CHARACTERISTICS OF CELLULAR COMPARTMENT CHANGES OF IMMUNE SYSTEM IN THE PATIENTS WITH CHRONIC POLYPOUS RHINOSINUSITIS DEPEND ON EFFICIENCY OF DRUG THERAPY

Despite numerous attempts to control the course of chronic rhinosinusitis with nasal polyps (CRSwNP) by means of pharmacological treatment and new surgical approaches, the majority of patients experience lifelong persistence of this disorder, at recurrence rates of 50-60% within 18 months after surgical treatment. Since CRSwNP is a chronic persistent inflammatory process, it affects the entire body condition, including the state of systemic immune response. An elevation of NK (CD3-CD16+CD56+), activated NK (CD8+CD3-), NKT cells (CD16+CD56+CD3+), Treg (CD4+CD25brightCD127low to neg) cells and activated T-lymphocytes (CD3+CD25+) was revealed elsewhere among all the patients with CRSwNP, using a flow ytometry method. There was no difference between various disease phenotypes. We analyzed the status of cellular component of systemic immunity, dependent on clinical course of the disease and efficiency of the administered therapy of CRSwNP. The patients were divided into three subgroups. The follow-up period was 1 year. The first group comprised the patients who showed positive dynamics after conservative therapy, resulting into regression of nasal polyps and their grade than a year ago. The second group included the patients in whom the size of polyps remained the same. The third group included the patients with higher incidence of nasal polyps than a year ago.We have shown a decrease of Treg, NKT cells, NK and activated NK, cytotoxic T-lymphocytes (CD3+CD8+), activated T-cell numbers in clinical group 3 with aggressive growth of polyps and low effect of standard therapy, which may cause deterioration of the immune system cellular populations, accompanied by presence of persistent productive inflammatory process of nasal cavity and paranasal sinuses. In the second group, a significant elevation of total lymphocyte number, total and activated T cells, T helpers (CD3+CD4+), cytotoxic T lymphocytes, NK and NKT cells was shown. Meanwhile, a decrease in absolute number of activated NK was observed despite the NK growth. Therefore, we can assume that the mechanism of their activation was disturbed and compensated by production of NKT cells and cytotoxic T lymphocytes. Moreover, we have shown in this group that the absolute number of Treg cells is increased; and these cells had a suppressive influence on effector cells of adaptive immune response, thus inducing incomplete elimination of infectious agents, which contribute to permanent incomplete course of inflammatory process. Chronic inflammatory process in CRSwNP affects systemic cellular immunity depending on the morbidity characteristics in the course of pathological process. The maximal intensity of systemic cellular immunity is observed in the group of patients that require permanent basic drug therapy. In case of aggressive CRSwNP and failure of standard drug therapy, we observed a decrease in absolute numbers of effector cells, along with decreased Treg lymphocyte numbers which may explain inefficient immune regulation of inflammatory process and medical interventions in this group of patients

Transforming growth factors TGF- β1, TGF- β2 and TGF- β3 in the tissue of nasal polyps in different phenotypes of chronic rhinosinusitis with nasal polyps

Chronic rhinosinusitis with nasal polyps (CRSP) is a heterogenous disease. We have earlier detected differences in severity of clinical manifestations, cellular infiltration degree shown in nasal polyps, of eosinophil-to-neutrophil ratio, efficacy of intranasal glucocorticosteroid baseline therapy, and various inflammatory patterns for several cytokines on the mRNA expression level in different phenotypes with isolated CRSP cases, CRSP associated with respiratory allergy (RA), or non-allergic bronchial asthma.The purpose of this work was to study the cytokines of TGF-â family in the tissues of nasal polyps in patients with different CRSP phenotypes. The research involved 292 patients suffering from CRSP divided into 3 phenotypic groups. Group I consisted of patients with isolated CRSP free of associated BA and/or sensitization to atopic allergens. Group II included patients with CRSP combined with respiratory allergy and was further divided into two subgroups. I.e., Group 2a comprised patients with CRSP, allergic BA (aBA), and allergic rhinitis (AR), while the patients with CRSP, AR, and non-allergic BA were placed to the group 2b. The patients suffering from CRSP complicated with non-allergic BA were allocated to the group III. The patients with hypertrophic rhinitis served as control. The levels of TGF-â1, TGF-â2, and TGF-â3 proteins (pg/mg) were measured by means of multiplex immunoassay approach in supernates of tissue homogenates from nasal polyps removed by surgery, and in posterior parts of inferior nasal conchae. The total protein level was determined in tissue supernatant, with cytokine contents recalculated for the mg/ml protein concentration for standardization of measurements.In the control group, trace concentrations of all three growth factors were detected. Significant difference in protein contents was found for the studied cytokines, depending on CRSP phenotype. The levels of TGF-â1 and TGF-â2 were statistically lower in isolated CRSP than in other groups of comorbid CRSP patients. TGF-â1 and TGF-â2 concentrations were significantly lower in CRSP + allergic BA group IIa than in CRSP + nonallergic BA and CRSP + RA groups. The amount of TGF-â3 cytokine was maximal in CRSP + non-allergic BA group III compared to the patients with isolated CRSP of group I and CRSP + non-allergic BA group 2a.Conclusions.The high level of all three TGF-â isoforms in patients with CRSP compared to the control group suggested a high potential of mucous membranes of paranasal sinuses for active tissue remodeling followed by nasal polype formation.Different mechanisms were presumed for development of local pathological process in different clinical phenotypes of CRSP, depending on the comorbid pathology, especially, BA or respiratory disorders.Minimal TGF-â1 and TGF-â2 levels were detected in isolated CRSP.The highest concentrations of TGF-â1, TGF-â2, and TGF-â3 were discovered in the patients with CRSP accompanied by non-allergic BA as compared to the groups with isolated CRSP and CRSP+allergic BA.5. Determination of TGF-â1, TGF-â2, and TGF-â3 levels can serve as an additional criterion for differentiating between the mechanisms of mucous membrane damage in local pathological process in tissues of comorbid patients with different CRSP phenotypes

Dynamics of local cytokine status in patients with parotid salivary gland sialadenosis depending on the treatment algorithm

Sialadenosis is a dystrophic disease of the salivary glands parenchyma, which leads to secretory disorders and hypertrophy of salivary glands. Sialadenitis develops in cases of secondary inflammation. Standard methods and medications for the treatment of sialadenosis lead to regression of clinical manifestations and remission. Usage of herbal extracts with prolonged action has a long-term local anti-inflammatory effect with minimal side effects, including those affecting oral mucosa. However, their use in the complex treatment of sialadenosis has been scarcely studied. Objective of our investigation was to estimate cytokine status dynamics in saliva from the parotid glands in the patients with sialadenosis and hypothyroidism during complex treatment which included the prolonged-action herbal remedy. 52 patients with sialadenosis of parotid salivary glands and hypothyroidism were divided into 2 groups: in the I group, 26 patients received basic therapy; in the II group, 26 patients received basic therapy + herbal drugs with prolonged effect as resorbable tablets. Control group consisted of 20 conditionally healthy people without disorders of parotid glands and thyroid gland. Comparative evaluation was performed 1 and 6 months after starting the treatment, with respect to clinical findings, sialometry and cytokine profile. The content of interleukins IL-1β, IL-6, IL-10 and tumor necrosis factor (TNF) was determined in saliva of parotid glands by ELISA technique. The 1st group of patients showed exacerbations within six months of basic treatment, and the sialometry data pointed to maintenance of decreased parotid function. In the 2nd group, when using basic treatment + herbal drugs, no clinical features of sialadenosis were evident within 6 months. The sialometry values were normalized, and the secretory function of the parotid glands was found to be increased. Therefore, it exerted an effect upon moisturization of oral mucosal and improvement quality of life in the patients. Regression of IL- 1β, IL-6 and TNF contents, and IL-10 increase in parotid gland secretions was significantly more pronounced at the terms of 1 and 6 months in cases treated with herbal drugs, compared to Group 1, where a conventional protocol was used. Addition of herbal drugs of prolonged action to the standard protocol of sialadenosis treatment is reasonable and effective

The role of leukotriene receptor blockers in the treatment of allergic rhinitis in combination with chronic rhinosinusitis with nasal polyps

Background. Leukotrienes play an important role in the pathogenesis of allergic rhinitis (AR) and eosinophilic type of chronic rhinosinusitis with nasal polyps (CRSwNP). There is a phenotype of CRSwNP in combination with AR, which has specifics of local inflammation.The aim of our study was to investigate the efficacy of using an antileukotriene drug in the treatment of AR in combination with CRSwNP.Materials and methods. 63 patients with AR and bilateral CRSwNP after endoscopic bilateral polypotomy were randomly divided into 2 groups. In the 1st group 32 people (age 50.28 ± 1.37 years) were prescribed a basic therapy with nasal spray of mometasone furoate at a daily dose of 400 µg in combination with montelukast 1 tab. 10 mg at night, in the 2nd group 31 people (age 50.31 ± 1, 16 years old) received only mometasone furoate monotherapy. Endoscopic examination of the nasal cavity was performed once every 3 months. The follow-up period was 1 year.Results. After 3 months in the 1st group of patients there was a recurrence of polyp growth was observed in 25% of cases, in the 2nd group in 35.5% of patients (p < 0.05). After 6 months, the number of relapses of CRSwNP decreased to 15.6% of cases in group 1 and to 22.6% in group 2 (p < 0.05). After 9 months in group 1 recurrence of NP was recorded in 12.5% of patients and nasal polyps were completely absent during endoscopic examination in 9.4% of cases, in the 2nd group, relapse was detected in 19.35% of patients (p < 0.05). 1 year after surgery, in group 1, relapse of NP was found in 12.5% of patients with AR and in 12.5% of cases was remission of the pathological process with cancellation of basic therapy. In group 2, recurrence of NP was in 16.1% of cases, there were no reasons for withdraw treatment of intranasal glucocorticosteroids in this group.Discussion. The clinical effectiveness of the addition of Montelukast to basic therapy has been reflected in a reduction in the growth rate of polyposic vegetation, the number of repeated operations and the stabilization of the flow of chronic inflammatory process.Conclusions. In the case of the clinical phenotype of AR with CRSwNP, the addition of a leukotriene receptor blocker montelukast to the basic therapy of intranasal glucocorticosteroids made it possible to improve drug control of both diseases and reduce the frequency of CRSwNP relapses

The role of innate immunity in the development of chronic rhinosinusitis and perspectives of its conservative management

Chronic rhinosinusitis (CRS) is a heterogeneous, multifactorial disease of unknown etiology, with an underlying deficient immune response to infectious and other triggers, leading to their incomplete elimination and persistence of inflammation. Development of CRS is made possible by a deficient response of the innate immunity of nasal and paranasal sinus mucosa. The main factors of non-specific defense system of nasal and paranasal mucosa are the function of cell junctions between epithelial cells, mucociliary clearance, pattern recognition receptors (PRRs), antigen presenting cells, and phagocytosis. The multirowed ciliate epithelium of nasal and paranasal sinus mucosa is covered by a thick layer of mucus containing more than 200 proteins. Changes in the qualitative composition of the nasal mucus in CRS manifests in overexpression of the main mucins MUC5AC and MUC5B and decreased synthesis of lactoferrin and lyzocin. Ciliary dyskinesia or abnormalities in their microstructure lead to decreased efficacy of mucociliary clearance. Diminished expression of proteins of tight junctions (TJ) ZO-1 and occluding results in decreased density of intercellular contacts and increased permeability of epithelial barrier. In addition, CRS is characterized by deficient Tolllike receptors (TLR) 9, 2 and 4, as well as increased counts of M2 macrophages in the mucosa. This results in suppressed phagocytosis and antimicrobial mucosal defense. Lower levels of STAT3 protein causes an imbalanced reaction of innate and adaptive immune response and disordered reparation processes. With abnormal functioning of all the above mentioned mechanisms, no immune elimination of infectious agents can take place, with increased susceptibility to viral and bacterial infections of the upper respiratory tract. This opens the door to development of CRS, including that with polyps. Investigation of the innate immunity factors would allow for predicting of inflammation in a given patient, as well as for development of new approaches to its conservative management

Features of the course of polypous rhinosinusitis combined with allergic rhinitis

Both allergic rhinitis (AR) and polypous rhinosinusitis (PRS) are a serious problem in context of their impact on quality of life, the risk of complications, overlay of bronchial asthma (BA) and medical control of these diseases. In most cases, T2 type eosinophilic inflammation lies beneath their pathogenesis, but the mutual influence of simultaneously existing chronic processes on each other appears under-investigated. Objective of the study: Compare the clinical and immunological characteristics of patients with polypous rhinosinusitis and concomitant allergic rhinitis and without respiratory allergy. All patients with PRS were divided into 2 phenotypic groups: Group 1 – PRS without bronchial asthma and respiratory allergy (54 people), Group 2 - PRS + allergic rhinitis, but without bronchial asthma (46 people). IL-1β-, IL-4-, IL-5-, IL-6-, IL-13-, IFN-γ-, TGF-β1-, TGF-β2-, TGF β-3 cytokines in nasal polyp tissue were determined using the Bio-Plex multiplex analysis system. Results: In patients with PRS combined with AR, the eosinophilic type of inflammation in the polyp tissue was determined in 100% of cases, it was accompanied by an increased level of IL-6, TGF-β1, TGF-β2, TGF-β3 and a reduced level of IL-5, IL-13 compared to PRS without comorbid pathology. Conclusions. Given the same clinical course of polypous rhinosinusitis, the identification of the difference in the cytokine profile in the nasal polyp tissue gives evidence of a different mechanism of the inflammatory response for different phenotypes of PRS. The polypous rhinosinusitis combined with allergic rhinitis is characterized by 100% eosinophilic type of inflammation, high levels of TGF-β family protein cytokines, pro-inflammatory cytokine IL-6 and a lower level of T2-cytokines IL-5 and IL-13 compared with the PRS group without comorbid pathology. The simultaneous treatment of PRS and allergic rhinitis using the joint efforts of otorhinolaryngologists and allergists will allow to achieve medical monitoring of both diseases and prevent their progression and development of complications

Basic principles for the treatment of chronic rhinosinusitis with nasal polyps

Introduction. Chronic rhinosinusitis with nasal polyps (CRSwNP) is based on a chronic inflammatory hyperplastic process in the mucosa membrane of the nasal cavity and paranasal sinuses (SNPs). According to the consensus on the biological treatment of CRSwNP with or without asthma, which is one of the latest consensus documents of the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), which was published in December 2019, the need for surgical treatment or systemic administration of corticosteroids due to the active nasal polyps growth are conditional signs for the decompensation of clinical control. Currently, the basic treatment for patients with CRSwNP is the long-term use of intranasal corticosteroids (INCS), which leads to an improvement in the quality of life, while minimizing the risk of exacerbations and complications.Research purpose. To evaluate the effectiveness of the basic therapy of intranasal glucocorticosteroid mometasone furoate for different phenotypes of CRSwNP.Methods. All patients with recurrent CRSwNP were divided into 3 equal phenotypic groups of 40 people each: group 1 – CRSwNP without asthma and respiratory allergies, group 2 – CRSwNP + atopy, group 3 – CRSwNP + non-allergic asthma. The observation period was 3 years.Results. Using the algorithm of stepwise therapy of CRSwNP, dynamic monitoring of these patients by an ENT and an allergistimmunologist, basic therapy with corticosteroids with constant treatment correction once every 3 months, it was possible to stabilize the inflammatory process throughout the respiratory tract and reduce the need for surgical treatment.Conclusion. With CRSwNP, long-term use of Mometasone furoate INCS is the main drug of basic therapy to minimize the recurrence of nasal polyp growth and is accompanied by clinical efficacy and the absence of adverse side effects

A multilateral approach to the problem of non-productive cough

Exhausting dry cough is the leading cause of seeking medical care because of the sharp decrease in the quality of life. There are psychological aspects of attitude to sick person suffering from bouts of non-productive cough. Pharmacotherapy of dry cough is complex and specific. Phytotherapy treatment should be pathogenetically validated and take into account potential side effects, as in the example with liquorice. The use of plantain and thyme extracts is feasible for relief of intrusive dry cough in acute inflammatory diseases of the upper respiratory tract

IMPORTANT FACTORS OF THE INFLAMMATORY PROCESS IN THE O ROPHARYNX AND OPTIMAL TREATMENT REGIMES SELECTION

Acute inflammatory diseases of the oropharynx dominate the medical aid appealability among all age categories. Such diseases are characterized by poly-ethiology and may form a mixed infection with bacteria and respiratory viruses. Components of bacterial cell walls, toxins, decay products of tissues during cytolysis or apoptosis of cells as a result of massive output of mature virions induce epithelial cells and macrophages for active synthesis of chemokines MCP-1, MCP-3, RANTES, IL-8, which leads to increased inflow of polymorphonuclear leukocytesin to the flammatory focus and a mass release of biogenic amines, lysosomal enzymes, cationic proteins, the release of arachidonic acid, which gradually turns into eicosanoids. Systemic use of NSAIDs can cause NSAID-associated gastropathies. Good accessibility of the target organ in diseases of the oropharynx allows target organspecific delivery of local treatment. Benzidamine hydrochloride (Tantum® Verde) refers to the group of anti-inflammatory suppressor of cytokines and also has a pronounced analgesic effect. The article provides data of the follow-up study of the efficacy of Tantum Verde® in the treatment of acute tonsillopharyngitis in outpatient settings

ANALYSIS OF CURRENT THERAPEUTIC APPROACHES TO CHRONIC RHINITIS ACCORDING TO THE POLYCLINIC DATA OF AMBULATORY SERVICE OF MOSCOW

The term «rhinitis» comprises a large heterogeneous group of diseases with different etiology and pathophysiological mechanisms. The latest consensual documents recommend that all rhinitis be classified into 3 main types: infectious, allergic (AR) and non-infectious and non-allergic with subsequent subdivision of each type into separate subtypes. In the Russian Federation, standards and clinical guidelines have been developed only for allergic rhinitis. The therapeutic agement of 779 patients with chronic rhinitis in outpatient settings have been analysed. When formulating the diagnosis, codes J31.0 and J30.0 and the terms «Hypertrophic rhinitis» and «Vasomotor rhinitis» were used for non-allergic rhinitis, while code J30.4 and the terms «Allergic rhinitis» or «Vasomotor-allergic rhinitis» were used for allergic genesis. The diagnosis «Intermittent AR» was indicated once, and severity was mentioned only in 2 patients. In AR group  (216 people), a comprehensive study was performed in 6.5% of cases, the diagnosis was established empirically in 52.7% of cases. Antihistamines were prescribed in 27.3% of cases, intranasal corticosteroids in 77.8%, montelukast in 9.7%, allergen-specific immunotherapy was performed in 1.9%. In non-allergic rhinitis (563 patients), 77.4% intranasal received corticosteroids, 7.5% received antihistamines, 3.7% – montelukast, 4.8% underwent surgical treatment. In both groups, original methods of therapy in the form of local antibiotics, homeopathic drugs, bacterial lysates were reported. In the AR group, a violation of the step-by-step therapy regimen was identified