RU2760825C1 - Method for treating patients with allergic rhinitis associated with chronic rhinosinusitis of bacterial etiology using a domestically produced topical immune corrector - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely, to allergology and immunology, and can be used for treating patients with allergic rhinitis associated with chronic rhinosinusitis of bacterial etiology. For this purpose, a topical immune corrector "KIP nasal" is used as an immunomodulatory product, constituting a lyophilised protein solution containing IgG, IgA, IgM-class immunoglobulins isolated from human blood plasma, administered intranasally 5 drops into each nasal passage 3 times per day for 5 days.

EFFECT: method ensures effective treatment of allergic rhinitis associated with chronic rhinosinusitis of bacterial etiology, reduces the frequency of exacerbations and hospitalisations, reduces the volume of basic and antibacterial therapy due to the normalisation of a number of indicators of the mucosal immunity.

1 cl, 4 tbl, 2 ex

Description

The invention relates to medicine, in particular to allergology and immunology, and can be used to treat patients with allergic rhinitis in combination with chronic rhinosinusitis of bacterial etiology (AR with CRSBE).

The greatest difficulty in matters of therapy is allergic rhinitis, complicated by chronic infection of the upper respiratory tract, due to the fact that the clinical manifestations of the disease are more severe, there is a long course, torpidity to pharmacotherapy; the possibilities of carrying out allergen-specific immunotherapy in this category of patients are difficult (Lopatin A.S. Rinit: a guide for doctors. - Litterara. Moscow, 2010. S. 417). According to a number of research works, almost 41% of patients with allergic rhinitis have a complicated course of the disease, a combination with chronic rhinosinusitis of bacterial etiology (Dzagoeva E.E., Enaldieva Z.N. in the modern information society. - 2018. - pp. 11-12.) The need for combined therapy of AR with CRBD is determined by the complexity of the pathogenesis of this condition. AR with CRBD is characterized by pronounced disorders of local mucosal immunity, which requires an integrated approach to treatment (Trigubenko R.A. Method of treating patients with allergic rhinitis with disturbed microbial landscape of the nasal mucosa / R.A. Trigubenko // Innovative medical technologies: Collection of scientific papers . Edited by R.N. Chirkov, S.V. Zhukov. - Tver, 2019. - pp. 66-71.). Persistent infection, the causative agents of which act as superantigens, has a cytopathic effect on the mucous membranes of the upper respiratory tract, contributes to the maintenance of the local inflammatory process and induces disturbances in the immune response (Balmasova I.P., Zhestkov A.V., Lebedin Yu.S. Immunological aspects of rhinology. Russian rhinology, 2000, No. 1. S. 33-36). A number of studies have shown that when AR is combined with foci of chronic infection, in addition to allergic inflammation in the mucosa, various disorders of mucosal immunity are noted, characterized by changes in the level of sIgA, IgA, IgM, IgG, cytokine profile and level of leukotrienes (Ryabova L.V. Kliniko- immunological features of the course of allergic rhinitis // VNMT. 2008. No. 2. URL: https://cyberleninka.ru/article/n/kliniko-immunologicheskie-osobennosti-techeniya-allergicheskogo-rinita (date of access: 10.08.2020); Bulkina, OZ Optimization of complex treatment of perennial allergic rhinitis complicated by foci of chronic infection of the oropharynx and nasopharynx: abstract of thesis for Candidate of Medical Sciences - M., 2009, p. 24). Due to the presence of immune disorders, due to the persistence of a bacterial infection, in AR with CRSBE, additional immunocorrection is required, since the means of etiotropic effect are not effective enough. Thus, the development of a complex treatment for AR with CRBD, which, along with its effectiveness, would be the safest possible, is a promising direction. Our study demonstrates the clinical and immunological efficacy and safety of complex treatment of AR with CRSBE with the inclusion of a new domestic topical immunocorrector ("Nasal CIP"). "Nasal KIP" is a lyophilized protein solution containing immunoglobulins of the IgG, IgA, IgM classes, isolated from human blood plasma. "KIP nasal" has a high titer of antibodies against a wide range of bacteria, which provides an effective clinical and immunological therapeutic effect of the drug in patients with the studied nosology. After intranasal use, the drug has a local effect in the nasopharynx, blocking the receptors of microbial cells, thereby reducing the adsorption of microbes on the epithelial cells of the nasal mucosa and inhibiting the multiplication of adsorbed microbial cells, weakening or preventing the development of the infectious process (Instructions for medical use KIP: registration number - ЛС-001690).

In the available literature, we did not find data on the use of the topical immunocorrector "Nasal KIP" in the complex therapy in patients with AR with CRBD. In terms of chemical composition and mechanism of action, "KIP nasal" has no analogues among domestic and foreign medicines. Currently, there are no other targeted immunoglobulin drugs. There is a domestic analogue of this drug in the form of delivery in the form of rectal and vaginal suppositories - the drug "Kipferon". "Kipferon" is used as part of complex therapy for the treatment of various chronic inflammatory processes of the intestines and genital organs. Its use is also known in respiratory pathology. The immunotropic effect of the drug is due to the content of immunoglobulins IgG, IgA, IgM in its composition. At the site of application of suppositories, the drug has a substitution effect, normalizing local immunity due to the intake of immunoglobulins, stabilizing interferon from secretions of mucous membranes and increasing the activity of locally formed cytokines (Feklisova L.V., Shebekova V.I., Tselipanova E.E., Afanasyev SS, Aleshkin VA, Matveevskaya NS, Efimova OG, Savitskaya NA "Kipferon, suppositories" in the treatment of children with acute respiratory diseases. Questions of modern pediatrics. - M. , 2003.S. 81-84). The disadvantage of the described analogue is the lack of a directed local influence in the focus of inflammation, namely, the mucous membrane of the nasal cavity.

An analogue of the claimed invention is the work on the use of a foreign drug "IRS19" in patients with chronic rhinosinusitis of bacterial etiology, the specific effect of which is due to the stimulation of sIgA production, and the nonspecific effect is due to an increase in the phagocytic activity of macrophages and an increase in the content of lysozyme (Savenkova M., Afanasyeva A., Minasyan V. ., Tyurkina S. Treatment of frequently ill children with mixed infection. Questions of modern pediatrics. M., 2011. S. 83–88.). The undoubted advantage of the drug is the topical effect on the mucosal immunity of the nasal mucosa, however, the drug does not contain ready-made replacement immunoglobulins, since it is a bacterial lysate. The disadvantage of the described analogue is that, in order to achieve the desired result, a long course of treatment is required (more than two weeks), in addition, this drug is of foreign production.

The most similar to the claimed invention in terms of the set of essential features for use is the method of introduction into the inferior turbinates on both sides of the immunomodulator "Polyoxidonium" - 6 mg within 5 days 48 hours after preliminary sanitation of the nasal sinuses with antibacterial drugs under local anesthesia. In the prototype and in the claimed study, therapy is carried out using rational pharmacotherapy. The disadvantage of the prototype is that this method is painful, since it requires the introduction of drugs into the inferior turbinates under local anesthesia. In addition, "Polyoxidonium" is an immunomodulator that also does not contain replacement immunoglobulins and affects the immune system indirectly (RF Patent No. 2314104).

The claimed invention is a method of therapeutic use of a domestic topical immunocorrector with a complex of substitutional immunoglobulins acting directly in the focus of inflammation of the nasal mucosa, which does not require invasive administration.

The objective of the claimed invention is to develop a method for treating AR patients with CRSBE, which improves the effectiveness of therapy for this disease, using the domestic topical immunocorrector "Nasal KIP", namely, the achievement of clinical and immunological remission for a long period of time. The claimed invention is aimed at solving the problem only in patients with AR with CRSBE, in the pathogenesis of which there is a secondary immunological deficiency, which was the indication for the use of the immunomodulator "Nasal KIP".

The problem is solved due to the fact that the proposed method for the treatment of AR with CRBD provides the following differences: 1) the proposed method differs in that, unlike the prototype, the claimed invention uses a drug with a substitutional immunomodulatory effect, with a shorter treatment regimen for the patient and with non-invasive administration; 2) the proposed method differs from the prototype in that in the claimed invention, in addition to the substitutional immunomodulatory effect, a new form of drug delivery is proposed, with the help of which it has an effect directly in the focus of inflammation. In the prototype, the drug is administered in the form of suppositories rectally, while a systemic immunomodulatory non-directional effect is realized. Taken together, similar to the prototype and distinctive features are necessary to achieve a stable positive therapeutic effect in patients with AR with CRBD.

The essence of the proposed method of treatment is that the proposed method of therapy for AR with CRSBE using the domestic topical immunocorrector "Nasal KIP". Patients were treated according to the following scheme: "Nasal CIP" was injected intranasally, 5 drops into each nasal passage 3 times a day for 5 days against the background of basic antiallergic therapy, which included antihistamines and intranasal glucocorticosteroids (GCS). It has been shown that complex therapy with the inclusion of the immunocorrector "Nasal KIP" is a safe highly effective method of therapy for AR with CRBE, influencing the pathogenetic mechanisms of inflammation in this pathology. Features of the application of this method are due to the pathophysiological properties of the local mucosal immune response in AR with CRBE. The drug has a targeted pathogenetic effect, normalizing the impaired indices of local immunity. This method of treatment, carried out in a timely manner to patients with AR with CRSBE, makes it possible to prevent the transition of the disease to more severe forms and to reduce the need for basic antiallergic drugs. The clinical effectiveness of this method is expressed in a decrease in the intensity of infectious and allergic inflammation, a change in the clinical symptoms of rhinitis, an increase in the control of the disease, a decrease in the frequency of relapses and a decrease in the amount of anti-inflammatory therapy. The method of treatment is characterized by a favorable safety profile and therapy regimen. This drug is administered according to the scheme we have selected, which, unlike other intranasal immunocorrectors, is much shorter and allows to achieve long-term clinical remission of ARs with CRBE, while the undoubted advantage of the drug is its local effect. "KIP nasal" meets all WHO requirements for immunoglobulin preparations.

There is currently no indication for use in AR with CRSBE in the instructions for the drug "Nasal KIP". In our country, this method of treatment has not been used before.

Information confirming the effectiveness of the invention.

To study the clinical and immunological effect and safety of the drug "Nasal KIP" as part of complex therapy in patients with AR with CRBD, 37 patients aged 18 to 55 years were examined. The patients were divided into two groups: the first - patients with AR with CRBD, who received basic anti-inflammatory therapy in combination with the immunocorrector "Nasal CIP" (n = 20), the second - patients with AR with CRBD, who received only basic therapy (n = 17). The study also included a control group (apparently healthy) (n = 30). The groups were comparable in terms of age, sex, severity and results of allergic-immunological examination. All patients received the same anti-inflammatory therapy in accordance with the recommendations, which included intranasal corticosteroids, antihistamines (symptomatically), with an exacerbation of the pyoinflammatory process - antibacterial drugs (EPOS 2012). As a result of the study, the clinical and immunological parameters were assessed before and after treatment in both groups of patients. "Nasal instrumentation" was administered to patients intranasally, 5 drops in each nasal passage 3 times a day for 5 days. For 5 days of treatment with the drug "Nasal KIP", a physical examination was carried out daily to assess the well-being of patients, the dynamics and control of the symptoms of AR with CRSBE (nasal congestion, sneezing, rhinorrhea) and to identify possible adverse reactions. Further dynamic observation of the patients and examination were carried out after 1 month and 6 months. A long-term assessment of the results of treatment was carried out by examining and collecting anamnesis one year after treatment. Observation of patients from the comparison group occurred with the same frequency. The efficacy of the drug was assessed based on symptom regression. The clinical efficacy of therapy was assessed at the end of the follow-up year (a decrease in the frequency of exacerbation and the severity of clinical symptoms, a decrease in the volume of basic therapy and the need for symptomatic drugs, an increase in the control of AR with CRBD). The results were assessed as excellent (no exacerbations were noted, clinical symptoms were absent or insignificant, the amount of basic therapy decreased significantly, there was an increase in AR control with CRBD), good (rare exacerbations, persistence of clinical symptoms of lower intensity, a decrease in the volume of medications used, an increase in AR control was observed with CRBE), satisfactory (maintaining the frequency of exacerbations, a slight decrease in the severity of clinical symptoms and the need for medication, the same control) and unsatisfactory (the clinical course was unchanged or worsened).

In order to assess the clinical efficacy of the proposed method of treatment, rhinitis control scales were used (Clinical guidelines "Allergic rhinitis", 2019). Control over the course of AR with CRSBE was assessed in points according to the frequency and severity of nasal symptoms, taking into account the need for basic medications over the last 7 days. The formula was used to calculate the adjusted score for nasal symptoms, taking into account the need for medicines for the last 7 days: TNSS (TNSS - Total nasal symptom score) the average total score of nasal symptoms for the last 7 days + MS (MS - medical score) the average total score for last 7 days. TNSS + MS = sum of points (where 0 points corresponded to the absence of symptoms, 12 points meant the maximum severity of rhinitis symptoms, despite the use of 3 lines of drugs). In addition, a visual analogue scale (VAS) was used to assess symptoms (EPOS, 2012), where 0 is the absence of complaints and symptoms, 10 is the most pronounced manifestations of the disease (results from 0 to 5 indicated a controlled course of the disease, from 5 and higher about uncontrolled flow of AR with CRSBE).

Allergic and immunological parameters of nasal secretion (IL4, IL10, TGF-β, γ-INF spontaneous and induced, sIgA, IgA, IgM, IgG), total IgE in serum and leukotrienes LT C4, D4, E4, LTB4 in blood plasma were determined ELISA method 1 month after treatment. Tolerability of the drug "nasal instrumentation" was assessed based on the analysis of the frequency of adverse events (AE).

All patients who received "Nasal CIP" showed varying degrees of improvement in the clinical course of AR with CRBD. Studies have shown that as a result of the treatment with the drug "Nasal KIP" nasal congestion, sneezing and rhinorrhea regressed in 90% of patients on days 7-10.

The inclusion of the domestic immunocorrector "KIP nasal" in the complex therapy of AR with CRSBE made it possible to achieve a stable remission of the disease in 75% of cases. On average, the frequency of exacerbations in the examined patients with AR with CRBD before treatment was 5.3 times a year. As a result of treatment with the drug "Nasal CIP", a decrease in the frequency of exacerbations was noted by 2.5 times, to 2.65 times a year (p <0.05). At the same time, in the group of patients who received only basic therapy, the frequency of exacerbations was 4.7 (p> 0.05) in comparison with the baseline data.

During the observation period, none of the patients in the first group had severe exacerbations of AR with CRBE, there were no hospitalizations for exacerbations, in contrast to patients in the second group, where 10.76% had severe exacerbations with hospitalization. Complex therapy with the inclusion of the drug "Nasal KIP" led to a decrease in the volume of basic anti-allergic and anti-inflammatory therapy. Intranasal glucocorticosteroids were received by 100% of patients before the start of the course of treatment, and 60% after a year of follow-up. The proportion of patients in the group with AR with CRBD who do not use antibacterial drugs for the symptomatic treatment of exacerbations in the future was 75% (p <0.05) compared to the baseline, while this trend was not observed in the second group. In the second group, the volume of anti-allergic and anti-inflammatory therapy remained the same. In the group of patients who received only basic therapy, 94.12% of people received intranasal glucocorticosteroids after the course of treatment, in comparison with 60% of patients after treatment with Nasal CIP (p <0.05). The study has convincingly demonstrated that "nasal CIP" changes the course and development of AR with CRSBE, as evidenced by the data obtained on a decrease in the use of basic drugs.

When calculating a questionnaire to control the course of AR with CRBE according to the formula, taking into account the frequency and severity of nasal symptoms and the need for medications, an improvement in rhinitis control and a decrease in the need for symptomatic basic drugs were revealed. The total score decreased against the background of the use of the immunocorrector "Nasal KIP" from 13 to 4 points (p <0.05), while in patients of the second group, such a significant trend was not observed. The total score in patients of the second group after treatment was 10 points (p> 0.05). According to the VAS assessment, after treatment with Nasal CIP, the control of ARs with CRBE increased in patients. The indicator decreased from 7.3 to 2.7 points (p <0.05) in the group receiving "nasal CIP", while in the second group the average score was 6.2 (p> 0.05).

The clinical efficacy of treatment with the drug "Nasal CIP", taking into account the excellent and good results, was 75.00% at the end of the observation, while the use of basic therapy provided the same results only in 29.41% of cases (Table 1).

Table 1. Comparative results of the clinical efficacy of AR treatment with CRBD

Treatment results "Nasal instrumentation" + basic therapy (n = 20) basic therapy (n = 17) Abs. % Abs. % excellent 3 15.00 0 0 good 12 60,00 5 29.41 satisfactory 5 25,00 10 58.83 unsatisfactory 0 0 2 11.76

At the end of the course of treatment with the drug "Nasal KIP" and the follow-up period, a dynamic assessment of the allergo-immunological parameters was carried out (Table 2).

Table 2. Comparative analysis of allergic-immunological parameters before and after treatment in patients with AR with CRBD.

Parameters Healthy
(n = 30) AR with CRBD before treatment (n = 37) AR with CRSBE "nasal instrumentation" + basic therapy (n = 20) AR with HRSBE
basic therapy (n = 17) Total IgE, ME / ml 55.08 ± 6.2 200.30 ± 10.09 * 79.42 ± 12.19 ** 141.81 ± 25.94 sIgA, ME / ml 16.44 ± 2.75 7.47 ± 0.75 * 16.65 ± 3.42 ** 9.68 ± 2.49 IgM, ME / ml 2.14 ± 0.25 1.45 ± 0.10 2.52 ± 0.23 ** 1.54 ± 0.17 IgA, ME / ml 2.28 ± 0.16 2.27 ± 0.12 2.63 ± 0.14 2.20 ± 0.24 IgG, ME / ml 13.37 ± 0.66 13.32 ± 0.5 13.57 ± 0.92 12.14 ± 0.83 IL10, pg / ml 4.13 ± 0.55 6.87 ± 0.81 4.8 ± 1.27 ** 5.65 ± 1.07 IL4, pg / ml 9.60 ± 1.38 32.38 ± 2.61 10.49 ± 2.7 ** 19.92 ± 5.44 ** TGF-β, pg / ml 520.69 ± 64.01 1390.54 ± 91.75 * 660.25 ± 128.64 ** 856.43 ± 153.83 ** γ-INF spontaneous,
pg / ml 1.25 ± 0.55 1.87 ± 0.56 1.26 ± 0.36 2.39 ± 1.34 γ-INF induced, pg / ml 215.20 ± 35.57 271.95 ± 62.91 269.89 ± 31.63 267.15 ± 125.84 LT C4, D4, E4, ng / ml 0.64 ± 0.12 3.25 ± 0.16 * 3.12 ± 0.18 3.13 ± 0.22 LTB4, ng / ml 1.52 ± 0.21 14.43 ± 0.57 * 8.04 ± 0.36 ** 14.5 ± 0.58

Note: * - statistically significant when comparing healthy people and patients before treatment, Mann-Whitney test, p <0.05.

** - statistically significant when comparing patients of the two groups after treatment, Wilcoxon test, p <0.05.

As a result of the analysis of immunological parameters before and after the use of nasal instrumentation (Table 2), a significant positive dynamics of regression of a number of values after therapy was revealed (p <0.05). During treatment in patients of the first group there was a significant change in a number of parameters, namely, total IgE, sIgA, IgM, cytokines IL10, IL4, TGF-β and LTB4 (p <0.05). Carrying out only basic therapy to AR patients with CRSBE allowed to achieve normalization of immunological parameters to an insignificant extent.

During treatment, patients of the first group showed a significant increase in sIgA from 7.47 IU / ml to 16.65 IU / ml (Wilcoxon test, p = 0.0085) and IgM from 1.45 IU / ml to 2.52 IU / ml (Wilcoxon test, p = 0.0040), decrease in total IgE from 200.30 IU / ml to 79.42 IU / ml (Wilcoxon test, p = 0.0010), cytokines IL4, IL10 and TGF-β from 32 , 38 pg / ml to 10.49 pg / ml (Wilcoxon test, p = 0.0004), 6.87 pg / ml to 4.8 pg / ml (Wilcoxon test, p = 0.0217) and 1390.54 pg / ml up to 660.25 (Wilcoxon test, p = 0.0018), respectively, and LTB4 from 14.43 ± 0.57 ng / ml to 8.04 ± 0.36 ng / ml (Wilcoxon test, p = 0.0000).

Thus, the inclusion of the topical immunomodulator "Nasal KIP" in the complex therapy of AR with CRBD has a normalizing effect on the indicators of mucosal immunity.

The analysis of the obtained results of allergic-immunological examination showed that the "Nasal CIP" has a targeted pathogenetic-directed effect, reduces the severity and intensity of infectious and allergic inflammation, which, thereby, leads to remission of the disease.

During treatment, only 2 patients (10%) who received nasal CIP had AEs in the form of a local reaction - a burning sensation in the nose. This AE occurred within the first 5 minutes after application of the drug and was observed, as a rule, within 15-20 minutes. In both patients, the local reaction persisted throughout the entire period of treatment. The observed AE did not require discontinuation of the "Nasal CIP" drug, changes in the dose and mode of administration, as well as the prescription of drugs in order to relieve the AE. In general, the drug was well tolerated, did not cause allergic and general adverse reactions.

Thus, patients with AR symptoms with CRSD, which is based on changes in the indices of immunoglobulins and cytokines in the nasal secretion, are potential candidates for the successful use of this method of treatment.

This method of treatment allows you to achieve:

- remission of AR with CRSBE in 75% of patients;

- reduction of recurrence of the disease, which leads to a decrease in the volume and duration of the use of basic anti-inflammatory and antiallergic drugs in patients with AR with CRBD;

- normalization of immunological parameters (in most patients), namely, total IgE, sIgA, IgM, cytokines IL10, IL4, TGF-β and LTB4,

which is an important criterion for the effectiveness of the use of the domestic immunocorrector "nasal KIP" in combination with basic therapy for AR with CRBD.

Example 1. Patient E. 19 years old, with complaints of shortness of nasal breathing, sneezing attacks, profuse mucous nasal discharge, decreased sense of smell. For the first time he was hospitalized in a hospital for chronic bacterial rhinitis 5 years ago, antibiotics, intranasal glucocorticosteroids, antihistamines and vasoconstrictor drugs, physiotherapy were used in therapy. Three years ago, symptoms of perennial allergic rhinitis joined. The basic therapy was used - cetirizine 1 tablet once a day, xylometazoline 1-2 injections up to 5-6 times a day, mometasone nasal spray 2 injections 1 time a day constantly. Exacerbations were noted from 3 to 6 times a year, with hospitalization 1 to 3 times a year, where antibiotic therapy was added to the basic treatment - ceftriaxone 1 g each. 2 times a day / m.

Survey methods:

- during an allergic examination, specific IgE antibodies to fungal and household allergens were revealed;

- bacteriological examination of smears from the nasal cavity revealed S. aureus in the diagnostic titer;

- during immunological examination, indicators of nasal secretion were determined (IL4, IL10, TGF-β, γ-INF spontaneous and induced, sIgA, IgA, IgM, IgG), total IgE in serum and leukotrienes LT C4, D4, E4, LTB4 in plasma blood (Table 3.)

Based on the examination, the diagnosis was made: Allergic persistent rhinitis, moderate severity, poorly controlled course (fungal and household sensitization). Chronic rhinosinusitis, recurrent course. Appointment of topical immunocorrector "KIP nasal" 5 drops 3 times a day for 5 days allowed to achieve clinical remission within a year. No AEs were observed during treatment. No exacerbations were registered. During the year of observation, the patient had rare symptoms of nasal congestion and rhinorrhea, arrested by symptomatic use of intranasal glucocorticosteroids in a short course. Changes in the immunological parameters of patient E. are presented in Table 3.

Table 3. Comparison of the immunological parameters of patient E. before and after treatment.

Immunological indicators Before treatment After treatment Total IgE, ME / ml 199.4 47.7 sIgA, ME / ml 8.0 28.0 IgM, ME / ml 1.4 2.2 IgA, ME / ml 0.7 2.0 IgG, ME / ml 7.0 10.0 IL10, pg / ml 3.8 0 IL4, pg / ml 74.2 6.4 TGF-β, pg / ml 1790.0 595.0 γ-INF spontaneous,
pg / ml 0.7 16.2 γ-INF induced, pg / ml 1248.0 921.6 LT C4, D4, E4, ng / ml 4.59 4.43 LTB4, ng / ml 14.34 9.94

The presented values, determined before and at the end of the course of treatment, significantly differ in the level of total IgE, sIgA, IgM, IL4, IL10, TGF-β and LTB4 (p <0.05).

Example 2. Patient A. 32 years old, with complaints of nasal congestion, profuse discharge from the nose, frequent episodes of sneezing, impaired sense of smell. These symptoms are observed almost daily for about 15 years. For a long time, it has been observed by an allergist, an ENT doctor with a diagnosis of Allergic persistent rhinitis, moderate course (household, epidermal sensitization). Symptoms of chronic bacterial rhinosinusitis joined five years ago. There were no hospitalizations in the anamnesis, but on an outpatient basis with exacerbations of rhinosinusitis, he takes antibacterial drugs - amoxicillin 500 mg 3 times a day. Basic antiallergic therapy includes - levocetirizine 5 mg per day and mometasone spray 1 injection into each nasal passage 1 time per day constantly.

Survey methods:

- during allergological examination, specific IgE antibodies to household and epidermal allergens were revealed;

- bacteriological examination of smears from the nasal cavity revealed S. aureus in the diagnostic titer;

- during immunological examination, indicators of nasal secretion were determined (IL4, IL10, TGF-β, γ-INF spontaneous and induced, sIgA, IgA, IgM, IgG), total IgE in serum and leukotrienes LT C4, D4, E4, LTB4 in plasma blood (Table 4.). Based on the examination, the diagnosis was made: Allergic persistent rhinitis, moderate course (household, epidermal sensitization). Chronic rhinosinusitis, recurrent course. Prescribing the drug "KIP nasal" 5 drops 3 times a day for 5 days allowed to achieve clinical remission. At the end of the course of treatment, nasal breathing and sense of smell were fully restored, rhinorrhea and sneezing disappeared. No AEs were observed during treatment. No exacerbations were registered during the year. During the observation period, the patient had infrequent symptoms of nasal congestion and rhinorrhea, which were relieved by symptomatic use of antihistamines with a short course. There was no use of antibacterial drugs. The dynamics of the immunological parameters of patient A. is presented in table 4.

Table 4. Comparison of the immunological parameters of patient A. before and after treatment.

Immunological indicators Before treatment After treatment Total IgE, ME / ml 313.6 44.7 sIgA, ME / ml 6.0 22.0 IgM, ME / ml 1.8 2.0 IL10, pg / ml 12.3 2.0 IL4, pg / ml 50.0 6.4 TGF-β, pg / ml 840.0 465.0 IgA, ME / ml 2.0 2.5 IgG, ME / ml 13.8 15.0 γ-INF spontaneous,
pg / ml 0.2 13.5 γ-INF induced pg / ml, 1558.0 885.9 LT C4, D4, E4, ng / ml 3.13 3.54 LTB4, ng / ml 19.72 10.11

The presented values before and after treatment significantly differ in the level of total IgE, sIgA, IgM, IL4, IL10, TGF-β and LTB4 (p <0.05).

Claims (1)

A method of treating patients with allergic rhinitis in combination with chronic rhinosinusitis of bacterial etiology against the background of basic antiallergic therapy, including antihistamines, intranasal glucocorticosteroids and immunomodulatory drugs, characterized in that as an immunomodulatory drug, a topical lymphoid corrector "Nasal KIP" is used. containing immunoglobulins of the classes IgG, IgA, IgM, isolated from human blood plasma, which is administered intranasally, 5 drops into each nasal passage 3 times a day for 5 days.