprofenic acid), enolic acids (piroxicam).

paracetamol, widely used in clinical practice.

. As early as 1919, Francis noted that phenacetin did not cause adverse reactions in individuals intolerant to aspirin. The mechanism of action of phenacetin is similar to paracetamol, but currently phenacetin is used in clinical practice extremely rarely due to severe side effects. Paracetamol is an analgesic and antipyretic with antipyretic, analgesic and weak anti-inflammatory effects. Paracetamol is well tolerated and does not cause bronchospastic reactions. However, when starting paracetamol therapy in patients with AA, no more than 500 mg should be prescribed and the patient should be monitored for 2-3 hours, since in 5% of patients this drug can cause an attack of suffocation.

Pathogenesis

Cells involved in inflammation in the airways produce various mediators that have a direct effect on bronchial smooth muscle, blood vessels and mucus-secreting cells, and also send signals to other cells, thereby attracting and activating them. leukotrienes are the most important.

. These substances can also cause swelling and hyperreactivity of the bronchi, and change mucus secretion.

The so-called slow-reacting substance of anaphylaxis (SRS-A) was discovered by Felberg and Kellaway in 1938, when these researchers injected cobra venom into the lungs of guinea pigs and showed that there was bronchospasm, not associated with the action of histamine, which occurred more slowly and lasted longer. Although Brockehurst et al. concluded in the 1960s that the substance MPC-A was a critically important mediator of allergy, Samuelsson and his colleagues, who established the structure of MPC-A, had to wait for the advent of better analytical methods to decipher it. Since it was discovered that MPC-A is in fact a leukotriene, significant research efforts have been made to understand the biological properties of leukotrienes and to develop drugs that are their antagonists or synthesis inhibitors.

Biochemistry of leukotrienes

Leukotrienes (LT) are synthesized from arachidonic acid, which is released upon immunological or non-immunological stimulation of various cells involved in inflammation. Arachidonic acid can undergo further metabolic transformations both through the cyclooxygenase system to form prostaglandins and thromboxanes, and through the 5-lipoxygenase enzyme system to form leukotrienes (Fig. 1). 5-lipoxygenase requires a membrane-bound protein called 5-lipoxygenase-activating protein to function. It appears to be a contact protein for arachidonic acid. Once 5-lipoxygenase converts arachidonic acid into leukotrienes, it is destroyed and inactivated. A natural intermediate product during the functioning of the 5-lipoxygenase enzyme system is leukotriene A4 (LTA4), an unstable epoxide, which then, when combined with water, can be converted non-enzymatically into dihydroxy acid leukotriene B4 (LTV4) or, when combined with glutathione, into cysteine leukotriene C4 (LTS4). LTS4 is further converted by g-glutamyltransferase into LTD4 and then by dipeptidases into LTE4, which undergoes further metabolism. In humans, a small but constant portion of LTE4 is excreted unchanged in the urine, making it possible to control the production of leukotrienes in asthma and other diseases.

Different cells synthesize LTB4 and cysteine leukotrienes in different ratios. Eosinophils, basophils, mast cells and alveolar macrophages are capable of synthesizing LTS4. Neutrophils synthesize predominantly LTV4.

Biological properties of leukotrienes

The receptors for LTV4 and cysteine leukotrienes are different. The main actions of LTV4 appear to be the recruitment and activation of cells involved in inflammation, primarily neutrophils and eosinophils. LTV4 is believed to play an important role in the development of suppurative inflammation, rheumatoid arthritis and other inflammatory diseases. However, its role in the pathogenesis of bronchial asthma is questionable and remains unclear. It has been shown that in asthma, LTV4 receptor antagonists do not affect the early and delayed phases of the response to antigen challenge.

Emphasizing the role of cystenyl-leukotrienes in the pathogenesis of AA, it should be noted the increased content of E4 leukotrienes (approximately 3-6 times) in urine and C4 in nasal secretions in comparison with other types of bronchial asthma. Provocation with aspirin sharply increases the amount of leukotrienes E4 and C4 in urine, nasal secretions and bronchial lavage.

The platelet theory is also of great interest

development of AA.
It was found that platelets from patients with AA, unlike platelets from healthy individuals, are activated in vitro
by NSAIDs, which is manifested by cell degranulation with the release of cytotoxic and proinflammatory mediators.
Other peripheral blood cells are not activated by NSAIDs in vitro
. As is known, NSAID-induced blockade of cyclooxygenase leads to inhibition of prostaglandin H2 production. The authors of the platelet theory suggest that a decrease in the level of this prostaglandin plays an important role in platelet activation in patients with AA.

The overwhelming majority of studies did not reveal the participation of the reagin mechanism in the development of aspirin asphyxiation. There are only isolated reports of the detection of specific immunoglobulins E to aspirin derivatives.

Diagnostics

Anamnesis data are important in making the diagnosis of aspirin-induced bronchial asthma.

about the patient’s reaction to taking painkillers or antipyretics. Some patients may have clear indications of the development of an attack of asthma after using NSAIDs. The absence of indications of intolerance to NSAIDs in a number of AA patients is usually due to the following reasons: a relatively low degree of hypersensitivity to drugs with anticyclooxygenase action; simultaneous use of medications that neutralize the bronchoconstrictor effect of NSAIDs (for example, antihistamines, theophyllines, sympathomimetics), delayed patient response to NSAIDs; rare use of NSAIDs. Attacks of asthma in AA patients who do not take NSAIDs may be associated with the consumption of natural salicylates, as well as foods preserved with salicylates. It should be noted that a significant proportion of patients are not aware that various NSAIDs are part of such commonly used combination drugs as citramon, pentalgin, sedalgin, baralgin, etc.

It is important to ask a patient with asthma about the effectiveness of using theophedrine to relieve an attack of asthma. Patients with AA usually indicate the ineffectiveness of theophedrine, or note its two-stage effect: first, bronchospasm decreases somewhat, and then increases again due to the presence of amidopyrine and phenacetin in theophedrine.

The intensity of the reaction to NSAIDs depends on the degree of sensitivity of the patient to the drug, and it also closely correlates with the anticyclooxygenase activity of the drug. Indomethacin has the greatest activity against cyclooxygenase among NSAIDs. The stronger the anticyclooxygenase effect of NSAIDs, the more intense the symptoms of intolerance to this group of drugs. The intensity of the reaction also correlates with the dose of the medication taken. The method of using NSAIDs also plays an important role. When administered by inhalation, intravenous or intramuscular route, the intensity of the reaction is usually maximum.

Thus, in making a diagnosis of aspirin-induced bronchial asthma, a large role is given to collecting anamnesis and clinical manifestations of the disease.

in vivo
challenge tests or
in vitro
can currently be used .
When performing a provocative test in vivo
, either taking aspirin orally or inhaling increasing concentrations of water-soluble aspirin - lysine-aspirin (aspisol) is used, followed by monitoring of bronchial patency indicators. Due to the possibility of developing an attack of suffocation, this test can only be performed by a specialist. It is necessary to have equipment and trained personnel ready to provide emergency assistance in the event of bronchospasm. The indication for a provocative test with aspirin is the need to clarify the clinical and pathogenetic variant of asthma. Patients whose FEV1 levels are at least 65-70% of the required values are allowed to undergo a provocative test. In addition to low EF values, contraindications to provocative tests are also the need for frequent use of sympathomimetics, dementia, pregnancy and severe bleeding. Antihistamines reduce the patient's sensitivity to aspirin, so they are discontinued at least 48 hours before the test. Sympathomimetics and theophylline preparations are discontinued depending on their pharmacokinetic properties, for example, salmeterol should be discontinued at least 24 hours before the test.

Currently, laboratory diagnostics of aspirin-induced bronchial asthma are being developed, associated with the determination of leukotrienes E4 in urine and C4 in nasal lavage. It should be noted that when conducting provocative tests with lysine-aspirin in the group of AA patients, the content of leukotriene E4 in urine and C4 in nasal lavage sharply increases. Apparently, in the near future certain standards will be recommended for the diagnosis of this variant of asthma.

Treatment

Currently, in the treatment of asthma, including aspirin, the main role is given to long-term use of anti-asthmatic anti-inflammatory drugs. To select adequate anti-inflammatory therapy, it is important to determine the severity of bronchial asthma. No test will allow us to accurately classify the severity of asthma. However, a cumulative assessment of symptoms and indicators of external respiratory function provides an indication of the severity of the disease. It has been shown that assessment of the course of asthma, based on the clinical manifestations of the disease, is associated with indicators of the degree of airway inflammation.

Both the level of obstruction and the degree of its reversibility make it possible to subdivide asthma according to severity into intermittent, mild persistent (chronic), moderate (moderate) and severe. Treatment of asthma currently uses a stepped approach, in which the intensity of therapy increases as the severity of asthma increases. The most commonly used drugs outside of exacerbation of bronchial asthma are inhaled corticosteroids, the dose of which depends on the severity of asthma, nedocromil and sodium cromoglycate, long-acting theophyllines and long-acting sympathomimetics.

Typically, patients with AA require high maintenance doses of inhaled corticosteroids, and long-term treatment of nasal symptoms with topical steroids is also necessary. Often it is necessary to resort to the prescription of systemic steroids. Therefore, various pathogenetic approaches to the treatment of AA are being developed.

One of the pathogenetic methods of treating aspirin-induced asthma is aspirin desensitization.

. The method is based on the phenomenon of the development of tolerance in an AA patient to repeated exposure to NSAIDs in the period 24–72 hours after choking caused by taking NSAIDs. Stevenson showed that aspirin desensitization was able to control the symptoms of rhinosinusitis and bronchial asthma. Desensitization with aspirin is also carried out in patients who need to be prescribed NSAIDs for other diseases (coronary artery disease, rheumatic diseases, etc.). Desensitization is carried out according to various schemes, which are selected individually. Desensitization is carried out only in a hospital by a doctor who knows this technique. Start with a dose of 5-10 mg and reach a dose of 650 mg and above. Maintenance doses – 325–650 mg per day. Contraindications to desensitization with aspirin are exacerbation of bronchial asthma, bleeding, gastric and duodenal ulcers, severe liver and kidney diseases, and pregnancy. Recent studies have shown that the mechanism of desensitization is associated with the formation of insensitivity of airway receptors to the effects of leukotrienes.

Currently, a new class of anti-inflammatory anti-asthmatic drugs has emerged - leukotriene receptor antagonists.

.
Research results indicate that these drugs rapidly reverse the basal airway tone created by leukotrienes due to chronic activation of the 5-lipoxygenase enzyme system. One of the representatives of this group is the highly selective and highly active drug zafirlukast
(acolat). Zafirlukast, when administered orally, leads to a significant increase in FEV1 in patients with impaired pulmonary function who have previously used effective antiasthmatic drugs, including inhaled corticosteroids.

Leukotriene antagonists are especially widely used in aspirin-induced bronchial asthma, since the pathogenesis of this form of asthma involves increased activation of the 5-lipoxygenase system and increased sensitivity of receptors to leukotrienes. Leukotriene antagonists improve airway function in these patients and block the effect of inhaled lysine aspirin. Thus, leukotriene antagonists have proven to be particularly effective in this group of patients, who are often difficult to treat.

In the studies conducted, the connection of zafirlukast

to therapy with aspirin BA causes an increase in FEV1, peak expiratory flow rates in the morning and evening, and a decrease in nocturnal asthma attacks compared to placebo. Zafirlukast is effective both in monotherapy and in combination with other drugs used as maintenance treatment for chronic asthma. Studies have also shown good effects of leukotriene antagonists in combination with inhaled and oral steroids. Zafirlukast helps maintain a stable clinical condition and has an additive clinical effect, allowing a reduction in the amount of steroid therapy. Thus, at present we can say that a class of drugs has emerged that affects the pathogenetic link of aspirin-induced bronchial asthma and has a pronounced clinical effect.

It should be noted once again that if it is necessary to prescribe drugs to reduce fever or relieve pain, paracetamol should be prescribed at an initial dose of 0.5 g per day.
When carrying out paracetamol therapy in patients with AA, the patient's condition should be monitored (preferably using a peak flow meter) for 2–3 hours, since in 5% of patients this drug can cause an attack of suffocation. If well tolerated, the dose can be increased if necessary. Literature
1. Bronchial asthma. Global strategy. Supplement to the journal Pulmonology. M., 1996; 196.

2. A.G. Chuchalin. Bronchial asthma. M., 1997.

3. J. Bousquet et al. Eosinophilic inflammation in asthma // N Engl J Med. 1990; 323:1033-9.

4. British Thoracic Society. Guidelines on the management of asthma // Thorax .1993; 48 (2): 1-24.

5. P. Burney. Current questions in the epidemiology of asthma, in: Holgate ST, et al (eds), Asthma: Physiology, Immunology and Treatment. London, Academic Press, 1993; 3-25.

6. JM Drazen, KF Austen. Leukotrienes and airway responses // Am Rev Respir Dis. 1987; 136:985-98.

7. S. Holgate, SE. Dahlen. SRS-A to Leukotrienes, 1997.

8. Speer F. Aspirin allergy: a clinical study // Southbern Med Journal.1975; 68: 314-8.

9. Stevenson DD Desensitization of aspirin-sensitive asthma: a therapeutic alternative? //J Asthma. 1983; 20 (1): 31-8.

Zafirlukast –

Akolat (trade name)

(AstraZeneca)

Applications to the article

Aspirin-induced asthma usually includes a triad of symptoms: polypous rhinosinusitis, asthma attacks and intolerance to NSAIDs.

Rice. 1. Scheme of formation of leukotrienes.

Leukotriene antagonists are particularly effective in aspirin-induced asthma

Results and discussion

Conducted clinical and laboratory studies showed that the increase in nasal obstruction in patients with PRS increased in proportion to the increase in the concentration in the blood serum of LTC4, the average normative values of which, according to our studies, were 0.256 nmol/mg.

The results obtained indicated the severity of allergic inflammation and were confirmed by histological examination of polypous tissue taken during a biopsy or removed during surgery.

Morphologically, the picture of vasculitis, pronounced plethora, marginal standing of leukocytes, and leukodiapedesis was determined. Scattered eosinophils were visible in large numbers in the edematous ground substance.

Due to the lack of recommendations to date on the duration and dosage of use of montelukast sodium, we have determined a treatment regimen for nasal obstruction in patients with PRS with continuous use of minimal doses (4-5 mg) of the drug recommended for the treatment of allergic rhinitis and bronchial asthma in children for 18 months. [10, 18-20].

The therapeutic effect of the leukotriene receptor blocker was assessed after 14 days, 1 month, 6 months and 1 year compared with baseline data.

It was found that when using this drug in patients with PRS, a decrease in the volume of polypous tissue was observed, which significantly affected the state of nasal breathing and was reflected in the indicators of anterior active rhinomanometry, acid-base balance and LTC4 concentration in the blood serum.

The most pronounced therapeutic effect of treatment was observed in patients with stage III-IV polyposis (Tables 1, 2). The decrease in LTC4 concentration occurred more intensely during the 1st month.

Table 1. Efficacy of conservative treatment of nasal obstruction in patients with stage III polyposis (n=43) Note. Here and in the table. 2: * - statistically significant differences for p<0.05 compared to the state before treatment. Table 2. Efficacy of conservative treatment of nasal obstruction in patients with stage IV polyposis (n=18)

After 2 weeks in patients with stage III polyposis, the concentration of LTC4 decreased by 15.4±0.033%, after 1 month from the start of treatment - by 18.7±0.039%, reaching the values of stage II polyposis. After 6 months, the concentration of leukotrienes decreased by 21.1±0.043%, and after 1 year - by 24.4±0.049% of the initial value.

Just as in patients with a lower degree of polyposis, in patients with stage IV the decrease in the concentration of leukotriene C4 occurred most intensively during the 1st month of treatment.

After 2 weeks, the concentration of LTC4 in patients with stage IV decreased by 30.9%, after 1 month from the start of treatment - by 43%, reaching the values of stage II polyposis. After 6 months, the concentration of leukotrienes decreased by 45.5%, and after 1 year - by 46.9% of the initial value.

A slow decrease in acid-base status in stage IV polyposis indicated the depth of tissue hypoxia.

During treatment, against the background of a decrease in LTC4 concentration, a qualitative change occurred in the composition of the study group: if before treatment the majority (70.1%) of patients were patients with stage III-IV nasal polyposis, then after 1 month the majority (81.6%) patients had stage I-II polyposis.

The use of a leukotriene receptor blocker for the treatment of nasal obstruction of polyposis allowed 73.8% of patients with stage III-IV polyposis to restore the adequacy of nasal breathing without resorting to surgical intervention, and to achieve stabilization of the process during dynamic observation from 1.5 to 3 years.

The effectiveness of using a leukotriene receptor blocker was confirmed histologically.

It was found that as a result of treatment with a leukotriene receptor blocker in both primary and recurrent polyposis, including in the presence of bronchial asthma, the exudative component of allergic inflammation disappeared, as evidenced by the absence of edema, plethora, and a significant decrease in eosinophilic infiltration.

The results obtained served as a morphological justification for the possibility and effectiveness of using minimal doses of a leukotriene receptor blocker for the pharmacological control of nasal obstruction in patients with PRS and formed the basis for the invention “Method for the treatment and prevention of nasal obstruction in patients with polypous rhinosinusitis” (patent No. 2499597 dated November 27, 2013).

Due to the low effectiveness of conservative treatment within 2 months, 26 of 87 (29.9%) patients with PRS underwent endonasal endoscopic polysinsotomy.