RU2403071C1 - Method of treating chronic recurring inflammatory diseases of nasal cavity and paranasal sinises by method of endonasal autolymphocyto therapy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to otolaryngology, and deals with treatment of chronic recurring inflammatory diseases of nasal mucosa and paranasal sinuses. Method includes preliminarily obtaining of autologic lymphocytes from venous blood of patient, cultivation of obtained lymphocytes together with immunomodulator, preferably immunofan. After that from 0.1 to 3.0 ml of lymphocyte suspension, which contains 10⁶-10⁷ cells/ml, is introduced into paranasal sinuses with intervals between introductions from 2 to 7 days.

EFFECT: method is efficient, including cases of recurring polyps rhynosinutisis, allows to reduce treatment terms, increase remission terms, reduce frequency of appearance of symptoms of main and accompanying disease with reduction of need in other therapy.

4 cl, 3 ex, 6 tbl

Description

The invention relates to medicine, namely to the treatment of chronic inflammatory diseases of LORorgan.

Inflammatory diseases of the paranasal sinuses occupy one of the leading places in the structure of diseases of the upper respiratory tract, purulent sinusitis affects from 10 to 30% of the urban and rural population. In some cases, there is an association of this pathology with inflammatory lung diseases.

Currently, despite the improvement of methods for the diagnosis and treatment of purulent sinusitis, their prevalence is not decreasing. Moreover, the inflammatory pathology of the paranasal sinuses maintains a growth trend, and there is an increase in recurrent and chronic forms of the disease.

The traditional treatment of purulent rhinosinusitis is aimed at the destruction of pathogens and includes the evacuation of pus from the cavities, local and general antibiotic therapy, antihistamines and vasoconstrictors. In the treatment of acute and chronic inflammation of the mucous membrane of the paranasal sinuses, the greatest therapeutic effect is achieved with local administration of drugs. Local use of antibiotics for uncomplicated forms of purulent sinusitis has shown greater efficacy compared with systemic antibiotic therapy.

However, in recent years, there has been increasing evidence of the ineffectiveness of antibiotic therapy due to the emergence of antibiotic-resistant strains of microorganisms. It is also known that the majority of antibiotics, when applied topically at therapeutic concentrations, inhibit the activity of the ciliated epithelium of the mucous membrane, thereby complicating the natural cleansing of the cavities. Moreover, antibiotics contribute to the destruction of the necessary saprophytic flora, and as a result, the development of dysbiosis. Many of the commonly used antibiotics also have an immunosuppressive effect.

The ineffectiveness of the traditional treatment of purulent sinusitis associated with the use of antibiotics may be associated with the development of antibiotic resistance of the pathogenic flora, as well as with the immunosuppressive effect of antibiotics at the local and systemic levels.

At the present stage of development of otorhinolaryngology, an essential role in the pathogenesis of purulent sinusitis is assigned to defects in the immune defense of the mucous membrane, which necessitates the spread of modern methods of treatment of purulent sinusitis among otolaryngologists using modern immunotherapy methods.

The specific protective mechanisms of the mucous membranes, forming a barrier that protects the macroorganism from the pathogenic effects of various pathogenic and opportunistic microflora, are called the immune system of the mucous membranes, including immunocompetent and auxiliary cells, immunoglobulins of various classes, including secretory, cytokines (Belyakov I.M. Mucosal Immune System Immunology 1997. 4: 7-13 Bykova VP Lymphoepithelial organs in the system of local immunity of the mucous membranes Arch. Patol. 1995. 1: 11-16. Kozlov .K. Modern immunotherapy with infectious pathology. Roncoleukin Previous clinical use of the drug. // Manual for Doctors. Publ .: St. Petersburg State University, 2001. 24 pp.).

Immunological protection of the mucous membrane of the upper respiratory tract is determined primarily by secretory antibodies.

Locally-produced immunoglobulins are represented mainly by secretory IgA, which blocks the adhesion of a wide range of microorganisms to the epithelial cells of the mucosal surface. Secretory IgA, due to the presence of a secretory component, shows its biological activity in environments with a high content of proteolytic enzymes, including inflammatory exudates.

IgM is also synthesized in the upper respiratory tract, but its concentration in nasal and bronchial secretions is more than 100 times lower than the IgA content.

Secretory antibodies (SIgA and SIgM) perform their biological functions in the mucin secretion layer of mucin, inhibiting the colonization of the epithelium by infectious agents and inhibiting the flow of soluble antigens. This type of secretory immunity of the mucous membranes represents the first line of humoral defense and is termed “immune exclusion”, since it prevents the entry of foreign antigens into the internal environment of the body. Their interaction with the immune system is limited to the surface of the mucous membranes and skin.

In nasal secretions of healthy individuals, relatively high concentrations of IgG and trace amounts of plasma IgE and IgD are detected, which are secreted by passive diffusion from interstitial tissue fluid through the surface of the epithelium. Local IgE production in the mucous membrane of the respiratory tract is rare, but mast cells sensitized by this class of immunoglobulins are common both in the connective tissue and in the epithelium of the mucous membrane of patients with allergic diseases.

The cell link of specific protection of the mucous membrane of the nasal cavity and sinuses are T-lymphocytes, which play an important role in stabilizing and regulating the reactions of local immunity (Freidlin I.S. Kinetics of inflammation and immune response / I.S. Freudlin // Medical immunology. - 1999 . - T.1. No. 3 - 4. - S.25-26).

Often, chronic rhinosinusitis is combined with polypous rhinosinusitis. Polypous rhinosinusitis (ORS) is a chronic inflammatory disease of the mucous membrane of the nasal cavity and paranasal sinuses (SNP), characterized by the formation and recurrent growth of polyps, consisting mainly of edematous tissue infiltrated by eosinophils. About 1% of the world's population suffer from polypous rhinosinusitis. There are no exact statistics. Undoubtedly, ORS is a very serious and unresolved problem in modern medicine. Patients with ORS make up 5% of those who go to ENT clinics and 4% of those who go to an allergist. ORS is often one of the manifestations of the general pathology of the respiratory tract, and its pathogenesis is closely associated with the pathogenesis of bronchial asthma, cystic fibrosis and intolerance to the pyrazolone drugs. (Lopatin A.S. Polypous rhinosinusitis. Consilium Medicum vol. 2, No. 2, 2002; Lopatin A.S. et al. // Vestn. Otorhinolar. 2000. No. 4. P.60. Lopatin A.S. // West Otorhinolar. 1999. No. 2. P.54. Maran GD, Lund VJ Clinical Rhinology. Stuttgart; NY, 1990. P.94).

The last decade was marked by intensive research on the pathogenesis of ORS, the search for new methods for its non-surgical treatment, and attempts to create international clinical guidelines and treatment standards.

There is still no agreement on the issue of whether nasal polyps are an independent nosological form or is this just one of the manifestations of other diseases, for example, bronchial asthma, intolerance to aspirin, cystic fibrosis, Cartagener syndrome, etc. It can be said with great certainty that they are solitary (for example, anthrochoanal) polyps are an independent disease that develops as a result of pathological conditions in the SNPs themselves. Such conditions can occur in the presence of a large additional anastomosis and hyperventilation of the maxillary sinus, which becomes the site of cyst formation and then a large polyp growing towards the nasopharynx. The opposite of solitary polyps is a common, or diffuse, SNP polyposis, when almost all the sinuses are filled with a thickened polypous mucosa and viscous rubber-like mucus. This condition, of course, is a manifestation of not a local, but a systemic pathology in the body associated with changes in the immune system and the general reactivity of the body.

Various nosological forms of diseases of the nose and paranasal sinuses are distinguished, where the presence of polyposis is indicated.

From a histological point of view, the nasal polyp consists of a damaged, often metaplastic epithelium located on the thickened basement membrane, and an edematous stroma containing a small number of glands and blood vessels and practically devoid of nerve endings. The stroma of a typical polyp contains fibroblasts that form the supporting frame, pseudocysts and cellular elements, the main of which are eosinophils located around blood vessels, glands and directly under the integumentary epithelium.

One of the popular theories of the pathogenesis of ORS suggests that at the early stage of polyp formation as a result of repeated infections, chronic edema of the own layer of the mucous membrane develops, caused by a violation of intracellular fluid transport. At a certain stage, this leads to rupture of the basement membrane of the epithelium, prolapse of its own layer and the formation of granulation tissue. (Larsen P.L., Tos M. // Rhinology. 1995. V.33. P.185. Ponikau J.U. et al. // Mayo Clin. Proc. 1999. V.74. P.877).

From a histological point of view, most polyps are characterized by eosinophilic inflammation, the causes of which are either increased migration of eosinophils, or an increase in their lifespan in the tissue, or a combination of these two factors. Eosinophils are usually involved in protecting the human body from larger non-phagocytized microorganisms and parasites. In this regard, the fungal theory of the pathogenesis of ORS looks outwardly logical and reasonable, which is as follows. Unlike healthy individuals' T-lymphocytes, the T-lymphocytes of ORS patients activate eosinophils and cause them to migrate to the mucus contained in the SNP, where fungi are always present in the sinuses during normal air exchange. Groups of eosinophils surround and destroy fungal elements by isolating toxic proteins contained in their cytoplasm, the main of which are the large basic protein, eosinophilic cationic protein, eosinophilic peroxidase and eosinophilic neurotoxin. As a result, a very thick mucin is formed in the lumen of SNPs, containing a large amount of these toxic proteins, which has a damaging effect on the mucous membrane, causing chronic inflammatory process and growth of polyps in it (Bachert C. et al. // ACI International. 1999. V .11. P.130).

At this stage, bacteria can also take part in the process, which get the opportunity to penetrate the damaged mucous membrane that has lost its protective mechanisms and contribute to the development of relapses of inflammation. Histologically, the polyp consists of a damaged, often metaplastic epithelium located on a thickened basement membrane. The stroma of the polyp is edematous, contains a small number of glands and blood vessels, the polyp is practically devoid of nerve endings. In the stroma - fibroblasts that form the supporting frame, pseudocysts and cellular elements. The main cells are eosinophils, lymphocytes (neutrophils), plasma cells. Biologically active substances are present in the polyp tissue: histamine, serotonin, leukotrienes, kinins, prostaglandins. All types of immunoglobulins.

Large basal protein released from eosinophil granules can also act on the electrolyte exchange of epithelial cells, blocking sodium pumps and enhancing the release of chlorine ions from the cell. As a result, interstitial edema develops, which also contributes to the growth of polyps.

Another pathogenetic mechanism of ORS, intensively studied in recent years, is a violation of the metabolism of arachidonic acid. The classical clinical picture of the “aspirin” triad implies the presence of bronchial asthma in combination with eosinophilic rhinitis or ORS, the manifestations of which are sharply enhanced after taking non-steroidal anti-inflammatory drugs (NSAIDs).

The hypothesis about the role of NSAIDs in the genesis of nasal polyps claims that most patients with ORS have latent intolerance to NSAIDs, although it does not manifest in a detailed clinical picture, for example, because these patients avoid taking aspirin. However, it is impossible to completely exclude NSAIDs, as they are found in many fruits and vegetables (oranges, grapes, strawberries, raspberries, cucumbers, tomatoes, currants, apples, etc.), some food colors and preservatives. The constant ingestion of various doses of NSAIDs with food into the patient’s body causes relapses of eosinophilic inflammation in the mucous membrane of the upper respiratory tract and leads to the growth of “aspirin-induced” polyps.

From a practical point of view, based on current data on polyposis rhinosinusitis, the following forms of polyposis rhinosinusitis should be distinguished:

1. Polyposis as a result of aerodynamic disturbances in the nasal cavity and paranasal sinuses.

2. Polyposis in cystic fibrosis, Kartagener syndrome.

3. Polyposis as a result of metabolic disorders of arachidonic acid.

4. Polyposis as a result of chronic purulent inflammation of the mucous membrane of the nasal cavity and paranasal sinuses.

5. Polyposis as a result of fungal infection of the mucous membrane.

Endonasal autolymphocytotherapy is indicated in the complex treatment of two forms of ORS:

Polyposis as a result of chronic purulent inflammation of the mucous membrane of the nasal cavity and paranasal sinuses.

Polyposis as a result of fungal damage to the mucous membrane.

It has become generally accepted that treatment of ORS (with the exception of solitary polyps) should begin with drug therapy, and surgery should only be performed if the conservative treatment is ineffective. Modern possibilities of intranasal surgery, such as the use of endoscopes and soft-tissue shavers, allow detailed removal of polyps and pathological contents from all affected SNPs, following the principles of minimal invasiveness. Minimally traumatic interventions give better results, are accompanied by fewer complications, less often contribute to the progression of the disease and the development of bronchial asthma than classical operations with radical removal of the mucous membrane and nasal concha.

The primary nature of drug treatment, the minimal invasiveness of surgical intervention and its mandatory combination with preoperative drug preparation and postoperative treatment are generally accepted positions practically all over the world.

To date, there is no single treatment regimen for patients with polyposis rhinosinusitis and bronchial asthma, but everyone knows its principles, which provide for the comprehensive treatment of such patients in collaboration with doctors of several specialties (pulmonologist, allergist, otorhinolaryngologist).

Known non-surgical methods for the treatment of polypous rhinosinusitis (ORS), such as:

- Corticosteroid therapy.

Glucocorticosteroids (CS) have long been widely used in the treatment of ORS. These drugs have a pronounced and rapidly manifesting anti-inflammatory and immunosuppressive effect. (Holmgren K., Karlsson G. // Eur. Resp. Rev. 1994. V.4. No. 20. P.260. Mygind N. et al. // Clin. Allergy. 1975. V.5. P.159 ; Lopatin A.S. Polypous rhinosinusitis. Consilium Medicum vol. 2, No. 2, 2002).

For the treatment of ORS and prevention of the growth of polyps after surgery, both systemic and topical CS-therapy can be used. A short course of systemic CS therapy, called "drug polypotomy," is widely used in the treatment of ORS, and its effectiveness in many cases is not inferior to the effectiveness of instrumental polypotomy performed using a loop. For "drug polypotomy," prednisone (preferably in tablets with a protective coating) is prescribed in a dosage of 0.5-1 mg per 1 kg of body weight, usually for 10 days. To prevent side effects, two-thirds of the daily dose should be taken early in the morning, the remaining dose during lunch. From the 11th day, the dose of prednisone is gradually reduced until completely withdrawn. The entire course of treatment takes 14-16 days. Such a course can be prescribed if there are contraindications to surgical intervention. If polyps recur in a very short time, when both the patient and the doctor are disappointed with the results of repeated operations, an alternative can also be courses of systemic KS therapy, prescribed no more than 2 times a year.

The optimal in the treatment of ORS, especially associated with bronchial asthma, intolerance to NPP, nasal and bronchial hyperreactivity, is a combination of systemic CS-therapy and surgical treatment. In these situations, an intervention is performed against the background of a short course of systemic CS therapy, prescribing prednisone 30-40 mg / day in two divided doses (20-30 mg at 8 am + 10 mg at lunch) for 3 days before and 3 days after operations. Treatment of CS before surgery reduces the size of polyps, reduces swelling and bleeding of tissues and allows the surgeon to perform the intervention with minimal trauma, while maintaining anatomical structures and a healthy mucous membrane.

Another method of systemic CS therapy is the introduction of deposited corticosteroids. There is currently no reliable data regarding the effectiveness and safety of this treatment method. Compared with the use of depot preparations, oral administration and intravenous administration look preferable, since tablet forms are cheaper and the dosage of drugs can be adjusted in accordance with the dynamics of the disease. It is believed that the release of the drug from the depot during the whole day suppresses the pituitary-hypothalamic-adrenal system more than a single dose taken orally in the morning.

It should be remembered that the introduction of deposited CS into the nasal concha and polyps is not local, but one of the varieties of systemic CS therapy. Studies have never been conducted comparing the effectiveness of intranasal and intramuscular injections, and, most likely, these two methods of administration do not differ in their effect on the symptoms of ORS and the size of nasal polyps. But injections of depot preparations into the nasal concha are associated with a risk of retinal vascular embolism and blindness.

Another type of CS therapy is the introduction of tetracosactide, a synthetic polypeptide with the properties of adrenocorticotropic hormone. This drug stimulates in the adrenal glands the initial phases of the synthesis of steroid hormones, in particular cortisol and cortisone. The course of treatment for ORS usually consists of two injections of 1 mg of the drug with a 48-hour interval. When prescribing tetracosactide, all precautions should be observed, as with systemic CS therapy, courses should not be repeated more often 3-4 times a year.

Attempts of topical application of CS in the treatment of ORS have been undertaken since the 50s of the XX century, but for almost 20 years they have been unsuccessful due to the lack of drugs with high topical activity. It turned out that after spraying the drug into the nasal cavity, most of it moves very quickly into the nasopharynx, is swallowed, enters the stomach and can cause the same undesirable side effects as the systemic purpose of this drug. Due to the intense blood supply to the nasal cavity immediately after injection into the mucous membrane of the nasal concha, almost the entire drug enters the general bloodstream. Thus, the use of hydrocortisone and betamethasone with 100% bioavailability in the form of nasal drops has practically no advantages over general CS therapy, since it leads to the same inhibition of the hypothalamic-pituitary-adrenal system.

An ideal topical KS preparation should have high local activity and minimal total bioavailability. The first of these drugs, beclomethasone dipropionate dosed intranasal aerosol (BDP), appeared in the early 70s, and already in 1975 very encouraging results of its use in PRS were published (N. Mygind, 1975). BJP is used in rhinology to this day, demonstrating good efficacy, however, in the following years 2 more drugs were developed - fluticasone propionate and mometasone furoate, which possess the desired properties of an “ideal” topical CS. Along with the very high local activity of fluticasone, propionate has a bioavailability of 1-2%, and mometasone furoate - only 0.1%. The usual daily dosage of mometasone furoate and fluticasone propionate is 400 mcg (2 doses in each half of the nose 2 times a day). The effectiveness of these drugs in ORS has been proven in controlled studies.

At the moment, long-term courses of treatment with topical CS (in the form of intranasal aerosols or nasal drops) remain the main method of treating ORS and preventing relapse after polyps are removed. The results of the use of topical CS in the form of monotherapy are encouraging, which in some cases can become an alternative to polypotomy.

- Antifungal treatment.

In connection with the emergence of the fungal theory of the pathogenesis of ORS in the last decade of the 20th century, the question arose about the possibility of using antifungal drugs in the treatment of this disease. Pilot tests of the effectiveness of the topical application of amphotericin B solution, which was prescribed in the form of nasal showers, were conducted. The first double-blind, placebo-controlled study of the effectiveness of topical treatment with amphotericin B solution is currently underway in the United States. In the near future, multicenter studies in Europe are planned. Attempts have been made to use systemic antifungal drugs, in particular itraconazole. The results of treatment with itraconazole were presented several times at international congresses by demonstrating impressive clinical cases, but no analysis of long-term results in a whole group of patients has yet been carried out. Keep in mind the hepatotoxicity of this drug, especially with prolonged use.

- Allergen-specific immunotherapy (ASIT).

ASIT, of course, is indicated for ORS patients who have sensitization to environmental allergens or dwellings confirmed by the results of an allergological examination. The question of ASIT in ORS becomes even more relevant in the light of the fungal theory of the disease. However, to date, industrial production of the necessary fungal allergens for ASIT, in particular the genus Bipolaris, which is considered one of the most important in the etiology of allergic fungal sinusitis and ORS, has not been established.

ASIT by bacterial allergens can theoretically be justified in view of the possible role of bacterial superantigens in the pathogenesis of ORS. Attempts to apply this method were made mainly in the 70s of the XX century. Individually prepared or standard bacterial allergens in increasing concentrations were administered subcutaneously, intradermally or by spraying in the nasal cavity and pharynx with courses of various durations (from 1 to 9 months). The effectiveness of such treatment in ORS is difficult to judge, since most of the observations relate to the treatment of "infectious-allergic rhinosinusopathy." Given the current principles of ASIT, allowing the use of only purified and standardized extracts and requiring strict adherence to indications, contraindications and the rules for its implementation, the use of individual and non-commercially available vaccines should be considered critically.

- Desensitization with aspirin.

The desensitization method is based on the phenomenon of tolerance to repeated NSAIDs. It is still rarely used in the treatment of recurrent ORS, but taking into account the results of a series of studies by J. Gosepath et al. (1999-2001), has good prospects.

In recent years, a new simplified regimen of oral desensitization has been used to treat recurrent ORS: 1st day 50 mg aspirin in the morning, 50 mg after 8 hours; 2nd day 500 mg; 3rd day 100 mg and then the same dose for at least 9 months. Desensitization is carried out in a hospital, before the first intake of aspirin, an intravenous catheter is installed in case of emergency. FVD is investigated at the beginning of treatment and after taking each subsequent dose of aspirin, desensitization is continued only if the FVD values are reduced by no more than 25% of the initial values.

In order to exclude the gastrointestinal effects of prolonged aspirin use, a method of topical intranasal desensitization was developed. For this, soluble forms of aspirin were used, and a solution for spraying in the nasal cavity was prepared ex tempore before each procedure. The course of treatment usually consists in the introduction of 8 mg of aspirin every other day for 6 months. Comparative studies have shown that intranasal aspirin desensitization is no less effective than topical corticosteroids in the prevention of polyposis recurrence.

- Antileukotriene preparations.

With the realization of the crucial role that leukotrienes play in the pathogenesis of bronchial asthma and ORS, the need for the development of drugs that could suppress the production of leukotrienes or their effect on tissues has become clear. Currently, there are 4 such drugs: zileuton (5-lipoxygenase inhibitor), zafirlukast, pranlukast and montelukast (LTD4 receptor antagonists), all of which are intended for oral administration. In patients with aspirin bronchial asthma, antileukotriene drugs are firmly included in the group of basic preventive therapy. There are few reports of the use of antileukotriene drugs for the treatment of ORS. At the moment, researchers are unanimous in the opinion that existing antileukotriene drugs are ineffective in the treatment of ORS, even in patients sensitized to aspirin.

- Antihistamines.

Views on the role of histamine and mast cells in the formation of nasal polyps have long been controversial. Recent studies have brought some clarity. The prevalence of ORS in healthy individuals and those with sensitization to environmental allergens and dwellings is almost the same. Moreover, it was shown that in patients with ORS that developed against the background of seasonal allergic rhinitis, the growth of polyps does not increase during the dusting season of causative plants. Now it is believed that mast cells and the histamine secreted by them do not play a primary role in the pathogenesis of ORS. Neither systemic nor topical antihistamines have a significant effect on the size of nasal polyps, but the latest generation of antihistamines can be prescribed to ORS patients to stop the accompanying manifestations of allergic rhinitis.

- Anti-inflammatory drugs.

Some anti-inflammatory drugs may find use in the treatment of ORS. The most powerful anti-inflammatory effect is possessed by CS. Fenspiride, a drug that has already found its place in the treatment of acute and chronic bronchitis and sinusitis, may have certain prospects.

- Antibacterial therapy.

Bacterial inflammation, apparently, is not the primary factor in the pathogenesis of PRS. Yet there are arguments justifying the use of antibiotics in the treatment of some forms of ORS. This is, firstly, the existence of the so-called neutrophilic polyps or polypous-purulent forms of chronic sinusitis. Secondly, the role of bacteria, in particular Staphylococcus aureus, as superantigens is possible. Thirdly, the possibility of damage to bone tissue and the appearance of foci of osteitis in the chronic inflammatory process in the paranasal sinuses is shown. In the treatment of ORS, antibiotics are used in combination with CS, and the treatment is carried out in long courses (up to 3 months or more). Macrolides, second and third generation cephalosporins and fluoroquinolones, especially their last generation with increased activity against pneumococcus (moxifloxacin, levofloxacin, etc.), are considered antibiotics of choice for ORS. In Russia, antibiotics are traditionally used only for the treatment of the polypous-purulent form of chronic sinusitis (which makes up no more than 10% of all cases of ORS) and, as a rule, in combination with surgical intervention. Pharmacoepidemiological observations show that Russian doctors do not always conduct empirical antibacterial therapy of OBRS taking into account the spectrum of activity of drugs with respect to the main pathogens. Often, drugs are prescribed, the spectrum of action of which is obviously not adapted to the main pathogens of bacterial rhinosinusitis, for example, lincomycin, gentamicin, ampiox, etc.

Other treatments.

- Diuretic drugs.

Furosemide is able to change the transmembrane potential of epithelial cells, normalize the transport of sodium and chlorine ions and reduce the amount of interstitial fluid. In one study, furosemide inhalation was used to prevent the recurrence of nasal polyps after surgery, and the treatment was carried out with repeated courses for up to 5 years. The results showed that furosemide has an anti-relapse effect, and its activity can be compared with the effect of CS.

- Immunomodulators.

Changes in the immune system, of course, occupy a leading place in the pathogenesis of ORS, and this fact has stimulated repeated attempts to use various immunomodulating drugs in anti-relapse treatment. Schemes included splenin injections, intranasal bacterial vaccines (IRS-19, bronchomunal), lycopide, polyoxidonium, cycloferon, thymalin, tactivin, immunofan, vilosen, etc. There were no controlled studies of the effectiveness of immunomodulators in ORS.

In recent years, in the treatment of acute purulent sinusitis, an immunomodulator roncoleukin has been used. The drug is widely used as an immunomodulator in various chronic inflammatory processes. Roncoleukin - recombinant yeast interleukin - 2 people - is a polypeptide consisting of 133 amino acids with a molecular weight of 15.3 kDa. The drug is obtained by modern protein chemistry methods from producer cells, which is a recombinant strain of non-pathogenic baker's yeast of the species Saccharomyces cerevisiae, in the genetic apparatus of which the human IL-2 gene is integrated. The drug is a lyophilized powder or a porous mass of white with a yellowish tinge. Sodium dodecyl sulfate was used as a solubilizer, D-mannitol was used as a stabilizer, dithiothreitol was used to protect SH groups from uncontrolled oxidation. The prepared preparation is administered at a dose of 0.5 mg (500,000 ME) in (3-5 ml) 0.9% NaCl solution into the cavity of the maxillary or frontal sinus during a puncture or trepanopuncture procedure.

In the treatment of acute purulent sinusitis, roncoleukin is administered once in each sinus. In some cases, in the absence of positive dynamics, 1-2 days after the administration of the drug, repeated administration of roncoleukin in the above doses is indicated (Lavrenova G.V. et al. Guidelines. St. Petersburg, 2003).

- In vitro methods.

There are first reports of the therapeutic effect of plasmapheresis in ORS, in particular, in the preoperative preparation of patients with concomitant bronchial asthma and allergic rhinitis.

Basic studies of extracorporeal immunopharmacotherapy indicate the high efficiency of autologous leukocytes activated in vitro by various immunomodulators in sepsis, burn disease, various bacterial and viral infections (Gushchin I.S., Leskov V.P. Extracorporal immunopharmacotherapy Int. J. Immunorehabilitation. 1999, No. 14, p. 103 .; Leskov V.P., Cheredeyev A.N., Gorlina N.K., Novozhenov V.G. Clinical immunology for doctors.Moscow "Medicine", 2005, 144 pp .; Cheever MAJExp Med., 1986, V. 63, p. 1100-1112).

- Physiotherapeutic treatment.

Attempts have repeatedly been made to use various physiotherapeutic methods (helium-neon and infrared lasers, magnetotherapy, intranasal and intrathoracic microwave therapy, intranasal electrophoresis, etc.) in the treatment of chronic sinusitis, including its polypous form. However, to evaluate the effectiveness of these methods in case of ORS, independent comparative studies are needed.

- YAMIK method.

The use of the JAMIC sinus catheter is not an independent treatment for ORS. In this case, a sinus catheter is an effective way to deliver known drugs to SNPs. The accumulated experience allows us to conclude that the YAMIK method is highly effective in the treatment of recurrence of sinusitis, including polyposis, after intranasal surgery.

Surgical treatments.

Surgical methods are widely used in the treatment of polypous rhinosinusitis. They pursue the following goals: restoration of free nasal breathing, complete removal of polypous tissue, maximum preservation of pathologically unchanged mucous membrane. The main problem that the rhinosurgeon often faces is the recurrence of polyposis. In some cases, the growth of polypous tissue is so intense that the patient is forced to resort to surgical treatment 2-3 or more times a year. Frequent polypotomies are especially undesirable for patients in whom polypous rhinosinusitis is combined with bronchial asthma, since any surgical intervention in the nasal cavity in such patients is fraught with the onset of an asthmatic attack or aggravation of the course of asthma. On the other hand, polyps greatly complicate nasal breathing, irritate the so-called "asthogenic zones" of the nasal cavity, thereby contributing to the progression of asthma.

To date, in our country, unfortunately, polyp loops are most often used for nose polypotomy. With their help, it is possible to restore normal nasal breathing, but it is difficult to completely remove all polypous tissue from the upper parts of the nasal cavity and from the middle nasal passage. In addition, large portions of the intact mucosa are often removed. In patients with bronchial asthma, such surgical tactics are extremely undesirable, since they are highly traumatic, accompanied by postoperative bleeding, require nasal tamponade, which negatively affects the state of the bronchopulmonary system in such patients.

A gentle and at the same time effective method for the treatment of polypous rhinosinusitis is developed - the method of endoscopic endonasal surgery. During operations carried out under the control of an endoscope, you can examine all parts of the nasal cavity and paranasal sinuses, remove almost all pathologically altered tissues. In this case, the mucous membrane not involved in the polypous process is completely preserved. Regardless of whether polypous rhinosinusitis proceeds in isolation or in combination with bronchial asthma, treatment of patients includes drug therapy with surgical intervention. Considering the fact that surgical treatment of ENT organs in bronchial asthma in many cases leads to a worsening of the bronchopulmonary process, to bronchospasm during surgery and in the postoperative period, this forces us to develop safe, effective management schemes for patients with bronchial asthma and polypous rhinosinusitis.

Laser destruction of polyps, in comparison with other types of surgical intervention, allows bloodless and sparing removal of pathological tissue in the nasal cavity, significantly reducing the number of intra- and postoperative complications. This method is well tolerated by patients and has virtually no contraindications. The main advantages of laser nasal polypotomies are low invasiveness, bloodlessness, good tolerance of exposure, even in patients with a burdened therapeutic history.

Comparing surgical and therapeutic methods, we can say that the use of even the latest achievements of rhinosurgery allows you to affect only the final result of the pathological process, without affecting the links of the pathogenesis of polyposis. In this sense, surgical treatment is symptomatic, saving the patient from the manifestations of the disease. It does not interrupt the chain of its development and therefore practically does not affect the duration of remission. The modern pharmacotherapeutic treatment of the polyposis form of allergic rhinosinusitis, unlike the surgical one, is pathogenetic in nature, since it is aimed at blocking the effects of biologically active substances and cells directly involved in the development of the pathological process. Therefore, the problem of treating polypous rhinosinusitis should be considered from a therapeutic rather than surgical perspective. A more detailed study of the etiology and pathogenesis of this disease, the creation of a basis for the development of new highly effective and safe medications that could allow achieving, if not cure, then at least prolonged remission, are necessary. Further progress in this area, according to many experts, should not be associated with the development of surgical technologies, but with the introduction of new therapeutic methods.

One of these areas is the local introduction of immunomodulators. It is also obvious that the most effective is the use of autolymphocytes or products secreted by them in the conduct of such therapy. In this case, the principle of an individualized approach to each patient is observed, and the number of undesirable side effects is also reduced.

The solution to this problem lies in the use of autologous immunocompetent cells themselves, which are introduced into the organ to be treated.

Figuratively, this can be compared with the specialized action of activated immune cells directly in the focus of "conflict." In this case, immunocompetent cells provide not only high efficiency and specialized orientation of immune responses, but their action is not accompanied by side, undesirable effects, i.e. immune processes of a generalized form. These include: an increase in body temperature, exacerbation of concomitant chronic infections, activation of allergic and autoimmune processes in the body.

Thus, a method is proposed for the treatment of chronic recurrent inflammatory diseases of the nasal mucosa and paranasal sinuses using endonasal autolymphocytotherapy, which includes the preliminary preparation of autologous lymphocytes from the patient’s venous blood, cultivation of the obtained lymphocytes together with immunomodulators, and subsequent administration to the paranasal sinuses, in doses from 1.0 to 3.0 ml of suspension of lymphocytes in an acceptable medium at a concentration of 10 ⁶ -10 ⁷ cells / ml, with an interval between administrations from 2 to 7 days.

Preferably, the culture of the obtained lymphocytes together with immunomodulators is carried out for 1-6 hours.

Preferably, immunofan is used as the immunomodulator.

Immunofan is an oligopeptide immunostimulant that has a mild immunoregulatory, detoxifying effect and inactivates free radical and peroxide compounds. The pharmacological effect of the peptide immunoxide reductant is based on the correction of the immune and oxidation-antioxidant systems of the body (Leskov VP, Gushchin I.S. Pulmonology. 1993, No. 3, pp. 10-15. Leskov VP and coauthors. Clinical immunology Moscow: “Medicine”, 2005, 144 pp.).

Immunofan is used for the prevention and treatment of immunodeficiency states of various etiologies in children and adults: combination therapy of tumors (including malignant), larynx and oropharynx papillomatosis in children, opportunistic infections (CMV and herpes infection, toxoplasmosis, chlamydia, pneumocystosis, cryptosporidiosis ), complex therapy of HIV infection, chronic viral hepatitis, chronic brucellosis, diphtheria (including bacteriocarrier), burns, septic endocarditis, non-healing wounds, purulent-septic e complications, bronchial obstruction, holetsistopankreatit, rheumatoid arthritis, psoriasis. As an adjuvant for vaccination against bacterial and viral infections in adults (Lebedev V.V. et al. Book edited by V.I. Pokrovsky. Moscow, 1998, p. 120).

It is preferable that the suspension of lymphocytes is carried out by the method of sinus catheterization using a NMR catheter, after preliminary evacuation of the contents.

Endonasal autolymphocytotherapy is indicated in the treatment of chronic recurrent inflammatory diseases of the nasal mucosa and ONP of bacterial, viral and fungal nature, including those complicated by polyposis rhinosinusitis.

The main indicators for the purpose of the method are:

- the severe course of chronic recurrent bacterial and viral diseases and the inefficiency of traditional therapeutic methods;

- to reduce the side effects of immunomodulators with concomitant chronic infections, allergic diseases, etc.

Several treatment regimens have been developed in which the number of injected lymphocytes, the frequency of their administration and the duration of the course vary.

Scheme No. 1 is used in case of chronic purulent rhinosinusitis with a long, often recurring course, as well as in polypous rhinosinusitis caused by chronic bacterial viral and fungal infections.

A suspension of autologous blood lymphocytes of a patient activated in vitro by immunofan is administered by an otolaryngologist using a special catheter - Sinus JAMIC, which is introduced into the paranasal sinuses: 1st injection of 0.5 × 10 ⁶ cells, 2nd injection of 1 × 10 ⁶ cells, 3rd introduction of 1 × 10 ⁷ cells, 4th introduction of 2 × 10 ⁷ cells, 5th and 6th introduction of 3 × 10 ⁷ cells, administration interval:

1st and 2nd introduction - twice a week;

3rd, 4th, 5th, 6th introduction - once a week.

Scheme No. 2 is used for pain of mild forms of chronic rhinosinusitis with predominant purulent inflammation of the nasal mucosa and reactive (non-purulent) inflammation of the mucosa of the sinuses.

A suspension of autologous blood lymphocytes of a patient activated in vitro by immunofan is administered by an otolaryngologist using a special catheter - Sinus JAMIC, which is introduced into the paranasal sinuses: 1st injection of 0.5 × 10 ⁶ cells, 2nd injection of 1 × 10 ⁶ cells, 3rd and 4th introduction of 1 × 10 ⁷ cells, administration interval:

1st, 2nd, 3rd, 4th introduction - twice a week.

Thus, the choice of treatment regimen depends on the severity of the disease, the severity of the process and the individual patient's response to the introduction of autolymphocytes.

Possible complications when using medical technology and methods for their elimination.

Endonasal autolymphocytotherapy in most cases is not accompanied by any complications, however, as with any type of immunopharmacotherapy, individual reactions to the administration of a mixture of autolymphocytes induced by immunopharmacological drugs are possible, which can manifest as discomfort during catheterization of the nasal passages, a slight manifestation of the symptoms of the disease: mucopurulent discharge, a slight increase in edema and hyperemia of the mucous membranes. With an increase in the symptoms of inflammation, symptomatic therapy for an exacerbation period is recommended, a temporary manifestation of the symptoms of rhinosinusitis is not a contraindication to the continuation of the course to autolymphocytotherapy.

Thus, contraindications to the use of endonosal autolymphocytotherapy are:

- oncological diseases;

- severe mental disorders;

- severe diseases of the organs of the cardiovascular system;

- pregnancy;

- chronic diseases of internal organs in the stage of severe decompensation.

The method is as follows.

The technique of isolation of lymphocytes.

1. A patient from the cubital vein is taken 20 ml of blood in a sterile vacuum tube with heparin.

2. Under sterile conditions, lymphocytes are isolated from heparinized blood in a ficoll solution (density 1.077 g / cm ³ ).

3. The isolated lymphocytes are transferred into a sterile centrifuge tube and washed four times with sterile RPMI 1640 medium by centrifugation for 7 minutes at 200 g (1500 rpm).

4. Cells are counted in the Goryaev chamber and the preparation is checked for the purity of the cell population and cell viability.

5. After the fourth washing, 1 ml of a 0.005% immunofan solution is added to a suspension of lymphocytes at a concentration of 1 × 10 ⁷ cells / ml and incubated for one hour at 37 ° C, then washed twice. 1st time - RPMI 1640, 2nd time - isotonic sodium chloride solution (0.9%).

6. After the last wash, the cells are resuspended in 1 ml of sterile isotonic sodium chloride solution (0.9%).

7. Cells are counted in the Goryaev’s chamber and the drug is checked for the purity of the cell population and cell viability (the concentration of lymphocytes is adjusted to 1 × 10 ⁷ cells / ml, the purity of the cell suspension for lymphocytes should not be less than 95%, and the viability in the test with trypan blue - not less than 90%).

In addition to saline, a suspension of autolymphocytes contains only trace amounts of immunophan.

The data presented in table 1 indicate a rather high degree of viability of the patient's autologous blood lymphocytes upon activation by immunofan, immediately after isolation, the cell viability was 90-97%. Three hours after activation, cell viability ranged from 80-90%. After a six-hour incubation, 81-77%, after 48 hours, 50-60%.

Thus, the data presented indicate a rather high degree of viability of autolymphocytes. The highest percentage of their viability was determined after a three-hour incubation with immunofan.

Endonasal administration of autolymphocytes activated by immunofan is carried out in a day hospital as prescribed and under the supervision of an otolaryngologist.

In the treatment room, a suspension of autologous lymphocytes of the patient’s blood, activated by immunofan using a special probe, is introduced into the sinuses of the patient’s nose.

Isolation of lymphoid cells from the patient’s venous blood, titration of their concentration, incubation with immunofan solution, purity and viability test are carried out by an immunologist.

Before each procedure, patients are examined by an otolaryngologist and an allergist-immunologist.

Table 1. The study of the viability of lymphocytes isolated from the peripheral blood of donors during their incubation with immunofan. Incubation Time (h) Viability (%) Concentration, C / ml × 10 ⁶ 0 97 6.7 3 85 0.26 6 81 0.63 48 75 0.52 0 95 9.8 3 81 0.2 6 77 0.45 48 51 0.77 0 96 10 3 93 one 6 93 one 48 85 one 0 85 3 3 80 1,2 6 82 1,2 48 84 1,2

Clinical case No. 1.

Patient N. was observed by an otolaryngologist for chronic purulent rhinosinusitis with repeated relapses.

The duration of the disease is about 5 years, over the past 2 years, exacerbations repeated at intervals of 6-8 weeks from 3 to 5 times a year.

During the examination, secondary immunodeficiency of the cellular immunity link was established.

In a bacteriological study: inoculation from the mucous membranes of the pharynx and nose revealed coccal flora (epidermal and Staphylococcus aureus). Pneumococcus is sown once.

The treatment was carried out: local administration of broad-spectrum antibiotics, lavage of the sinuses with disinfectant solutions, vasoconstrictor drugs, nasonex. Laser therapy was also conducted 2 courses of 10 days, as well as 1 course of Roncoleukin. An immunomodulator was introduced into the cavity of the maxillary and frontal sinuses at a dose of 500,000 ME.

Conducted comprehensive treatment gave a short-term effect. Due to the insufficient effectiveness of the therapy, a course of endonosal autolymphocytotherapy was prescribed.

The treatment was carried out according to scheme 1.

A suspension of autologous blood lymphocytes of a patient activated in vitro by immunofan was introduced by an otolaryngologist using a special catheter - Sinus JAMIC in the sinuses: 1st injection of 0.5 × 10 ⁶ cells, 2nd injection of 1 × 10 ⁶ cells, 3 the introduction of 1 × 10 ⁷ cells, the 4th introduction of 2 × 10 ⁷ cells, the 5th and 6th introduction of 3 × 10 ⁷ cells, the administration interval is

1st and 2nd introduction - twice a week;

3rd, 4th, 5th, 6th introduction - once a week.

The treatment results were evaluated by the dynamics of clinical symptoms and immunological examination data are given below.

Table number 2 Dynamics of immunological parameters before and after treatment. Indicator norm before treatment after treatment White blood cells × 10 ^ 9 / L 4-8.8 6.5 5,6 Neutrophils,% 48-75 66 49 Neutrophils × 10 ^ 9 / L 2.1-5.6 4.2 4.6 Lymphocytes,% 19-37 twenty 24 Lymphocytes × 10 ^ 9 / L 1.2-3.0 1.3 1,6 Monocytes,% 3-11 10 8.0 Monocytes, × 10 ^ 9 / L 0.09-0.6 0.5 0.3 Red blood cells, × 10 ^ 12 / l 3.7-4.7 3.9 4.1 Hemoglobin, g / l 120-150 127 122 Hematocrit% 36-42 36 38 Wed erythrocyte volume, μm ^ 3, f 80-100 93 86 Wed soda hemoglob. in erythr., pg 26-34 33 32 Wed conc. hemogl. in erythr.,% 30-38 35 34 Platelets × 10 ^ 9 / L 180-320 193 196 CD45 / CD3, +% weight T-lymph. 55-75 82 56 CD45 / CD3 +, × 10 ^ 9 / L all T-lymph. 0.9-2.2 1,1 1.8 CD45 / CD3 + / CD4 +,% T-helpers 35-65 47 54 CD45 / CD3 + / CD4 +, × 10 ^ 9 / l T-help. 0.6-1.9 0.6 0.8 CD45 / CD3 + / CD8 +,% cytotox. whether 12-30 32 fourteen CD45 / CD3 + / CD8 +, × 10 ^ 9 / L cytot. 0.3-0.8 0.4 0.5 CD4 / CD8 1.2-2.5 1,5 1.3 CD45 / CD19 +,% B-lymphocytes 5-15 10 12 CD45 / CD19 +, × 10 ^ 9 / l B-lymph. 0.12-0.45 0.13 0.14 CD45 / CD3- / CD16 + CD56 +,% NK-cl 12-25 12 16 CD45 / CD3- / CD16 + CD56 +, × 10 ^ 9 / l 0.3-0.6 0.3 0.4 CD45 / CD3 + / CD16 + CD56 +,% T-kil 0-5 0 0 CD45 / CD3 + / CD16 + CD56 +, × 10 ^ 9 / l 0-0.1 0 0 Lake / T-lymph. Index 4-7 5,0 5.2

Table number 3 Results of sowing a throat swab on the flora Indicator Before treatment After treatment Staphylococus aureus 10 ** 1 (normal-) Sowing growth did not give Streptococcus viridans 10 ** 7 (norm 10 ** 5) Corynebacterium Neisseria Klebsiella Citrobacter Enterobacter Proteus et al. Conditional pathogen. Bacteria of the family. Enterobacteraceae Mushrooms p. Candida

Table number 4 Data of clinical indicators. Before treatment After treatment Complaints of nasal congestion, mucopurulent discharge, weakness, malaise, headaches. Nose: pink mucosa, slightly swollen. In the nasal passages - a small amount of mucous discharge. Objectively: Hoc - the mucous membrane is edematous, hyperemic, stagnant. In the nasal passages - mucopurulent discharge. The lower nasal concha is edematous, moderately hypertrophied. Pharynx: the mucous membrane is swollen, along the back wall of the pharynx is a thick mucopurulent discharge.

The clinical observation data shown in table No. 4, indicate a positive trend in clinical symptoms. The results of an instrumental examination 2 weeks after the end of the course of treatment revealed the absence of pathological changes in the paranasal sinuses.

Clinical case No. 2.

A patient, 45 years old, was observed for: bronchial asthma, mixed form, moderate severity, DN 1, concomitant diseases: chronic purulent sinusitis, recurrent polyposis rhinosinusitis, allergic rhinitis, hay fever, allergic rhinoconjunctivitis. Sensitization to household, epidermal allergens.

Complaints: constant nasal congestion, nasal discharge of a mucopurulent nature, attacks of shortness of breath, cough.

For ten years - chronic purulent rhinosinusitis, since 2003 - recurrent polypous rhinosinusitis, about which six surgical interventions were performed.

Since 2005, frequent bronchitis with an asthmatic component against the background of physical activity and in contact with household, epidermal allergens began to disturb. In March 2008, a course of autolymphocytotherapy (8 procedures) was carried out, autologous lymphocytes were injected subcutaneously in an increasing dose into the lateral surface of the shoulder. After the course of treatment, attacks of breathing difficulties began to bother much less often, the manifestations of rhinoconjunctivitis decreased, and constant nasal congestion remained.

Allergic history: In contact with pets, physical exertion - asthma attacks, cough, rhinoconjunctivitis.

Objectively: The condition is satisfactory. The skin is clean, normal color, rashes, no swelling. Nasal breathing is free. In the lungs, vesicular breathing, no wheezing. Heart sounds are clear, rhythmic. Heart rate = 78 per minute. HELL = 110/70 mm Hg

On examination:

Complete blood count: hemoglobin 11.7 g / dl (normal 12-16), red blood cells - 4.07 · 10 ⁶ / μl (normal 3.9-5), white blood cells 8.7 · 10 ³ / μl, lymphocytes 27% (norm 20-37), monocytes 6% (norm 2-8), eosinophils 2% (norm 1-4), basophils 0 (norm 0-1), fifth neutron. 3% (norm 1-4), neutral. 62% (norm 52-72), platelets 327 · 10 ³ / μl (norm 130-400), ESR 7 mm / h (norm 0-20).

Biochemical blood test: total bilirubin 10.3 μmol / l; direct bilirubin 1.8 μmol / l (norm 0-3.4). ALT 15 IU / L (0-34), ACT 16 IU / L (normal 0-34), alkaline phosphatase 44 IU / L (normal 47-119 IU / L), gamma GT 14 IU / L (normal 0-38 ), glucose 5 mmol / L (norm 4.1-5.9), urea 2.2 mmol / L (norm 2.8-7.2), creatinine 69 μmol / L (norm 58-96), uric acid 178.7 (norm 154.7-357), iron 15.6 μmol / L (norm 10.7-32.2), triglycerides 0.96 mmol / L (norm less than 1.7), total cholesterol 5.7 mmol / l (norm less than 5.2).

General analysis of urine: color - salt. yellow, rel. density 1020, reaction 7, protein - traces, epitopic flat - single in the field of view, white blood cells 0-3 in the field of view, erythrocytes. - absent., bilirubin - absent., nitrites - negative., cylinders - absent., glucose - absent., ketone bodies - absent., salts - absent., bacteria - absent.

In the inoculation from the nasal mucosa, isolated: Streptococcus viridans 10 ⁶ (norm 10 ⁶ ).

Sputum cytology: epithelium - in a moderate amount in the field of view; leukocyte reaction - in a single amount in the field of view, the composition of the microflora is gram (+) cocci in a moderate amount.

FVD (02/12/08): Moderate obstructive respiratory dysfunction. The test with ventolin is positive (+ 32%).

Blood test for AT cytomegalovirus IgG 13.4 (more than 1.1 - positive.)

Positive skin scarification tests with household allergens.

Primary ENT consultation:

The mucous membrane of the oropharynx is pink, tonsils are normal, the gaps are clear, the back of the pharynx is unchanged, the mucous membrane of the larynx is pink, the vocal cords are gray, mobile, close.

The mucous membrane of the nose is swollen, mucopurulent discharge in the nasal passages, polypous growth of the nasal mucosa on both sides, the sinuses are filled with a thickened polypous mucosa.

Conclusion: chronic purulent sinusitis, recurrent polypous rhinosinusitis.

The treatment was carried out according to scheme No. 1:

A suspension of autologous blood lymphocytes of a patient activated in vitro by immunofan was introduced by an otolaryngologist using a special catheter - Sinus JAMIC, which is inserted into the paranasal sinuses: 1st 0.5 × 10 ⁶ cells, 2nd injection 1 × 10 ⁶ cells 3rd introduction of 1 × 10 ⁷ cells, 4th introduction of 2 × 10 ⁷ cells, 5th and 6th introduction of 3 × 10 ⁷ cells, administration interval 1st and 2nd introduction - twice a week ;

3rd, 4th, 5th, 6th introduction - once a week.

During treatment, with an increase in the dose of autolymphocyte suspension during the day after 4 and 6 injections, a slight increase in the symptoms of the disease was noted in the form of nasal congestion and swelling of the nasal mucosa. Additional symptomatic therapy was carried out, antihistamines stopped the swelling of the nasal mucosa during the day.

A month after the treatment, the patient fully recovered nasal breathing and smell (the patient did not smell for more than ten years).

A repeated examination of the otolaryngologist revealed a significant decrease in polypous growths of the nasal mucosa and sinuses. Mucosal edema was practically absent. In addition, the need for basic steroid inhalation therapy, which the patient received for bronchial asthma, decreased: the daily dose of flixotide decreased from 1000 μ / g to 500 μ / g.

Clinical case No. 3.

A patient, 21 years old, was observed for chronic purulent rhinosinusitis.

Upon treatment, he complained of an almost constant nasal congestion and mucopurulent discharge from the nose, frequent headaches, and worsening during the year. After surgery for the curvature of the septum, from then on, nasal congestion began to be permanent, noted frequent mucopurulent discharge from the nose and headaches. Over the course of the year, sanitation of the paranasal sinuses and local and general antibacterial therapy in combination with antihistamines and vasoconstrictive endonosal sprays were repeatedly performed.

Initial consultation of ENT: the mucous membrane of the oropharynx is pink, the tonsils are ordinary, the back wall of the pharynx is hypertrophied, the mucous membrane of the larynx is pink, the vocal cords are gray, mobile, close. Nasal mucosa - hypertrophic, congestive, edematous. In the nasal passages - mucopurulent discharge. Auditory passages, eardrums are not changed.

Conclusion: chronic purulent rhinosinusitis.

During the examination: skin allergological tests with household, epidermal, pollen allergens are negative. IgE total 90 cells / E (within normal limits), cytological examination of a smear from the nasal mucosa - cells of squamous and cylindrical epithelium, leukocytes up to 40 in the field of vision were detected. Cytological picture of the inflammatory process of the nasal mucosa.

When sowing a nasal swab, polyvalent microflora was found.

Table number 5 Sowing results of a nasal swab on the flora. No. Selected microflora CFU / ml Norm one Staphylococcus aureus 10 ** 2 - 2 Klebsiella pneumoniae / pneumoniae 10 ** 2 - 3 Acinetobacter sp. 10 ** 6 - four Streptococcus viridans 10 ** 5 10 ** 5

When examining the immune status, an increase in the relative and absolute number of T-lymphocytes, T-cytotoxic lymphocytes, B-lymphocytes is noted. The decrease in the relative absolute number of NK cells. Decreased white blood cell count. / T lymph. index.

Table number 6 Survey results Research name Result One Reference interval General blood test Wbc 7.50 10 ^ 9 / l 4.00-15.00 Rbc 5.19 10 ^ 12 / l 4.60-6.20 Hgb 153 g / l 130-160 HCT 47 % 43-49 Mcv 91 fl 80-100 Mch thirty pg 27-33 ICSU 325 g / l 320-360 Plt 248 10 ^ 9 / l 150-400 Lym% 45 % 25-70 NEUT% - % 50-70 MXD% - % LYM # 3.4 10 ^ 9 / l 1.0-6.0 MXD # - 10 ^ 9 / l 0.2-1.0 NEUT # - 10 ^ 9 / l 2.0-7.0 RDW 13 fl 37-46 PDW 17 fl 9-14 MPV 12 fl 8-12 P-LCR 43 % 15-35 Immune status T-lymphocytes% (CD45 / CD3 +) 78 % 55-75 T-lymphocytes (CD45 / CD3 +) 2618 cells / μl 900-2500 T-helpers% (CD45 / CD3 + / CD4 +) 42 % 35-65 T-helpers (CD45 / CD3 + / CD4 +) 1398 cells / μl 600-1900 T-cytotox% (CD45 / CD3 + / CD8 +) 34 % 12-30 T-cytotox (CD45 / CD3 + / CD8 +) 1152 cells / μl 300-800 CD4 / CD8 1.21 1.20-2.50 B-lymphocytes% (CD45 / CD19 +) 19 % 5-15 B lymphocytes (CD45 / CD19 +) 640 cells / μl 120-450 NK cells% (CD45 / CD3- / CD16 + CD56 +) four % 12-25 NK cells (CD45 / CD3- / CD16 + CD56 +) 135 cells / μl 300-600 ECT% (CD45 / CD3- / CD16 + CD56 +) 0 % 0-5 ECT (CD45 / CD3- / CD16 + CD56 +) 0 cells / μl 0-100 Leukocyte / T-lymph index 2.2 4.0-7.0

A course of endonasal autolymphocytotherapy according to scheme No. 2 was carried out.

A suspension of autologous blood lymphocytes of a patient activated in vitro by immunofan is administered by an otolaryngologist using a special catheter - Sinus JAMIC, which is introduced into the paranasal sinuses: 1st injection of 0.5 × 10 ⁶ cells, 2nd injection of 1 × 10 ⁶ cells, 3rd and 4th introduction of 1 × 10 ⁷ cells, the interval of introduction of the 1st, 2nd, 3rd, 4th introduction - twice a week.

After the treatment, normal nasal breathing was restored for a month, the mucopurulent discharge from the nose stopped.

Repeated consultation of the otolaryngologist: no complaints, the mucous membrane of the oropharynx pink, the tonsils are normal, the back wall of the larynx is pink, the vocal cords are gray, mobile, close, the nasal mucosa is normal. Auditory passages and eardrums are not changed. With a repeated cytological examination of the smear of the nasal mucosa, there are no signs of an inflammatory process. No pathogenic flora was found in the culture of the smear from the nasal mucosa.

Our results demonstrated the clinical effectiveness of the proposed method of treatment. The proposed method, subject to the principle of an individualized approach to each patient, reduces the amount of unwanted side effects, allows you to normalize your immune status, and reduces the severity of inflammatory phenomena.

Claims (4)

1. A method for the treatment of chronic recurrent inflammatory diseases of the nasal mucosa and paranasal sinuses using endonasal autolymphocytotherapy, which includes the preliminary preparation of autologous lymphocytes from the patient’s venous blood, cultivation of the obtained lymphocytes together with immunomodulators and subsequent administration to the paranasal sinuses in doses from 0.1 to 3.0 ml of suspension of lymphocytes in an acceptable medium at a concentration of 10 ⁶ -10 ⁷ cells / ml, with an interval between administrations from 2 to 7 days. 2. The method according to claim 1, characterized in that the cultivation of the obtained lymphocytes together with immunomodulators is carried out for 1-6 hours 3. The method according to claim 1, characterized in that imunofan is used as an immunomodulator. 4. The method according to claim 1, characterized in that the suspension of lymphocytes is carried out by the method of sinus catheterization using a NMIC catheter after preliminary evacuation of the contents.