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The issues of recurrencies in chronic rhinosinusitis with nasal polyps (CRSwNP) still remain unresolved. Therefore, detection patients with uncontrolled clinical course of CRSwNP is required.The aim of the present study was to assess cytokine profile in nasal polyps as well as clinical characteristics of patients with CRSwNP at varying levels of therapeutic control.The study included 99 patients with chronic rhinosinusitis. The contents of interferon IFNγ, interleukin IL- 1β, IL-4, IL-5, IL-13, tumor necrosis factor TNFα, transforming growth factors TGF-β1, TGF-β2, TGF-β3 were measured in polyp tissue samples by means of multiplex analysis. The patients were treated according to a stepwise СRSwNP therapeutic algorithm [9]. Following observation for 5 years, all patients were divided into groups, as based on medical control degree. Group 1 included patients with mild CRSwNP, who mainly received stage I and II treatment for the entire observation period. Group 2 was presented by moderate- severity CRSwNP, with stage II or III therapy according to the referred algorithm. Group 3 included the patients with severe CRSwNP who received one or more stage IV courses. The patients underwent repeated SNOT-22 questionnaire, endoscopic examination, clinical assessment. In case of bronchial asthma (BA), ACQ-7 was repeated. Initial cytokine profile of nasal polyps was analyzed by the mentioned clinical groups.Results:After 5 years of observations in group 1 (mild CRSwNP), we found a minimal decrease in quality of life (SNOT-22), severity of nasal congestion, or smell impairment. Bronchial asthma duration in these patients was significantly lower compared to group 3, the patients had better asthma control level. Cytokine profile of nasal polyps was characterized by the highest IL-4 concentration, average values IL-1β, TNFα, IFNγ and minimal TGF-β1 values.In group 2 (moderate CRSwNP), we noted more pronouced impairment of smell, nasal congestion and quality of life. Bronchial asthma was less controlled than in group 1. The maximal concentrations of IFNγ, IL-1β, TNFα, IL-5, TGF-β1, TGF-β2 were registered.In group 3 with poor CRSwNP control, the highest SNOT-22 scores, severity of difficulty in nasal breathing, impaired sense of smell were revealed. Duration of bronchial asthma was longer, with lowest levels of medical control. In nasal polyps, minimal levels of IFNγ, IL-1β, TNFα, IL-4, IL-5, TGF-β2, TGF-β3 were noted.Treatment of patients depending on the clinical phenotypes of CRSwNP in the presence/absence of allergic rhinitis or bronchial asthma may improve control and reduce incidence of relapses in CRSwNP.

Long-term persistence of inflammation is the main factor of pathogenesis in chronic polypous rhinosinusitis (CRSwNP). Prospectives of current clinical otorhinolaryngology include modification of drugs containing topical glucocorticosteroids in order to increase local bioavailability, reduce the concentration of glucocorticosteroids, and alleviate the local inflammatory response. The aim of our work was to evaluate the effect of urea, magnesium sulfate, and mannitol on the concentrations of mometasone furoate and IL-5 in the polypous tissue of patients with CRSwNP. The study included 146 patients with CRSwNP aged 18 to 62 years. Biopsies of polypous tissue were taken during polypotomy. In the fluid samples obtained by microdialysis of polypous tissues, mometasone concentrations were determined by high-performance liquid chromatography. Concentrations of IL-3, IL-4, IL-5 and IL-10 cytokines in blood serum, and IL-5 in microdialysates of polypous tissue were measured by ELISA technique. The average age of patients with CRSwNP was 42.9±7.2 years, with prevalence of male patients (n = 93, 63.7%) over females (n = 53, 36.3%). Severity parameters of the disease by the SNOT-22 scale were significantly higher in CRSwNP patients than in control group (p ≤ 0.05). The results of biochemical analysis of microdialysates from polypous tissue showed increased content of Na+ ions in the resistant clinical cases of CRSwNP compared with the sensitive and dependent clinical forms (p < 0.05). Curves with the level of mometasone furoate were obtained in all the studied samples. It was found that the addition of magnesium sulfate solution to mometasone increases the Cmax of mometasone to 154 ng/mL in biological fluids after microdialysis. When urea solution is added to mometasone, Cmax increases to 198 ng/mL. In the native nasal polypous tissue dialysate, IL-5 levels were 89±2.01 pg/mL. Two hours after the addition of mometasone furoate, IL-5 concentrations decreased to 61±3.5 pg/mL, upon addition of urea, it changed to to 69±2.98 pg/mL (p ≤ 0.01, compared with the control without the addition of drugs). Analysis of serum cytokine levels showed that IL-5 concentrations in the patients with CRSwNP significantly exceeded (> 3-fold) those in the control group (p ≤ 0.05). There was a trend for increase of IL-3 and IL-4 (2-fold) and to decreased IL-10 levels in blood sera (> 1.5-fold) in patients with CRSwNP compared with controls. These results may be helpful for development of novel clinical approaches, in order to increase bioavailability of topically administered glucocorticosteroids, thus allowing to promote the effectiveness of basic therapy of CRSwNP and to develop therapy for the prevention of resistant forms of polyposis.

The aim of present study was to investigate the hBD-3 gene expression in the surface epithelium of mucosa in ORL organs. We have studied a total of 210 mucosal samples, obtained at the most frequent surgical intervantions from 5 different anatomical functional areas: nose and paranasal sinuses, middle ear, nasopharynx, oropharynx, larynx. The inferior turbinate mucosa (1) and the normal middle nasal passage mucosa (2) served as controls. Estimation of hBD-3 and β-actin gene expression was performed by reverse transcription and realtime PCR. In the nasal and sino-nasal mucosa, only negligible expression levels were detected in 14.29-33.33% of samples, most often in the specimens from the middle nasal passage and ethmoid labyrinth polyps (53.84%), being absent in hypertrophic inferior turbinate. In the middle ear cavity, the frequency detection of the hBD-3 gene expression varied from 7.69% in the stapes superstructures mucosa to 53.85% of the mucosal samples in the presence of cholesteatoma. hBD-3 gene expression was detected in most tissue samples with high microbial contamination: palatine tonsils (100%); adenoid hypertrophy (84.62%); adenoids in hypertrophic states of adenoids and palatine tonsils (87.5%); laryngeal fibrous-vascular polyps (87.5%); other laryngeal pathology (77.78% of the samples). The highest levels of hBD-3 gene expression were found in laryngeal fibrous-vascular polyps. The findings presumed two functionally different types of immune response in mucosa of the ORL organs. In the anatomical-functional areas lined with ciliated epithelium (middle and inferior nasal passages, maxillary and ethmoid sinuses, middle ear), significantly lower frequencies (Fisher's exact test, p < 0.05 to p < 0.001) and levels (Mann-Whitney test, p < 0.05 to p < 0.001) of hBD-3 gene expression were detected, except of polyps of the middle nasal passage and ethmoid labyrinth, and mucosa of the tympanic cavity in cholesteatoma, which may be related to the nature of the pathological process. In the areas lined with squamous epithelium or a combination of squamous and ciliated epithelium, hBD-3 gene expression was detected almost everywhere and at significantly higher levels. In the context of chronic inflammation and infection-related diseases of the ORL organs, in addition to the direct microbicidal activity of hBD-3 as the first line of immune response, one may suggest peptide dysregulation and, even, pathogenetic effects of hBD-3, e.g., increased sensitivity to infections, pathological changes in the composition of the commensal bacteria, fibrous remodeling.

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.

Objectives to assess the features of the inflammatory process of the nasal mucous membrane and sinuses in patients with сhronic rhinosinusitis with nasal polyps (CRSwNP). Material and methods. We analyzed the results of examination of 44 patients with CRSwNP. The objects of investigation were smears-reprints from the mucous membrane of the middle turbinate (rhinocytograms) and the intensity of the extracellular peroxidase activity of the lavage fluids of the maxillary sinuses. The data obtained were processed using the Statistica 8.0 software. Results. When analyzing rhinocytograms of the mucous membrane of the middle turbinates, the epithelial type of rhinocytogram was most often detected in 65.9% of cases (epithelial cells more than 50%); the eosinophilic type in 22.7% (eosinophils more than 1%) and smears with mast cells in 4.6% of cases; the neutrophilic type was less frequent (neutrophils more than 50%) 6.8% of cases. In 34.1% of patients, the cells of the columnar epithelium had pronounced changes in the cytoplasm (vacuolization and enzymatic activity); and in 38.6% of cases the gross pathology was recorded directly in the nucleus of the cells (nucleoli, granules, destruction of the nucleus). The revealed pathology of the cell nucleus suggests the viral etiology of the development of productive inflammation in the nasal cavity and sinuses In the lavage fluids of the maxillary sinuses, a high intensity of extracellular peroxidase activity was recorded (1777.9132.4 a.u. compared to 1225.0190.9 a.u. in patients with chronic purulent rhinosinusitis and 1245.0362.3 a.u. in patients with purulent-polypous rhinosinusitis). Conclusion. Chronic rhinosinusitis with nasal polyps is accompanied by a pronounced inflammatory process of the nasal mucous membrane and paranasal sinuses in the form of structural and functional changes in the cells of the columnar epithelium and a high intensity of extracellular peroxidase activity. The epithelial nucleus damage (the presence of nucleoli, granules, destruction of the nucleus) suggests a viral nature with the development of productive inflammation in the nasal cavity and sinuses.

Intriduction. Chronic rhinitis and rhinosinusitis noticeably deteriorate the patients’ quality of life and lead to the accompanying upper airway pathology development. The main purpose of treatment of this group of patients is to decrease severity of symptoms and the second one to prevent complications. The optimal therapy will help patients to maintain their lifestyle. Intranasal glucocorticosteroids are first-line drugs to treat acute rhinosinusitis or exacerbations of chronic rhinosinusitis in adults (including the elderly) and adolescents aged 12 years and older as an auxiliary therapeutic agent if treated by antibiotics, and to treat acute rhinosinusitis with mild to moderate symptoms without signs of severe bacterial infection. In the number of trials, mometasone furoate effectiveness in regard to decreasing of prominent symptoms with no side effects development has been shown.Objective: this article reviews available data on the effectiveness of intranasal corticosteroids – mometasone furoate – in the treatment of different forms of chronic inflammatory diseases of the nose and paranasal sinuses.Methods: information for this review was identified through a RISC and MEDLINE databases applying key words.Conclusions: based on the available data, treatment of chronic rhinosinusites and rhinitis should be initiated by conservative therapy. Summarizing information from the available literature we can conclude that treatment by mometasone furoate improve quality of life decreasing clinical symptoms of chronic rhinosinusitis and rhinitis.

Objective: To conduct a comparative analysis of the effectiveness of endoscopic and traditional surgeries in patients with chronic rhinosinusitis with nasal polyps. Methods: At the age of 21 to 65 years, 56 of patients with chronic rhinosinusitis with nasal polyps were diagnosed. Patients were divided into two groups: 1st group (31 patients – the main group), in which surgical interventions were performed endoscopically and 2nd group (25 patients – control group), in which patients underwent surgery using traditional methods. Results: The effectiveness of the method was estimated based on the relapse frequency of the patients who underwent surgery. Analysis of the long-term results showed that relapse of the disease was detected in 12.9% of the patients of the main group and 40% of the control group. Conclusion: The method of endonasal endoscopic rhinosinusotomy in chronic rhinosinusitis with nasal polyps proved to be more effective than traditional method of treatment.

Polypous rhinosinusitis is a chronic disease of the nasal mucosa and paranasal sinuses, which is characterized by recurrent growth of nasal polyps. This disease is found in 1-5% of the population. According to the data of 2017, patients with nasal polypous rhinosinusitis account for 13% of all patients treated in our clinic. Polypous rhinosinusitis can be either an independent disease or a manifestation of other diseases. Aim - to present a case from practice, which is interesting due to the fact that two independent diseases were hiding under the mask of polypous rhinosinusitis. Results. Strict administration of the diagnostic algorithm, modern principles of functional surgery of the paranasal sinuses led to the recovery of the patient.

Clinical phenotypes of chronic rhinosinusitis with nasal polyps (CRSwNP) are characterized with different inflammation patterns of mRNA expression of cytokines and depend on presence of allergic rhinitis (AR), atopic bronchial asthma (aBA) or nonatopic bronchial asthma (nBA)., Objective: To compare inflammation response in patients with different phenotypes of CRSwNP according to level secretion of the key cytokines in nasal polyp tissue., Material and Methods: 292 patients with CRSwNP were divided into four phenotypes: group 1 - CRSwNP without respiratory allergy (RA) and without BA; group 2a - CRSwNP+ AR with aBA; group 2b - CRSwNP+AR without aBA; group 3 - CRSwNP+nBA. Control group ( n =36) included patients with hypertrophic rhinitis without atopy or BA. Using multiplex assay we defined the level of IL-1β, IL-4, IL-5, IL-6, IL-13, IFN-γ, TGF-β1, TGF-β2, TGF-β3 in nasal polyp tissue., Results: The evaluation of cytokines levels in nasal polyps in different CRSwNP phenotypes showed a pleiotropy of different cytokine secretion depending on different comorbid pathology. In control group we estimated the lowest levels of all detected cytokines in comparison with other CRS groups. High levels of local proteins IL-5 and IL-13 and low levels of all isoform of TGF-β characterized CRSwNP without RA and BA. The combination of CRSwNP with AR showed high levels of proinflammatory cytokines IL-6 and IL-1β, and high levels of TGF-β1 and TGF-β2. The combination of CRSwNP with aBA estimated low levels of proinflammatory cytokines IL-1β, IFN-γ; in case of CRS+nBA we determined the highest levels of TGF-β1, TGF-β2 and TGF-β3 in nasal polyp tissue., Conclusions: Each CRSwNP phenotype is characterized by different mechanism of local inflammation. This underlies the necessity to diagnose BA and respiratory allergy among these patients. The evaluation of local cytokine profile in different CRSwNP phenotypes can help to determine the target anticytokine therapy for patients who has low efficacy of basic corticosteroid therapy.

Chronic polypous rhinosinusitis (CPR) is characterized by refractory to drug therapy and a high potential for recurrence after surgical treatment. One of the important factors limiting the effectiveness of drug therapy of CPR, in particular intranasal glucocorticosteroids (inGCSs), is the insufficient level of adherence to treatment of patients with CPR., Objective: Generalization of data on the significance and ways to increase adherence to treatment of patients with CPR., Material and Methods: Materials of scientific publications included in the Cochrane Library, Russian Science Citation Index, MEDLINE, PubMed information bases were used as a data source. The material was selected based on the following keywords: "chronic rhinosinusitis", "nasal polyps", "intranasal glucocorticosteroids", "adherence to treatment"., Results: Despite the fact that inGCSs are one of the main pathogenetically justified methods of treating CPR, their use is limited by many factors, one of which is the level of patient compliance with the treatment regimen., Conclusion: Improving adherence to treatment is one of the important reserves for increasing the effectiveness of drug therapy for chronic polypous rhinosinusitis.

Cystic fibrosis is genetic multisystem disorder with a predominant lesion of the respiratory tract. The duration and quality of life of these patients depends on the state of respiratory function. Progressive lung dysfunction is still the leading cause of mortality patients with cystic fibrosis. End-stage lung diseases in patients with cystic fibrosis, lung transplantation is a viable method of treatment. It has the ability to prolong life of these patients. Survival in cystic fibrosis has steadily increased medical treatment and post-transplant. Chronic rhinosinusitis (with nasal polys and without) impacts almost all cystic fibrosis patients, leading to significant reductions in quality of life. Chronic rhinosinusitis with nasal polyps is prevalent in the cystic fibrosis patients, and it is often a recalcitrant infection with multidrug resistant organisms. Medical therapies such as nasal irrigations, nasal steroids, and antibiotics are critical for managing symptoms, but functional endoscopic sinus surgery is necessary for refractory cases. The unified airway hypothesis suggests that sanitation bacterial infection in the upper airway can also decrease bacterial burden in the lungs. The article presents a clinical case of successful endoscopic sinus surgery in a 15-year-old patient with chronic rhinosinusitis with nasal polyps and cystic fibrosis after lung transplantation. The intervention was performed under General anesthesia and controlled hypotension. Bilateral antrostomy, ethmoidectomy and Draf IIb frontal sinusotomy were performed by endoscopic endonasal approach. There were no intra - and post-operative rhinosurgical or lung complications. The follow-up period was 18 months. At present, there is no relapse of chronic polypous rhinosinusitis, and there are no indications for revision intervention.

Annotation: Polypous rhinosinusitis (PRS) is a hardly treatable disease due to the unknown etiology and recurrent course. Standard treatment regimens are aimed at removing polyps and reducing the activity of inflammation, while little attention is paid to pathogenesis factors such as oxidative stress and mucociliary insufficiency., Objective: To improve the combined treatment of PRS., Material and Methods: The study involved 98 patients (50 people - the study group, 48 people - control group). The structure of the comorbid pathology of patients in the control group was selected so as to correspond to the pathology in the study group. Patients of both groups received combined treatment, including surgical treatment in accordance with the FESS principles, followed by the prescription of 200 mcg mometasone furoate in each half of the nose for 6 months. The treatment of patients of the study group also included the drug N-acetylcysteine - 3 ml (300 mg) in each maxillary sinus intrasurgicaly, then 600 mg orally in the morning after meals for 6 months. Survey methods included a questionnaire survey using the SNOT-22 questionnaire, the prevalence of the polypous process was assessed by endoscopy (Claus Bachert scale) and CT (Lund-Mackay scale), and mucociliary function was also evaluated by performing a saccharin test. The results were compared with each other before surgery and after 6, 12 and 24 months after surgery., Results: Patients who have been taking N-acetylcysteine for a long time have a more pronounced and long-term improvement in their general condition (according to SNOT-22, an average by 1.7 times, p <0.05) compared with patients in the control group. Also, the frequency of relapses decreases and the effectiveness of surgical treatment increases (according to the Lund-Mackey scale - 5.02 in the experimental group and 10.75 in the control; according to S. Bachert - 1 point and 3 points, respectively)., Conclusions: Long-term use of N-acetylcysteine in PRS increases the effectiveness of surgical treatment, reduces the frequency of relapses, and also improves the general condition of patients.

In connection with the prevalence and tendency to relapse, chronic rhinosinusitis with nasal polyps is an urgent problem not only for otorhinolaryngologists, but also for specialists whose therapeutic activity is somehow related to the respiratory system. Based on clinical observations, 5 phenotypes of this pathology were identified, each of which requires an individual approach to treatment and prevention. As a rule, the first stage is functional endoscopic rhinosinus surgery, the volume of which is determined depending on the phenotype. But even with a carefully performed operation, the result of surgical treatment may be unsatisfactory if there was no adequate care in the early inpatient and outpatient periods. This paper highlights the features of dynamic monitoring of patients with different phenotypes of chronic rhinosinusitis with nasal polyps.

Objective: To evaluate the effectiveness of the use of bioregulatory drugs for the prevention of complications in the early postoperative period in patients after septoplasty and FESS., Patients and Methods: We performed surgical treatment of 25 patients with chronic rhinosinusitis with frequent exacerbations without polyps. The extent of operation was septoplasty and FESS (polysinusotomy). In the postoperative period after septoplasty and functional endoscopic surgery on the paranasal sinuses (PNSs), along with systemic antibiotic therapy, irrigation therapy and nasal cavity cleaning under the endoscope control, Traumeel S in tablets was used 1 tablet 3 times a day 15 minutes before meals for 10 days. In the nasal cavity, after washing with a normalized solution of sea salt, Euphorbium Compositum Nazentropfen S, 1-2 spray 3 times a day for 10 days, was used as monotherapy. The control group included 25 patients with chronic rhinosinusitis with frequent exacerbations without polyps, comparable in age, sex, duration of the disease and the extent of surgery with the main group., Results: Accelerating the processes of wound healing, re-epithelialization, reducing reactive changes in the mucous membranes of PNSs, reducing postoperative edema with the use of naturally occurring drugs Euphorbium Compositum Nazentropfen S and Traumeel S helps minimize pathological effects on the epithelium of PNSs and the nasal cavity, accelerates the regeneration time of the ciliary epithelium and improves mucus function., Conclusion: The bioregulatory drugs Euphorbium Compositum with Nazentropfen S and Traumeel S can be effectively used in the treatment of patients after rhinosurgical interventions in order to accelerate reparative processes and restore the function of the ciliated epithelium, do not cause addiction and "withdrawal syndrome" and do not have an irritating effect on the nasal mucosa and PNSs.

The present study inluded 22 patients presenting either with very severe or moderately severe aspirin triad 17 of whom suffered exacerbation of chronic polypous suppurative rhinosinusitis. The reference group comprised 10 patients with exacerbation of chronic polypous suppurative rhinosinusitis in the absence of concomitant bronchial asthma. The control group included 25 practically healthy subjects having neither chronic somatic diseases nor ENT organ pathology. Conventional otorhinolaryngological examination of the patients was supplemented by cytological studies of the secretion from maxillary sinuses (MS) and inranasal mucosa, measurement of viscosity and pH of MS secretion. It was shown that eosinophil count in the MS secretion was several-fold higher than that in the secretion from nasal cavity mucosa . Polypotomy in the nasal cavity was performed after the preoperative treatment of the patients using sparing procedures, such as laser irradiation and a radiofrequency loop. This approach allowed to reduce the probability of enhancement of bronchial resistance during surgery and in the immediate postoperative period; moreover, it made it possible to continue puncture therapy of patients experiencing exacerbation of the chronic inflammatory process in the maxillary sinuses.