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.

[Pleiomorphism of the cytokine profile in nasal polyp tissue depending on the phenotype 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.

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

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.

/pdf/printsipy-bazisnoi-terapii-polipoznogo-rinosinusita-14iwdpqzn6.pdf

Принципы базисной терапии полипозного риносинусита

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.

/pdf/the-role-of-leukotriene-receptor-blockers-in-the-treatment-2x3d6wo7.pdf

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

Expression of the TNFSF13B, APRIL, VEGF, FGF1 и EGF genes in different phenotypes of chronic rhinosinusitis with nasal polyps

Diagnostic and treatment algorithm for different phenotypes of chronic rhinosinusitis with nasal polyps

Introduction. Cancer remains one of the most common causes of death in the world, second only to cardiovascular diseases. The use of novel chemotherapeutic and targeted agents has significantly improved the prognosis of this group of patients. However, this significantly increased the number of cardiotoxic complications of anticancer therapy, including arrhythmias, in particular atrial fibrillation (AF), which negatively affects the prognosis.Brief description. The purpose of this article was to describe the case of a 64-yearold woman with central right lung lower lobe cancer. Upon admission to the chemotherapy department, the patient was first diagnosed with paroxysmal AF. After chemical cardioversion, the first course of multiagent chemotherapy (MAC) was performed as follows: paclitaxel 280 mg and carboplatin 450 mg, which was complicated by the development of recurrent AF episode. During subsequent MAC courses, arrhythmia episodes regularly occurred. During the next AF episode, the patient was hospitalized at the City Clinical Hospital № 51, where she died despite intensive therapy. Postmortem examination ruled out tumor invasion into the left atrium.Discussion. For the AF development, the patient had prerequisites in the form of a significantly remodeled left atrial myocardium. Chemotherapy agents used as antitumor therapy are characterized by the common development of cardiotoxicity, including variety of arrhythmias. The occurrence of AF episodes coincided with the course of MAC, which suggested its cardiotoxic manifestations. Postmortem examination confirmed the high probability of an association between AF episodes and MAC.Conclusion. The presented case illustrates the difficulties encountered by oncologists and cardiologists in determining the genesis and treatment of complex arrhythmias in cancer patients.

Atrial fibrillation in a patient with lung cancer: a case report

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Diagnostic and treatment algorithm for different phenotypes of chronic rhinosinusitis with nasal polyps

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

Expression of the TNFSF13B, APRIL, VEGF, FGF1 и EGF genes in different phenotypes of chronic rhinosinusitis with nasal polyps

Atrial fibrillation in a patient with lung cancer: a case report